Steroid Treatment for Kidney Disease
Condition: Nephrosis; Focal Lipoid Glomerulosclerosis
MeSH terms: Nephrosis
Intervention: Oral dexamethasone
Intervention description: Stage I: Dexamethasone 25 mg/m2, 2 doses every 2 weeks over 48 weeks or dexamethasone 25 mg/m2, 4 doses every 4 weeks over 48 weeks.
Stage II: 1.) Dexamethasone 50 mg/m2, 2 daily doses every 12 weeks, followed by 25 mg/m2, 2 daily doses every 2 weeks over 36 weeks, or 2.) Dexamethasone 50 mg/m2, 4 daily doses every 4 weeks over 12 weeks, followed by 25 mg/m2, 4 daily doses every 4 weeks over 36 weeks.
over 36 weeks.
Intervention MeSH terms: Dexamethasone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No
Keywords: Steroids; Osteoporosis; Proteinuria; Minimal Change Disease; Focal Segmental Glomerulosclerosis; FSGS; MCD; Kidney Disease

Summary:

      Focal segmental glomerulosclerosis (FSGS) and minimal change disease are kidney diseases that
      are associated with increased excretion of protein in the urine. Approximately half of FSGS
      patients will lose kidney function within 8 years of diagnosis and will require dialysis. The
      purpose of this study is to determine whether intermittent oral steroid therapy can cause
      sustained remission of FSGS and MCD.

      Approximately 70 participants, including adults and children older than age 2, will be
      enrolled in this study. They will receive 48 doses of oral dexamethasone over a period of 48
      weeks. One group will take two daily doses every 2 weeks; the other group will take four
      daily doses every 4 weeks. Doctors will monitor participants before, during, and after the
      steroid treatment with extensive exams and testing. At the completion of the study,
      researchers will evaluate the safety and efficacy of the drug treatment.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Adults and children greater than 2.0 years of age are eligible. We will exclude
                  children less than 2.0 years of age in light of the higher risk of steroid
                  therapy in this age group and the higher likelihood genetic or syndromic FSGS,
                  which is less likely to respond to steroids.

               2. Diagnosis:

                  A) Biopsy-proven MCD and its variants, including IgM nephropathy and MCD with
                  mesangial hypertrophy.

                  B) Biopsy-proven FSGS, including idiopathic FSGS and collapsing FSGS. We will
                  exclude patients with HIV-associated FSGS, as the risks of steroids are increased
                  in these patients. We will exclude hyperfiltration FSGS associated with morbid
                  obesity (BMI greater than 40 kg/m(2)), sickle cell anemia, reflux nephropathy,
                  chronic tubular injury, congenital renal anomalies, and reduced nephron mass; the
                  rationale is that these FSGS variants are considered refractory to steroids.

               3. Proteinuria: patients must have nephrotic range proteinuria. Baseline tests will
                  be obtained when patients have been off all immunosuppressive therapy for greater
                  than or equal to 1 month.

               4. Renal function: estimated GFR must be greater than or equal to 40 ml/min/1.73m(2)
                  at the time of study entry; In children weighing less than 40kg, GFR will be
                  estimated by the Schwartz formula and expressed as GFR/1.73m(2): GFR equal to
                  [0.7 (males) or 0.57 (females) X height (cm)]/ serum creatinine.

               5. Angiotensin antagonists: Patients must be receiving angiotensin antagonist
                  therapy, at any dose approved by the FDA. Nephrotic range proteinuria will be
                  defined as urine protein greater than or equal to 3.5 g/1.73m(2)/d (adults) and
                  greater than 50 mg/kg (children less than 40 kg) while receiving maximally
                  tolerated dose of angiotensin antagonist therapy for at least 4 weeks prior to
                  study entry.

               6. Prior immunosuppressive therapy:

                  For children with MCD, we require a minimum of 4 weeks and a maximum of 10 weeks
                  of daily steroid therapy at a dose of greater than or equal to 60 mg/m(2) with
                  proteinuria persisting in the nephrotic range (excluding steroid-sensitive,
                  steroid-dependent and frequently relapsing MDC).

                  For children with FSGS and adults with MCD and FSGS, we require no minimum and a
                  maximum of 8 weeks of daily or alternate day steroids at a dose of greater than
                  0.5 mg/kg with proteinuria persisting in the nephrotic range.

                  Patients with prior immunosuppressive therapy other than steroids are eligible.

               7. If hypertensive, adequate blood pressure control (target BP less than 125/75 mm
                  Hg at greater than 75% of measurements in adults).

               8. Women with reproductive potential who are sexually active must maintain an
                  effective birth control regimen (oral contraceptive, intrauterine device, or
                  barrier method plus spermicide) and must have a negative urine HCG test prior to
                  beginning therapy.

               9. Patients must either have a negative PPD test within 3 months of study entry
                  while off immunosuppressive therapy or, if they have a history of positive PPD,
                  they must have appropriate evaluation to exclude untreated tuberculosis (with the
                  advice of an Infectious Disease consultant).

        EXCLUSION CRITERIA:

          1. Patients with diabetes mellitus type 1 will be excluded, as these patients typically
             have brittle diabetic control that increases the risk of steroid treatment. Patients
             with diabetes mellitus type 2 will be included they manifest good glycemic control
             (glycosylated hemoglobin less than 7.5%), if they have lack proliferative retinopathy
             (the presence of proliferative retinopathy would place them at high risk for vision
             loss if steroids worsened glycemic control) and if they have had a renal biopsy within
             6 months of study entry that shows no evidence for diabetic nephropathy.

          2. Poorly controlled hypertension (greater than 25% of values greater than 125/75).

          3. Evidence of significant chronic or occult infection. Specifically, subjects must not
             have evidence of active hepatitis B or hepatitis C infection, or HIV-1 infection, or
             untreated mycobacterial infection. Minor infections, such as skin or nail fungal
             infections or other infections with the advice of an Infectious Disease consultant,
             will not be the basis for exclusion.

          4. Immunosuppressive medication other than glucocorticoids, whether for podocyte disease
             or another indication, must have been discontinued greater than 8 weeks prior to study
             entry. This does not apply to topical immunosuppressant medication.

          5. Pregnancy.

          6. Existence of any other condition that would complicate the implementation or
             interpretation of the study.