This document discusses diabetic nephropathy, including its causes, risk factors, stages, diagnosis, progression, and treatment strategies. It notes that diabetic nephropathy is a major complication of diabetes and a leading cause of end-stage renal disease. Key points include that strict control of blood pressure, blood glucose, diet, and lifestyle factors can help prevent or slow the progression of kidney damage caused by diabetes.

1. Diabetic Nephropathy Dr Mohamed Alamin Nephrology and Renal Transplant Specialist KAAH & OC Jiddah KSA

2. بسم الله الرحمن الرحيم

5. Diabetic Nephropathy USRDS 2006

6. Diabetic Nephropathy Saudi Arabia 2006

7. DN: Diagnosis What are the Diagnostic Criteria ? Who are the Susceptible Patients ?

8. DN: Diagnosis What are the Diagnostic Criteria ? Who are the Susceptible Patients ?

12. Diabetic Patient IN Development Of In The Presence Of Diabetic Retinopathy Hypertension Progressive Renal Deterioration Absence of other causes P ersistant Proteinuria > 300 mg / day DN: Diagnostic Criteria Type 1> 10 Y Type 2 at Diagnosis

13. 1. Duration of Diabetes in DN Average Type 1: Overt DN Rarely occur before 10 yrs. Type 2: May be present in newly diagnosed patients . Peak Peak incidence  10 to 20 y duration If duration > 30 y + Normoalbuminuria Risk is Very Low DN: Diagnostic Criteria Decline After 20 y  Progressive decline in incidence takes place.

14. Normal Protein in urine should not exceed 150 mg /day 2. Abnormal Urinary Albumin Excretion DN: Diagnostic Criteria

16. The structural damage in DN leads to Albumin in urine = Albuminuria 2. Abnormal Urinary Albumin Excretion DN: Diagnostic Criteria

19. 3. Retinopathy DN: Diagnostic Criteria

20. 3. Retinopathy DN: Diagnostic Criteria

21. Higher levels of blood pressure are associated with more rapid progression of diabetic kidney disease Most patients with diabetic kidney disease are hypertensive Hypertension is both a cause and a consequence of renal disease and the kidney is both villain and victim in hypertension. Critchley JA et al. Chin Med J (Engl). 2002 Jan;115(1):129-35. 4. Hypertension DN: Diagnostic Criteria

22. 4. Hypertension DN: Diagnostic Criteria With Macroalbuminuria: >90% With Microalbuminuria: 80% At Diagnosis: 50% Type 2 With Macroalbuminuria: 65-88% With Microalbuminuria: 30-50% At Diagnosis: 20-40% Type 1

25. 4. Hypertension Effect On Glomerulus Hypertension Dilatation of Afferent Arteriole Increase Intraglomerular Pressure Hyperfiltration Hemodynamically Mediated Damage Evans CT. Clin Diab. VOL. 18 NO. 1 2000

27. 4. Hypertension Strong Or The Strongest Aggravating Factor For DN

29. 5. Progressive Deterioration of RF DN: Diagnostic Criteria

31. Lack of Retinopathy or Neuropathy Persistent Hematuria (microscopic or macroscopic) Signs or symptoms of Systemic Disease Rapidly Rising Creatinine High SCr with little or no Proteinuria F/H of Nondiabetic Renal Disease (e.g. polycystic kidney disease or Alport syndrome) Short Duration of Diabetes 6. Exclusion of Other Causes Markers of Non Diabetic Renal Diseases Indications of Renal Biopsy in Diabetes 1 2 3 4 5 6 7

32. Diabetic Nephropathy Pathogenesis of DN

33. Intra glomerular HTN Hyperperfusion Aff VD/ Eff VC Hyperfiltration Polyol Pathway Protein Kinase C GF, Cytokines(TGF-B) ROS  Gl.Hydrolic Pressure Endothelial Dysfunction Angitensin II Glucotoxicity Structural Changes Metabolic Changes Functional Changes AGEs  Renal Plasma Flow Glomerulosclerosis Thickening of GBM Mesangial Expansion Hyperglycemia Renal Hypertrophy

34. DN: Pathogenesis

35. DN: Pathogenesis

36. Diabetic Nephropathy Stages of DN

37. <30mg/day 30-300mg/day >300mg/d DN: Stages

38. Natural History of Type 1 Diabetic Nephropathy DN: Natural History

39. Susceptibility Silent Silent Incipient Overt ESRD DN: Natural History Natural History of Type 2 Diabetic Nephropathy

40. Diabetics with Macroalbuminuria are More Likely to Die than Develop ESRD C V D E A T H The United Kingdom Prospective Diabetes Study (approx. 5000 Type 2 Diabetics) Newly diagnosed, predominantly white, medically treated Adler et al. Kid Int, 2003 Elevated Serum Creatinine 19% No albuminruia 1.4% Microalbuminruia 3.0% Macroalbuminruia 4.6%

41. Diabetic Nephropathy Death Rate In Diabetic Patients on RRT 54.1

42. Causes of Death DN: Causes of Death Stroke Myocardial Infarction Heart Failure Sudden Death

44. Microalbuminuria Macroalbuminuria 80%/10-15y Macroalbuminuria ESRD 50%/ 10y 75%/ 20y Without Specific Interventions in type 1 DM Microalbuminuria Macroalbuminuria Macroalbuminuria ESRD 20%/ 20y Without Specific Interventions in type 2 DM 20-40 % American Diabetic Association. Diab Care 2004 DN: Prognosis

45. DN: Where to Meet the Patients? Susceptibility Silent Silent Incipient Overt ESRD Screening and Prevention of Type 2 Diabetes Screening and Prevention of Diabetic Nephropathy Natural History of Type 2 Diabetic Nephropathy Prevention of progression of MiA to overt DN

46. Preventive/ Pre-emptive Strategies Screening For DN Prevention Of DN

47. 1 American Diabetes Association: Nephropathy in Diabetes (Position Statement). Diabetes Care 27 (Suppl.1): S79-S83, 2004 BP UAE Lipid At Least Annually < 150mg/dl TG < 100 mg/dl LDL > 40mg/dl HDL DN: Screening

48. DN: Screening

50. DN: Screening

51. Dietition Endocrinologist Physician Trained Diabetes Nurse General Practitioner Multiseciplinary Approach Prevention Of DN Requirements DN: Prevention/Preemptive St.

56. Treatment of Overt DN

57. The Renal Injury Triad Angiotensin II Proteinuria Hypertension In Diabetes Smoking Hyperlipidemia Hyperglycemia Dietary protein

74. Role of Spironolactone

75. Role of Spironolactone

76. THANKS Dr. Mohamed Alamin