Multidrug Approach Shows Promise to Arresting Kidney Disease Progression in Alport Patients

A multidrug cocktail known to halt the progression of  kidney disease in non-diabetic patients was seen to effectively improve kidney function and slow disease progression in a small group of patients with Alport syndrome.

The study, “A Multidrug, Antiproteinuric Approach to Alport Syndrome: A Ten-Year Cohort Study,” published in the journal Nephron, underscored that the results were particularly good in patients who had not yet developed kidney insufficiency.

Studies, in both humans and mouse models of Alport syndrome, suggest that treatment with angiotensin-converting-enzyme (ACE) blocking drugs is only effective if started before kidney disease advances to a stage where significant amounts of protein is found in the urine. Such early treatment can prevent its progression to chronic kidney disease.

There is also evidence that using several types of medicines that can act in a synergistic fashion may also improve outcomes in Alport patients.

In a joint effort between researchers at the Clinical Research Centre for Rare Diseases Aldo and Cele Daccò at IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, in Italy, and the Icahn School of Medicine at Mount Sinai, scientists explored a multidrug approach in nine patients with Alport syndrome.

All patients, recruited between 2004 and 2007, had albumin in their urine, and first went through a one-month washout period, where they stopped taking all medications.

They then entered a four-month period of successive add-on treatments. Month one started with the ACE-inhibitor Lotensin (benazepril) at 10-20 mg/day. Month two was followed with 80-160 mg per day of the angiotensin receptor blocker Diovan (valsartan). In month three, the calcium channel blocker Dilacor XR (diltiazem) was added at 60-120 mg per day, and for month four, 40-80 mg per day of the statin Lescol (fluvastatin).

This was followed by a one-month period of treatment withdrawal. In an extension part of the study, the procedure was repeated and patients were assessed every three months until the study finished in July 2014, or until they progressed to an end-stage renal disease or dropped out of the study.

During the treatment period, urine albumin levels decreased from a median of 657.7 μg/min to 71.4 μg/min. At the end of the one-month recovery period, the levels again increased to 404.3 μg/min.

Eight of the nine patients continued in the long-term extension part of the study, and one reached end-stage kidney disease. Urine protein measurements at the end of the extension study were similar as those at the end of the first treatment period, indicating that the disease had not progressed significantly in these patients.