DIABETICDIABETIC NEPHROPATHYNEPHROPATHY

Presented ByPresented By

Rashi TantiaRashi Tantia

INTRODUCTION and EPIDEMIOLOGYINTRODUCTION and EPIDEMIOLOGY

India has increased burden of chronic diseases India has increased burden of chronic diseases like Hypertension and Diabeteslike Hypertension and Diabetes

India has largest number of diabetics in the world India has largest number of diabetics in the world with prevalence of 3.8% in rural and 11.8% in with prevalence of 3.8% in rural and 11.8% in urban adultsurban adults

25-40% of these develop End Stage Renal 25-40% of these develop End Stage Renal Disease which is now known as CKDDisease which is now known as CKD

Both type 1 and type 2 diabetes lead to ESRD but Both type 1 and type 2 diabetes lead to ESRD but majority of patients are those with NIDDMmajority of patients are those with NIDDM

In Diabetic Nephropathy, Glomeruli and Kidneys In Diabetic Nephropathy, Glomeruli and Kidneys are normal or increased in size unlike Polycystic are normal or increased in size unlike Polycystic kidney disease where their size is reduced kidney disease where their size is reduced

GOALS and OBJECTIVESGOALS and OBJECTIVES

To discuss the risk of development of To discuss the risk of development of Diabetic nephropathyDiabetic nephropathy

To discuss the screening methods and To discuss the screening methods and diagnosis of Diabetic nephropathydiagnosis of Diabetic nephropathy

To discuss the implications of To discuss the implications of MicroalbuminuriaMicroalbuminuria

To discuss the management of nephropathy To discuss the management of nephropathy through Diet, Control of Blood Pressure, and through Diet, Control of Blood Pressure, and Dialysis and Transplantation Dialysis and Transplantation

RISK FACTORSRISK FACTORS

Genetic FactorsGenetic Factors:- Person having family :- Person having family history of Diabetic nephropathy is more history of Diabetic nephropathy is more likely to develop it as welllikely to develop it as well

Inadequate Glucose ControlInadequate Glucose Control:- Improved :- Improved blood glucose level has found to reduce the blood glucose level has found to reduce the risk of nephropathyrisk of nephropathy

High blood pressureHigh blood pressure:- Usually it occurs as a :- Usually it occurs as a result of kidney disease but is also result of kidney disease but is also associated with progression and associated with progression and pathogenesis of nephropathy pathogenesis of nephropathy

Contd.Contd.

HyperlipidemiaHyperlipidemia SmokingSmoking Long Standing Diabetes:Long Standing Diabetes:- Patients having - Patients having

long standing diabetes have higher risk of long standing diabetes have higher risk of developing nephropathydeveloping nephropathy

PregnancyPregnancy:- During pregnancy, there is :- During pregnancy, there is rise in GFR which returns to normal after rise in GFR which returns to normal after delivery. But hypertensive women or those delivery. But hypertensive women or those with renal disease prior to conception with renal disease prior to conception have higher risk of progression of the have higher risk of progression of the disease disease

Natural History of Kidney Natural History of Kidney DiseaseDisease

Diabetic Nephropathy Diabetic Nephropathy progressesprogresses through through five predictable five predictable stagesstages which are as follows:- which are as follows:-

Stage 1 (very early diabetes)

•Increased demand upon the kidneys is indicated by an above-normal glomerular filtration rate (GFR).

•Hyperglycemia leads to increased kidney filtration (see later)

•This is due to osmotic load and to toxic effects of high sugar levels on kidney cells

•Increased Glomerular Filtration Rate (GFR >90ml/min) with enlarged kidneys

Stage 2 (developing diabetes)

•Clinically silent phase with continued hyper filtration and hypertrophy

•The GFR remains elevated or has returned to normal (GFR 60-89ml/min), but glomerular damage has progressed to significant microalbuminuria (small but above-normal level of the protein albumin in the urine).

•Significant microalbuminuria will progress to end-stage renal disease (ESRD).

•Therefore, all diabetes patients should be screened for microalbuminuria on a routine basis.

Stage 3 (overt, or dipstick-positive diabetes)

•Glomerular damage has progressed to clinical albuminuria with GFR 30-59ml/min.

•Basement membrane thickening due to AGEP

•The urine is "dipstick positive," containing more than 300 mg of albumin in a 24-hour period.

•Hypertension (high blood pressure) typically develops during stage 3.

Stage 4 (late-stage diabetes)

•Glomerular damage continues, with increasing amounts of protein albumin in the urine.

•The kidneys’ filtering ability has begun to decline steadily, and blood urea nitrogen (BUN) and creatinine (Cr) has begun to increase.

•The glomerular filtration rate (GFR) decreases further more with (GFR 15-29ml/min). Almost all patients have hypertension at stage 4.

Stage 5 (end-stage renal disease, ESRD or CKD, chronic kidney disease)

•GFR has fallen to <15 ml/min and renal replacement therapy (i.e., haemodialysis, peritoneal dialysis, kidney transplantation) is needed.

KIDNEY FUNCTIONKIDNEY FUNCTION

Functional unit is NephronFunctional unit is Nephron It filters the blood into the tubules It filters the blood into the tubules

which have very thin wallswhich have very thin walls Normally, materials that body needs Normally, materials that body needs

flow back and wastes are thrown flow back and wastes are thrown back across these wallsback across these walls

Most important is Glucose which is Most important is Glucose which is reabsorbed back completely reabsorbed back completely

STRUCTURE OF A NEPHRONSTRUCTURE OF A NEPHRON

Normal v/s Declining Function of the KidneyNormal v/s Declining Function of the Kidney Removal of nitrogenous Removal of nitrogenous

waste productswaste products Fluid and electrolyte and Fluid and electrolyte and

acid-base balanceacid-base balance BP ControlBP Control Excretion of certain drugsExcretion of certain drugs Production of Production of

erythropoietinerythropoietin Formation of 1,25-Formation of 1,25-

dehydroxy vitamin Ddehydroxy vitamin D

Increased serum BUN and Increased serum BUN and creatininecreatinine

Fluid and sodium retention Fluid and sodium retention and increased serum and increased serum potassium and metabolic potassium and metabolic acidosisacidosis

HypertensionHypertension Alteration of drug activityAlteration of drug activity Decreased production of Decreased production of

Erythropoietin and hence Erythropoietin and hence RBC’s and lead to anaemia RBC’s and lead to anaemia and HbA1C would always and HbA1C would always be low.be low.

Decreased Calcium Decreased Calcium absorptionabsorption

SCREENING METHODSSCREENING METHODS

It can be done by 3 methodsIt can be done by 3 methods:-:- A random spot collection to ACRA random spot collection to ACR A 24-hr collection for creatinineA 24-hr collection for creatinine A timed (4-hr) collection A timed (4-hr) collection

Contd.Contd.

Annual check for proteinuria in fasting Annual check for proteinuria in fasting urine sample using a urine dipstick:-urine sample using a urine dipstick:-

If it is +ve, person should check for If it is +ve, person should check for urinary infection and a lab urine PCR urinary infection and a lab urine PCR (Protein:Creatinine ratio)(Protein:Creatinine ratio)

If it is –ve, urine albumin should If it is –ve, urine albumin should check using a lab ACR check using a lab ACR (Albumin:Creatinine ratio) (Albumin:Creatinine ratio)

Contd.Contd.

If PCR or ACR are elevated check If PCR or ACR are elevated check should be repeated twice in next 4 should be repeated twice in next 4 months.months.

ACR ACR <2.5mg/mmol<2.5mg/mmol is normal in is normal in malesmales

ACR ACR <3.5mg/mmol<3.5mg/mmol is normal in is normal in females females

ADA and CDA Recommended Urine ADA and CDA Recommended Urine LevelsLevels

Urine Urine dipstick dipstick for for proteinprotein

Urine Urine ACRACR

mg/mmolmg/mmol

24-hr24-hr urine urine collection collection for for albuminalbumin

NormalNormal NegativeNegative <2.0(men)<2.0(men)

<2.8(women<2.8(women))

<30mg/day<30mg/day

MicroalbuMicroalbuminuriaminuria

NegativeNegative 20-20.0(men)20-20.0(men)

2.8-2.8-28(women)28(women)

30-300mg/30-300mg/dayday

Overt Overt nephropatnephropathyhy

NegativeNegative >>20(men)20(men)

>28(women)>28(women)

>300mg/day>300mg/day

MANAGEMENTMANAGEMENT

Presence of Presence of Microalbuminuria Microalbuminuria indicates that indicates that treatment should be started:-treatment should be started:-

Use of ACE Inhibitor is essential as Use of ACE Inhibitor is essential as microalbuminuria indicates increased pressure in microalbuminuria indicates increased pressure in kidney.kidney.

BP should be managed to achieve <130/80mmHg.BP should be managed to achieve <130/80mmHg. HbA1c should be managed to <6.5%.HbA1c should be managed to <6.5%. Reduce protein in diet to 0.8-1.0gm/Kg body Reduce protein in diet to 0.8-1.0gm/Kg body

weight in early stages and to <0.8gm in later weight in early stages and to <0.8gm in later stages of CKD.stages of CKD.

Lipid management, non-smoking, aspirin therapy is Lipid management, non-smoking, aspirin therapy is also helpful.also helpful.

When GFR falls <60ml/min/1.73mt.sq. BSA, person When GFR falls <60ml/min/1.73mt.sq. BSA, person should be referred to a Nephrologist.should be referred to a Nephrologist.

PREVENTION OR DELAYPREVENTION OR DELAY

Achieving blood glucose level in normal Achieving blood glucose level in normal range can either delay the start or range can either delay the start or progression of progression of MicroalbuminuriaMicroalbuminuria to to Macroalbuminuria. Macroalbuminuria. (DCCT&UKPDS)(DCCT&UKPDS)

Lowering BP reduces the development Lowering BP reduces the development of kidney disease. (UKPDS-1998)of kidney disease. (UKPDS-1998)

According to (DCCT-1993), intensively According to (DCCT-1993), intensively managed group had managed group had 40% decrease40% decrease in in the occurrence of the occurrence of Microalbuminuria Microalbuminuria and and 50% decrease50% decrease in the occurrence in the occurrence of of Macroalbuminuria.Macroalbuminuria.

SYMPTOMSSYMPTOMS

No symptoms of early kidney No symptoms of early kidney disease.disease.

If one waited for symptoms to If one waited for symptoms to appear, person would have appear, person would have significant disease on diagnosis. significant disease on diagnosis.

Solution at this stage is either Solution at this stage is either DialysisDialysis or or Kidney Kidney Transplantation. Transplantation.

DIALYSISDIALYSIS

It is a method where blood is cleaned It is a method where blood is cleaned off wastes artificially when kidneys off wastes artificially when kidneys are not able to do it properly.are not able to do it properly.

There are two types of Dialysis:-There are two types of Dialysis:- HemodialysisHemodialysis Peritoneal Dialysis Peritoneal Dialysis

HEMODIALYSISHEMODIALYSIS

Contd.Contd.

As you can see, it uses a machine to As you can see, it uses a machine to take over the function of the kidney.take over the function of the kidney.

It requires a surgical procedure to It requires a surgical procedure to create a shunt between arteries and create a shunt between arteries and veins known as veins known as AV FistulaAV Fistula. .

PERITONEAL DIALYSISPERITONEAL DIALYSIS

Contd.Contd.

As you can see, in this, a solution is As you can see, in this, a solution is run into the abdominal cavity, left for run into the abdominal cavity, left for few hours and drained off, taking few hours and drained off, taking with it wastes from the blood.with it wastes from the blood.

People can do this at homes during People can do this at homes during sleeping hours. sleeping hours.

KIDNEY TRANSPLANTATIONKIDNEY TRANSPLANTATION

Also known as Renal TransplantAlso known as Renal Transplant Quite common now a days mostly in Quite common now a days mostly in

young patientsyoung patients Good success rates if kidney is Good success rates if kidney is

received from a living relativereceived from a living relative

To Wrap UpTo Wrap Up:- :- Diabetic nephropathy is a disease that Diabetic nephropathy is a disease that

develops slowly and if treated early, develops slowly and if treated early, progression can be delayed.progression can be delayed.

There are no signs and symptoms of early There are no signs and symptoms of early disease so screening is important.disease so screening is important.

Aggressive treatment of Blood glucose, BP, Aggressive treatment of Blood glucose, BP, Lipids helps in prevention of renal function Lipids helps in prevention of renal function and can improve the outcome.and can improve the outcome.

In CKD, some people progress to Dialysis In CKD, some people progress to Dialysis and few to Kidney Transplantation. and few to Kidney Transplantation.

THANK YOUTHANK YOU

BIBLIOGRAPHYBIBLIOGRAPHY

1. Diabetes Education Module, 20061. Diabetes Education Module, 2006

2. ADA, 2007;CDA,20032. ADA, 2007;CDA,2003

3. IDF,2005;ADA,20073. IDF,2005;ADA,2007

4. Malhotra, 19994. Malhotra, 1999

5. UKPDS,1998 and DCCT,1993 5. UKPDS,1998 and DCCT,1993

6.6.http://www.slideworld.org/slideshow.aspx/http://www.slideworld.org/slideshow.aspx/diabetic nephropathy pptdiabetic nephropathy ppt

7.The Everything Diabetes Book, Ford Martin 7.The Everything Diabetes Book, Ford Martin with Blumer, M.D. with Blumer, M.D.