1. 1

2. DIABETIC NEPHROPATHY Dr. Shahrzad Shahidi 2

3. 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 3

4. 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. 4

5. 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 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 5

6. 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 6

7. ADA Diagnostic Criteria: Clinical Practice Recommendations 2015 In the absence of unequivocal hyperglycemia, criteria 1, 2, and 4 should be confirmed by repeat testing. ParameterNormalDiabetesPre- diabetes Method 1 Fasting Plasma Glucose (mg/dl) <100≥126100–125 No caloric intake for at least 8 h 2 2-h plasma glucose on OGTT (mg/dl) <140≥200140–199 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≥6.55.7 – 6.4 NGSP certified method standardized to the DCCT assay 7

8. 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 OGTT OR  A random plasma glucose ≥ 200 mg/dL 8

9. 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 9

10. 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 10

11. Mean Glucose Levels for Specified A1C levels 11 HbA1C (%) Mean Plasma Glucose (mg/dL) 6126 7154 8183 9214 10240 11269 12298

12. Glycemic Recommendations for Nonpregnant Adults with DM 12 A1C< 7% Preprandial capillary plasma glucose 80–130 mg/dL Peak postprandial capillary plasma glucose† < 180 mg/dL

13. Goals Should be Individualized Based on: 13  Duration of diabetes  Age/life expectancy  Comorbid conditions  known CVD or advanced microvascular complications  Hypoglycemia unawareness  Individual patient considerations

14. Diabetic Nephropathy 14  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.

15. Diabetic Nephropathy 15  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.

16. Diabetic Nephropathy  Over 40% of new cases of end-stage renal disease (ESRD) are attributed to diabetes.  The 5-year mortality rate for a dialysis patient with diabetic nephropathy is 93%.  Dialysis for one patient costs over $50,000 annually.

17. Diabetic Nephropathy  Definition or Criteria:  Presence of persistent proteinuria in sterile urine of diabetic patients with concomitant diabetic retinopathy & HTN. 17

18. 18

19. Stages of Diabetic Nephropathy I II III IV V 19

20. Recommendations to Reduce the Risk or Slow the Progression of DN 20  Optimize glucose control  Optimize BP control (< 140/90)

21. Recommendations to Reduce the Risk or Slow the Progression of DN 21  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

22. Diabetic Nephropathy: Treatment 22  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.

23. Diabetic Nephropathy: Treatment 23  Referral to a Nephrologist when:  There is uncertainty about the etiology of kidney disease  Difficult management issues  Advanced kidney disease

24. Diabetic Nephropathy: Treatment 24  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.

25. Management of CKD in DM 25 GFR (mL/min/1.73 m2) Recommended management All patientsYearly measurement of Cr, urinary albumin excretion, K

26. Management of CKD in DM 26 GFR (mL/min/1.73 m2) Recommended management 45–60Referral 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

27. Management of CKD in DM 27 GFR (mL/min/1.73 m2) Recommended management 30–44Monitor 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 < 30Referral to a nephrologist

28. 28 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

29. 29 Q. Which features are typical of DN at presentation ?  HaematuriaNO  Small scarred kidneysNO  Progress to ESKD in <2yrs NO  Associated retinopathyYES  β-blockers better than ACE-I Rx NO

30. 30