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DIABETIC NEPHROPATHY

Dr. Shahrzad Shahidi

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CLASSIFICATION

1. Type 1 (due to b-cell destruction, usually leading to absolute insulin deficiency)

2. Type 2 (due to a progressive insulin secretory defect on the background of insulin resistance)

3. Gestational DM (GDM) (diabetes diagnosed in the second or third trimester of pregnancy that is not clearly overt diabetes)

4. Specific types of diabetes due to other causes, e.g:

Monogenic diabetes syndromes(such as MODY)

Diseases of the exocrine pancreas (such as cystic fibrosis)

Drug- or chemical-induced diabetes

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Testing to Assess Risk for Future DM in Asymptomatic People

1. Adults of any age who are overweight or obese (BMI ≥25) & who have ≥ 1 additional risk factors for DM.

2. For all patients, particularly those who are overweight or obese, testing should begin at age 45 years.

3. Testing to detect prediabetes should be considered in children & adolescents who are overweight or obese & who have ≥ 2 additional risk factors for DM.

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Risk Factors Physical inactivity First-degree relative with DM High-risk race/ethnicity Women who delivered a baby weighing>4 kg

or were diagnosed with GDM Hypertension HDL cholesterol <35 mg/dL &/or a TG >250 mg/dL

Women with polycystic ovary syndrome A1C ≥ 5.7%, IGT, or IFG on previous testing Other clinical conditions associated with

insulin resistance (e.g., severe obesity, acanthosis nigricans)

History of CVD

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Testing to Assess Risk for Future DM in Asymptomatic People

In patients with prediabetes, identify &, if appropriate, treat other cardiovascular disease (CVD) risk factors.

If tests are normal, repeat testing carried out at a minimum of 3 year intervals is reasonable.

To test for prediabetes, the A1C, FPG, & 2-h PG after 75-g OGTT are appropriate. Then yearly

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ADA Diagnostic Criteria:Clinical Practice Recommendations 2015

In the absence of unequivocal hyperglycemia, criteria 1, 2, and 4 should be confirmed by repeat testing.

Parameter

Normal

Diabetes

Pre-diabetes

Method

1 Fasting Plasma Glucose (mg/dl)

<100 ≥126 100–125 No caloric intake for at least 8 h

2 2-h plasma glucose on OGTT (mg/dl)

<140 ≥200 140–199 WHO method: 75 g glucose load

3 Random plasma glucose (mg/dl)

<140 ≥200 - with classic symptoms of hyperglycemia or crisis

4 Hb A1C (%) <5.7 ≥6.5 5.7 – 6.4 NGSP certified method standardized to the DCCT assay

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Criteria for the Diagnosis of Diabetes

HbA1C ≥ 6.5% (fasting not required)

OR FPG ≥ 126 mg/dL

Fasting is defined as no caloric intake for at least 8 h

OR 2-h PG ≥ 200 mg/dL during an

OGTTOR

A random plasma glucose ≥ 200 mg/dL

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Components of the Comprehensive Diabetes Evaluation

Laboratory evaluation: A1C, if results not available within past 3 ms If not performed/available within past year

Fasting lipid profile, including total, LDL, & HDL cholesterol & TG, as needed

Liver function tests Test for urine albumin excretion with spot urine

albumin-to-cr ratio Serum cr & calculated GFR TSH in type 1 DM, dyslipidemia, or women > 50 ys

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Referrals

1. Eye care professional for annual dilated eye exam

2. Family planning for women of reproductive age

3. Registered dietitian for medical nutrition therapy

4. DSME/DSMS

5. Dentist for comprehensive periodontal examination

6. Mental health professional, if needed

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Mean Glucose Levels for Specified A1C levels

HbA1C (%)

Mean Plasma Glucose (mg/dL)

6 1267 1548 1839 214

10 24011 26912 298

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Glycemic Recommendations for Nonpregnant Adults with DM

A1C < 7%

Preprandial capillary plasma glucose

80–130 mg/dL

Peak postprandial capillary plasma glucose†

< 180 mg/dL

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Goals Should be Individualized Based on:

Duration of diabetes Age/life expectancy Comorbid conditions known CVD or advanced microvascular

complications Hypoglycemia unawareness Individual patient considerations

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Diabetic Nephropathy

Diabetic kidney disease occurs in 20–40% of patients with diabetes & is the leading cause of ESRD.

Persistent increased albuminuria in the range of UACR 30–299 mg/g is an early indicator of diabetic kidney disease in type 1 & a marker for development of diabetic kidney disease in type 2 .

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Diabetic Nephropathy

Diabetic kidney disease occurs in 20–40% of patients with diabetes & is the leading cause of ESRD.

Persistent increased albuminuria in the range of UACR 30–299 mg/g is an early indicator of diabetic kidney disease in type 1 & a marker for development of diabetic kidney disease in type 2 .

Diabetic Nephropathy

Incidence of ESRD Resulting from Primary

Diseases (1998)

43%

23%

12%

3%

19%

Diabetes

Hypertension

Glomerulonephritis

Cystic Kidney

Other Causes

h Over 40% of new cases of end-stage renal disease (ESRD) are attributed to diabetes.

h The 5-year mortality rate for a dialysis patient with diabetic nephropathy is 93%.

h Dialysis for one patient costs over $50,000 annually.

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Diabetic Nephropathy

Definition or Criteria: Presence of persistent proteinuria in sterile urine of diabetic patients with concomitant diabetic retinopathy & HTN.

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Stages of Diabetic Nephropathy

020406080

100120140160180

0 5 10 15 20 25 30

Duration of Diabetes

GFR

III

III

IV

V

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Recommendations to Reduce the Risk or Slow the Progression of DN

Optimize glucose control

Optimize BP control (< 140/90)

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Recommendations to Reduce the Risk or Slow the Progression of DN

Screening at least once a year, quantitatively assess urinary albumin (e.g., UACR) & eGFR in patients: Type 1 diabetes duration of ≥ 5 years All patients with type 2 diabetes

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Diabetic Nephropathy: Treatment

An ACEI or ARB is not recommended for the primary prevention of DN in patients with diabetes who have normal BP & normal UACR (<30 mg/g).

Either an ACEI or ARB is suggested for the treatment of the nonpregnant patient with modestly elevated urinary albumin excretion (30–299 mg/d) & is recommended for those with urinary albumin excretion < 300 mg/d.

When ACEIs, ARBs, or diuretics are used, monitor serum Cr & K levels.

Continued monitoring of UACR in patients with albuminuria is reasonable to assess progression of DN.

When eGFR is < 60 mL/min/1.73 m2, evaluate & manage potential complications of CKD.

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Diabetic Nephropathy: Treatment

Referral to a Nephrologist when: There is uncertainty about the

etiology of kidney disease Difficult management issues Advanced kidney disease

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Diabetic Nephropathy: Treatment

Nutrition: For people with DN, reducing the

amount of dietary pr below the recommended daily allowance of 0.8 g/kg/day (based on ideal body weight) is not recommended because it does not alter glycemic measures, cardiovascular risk measures, or the course of GFR decline.

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Management of CKD in DM

GFR (mL/min/1.73 m2) Recommended management

All patients Yearly measurement of Cr, urinary albumin excretion, K

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Management of CKD in DM

GFR (mL/min/1.73 m2) Recommended management

45–60 • Referral to a nephrologist if possibility for nondiabetic kidney disease

• Consider the need for dose adjustment of medications

• Monitor eGFR every 6 months

• Monitor electrolytes, HCO3, Hb, Ca, P, PTH at least yearly

• Assure vitamin D sufficiency

• Consider bone density testing

• Referral for dietary counseling

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Management of CKD in DM

GFR (mL/min/1.73 m2) Recommended management

30–44 • Monitor eGFR every 3 ms• Monitor electrolytes, HCO3,

Ca, P, PTH, Hb, Alb, weight every 3–6 ms

• Consider the need for dose adjustment of medications

< 30 Referral to a nephrologist

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Q. Which features are typical of DN at presentation ?

Haematuria Small scarred kidneys Progress to ESKD in <2yrs Associated retinopathy β-blockers better than ACE-I Rx

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Q. Which features are typical of DN at presentation ?

Haematuria NO Small scarred kidneys NO Progress to ESKD in <2yrs NO Associated retinopathy YES β-blockers better than ACE-I Rx NO

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