Diabetic Nephropathy

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DIABETIC NEPHROPATHY

Upendra Reddy. K

2010H146037H

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Diabetes has become the most common single cause of end-stage renal disease (ESRD).

Accounts for over one-third of all patients who are on dialysis.

About 20–30% of patients with type 1 or type 2 diabetes develop evidence of nephropathy.

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Epidemiology

Type 1 Diabetic 25 - 45% will develop diabetic nephropathy 80 - 90% with micro albuminuria will

progress to overt diabetic nephropathy in 5 - 10 years

nearly 100% with gross proteinuria will progress to ESRD in 7 - 10 yrs

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Epidemiology

Type 2 Diabetic

50% will have micro albuminuria at the time of presentation with hypertension

10-20% with micro albuminuria will progress to overt nephropathy.

Minority populations have a 2 to 20-fold higher incidence of diabetic nephropathy.

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Risk Factors:

Age, Race, Ethnicity (native Americans, Mexican Americans,

African Americans) History of micro albuminuria Hypertension Poor glycemic control Smoking Family history of nephropathy.

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Stage I – Hyper filtration - increased blood flow through the kidney, early renal hypertrophy

Stage II - Glomerular lesions without clinically evident disease

Stage III - Incipient nephropathy with micro albuminuria - alb/cr ratio .03 - .3 or albumin 20-200 mcg/min on timed specimen

Stages of Diabetic Nephropathy

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Stages of Diabetic Nephropathy

020406080

100120140160180

0 5 10 15 20 25 30

Duration of Diabetes

GF

R

III III

IV

V

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Stage IV - Overt diabetic nephropathy with proteinuria >500 mg/24 hr creatinine clearance <70 ml/min

Stage V – End stage renal disease (ESRD)

- creatinine clearance <15 ml/min - creatinine = 6mg/dl

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Signs & symptoms:

Fatigue

Protein in urine

Foamy appearance/excessive frothing of urine

Frequent hiccups

Swelling of the legs

Unintentional weight gain(from fluid build up)

Diabetic nephropathy :Diagnosis & treatment

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Screening for micro albuminuria:

I. Measurement of the albumin-to-

creatinine ratio in a random spot

collection;

II. 24-h collection with creatinine,

allowing the simultaneous

measurement of creatinine

clearance;

III. Timed (e.g., 4-h or overnight)

collection.

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SCREENING FOR NEPHROPATHYWHEN: Type 1 - annually after puberty and 5 years of DM

Type 2 - at diagnosis and then annually

WHAT: random urine ACR;

and random urine dipstick

Normal< 2.0 mg/mmol men

< 2.8 mg/mmol womenRescreen in 1 year

Microalbuminuria2.0 - 20 mg/mmol men

2.8 - 28 mg/mmol women

Macroalbuminuria> 20 mg/mmol men

> 28 mg/mmol womenDiabetic nephropathy

diagnosed

Up to 2 repeat random urine ACRs performed 1 week to 2

months apart

Suspicion of nondiabetic

renal disease?

Yes

Workup or referral fornondiabetic renal

diseaseNo

Check ACR results

Only 1 abnormal ACR: Repeat screen

in 1 year

Any 2 abnormal out of 3 ACRs: Diabetic

nephropathy diagnosed

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Treatment of Diabetic Nephropathy

Hypertension Control - Goal: lower blood pressure to <130/80 mmHg

ACE inhibitors: captopril, enalapril, lisinopril, benazepril, fosinopril,

ramipril, quinapril, perindopril, trandolapril, moexipril

Angiotensin receptor blockers(ARB) candesartan cilexetil, irbesartan, losartan potassium,

telmisartan, valsartan, esprosartan

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Treatment of Nephropathy:

Patients starting therapy with an ACE inhibitor or ARB should be monitored at 1 to 2 weeks for significant worsening of kidney function or the development of significant hyperkalemia. Serum creatinine typically rises up to 30% above baseline after initiating an ACE inhibitor or ARB, and usually stabilizes after 2 to 4 weeks.

Patients who develop mild to moderate hyperkalemia should receive nutritional counseling regarding a potassium-sparing diet and consideration should be given to the use of non-potassium-sparing diuretics.

TREATMENT

Treatment group Preferred agent

Type 1 diabetes ACE inhibitor

Type 2 diabetes Cr Cl > 60 mL/min Cr Cl < 60 mL/min

ACE inhibitor or ARBARB

Second-line renal protective agents (non-dihydropyridine calcium channel blockers) can be considered in those unable to tolerate an ACE inhibitor or an ARB.

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TREATMENT OF NEPHROPATHY

Already on ACE inhibitor?

Choose 2nd line therapy: ACE +ARB or add non-DHP CCB

NO

On first-line nephropathydrug?

NO

First line drug atmaximum dose?

YES

Add first-line drug;Recheck ACR in 2 weeks to 2 months

ACR normal?

First line drugs:Type 1- ACE inhibitorType 2 with Cr Cl > 60 mL/min - ACE inhibitor or ARBType 2 with Cr Cl 60 mL/min - ARB

Titrate up; recheck ACR in

2 weeks to 2 months

YES

Yes Remeasure ACR in 1 year

NONO

YES

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Ongoing clinical trials:

Drug Clinical trial phase

Company Last updated

LY2382770 Phase-II Eli Lilly March 14,2011

PH3 Phase-II Phytohealth corporation

Jan 4, 2011

N-acetyl cystein

Phase-II The university of Texas health science

Sep 17 ,2010

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References: American Diabetes Association. Standards of medical care

in diabetes--2010. Diabetes Care. 2010 Jan;33 Suppl 1:S11-61

American Diabetes Association (2004). Nephropathy in diabetes. Clinical Practice Recommendations 2004. Diabetes Care. 27(Suppl 1): S79–S83

DeFronzo RA: Diabetic nephropathy: etiologic and therapeutic considerations. Diabetes Reviews 3:510-547, 1995

www.clinicaltrials.gov.in