Aliskiren in Patients With Idiopathic Membranous Nephropathy

A Pilot Study to Evaluate the Antiproteinuric Effect of Renin Inhibition With Aliskiren in Patients With Idiopathic Membranous Nephropathy

The goal of this proposal is to conduct a pilot study to access the antiproteinuric effect of aliskiren in patients with idiopathic membranous nephropathy. Patients will be treated for 3 months with aliskiren aiming to achieve the maximum tolerated dose and blood pressure (>100 but <125 mmHg systolic BP >75% of the readings).

Study Overview

• Status: Withdrawn
• Conditions: Idiopathic Membranous Nephropathy
• Intervention / Treatment: Drug: Aliskiren

Detailed Description

In patients with nephrotic syndrome, including patients with membranous nephropathy (MN), conservative therapy consists of restricting dietary protein intake, and controlling blood pressure (target blood pressure is ≤ 125/75 mmHg), hyperlipidemia, and edema. Angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin II receptor blockers (ARB) are effective anti-hypertensive agents that can reduce proteinuria and slow progression of renal disease in both diabetic and nondiabetic chronic nephropathy patients and for these reasons they are the preferred agents to treat hypertension in proteinuric renal diseases.

Recent studies suggest that renin inhibition with aliskiren may be renoprotective and reduce proteinuria in patients with type 2 diabetes. Similar observations have also been reported in patients with membranous nephropathy and proteinuria in the range of 1-3 g/24h. These observations suggest that aliskiren may have powerful antiproteinuric. However, it is important to emphasize, that none of the patients in these studies had proteinuria greater than 3.0 g/24h. Thus, the antiproteinuric effect of aliskiren in patients with heavy proteinuria (e.g. >4g/24h) is unknown.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Idiopathic MN proven by diagnostic kidney biopsy.
• Age ≥18 years but ≤ 80 years.
• Proteinuria as measured by urinary protein/urinary creatinine > 4.0 on a spot sample aliquot from a 24-hour urine collection.
• Estimated GFR ≥ 30 ml/min/1.73m^2 using the 4 variable Modification of Diet in Renal Disease (MDRD) equation.

Exclusion Criteria

• Age <18 years.
• Estimated Glomerular Filtration Rate (GFR) < 30 ml/min/1.73m^2, or serum creatinine >3.0 mg/dl.
• Patient must be off prednisone, calcineurin inhibitor or mycophenolate mofetil for > 1 month and alkylating agents for > 6 months.
• Patients with presence of active infection or a secondary cause of MN (e.g. hepatitis B, HIV, systemic lupus erythematosus (SLE), medications, malignancies).
• Type 1 or 2 diabetes mellitus. Patients who have recent history of steroid induced diabetes but no evidence of diabetic nephropathy on renal biopsy performed within 6 months of entry into the study are eligible for enrollment.
• Pregnancy or nursing for safety reasons.
• Acute renal vein thrombosis documented prior to entry by renal US or CT scan.
• Previous therapy with Aliskiren

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aliskiren; Aliskiren dose will begin with 150mg per day and later up-titrated to the maximum available dose of 300mg per day.	Drug: Aliskiren; Aliskiren dose will begin with 150mg per day and later up-titrated to the maximum available dose of 300mg per day.; Other Names: Tekturna

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine protein excretion	Urine protein excretion at 12 weeks of renin inhibition with aliskiren	one year

Secondary Outcome Measures

Outcome Measure	Time Frame
Blood pressure control; tolerability and side effects	one year

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Fernando Fervenza, MD, PhD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: March 24, 2010
• First Submitted That Met QC Criteria: March 24, 2010
• First Posted (Estimate): March 26, 2010

Study Record Updates

• Last Update Posted (Estimate): March 13, 2013
• Last Update Submitted That Met QC Criteria: March 12, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: membranous nephropathy aliskiren proteinuria, glomerulonephritis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Kidney Diseases; Glomerulonephritis, Membranous
• Other Study ID Numbers: 09-007837