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1
Question:

A 22-year-old man comes to the urgent care clinic for evaluation due to dark urine that he noticed earlier this morning.  The patient is recovering from an upper respiratory tract infection that started 3 days ago, for which he has been taking ibuprofen as needed.  Medical and family histories are unremarkable.  Temperature is 37.7 C (99.9 F), blood pressure is 145/92 mm Hg, pulse is 80/min, and respirations are 14/min.  Physical examination shows no rash or joint abnormalities.  Laboratory results are as follows:

Urinalysis
Glucosenegative
Protein1+
Leukocyte esterasenegative
White blood cells3-6/hpf
Red blood cells30-50/hpf
Castsred blood cells
Serum chemistry
Blood urea nitrogen18 mg/dL
Serum creatinine1.4 mg/dL

Serum complement levels (C3, C4) are within normal limits, and other serologic workup is pending.  Which of the following is the most likely diagnosis in this patient?

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Explanation:

This patient's gross hematuria, elevated creatinine, and hypertension after an upper respiratory infection (URI) raise concern for acute poststreptococcal glomerulonephritis (APSGN) or IgA nephropathy.  APSGN classically causes symptoms weeks after group A Streptococcus infection (eg, pharyngitis, impetigo), and complement levels are low (Choice B).  This patient has normal serum complement levels and onset of symptoms days after a URI (synpharyngitic), findings suggestive of IgA nephropathy, which is more common in adults.

Mucosal infection can trigger production of pathogenic IgA, which is then deposited in the mesangium.  Patients can develop asymptomatic, microscopic hematuria or gross hematuria with nephritic syndrome.  Flank pain, low-grade fever, and hypertension may be present.  Characteristic urinalysis findings include proteinuria, hematuria, and red blood cell (RBC) casts.  Serum complement levels are normal because of the weak complement-fixing activity of IgA.  Creatinine may be elevated.

The diagnosis is typically clinical but can be confirmed with kidney biopsy.  Although episodes may recur, IgA nephropathy is often a benign disease with no chronic kidney injury.  Clinical predictors of progressive disease include hypertension, elevated creatinine, and persistent proteinuria.

(Choice A)  Acute interstitial nephritis is an inflammatory process involving the renal tubules and interstitium following exposure to a drug (eg, nonsteroidal anti-inflammatory drugs).  Patients typically have fever and rash, findings not seen in this patient.  Urinalysis would also show white blood cell, not RBC, casts.

(Choice C)  Anti–glomerular basement membrane (anti-GBM) disease is due to anti-GBM antibodies against type IV collagen in the glomeruli and alveolar lining.  Manifestations include rapidly progressive glomerulonephritis with or without alveolar hemorrhage.  This patient's recent URI and lack of significantly elevated creatinine make this rare diagnosis less likely.

(Choice D)  Hereditary nephritis (Alport syndrome) due to defective type IV collagen causes hematuria and progressive renal insufficiency.  However, most male patients have hematuria beginning in early childhood and develop hearing loss in adolescence.  This patient's unremarkable medical and family histories make this diagnosis less likely.

(Choice F)  Thin basement membrane disease is a benign familial condition that presents as microscopic or gross hematuria, which can occur after URI.  A family history of hematuria usually exists, and hypertension and/or elevated creatinine is not typically seen.

Educational objective:
IgA nephropathy is characterized by mesangial IgA deposition, usually within days after an upper respiratory infection.  Characteristic features include hematuria with red blood cell casts on urinalysis and normal complement levels; hypertension and elevated creatinine are common.