D.N

• Diabetic nephropathy


  Affect on kidneys and cause functional and structural changes, one of the chronic complications of DM
• Lesions occurring in the kidney in patients with DM


  • Glomerulosclerosis
  • Arteriosclerosis
  • Chronic interstitial nephritis
  • Papillary necrosis
  • Various tubular defects
• Papilla of renal cortex will suffer blunting and necrosis in diabetic nephropathy, similar to acute obstructive uropathy (e.g. stone)
• Glomerulosclerosis worsens (heavy proteinuria develops) until glomeruli are progressively lost and renal function deteriorates
• Presentation of diabetic nephropathy


  Asymptomatic proteinuria may progress to nephrotic syndrome, acute renal failure, rapidly progressive glomerulonephritis, and chronic renal failure
• Diabetic nephropathy is usually presented with advanced stages
• Histological picture of diabetic nephropathy


  • Increased width of GBM
  • Various exudative lesions
  • Hyaline arteriosclerosis (mainly affecting arterioles)

  
• In diabetic nephropathy, biopsy is usually not required as the history is obvious, patient is young, normotensive, and has uncontrolled DM with no renal impairment
• Nodular glomerulosclerosis (Kimmelstiel-Wilson lesion)


  Reasonably specific for juvenile DM, PAS positive, acellular, laminated, intercapillary nodule, increased mesangial matrix
• Nodular glomerulosclerosis is only seen in type 1 DM (insulin dependent) with no obvious immune reaction
• Periodic acid-Schiff (PAS) stain is used to detect polysaccharides, glycoproteins, glycolipids, and mucosubstances
• Pathophysiology of diabetic nephropathy


  1. Hyperglycemia

  2. Increased renal perfusion

  3. Hyperfiltration
• Hyperfiltration in diabetic nephropathy


  Mediated by proportionately greater relaxation of the afferent arteriole than the efferent arteriole, leading to increased glomerular blood flow and elevated glomerular capillary pressure
• Hemodynamic changes related to the aldose reductase pathway lead to hyperfiltration and loss of negatively charged heparan sulfate in podocytes, which leads to proteinuria
• Stages of diabetic nephropathy


  • Stage of normoalbuminuria
  • Stage of microalbuminuria (30-300 mg/day)
  • Stage of overt proteinuria (>300 mg/day)

  
• In the early stage of diabetic nephropathy, there is an increase in GFR above normal due to increased renal perfusion
• In the microalbuminuria stage, blood pressure is still normal and renal function is normal
• In the overt proteinuria stage, protein excretion increases to 300 mg - 3.5 g/day and blood pressure starts to rise with renal impairment
• Diabetic kidneys are not palpable, unlike in polycystic kidney disease or renal malignancy
• Treatment of diabetic nephropathy


  1. Intensive insulin treatment to improve glycemic control

  2. Use of safe drugs like sulfonylureas, thiazolidinediones, meglitinides, and incretins

  3. Avoid unsafe drugs like metformin and first-generation sulfonylureas

  4. Start ACE inhibitors, ARBs, and non-dihydropyridine CCBs

  5. Manage cardiovascular risk factors
• In type 1 diabetic patients with renal impairment, insulin may accumulate leading to frequent hypotension
• Risk factors for diabetic nephropathy


  • Poor control of blood glucose
  • Long duration of diabetes
  • Presence of other microvascular complications
  • Ethnicity (e.g. Asian races, Pima Indians)
  • Pre-existing hypertension
  • Family history of diabetic nephropathy
  • Family history of hypertension
• Patients with type 1 diabetes should be screened for diabetic nephropathy annually from 5 years after diagnosis, and patients with type 2 diabetes should be screened annually from the time of diagnosis

  
• Hypertensive nephrosclerosis


  Clinical syndrome characterized by long-term essential hypertension, hypertensive retinopathy, left ventricular hypertrophy, minimal proteinuria, and progressive kidney failure
• Histology of hypertensive nephrosclerosis


  • Arteriosclerosis, chronic nephrosclerosis (without immune deposits)
• Complications of hypertensive nephrosclerosis


  • Malignant hypertension
  • Fibrinoid necrosis
  • Thrombotic microangiopathy
  • Acute renal failure
  • Nephrotic syndrome