mycophenolic-acid and Hypertrichosis

We performed a multi-centre randomized controlled trial to compare the efficacy of mycophenolate mofetil (MMF) to that of cyclosporine A (CsA) in treating children with frequently relapsing nephrotic syndrome and biopsy-proven minimal change disease. Of the 31 randomized initially selected patients, seven were excluded. The remaining 24 children received either MMF 1200 mg/m(2) per day (n = 12) or CsA 4-5 mg/kg per day (n = 12) during a 12-month period. Of the 12 patients in the MMF group, two discontinued the study medication. Evaluation of the changes from the baseline glomerular filtration rate showed an overall significant difference in favour of MMF over the treatment period (p = 0.03). Seven of the 12 patients in the MMF group and 11 of the 12 patients in the CsA group remained in complete remission during the entire study period. Relapse rate in the MMF group was 0.83/year compared to 0.08/year in the CsA group (p = 0.08). None of the patients reported diarrhea. Pharmacokinetic profiles of mycophenolic acid were performed in seven patients. The patient with the lowest area under the curve had three relapses within 6 months. In children with frequently relapsing minimal change nephrotic syndrome, MMF has a favourable side effect profile compared to CsA; however, there is a tendency towards a higher relapse risk in patients treated with MMF.

Topics: Adolescent; Biopsy; Blood Pressure; Child; Child, Preschool; Cyclosporine; Disease-Free Survival; Female; Gingival Hyperplasia; Glomerular Filtration Rate; Humans; Hypertrichosis; Immunosuppressive Agents; Male; Mycophenolic Acid; Nephrosis, Lipoid; Remission Induction; Secondary Prevention; Treatment Outcome

Nephrotoxicity is a well-known adverse effect of cyclosporine A (CyA) treatment in children with steroid-dependent (SD) and steroid-resistant (SR) nephrotic syndrome (NS). We analyzed nine children (age: 3.3-15.7 years, two girls) with SD or SR NS who experienced a significant decrease in their GFR under CyA treatment as measured by inulin clearance (C(IN)). Mycophenolate mofetil (MMF) was introduced progressively until doses of 1 g/1.73 m(2) twice daily were reached. CyA treatment was stopped after introduction of MMF and oral steroids were reduced if possible. After a median follow up of 261 days, no adverse effects of MMF such as diarrhea or hematological anomalies occurred in our patients. After switching from CyA to MMF, those children with SD NS remained in remission without proteinuria and those with SR NS did not show any significant changes in their residual proteinuria. The serum protein level did not change significantly in any of the children analyzed. GFR increased from a mean of 76.9+/-4.8 to 119.9+/-5.9 mL/1.73 m(2) per min (P<0.001). Oral steroid treatment could be reduced from a median [range] prednisone dose of 0.85 [0.26-2.94] mg/kg/d pre-MMF to 0.29 [0-1.1] mg/kg per day (P=0.026), and blood pressure decreased moderately after CyA withdrawal, but the difference did not reach statistical significance. We conclude that a switch from CyA to MMF seems to be safe for children with SDNS and SRNS in terms of side effects as well as disease control, at least in the short term. Interruption of CyA treatment lead to rapid amelioration of kidney function in these children, often associated with steroid sparing, which may lead to additional benefit for growth velocity, blood pressure and physical appearance.

Topics: Adolescent; Child; Child, Preschool; Cyclosporine; Female; Gingival Hypertrophy; Glomerular Filtration Rate; Humans; Hypertrichosis; Immunosuppressive Agents; Kidney; Male; Mycophenolic Acid; Nephrotic Syndrome; Retreatment; Treatment Outcome