A 33-year-old man comes to the hospital due to left flank pain. The patient has never had these symptoms previously. He has been told during past physicals that his blood pressure is elevated, but he never followed up. The patient's father died suddenly in his sleep at age 42. Blood pressure is 170/100 mm Hg in both arms, and pulse is 82/min. Cardiopulmonary examination is normal. The abdomen is soft, and mild tenderness is noted in the left flank. Renal ultrasonogram reveals mildly enlarged kidneys containing multiple cysts of varying sizes; echogenic foci compatible with nephrolithiasis are also noted in the left kidney. The patient's pain is well controlled with analgesics. However, his blood pressure remains elevated. Which of the following is the most likely cause of hypertension in this patient?

Question

A 33-year-old man comes to the hospital due to left flank pain.  The patient has never had these symptoms previously.  He has been told during past physicals that his blood pressure is elevated, but he never followed up.  The patient's father died suddenly in his sleep at age 42.  Blood pressure is 170/100 mm Hg in both arms, and pulse is 82/min.  Cardiopulmonary examination is normal.  The abdomen is soft, and mild tenderness is noted in the left flank.  Renal ultrasonogram reveals mildly enlarged kidneys containing multiple cysts of varying sizes; echogenic foci compatible with nephrolithiasis are also noted in the left kidney.  The patient's pain is well controlled with analgesics.  However, his blood pressure remains elevated.  Which of the following is the most likely cause of hypertension in this patient?

Quizplus · Accepted Answer

This patient likely has autosomal dominant polycystic kidney disease (ADPKD). Affected patients begin developing asymptomatic kidney cysts early in life. By age 30-40, the cystic changes have often progressed to the point that disease manifestations become clinically apparent. The most common early disease manifestations include flank pain, hematuria, and hypertension. Hypertension typically precedes any clinically detectable renal dysfunction and its progression correlates with the cystic structural derangement of the kidneys. It is believed the hypertension results from cyst expansion leading to localized renal ischemia and consequent increased renin release. The increased activation of the renin-angiotensin-aldosterone system (RAAS) in effect leads to secondary hyperaldosteronism. Due to their inhibition of RAAS, ACE inhibitors (eg, lisinopril) are the drugs of choice for treating hypertension in ADPKD. Other complications of ADPKD include nephrolithiasis (most commonly uric acid stones due in part to a tendency toward acidic urine in ADPKD) and cerebral aneurysms. The sudden death of this patient's father at a young age suggests rupture of a cerebral aneurysm in the setting of ADPKD. (Choice A) Urine concentrating ability is reduced in ADPKD due to cystic destruction of nephron distal tubules and impairment of vasopressin (V2) receptors. In effect, a mild nephrogenic diabetes insipidus is created, leading to upregulated and increased production of vasopressin. (Choices B and F) Renal blood flow (RBF) decreases as cystic structural derangement of the kidneys progresses and damages the renal vasculature. In response, production of prostaglandins increases to attempt to dilate renal afferent arterioles and restore RBF. (Choices C and D) Circulating norepinephrine levels are increased in pheochromocytoma, and cortisol production is increased in Cushing syndrome. Both disorders commonly result from a functioning adrenal adenoma and lead to secondary hypertension; however, this patient's multiple renal cysts make ADPKD more likely. (Choice E) Early in the course of ADPKD, erythropoietin levels may be increased, resulting in mild polycythemia; however, the increase is not a major cause of hypertension. As ADPKD progresses, erythropoietin levels decrease as structural derangement progresses and chronic kidney disease develops. Educational objective: Hypertension is one of the earliest clinical manifestations of autosomal dominant polycystic kidney disease. It likely results from cyst expansion leading to localized renal ischemia and consequent increased renin production with activation of the renin-angiotensin-aldosterone system. Therefore, the hypertension is best treated with ACE inhibitors (eg, lisinopril). References: Hypertension in autosomal dominant polycystic kidney disease. (http://www.ncbi.nlm.nih.gov/pubmed/20219618)

A 33-Year-Old Man Comes to the Hospital Due to Left