1. Chronic Kidney Disease and Diabetes Dr Garth Hanson

2. Talk Pathology of Diabetes Mellitus (DM) DM and Renal Disease Treatment of Hyperglycemia in DM DM Treatment CKD Stage III – IV, Stage V HD, Stage V PD and Renal Transplant Special Considerations

3. Pathology of Diabetes

4. Hyperglycemia

5. Pancreas Hyperglycemia Reduced insulin production

6. Pancreas muscle Hyperglycemia Reduced insulin production Reduced uptake glucose

7. Pancreas muscleliver Hyperglycemia Reduced insulin production Reduced glycogen production or increased gluconeogenasis Reduced uptake glucose

8. Hyperglycemia

9. Non enzymatic glycation of tissues (AGE products)

10. Hyperglycemia Non enzymatic glycation of tissues (AGE products) Cytokine production (VGEF, TGF-beta)

11. Hyperglycemia Non enzymatic glycation of tissues (AGE products) Cytokine production (VGEF, TGF-beta) Tissue ischemia due to microvascular damage

12. Hyperglycemia Non enzymatic glycation of tissues (AGE products) Cytokine production (VGEF, TGF-beta) Tissue ischemia due to microvascular damage ?

15. Basement membrane thickening Glomerular sclerosis Mesangial expansion Arteriolar hyalineosis

16. DM Pathology

17. DM and Renal Outcomes

18. DM and Renal Disease

19. Treatment of Hyperglycemia in DM

20. Reduce Glucose muscle liver pancrease kidney intestine DPP4 GLP

21. Reduce Glucose muscle liver pancrease kidney intestine DPP4 GLP insulin

22. Reduce Glucose muscle liver pancrease kidney intestine DPP4 GLP Alpha glucosidase inhib insulin

23. Reduce Glucose muscle liver pancrease kidney intestine DPP4 GLP metformin Alpha glucosidase inhib insulin

24. Reduce Glucose muscle liver pancrease kidney intestine DPP4 GLP metformin Alpha glucosidase inhib insulin meglithinides sulfonylureas

25. Reduce Glucose muscle liver pancrease kidney intestine DPP4 GLP metformin thioazolinadimediones Alpha glucosidase inhib insulin meglithinides sulfonylureas

26. Reduce Glucose muscle liver pancrease kidney intestine DPP4 GLP metformin thioazolinadimediones Alpha glucosidase inhib DPP4 inhib GLP 1 agonists insulin meglithinides sulfonylureas

27. Reduce Glucose muscle liver pancrease kidney intestine DPP4 GLP metformin thioazolinadimediones Alpha glucosidase inhib DPP4 inhib GLP 1 agonists insulin meglithinides sulfonylureas SGLT2

28. DM Treatment in CKD

29. CKD Stage III - IV RAS Blockage/HTN control Lipids Antiplatelet /Anticoagulation Glucose Control

30. CKD Stage III - IV RAS Blockage/HTN control Each 10 mmHg of systolic BP 13% reduction in microvascular complications (UKPDS) After ACCORD, target 140 mmHg and above 120 mmHg.

31. CKD Stage III - IV RAS Blockage/HTN control ACE and ARB reduce progression by 16% to 30%. Dual RAS blockage not helpful (ONTARGET, NEHRON-D, ALTITUDE) African Americans may not benefit as much. Long acting agents usually chosen (Ramipril, Perindopril)

32. CKD Stage III - IV Lipids Secondary prevention of CVD events definitely beneficial (TNT trail) target to 1.8 LDL Primary prevention of CVD likely beneficial (CARDS, SHARP). Combination therapy not likely of benefit (ACCORD, ENHANCE).

33. CKD Stage III - IV Lipids Statin therapy does not appear to reduce progression to ESRD (SHARP, CARDS). Watch high dose rosuvastatin and simvastatin atorvastatin safe at all doses

34. CKD Stage III - IV Antiplatelet /Anticoagulation Secondary prevention beneficial Primary prevention in doubt except for highest risk. Newer agents have little data

35. CKD Stage III - IV Glucose Control DM 1 - 8% HA1C vs 9%-10% reduced progression of nephropathy by 50%. DM 2 – UKDPS 21% reduction in progression of nephropathy, ACCORD 32% reduction in nephropathy with lower HA1C (under 7%) BUT mortality unchanged or increased.

36. CKD Stage III - IV Glucose Control metformin should be stopped at GFR 30 ml/min Insulin has prolonged halflife Thiazolindinediones may cause volume and bone issues SGLT2 inhibitors less efficacious under GFR 45 ml/min

37. CKD V-Hemodialysis RAS Blockage/HTN control Lipids Antiplatelets /Anticoagulation Glucose Control

38. High Quality Evidence in HD

39. DM and Hemodialysis DM monitoring – HA1C may be inaccurate due to RBC turnover, uremic toxins, acidosis – Low sugars more common due to prolonged insulin lifespan – Tolerate very high glucose levels due to no urine output DM control – Insulin safest but use reduced dose – Linagliptin (Trajenta) safe – Repeglinide (Gluconorm) safe

40. CKD V-Peritoneal Dialysis RAS Blockage/HTN control Lipids Antiplatelets /Anticoagulation Glucose Control

41. High Quality Evidence in PD

42. DM and PD DM monitoring – HA1C inaccurate with high turnover of RBC with epo agents – Icodextran converted to maltose messes up meters DM Treatment – May need massive insulin doses with glucose load in PD fluid

43. CKD V-Transplant RAS Blockage/HTN control Lipids Antiplatelets /Anticoagulation Glucose Control

44. DM and Transplants Prednisone will increase glucose intolerance Calcinurin inhibitors (tac > cyclo) cause DM due to islet cell toxicity No metformin Repeglinide, trajenta, insulin ok

45. Special Considerations Hyperglycemia – Very high levels can be tolerated – High K due to osmotic shift – Low Na due to osmotic shift – Treat with insulin infusion not fluid load Hypoglycemia – Anorexia due to uremia. Watch for malignancy and infection – Avoid long acting oral agents and long acting insulin

46. Special Considerations Hypo alternating with Hyper – Gastroporesis may alter glucose absorption, gastric emptying study will diagnose. Treat with promotility agents. – Watch for non compliance with PD as cause (lower sugar load).

47. QUESTIONS?