1. Diabetic nephropathy

2. Diabetic nephropathy- definition Chronic microangiopathy type complication of DM characterized by: 1. proteinuria 2. hypertension 3. progressive loss of GFR leading to ESRD

3. Microalbuminuria 1. albumin excretion in urine 30 – 300 mg/d or 20 – 200 ug/min 2. If temporary, but >80 mg/d it means in 95% progression to continuous microalbuminuria 3. If continuous - it means threatening nephropathy. Not treated increases 20 – 40% a year. After 5 years becomes macroalbuminuria = evident diabetic nephropathy

4. Macroalbuminuria 1. Albumin excretion in urine >300 mg/d 2. It may lead to development of nephrotic syndrome (proteinuria, hypoalbuminaemia, hyperlipidaemia, edema) 3. ESRD appears usually after 5 years

5. Time course of DN according to type of DM (Mogensen scale) IDDM NIDDM IDDM NIDDM I stadium (0-2 yrs) hyperfiltration (100%) (unnoticeable) II stadium (2-5yrs) silent DN (100%) (100%) III stadium (>5 yrs) threatening DN (30%) (30%) IV stadium (>15 yrs) evident DN (25%) (25%) V stadium (>15 yrs) ESRD (20%) (20%)

6. Factors contributing to development of DN 1. Long-lasting hyperglycemia 2. Family predisposition 3. HT 4. High-protein diet 5. Cigarette smoking 6. hyperlipidaemia

7. BP in children of DM patients without DN with DN SBP117 +13 mmHg 125 +17 mmHg Strojek i wsp. Mutual coincidence of DM and HT

8. DM patients with HT  Age of DM patients = % of patients with HT

9. BP, DM control and loss of GFR [ml/min/r] MABP [mm Hg] 9198102105112 HbA1c <9% 1,41,53,64,46,0 HbA1c >9% 3,33,54,66,17,5

10. Treatment of DN 1. Proper treatment of DM 2. Proper treatment of HT 3. Quit smoking habit 4. Control of protein content in diet 5. Early treatment of anaemia 6. Early kidney replacement therapy

11. Proper treatment of DM 1. „Almost normal” glycaemia: fasting 60 – 140 mg/dl 2 h after meal <200 mg/dl 2. Proper body mass 3. Correction of hyperlipidaemia

12. Proper treatment of BP 1. Lowest tolerable BP 2. Treatement with ACE-I & AT-II

13. Nutrition state (albuminaemia) and the risk of death Hakim1994

14. Early treatment of anaemia with epo Anaemia… when? glomerulonephritis DN glomerulonephritis DN GFR <25-30 ml/min <35-40 ml/min creatinine >3-4 mg/dl>2-3 mg/dl Attention: ACE-I may contribute to anaemia!

15. Early start of renal replacement therapy 1. creatinine >3,5 – 4 mg/dl – a-v fistula! 2. creatinine >4,5 – 5 mg/dl (GFR 4,5 – 5 mg/dl (GFR <20 ml/min):- consider KTx (<45 yrs & IDDM) - consider KTx and pancreas Tx (>45 yrs & NIDDM) - start RRT

16. HD therapy in DM patients Pro: Contra: High efficiacy CVS damage Frequent control problems with a-v fistula No protein loss Hypotonia frequent hypoglycaemia frequent hyperkalaemia

17. CADO treatment in DM patients Pro: Contra: CVS neutral risk of infection No a-v protein loss Good control of kalaemiahernias Good control of glycaemiahelper required

18. Glycaemia regulation in DM patients with ESRD 1. Gluconeogenesis decreased by 30 – 40% 2. Insulin requirement decreased 3-4x 3. Decreased metabolism of some oral drugs (eg. metformin) 4. During HD glucose is „hemodialysed” and lost All the above may lead to hypoglycaemia!

19. DM patient on HD therapy- what should be the treatment? 1. Insulin – 2-3x lower doses! 2. Oral drugs – short acting, metabolized in liver eg: - glipizyd (Glipizyd, Minidiab, Glibenese GITS) - gliclazyd (Diaprel, Diabezyd) - glikwidon (Glurenorm)