What are the clinical features and management of Diabetic Glomerular Nephropathy (DGn)?

From the Guidelines

Diabetic Glomerular Nephropathy (DGN) management should prioritize a multifaceted approach including glycemic control, blood pressure management, and lifestyle modifications to improve outcomes and slow disease progression, as recommended by recent guidelines 1.

Clinical Features

DGN is characterized by progressive kidney damage due to diabetes, presenting initially with microalbuminuria (30-300 mg/day), followed by macroalbuminuria (>300 mg/day), and eventually declining glomerular filtration rate (GFR) leading to end-stage renal disease. Early signs include hypertension and edema, while laboratory findings show elevated serum creatinine, blood urea nitrogen, and proteinuria.

Management

Management requires:

• Glycemic control with a target HbA1c of <7%, using medications like metformin (500-2000 mg daily), SGLT2 inhibitors (empagliflozin 10-25 mg daily or dapagliflozin 5-10 mg daily), and GLP-1 receptor agonists 1.
• Blood pressure control aiming for <130/80 mmHg, primarily using ACE inhibitors (like lisinopril 10-40 mg daily) or ARBs (such as losartan 50-100 mg daily), which also reduce proteinuria.
• Additional measures include:
  • Dietary protein restriction (0.8 g/kg/day)
  • Sodium restriction (<2 g/day) as recommended by KDIGO guidelines 1
  • Smoking cessation
  • Weight management
  • Regular exercise

Monitoring and Referral

Regular monitoring of kidney function, albuminuria, and electrolytes is essential, with referral to a nephrologist when GFR falls below 30 ml/min/1.73m². Advanced cases may require renal replacement therapy including dialysis or kidney transplantation. Early intervention is critical as DGN damage is often irreversible, with SGLT2 inhibitors showing particular promise in slowing progression through mechanisms beyond glycemic control 1.

From the FDA Drug Label

1. 3 Nephropathy in Type 2 Diabetic Patients Losartan is indicated for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g) in patients with type 2 diabetes and a history of hypertension

• The clinical features of Diabetic Glomerular Nephropathy (DGn) that are relevant to the use of losartan include:
  • Elevated serum creatinine
  • Proteinuria (urinary albumin to creatinine ratio ≥300 mg/g)
  • History of hypertension
• The management of DGn with losartan includes reducing the rate of progression of nephropathy as measured by the occurrence of doubling of serum creatinine or end stage renal disease (need for dialysis or renal transplantation) 2

From the Research

Clinical Features of Diabetic Glomerular Nephropathy

• Diabetic nephropathy (DN) is characterized by persistent albuminuria and a progressive decline in renal function 3
• The classical presentation of DN is characterized by hyperfiltration and albuminuria in the early phases, followed by a progressive renal function decline 4
• Nephrotic syndrome is defined as urine total protein excretion greater than 3.5 g/d or total protein-creatinine ratio greater than 3.5 g/g, low serum albumin level, high serum cholesterol level, and peripheral edema 5
• Diabetic kidney disease (DKD) can vary in presentation, especially in patients with type 2 diabetes, where concomitant presence of other glomerular/tubular pathologies and severe peripheral vascular disease can become important confounders 4

Management of Diabetic Glomerular Nephropathy

• Standard therapy is blood glucose and blood pressure control using the renin-angiotensin system blockade, targeting A1c < 7%, and <130/80 mmHg 6
• Regression of albuminuria remains an important therapeutic goal 6
• In addition to conventional therapies, vitamin D receptor activators, incretin-related drugs, and therapies that target inflammation may also be promising for the prevention of DN progression 6
• Management of metabolic and hemodynamic perturbations for the prevention and for the delay of progression of DKD is very important 4

Diagnosis and Screening

• Screening for microalbuminuria should be performed annually, starting 5 years after diagnosis in type 1 diabetes and at diagnosis and annually thereafter in type 2 diabetes 6
• Diagnosis of DKD is based on the presence of albuminuria or reductions in renal function 3
• The term diabetic kidney disease (DKD) is now commonly used to encompass the spectrum of people with diabetes who have either albuminuria or reductions in renal function 3