A 47-year-old woman presents to the clinic with 3 weeks of increased thirst and urination. She has a history of obesity, hypertension, and depression for which she takes losartan and sertraline. She has smoked 1 pack of cigarettes per day for 30 years. Her temperature is 99.5°F (37.5°C), blood pressure is 148/90 mmHg, pulse is 84/min, and respirations are 15/min. Physical exam is unremarkable, including no costovertebral or suprapubic tenderness to palpation. Laboratory studies are performed and show:

Serum:
Na+: 140 mEq/L
K+: 4.4 mEq/L
HCO3-: 21 mEq/L
Blood urea nitrogen (BUN): 38 mg/dL
Creatinine: 1.1 mg/dL
Glucose: 215 mg/dL

Which of the following is the most appropriate screening test for nephropathy in this patient?
Creatinine clearance
Oral glucose tolerance test
Urine albumin-to-creatinine ratio
Hemoglobin A1c
Urine albumin-to-creatinine ratio
This patient with a history of obesity and hypertension presenting with polyuria and polydipsia in the setting of an elevated random blood glucose (> 200 mg/dL) likely has a new diagnosis of type 2 diabetes mellitus. The urine albumin-to-creatinine ratio is the most appropriate early test for diabetic nephropathy.

Early detection of diabetic nephropathy is key to management, as the complication eventually leads to overt kidney disease and renal failure. The diagnosis of diabetic nephropathy is based on > 30 mg/g of albuminuria for > 3 months. Patients with type 2 diabetes mellitus should be screened annually with a random urine albumin-to-creatinine ratio starting at diagnosis. Elevation of urine albumin warrants treatment with ACE inhibitors or angiotensin receptor blockers. Blood pressure control slows the progression of diabetic nephropathy. Patients with type 2 diabetes mellitus and diabetic nephropathy should be started on a sodium-glucose cotransporter 2 (SGLT2) inhibitor. Patients with persistent albuminuria despite both ACE/ARB and SGLT2 inhibitor therapy should be started on the nonsteroidal selective mineralocorticoid receptor antagonist (MRA) finerenone.

Bakris et al. study the efficacy of finerenone, a nonsteroidal selective MRA, in the treatment of patients with albuminuria in patients with chronic kidney disease (CKD) and type 2 diabetes. The authors found in a randomized control trial that finerenone reduced the incidence of a composite outcome of kidney failure. The authors recommend the use of finerenone in patients with persistent albuminuria despite optimal medical therapy to prevent risks of CKD progression and cardiovascular events.

Incorrect Answers:
Answer A: Creatinine clearance changes over the time course of diabetic nephropathy and can be normal or elevated (due to glomerular hyperfiltration) in early diabetic nephropathy. Therefore, it is an unreliable test for early diabetic nephropathy compared to the more sensitive urine albumin-to-creatinine ratio.

Answer B: Hemoglobin A1c is a test that reflects the average blood glucose over the past 2 to 3 months. While this test provides information on a patient's glycemic control, it does not directly assess the presence or extent of diabetic nephropathy.

Answer C: Oral glucose tolerance test is the test of choice for diagnosing gestational diabetes. It does not play a role in the detection of diabetic nephropathy.

Answer E: Urine protein dipstick is a useful test to detect proteinuria. This test is insensitive to low levels of albumin. Therefore, it is considered an inferior test to urine albumin-to-creatinine ratio in the diagnosis of diabetic nephropathy.

Bullet Summary:
Urine albumin-to-creatinine ratio testing is the most sensitive test to detect moderately elevated levels of urinary albumin excretion, a known byproduct of diabetic nephropathy.