Alport syndrome is caused by a mutation in genes that encode for a structural protein called type 4 collagen. This results in kidney problems, eye abnormalities, and hearing loss. There is currently no cure for Alport syndrome, but several treatments can support kidney function and delay the onset of end-stage kidney disease or kidney failure.
How statins work
Statins are a group of therapies that inhibit an enzyme called HMG-CoA reductase. This enzyme is involved in one of the key steps in synthesizing cholesterol in the body. By blocking this enzyme, cholesterol levels in the blood are reduced.
It is thought that statins help protect the kidneys in Alport syndrome also by inhibiting the growth of mesangial cells. The abnormal growth of these cells in the kidneys is believed to be one of the first stages of fibrosis (scar tissue) formation, and later, kidney failure.
Statins also inhibit the production of a cell-signaling molecule, TNF-alpha, that is up-regulated in inflammation. By reducing this inflammatory pathway, fibrosis also is reduced.
Examples of statins
Lipitor (atorvastatin), Lescol (fluvastatin), and Altoprev (lovastatin) are all examples of statins, though many others are now available. Patients should discuss with their physician which statin may be right for them.
Statins in clinical trials for Alport syndrome
A preclinical study published in the journal Nephrology Dialysis Transplantation demonstrated that in a mouse model of Alport syndrome, treatment with cerivastatin increased the lifespan of the animals while reducing proteinuria (the presence of protein in the urine) and delaying the onset of hematuria (the presence of blood in the urine). The treatment, marketed under the brand name Baycol, has been withdrawn from the market in the U.S. and Canada due to concerns that it may cause rhabdomyolysis (the breakdown of skeletal muscle).
A Phase 2 clinical trial (NCT00309257) assessed the effect of benazepril (an ACE inhibitor), valsartan (an angiotensin 2 receptor blocker), diltiazem (a calcium channel blocker), and fluvastatin (a statin) in nine patients with Alport syndrome. Patients received the treatment for four months as an add-on treatment followed by a one-month wash-out period. At month 4, protein levels in patients’ urine were assessed. After the final wash-out period, one patient declined to continue the trial, one patient reached kidney failure, and seven patients had normal blood levels of creatinine (a measure of kidney function). These patients continued treatment for 10 years from the beginning of the study with kidney function being assessed monthly until either withdrawal from the trial or the onset of kidney failure. At the final visit, three patients had extremely low levels of protein in the urine, and one patient had protein in the urine that returned to normal levels. The researchers concluded that this combination therapy may be promising in halting disease progression in patients who do not yet have kidney failure. The results were published in the scientific journal Nephron.
An observational clinical trial (NCT02378805) is currently recruiting 500 Alport syndrome patients in Germany. Patient outcomes will be examined through hospital treatment records. Untreated patients (mostly older relatives with kidney failure) will be compared to patients in early and late treatment stages. Patients who have just one copy of the disease-causing mutation also will be examined, whether requiring treatment or not. Patients will be eligible to take part in the study if they are being treated with combination therapies, including ACE inhibitors and statins. The primary outcome measures will be the age at which kidney failure occurs and lifespan.
Side effects of statins include muscle pain and damage, liver damage, increased blood sugar or type 2 diabetes, and neurological problems such as memory loss and confusion.
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