“CLINICAL, AND BIOCHEMICAL SPECTRUM OF CHRONIC KIDNEY DISEASE IN TERTIARY

CARE CENTER”

BY

Dr. RENUKAPRASAD Y.S. M.B.B.S.,

Dissertation submitted to theRajiv Gandhi University of Health Sciences, Karnataka, Bangalore.

In Partial fulfillmentOf the requirements for the degree of

DOCTOR OF MEDICINEIN

GENERAL MEDICINE

Under the guidance ofDr. B.M. VISHWANATH

M.D., MRCP (UK), MRCP (IRELAND) PROFESSOR

DEPARTMENT OF GENERAL MEDICINEJ.J.M. MEDICAL COLLEGE

DAVANGERE – 577 004.

2012

i

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA

DECLARATION BY THE CANDIDATE

I hereby declare that this dissertation entitled “CLINICAL, AND

BIOCHEMICAL SPECTRUM OF CHRONIC KIDNEY DISEASE IN

TERTIARY CARE CENTER” is a bonafide and genuine research work carried

out by me under the guidance of Dr. B.M. VISHWANATH M.D., MRCP

(UK), MRCP (IRELAND) Professor, Department of Medicine, J.J.M .Medical

College, Davangere.

PLACE : DAVANGERE

DATE : / /2011 (Dr. RENUKAPRASAD Y.S.)

ii

CERTIFICATE BY THE GUIDE

This is to certify that this dissertation entitled “CLINICAL, AND

BIOCHEMICAL SPECTRUM OF CHRONIC KIDNEY DISEASE IN

TERTIARY CARE CENTER” is a bonafide research work done by

Dr. RENUKAPRASAD Y.S. in partial fulfillment of the requirement for the degree

of M.D. (General Medicine).

PLACE : DAVANGERE

DATE : / /2011 Dr. B.M. VISHWANATH M.D., MRCP(UK), MRCP (IRELAND)

PROFESSORDEPARTMENT OF GENERAL MEDICINE

J.J.M. MEDICAL COLLEGEDAVANGERE – 577 004.

iii

ENDORSEMENT BY THE HOD,

PRINCIPAL/HEAD OF THE INSTITUTION

This is to certify that this dissertation entitled “CLINICAL, AND

BIOCHEMICAL SPECTRUM OF CHRONIC KIDNEY DISEASE IN

TERTIARY CARE CENTER” is a bonafide research work done by

Dr. RENUKAPRASAD Y.S. under the guidance of Dr. B.M. VISHWANATH

M.D., MRCP (UK), MRCP (IRELAND) Professor, Department of Medicine, J.J.M.

Medical College, Davangere.

Dr. G. RAJASEKHARAPPA M.D.,

PROFESSOR AND HEAD,DEPARTMENT OF GENERAL MEDICINE,J.J.M. MEDICAL COLLEGEDAVANGERE – 577 004.

Dr. H.R. CHANDRASEKHAR M.D.,

PRINCIPAL, J.J.M. MEDICAL COLLEGEDAVANGERE – 577 004.

DATE : / /2011

PLACE : DAVANGERE

DATE : / /2011

PLACE : DAVANGERE

iv

COPYRIGHT

Declaration by the Candidate

I hereby declare that the Rajiv Gandhi University of Health Sciences,

Karnataka shall have the rights to preserve, use and disseminate this dissertation /

thesis in print or electronic format for academic / research purpose.

PLACE : DAVANGERE

DATE : / /2011 (Dr. RENUKAPRASAD Y.S.)

Rajiv Gandhi University of Health Sciences, Karnataka.

v

ACKNOWLEDGEMENT

I take this opportunity to extend my gratitude and sincere thanks to all those

who have helped me to complete this dissertation.

I am extremely indebted and remain grateful forever to my guide

Dr. B.M. VISHWANATH M.D., MRCP (UK), MRCP (IRELAND) Professor of

Medicine, for his constant able guidance and constant encouragement in preparing

this dissertation during my post-graduate course.

It gives me pleasure to express my gratitude to my guide and Professor and

Head of Department of Medicine Dr.G.RAJASEKHARAPPA, M.D., for his

excellent guidance, encouragement and constant inspiration during my P.G. course.

I owe a great sense of indebtedness to Dr. H. GURUPADAPPA M.D.,

Director P.G. Studies and Research, J.J.M. Medical College, Davangere, who has

been a constant source of inspiration during my post graduate course.

My sincere thanks and gratitude to Emeritus Professor Dr. S.M. YELI, M.D.,

for his excellent guidance and constant inspiration during my study period.

My sincere thanks and gratitude to Emeritus Professor Dr. P.M. UPASI

M.D., for his excellent guidance and constant inspiration during my study period.

It gives me immense pleasure to express my deep sense of gratitude and

sincere thanks to Dr.MANJUNATH ALUR, M.D., Dip.Diab.,

Dr.S.N.VISHWAKUMAR, M.D., Dr.P.E.DHANANJAYA, M.D.,

Dr.SRINATH .K.V. M.D., Dr.K.SRIHARSHA M.D., Dr.N.S.BRID M.D.,

Dr.B.D.CHAVAN M.D Dr.K.V.CHANDRASHEKAR M.D., for their guidance

and encouragement during my postgraduate course.

I am very much thankful to Dr.P.MALLESH, M.D., D.M (Cardio) and

Dr.RAJEEV AGARAWAL, M.D., DNB(Nephro), Dr. ARPANDEV

BHATTACHARYA, D.M,(Endocrine) Dr. L. KRISHNAMURTHY D.M., (Neuro)

for their encouragement and advice.

vi

I express my sincere thanks to Dr.A.P.THIPPESWAMY M.D.,

Dr.B.G.KARIBASAPPA M.D., Dr. B.G SHIVAKUMAR. M.D,

Dr.GURUSHANTHAPPA, M.D., Dr.S.S.SAWKAR M.D., Dr.VINAY SWAMY

M.D., Dr. VINAY YELI, M.D., Dr.S.CHANDRASHEKAR, M.D., Dr

MRUTHUNJAYA C.T M.D. Dr.SURENDRA E.M., M.D., Dr. SHAH ABRAR

M.D., Dr.MAHESH D M.D., M.D., Dr.U.R.RAJU M.D.,

Dr.MAHABALESHWAR MAYYA M.D., for their valuable advice during my P.G.

Course.

My special thanks to Superintendent and Staff of Chigateri General Hospital

and Bapuji Hospital.

I thank Mrs.RAJESHWARI Bio-statistician, Mr.MAHESH, Chief

Librarian and Staff of library of J.J.M.M.C., Davangere.

My Special thanks to my friends.

I extend my sincere thanks to my post-graduate colleagues and all my

Friends, who had helped me in preparing this dissertation.

I must give my sincere thanks to my PARENTS for their valuable support,

love and constant encouragement.

I thank Mr.SANJEEV KUMAR G.P. of M/s GUNDAL Computer-Center,

for their meticulous computerized layout of this dissertation.

My heart full thanks to all patients who formed this study group and co-

operated wholeheartedly.

I thank the Almighty

PLACE : DAVANGERE

DATE : / /2011 (Dr. RENUKAPRASAD Y.S.)

vii

LIST OF ABBREVIATIONS USED

AIN : Acute intestinal nephritis

ATN : Acute tubular necrosis

BUN : Blood urea nitrogen

CAPD : Chronic ambulatory peritoneal dialysis

CGN : Chronic glomerulonephritis

CKD : Chronic kidney disease

CPN : Chronic pyelonephritis

CRF : Chronic renal failure

CRI : Chronic renal insufficiency

DN : Diabetic nephropathy

ECF : Extra cellular fluid

ESRD : End stage renal disease

GFR : Glomerular filtration rate

HD : Hemodialysis

HTN : Hypertension

K/DOQI : Kidney disease outcome quality initiative

LVH : Left ventricular hypertrophy

NSAID : Non steroidal anti inflammatory drugs

OU : Obstructive uropathy

P.m.p : Population per million

PCKD : Polycystic kidney disease

PD : Peritoneal dialysis

PTH : Parathormone

RAS : Renal artery stenosis

rHuEPO : Recombinant human erythropoietin

RRT : Renal replacement therapy

viii

ABSTRACT

Background and objectives :

A prospective study was carried out in 50 patients detected to have chronic

renal failure to determine the aetiology, laboratory and clinical profile of these

patients.

Materials and Methods :

50 patients with CRF were included who fulfilled the criteria set by the

National Kidney Foundations, Kidney Disease outcome quality initiative for

diagnosing CRF by subjecting them to clinical assessment, laboratory analysis and

ultrasonography of the abdomen and pelvis.

Results :

The aetiology of CRF in our patients was found to be diabetic nephropathy in

38%, Hypertensive Nephropathy in 28%, Chronic Glomerulonephritis in 24%,

Obstructive Uropathy in 6%, polycystic kidney disease in 2% and chronic

pyelonephritis in 2%. The abnormality in the laboratory profile of the patients were

found to be Anaemia in 90%, Hypocalcemia in 46%, Hypoalbuminaemia in 34%,

Hyperkalemia in 34% and Hyponatremia in 24%. The commonest clinical symptoms

seen in our patients were Pedal edema in 78% and Oliguria 76%. The commonest

clinical signs were Hypertension in 92% and Pallor 90%.

Interpretation and conclusion :

The major concern which our study highlights is the need for the prompt

detection and management of renal insufficiency before the need to initiate renal

replacement therapy. Our study also shows the growing incidence of CRF due to

hypertension, diabetes and obstructive uropathy which emphasizes the need for the

prompt detection of the above disorders to prevent renal damage.

KEY WORDS :

ix

TABLE OF CONTENTS

PAGE NO

1. INTRODUCTION

2. OBJECTIVES

3. REVIEW OF LITERATURE

4. METHODOLOGY

5. RESULTS

6. DISCUSSION

7. CONCLUSION

8. SUMMARY

9. BIBLIOGRAPHY

10. ANNEXURES

PROFORMA

MASTER CHART

x

LIST OF TABLES

SL.NO. TABLES PAGE

xi

LIST OF GRAPHS

SL.NO. LIST OF GRAPHS PAGE NO.

LIST OF FIGURES

LIST OF FIGURES Page No.

xii

INTRODUCTION

Chronic kidney disease is characterized by a decrease in glomerular

filtration rate and histological evidence of reduction in nephron population.

The clinical course is typically one of a progressive and unrelenting loss of

nephron function ultimately leading to end stage renal disease. Kidney failure

is the most visible aspect of the spectrum, but it represents only a minority of

the total population affected by kidney disease.

The time between initial onset of disease and development of terminal

renal failure may vary considerably not only between different diseases but

also in different patients with similar disease processes. The progressive

nature of CKD and the ensuing ESRD is putting a substantial burden on

global health resources since all modalities of treatment are expensive.

There are multiple causes of kidney injury that lead to the final

common pathway of ESRD, and this syndrome is characterized by

hypertension, anemia, renal bone disease, nutritional impairment, neuropathy,

impaired quality of life, and reduced life expectancy. Increasing evidence

acquired in the past decades indicates that the adverse outcomes of CKD such

as renal failure, cardiovascular disease, and premature death can be prevented

or delayed by early detection of CKD. Earlier stages of CKD can be detected

through laboratory testing only. Treatment of earlier stages of chronic kidney

disease, as well as initiation of treatment of cardiovascular risk factors at

early stages of CKD should be effective in reducing the rate of progression of

CKD to ESRD.

1

Unfortunately, despite the evident importance of CKD there is limited

data on its epidemiology within the general population, especially from

developing countries like India. Two community-based studies have shown a

prevalence of chronic renal failure of 0.16%1 and 0.79%2.

Renal failure registry data is unlikely to be representative of the

broader spectrum of CKD. There is a wide variability both within and

between countries in the occurrence, clinical characteristics and outcomes of

patients with kidney failure and there have been substantial changes over

time. Only 3% to 5% of all patients with ESRD in India get some form of

renal replacement therapy. Thus, planning for prevention of CKD on a long-

term basis is the only practical solution for India 3.

2

OBJECTIVES

The prsent study is undertaken with the following objectives:

1. To assess the cliical profile of patients with chronc renal failure at the

time of presentation.

2. To assess the biochemical profile of patients with chronic renal failure.

3. To determine the aetiology of chronic renal failure wherever

possible.

3

REVIEW OF LITERATURE

CHRONIC KIDNEY DISEASE

Chronic kidney disease represents the entire spectrum of disease that

occurs following the initiation of kidney damage. The introduction of a formal

definition for CKD has enabled standardize current medical communication,

facilitate appropriate population based screening, and encourage timely

prevention and treatment of kidney disease.

DEFINITION4

1. Kidney damage for 3 months, as defined by structural or functional

abnormalities of the kidney, with or without decreased GFR, manifest by

either

a. Pathological abnormalities; or

b. Markers of kidney damage, including abnormalities in the

composition of the blood or urine, or abnormalities in imaging

test.

2. GFR < 60 ml/min/1.73 m2 for 3 months, with or without kidney damage.

The GFR is considered the best measure of overall kidney function. A

GFR below 60 mL/min/1.73m2 represents loss of one half of more of the

adult level of normal kidney function. Normal GFR varies according to

patient age, sex, and body size.

4

Recommended equations for estimation of GFR using serum creatinine

(pl creatinine), Age, Sex, Race and Body weight.

1) Cockcroft – Gault formla5

Estimated creatinien clerance

(140−age ) xbody weight∈kg72x patient creatnine

(multiply by 0.85 for women).

2) MDRD formula (Modification of diet in renal disease study)

Estimated GFR (ml/mt per 1.73 m2).

= 1.86 x (pl creatinine) -1.154 x (age)-0.203

Multiply by 0.742 for women

Multiply by 1.21 for African Amercians.

AGE, SEX, RACE DIFFERENCES :

AGE: In young adults, the normal GFR is approximately 120 to 130 mL

/minute / 1.73 m2 and declines with age.6 A decreased GFR in an elderly

patient appears to be an independent predictor of adverse outcomes such as

mortality and cardiovascular disease7,8 . Because of the age-related decline in

GFR, the prevalence of chronic kidney disease increases with age;

approximately 17 percent of persons older than 60 years have an estimated

GFR of less than 60 mL / minute /1.73 m2.

GENDER

Male gender has been recognized as an important factor in the

development of CKD9. Gender-based genetic variability has been linked to

5

differences in BP in both black10 and white individuals11. Males may be more

susceptible to CKD, which would explain the higher proportion in renal

replacement therapy programmes. In contrast to testosterone, l2,13 estrogens

may attenuate CKD progression by lowering the cardiovascular stress

response to adrenergic stimuli14.

Chronic kidney disease is a national public health problem be set by

inequities in incidence, prevalence, and complications across race/ethnicity,

and socioeconomic status.

SOCIOECONOMIC STATUS

In U.S, geographic analyses have revealed community-level poverty

was strongly associated with higher ESRD incidence but was a more powerful

predictor for black than for white individuals. 15 Racially divided communities

may share low-income status but often differ in wealth, community assets,

exposure to heavy metals or excess ambient air particulate matter, and other

variables that may influence CKD-related outcomes. 16

RACE

Racial factors also have a role in the susceptibility to CKD as shown

by high prevalence of CKD related to hypertension, diabetes, or both, among

Africans and native Americans in USA as well as Afro-Caribbean and Asian

individuals in UK.17 In U.S, ESRD rates in minorities ranged from 1.5 to 4

times those of age-adjusted counterparts, despite similar rates for the early

stages of CKD.18

6

THE INCIDENCE AND PREVALENCE

Chronic renal insufficiency is a major public health problem. Over the

years the number of patients with end stage renal disease has steadily

increased. In the United States the rate of increase has been reported as 6-7%

per year. In USA more than 80000 patients were supposed to have developed

end stage renal disease in 2008 19 and more than 11% of US population had

renal dysfunction (serum creatinine >1.5mg/dl) 20.

In the year 2008, approximately 205000 and 240000 patients with

ESRD were currently maintained on chronic dialysis in Japan and the United

States respectively21.

The burden to the exchequer is also quite high. The current cost for

ESRD in Japan and the United States (including about 90000 transplant

recipients in the United States) amounts to approximately US $ 10 and 15

billion, respectively21.

A prospective study in the United Kingdom, there were approximately

600 patients per million population (p.m.p.) with established renal failure not

requiring renal replacement treatment and an annual incidence of end stage

renal failure needing dialysis of 78 p.m.p39.

In other countries the incidence varies from as low as 4 p.m.p. in

Bolivia22 to as high as 254 p.m.p. in Puerto Rico 23. Barsoum reported an

incidence of 200 p.m.p in the Egyptian population 24.

In India studies have shown that upto 0.8% of the population may

suffer from chronic kidney disease thereby putting the number at about 8

million of the 1 billion population2.

7

In India where the average per capita income is Rs 12,989/- per annum

and with 36% of the population below the poverty line, ours is a country,

which cannot afford to treat end stage renal disease.

AETIOLOGY OF CHRONIC KIDNEY DISEASE :

There are many causes of chronic renal failure for most renal diseases

can eventually lead to a significant reduction in function.

Not only has there been a dramatic increase in incidence of ESRD but

also a relative shift in etiologies. Diabetic and hypertensive nephropathies are

more frequent when compared to glomerulonephritis 25.

The causes of end stage renal failure in the elderly differ substantially

from those in younger populations. The most common disorders leading to

renal failure at this age are nephrosclerosis, diabetes, and obstructive

uropathy although in as many as one-third it proves impossible to

identify any specific cause26.

The influence of age on causes of chronic renal failure is illustrated by

the higher prevalence of obstructive uropathy and reno-vascular disease

(ischaemic renal disease) in the elderly. So also is myeloma and

amyloidosis27.

In women there is a higher prevalence of reflux and analgesic

nephropathies, there is evidence of a faster rate of deterioration in male

patients with polycystic disease and some forms of glomerulonephritis, which

may explain the higher number of male patients treated by renal replacement

therapy27.

8

Traditionally, hypertensive, and diabetic patients comprise the largest

risk group for the development and progression of CRI.

RENAL CAUSES4

Glomerulonephritides

These manifest as haematuria, signs of a nephrotic syndrome

(tiredness, weight gain, oedema, susceptibility to infection, hyperlipidaemia),

and/or hypertension. With more frequent, regular health screening, one of the

most common presentations of chronic glomerulonephritis (e.g. IgA

nephropathy) is the detection of dipstix proteinuria (and/or haematuria),

hypertension and/or elevated serum creatinine in an asymptomatic patient.

Reflux nephropathy

Usually diagnosed in childhood during investigation of urinary

infection or screening in families, it may, however, escape discovery until

adult life when it is detected during investigation of urinary infection,

especially in pregnancy, hypertension, or renal failure. Though often silent,

there may be a history of recurrent episodes of flank pain, dysuria, fever, and

rigors. CKD in adult life peaks in the twenties and thirties and is uncommon

after the age of 50.

Secondary chronic pyelonephritis

This is the etiology in patients with CKD and a history of stone

disease, obstruction, or neuropathic bladder.

9

Medication related

Both over the counter as well as prescribed and recreational drugs are

implicated in this category. Chinese herb nephropathy (caused by Aristolochia

fangchi) is an example where fibrosis and tubulointerstitial changes persist

for months or years after discontinuation of the toxin though slow recovery

may occur on stopping. Prolonged consumption of non-steroidal anti-

inflammatory drugs (NSAlDs) and selective COX-2 agents has also been

implicated in the etiology of CKD (analgesic nephropathy). These drugs also

cause a reduction in GFR in patients with glomerulonephritis, due to

inhibition of vasodilatory prostaglandins, acute interstitial nephritis, nephrotic

syndrome or papillary necrosis. Angiotensin-converting enzyme (ACE)

inhibitors and/or Angiotensin II Receptor Blockers may cause renal

insufficiency in patients with bilateral renal artery stenosis or renal artery

stenosis in a single kidney due to renal hypoperfusion.

Hereditary nephritis

Autosomal Dominant Polycystic Kidney Disease (APKD) is the most

frequent cause of CKD in hereditary nephritis. Renal failure usually occurs in

the third to fifth decade; family history is positive in ~ 75% cases. Similarly,

a positive family history is usual in the rarer types of renal cystic disease such

as tuberous sclerosis and medullary cystic disease. Alport's syndrome is

another important hereditary nephritis characterized by progressive nephritis

with haematuria and sensori-neural hearing loss.

10

Infections

Renal tuberculosis is a rare cause of CKD. Classically, the presentation

is of dysuria, fever and sterile pyuria and is confirmed by urine culture and

renal imaging (calcified renal substance). Interstitial renal tuberculosis

causing renal failure with small kidneys on imaging and without the tell-tale

renal calcification is diagnosed by renal biopsy or inferred from evidence of

tuberculosis in other systems. Another infection associated with CKD 5 that

shows a geographic variation is schistosomiasis which is an important cause

in Egypt.

Substance abuse

Heroin-associated nephropathy (was an important cause of CKD 5 in

New York)28

SYSTEMIC DISEASES

Diabetes mellitus

Diabetes mellitus is the most frequent cause of renal involvement in a

systemic disease. Renal involvement occurs as frequently in type II as in type

I diabetes. The increasing prevalence of CKD in the developed world in

particular is predominantly accounted for by type II diabetic nephropathy 29.

Hence, the need for good control of blood sugars to prevent microalbuminuria

and therafter ACE inhibitors and/or ARBs to retard progression.

Hypertension

Long-standing 'benign' hypertension is also an important cause

of CKD, particularly in the elderly age group, but is difficult to differentiate

11

from occult renal diseases with secondary hypertension except by renal

biopsy30.

Systemic Lupus Erythematosus (SLE)

A diagnosis of SLE may be initially suspected clinically and then a

renal biopsy is done to assess the severity of renal illness or else it is

diagnosed when a renal biopsy is performed in any patient with proteinuria or

abnormal urinary sediment. Therefore most patients should have one at the

time of their initial assessment for renal insufficiency 30.

Amyloidosis

Secondary amyloidosis is suspected when CKD complicates long-

standing inflammatory diseases (like severe rheumatoid arthritis) or chronic

infections (such as destructive lung tuberculosis). It presents as a nephrotic

syndrome. Primary amyloidosis occurs due to the proliferation of a single

clone of plasma cells in middle and old age presenting with renal

insufficiency and proteinuria. In patients with plasma cell dyscrasias, renal

failure may also result from myeloma cast nephropathy, light chain deposition

disease or hyperviscosity syndrome30.

Systemic vasculitis and anti-glomerular basement membrane disease:

Systemic vasculitis and Anti-glomerular basement membrane disease

usually present as rapidly progressive renal failure. A history of haemoptysis

and dyspnoea, together with rapidly deteriorating renal function and an active

urine sediment, suggest antiglomerular basement membrane disease

(Goodpasture's syndrome) but can also occur in systemic vasculitis. Other

significant symptoms are of persistent sinusitis with dyspnoea, cough, and

12

haemoptysis (Wegener's disease) or only systemic symptoms (microscopic

polyangitis).

Thrombotic microangiopathy

This may occur due to haemolytic uraemic syndrome,

thrombotic thrombocytopenic purpura or anti phospholipids antibody

syndrome.

Occupational renal diseases

Occupational renal diseases causing CKD is an extremely rare entity

with the exception of lead toxicity. Theses patients have hyperuricaemia,

hypertension and small kidneys. The diagnosis is best made by demonstrating

an increase in urinary lead excretion following an infusion of EDTA. More

recently, long-term occupational or environmental exposure to relatively low

levels of cadmium has been shown to cause CKD31.

POSTRENAL CAUSES

Prostatic hypertrophy

This presents with obstruction of the lower urinary tract is common in

elderly males and is usually symptomatic. However, 40 per cent of men over

the age of 65 have some of the symptoms of hesitancy, slow and forked

stream, urgency with or without urge incontinence, frequency, intermittency,

nocturia, and terminal dribbling32. Pressure-flow measurements have shown

that two-thirds of these patients have some degree of outflow obstruction and

are at risk of urinary retention33. A useful clinical clue to serious outflow

obstruction is palpation of a distended bladder after micturition (confirmed

more reliably by ultrasonography before and after micturition).

13

Other causes of obstruction are retroperitoneal fibrosis, sloughed

papillae and renal calculi inducing hydronephrosis and a deterioration of

renal function.

14

CLASSIFICATION OF CHRONIC KIDNEY DISEASE BY

PATHOLOGY, AETIOLOGY AND PREVALENCE IN PATIENTS WITH

END-STAGE RENAL DISEASE AS PER KIDOQI4

Pathology Aetiology (examples*)

Prevalence among

patient with ESRD**

Diabetic glomerulosclerosis Diabetes MellitusType 1Type 2

33%

Glomerular Diseases (Primary or Secondary) Proliferative

glomerulonephritis Mesangial proliferative

glomerulonephritis Membranoprliferative

glomerulonephritis Focal proliferative

glomerulonephritis Diffuse proliferative

glomerulonephritis Crescentic

glomerulonephritis

Systemic lupus erythematosis, vasculitis, bacterial endocarditis, chronic hepatitis B or C, HIV infection

19%

Nononflammatory glomerular diseases Minimal change disease Focal glomerular sclerosis Membranous nephropathy Fibrillary glomerular

diseases Hereditary nephritis

(Alport's)

Hodgkin's disease HIV infection, 19%heroin toxicity Drug toxicity, solid tumors Amyloidsis, light chain disease

Vascular disease Diseases of large-size

vessels Diseases of medium-size

vessels –Nephrosclerosis Diseases of small vessels –

Microangiopathy

Renal artery stenosis Hypertension

Sickle cell disease, hemolytic uraemic syndrome (including cyclosporin or tacrolimus toxicity)

21%

Tubulointerstitial diseases 4%

15

Tubulointerstitial nephritis

Pyelonephritis

Analgesic nephropathy

Allergic interstitial nephritis

Granulomatous interstitial nephritis

Autoimmune interstitial nephritis

Infection, stones

NSAID

Antibiotics

Sarcoidosis

Uveitis

Noninflammatory tubulointerstitial diseases

Reflux nephropathy Obstructive nephropathy Myeloma kidney

Vesico-ureteral reflux

Malignancy, prostatism, stones

Multiple myeloma

4%

Cystic diseases

Polycystic kidney disease Tuberous sclerosis Von hippel lindau Medullary cystic disease

Autosomal dominant or recessive 6%

Diseases in the transplant

Chronic rejection Drug toxicity Recurrent disease Transplant glomerulopathy

Cyclosporine or tacrolimus

Glomerular diseases

Not considered

16

RISK FACTORS FOR CHRONIC KIDNEY DISEASE AND ITS

OUTCOMES4

Type Definition Examples

Susceptibility

factors

Factors that increase

susceptibility to kidney

damage

Older age, family history of

chronic kidney disease,

reduction in kidney mass, low

birth weight, racial or ethnic

minority status, low income or

educational level

Initiation

factors

Factors that directly

initiate kidney damage

Diabetes mellitus, high blood

pressure, autoimmune diseases,

systemic infections, urinary

tract infections, urinary stones,

obstruction of lower urinary

tract, drug toxicity

Progression

factors

Factors that cause

worsening kidney damage

and faster decline in

kidney function after

kidney damage has started

Higher level of proteinuria,

higher blood pressure level,

poor glycemic control in

diabetes, smoking

End-stage

factors

Factors that increase

morbidity and mortality in

kidney failure

Infection, cardiovascular

factors, anemia, low serum

albumin level, late referral for

dialysis

17

SPECIFIC DIAGNOSIS

A history of nephritic syndrome suggests primarily previous

glomerular disease as a cause of the CRF/ Recurrent gross hematuria may

accompany IgA nephropathy or membranoproliferative glomerulonephritis.

A careful personal and family history for hypertension and diabetes

mellitus should be obtained, including information on any family members

in whom ESRD developed. It now appears that some families have a genetic

predisposition not only for essential hypertension and diabetes mellitus but

also for the development of renal disease secondary to these systemic

diseases. A history of recurrent renal stones or obstructive uropathy,

including prostatism, or excessive mixed analgesic intake may suggest

primarily tubulointerstitial disease. The family history is also very helpful in

the diagnosis of autosomal dominant polycystic kidney disease - although in

about 30% a spontaneous mutation occurs - familial glomerulonephritis

(Alport's syndrome), IgA nephropathy, and medullary cystic kidney disease.

On physical examination, signs of hypertensive (left ventricular

hypertrophy and hypertensive retinopathy) or diabetic disease (peripheral

neuropathy, diabetic retinopathy) are important. Knobby, bilaterally enlarged

kidneys support a diagnosis of polycystic kidney disease and a palpable

bladder or large prostate suggests obstructive uropathy and is an indication

for measurement of residual urinary volume after voiding. Gouty tophi and

a history of gout may be relevant. Signs and symptoms of polyarteritis

nodosa, systemic lupus erythematosus, Wegener's granulomatosis,

scleroderma and essential mixed cryglobulinemia should be sought because

these systemic disease often involve the kidney. The findings of rheumatoid

18

arthritis are important because this disease is now the most common cause of

systemic amyloidosis, which often involves the kidneys. Hepatosplenomegaly

and macroglossia also suggest renal amyloidosis.

LABORATORY INVESTIGATIONS

After history and clinical examination, the relevant investigations

(urine, blood, radiology and histology) are to be done to confirm the

diagnosis.

Urine

Urinalysis and microscopy

Dipstick examination of a fresh mid-stream urine sample is useful to

assess the urinary pH and screen for leucocyturia, proteinuria, haematuria,

and glucosuria. The pH is usually low in CKD, unless the patient is on a very

low protein diet. If the urine contains non-albumin proteinuria, then the

dipstick test will be negative with the 24-hour quantification showing

significant proteinuria.

Microscopy of the urine sediment may reveal erythrocytes

(dysmorphic if glomerular in origin), leucocytes and casts. Erythrocyte

casts are seen in glomerulonephritis (IgA, postinfectious, and SLE) and in

cases of vasculitis. Leukocyte casts identify pyuria as coming from the kidney

and are found in stone disease, tuberculosis, analgesic nephropathy and other

causes of chronic interstitial nephritis.

Quantitation of proteinuria (24-hours)

Quantitation of proteinuria (24-hours) is used to measure proteinuria.

Proteinuria is almost universal in CKD with the proteinuria in the nephrotic

19

range in conditions like diabetic nephropathy. The accuracy of the collection

is checked by quantitating total urinary creatinine, which is fairly constant

(range 10-14 mmol/day in females and 12-18 mmol/day in males). The degree

of proteinuria can be also be "measured" by the spot urine protein/creatinine

ratio and a good correlation has been shown between the two measures 34,

although the accuracy decreases at extremes of creatinine excretion (e.g.

muscular men who have high and cachextic patients who and low urinary

creatinine concentrations, respectively).

Blood

Hematology

A full hemogram is important to establish the type of anaemia in a

patient with CKD. A Coomb's test is done if clinically indicated to exclude

autoantibody-induced haemolysis (as can occur in SLE). A peripheral blood

smear may show microangiopathic haemolytic anaemia (fragmented and

helmet-shaped erythrocytes and burr cells). If this occurs in combination with

thrombocytopenia, it is suggestive of the haemolytic uraemic syndrome or

thrombotic thrombocytopenic purpura.

Biochemistry

Serum creatinine concentration provides only a rough approximation of

GFR as the amount excreted increases with a decline in GFR 35.

The electrolyte profile shows the presence of hyperkalemia and severe

metabolic acidosis. Blood sugar estimation and liver function tests provide

information about underlying diseases such as diabetes mellitus and liver

failure.

20

Serology

Serological tests can give additional support in the assessment of a

diagnosis and underlying disease activity. Serum total haemolytic complement

and C3 can be decreased in mesangiocapillary glomerulonephritis,

postinfectious glomerulonephritis (including endocarditis), cryoglobulinaemia

and lupus nephritis. Elevated titres of serum anti-nuclear antibody and anti-

double-stranded DNA support the diagnosis of lupus. In a patient with

rapidly progressive renal failure with an active urine sediment, antiglomerular

basement membrane antibodies confirm a diagnosis of Goodpasture's disease

while Anti-Neutrophil Cytoplasmic Antibodies support a diagnosis of

systemic vasculitis (Anti-proteinase 3 - specific for Wegener's granulomatosis

or Anti-myeloperoxidase - associated with microscopic polyangitis).

Virology

Patients with CKD are commonly tested for antibodies against Human

Imunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) and Hepatitis

B surface antigen (HBsAg). HBsAg is associated with membranous

glomerulopathy, IgA nephropathy and mixed cryoglobulinaemia. HCV

infection is associated with type 1 membranoproliferative glomerulonephritis

and cryoglobulinaemia. About 95 per cent of patients with mixed essential

cryoglobulinaemia have evidence of HCV infection (by testing for anti-

HCV antibodies and HCV RNA).

Knowing the virology status is also important in vaccinating against

Hepatitis B virus to protect against infection from dialysis and blood

transfusions.

21

Radiological investigations

Renal ultrasonography is valuable in assessment of a patient of CKD.

The renal size, renal cortical thickness and echogenicity can be determined.

The presence of cysts and hydronephrosis can be demonstrated. If calculi are

suspected, plain x-ray of the urinary tract can be done followed by

intravenous urography (if renal function is normal) or non-contrast spiral

computerized tomography (CT). CT with intravenous contrast and

arteriography (or magnetic resonance imaging with angiography) is required

for diagnosis of classical polyarteritis nodosa and renovascular disease.

However, angiogaphy remains the 'gold standard' for diagnosing

renovascular disease.

Role of biopsy

In places where routine health checks are common place or if the

patient has presents early in the course of the illness, a renal biopsy is

mandatory (in most) to establish a diagnosis, to assess the extent of damage

and to plan therapy. In others, it may have been deemed unnecessary because

the diagnosis was established on clinical grounds, for example, in diabetes. If

the kidneys are small, the hazards of the procedure are increased and have to

be weighed against the small chance of finding a reversible cause.

STAGES OF KIDNEY DISEASE

Glomerular filtration rate (GFR) is accepted as the best index of

overall kidney function in health and disease. Several stages of CKD, defined

22

as structural abnormalities of the kidney that can lead to decreased GFR, are

recognized4,30.

1.KIDNEY DAMAGE(GFR, ≥90 mL/min/1.73 m2)

This stage is defined as the presence of structural or functional

abnormalities of the kidney, initially without decreased GFR, which over time

can lead to decreased GFR.

2.Mild reduction in GFR (60 to 89 mL/min/1.73 m2)/Early CRF

At this stage, patients usually have hypertension and may have

laboratory abnormalities indicative of dysfunction in other organ systems, but

most are asymptomatic. If the serum creatinine level is elevated, it may be no

more than borderline and of equivocal significance.

3.Moderate reduction in GFR (30 to 59 mL/min/1.73 m2)/Moderate CRF

This stage is characterized primarily by the presence of azotemia,

defined as the accumulation of the end products of nitrogen metabolism in the

blood and expressed by an elevation in serum creatinine and serum urea

nitrogen (SUN) concentrations. Erythropoietin production decreases, and

laboratory abnormalities reflecting dysfunction in other organ systems are

usually present. Although patients may have symptoms, they often remain

remarkably asymptomatic even though their kidney function may be reduced

by as much as 70%.

STAGES OF CKD WITH THE FREQUENCY OF COMPLICATIONS

Stage Descrption GFR (mL/min/

Symptoms or signs

23

1.73m2)

1Chronic kideny damage

with normal or increased GFR

≥90

Anaemia 4%

Hypertension 40%

5 year mortality 19%

2 Mild GFR loss 60-89

Anaemia 4%

Hypertension 40%

5 year mortality 19%

3 Moderate GFR loss 30-59

Anemia 7%

Hypertension 55%

5 year mortality 24%

4 Severe GFR loss 15-29

Hyperphosphatemia 20%

Anemia 69%

Hypertension >75%

3 year mortality 14%

5 Kidney failure ESRD <15

Hyperphosphatemia 50%

Anemia 69%

Hypertension >75%

3 year mortality 14%

4.Severe reduction in GFR (15 to 29mL/min/1.73 m 2)/Pre-ESRD

In this extremely tenuous stage of CKD, the worsening of azotemia,

anaemia, and other laboratory abnormalities reflect dysfunction in several

organ systems. However patients usually have mild symptoms.

5.Kidney failure (GFR, < 15 ml/min/1.73 m2 )/ ESRD

In most cases, this level of kidney function is accompanied by a

constellation of symptoms and laboratory abnormalities in several organ

24

systems, which are collectively referred to us uremia, initiation of kidney

replacement therapy (dialysis or transplantation) is typically required for

treatment of comorbid conditions or complications of decreased GFR, which

would otherwise increase the risk of morbidity and mortality.

PATHOPHYSIOLOGY OF CHRONIC RENAL FAILURE

Renal disease is often attributed to classic antibody-mediated or cell-

mediated immunologic renal injury. However, renal injury complicating

such common disorders as diabetes and hypertension has no apparent

immunologic basis. Therefore, the pathogenesis of injury in these conditions

must occur by way of nontraditional (nonimmune) pathways,

Several nonimmune mechanisms of renal injury have recently been

elucidated including alterations in circulating lipids, abnormal

systemic and internal hemodynamics and disordered regulation of

endogenous renal cell function36.

An important clinical observation in patients with nonimmunologic

renal disease is the invariable progression to ESRD once the baseline serum

creatinine is more than 1.5 to 2.0 mg/dL, even in the absence of the original

inciting event.

This observation has advanced the hypothesis that nephron loss

serves to promote further nephron loss, although the mechanisms responsible

for this inexorable course remain incompletely understood. It is thought that

adaptive changes occur in the remaining functional nephrons and promote

progressive renal scarring. Studies in rats show that experimental ablation of

renal mass promotes progressive loss of renal function, and the relative

25

reduction in total renal mass correlates with the rate of progressive renal

injury.

Adaptive changes associated with nephron ablation have been the

subject of intense investigation over the past decade. Among these

"adaptations," changes in intraglomerular hemodynamics have been

investigated most intensively37. Remnant nephrons undergo marked

sustained increase in single nephron plasma flow (hyperperfusion), single

nephron glomerular filtration rate (hyperfiltration), and glomerular hydraulic

pressure (glomerular hypertension) in response to ablation of renal mass.

Glomerular hypertension, characterized by increased glomerular

capillary hydrostatic pressure, appears to be of considerable importance. In

fact, agents that attenuate glomerular hydraulic pressure, such as

angiotensin-converting enzyme (ACE) inhibitors and protein-restricted diets,

can protect against progressive renal scarring. These observations form the

basis of studies evaluating the clinical effects of sustained use of ACE

inhibitors in patients with chronic renal failure.

While hemodynamic factors have been extensively studied, the specific

cellular and biochemical pathways that link altered glomerular

hemodynamics with progressive renal scarring are still poorly understood.

Moreover, recent studies (3-5) have suggested that a variety of perhaps

complementary mechanisms contribute to progressive renal scarring,

including proteinuria and alterations in levels of circulating lipids, hormones

and electrolytes. Collectively, these factors may contribute to progressive

renal injury by changing the function of various resident renal cells, such as

macrophages and mesangial cells38.

26

Two other important concepts in understanding progression of CRF

are the intact-nephron hypothesis and the trade-off hypothesis 39. The first

states that in general, adapted nephrons behave like normal nephrons.

Some of the failure to regulate sodium and water relates to increased solute

excretion per nephron-in effect, an osmotic diuresis of the remaining

nephrons that impairs sodium and water conservation, especially in states of

extracellular fluid volume depletion. Thus renal concentrating ability is lost,

as well as the ability of the remaining nephrons to adjust to low and high

intake of sodium, water, potassium and other dietary solutes because these

nephrons are functioning at maximum capacity even with normal intake of

these substances.

The "trade off hypothesis is to be considered together with the intact

nephron hypothesis, that is the concept that adaptations arising in chronic

renal failure may control one abnormality, but only in such a way as to

produce other changes characteristic of the uremic syndrome. The best

example is increase of parathormone secretion which is essential for

increased fractional excretion of phosphate; as the glomerular filtration rate

falls, plasma phosphate is lowered by decreased tubular reabsorption. The

consequence of normal plasma phosphate is then secondary

hyperparathyroidism and metastatic calcification 27,39.

PATHOPHYSIOLOGY OF UREMIA

Although the pathogenesis of the different uremic symptoms is not

completely understood, three major mechanisms are involved: diminished

27

excretion of electrolytes and water, reduced excretion of organic solutes and

decreased hormone production40.

Diminished excretion of electrolytes and water

An important function of the healthy kidney is to excrete the

electrolytes and water generated from dietary intake in order to maintain a

steady state in which intake and urinary excretion are roughly equal. The

conditions that cause loss of kidney function induce adaptive mechanisms

that attempt to preserve the homeostatic state of electrolyte and water

balance. If, for example, three quarters of nephrons have been lost, then each

remaining nephron must excrete four times the amount of electrolytes and

water to maintain the excretion at the same level of dietary intake 40.

However, all these compensatory mechanisms eventually fail, at

which stage the continual loss of function results in the kidney's inability to

maintain balance. At this point, patients are said to have end-stage renal

disease (ESRD). The number of functioning nephrons at this time is so small

that urinary excretion cannot achieve a level equal to intake. Clinical

manifestations include edema and hypertension (caused by sodium

retention), hyponatremia (resulting from free water retention)

hyperkalemia, metabolic acidosis, hyperuricemia and hyperphosphatemia.

Reduced excretion of organic solutes

The kidneys excrete a variety of organic solutes, the most commonly

measured ones being urea and creatinine. Unlike the excretion of electrolytes

and water, the excretion of urea and creatinine is not actively regulated. Thus

the plasma level of these solutes begins to rise with the initial decline in GFR

28

and increases progressively as kidney function deteriorates. Once the GFR

falls below 15 mL/min/1.73m2, patients begin to complain of many of the

manifestations. It is thought that many of these symptoms are mediated by an

accumulation of uremic toxins. However, it is not yet possible to identify the

toxins responsible for most uremic symptoms 41. Although it has been

postulated that urea may be an important toxin, symptoms of uremia correlate

only inconsistently with the level or urea.

Decreased hormone production

The kidneys normally produce several hormones, including

erythropoietin and calcitriol (1,25-dihydroxycholecalciferol), the active form

of vitamin D. the decreased production of these two hormones plays an

important role in the development of anaemia and bone disease, respectively.

29

CLINICAL ABNORMALITIES IN UREMIA42

Fluid and electrolyte disturbances

Volume expansion Hyponatremia Hyperkalemia Hyperphosphatemia

Neuromuscular disturbances

Fatigue Sleep disorders Headache Impaired

mentation Lethargy Asterixis Muscular

irritability Peripheral

neuropathy Restless legs

syndrome Myoclonus Seizures Coma Muscle cramps Myopathy

Dermatologic disturbances

Pallor Hyperpigmentation Pruritus Ecchymoses Nephrogenic

fibrosing dermopathy

Uremic frost Endocrine-metabolic disturbances

Secondary hyperparathyroidism

Adynamic bone Vitamin D-deficient

osteomalacia Carbohydrate resistance Hyperuricemia Hypertriglyceridemia Increased Lp(a) level Decreased high-density

lipoprotein level Protein-energy malnutrition Impaired growth and

development Infertility and sexual

dysfunction Amenorrhea

Gastrointestinal disturbances

Anorexia Nausea and vomiting Gastroenteritis Peptic ulcer Gastrointestinal

bleeding Idiopathic ascites Peritonitis

Cardiovascular and pulmonary disturbances

Arterial hypertension

Congestive heart failure or pulmonary edema

Pericarditis Hypertrophic or

dilated cardiomyopathy

Uremic lung Accelerated

atherosclerosis

Hematologic and immunologic disturbances

Anemia Lymphocytopenia Bleeding diathesis Increased

susceptibility to infection

Leukopenia Thrombocytopenia

30

CLINICAL MANIFESTATIONS OF CHRONIC KIDNEY DISEASE AND

UREMIA

Uremic syndrome consists of an array of complex symptoms and signs

that occur when advanced kidney failure prompts the malfunction of virtually

every organ system. However, the onset of uremia is slow and insidious,

beginning with rather nonspecific symptoms such as malaise, weakness,

insomnia and a general feeling of being unwell. Patients may lose their

appetite and complain of morning nausea and vomiting. Eventually, signs and

symptoms of multisystem failure are evident.

Electrolyte disturbances

CKD leads to a variety of disturbances in electrolytes and fluid

balance.

Sodium balance

Sodium balance remain virtually normal until very late in the course of

CKD, because the kidney can markedly increase the amount of sodium

excreted per nephron by reducing tubular sodium reabsorption. Although

sodium balance is maintained, the kidney loses its ability to adapt to large

variations in salt intake. Indeed, intake of large amounts of sodium can easily

overwhelm the excretory capacity of the failing kidney and result in fluid

retention, edema, and hypertension. Likewise, if diuretics are used

overzealously, the patient may become volume-depleted, with further

aggravation of the kidney failure. Wasting of sodium by the chronically

diseased kidney-so-called sodium-wasting nephropathies-is rare.

31

Clinically evident edema is uncommon until the GFR fails to less than

125 mL/min/1.73m2. However, edema can occur at higher GFR levels in

patients with glomerular disease and significant proteinuria (i.e., nephrotic

syndrome) and in those with heart failure. The cornerstone of treatment of

edema (and hypertension) is restriction of dietary sodium to a level

lower than that recommended for uncomplicated hypertension

(<100mEq/day; 2.3 g of sodium or 6 g of salt)43.

If sodium restriction is not effective or not achieved, diuretics should

be used44. Thiazide diuretics are usually ineffective if the serum creatinine

level is greater than 3 mg/dL (>265 micromole/L). Thus, more potent loop

diuretics are the agents of choice in patients with CKD. The initial aim is to

determine the threshold dose that is effective. Patients with advanced CKD

may require doses of furosemide (Lasix) as high as 400 mg per day. Lack of

response to high doses of loop diuretics often is due to noncompliance with

dietary sodium restriction. In such cases, a combination of a thiazide diuretic

or metolazone given before the loop diuretic may induce diuresis. For

maximum efficacy, the thiazide diuretic should be given 30 minutes before

the loop diuretic. Potassium-sparing diuretics (e.g. Sprionolactone

[Aldactone]) are contraindicated because of the risk of inducing

hyperkalemia.

Potassium balance

Potassium balance and plasma potassium level are also maintained

until very late in CKD, mainly because of an increase in renal excretion of

potassium per functioning nephron and an increase in potassium output in the

stool45. Hyperkalemia may develop earlier in the course of CKD in patients

32

with hyporeninemic hypoaldosteronism, a complication usually seen in

patients with diabetic nephropathy or tubulointerstitial disease.

Hyperkalemia may occur in association with dietary indiscretion

(e.g. Excessive consumption of chocolate, dried fruits, or bananas), use of

potassium-containing salt substitutes, increased catabolism (as with severe

intercurrent illness), metabolic acidosis. It may also be seen with the use of

potassium sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors,

and nonsterodial anti-inflammatory drugs (NSAIDs). Hypokalemia may

occasionally occur in patients with CKD, and it is sually due to

gastrointestinal losses or excessive use of the cation exchange resinsodium

polystyrene sulfonate46.

Mild hyperkalemia in the range of 5 to 5.5 mEq/L is a common feature

inpatients with CKD and requires dietary potassium restriction to 2 to 3 g (50

to 75 mEq) per day as well as discontinuation of any offending drug. Patients

with serum potassium concentration below 6 mEq/L usually respond to a

combination of a loop diuretic and low-potassium diet. Asymptomatic patients

with a serum potassium level above 6 to 6.5 mEq/L can be treated with

sodium polystyrene sulfonate, given orally or by colonic enema at a dose of

15 to 30 g every 6 hours with sorbitol.

More marked or symptomatic hyperkalemia, particularly in the

presence of electrocardiographic changes, is treated with combinations of

intravenous calcium gluconate (for urgent situations) and infusions of glucose

and insulin with or without bicarbonate. This therapy transiently drives

potassium into the cells until excess potassium can be removed from the body.

33

The latter can be achieved with sodium polystyrene sulfonate or diuretics at

high doses. In patients with kidney failure, dialysis may be required.

Water balance

The ability to concentrate or dilute urine is impaired inpatients with

CKD, which makes them more susceptible to hypernatremia and

hyponatremia. Hypernatremia may occur if water consumption is not

sufficient to replace fluid loss. More commonly, hyponatremia develops in

patients with CKD because they either drink water or are given hypotonic

fluids in excess of their ability to excrete water. To prevent hyponatermia,

most patients are permitted a modest fluid intake of 1.5 L per day. Also,

intravenous administration of hypotonic solutions should be avoided.

Metabolic acidosis

Most patients with CKD develop metabolic acidosis because of their

reduced ability to excrete the hydrogen ions generated mainly from the

metabolism of sulfur-containing amino acids 47,48. As a patient's condition

approaches ESRD, serum bicarbonate concentration often falls to between 12

and 20 mEq/L and the anion gap increases. A level below 10 mEq/L is

unusual, because buffering of the retained hydrogen ions by intracellular

buffers prevents a progressive fall in the concentration of serum bicarbonate.

Treatment of metabolic acidosis appears to be justified because chronic

acidemia has been associated with worsening of hyperparthyroid-induced

kidney bone disease and negative calcium balance, enhanced skeletal muscle

breakdown and catabolism, growth retardation in children, and probably faster

34

progression of GFR loss49. The goal is to maintain the serum bicarbonate level

above 20 mEq/L. Sodium bicarbonate in a dose equivalent to the daily

production of acid (0.5 to 1 mEq/kg body weight per day) is generally

recommended. Because of the concomitant sodium load, diuretic therapy may

be necessary to avoid edema and hypertension.

Sodium citrate is better tolerated than sodium bicarbonate because it

does not produce carbon dioxide gas in the stomach. However, sodium citrate

should not be used in patients taking aluminum-containing phosphate binders,

because it markedly increases aluminum absorption and increases the risk of

aluminum intoxication. Calcium carbonate, which is often used as a phosphate

binder, can help control acidemia as well.

Hypoalbuminemia and nutritional disorders

Hypoalbuminemia is highly prevalent in patients starting dialysis 50. Its

cause is multifactorial. CRI disrupts several components of protein

metabolism, increasing nitrogen and essential amino acid requirements 51.

Concomitant disease, such as hepatic impairment, nephrotic syndrome, and

volume overload, can contribute to hypoalbuminemia. Factors associated with

socioeconomic status and access to medical care have also been implicated 50.

Using data from the US Renal Data System maintained by the Health

Care Financing Administration, a recent study documented the high frequency

of hypoalbuminemia in patients entering dialysis. Of 74,232 patients who

began dialysis between April 1995 and June 1997 and for whom the relevant

data were available, 60% had serum albumin levels below the lower normal

limit for the testing laboratory and 37% had levels 3.0 g/dL. Multivariate

35

analysis showed that hypoalbuminemia was associated with female gender,

black or other non-Caucasian race, nonprivate or no insurance, and diabetes.

Stall et al52 found that, even once dialysis was initiated and an "adequate"

dialysis regimen was provided, many patients were not attaining acceptable

levels of nutrition as evidenced by continued hypoalbuminemia and changes

in body composition.

The impact of hypoalbuminemia and malnutrition on overall morbidity

and mortality rates has been well documented. The presence of malnutrition

and level of serum albumin are both predictors of mortality in patients who

begin either hemodialysis or peritoneal dialysis. 53,54 Three studies have found

hypoalbuminemia to be associated with higher rates of hospitalization in

ESRD patients.55,56,57 Finally, hypoalbuminemia in renal patients appears to be

a risk factor for development of pulmonary edema and infectious

complications55. To date, however, no trails have established that there is

effective treatment that either restores albumin levels to normal or reduces

any of the long-term risks of hypoalbuminemia in ESRD. Recent data suggest

that hypoalbuminemia may be a reflection of chronic inflammation rather than

nutrition per se. Clearly, better efforts are needed to assess the degree of

malnutrition and the presence of chronic inflammation during both the CRI

and ESRD periods so as to develop appropriate means of early intervention 58.

Gastrointestinal complications

Anorexia, nausea, and vomiting are common in advanced kidney

failure59. These symptoms are usually corrected by dialysis. Peptic ulcer

disease as well as atrophic gastritis are known complications.

Similarly, angiodysplasia of the gastrointestinal tract, in particular the

36

colon, is relatively common and can cause severe and protracted bleeding.

Gastrointestinal bleeding in renal failure is exacerbated by the

underlying bleeding diathesis when uremia is advanced.

However, malnutrition is a common problem in CKD patients, and

nutritional support coordinated with an experienced renal dietician is an

important component of management of these patients 60.

Neurological complications

The function of the central and peripheral nervous systems may be

disturbed in chronic renal failure. Cerebrovascular accidents of all types are

common in CKD. Encephalopathy is a feature of severe uremia and is

characterized by a decline in higher mental functions, causing confusion, loss

of memory, apathy, and irritability. These are often followed by motor

disturbances causing myoclonic jerks, flapping tremor (asterixis), and

seizures. Uraemic peripheral neuropathy is mixed motor and sensory in

nature. Its presence is an indication to start dialysis. It causes paraesthesiae,

including restlessness or burning feet. Autonomic nervous system dysfunction

has also been described in uraemic patients and may cause postural

hypotension and impotence61.

37

CARDIOVASCULAR COMPLICATIONS

Patients with kidney failure are at high risk of cardiovascular

mortality62. They experience a high rate of fatal and nonfatal cardiovascular

disease events prior to reaching kidney failure. 63,64 Patients in all stages of

CKD are therefore considered in the "highest risk group" for development of

cardiovascular disease and CKD is recognized as a cardiovascular risk

equivalent.65,66 CKD is a risk factor for cardiovascular disease and

cardiovascular disease may be a risk factor for CKD. Analysis of community-

based studies including Atherosclerosis Risk in Communities Study,

Cooperative Health Study, Framingham Heart Study, and the Framingham

Offspring Study, CKD defined as GFR of 15 to 60 ml/min/1.73 m 2, was an

independent predictor of a composite outcome of all-cause mortality as well

as fatal and nonfatal cardiovascular disease events 67. Several studies has

established urinary albumin excretion as an independent predictor of

cardiovascular outcomes68 in CKD patients.

Patients with CKD are much more likely to suffer from atherosclerosis

and heart failure, resulting in cardiovascular death, than to eventually require

renal replacement therapy. This is likely due in part to accelerated rates of

cardiovascular disease among those with CKD. In addition, patients with

CKD are more likely to present with atypical symptoms, which may delay

diagnosis and adversely affect outcomes. Traditional cardiovascular risk

factors, such as hypertension smoking history, diabetes mellitus, dyslipidemia

and older age, are highly prevalent in CKD populations. 69,70 Patients with

CKD are also more likely to have the metabolic syndrome, which could

contribute to the increase in cardiovascular risk. 71,72 Increased arterial

38

stiffness is noted in patients with CKD is also a possible risk factor .Some

risk factors are relatively unique to patients with moderate to severe CKD.

These include retention of uremic toxins, anemia, increased calcium intake,

abnormalities in bone mineral metabolism, and proteinuria.

The overall absolute risk of future adverse cardiovascular events is

somewhat lower with CKD patients than that observed in patients with a

history of prior heart disease, but without CKD. In general, the risk is

approximately 50 percent lower with CKD alone, although the risk increases

with increasing renal dysfunction and/or severity of proteinuria. All patients

with the same degree of renal dysfunction also do not have the same risk of

cardiovascular disease. Thus, in addition to the evaluation for the presence of

CKD, the proper assessment of overall cardiovascular risk requires an

adequate assessment for the presence and severity of the other major risk

factors for cardiovascular disease

ISCHEMIC HEART DISEASE

Ischemic heart disease most commonly results from atherosclerosis of

the coronary arteries. The processes that contribute to accelerate

atherosclerosis include a dyslipidemia characterized by decreased function of

lipoprotein lipase, reduced HDL-C, elevated TG, and elevated LDL-C. Both

uremia and dialysis therapy markedly enhance oxidant stress through the

production of proinflammatory complement fragments, cytokines, and

increased adhesion molecules in endothelial cells 74. Endothelial dysfunction

begets cardiac and arterial remodeling with resultant cardiovascular events.

Potentially important in the inflammatory cascade and ensuing cardiovascular

39

mortality among kidney patients are C-reactive protein (CRP) and asymmetric

dimethyl-arginine.

HEART FAILURE

About 40% of people starting dialysis therapy have a history of heart

failure symptoms, which is a risk factor for significant morbidity and

mortality in this group75. For those without heart failure symptoms at the

commencement of dialysis, 25% will develop it within 3½ years (7% per

year)76. Age (risk increased by 30% for every 10 years), female sex,

hypertension, diabetes, conditions of atherosclerosis (CAD, cerebrovascular

or peripheral vascular disease), pericarditis, and structural cardiac

abnormalities (left ventricular hypertrophy, clinical cardiomegaly) were all

associated with heart failure. Multiple studies of patients with class II and III

HF, in whom a low cardiac output state is not present, have shown decreased

survival in a graded fashion related to renal impairment.

Hematologic abnormalities

Progressively more severe normochromic, normocytic anemia develops

as the GFR & renal erythropoietin secretion decreases. In most of the patients,

the hematocrit reaches about 20-25% by the time that ESRD develops.

The pathogenesis of the anemia of chronic renal disease is related to:

To the etiology of the renal disease

To the failure of renal excreatory function

To the failure of renal endocrine function.

Failure of renal excreatory function leads to an increased demand for

red blood cells because of shortning of red blood cells life span, impaired

40

utilization of iron, decreased responsiveness to erythropoietin & increased

blood loss. Failure of renal endocrine function leads to a decreased

erytliropoitic response to these demands because of impaired production of

erythropoietin. A greater degree of anemic hypoxia is required to generate

the necessary amount of erythropoietin, and equilibrium between demand &

supply is first established at anemic levels 77.

Uremic coagulopathy is secondary to a defect in platelet function as

well as factor VIII function. It is characterize by a prolonged bleeding time

but usually normal clotting time. The platelet dysfunction responds to dialysis

and to infusion of desmopression. Epistaxis, menorragia, bruising & parpura

as well as gut bleeding may also occur.

Uremic patients should be regarded as immunocompromised and

infection is an important cause of death in chronic renal failure and dialysis

patients. The leukocyte count, but not polymorphonuclear function is

commonly normal with a normal differential, as are total immunoglobulin and

complement levels. Cellular immune function is depressed, however antibody

response to hepatitis B & influenza immunization, for eg., are less than in

normal subjects, but protection is still indicated & feasible.

Bone disease

Metabolism of calcium and phosphorus is abnormal in patients with

CKD and is associated with the development of bone disease. Phosphate

retention occurs as GFR declines. Both hyperphosphatemia and more

important, reduction in the active form of vitamin D (1,25-

dihydroxycholecalciferol) lead to hypocalcaemia. (The active form of vitamin

41

D is normally produced by the kidney and increases calcium absorption in the

intestine.) As attempts are made to normalize the serum calcium level,

secondary hyperparathyroidism can develop, causing significant bone damage

occur.78,79

The spectrum of bone disease, also known as renal osteodystrophy,

includes osteitis fibrosa, osteomalacia, and adynamic bone disease. The most

common form is osteitis fibrosa caused by secondary hyperparathyroidism.

Although initially asymptomatic, osteitis fibrosa can produce bone pain,

pathologic fractures, and metastatic calcifications in its more advanced stages.

The complications associated with hyperparathyroidism can be prevented or

minimized by controlling hyperphosphatemia and by lowering the parathyroid

hormone level80.

Pathogenic factors in renal osteodystrophy81

Hypocalcaemia

Phosphorus retention

Impaired calcaemic response to PTH

Altered degradation of PTH by the kidney

Disordered regulation of PTH and calcitonin

Altered Vitamin D metabolism

Dyslipidemia

Abnormalities of lipid metabolism appear to occur early in the course

of kidney failure and are another treatable complication of CRI. Lipoprotein

lipase activity falls in patients with glomerular filtration rates (GFRs) of 50

mL/min or less, and triglyceride values rise with GFRs in the range of 15

42

to30mL/min.82,83 As kidney failure progresses, a generalized disorder of lipid

metabolism becomes apparent, irrespective of the underlying cause of the

kidney disease. Abnormalities include hypercholesterolemia, elevated ratio of

low-to high-density lipoproteins, elevation of lipoprotein(a), and elevated

chylomicron remnant level84.

Hyperlipidemia is among the many contributors to atherosclerosis in

patients with ESRD. Treatment during the CRI stage may help prevent such

complications, although specific data on the benefits of such intervention are

not currently available. Standard regimens for the management of

dyslipidemia can be employed in CRI, with appropriate modification of drug

dosages based on the level of kidney function.

Thyroid disease in ESRD

ESRD is a non-thyroidal illness, which affects the thyroid hormone

metabolism. Multiple other comorbid conditions that affect the thyroid

hormone metabolism (diabetes mellitus, malnutrition, frequent infections) are

also common in ESRD. Certain thyroid diseases occur in increasing frequency

in these patients and they include goiter, thyroid nodules and thyroid cancer.

Incidence of hyperthyroidism is the same as in the general population

but primary hypothyroidism occurs more frequently. Incidence in literature

varies from 0% in Austria to 9.5% in Michigan, where the incidence of

primary hypothyroidism in the general population is 0.6-1.1%.

Chronic renal failure and the skin

The cutaneous manifestations of chronic renal failure include pruritus,

dry flaky skin, as well as darkening and yellow pigmentation of the skin,

43

made more obvious by the pallor of anaemia. Bullous lesions in sun-exposed

areas (pseudoporphyria cutanea) are occasionally seen in patients on dialysis.

Proximal skin necrosis (thighs and trunk) is a consequence of ischemia

resulting from calcification and occlusion of arterioles. Trophic nail changes

are frequent, including brown nail arcs (half-and-half nails).

Most common causes of death among patients with CKD73

Heart failure 31.2%

Myocardial infarction 15.6%

Sepsis 11.3%

Withdrawal from dialysis 5.2%

Strokes 6.4%

Malignant neoplasm 3.8%

Other 26.5%

TREATMENT OF CKD

Attenuation of progression

Once a diagnosis of CKD is made, there are certain medical measures

that can be undertaken to attenuate the progression. Blood pressure control

The importance of the control of blood pressure in patients with renal

disease cannot be overemphasised. Hypertension is common in patients with

CKD and the rate of decline in renal function increases with increasing blood

pressure185,86 and also reduction in blood pressure attenuates the deterioration

of renal function (first convincing demonstration was in diabetic

nephropathy).87,88

44

Two important factors contribute to the rise in blood pressure of

patients with CKD. First, most renal diseases are associated with sodium

retention, which results in an increase in extracellular fluid volume and an

increase in peripheral vascular resistance. Second, activation of the renin-

angiotensin-aldosterone system results in increased circulating angiotensin II,

which in addition to being a potent vasoconstrictor, also enhances sodium

retention by the kidney. Hence, the two initial steps in the treatment of

hypertension in CKD should consist of a reduction in sodium intake, with or

without the use of diuretics, and treatment with agents that block the effects

of angiotensin II, that is, ACE inhibitors or ARBs. Other antihypertensives

that are commonly prescribed are calcium channel blockers, beta adrenergic

antagonists, a-adrenoceptor blockers and diuretics.

The target blood pressure in patients with CKD is 120/70 mmHg

especially with proteinuria of over 1 g/day. 89,90 Regular follow-up is essential

as it has been demonstrated that patient compliance, efficacy of

antihypertensive treatment, and retardation of renal failure are clearly related

to the number of outpatient visits91.

Dietary recommendations

Sodium restriction

In patients with CKD, the ability to excrete sodium usually is limited.

Thus, a sodium-restricted diet of 6 g/day is a useful initial step in the

treatment of hypertension. Determining a 24 h urinary sodium excretion can

check compliance with the sodium restricted diet.

45

Sodium depletion may occur in patients with CKD due to

tubulointerstitial disease such as pyelonephritis, interstitial nephritis or

hydronephrosis. In these, sodium has to be monitored closely and often

restriction is not advisable.

Protein restriction

The initial observations in the rat model with reduced renal mass had

shown that protein restriction attenuated the development and progression of

renal failure. Thereafter, some retrospective studies and several (but not all)

randomized prospective studies confirmed that a low protein diet might have

the same effect in humans. In the initial analysis of the Modification of Diet

in Renal Disease (MDRD) Study,4 (which was the largest trial to date on the

effect of protein restriction on CKD in man) the effects of dietary protein

restriction and blood-pressure control on the progression of CKD, the

investigators reported a small beneficial effect of the low-protein diets on the

course of renal function after an average follow-up period of 2.2 years. When

the initial 4 months of low-protein diet were excluded from the analysis, the

decline in GFR of protein-restricted patients was attenuated 92. This secondary

analysis of the MDRD trial patients also revealed a high protein intake was

associated with a more rapid decline in GFR. It was calculated that each 0.2

g/kg body weight reduction in protein intake resulted in a 29 percent

reduction in the rate of decline in GFR.

The effect of protein restriction on the progression of CKD has been

analysed in two meta-analyses.93,94

46

Altogether, it can be concluded from these studies that protein

restriction causes a modest reduction in the progression of CKD in man. It

was concluded that dietary protein restriction significantly reduced the risk

for renal insufficiency or death with a relative risk of 0.67 (95% confidence

interval 0.50-0.89) in patients with non-diabetic renal failure and 0.56 (95%

confidence interval 0.40-0.77) in patients with diabetic nephropathy.

Currently, mild protein restriction to 0.6 to 0.8 grams per kg is recommended.

Calorie intake is kept at 30 kcal/kg body weight/day or more.

Dietary protein restriction also helps to alleviate the symptoms of

uraemia in those not being considered for dialysis in addition to attempting to

slow the progression of renal insufficiency without negatively jeopardizing

nitrogen balance. Dietary compliance is monitored most readily by measuring

the serum urea : creatinine ratio (which should be reduced by treatment) and

the 24-h urinary urea excretion. For example, a 40 g protein diet should

produce about 150 mmol of urea.

Fluid balance

In CKD, the regulatory capacity of the kidney is progressively reduced.

Both excretion and conservation of electrolytes and water are impaired; when

sudden loads of potassium, acid, or fluid has to be handled the limitations of

renal functional reserve become apparent and signs of decompensation may

occur. Consequently, water and electrolyte intakes must be adapted to renal

excretory capacity.

In the subset of patients who are fluid overloaded, both sodium and

water have to be restricted. On the other hand, in patients with conditions that

47

predominantly affect the renal medulla (for example, interstitial nephritis and

pyelonephritis), defective urinary concentrating ability is particularly

common and dehydration occurs easily in patients with inadequate fluid

intake, due to persistent diuresis despite fluid deprivation. Several

mechanisms are responsible for the inability to excrete concentrated urine,

including the increased solute load in remnant nephrons resulting in an

osmotic diuresis, alteration of medullary interstitial solute concentrations as a

result of the damaged countercurrent exchange system and impaired

medullary blood flow. In addition, impaired sensitivity to antidiuretic

hormone causes decreased outward water transport in the distal nephron

segments. As a result of decreased concentrating capacity, urine osmolality is

roughly that of plasma, approximately 300 mOsm/kg H 20, in patients with

CKD. If the obligatory osmolar production in an adult is around 600 mOsm/kg

H20, daily urine output will be roughly 2 1 per day. Fluid intake should

therefore be approximately 2-3 1/day in order to ensure adequate urine flow

rates and to prevent dehydration. In some patients who are 'salt losers', fluid

requirements may be even greater.

Potassium

Patients with CKD are usually able to maintain serum potassium within

normal imits until oliguria occurs or GFR is less than 5 ml/min. Preservation

of normokalaemia results from an adaptive increase in potassium excretion by

remnant nephrons and increased bowel loss. However, hyperkalaemia may be

an early feature of renal failure in patients with hyperchloraemic metabolic

acidosis and hyporeninaemic lypoaldosteronism, which occur particularly in

patients with chronic tubulointerstitial nephritis and diabetic nephropathy.

48

Hyperkalaemia also complicates an acute potassium oad (e.g. blood

transfusion, or medication, which interferes with potassium secretion, for

example, potassium sparing diuretics, ACE inhibitors, -blockers, and

NSAIDs) Foods containing high levels of potassium like nuts, chocolate,

fruits, wine and fruit juice and salt substitutes (containing potassium) are

particularly dangerous. Therefore a judicious restriction of potassium rich diet

and monitoring of serum potassium while on ACE inhibitors and ARBs is

warranted.

Other medications

Phosphate binders and calcitriol

Skeletal abnormalities occur early in renal failure, well before

symptoms develop.95 A variety of biochemical and radiological investigations

are available to assist n the diagnosis and monitoring of renal osteodystrophy

of which serum parathyroid lormone (PTH) remains the single most useful

biochemical test in predicting bone listology in an individual patient. 96

In early CKD, it would appear that adynamic bone disease is the

principal type of xme lesion with high turnover bone disease developing with

more advanced renal failure. As renal insufficiency progresses, higher levels

of PTH are necessary for normal bone remodeling. The cause of this 'skeletal

resistance' to PTH in uraemia is probably multifactorial. Inhibition of

osteoclastic bone resorption appears to be the central mechanism. Therefore a

plasma PTH of two to three times the normal value is usually required to

maintain normal bone turnover.

49

When the patient is seen in the early phases of CKD, the objective is to

maintain normal bone turnover by maintaining serum calcium, phosphate,

PTH and calcitriol and blood pH in the normal range.

The mainstay in preventing secondary hyperparathyroidism is strict

phosphorus control. Some dietary phosphate restriction is usually required

once GFR is less than 50 ml/min. Care must be taken in maintaining a

sufficient protein intake, however, and adequate nutrition must be maintained.

Dietary restriction alone is usually inadequate in controlling serum phosphate

once GFR is less than 25 ml/min. Phosphate binders are then added to reduce

phosphorus absorption from the intestine. Calcium carbonate i 500-2000mg

thrice daily) is effective and probably the most widely used phosphate binder.

It must be taken with food to give optimal phosphorus binding and to reduce

the risk of hypercalcaemia. If hyperphosphataemia persists despite

administration of calcium carbonate, excess dietary intake (e.g. dairy

products) should be excluded and alternative phosphorus binding agents

substituted. Another commonly used calcium containing binders is calcium

acetate. It is a more effective binder than calcium carbonate and is less ikely

to be associated with hypercalcaemia. The downside of using calcium

containing phosphate binders is the risk of a positive calcium balance which

in dialysis patients is associated with vascular calcification and a raised

calcium x phosphate product is associated with a higher relative risk of death.

In the face of hypercalcemia, other phosphate binders like sevelemar

hydrochloride and lanthanum carbonate may need to replace calcium based

products. Others still being evaluated include polynuclear iron preparations.

50

In some patients, aluminium-containing phosphate binders have to be

resorted to. If needed, they should be used only for a limited period of time

since aluminium is absorbed to a variable extent and can lead to aluminium

overload, manifesting as anaemia and aluminium-mediated bone disease.

In patients with lower stages of CKD, administration of l,25-(OH) 2 D3

(calcitriol) 0.25 µg/day causes a rise in serum calcium, a fall in serum

phosphorus and alkaline phosphatase, and retards the development of

histological bone abnormalities.97

Careful monitoring of serum calcium is required, since hypercalcaemia

may accelerate the decline in renal function. Though new vitamin D

metabolites are available such as 22-oxacalcitriol, paracalcitriol (19 nor-1,25

dihydroxy-vitamin D2), and doxercalciferol (1-hydroxy-vitamin D2), their

benefits over conventional calcitriol and alfacalcidol remain to be

established98. Bone biopsy is generally reserved for patients with unusual

biochemical and radiological evidence of bone disease.

Treatment of anemia

Anaemia is a predictable consequence of CKD and is directly related to

its severity. It frequently occurs early with one study reporting a prevalence

of 45% in patients with a serum creatinine 2 mg/dl99. Monitoring anaemia

is important to determine if it becomes disproportionate to the stage of CKD.

A haemoglobin of less than 6 g/dl is rarely due to CKD alone. Red cell

indices should be scrutinized to detect the onset of iron, folate or vitamin B12

deficiency. Functional iron deficiency is common and should be confirmed by

measurement of percentage of hypochromic red cells, serum iron, transferrin

51

and ferritin. As oral iron is often poorly tolerated, intravenous iron is now

frequently administered to predialysis patients. Occult gastrointestinal

bleeding is common in patients with advanced stages of CKD and is most

commonly due to superficial upper gastrointestinal lesions 100.

Recombinant human erythropoietin (rhEPO) is effective in treating

anaemia in adults and children with CKD both prior to and while on dialysis.

Benefits of correcting anaemia include increased quality of life, reduced

morbidity and improved survival. This may be related to reduction in left

ventricular mass and normalization of cardiac output with partial correction of

anaemia. There is also evidence to suggest that rhEPO therapy may retard the

progression of CKD and delay the onset of dialysis by as much as 6

months.101,102

Treatment of hyperlipidemia

Hyperlipidaemia is often present in patients with CKD 35. Nonetheless,

there are only a limited number of studies, usually with a small number of

patients, in which the effects of treatment of hyperlipidaemia has been

investigated. A meta-analysis by Freid et al showed clearly that treatment of

hyperlipidaemia ameliorates the progression of CKD. 103,104

Other recommendations

Obesity is clearly associated with hypertension, and reduction of body

weight should be recommended to obese patients. Increasing physical exercise

and reducing calorie intake may achieve this. In patients with advanced CKD,

caution must be exercised in severe calorie restriction because of the risk of

catabolism.

52

Alcohol abuse can also contribute to hypertension and may also

interfere with adherence to antihypertensive or other therapy. It is advisable

to limit alcohol intake to less than 21 units in men and 14 units in women.

In patients with CKD, it has been shown that cigarette smoking

enhances the rate of progression of disease.105,106 Thus, patients with CKD

should be strongly advised to quit smoking.

INDICATIONS FOR DIALYSIS:

ESTABLISHED INDICATIONS - There are a number of absolute

clinical indications to initiate maintenance dialysis . 107 These include :

Pericarditis.

Fluid overload or pulmonary edema refractory to diuretics

Accelerated hypertension poorly responsive to antihypertensive

medications

Progressive uremic encephalopathy or neuropathy, with signs such as

confusion, asterixis, myoclonus, wrist or foot drop, or in severe cases,

seizures.

A clinically significant bleeding diathesis attributable to uremia

Persistent nausea and vomiting

Plasma creatinine concentration above 12 mg / dL (1060 )Limol/L) or

blood urea nitrogen (BUN) greater than 100 mg/dL (36 mmol/L)

However, these indications are potentially life threatening and the

patient is generally known to have advanced chronic renal failure. As a result,

53

most nephrologists agree that delaying initiation of dialysis until one or more

of these complications is present may put the patient at unnecessary jeopardy.

RELATIVE INDICATIONS - Since an important goal of dialysis is to

enhance the quality of life as well as prolong survival, it is therefore

important to consider less acute indications for dialysis. These relative

indications include anorexia progressing to nausea and vomiting, decreased

attentiveness and cognitive tasking, depression, severe anaemia unresponsive

to erythropoietin, persistent pruritus or the restless leg syndrome. 108

Unfortunately, the expression of these signs and symptoms is variable

in patients with slowly progressive renal disease. The following are some of

the factors that may contribute to this variability.

Some patients accommodate to these symptoms and downgrade their

sense of well-being as renal failure progresses.

Many of the medications given to patients with chronic renal failure

have side effects that mimic uremic symptoms. As examples, oral iron

therapy often leads to nausea and centrally acting antihypertensive

drugs can induce drowsiness independent of the degree of renal failure.

On the other hand, partial correction of anaemia by erythropoietin may

improve that patients sense of wellbeing without effecting the extent of

uremia.

These factors illustrate the need to identify more objective markers of

renal failure in order to lessen the subjective component of the decision to

initiate dialysis.

54

Peritoneal Dialysis (PD)

Chronic ambulatory PD (CAPD) and other PD modalities may provide

a less expensive means to treat patients with ESRD who require chronic

regular dialysis. There are certain advantages in PD over hemodialysis (HD),

but PD has not been widely used in Japan and other countries; infact PD has

been used in less than 5% of patients with ESRD. There are several medical

and non-medical reasons for the same. Some patients will be placed on PD

purely for medical reasons. However, when there is no particular reason to

choose either HD or PD, many patients will be placed on HD. One of the main

reasons is the fact that 70 to 80% of patients will not be able to be on a

chronic dialysis program more than 5 year as a result of loss of peritoneal

function. This is particularly true in Japan, where the majority of patients will

be maintained on HD longer than 10 years.

In India, CAPD is reserved as a last option for most patients of ESRD.

Patients not suitable for transplantation and who can afford peritoneal dialysis

are offered this modality of treatment.109

Complications of Chronic Dialysis

Although retarding the progression of chronic renal disease is crucial

to the treatment of ESRD, prevention and management of various

complications of chronic dialysis patients are also of critical importance in

maintaining the quality of life of these patients. Although there are many

complications that are particular to chronic dialysis patients, including

vascular disease, peritonitis (for PD), bone disease, dialysis amyloidosis, and

malnutrition, a recent proposal of the possible role of carbonyl stress as an

55

underlying biochemical mechanism for some of these complications is of

particular importance. This carbonyl stress hypothesis suggests that through

continuous oxidative as well as nonoxidative stresses, several carbonyl

compounds will be generated in quantities so massive (compared with any

other medical condition, including diabetes) that extraordinary amounts of

glycation end products will accumulate, thus modifying proteins throughout

the body. This is a new and attractive hypothesis with a solid scientific,

experimental, and clinical basis, and thus, it warrants further investigation

and development.

Renal transplantation is the best option available to patients with

ESRD. However, cultural and social factors have hampered the increase in

renal transplantation in certain parts of the world, including India and other

Asian countries. In fact, in Japan, most renal transplantation procedures have

been performed with donations from a living relative, but the number never

exceeded 100 per year despite having a large number of patients with ESRD 21.

A marked shortage of donor kidneys, the lack of good cadaver

program, and large scale poverty have led to trafficking of organs. It is

estimated that 50% to 50% of kidneys transplanted in India come from living

unrelated donors110.

The annual cost of renal replacement therapy (RRT) is more than 10

times the per capita gross national product (GNP) in most developing

countries. The high cost of RRT in the non-state funded infrastructure in the

developing countries poses a major challenge to proper treatment of patient

having end stage renal disease.

56

METHODOLOGY

Source of data :

Patients admitted in Chigateri General Hospital and Bapuji Hospital,

attached to J.J.M. Medical College, Davangere, between 2009 to 2011.

Method of collection of data :

A minimum fifty pateints both male and female with chronic renal

failure shall be included according to inclusion criteira set by National

Kidney Foundation. K/DOQ1.

Inclusion criteira :

Patients with serum creatinine above 2mg% with abnormal findings on

renal ultrasound : asymetric kidney size, small kidneys (less than 9cm)

or large polycystic kidneys.

Elevated serum creatinine with no improvement for more than 3

months.

Uremic symptoms over three monthys with elevated serum creatinine.

Exclusion criteria :

Patients below the age of 17 years were not included in this study.

A detailed history and thorough physical examination was carried out

in all patients. Data recorded in each patient included age, sex the underlying

primary renal disease, clinical and biochemical features of chronic renal

failure on a standard proforma. An aetiological diagnosis was made on each

patient even though it could not always be confirmed by histopathology.

57

Chronic Glomerulonephritis was diagnosed in patients with history of

oedema, hypertension and documented nephritic range of proteinuria.

Hypertensive nephropathy was diagnosed in patients with long history of

hypertension and other target organ damage. Diabetic Nephropathy was

diagnosed in patients with long history of diabetes, presence of diabetic

retinopathy and proteinuria more than 500mg in 24 hours. Chronic

Pyelonephritis was diagnosed on ultrasonogram when there is presence of

small kidneys with irregular borders.

Obstructive Uropathy, Autosomal dominant polycystic kidney disease

and Obstructive nephropathy were diagnosed by ultrasonogram.

Creatinine clearance to be calculated using Cockcroft-Gault formula:

Creatinine clearance=(140−age ) (weight∈kg )X (0.85 if female)

(72 )(s . creatinine∈mg /dl)

Statistical analysis of data was done using standard statistical

techniques.

58

RESULTS

Table 1 Age and Sex Incidence

Male Female TotalNumber of patients 34 16 50

Mean Age 50.9 yrs 46.1 yrs 49.3 yrsYoungest Patient 17 yrs 23 yrs -

Eldest Patient 80 yrs 70 yrs -Note : Male Female ratio : 2.12 : 1

Table 2 Aetiology of Chronic Renal failure

Aetiology No.of pateints PercentageChronic glomerulonephritis 12 24

Diabetic nephropathy 19 38Hypertensive nephropathy 14 28

Obstructive uropathy 3 6Polycystic disease of kidney 1 2

Chronic pyelonephritis 1 2Total 50 100

Graph -1 Etiology of Chronic Renal Failure

Chronic glomeru-

lonephritis

Diabetic nephropathy

Hypertensive nephropathy

Obstructive uropathy

Polycystic disease of

kidney

Chronic pyelonephritis

0

2

4

6

8

10

12

14

16

18

20

12

19

14

3

1 1

No.

of p

atien

ts

59

Fable 3: Haemoglobin levels in chronic renal failure

Haemoglobin (gm%) No.of pateints Percentage

<5 3 6

5-10 42 84

>10.1 5 10

Total 50 100

The above table reveals that 84% of the patients have their

haemoglobin level in the range of 5-10 gm%. Only 6% of the patients have its

value below 5mg%, but 10% of the patients exhibit that their haemoglobin

level more than 10 mg%.

Graph - 2 Haemoglobin Levels in Chronic Renal Failure

<5 5-10 >10.10

5

10

15

20

25

30

35

40

45

3

42

5

No.

of p

atei

nts

60

Table 4 Blood urea value in chronic renal failure

Blood urea (mg/dl) No.of pateints Percentage

<50 1 2

50-100 12 24

101-150 22 44

151-200 9 18

>200 6 12

Total 50 100

From the table it is clear that almost 44% have their blood urea level in

the range 101-250 mg/dl. Also one can see from the table that only 12% of

patients have their blood urea level more than 300 mg/dl and hardly 2 % had

the value below 50 mg/dl.

Graph - 3 Blood Uioa values in Chronic Renal Failure

<50 50-100 101-150 151-200 >2000

5

10

15

20

25

1

12

22

9

6

Blood urea level (mg/dl)

No.

of p

atei

nts

61

Table 5 : Serum Creatinine Values in Chronic Renal Failure

Serum creatinine (mg/dl) No.of pateints Percentage

2-5 18 36

5.1-12 31 62

>12.1 1 2

Total 50 100

The above table reveals that 62% of the patients have their Serum

Creatinine value in the range of 5-12 mg/dl. Only 2% of the patients have its

value greater than 12.1 mg/dl; but 36% Of the patients exhibit that their serum

Creatinine value in the range 2-5 mg/dl.

Graph-4 Serum Creatinine value in Chronic Renal Failure

2-5 5.1-12 >12.10

5

10

15

20

25

30

35

18

31

1

Serum creatinine level (mg/dl)

No.

of p

atei

nts

62

Table 6 Creatinine Clearance in Chronic Renal Failure

Creatinine clearance (ml/mt) No.of pateints Percentage

<5 2 4

5.1-10 25 50

10.1-15 13 26

15.1-20 5 10

20.1-25 2 4

>25 3 5

Total 50 100

The table shows that 50% of patients have their clcr value within the

range 5.1-10 ml/mt where as 26% of them have this value in the range 10.1-15

ml/mt. Purther 10% of patients had this value in the range 15.1-20 ml/mt.

Only 4% hade the value below 5 ml/mt and the same percentage of patients

can be seen in the range 20.1-25 ml/mt. Only 6% of patients had creatinine

clearnace >25.

Graph 5: Creatinine Clearance in Chronic Renal Failure

<5 5.1-10 10.1-15 15.1-20 20.1-25 >250

5

10

15

20

25

2

25

13

5

23

Creatinine clerance (ml/mt)

No.

of p

atei

nts

Table 7: Serum Potassium levels in Chronic Renal Failure

63

S. Potassium (mEq/l) No.of pateints Percentage

<3.5 2 4

3.5-5 31 62

>5 17 34

Total 50 100

From the table we see that 34% patients have Hyperkalemia. 62% had

the value within normal limits (3.5-5 mEq/1). Only 4% had the value less than

3.5 mEq/1.

Graph -6 Serum Potassium Levels in Chronic Renal Failure

<3.5 3.5-5 >50

5

10

15

20

25

30

35

2

31

17

Serum pottasium (mEq/l)

No.

of p

atei

nts

64

Table 8 Serum Sodium levels in Chronic Renal Failure

S. Sodium (mEq/l) No.of pateints Percentage

<130 12 24

130-145 37 74

>145 1 2

Total 50 100

From the table it appears that hyponatremia (Serum sodium level < 130

mEq/l) is present in 24% of patients. Further in 74% cases this value lies

between the normal limits (130-145 mEq/l). Only 2% had the value > 145

mEq/l.

Graph-7 Serum Sodium Levels in Chronic Renal Failure

<130 130-145 >1450

5

10

15

20

25

30

35

40

12

37

1

Serum Sodium (mEq/l)

No.

of p

atei

nts

65

Table 9 : Serum Calcium levels in Chronic Renal Failure

S. Calcium (mg/dl) No.of pateints Percentage

<8 23 46

8-10 26 52

>10 1 2

Total 50 100

Hypocalcaemia (<8 mg/dl) can be seen in 46% of cases. 52% of cases

have this value within normal limits (8.10 mg/dl).

Graph-8 Serum Calcium Levels in Chronic Renal Failure

<8 8-10 >100

5

10

15

20

25

30

23

26

1

Serum Calcium (mg/dl)

No.

of p

atei

nts

66

Table 10 : Serum Albumin levels in Chronic Renal Failure

S. Albumin (g/dl) No.of pateints Percentage

<3.5 17 34

3.5-5 33 66

Total 50 100

Hypoalbuminemia (Serum Albumin < 3.5g/dl) can be seen in 34% of

cases. 66% of cases have this value within normal limits (3.5 - 5 g/dl).

Graph - 9 Serum Albumin Levels in Chronic Renal Failure

<3.5 3.5-50

5

10

15

20

25

30

35

17

33

Serum Albumin (g/dl)

No.

of p

atei

nts

67

Table 11: Kidney Size (by USG) in Chronic Renal Failure

Size (cms) No.of pateints Percentage

Normal 15 30

Decreased 32 64

Increased 3 6

Total 50 100

64% of the cases seem to have decreased kidney size and 6% appears

to have an increased kidney size. Where as 30% of the patients have exhibited

normal size.

Graph-10 Kidney Size (by USG) in Chronic Renal Failure

Normal Decreased Increased0

5

10

15

20

25

30

35

15

32

3

No.

of p

atei

nts

68

Table 12 : Signs of Chronic Renal Failure

Signs No.of pateints Percentage

Pallor 45 90

Hypertension 46 92

Pedal Edema 39 78

Ascites 12 24

Pulmonary Edema 2 4

Palpable Kidney 3 6

Nail Changes 1 2

Pleural Effusion 1 2

Skin Changes 2 4

Peripheral neuropathy 1 2

The clinical examination reflects that almost 90 % of the patients had

pallor, 92% reflected the.presence of hypertension and 78% had pedal edema.

24% of them had ascites and all the other signs were found to be below 6%.

Graph-11 Signs of Chronic Renal Failure

Pallor

Hypert

ensio

n

Pedal

Edem

a

Ascites

Pulmonary

Edem

a

Palpab

le Kidney

Nail Chan

ges

Pleural

Effusio

n

Skin Chan

ges

Periphera

l neu

ropath

y05

101520253035404550 45 46

39

12

2 3 1 1 2 1No.

of p

atei

nts

69

Table 13: Symptoms of Chronic Renal Failure

Symptoms No.of patients Percentage

Pedal edema 39 78

Oliguria 38 76

Breathlessness 34 68

Vomiting 23 46

Anorexia 16 32

General Weakness 13 26

Facial edema 1 22

Flank pain 5 10

Hematuria 9 18

Abdominal distention 11 22

Altered sensojium 5 10

Convulsions 2 4

Polyuria 3 6

Dysuria 1 2

The presences of various symptoms observed in 50 patients are

presented in the above table. We see that 78% of the cases had pedal edema

followed by the most common urinary symptom Oliguria that is 76%. The

Gastrointestinal symptom namely anorexia is found in 32%. 26% had general

weakness and 46% were having vomiting as symptom. The numbers of cases

having facial edema were 22% and 68% of the cases exhibited breathlessness

as a symptom. The percentage of patients having various other symptoms can

be seen from the table.

70

Graph – 12 : Symptosm of chronic renal failure

Pallor

Hypert

ensio

n

Pedal

Edem

a

Ascites

Pulmonary

Edem

a

Palpab

le Kidney

Nail Chan

ges

Pleural

Effusio

n

Skin Chan

ges

Periphera

l neu

ropath

y0

5

10

15

20

25

30

35

40

45

50

4546

39

12

23

1 12

1

No.

of p

atei

nts

71

Table-14: The Comparison between groups based on Serum Creatinine

levels in terms of Haemoglobin, Potassium, Calcium and Albumin Levels.

Group Serum creatinine

No % Hb% (gm/dl)

K+ S.calcium S.Alb

No %

I 2-5 18 36 8.31± 2.48

4.51± 0.75

8.14± 1.10

3.59± 0.45

II 5.1-12 31 62 7.48± 1.55

4.85± 0.88

7.94± 0.89

3.56± 0.53

III >12.1 1 2 5.00 5.80 7.60 2.20

ANOVA F 2.03 1.76 0.55 3.62

P 0.14 NS

0.18 NS

0.58 NS 0.03 S

p>0.05 Non significant (NS), p<0.05 Significant (S)

In the first group of pateints average haemoglobin level was found to

be 8.31 with standard diviation of 2.48. In second group average

haemoglobin level was found to be 7.48 with SD of 1.55. In third group

average haemoglobin was 5 ‘p’ value was found to be 0.14 which indicates

there is insignificant decrease in haemoglobin with increase in serum

creatinine.

Serum potassium in first, second, and third group were 4.51 with SD of

0.75, 4.85 with SD of 0.88 and 5.8 respectively. ‘p’ value was found to be

0.18 which indicates insignificant increase serum potassium with increase in

serum creatinine.

Serum calcium in first, second, and third group were 8.14 with SD of

1.10, 7.94 with SD of 0.89 and 7.60 respectively. with ‘p’ value of 0.58

which indicates insignificant decrease in serum calcium with increse in serum

creatinine.

72

Serum albumin in first, second and third group were 3.5 with SD of

0.45, 3.56 with SD 0.53 and 2.2 respectively with ‘p’ value of 0.03 which

indicates significant decrease in serum albumin with increase in serum

creatinine.

73

DISCUSSION

The present study consisted of 50 patients of CRF who were admitted

to the hospital or were on regular dialysis on OPD basis. These patients

fulfilled the criteria set by the National Kidney Foundations' Kidney Disease

Outcome Quality Initiative for diagnosing CRF. They were studied and

evaluated clinically and laboratory investigated and ultrasonography of

abdomen was done.

Tn our study of 50 patients there was a male : female ratio of 2.12:1.

The mean age was 49.3 years. The youngest patient was 17 years of age and

the oldest 80 years of age. This shows the broad variation in age in our study

group highlighting the preponderance of CRF across a very large age group.

Out of the 18 studies analyzed by the National Kidney Foundations K/DOQI,

17 reported that the male sex was more at risk for CRF and 14 showed mat the

male sex was associated with a faster rate of progression to BSRD. Our

studies showed that the prevalence of chronic kidney damage as a result of

hypertension and diabetes is far lower in younger age groups than in adult

patients above the age of 30 years. Our findings are similar to those reported

by the National Kidney Foundations KVDOQI subgroup on children and

adolescents study conducted by Fivush et al111.

In our study an increasingly high number of patients were found to be

diabetic(37%) and hypertensive(24%). This trend is similar to that reported by

Dash and Agarwal in the study conducted at the All India Institute of Medical

Sciences112.

74

Lysaght et al have also demonstrated similar trends in American

populations113. In the study conducted by Xue et al the number of patients

with diabetic nephropathy was almost 50% of the study groups 114. The

aetiological data also shows the prevalence of Chronic glomerulonephritis at

23% which is concurrent with the data from other developing countries like

Egypt and Bolivia.21,24

The haemoglobin levels were below 10 gm/dl in 90% of the patients

thereby emphasizing the need for correction of anaemia in patients with CRF.

It is well established that anaemia develops in the course of chronic renal

disease and is nearly universal in patients with chronic renal failure. Lower

haemoglobin levels may result from a loss of erythropoietin synthesis on the

kidneys and/or the presence of inhibitors of erythropoietin synthesis.

Numerous articles describe the association of anaemia with kidney failure and

describe its various causes. McGonigle, Wallin et al studied 863 patients for

anaemia and found upto 90% of patients to have haemoglobin less, than 10

gm/dl115. They also established that erythropoietin deficiency and disorders

related to its synthesis are the main cause of "anaemia in patients with CRF.

These findings are consistent with our study. Furthermore they also

established that the severity of anaemia is related to duration and extent of

kidney damage. The lowest haemoglobin levels were found in anephric

patients and those who commenced dialysis at very severely decreased levels

of kidney function. Our studies showed that patients with creatinine levels

above 12 mg/dl had an average haemoglobin of 5emphasizing again that

greater the extent of kidney damage more the severity of the anaemia.

75

The incidence of Hyperkalemia was 34% which shows the need for the

early detection and management of this dangerous complication.

Hyperkalemia is a known complication of CRF which may be precipitated in a

number of conditions but certain aetiologies of CRF may be associated with

more earlier and more severe disruption of potassium secretory mechanisms

in the distal nephron, relative to the reduction in GFR. Most important are

conditions associated with hyporeninemic hypoaldosteronism like diabetic

nephropathy and renal tubular acidosis.

Hyponatremia was reported at an incidence of 24% in our study which

is also a known association with CKD. Hyponatremia in itself is an

uncommon complication in predialysis patients, and water restriction is

necessary only when hyponatremia is documented.

Hypocalcemia is a known entity in patients with CRF and our studies

showed the prevelance at 46%. It is known that bone disease and disorders of

calcium and phosphorus metabolism develop during the course of CKD.

Radiological and histologic demonstration of bone disease can be

demonstrated in nearly 40% of patients with severely decreased kidney

function. Reduced levels of calcium have been described in patients with GFR

less than 70 ml/ min in various studies. Histological changes in the bone have

also been shown to occur at earlier stages of CKD. In a study of 176 patients

with creatinine clearances of 15 to 50 ml/ min, 75% had "important

histological abnormalities, with the majority having osteitis fibrosa with or

without osteomalacia" as reported by Hamdy et al in their study on the effect

of alfacalcidol on natural course of renal bone disease in mild to moderate

renal failure116. In another study of patients by Coen et al (Metabolic

76

acidosis and osteodystrophic bone disease in patients with CRF) patients with

creatinine clearance of 20 to 59 ml/ min, 87% of patients had abnormal bone

histology and the majority had lesions of high bone formation rate associated

with hyperparathyroidism117.

The kidney size was decreased in 64% of the patients. The normal

sized kidneys in 30% of the patients is attributable to the large number of

diabetic nephropathy cases in which normal kidney size is a known entity.

The small hyperechoic kidneys which are characteristic of CKD were found in

the patients with decreased kidney size.

The serum Albumin levels were decreased in 34% of the patients and

this is consistent with known studies like Koppel et al -Modification of diet

in" renal disease(MDRD study group)118. The serum albumin is found to be

lower at levels of GFR below 30 ml/min, indicating a decline in circulating

protein levels or serum protein concentrations, protein- losses or

inflammation. An acceptable goal fcr albumin level is above 4.0 mg/dl by

bromocresol green method. Using data from the US Renal Data System

maintained by the Health Care Financing Administration, a recent study

documented the high frequency of hypoalhuminemia in patients entering

dialysis. Of 74,232 patients who began dialysis between April 1995 and June

1997 and for whom the relevant data were available, 60% had serum albumin

levels below the lower normal limit for the testing laboratory and 37% had

levels of 3.0 g/dL. Multivariate analysis showed that hypoalbuminemia was

associated with female gender, black or other non-Caucasian race, nonprivate

or no insurance, and diabetes. Stall et al found that, even once dialysis was

initiated and an "adequate" dialysis regimen was provided, many patients

77

were not attaining acceptable levels of nutrition as evidenced by continued

hypoalbuminemia and changes in body composition.

The most common symptoms in our patients were pedal oedema.

(78%), oliguria (76%), breathlessness (68%), vomiting (44%) and

anorexia(32%). CNS symptoms like convulsion and altered sensorium were

found in 4% and 10% of patients respectively. Decrease GFR in NHANES III

patients was associated with impaired walking and lifting ability. In another

subgroup in the above study, patients with decreased GFR the impairment of

physical function was not significantly related to the level of kidney function,

but physical impairment was 8 times worse than in the general population.

Dialysis patients report greater physical dysfunction than transplant recipients

and diabetic dialysis and transplant patients are more likely to report physical

dysfunction than those patients who do not have diabetes. Poor kidney fur.-

tion is also associated with lower employment in the above study. Full time

employment is higher for those with decreased GFR ( mean serum creatinine

5.4 mg/dl, 69%) compared with those with kidney failure ( mean serum

creatinine 13.7 mg/d , 12%). The above study also reported reduced social

activity, social functioning and social interaction as a result- of the CRF

symptoms. Anorexia was evidenced by almost a third (32%) of our patients.

Anorexia in CRF is evidenced by decreased dietary protein intake, which are

hallmarks of CRF. As limitation of protein intake reduces the accumulation of

toxic substances derived from the metabolism of protein. Decreased dietary

protein intake may be viewed as adaptive in patients with CKD. Thus, the

overall outcome of this adaptive procedure may be the increased prevalence

of protein energy malnutrition in patients with CKD.

78

The most common signs were hypertension (92%) and pallor (90%).

Pedal oedema (78%) and ascites (24%). Other signs like palpable kidney,

pulmonary oedema, skin and nail changes, pleural effusion etc were found in

less than 10% of patients. National Kidney Foundations K/DOQI evaluated 26

studies which related blood pressure to the level of GFR decline in univariate

and/or multivariate analysis. Most studies reporting multivariate analysis

showed a significant association between elevated blood pressure, based on

any measures of blood pressure, and faster rate of GFR decline. These data

confirm that elevated blood pressure is associated with faster rate of GFR

decline when controlling other factors. Pedal oedema arid ascites are

associated with deranged biochemical parameters and the correction of the

same has shown to improve outcomes.

79

CONCLUSION

We aim to spotlight the growing incidence of CRF among the

population. The growing incidence of this problem is a major health hazard in

our country which we can ill afford.

Out of 50 patients in our study, the majority (66%) were having CRF as

a result of Diabetes and Hypertension , which when detected and managed at

early stages can halt the progress to chronic kidney, disease and renal

replacement therapy. Other manageable conditions like Obstructive Uropathy

should also be detected and managed at an early stage to prevent irreversible

kidney damage.

The other complications like Anaemia, Hypocalcemia, Hyponatremia

and Hyperkalemia were also present in significant numbers and emphasize the

need for the detection and correction of these complications.

80

SUMMARY

In the present study, patients diagnosed with CRF admitted on

receiving dialysis at Chigateri General Hospital and Bapuji Hospital attached

to J.J.M. Medical College, Davangere between August 2010 and August 2011

wer included in this study.

50 consecutive pateints with CRF the aetiology, laboratory and clincal

profile were studied.

The study revealed that diabetic nephropathy (38%) hypertnsive

nephropathy (28%) and chronic glomerulonephritis (24%) were the most

common causes of CRF in our patients.

The also revealed a high number of patients with anaemia,

hypocalcemia and hyperkalimia. The major concern of this study to highlight

the high prevalence of diabetes and hypertension as a cause for CRF and the

need to initiate step for early detection and management of these conditons.

81

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ANNEXURE – I

PROFORMA

NAME : IP.NO. :

AGE : D.O.A. :

SEX : D.O.D. :

RELIGION :

ADDRESS :

PRESENTING COMPLAINTS:

Oliguria :

Dysuria :

Nocturia :

Polyuria :

Haematuria :

Facial oedema :

Pedal oedema :

Anorexia :

Vomiting :

Other symptoms :

Flank pain :

Abdominal distension :

Altered sensorium :

Convulsions :

Pruritis :

Skin rashes :

Bone pain :

Breathlessness :

Generalized weakness :

HISTORY OF PRESENTING ILLNESS:

PAST HISTORY

Diabetes mellitus

Hypertension

Renal disease

Prostatic symtoms

Any other systemic illness in the past

UTI

Stone disease

Drug history

96

PERSONAL HISTORY:

Sleep

Appetite

Bowel

Bladder

Smoker/chewing tobacco

Alcohol consumption

FAMILY HISTORY

GENERAL/ PHYSICAL EXAMINATION

PULSE: BP: RESP. RATE:

TEMP: WEIGHT: JVP:

BUILT: PALLOR: ICTERUS:

CLUBBING: LYMPHADENOPATHY:

OEDEMA: PEDAL / FACIAL/ GENERALIZED

SYSTEMIC EXAMINATION

ABDOMEN

Renal Mass Renal. Bruit Spleen

Renal angle Tenderness Liver Ascites

Other findings

CARDIOVASCULAR SYSTEM

RESPIRATORY SYSTEM

97

CENTRAL NERVOUS SYSTEM:

NEUROLOGICAL DEFICIT

SENSORIUM

OTHER FINDINGS

INVESTIGATIONS

BLOOD

Hb Urea Calcium

TC Cratinine Chloride

DC: N L E B M Sodium Phosphorus

ESR Potassium Magnesium

RBS

ANAfif relevant) LE cell(if relevant)

Total protein Albumin Globulin

S. Cholesterol

URINE

Protein: Sugar: Microscopy:

ULTRASOUND ABDOMEN:

Liver: Spleen: Ascites:

Gall bladder:

Kidneys: Right Left

Kidney Size:

Parenchymal changes:

Cortico medullary differentiation:

Pelvicalcylelal system

Bladder:

Kidney Biopsy (if done):

Diagnosis: (cause of Renal Failure)

Dialysis: Done/ Not Done

Renal Transplantation: Done/ Not Done

98