A 44-year-old man who was recently diagnosed with idiopathic membranous nephropathy after developing edema comes to the office due to a sudden onset of left flank pain and gross hematuria. The patient has no other medical problems. He is taking furosemide and ramipril. Blood pressure is 135/85 mm Hg and pulse is 88/min. On examination, there is left flank tenderness. The patient's edema has improved from the previous visit. There is a left-sided varicocele that the patient has not noticed before. Urinalysis shows increased proteinuria and new hematuria. Serum lactate dehydrogenase is elevated. Urinary loss of which of the following substances most likely predisposed this patient to his acute condition?

Question

A 44-year-old man who was recently diagnosed with idiopathic membranous nephropathy after developing edema comes to the office due to a sudden onset of left flank pain and gross hematuria.  The patient has no other medical problems.  He is taking furosemide and ramipril.  Blood pressure is 135/85 mm Hg and pulse is 88/min.  On examination, there is left flank tenderness.  The patient's edema has improved from the previous visit.  There is a left-sided varicocele that the patient has not noticed before.  Urinalysis shows increased proteinuria and new hematuria.  Serum lactate dehydrogenase is elevated.  Urinary loss of which of the following substances most likely predisposed this patient to his acute condition?

Quizplus · Accepted Answer

This patient with membranous nephropathy, flank pain, hematuria, and left varicocele likely has renal vein thrombosis (RVT) as a result of nephrotic syndrome. Due to increased glomerular capillary wall permeability in nephrotic syndrome, many important substances are lost in the urine, causing a number of complications. Loss of anticoagulant factors, especially antithrombin III, leads to a hypercoagulable state, of which RVT can be a manifestation. Patients with RVT can develop sudden-onset abdominal or flank pain and gross hematuria with elevated lactate dehydrogenase as a result of renal infarction. Left-sided varicoceles are relatively common in healthy pubertal men as the aorta and superior mesenteric artery can compress the left renal vein ("nutcracker effect"), resulting in increased intravascular pressure in the left gonadal vein with retrograde blood flow and varicocele formation. However, a new-onset left varicocele associated with ipsilateral flank pain and hematuria should raise suspicion for RVT causing impaired left gonadal venous drainage. (Choice A) Albumin is also lost in massive quantities in urine in nephrotic syndrome, leading to hypoproteinemia, decreased intravascular oncotic pressure, and fluid shifts into the interstitium. Albuminuria explains the patient's edema (improved from his previous visit) but not his acute flank pain, hematuria, and left-sided varicocele, which are more likely due to thrombosis. Protein loss also results in a negative nitrogen balance. (Choice B) Alpha-1 antitrypsin deficiency is an inherited condition that results in early emphysema and liver cirrhosis. (Choice D) Serum ceruloplasmin is decreased in Wilson disease (hepatolenticular degeneration), which is clinically characterized by liver disease, motor abnormalities, and psychiatric symptoms. Ceruloplasmin has no role in the pathogenesis of nephrotic syndrome. (Choice E) The loss of immunoglobulins and low-molecular-weight components of complement (such as factor B) makes patients with nephrotic syndrome vulnerable to infections, especially pneumococcal infections. (Choice F) Lipiduria is common in nephrotic syndrome as a result of increased lipoprotein synthesis by the liver and increased glomerular capillary wall permeability, leading to lipid loss in the urine in the form of free fat and oval fat bodies (with characteristic Maltese cross appearance under polarized light). However, lipiduria does not contribute to the hypercoagulable state. Educational objective: Nephrotic syndrome is a hypercoagulable state. Sudden-onset abdominal or flank pain, hematuria, and left-sided varicoceles suggest renal vein thrombosis, a well-known complication of nephrotic syndrome. Loss of anticoagulant factors, especially antithrombin III, is responsible for the thrombotic and thromboembolic complications of nephrotic syndrome. __________ References: Renal colic as the first symptom of acute renal vein thrombosis, resulting in the diagnosis of nephrotic syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/19384237) Unilateral renal vein thrombosis and nephrotic syndrome. Report of a case with protein selectivity and antithrombin III clearance studies. (http://www.ncbi.nlm.nih.gov/pubmed/937349)

A 44-Year-Old Man Who Was Recently Diagnosed with Idiopathic Membranous