Diabetic Nephropathy

GENERAL PRINCIPLES

Epidemiology

Approximately 20%-40% of patients with either type of diabetes develop clinically evident diabetic nephropathy during their lifetime. Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in the United States and a major cause of morbidity and mortality in patients with diabetes.

Risk Factors

Albuminuria is defined as an urinary albumin-to-creatinine ratio #8805;30 mg/g. Poor glycemic control is the major risk factor for diabetic nephropathy, but hypertension and smoking are contributors. Obesity may contribute to kidney damage in T2DM.

Prevention

Prevention of diabetic nephropathy starts at the time of diagnosis with achievement of glycemic, blood pressure, and lipid targets and smoking cessation. Patients with CKD are at higher risk for CVD and mortality, so management of other CV risk factors is particularly important.

DIAGNOSIS

• Measurement of the albumin-to-creatinine ratio (normal, lt;30 mg of albumin/g of creatinine) in a random urine sample is recommended for screening annually for individuals with T1DM gt;5 years and T2DM beginning at diagnosis. At least two to three measurements within a 6-month period should be performed to establish the diagnosis of diabetic nephropathy.

• Measurement of serum creatinine and serum urea nitrogen should be performed annually, along with calculation of the estimated GFR. Patients with diabetes may have reduced kidney function without manifesting albumin in their urine. Testing and treatment of associated disorders such as anemia, secondary hyperparathyroidism, hyperkalemia, and acid-base disturbances should begin when the estimated GFR is lt;60 mL/min/1.73 m² or during stage 3 CKD (see Chapter 13, Renal Diseases).

TREATMENT

Intensive control of both diabetes and hypertension is important to reduce the rate of progression of CKD due to diabetes.

Medications

• Antihypertensive treatment with ACE inhibitor or ARB drugs is recommended as first-line therapy for all patients with diabetes and hypertension and may be considered in patients with normal blood pressure or prehypertension.

• SGLT2 inhibitors have demonstrated benefit in reducing risk of progression of kidney disease and should be used regardless of A1C or concomitant therapy. Empagliflozin and canagliflozin can be initiated at eGFR of 30 mL/min/1.73 m² and continued until renal replacement is planned.

• Diuretics and dihydropyridine calcium channel blockers can be added. Mineralocorticoid receptor antagonist can be added if not at goal on above agents; however, hyperkalemia is common. The nonsteroidal mineralocorticoid receptor antagonist, finerenone, has been shown to reduce progression of CKD and provide CV benefit with less hyperkalemia in persons with T2DM and CKD.³²

Lifestyle/Risk Modification

• Dietary protein intake of 0.8 g/kg/d (based on ideal body weight) is recommended. Further reduction does not alter glycemic control, CVD risk, or kidney function decline.

• Avoidance of renal toxins is important for preservation of kidney function.