Diabetic nephropathy (DN) Renal Long-Term complications of DM (Diabetes Mellitus)

Diabetic nephropathy (DN) is responsible for high morbidity and mortality. DN is associated with diabetic retinopathy and hy­perglycemia. DN is due to the effect of growth factors, Angiotensin Il, endothelin, AGEs. A high body mass index (BMI) has been associated with an increased risk of chronic kidney disease among patients with diabetes

• Smoking aggravates renal disease Diabetic nephropathy (DN) Renal complications of DM.
• In Type I and Type Il DM sequence of events is same.
• There is increase in glomerular filtration rate (GFR), there is thickening of glomerular basement mem­brane, glomerular hypertrophy, and GFR returns to normal.
• After 5 – 10 yrs of type I DM most patients have albuminuria.
• Microalbuminuria is 30 – 300 mgjday in 24-hour urine sample or 30 – 300 IJgjmg creatinine in a spot collec­tion.
• Overt proteinuria is more than 300 mgjday. Blood pressure may be normal.
• With overt proteinuria GFR decreases and after about 7 years end-stage renal disease (ESRD) occurs. Overt nephropathy is irreversible.
• In type Il DM microalbuminuria and even overt neph­ropathy may be present at the time of diagnosis. In Type Il DM usually there is hypertension with nephropathy. ,
• In type Il DM albuminuria may be due to hyperten­sion, congestive heart failure, prostatic disease, or infection, besides nephropathy.
• Renal tubular acidosis type IV (hypo-reninemic hypoaldosteronism) may occur in type I or II DM.
• There is hyperkalemia, increased with ACE inhibitors (angiotensin converting enzyme inhibitors) and ARBs (Angiotensin receptor blockers).
• There is increased risk of nephrotoxicity with radio contrast especially in patients with nephropathy and volume depletion.
• Before giving radio-contrast dyes, patients should be given IV fluids and serum creati­nine monitored.
• Also, acetyl cysteine – 600 mg BD a day before and on the day of study can protect high risk patients with serum creatinine more than 2.4 mg/ dl.

PATHOLOGY Diabetic nephropathy (DN) Renal complications of DM —

• different pathogenetic processes leading to the pathologic mechanisms in diabetic nephropathy.
• Pathologic abnormalities are noted in patients with long-standing diabetes mellitus before the onset of microalbuminuria.
• There are three major histologic changes in the glomeruli in diabetic nephropathy:
  • mesangial expansion; glomerular basement membrane thickening; and glomerular sclerosis

Treatment of Renal complications of DM (Diabetes Mellitus)

• Prevention is by detection of microalbuminuria and treating it by strict blood pressure control, control­ling blood sugar, ACE inhibitors, ARBs, lipid lowering drugs.
• Angiotensin converting enzyme inhibitors or angiotensin II receptor blockers have been evaluated for efficacy in the primary prevention of diabetic nephropathy
• When the renal function declines insulin requirement falls because kidney is the site of insulin breakdown.
• Sulphonylureas and Metformin are contraindicated in advanced renal failure.
• BP Strict blood pressure control
  • should be maintained at less than 130/80 mm in patients without proteinuria.
  • Strict blood pressure control is important for preventing progression of diabetic nephropathy and other complications in patients with type 2 diabetes,
• For patients with microalbuminuria or overt nephr­opathy BP should be maintained at less than 125 / 75.
• In patients of Type I and II DM with microalbuminuria ARBs and ACE inhibitors must be prescribed.
• ACE inhibitor in type 1 diabetes can be demonstrated early in the course of the disease when microalbuminuria is the only clinical manifestation
  • Dose of ACE inhibitors and ARBs should be increased after 3 months to a maximum so as to stop albumin­uria.
  • If there are side effects with ACE inhibitors like hyperkalemia, cough or, if, ACE inhibitors cannot be given due to renal insufficiency, then calcium channel blockers may be used.
  • ACE inhibitors may be recom­mended in Type I DM and ARBS in type II DM.
• Protein restriction to 0.8 gm/Kg/day may be advised.
• In ESRD hemodialysis may be required.
• In ESRD due to DM there is greater incidence of hypotension, diffi­cult vascular access, retinopathy. Survival is short in patients of ESRD.
• Hyperlipidemia should be treated strictly.
• Renal transplant from a related donor may be done with chronic immunosuppression.
• Combined pancreas and kidney transplant is best but requires great expertise.