Kiyoshi Nishikura

Systemic effects of transdermal testosterone for the treatment of microphallus in children

Abstract Objectives : To elucidate the metabolic effects of topical testosterone for the treatment of microphallus in children.

Effectiveness of high trough levels of cyclosporine for 5 months in a case of steroid-dependent nephrotic syndrome with severe steroid toxicity.

SUMMARY:  Glucocorticoid treatment for steroid‐dependent nephrotic syndrome (NS) is associated with severe adverse effects, such as bone fractures and epidural lipomatosis. Furthermore, a high trough level of cyclosporine (CsA) over an extended period of time is known to induce CsA nephropathy. We present a girl with steroid‐dependent NS and steroid‐induced vertebral compression fractures and epidural lipomatosis who was treated with a high‐dose of prednisolone after experiencing several relapses. A high CsA trough level (between 147 and 225 ng/mL) over a period of only 5 months was effective in improving the vertebral compression fractures, alleviating the epidural lipomatosis by enabling the discontinuation of prednisolone treatment. Thus, high trough levels of CsA over a short period of time may enable prednisolone to be discontinued in cases of steroid‐dependent NS without causing any clinical, histological, serum and/or urinary CsA‐related adverse effects.

Skeletal effects of short-term prednisolone therapy in children with steroid-responsive nephrotic syndrome

AbstractBackground. Osteoporosis or bone fracture can be induced in nephrotic children treated long-term with high doses of glucocorticoids. The purpose of this study was to determine whether short-term prednisolone therapy affects the skeleton in children with steroid-responsive nephrotic syndrome (NS). Methods. Bone mineral density (BMD) and biochemical parameters of mineral and skeletal homeostasis in nine children (four girls, five boys) aged between 2 and 7 years at the first episode of NS were measured. Prednisolone was started at 60 mg/m2 for 4 weeks, then decreased every 2 weeks for 12 weeks. All patients were steroid-responsive and had no relapse. All patients were examined at 0, 4, and 12 weeks of prednisolone therapy, and 16 weeks after the cessation of prednisolone therapy. Results. The Z-scores (BMD) before prednisolone therapy (−0.79 ± 0.51) were slightly low. The Z-scores at 4 weeks (−1.37 ± 0.46) and at 12 weeks of therapy (−1.22 ± 0.36) were significantly lower than those at 16 weeks after the cessation of prednisolone therapy (−0.29 ± 0.29). There was also a significant decrease in the mean serum levels of alkaline phosphatase, osteocalcin, and urinary deoxypyridinoline during the short-term prednisolone therapy. However, BMD and biochemical parameters of mineral and skeletal homeostasis returned to normal values at 16 weeks after the cessation of prednisolone therapy. Conclusions. Skeletal effects of short-term prednisolone therapy for 16 weeks were transient in children with steroid-responsive NS without relapse.

Skeletal effects of low-dose cyclosporin A therapy in children with nephrotic syndrome

AbstractBackground. High doses of cyclosporin A (CsA) produce high-turnover osteopenia in rats. The aim of this study was to determine whether low-dose CsA affects the skeleton in children with nephrotic syndrome. Methods. Biochemical parameters of mineral and skeletal homeostasis, and bone mineral density (BMD) in eight boys with steroid-dependent, frequently relapsing minimal change nephrotic syndrome who had received low-dose CsA (between 1.6 and 3.1 mg/kg per day) for 2 years were compared with measurements in the same patients before CsA therapy and who had received glucocorticoids for long periods, and with measurements in age-matched controls. Results. It was possible to discontinue glucocorticoid therapy within 4 months after the start of CsA therapy. There was a significant increase in the mean serum alka-line phosphatase concentration in CsA therapy patients compared with the same patients before CsA therapy and the controls. Serum osteocalcin and tartrate-resistant acid phosphatase, and urinary deoxypyridinoline concentrations in CsA therapy patients did not differ from those in the controls. BMD in CsA therapy patients was increased significantly compared with values in the same patients before CsA therapy. BMD in CsA therapy patients was lower than that in the controls, but remained within 80% of the overall mean BMD value. Conclusions. Two years of low-dose CsA therapy without glucocorticoids does not appear to induce high-turnover osteopenia in children with steroid-dependent nephrotic syndrome.

A patient with membranoproliferative glomerulonephritis diagnosed by the third biopsy via endocapillary proliferative glomerulonephritis and focal membranoproliferative glomerulonephritis.

We present a girl with type I membranoproliferative glomerulonephritis (MPGN) diagnosed by the third renal biopsy. The first renal biopsy was performed at age 11.2 years after microscopic hematuria (which was revealed by school urinary screening) had persisted for 3 months, along with a low level of serum C3. Pathological examination of the biopsied specimen revealed endocapillary proliferative glomerulonephritis with multiple humps. The serum C3 level increased to within the normal range 2 months after the first renal biopsy, and the microscopic hematuria disappeared at age 12.3. However, microscopic hematuria, proteinuria, and the low serum complement level reappeared at age 12.8. Pathological examination of a further renal biopsy that was performed at age 13.2 revealed focal MPGN with humps. Prednisolone therapy was subsequently initiated. Fluvastatin was added to her treatment regime when she developed hypercholesterolemia at age 13.6 and was continued even after normal cholesterol levels were reestablished. Pathological examination of the third renal biopsy, which was performed at age 15.2, revealed type I MPGN with humps. Serum C3 normalized 6 months after the cessation of prednisolone at age 15.9. It is clinically important that patients with nontypical acute glomerulonephritis should be observed over a long period and repeated renal biopsies should be performed.