A multidrug, antiproteinuric approach to alport syndrome: a ten-year cohort study.

Abstract

BACKGROUND/AIMS:

Combined ACE inhibitor, angiotensin-receptor-blocker, non-dihydropyridine calcium-channel-blocker, and statin therapy (Remission Clinic) reduced proteinuria and halted progression in non-diabetic nephropathies, but their efficacy in Alport syndrome (AS) nephropathy is unknown.

METHODS:

From February 2004 to September 2007, we included nine albuminuric AS adults with creatinine clearance >20 ml/min/1.73 m(2) in a single-center, open-label, prospective, off-on-off academic study. After the 1-month wash-out from RAS inhibition (Run-in), patients entered the 4-month, add-on, treatment period with benazepril (10-20 mg/day), valsartan (80-160 mg/day), diltiazem (60-120 mg/day), and fluvastatin (40-80 mg/day) followed by the 1-month wash-out (Recovery). The primary outcome was albuminuria at month 4. After recovery, patients were kept on the Remission Clinic protocol and followed until July 2014 (Extension).

RESULTS:

The median (IQR) albuminuria progressively declined from 657.7 (292.7-1,089.6) μg/min at baseline to 71.4 (21.7-504.9) μg/min at treatment end (p = 0.009) and raised to 404.3 (167.9-446.8) μg/min after recovery. Albumin and IgG fractional clearances significantly (p ≤ 0.005) decreased from 66.9 (53.6-80.8) to 9.4 (4.6-26.0) and from 5.1 (3.0-8.4) to 1.1 (0.6-3.2), and then recovered toward baseline. Blood pressure and lipids significantly decreased on treatment, without changes in inulin-measured GFR or para-aminohippuric-measured RPF. After recovery, one patient refused to enter the extension, one with severe renal insufficiency at baseline reached ESRD, and seven retained normal serum creatinine until the end of the study. At the final visit, three were microalbuminuric and one was normoalbuminuric. Treatment was well tolerated.

CONCLUSION:

The Remission Clinic approach safely ameliorated albuminuria, blood pressure, lipids, and glomerular selectivity in AS patients and halted long-term progression in those without renal insufficiency to start with.

• Authors: Erica Daina, Paolo Cravedi, Mirella Alpa, Dario Roccatello, Sara Gamba, Annalisa Perna, Flavio Gaspari, Giuseppe Remuzzi, Piero Ruggenenti
• Journal: Nephron (Nephron) Vol. 130 Issue 1 Pg. 13-20 ( 2015) ISSN: 2235-3186 [Electronic] Switzerland
• PMID: 25895746 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Angiotensin-Converting Enzyme Inhibitors
• Benzazepines
• Calcium Channel Blockers
• Fatty Acids, Monounsaturated
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Indoles
• Fluvastatin
• Valsartan
• Diltiazem
• benazepril

Topics

• Adult
• Aged
• Albuminuria (drug therapy)
• Angiotensin II Type 1 Receptor Blockers (therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Benzazepines (therapeutic use)
• Calcium Channel Blockers (therapeutic use)
• Cohort Studies
• Diltiazem (therapeutic use)
• Drug Therapy, Combination (methods)
• Fatty Acids, Monounsaturated (therapeutic use)
• Female
• Fluvastatin
• Follow-Up Studies
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Indoles (therapeutic use)
• Kidney Function Tests
• Male
• Middle Aged
• Nephritis, Hereditary (drug therapy)
• Prospective Studies
• Proteinuria (drug therapy)
• Valsartan (therapeutic use)