A 62-year-old woman comes to the office due to urinary frequency and burning during urination. The patient reports no fever, chills, nausea, back pain, or abdominal pain. Her medical history is significant for long-standing diabetes mellitus and hypertension, for which she takes metformin and lisinopril. The patient does not use tobacco or alcohol. Blood pressure is 149/100 mm Hg and heart rate is 70/min. Hematocrit is 43% and WBC count is 8,500/mm³. Creatinine is 1.1 mg/dL. Urinalysis results are as follows: The patient is given a course of trimethoprim-sulfamethoxazole. Two weeks later, urinalysis reveals 2+ protein but no nitrites, white blood cells, or red blood cells. Her urinary symptoms have resolved. Repeat serum creatinine is 1.1 mg/dL. Which of the following is most likely responsible for her persistent urinalysis abnormality?

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Explanation: 11ec25c8_d13a_a0bf_bc81_5f1bd25f4bf4_MD0003_00 This patient's presenting symptoms of dysuria and urinary frequency, combined with abnormal urinalysis (eg, hematuria, leukocytes, positive nitrites), suggest urinary tract infection. However, after treatment and resolution of urinary symptoms, she continues to have persistent proteinuria. In the context of her long-standing diabetes and poorly controlled hypertension, persistent proteinuria suggests diabetic nephropathy (DN). Metabolic by-products (eg, advanced glycation end-products, reactive oxygen species) associated with diabetes lead to irreversible changes of DN, primarily affecting the glomerular basement membrane and surrounding structures. These include: Glomerular hyperfiltration Glomerular basement membrane fibrosis and thickening Interstitial fibrosis, mesangial thickening, and nodules (Kimmelstiel-Wilson lesion) A common clinical abnormality in DN is persistently elevated albumin excretion, known as moderately increased albuminuria (ie, albumin-creatinine ratio of 30-300 mg/g). Therefore, screening via random urine albumin-creatinine ratio should be performed at least annually, starting either at diagnosis (type 2) or 5 years after diagnosis (type 1). Risk factor modification (eg, diet optimization, exercise, smoking cessation), glycemic control (A1c ≤7.0%), and medical management of hyperlipidemia and hypertension (eg, ACE inhibitors) also help slow the progression of DN. (Choice A) Acute interstitial nephritis (AIN) can be caused by antibiotics (eg, methicillin), infections (eg, Legionella), or systemic disease (eg, sarcoidosis). Trimethoprim-sulfamethoxazole can be a potential cause of AIN; however, this patient lacks the typical AIN findings of acutely elevated creatinine, pyuria (eg, eosinophiluria), and white cell casts in the urine. (Choice B) Atherosclerotic vascular disease can lead to renal artery stenosis, the most common cause of secondary hypertension in adults. Poorly controlled hypertension is a hallmark of this condition; however, this patient's persistent proteinuria is an uncommon finding. (Choice D) Sulfonamide antibiotics can lead to insoluble crystal precipitation in kidney tubules and subsequent obstruction and acute kidney injury. Other causes include acyclovir, excessive vitamin C, and methotrexate. However, crystal-induced obstruction would not cause persistent proteinuria; moreover, findings of acute creatinine elevation or crystalluria would be expected. (Choice E) In adults, vesicoureteral reflux (ie, retrograde passage of urine into the renal pelvis) is associated with neurogenic bladder and can cause frequent urinary tract infections. Long-standing diabetes may cause autonomic bladder dysfunction; however, this patient does not have associated symptoms of chronic incontinence, and persistent proteinuria would be uncommon. Educational objective: Diabetic nephropathy is characterized by glomerular hyperfiltration, basement membrane thickening, and mesangial nodules. Persistent proteinuria in a patient with long-standing diabetes and poorly controlled hypertension should raise suspicion for this diagnosis. References: Markers of inflammation and oxidative stress in the development and progression of renal disease in diabetic patients. (http://www.ncbi.nlm.nih.gov/pubmed/27344598)

A 62-Year-Old Woman Comes to the Office Due to Urinary