CHRONIC RENAL FAILURE

The Clinical Approach

Dr. Manoj Chaudhary

Consultant Nephrologist

Kidney Hospital, Jalandhar

Why to know about CRF/CKD

• IndiaWorld’s sharpest due to Type II DM, Hypertension (CAUSE-VASCULAR DYSFUNCTION)

• Death from communicable disease - 20 million-starting to decline,

• CVS disease to 26 million in 2020, • DM-150 million in 2000 will to 370 million

in 2030 (75% in developing world)• Estimation of CRF/CKD - 1 lakh/yr

Minority seen by Nephrologists

• CRD - Pathophysiologic process with multiple etiologies, resulting in inexorable attrition of nephron number and function frequently leading to End stage renal disease.

• ESRD - Clinical state or condition that has irreversible loss of endogenous renal function of sufficient degree to render the patient dependent on Dialysis or Transplantation in order to avoid Uraemia.

• Uraemia - Clinical and laboratory syndrome, reflecting all organ system dysfunction as result of untreated or treated Acute or CRF.

STAGES OF CHRONIC RENAL DISEASE

STAGE GFR,ML/MIN/1.73M2

1 KIDNEY DAMAGE WITH NORMAL OR INCREASED GFR

90

2 KIDNEY DAMAGE WITH MILDLY DECREASED GFR

60-89

3 MODERATELY DECREASED GFR

30-59

4 SEVERLY DECREASED GFR

15-29

5 RENAL FAILURE <15(OR DIALYSIS)

COCKROFT AND GAULT EQUATION

CREATININE.CLEARENCE (ml/min.)

= (140 - AGE) X BODY WT. (kg)

72 X PCr (mg/dl)

Multiply 0.85 for women

CAUSES OF CRF: [SGPGI,PGI,AIIMS]

DIABETIC NEPHROPATHY 34.98%

CGN 26.98%

CIN 24.69%

PKD 3.96%

HYPERTENSIVE NEPHROSCLEROSIS

5.34%

CALCULUS DISEASE 0.92%

REFLUX NEPHROPATHY 0.85%

OBSTRUCTIVE UROPATHY 1.86%

UNSPECIFIED CAUSE 0.51%

DIAGNOSIS OF CRF

• HISTORY

• FACTORS SUGGESTING CHRONICITY– Duration of symptoms for months.– Nocturia– Absence of acute illness in face of high urea

and creatinine.– Anaemia of chronic disorders– Bone disease– Sexual dysfunction– Nail changes, Pruritis– Neurological complications– Small kidneys on renal imaging

•LAB

- Hb, Ca 2+, PO43-, Alk. Phos., HCO3,

Alb., 24hrs. U.protein, Urine R/M, Broad Cast, PTH levels.

•IMAGING

- USG, MCU (Reflux), Renal Doppler, MRA

•RENAL BIOPSY

- If clear cut Dx not possible in kidney of Normal size.

SODIUM AND WATER HOMEOSTATIS

• Stable CRD- Increased Total Body Na & H2O -Not clinical apparent

• Hyponatremia-Restrict water intake• Wt. gain offset by concomitant loss of lean

body mass• Expanded ECFV

Restrict saltRestrict fluidLoop diuretics + Metalozone (distally

acting diuretics)• Volume depletion-resuscitated with normal

saline.

ANAEMIA• CLINICAL EFFECTS

O2 delivery & utilization CO• Cardiac enlargement• Ventricular hypertrophy• Angina• CHF Cognition & mental acuity• Altered menstrual cycles• Bleeding diathesis• Impaired host defence against infection• Growth retardation in children

ANAEMIA Contd…..

• Normocytic Normochromic Anaemia

• Reticulocyte count low

• Reduced, Normal or Bone marrow cellularity, M:E

• Reduced red cell life span, Erythropoiesis

IRON STUDIES

• S.Fe, TIBC, S.Ferritin

• If TSAT<20% S.Ferritin<100ng/l give Fe(50-100mg iv) Thrice weekly x 5weeks

• If still low repeat same course

• Withhold therapy TSAT>50% S.Ferritin>800mg/ml (>800g/L)

ERYTHROPOIETIN

• Starting dose 50-150 units/kg/wk IV or S.C (once, twice or thrice/ wk)

• TARGET Hb-11-12gm/dl

• Optimal rate of correction-1-2gm/dl over 4 wks.

EPO BENEFITS

• Increased Exercise tolerance• Normalization of elevated Cardiac Output• Increased BP in 30% of patients• Decreased Symptom of Angina• Decreased LVH• Decreased Cardiac size on chest X-Ray PA • Improved quality of life• Decreased Uraemic bleeding• Improved platelet function• Enhanced immune function• Decreased Uraemic pruritis

ADVERSE EFFECT OF EPO

• Hypertension

• Seizures/ Encephalopathy

• Clotting of dialysis lines

• Hyperkalemia

• Myalgia/ Influenza like syndrome

DARBOPOIETIN ALPHA• Analogue of EPO

-Greater biological activity -Prolonged half life

• Starting dose -0.45mg/kg iv or s.c. weekly or single

dose 0.75mg/kg single iv or s.c. every 2 wks.

• Optimal rate of correction-Hb by 1-2 gm/dl over 4 wk period

ORAL IRON

• POOR ABSORPTION

• INTOLERANCE

•DIALYSIS Adequate dialysis.(CAPD better HD for 3 yrs., then same.)

BLOOD TRANSFUSION

• Suppresses residual EPO production

• Iron overload deleterious effect on heart, liver, pancreas

• Infection HepB, HepC, HIV, CMV

• Exposure to wide range of HLA Cytotoxic Ab Risk of +ve crossmatch and Ac. rejection

ANDROGEN THERAPY

• Effective in mild cases only S/E-Virilization, Muscle & Liver damage, Cholestasis

BONE DISEASE AND DISORDERS OF CALCIUM AND PHOSPHATE

METABOLISM

• High turnover bone disease

• Low turnover bone disease– Osteomalacia– Adynamic bone disease

• LABS: Ca2+, Phosporous, Alk. Phosphatase, S.PTH

PRACTICAL RECOMMENDATION

• Early CRF CaCO3 2gms/day Dietary Phosphate<1000 mg

• Advanced CRF (Cr.Cl-60-40 ml/min)– Phosphate 800-900 mg/day

Ca supplement– If S.Calcediol < 20ng/ml

Add the metabolite 2g/day- Metabloic acidosis - Ca Co3/ and or bicarbonate- Avoid citrate - increased absorption of

aluminum

• FAR advanced stages

– Daily phosphate - 600-750 mg/day– CaCo3 - 3gm /day– Watch for Metabolic acidosis - NaHCO3

– Plasma calcidiol – Add Calcitriol 0.25 pg daily

– If hypercalcemia - restrict or half the dose calcidiol

– hyperphosphatemia - target PTH around 2-3 times

the upper limit

•Sevalamer– Non reabsorbable, – Non calcium containing polymer, – No Hypercalcemia

• Attenuates calcium deposition in coronary arteries and aorta.

• Adynamic bone diseaseOverzealous suppression of secondary Hyperparathyroidism (keep PTH<120 pg/ml)

CARDIOVASCULAR ABNORMALITIES

Leading cause of mortality and morbidity

• IHD Classical risk factors

• Hypervolumia• Dyslipidemia• Sympathetic overactivity• S Hyperhomocysteinemia• Tt - HMG COA if + Gem fibozil Risk of Myositis

CRD RELATED• Anaemia

• Hyperphosphatemia

• Hyperparathyroidism

• Microinflammation-IL6, CRP

• NO

CHF• Abnormal cardiac function secondary to IHD

or LVH, Salt and Water retention

• Unique feature - Even in absence of volume overload there is normal or increased Intracardiac or PCWP

• Butterfly wing distribution due to increased permeability of capillary alveolar membrane leading to low pressure pulmonary edema.

- Treatment by vigorous dialysis

HYPERTENSION

• Most common complication• Develop early in course associated with

adverse outcome• LVH & Cardiovascular morbidity• Anaemia & LVFIf Hypertension absent

Salt wasting renal disease, Medullary cystic disease, Chronic T1 disease, Volume depletion or Reduced cardiac index.

Treatment: • Slow progression of disease• Prevent complication - CVS disease and

stroke• Target BP – 130/ 80 – 85 (Protenuria < 1gm/

24hrs)• If protenuria > 1gm/ 24hrs – Target BP 125/

75• Volume Control

- Salt restriction- Diuretics

• Ace inhibitor can be used• Avoid direct Vasodilators – Minoxidil

Hydralaizne

• If increased Cardiac hypertrophy- Use only in Refractory hypertension- Target BP-->130/80-85

(Protenuria<1gm/24hrs)• If protenuria>1gm/24hrs-Target BP 125/75• Volume control--> Salt restriction

--> Diuretics• ACE or ARB ? Or both ? • Avoid direct vasodilators

– Minoxidil – HydralazineLeads to Cardiac hypertrophy– Use only in refractory hypertension

NUTRITIONPEM- Common problemIndian scenario-malnutrition widely prevalent

CAUSES:• Anorexia• Altered taste sensation• Intercurrent stress• Unpalatable prescribed diets• Catabolic response to superimposed illness• Endocrine disorders of uraemia (resistance

to IgF, hyperglucagonemia, hyperparathyroidism)

Energy - 35 k cal/kg/day

On vegetarian diet-Av. Protein intake 0.64 + 0.15 gms/kg/day

Diabetic pt.- 30-35 kcal/kg of IBW/day, 60% carbohydrates, 30% - fats

15% from mono unsaturated fats.

For MHD- Calories - same Protein -1.2 gm/kg. (50% HBV)

INDICATIONS OF RENAL REPLACEMENT THERAPY

• Anorexia & nausea• Fluid & Electrolytes abnormalities that are

refractory to conservative means– Volume overload refractory to diuretics– Hyperkalemia unresponsive to protein restricted– Progressive metabolic acidosis that cannot be

managed by alkali

• Pericarditis• Progressive neuropathy attributable to

ureamia• Encephalopathy• Muscle irritability

CLINICAL CLUES INDICATING DEVELOPMENT OF URAEMIC

COMPLICATIONS• Morning nausea• Vomiting• Intractable pruritis• H/O Hiccuping• Muscle twitching & cramps• Presence of asterixis• Pt’s whose follow up and compliance with

conservative management is difficult- considered for earlier managementConsiderable interindividual variability in severity of uraemic symptoms and renal function It is ill advised to assign a certain usual level of BUN, S.creatinine, GFR to need to start Dialysis

Recent controlled studies failed to show a survival advantage for early initiation of

RRT prior to onset of clinical indications.

Modality of RRT

• Haemodialysis

• Chronic Ambulatory Peritoneal Dialysis

• Renal Transplantation

HD- most common modality of ESRD (USA- 80%)

PD- Younger pt-because of better manual dexterity and greater visual acuity Difficult vascular access

Larger pt-Truncal obesity (>80kg) suited for HD