Diabetic Nephropathy

Patients are tested for proteinuria by routine urinalysis; if proteinuria is present, testing for microalbuminuria is unnecessary because the patient already has macroalbuminuria suggestive of diabetic renal disease. In patients without proteinuria on urinalysis, an albumin/creatinine ratio should be calculated from a mid-morning urine specimen. A ratio ≥ 30 mg/g (≥ 34 mg/mmol) indicates microalbuminuria if it is present on at least 2 of 3 specimens within 3 to 6 months and if it cannot be explained by infection or exercise.

Some experts recommend that microalbuminuria be measured from a 24-hour urine collection, but this approach is less convenient, and many patients have difficulty accurately collecting a specimen. The random urine albumin/creatinine ratio overestimates 24-hour collection of microalbuminuria in up to 30% of patients > 65 due to reduced creatinine production from reduced muscle mass. Inaccurate results can also occur in very muscular patients or if vigorous exercise precedes urine collection.

For most patients with diabetes who have proteinuria, the diagnosis is clinical. Renal biopsy Renal biopsy Biopsy of the urinary tract requires a trained specialist (nephrologist, urologist, or interventional radiologist). Indications for diagnostic biopsy include unexplained nephritic or nephrotic... read more can confirm the diagnosis but is rarely necessary.

Patients with type 1 diabetes without known renal disease should be screened for proteinuria and, if proteinuria is absent on routine urinalysis, for microalbuminuria, beginning 5 years after diagnosis and at least annually thereafter.

Patients with type 2 diabetes should be screened at the time of diagnosis and annually thereafter.

Primary treatment is strict glucose control to maintain HbA1C ≤ 7.0; maintenance of euglycemia reduces microalbuminuria but may not retard disease progression once diabetic nephropathy is well-established.

Glucose control must also be accompanied by strict control of BP to < 130/80 mm Hg, although some experts now recommend BP < 140/90 mm Hg. Some suggest BP should be 110 to 120/65 to 80 mm Hg, particularly in patients with protein excretion of > 1 g/day; however, others claim that BP values < 120/85 mm Hg are associated with increased cardiovascular mortality and heart failure.

Angiotensin inhibition is first-line therapy. Thus, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) are the antihypertensives of choice; they reduce BP and proteinuria and slow the progression of diabetic nephropathy. ACE inhibitors are usually less expensive, but ARBs can be used instead if ACE inhibitors cause persistent cough. Treatment should be started when microalbuminuria is detected regardless of whether hypertension is present; some experts recommend medications be used even before signs of renal disease appear.

Diuretics are required by most patients in addition to angiotensin inhibition to reach target BP levels. Dose should be decreased if symptoms of orthostatic hypotension develop or serum creatinine increases by more than 30%.

Nondihydropyridine calcium channel blockers (diltiazem and verapamil) are also antiproteinuric and renoprotective and can be used if proteinuria does not meaningfully decrease when target BP is reached or as alternatives for patients with hyperkalemia Hyperkalemia Hyperkalemia is a serum potassium concentration > 5.5 mEq/L (> 5.5 mmol/L), usually resulting from decreased renal potassium excretion or abnormal movement of potassium out of cells. There... read more or other contraindications to ACE inhibitors or ARBs.

In contrast, dihydropyridine calcium channel blockers (eg, nifedipine, felodipine, amlodipine) do not reduce proteinuria, although they are useful adjuncts for BP control and may be cardioprotective in combination with ACE inhibitors. ACE inhibitors and nondihydropyridine calcium channel blockers have greater antiproteinuric and renoprotective effects when used together, and their antiproteinuric effect is enhanced by sodium restriction. Nondihydropyridine calcium channel blockers should be used with caution in patients taking beta-blockers because of the potential to worsen bradycardia.

Dyslipidemia Dyslipidemia Dyslipidemia is elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high-density lipoprotein cholesterol (HDL-C) level that contributes to the development of atherosclerosis... read more should also be treated.

Statins should be used as first-line therapy for dyslipidemia treatment in patients with diabetic nephropathy because they reduce cardiovascular mortality and urinary protein.

Dietary protein restriction yields mixed results. The American Diabetes Association recommends that people with diabetes and overt nephropathy be restricted to 0.8 to 1.2 g protein/kg/day. Significant protein restriction is not recommended.

SGLT 2 inhibitors should also be given to patients with type 2 diabetes, but not those with type 1 diabetes or those with an eGFR of < 20 mL/minute. Inhibition of the sodium glucose transporter has been shown to reduce the progression of kidney disease (1, 2, 3 Treatment references Diabetic nephropathy is glomerular sclerosis and fibrosis caused by the metabolic and hemodynamic changes of diabetes mellitus. It manifests as slowly progressive albuminuria with worsening... read more ).

Vitamin D supplementation, typically with cholecalciferol (vitamin D3).

Sodium bicarbonate, given to maintain a serum bicarbonate concentration > 22 mEq/L (22 mmol/L), may slow disease progression in patients with chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more and metabolic acidosis Metabolic Acidosis Metabolic acidosis is primary reduction in bicarbonate (HCO3⁻), typically with compensatory reduction in carbon dioxide partial pressure (Pco2); pH may be markedly low or slightly... read more .

Treatments for edema can include the following:

Kidney transplantation Kidney Transplantation Kidney transplantation is the most common type of solid organ transplantation. (See also Overview of Transplantation.) The primary indication for kidney transplantation is End-stage renal failure... read more with or without simultaneous or subsequent pancreas transplantation Pancreas Transplantation Pancreas transplantation is a form of pancreatic beta-cell replacement that can restore normoglycemia in diabetic patients. (See also Overview of Transplantation.) Because the recipient exchanges... read more is an option for patients with end-stage kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more . The 5-year survival rate for patients with type 2 diabetes receiving a kidney transplant is almost 77%, compared with 88% for patients who do not have diabetes. Kidney allograft survival rates are > 97% and 77% among living and deceased donor transplant recipients, respectively, at 5 years (4, 5 Treatment references Diabetic nephropathy is glomerular sclerosis and fibrosis caused by the metabolic and hemodynamic changes of diabetes mellitus. It manifests as slowly progressive albuminuria with worsening... read more ).