What are the indications for nephrology evaluation in a diabetic patient with albuminuria (microalbuminuria)?

From the Guidelines

Diabetic patients with albuminuria should be referred for nephrology evaluation when they have persistent albuminuria (urine albumin-to-creatinine ratio >30 mg/g) despite optimal treatment with ACE inhibitors or ARBs for 3-6 months, especially if the ratio exceeds 300 mg/g, or if estimated glomerular filtration rate (eGFR) falls below 60 mL/min/1.73m², as indicated by the 2018 standards of medical care in diabetes 1.

Key Considerations

• The presence of albuminuria is a well-established marker of increased cardiovascular disease (CVD) risk and a potential early stage of diabetic nephropathy in type 1 diabetes and a marker for development of nephropathy in type 2 diabetes, as noted in the 2014 standards of medical care in diabetes 1.
• First-line treatment should include an ACE inhibitor like lisinopril (10-40 mg daily) or an ARB such as losartan (50-100 mg daily), along with optimal glycemic control targeting HbA1c <7% and blood pressure <130/80 mmHg.
• SGLT2 inhibitors (empagliflozin 10-25 mg daily or dapagliflozin 5-10 mg daily) should be added as they provide renoprotection independent of glycemic control, as supported by recent clinical guidelines.
• GLP-1 receptor agonists may also be beneficial in managing diabetic kidney disease.

Referral Criteria

• Persistent albuminuria (urine albumin-to-creatinine ratio >30 mg/g) despite optimal treatment with ACE inhibitors or ARBs for 3-6 months.
• Estimated glomerular filtration rate (eGFR) falls below 60 mL/min/1.73m².
• Rapid decline in kidney function (>5 mL/min/1.73m² per year).
• Uncertainty about the etiology of kidney disease, difficult management issues, and rapidly progressing kidney disease, as recommended by the 2018 standards of medical care in diabetes 1.

From the FDA Drug Label

The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation Trial (CREDENCE) was a multinational, randomized, double-blind, placebo-controlled trial comparing canagliflozin with placebo in adult patients with type 2 diabetes mellitus, an eGFR ≥ 30 to < 90 mL/min/1. 73 m 2and albuminuria (urine albumin/creatinine > 300 to ≤ 5,000 mg/g) who were receiving standard of care including a maximum-tolerated, labeled daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB)

The indication of nephrology evaluation for a diabetic patient with albuminuria is not directly stated in the provided drug label. However, the CREDENCE trial included patients with type 2 diabetes mellitus and albuminuria, suggesting that these patients may benefit from nephrology evaluation and management.

• Key points:
  • The CREDENCE trial demonstrated the efficacy of canagliflozin in reducing the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, and renal or CV death in patients with type 2 diabetes mellitus and albuminuria.
  • Patients in the trial had an eGFR ≥ 30 to < 90 mL/min/1.73 m^2 and albuminuria (urine albumin/creatinine > 300 to ≤ 5,000 mg/g).
  • The trial results suggest that nephrology evaluation and management may be beneficial for diabetic patients with albuminuria, particularly those with established nephropathy 2.

From the Research

Indications for Nephrology Evaluation

The presence of albuminuria in diabetic patients is a significant indicator for nephrology evaluation. Key points to consider include:

• Albuminuria is characterized as an early predictor for the progression of diabetic nephropathy (DN) 3
• Proteinuria, or macroalbuminuria, is a universal finding in progressive renal disease and is viewed as a measure of the severity and determinant for diabetic renal disease progression 3
• Albuminuria is a marker for early DN, an independent predictor for mortality, and is associated with renal and cardiovascular risks 3

Diagnostic Considerations

Diabetic nephropathy (DN) is a major healthcare challenge, occurring in up to 50% of those living with diabetes, and is a major cause of end-stage kidney disease (ESKD) that requires treatment with dialysis or renal transplantation 4. 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 4.

• Urine albumin-to-creatinine ratio (UACR) is a sensitive and early indicator of kidney damage, which should be used routinely to accurately assess CKD stage and monitor kidney health 5
• The classical presentation of DN is characterized by hyperfiltration and albuminuria in the early phases, which is then followed by a progressive renal function decline 6

Management and Prognosis

The management of metabolic and hemodynamic perturbations for the prevention and for the delay of progression of DKD is very important 6.

• Tight glycemic control reduces the risk of progression from normoalbumuria to microalbuminuria, as well as from microalbuminuria to proteinuria 3
• Albuminuria, elevated serum creatinine, and low estimated glomerular filtration rate (eGFR) are pivotal indicators of kidney decline, and are associated with a greater risk of experiencing clinical outcomes, including kidney disease progression and cardio-renal outcomes 7