Diabetic kidney disease

Diabetic kidney disease (DKD) is usually a clinical diagnosis in a patient with long-standing diabetes (>10 years) with albuminuria and/or reduced estimated glomerular filtration rate (eGFR) in the absence of signs or symptoms of other primary causes of kidney damage.

Symptoms, which may be absent until the disease is advanced, include fatigue, anorexia, and swelling of the extremities. Signs include hypertension, edema, and findings of associated microvascular complications (diabetic retinopathy and neuropathy). As patients become clinically uremic, encephalopathy, nausea and vomiting, dysgeusia (altered taste), bleeding, myoclonus, and pericarditis may be present.

Albuminuria is the characteristic laboratory finding. Deterioration in renal function may develop as the disease advances. However, the pattern of albuminuria and reduced glomerular filtration rate (GFR) is changing, and reduced GFR without albuminuria is becoming more common. Such patients usually have a better renal prognosis than those with overt albuminuria. Progression of DKD may occur even in patients in whom control of diabetes mellitus has been achieved in accordance with guidelines.

Treatment includes intensive management of hyperglycemia and treatment of hypertension with ACE inhibitors, angiotensin-II receptor antagonists, or other antihypertensives. Lipid reduction and smoking cessation may be beneficial. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are moderately to highly effective at glycemic control and very effective at reducing proteinuria and slowing the progression of DKD. Glucagon-like peptide 1 (GLP-1) receptor agonists are highly effective antidiabetic medications with benefits of moderate to marked weight loss, and their use improves kidney and cardiovascular outcomes. Finerenone is the first nonsteroidal mineralocorticoid receptor antagonist to demonstrate positive renal and cardiovascular outcomes in patients with DKD.

Complications include hypoglycemia due to intensive treatment of hyperglycemia, hyperkalemia as an adverse effect of ACE inhibitors or angiotensin-II receptor antagonists, volume depletion due to osmotic diuresis from glycosuria, and inadequate protein/caloric intake leading to malnutrition. Some patients may reach end-stage renal failure, requiring dialysis.

Diabetic kidney disease (DKD) is defined by albuminuria (increased urinary albumin excretion is defined as ≥30 mg/g) and progressive reduction in estimated glomerular filtration rate (eGFR) in the setting of a long duration of diabetes (>10 years' duration of type 1 diabetes; may be present at diagnosis in type 2 diabetes), and is typically associated with retinopathy.[1]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care. 2024 Jan;47(suppl 1):S1-321. https://diabetesjournals.org/care/issue/47/Supplement_1 In most patients with diabetes, chronic kidney disease (CKD) can be attributable to diabetes if these features are met; however, CKD may be present without retinopathy in type 2 diabetes, and without albuminuria in type 1 and type 2 diabetes.[1]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care. 2024 Jan;47(suppl 1):S1-321. https://diabetesjournals.org/care/issue/47/Supplement_1 Other cause(s) of CKD should be considered in the presence of rapidly increasing albuminuria or nephrotic syndrome, rapidly decreasing eGFR, active urinary sediment (e.g., cellular casts in urine), the absence of diabetic retinopathy in patients with type 1 diabetes, or signs or symptoms of other systemic disease.[1]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care. 2024 Jan;47(suppl 1):S1-321. https://diabetesjournals.org/care/issue/47/Supplement_1 The diagnosis of DKD is most conclusively made by findings of mesangial expansion and nodular glomerulosclerosis on kidney biopsy, though kidney biopsy is rarely necessary.