Mycophenolate Mofetil and Tacrolimus Versus Tacrolimus for the Treatment of Idiopathic Membranous Glomerulonephritis

Phase 4

Completed

Brief Summary: Study Hypothesis: When mycophenolate mofetil is added to tacrolimus in the treatment of membranous glomerulonephritis it is likely to improve the initial response to treatment and reduce the risk of relapse on stopping therapy.

Detailed Description: Membranous nephropathy is a common cause of nephrotic syndrome in adults. It is difficult to treat and if persistent leads to end stage renal failure in a significant number of patients. It is currently treated in this institution with tacrolimus monotherapy. This is effective in the majority of patients in reducing proteinuria but the remissions are often partial and patients tend to relapse when the tacrolimus treatment is stopped. We propose to use mycophenolate mofetil in combination with tacrolimus with the aim of obtaining a more complete initial response to treatment, a decreased rate of relapse on withdrawal of therapy and less progression of renal failure. This will be a randomised control trial, patients will be randomised to receive treatment with tacrolimus alone (our current standard therapy)or treatment with tacrolimus and mycophenolate mofetil. Participants will receive treatment for up to 2 years and then be monitored for relapse of their nephrotic syndrome.

Recruitment & Eligibility

Inclusion Criteria

Idiopathic membranous glomerulonephritis on renal biopsy
Proteinuria - protein/creatinine ratio (PCR) > 100 units with hypoalbuminaemia or PCR > 300 units with normal serum albumin despite 3 months treatment with maximum tolerated doses of ace inhibitors and angiotensin 2 antagonists (or shorter if life threatening complications of nephrotic syndrome require institution of immediate immunosuppression)
Male or female patients aged 18 to 80 years

Exclusion Criteria

Hepatitis B hepatitis C or HIV positive
Malignancy (all patients must have a CT chest abdomen and pelvis and other investigations if clinically indicated)
Untreated infection
Females who are pregnant, breast feeding, or at risk of pregnancy and not using a medically acceptable form of contraception
Any condition judged by the investigator that would cause the study to be detrimental to the patient

Arm && Interventions

Group	Intervention	Description
tacrolimus and mycophenolate mofetil	tacrolimus and mycophenolate mofetil	tacrolimus 2mgs bd (adjusted to obtain levels 5-12mg/L and mycophenolate mofetil 500mg bd adjusted to obtain levels 1.5-3mg/L
tacrolimus	tacrolimus	Intervention type -drug tacrolimus therapy 2mg bd adjust to obtain levels of 5-12ng/L

Primary Outcome Measures

Name	Time	Method
Number of Patient Who Gained Remission From the Nephrotic Syndrome	10-109 weeks	Efficacy of mycophenolate in preventing relapse of nephrotic syndrome secondary to membranous glomerulonephritis on withdrawal of tacrolimus therapy.

Secondary Outcome Measures

Name	Time	Method
Number of Patients Achieved Remission	6-12 months	The degree of remission of proteinuria obtained (complete or partial) The rate of decline of renal function measured by the Modification of Diet in Renal Disease equation for glomerular filtration rate.