Effects of an Intensified Treatment With ACE-I,ATA II and Statins in Alport Syndrome

• Status: Completed
• Trial end date: 2009-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Alport syndrome (AS) represents a form of progressive hereditary nephritis in which the genetic defect resides in the synthesis of one of several subunits of type IV collagen, the predominant constituent of basement membranes in renal glomeruli. Renal impairment occurs with time and severe renal failure with hypertension and uremia represent the end stage of the disease, even if a high variability in the rate of progression is described.Males are usually affected by a progressive form of the disease. Affected females with X-linked syndrome usually have a good prognosis with a mild renal impairment. The disease is also associated to a sensor neural deafness which can occur in approximately half of the patient affected and usually correlates with renal impairment. No definite treatment exists in order to delay the time of dialysis or a kidney transplant. Many studies showed that Angiotensin converting enzyme (ACE) inhibitors slow glomerular filtration rate (GFR) decline and limit progression to end stage renal disease (ERDS) and dialysis in several chronic nephropathies associated with proteinuria. The combination of ACE-I with Angiotensin II receptor antagonists may reduce proteinuria more effectively than the two drugs alone. Moreover the addition of statins may synergize the antiproteinuric effects of ACE-I and ATAII antagonists in experimental models of chronic renal diseases.

The purpose of this study is to evaluate the effect of a standardized multimodal nephroprotection intervention (Remission Clinic) in Alport patients with renal involvement.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mario Negri Institute for Pharmacological Research
• Treatments: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Benazepril; Fluvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Valsartan

Criteria

Inclusion Criteria:

• age ≥15 years

• Alport disease

• Creatinine clearance >20 ml/min/1.73 mq with variation of less than 30% in the three months prior to study entry

• written informed consent. For patients <18 years old a written informed consent of both parents is needed

Exclusion Criteria:

• treatment with immunosuppressive drugs in the six months preceding the study

• vascular disease of the kidney

• obstructive uropathy, prostatic hypertrophy, incomplete bladder emptying

• transplanted kidney

• clinically relevant electrolyte imbalance (e.g., hyperkaliemia with serum K+ > 5.5 mEq/l)

• any concomitant medication with drugs that may directly affect UAE including ACE-inhibitors, angiotensin II receptor antagonists, non dihydropyridine CCBS, HMGCoA reductase inhibitors in the last one month

• history of hypersensitivity to the study drugs

• impossibility to temporary withdrawn ACE-I or ATA II or statins (heart failure, cardiovascular events over the last three months)

• any clinically relevant condition that may affect study participation and/or study results

• pregnancy, ineffective contraception, breast feeding

• inability to fully understand the purposes/risks of the study and/or to provide a written informed consent