A 39-year-old man comes to the physician with 3 weeks of progressive pedal edema. The edema is mild on awakening in the morning but gets worse as the day progresses. He has no shortness of breath, lower-extremity pain or warmth, or history of heart or liver disease.
His blood pressure is 155/96 mm Hg and pulse is 72/min. Jugular venous pressure is normal. Cardiopulmonary, abdominal, and neurologic examinations are within normal limits. There is soft, 2+ pitting edema of his legs below the knees.
After initial evaluation, the patient undergoes renal biopsy, which is consistent with focal segmental glomerular sclerosis.
Angiotensin-converting enzyme inhibitor therapy is most likely to delay progression of this patient's renal disease in the presence of which of the following additional findings?

Question

A 39-year-old man comes to the physician with 3 weeks of progressive pedal edema.  The edema is mild on awakening in the morning but gets worse as the day progresses.  He has no shortness of breath, lower-extremity pain or warmth, or history of heart or liver disease.
His blood pressure is 155/96 mm Hg and pulse is 72/min.  Jugular venous pressure is normal. Cardiopulmonary, abdominal, and neurologic examinations are within normal limits.  There is soft, 2+ pitting edema of his legs below the knees.
After initial evaluation, the patient undergoes renal biopsy, which is consistent with focal segmental glomerular sclerosis.
Angiotensin-converting enzyme inhibitor therapy is most likely to delay progression of this patient's renal disease in the presence of which of the following additional findings?

Quizplus · Accepted Answer

This patient with hypertension, edema, and focal segmental glomerular sclerosis on kidney biopsy would benefit most from angiotension-converting enzyme (ACE) inhibitor therapy. Several studies have shown that high levels of daily protein excretion (> 1 g/day) cause a more rapid decline of glomerular filtration rate (GFR) and kidney function regardless of the initial GFR or primary cause of renal dysfunction. ACE inhibitors and angiotensin receptor blockers (ARBs) decrease intra-glomerular pressure through dilation of both efferent and afferent glomerular arterioles and decrease proteinuria by as much as 35%-40%. In addition, ACE inhibitors have an antifibrotic effect on renal tubules to possibly further delay end-stage renal disease progression. These effects are seen even in patients without hypertension, thus supporting the use of these drugs for proteinuria. Some small studies have shown larger reduction in proteinuria with combination therapy of ACE inhibitors and ARBs. However, combination therapy is not routinely recommended due to greater risk of adverse outcomes. Aldosterone antagonists (eg, spironolactone) further reduce proteinuria when added to ACE inhibitors or ARBs but have a higher risk of hyperkalemia. Direct renin inhibitors also decrease proteinuria when used in combination, but more clinical trials are needed to determine the degree of efficacy. Non-dihydropyridine calcium-channel blockers (eg, verapamil, diltiazem) have significant anti-proteinuric effects compared to dihydropyridine calcium-channel blockers. Diuretics, alpha-blockers, and beta-blockers have little to no effect on proteinuria. (Choices B, C, D, and E) Initial GFR, hemoglobin levels, plasma renin/aldosterone ratio, and LDL cholesterol values are not as good prognostic indicators of decline in renal function as proteinuria (> 1 g/day). Although ACE inhibitors may slow decline in GFR and decrease LDL cholesterol levels, these effects are secondary to their effects on decreasing proteinuria. ACE inhibitors are not known to have any effect on anemia of chronic kidney disease. Educational objective: Daily protein excretion (> 1 g/day) has a more detrimental effect on kidney function than initial glomerular filtration rate or the primary cause of renal dysfunction. Angiotension-converting enzyme inhibitors decrease proteinuria, slow the rate of progression to renal failure in most patients, and are recommended for both primary and secondary focal segmental glomerular sclerosis. __________ References: Differential effects of enalapril and atenolol on proteinuria and renal haemodynamics in non-diabetic renal disease. (http://www.ncbi.nlm.nih.gov/pubmed/1932973) Treatment and landmark clinical trials for renoprotection. (http://www.ncbi.nlm.nih.gov/pubmed/21659771) The Remission Clinic approach to halt the progression of kidney disease. (http://www.ncbi.nlm.nih.gov/pubmed/21534237) Proteinuria as a risk marker for the progression of chronic kidney disease in patients on predialysis care and the role of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker treatment. (http://www.ncbi.nlm.nih.gov/pubmed/23128440)

A 39-Year-Old Man Comes to the Physician with 3 Weeks