A 24-year-old man presents to the emergency department with a complaint of one day of painless dark urination. He reports mild bilateral flank pain and denies joint pain and abdominal pain. He has no past medical history but notes that he did have a sore throat a few days ago that resolved without any treatment. His only medication is a multivitamin and 5 grams of creatine daily. His father passed away from urothelial bladder cancer two years ago, and his mother has type 2 diabetes mellitus. He does not drink alcohol or smoke cigarettes. Vital signs include a temperature of 37.1° C (98.6° F), blood pressure 145/90 mmHg, pulse 90 beats/min, and respirations 17/min. Physical examination shows mild pitting edema in his bilateral ankles. Complete blood count is normal. Serum creatinine is 1.5 mg/dL which is elevated from 1.0 mg/dL at his last primary care visit 2 months ago. Serum C3 and C4 are within normal limits. A urinalysis shows the following:
The urine protein-to-creatinine ratio is 1.8 g/day. Which of the following pharmacotherapies is the most appropriate treatment for this patient?
C) Sparsentan
Based on the clinical presentation and urinalysis findings, the most likely diagnosis is IgA nephropathy (IgAN). The presence of hematuria, mild proteinuria, and RBC casts following a recent upper respiratory infection is highly suggestive of IgAN. This is a type III hypersensitivity in which IgA immune complexes deposit within the glomeruli.
The management of primary IgAN focuses on supportive care which includes controlling blood pressure to optimal targets, smoking cessation, and limiting dietary sodium intake. For patients with IgAN and proteinuria ≥500 mg/day, an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) is indicated.
Sparsentan is a relatively new FDA-approved drug for the treatment of IgAN and has a unique mechanism as both an endothelin antagonist and an angiotensin receptor blocker. Through these two mechanisms, sparsentan has shown to reduce blood pressure, decrease proteinuria, and protect the kidneys in IgAN. Sparsentan can be used for patients with IgAN and who are at risk of rapid disease progression defined as a urine protein-to-creatinine ratio ≥1.5 g/day.
Patients who are at high risk of disease progression defined as proteinuria greater than 1 g/day may be given oral glucocorticoids.
Answer choice A: Cisplatin, is incorrect. Cisplatin is one of the drugs used to treat urothelial bladder cancer which also tends to present with painless hematuria. This patient does have a family history of urothelial bladder cancer in his father, but the patient’s young age, lack of smoking or other risk factors (Azo dyes), and prior upper respiratory infection point more towards a diagnosis of IgAN.
Answer choice B: Penicillin, is incorrect. Penicillin would be the correct answer if this patient had post streptococcal glomerulonephritis (PSGN). PSGN presents similarly to IgAN but occurs one week or more after streptococcal pharyngitis, whereas IgAN has an onset shortly after an upper respiratory infection. While both conditions can cause hematuria and elevated blood pressure, the time course of this presentation plus the normal complement levels point towards IgAN.
Answer choice D: Tamsulosin, is incorrect. There is no evidence supporting the use of tamsulosin, an alpha-1 antagonist, in the treatment of IgAN. It remains a staple of the treatment of benign prostatic hyperplasia.
Answer choice E: Trimethoprim-sulfamethoxazole, is incorrect. Trimethoprim-sulfamethoxazole would be an appropriate option if this patient had a urinary tract infection. However, he does not have painful urination or evidence of infection on urinalysis (e.g., positive white blood cells, leukocyte esterase, or nitrites).
Key Learning Point
The management of primary IgAN focuses on supportive care which includes controlling blood pressure to optimal targets, smoking cessation, and limiting dietary sodium intake. For patients with IgAN and proteinuria 500 mg/day, an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker is indicated. Sparsentan, an endothelin antagonist and angiotensin receptor blocker, can be used for patients with IgAN and who are at risk of rapid disease progression defined as a urine protein-to-creatinine ratio ≥1.5 g/day.
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