Sachio Ito

Thyroid function in children with nephrotic syndrome

The thyroid function of seven children with untreated nephrotic syndrome who had a normal serum creatinine concentration was compared with that of the same patients in remission and age-matched controls. There was a significant decrease in serum thyroxine (T4), tri-iodothyronine (T3) and thyroid-binding globulin (TBG) concentrations in untreated nephrotic children compared with the same patients in remission and age-matched controls. Most values for serum free T4, free T3 and thyroid-stimulating hormone (TSH) in the patients with nephrosis were within the normal range. However, the mean serum free T4 and free T3 concentrations were significantly (P<0.05) lower in the untreated patients than in the same patients in remission, and the mean serum TSH concentrations were significantly (P<0.05) higher in the untreated patients than in the same patients in remission. There were massive urinary losses of T4, T3, TBG. free T4 and free T3 in the untreated nephrotic children compared with the same patients in remission and age-matched controls. The daily urinary protein excretion showed a positive correlation with the urinary T4, T3, free T4, free T3 and TBG excretion. Furthermore, the urinary protein excretion showed a negative correlation with the serum T4, T3, free T4, free T3 and TBG levels. There was a negative correlation between serum albumin and serum TSH. These findings provide evidence of mild hypothyroidism in children with untreated nephrotic syndrome, partly because of losses of T4, T3, free T4, free T3 and TBG into the urine.

Uncommon multisystemic involvement in a case of Henoch‐Schönlein purpura

Abstract A case of Henoch‐Schönlein purpura (HSP) characterized by several unusual complications is reported. A 10‐year‐old boy was hospitalized with acute abdomen and developed purpura on the lower extremities after 4 days of hospitalization. He had protein‐losing enteropathy, diagnosed by an elevated fecal α‐1‐antitrypsin clearance. The colicky abdominal pain and protein‐losing enteropathy subsided after methylprednisolone pulse therapy was administered. He had left hydronephrosis and gall‐bladder abnormalities detected by ultrasonography, and purpura nephritis. However, after improvement of these abnormalities, he showed steroid‐induced epidural lipomatosis, detected by magnetic resonance imaging, which resolved with steroid reduction. Ultrasonography and magnetic resonance imaging were useful for detecting these uncommon multisystemic involvements in HSP.

No evidence for pathogenic role of IgE in Henoch-Schoenlein purpura nephritis

AbstractBackground. The incidence of increased plasma IgE levels was reported to be significantly higher in Henoch-Schoenlein purpura nephritis (HSPN) than in IgA nephropathy (IgAN), and IgE deposits were demonstrated on epidermal Langerhans cells and dermal mast cells in four of six patients with HSPN in two European studies. We designed this study to investigate whether levels of clinical and biological markers of atopy in children with HSPN were significantly higher than those in children with IgAN, non-IgA glomerulonephritis (non-IgAGN), or microhematuria. Methods. The incidence of atopic disease, increased IgE levels, and positive radioallergosorbent test (RAST) results was investigated in 28 children with HSPN, 26 with IgAN, 28 with non-IgAGN, and 30 with microhematuria, all aged 8–16 years. All patients except for those in the microhematuria group, had proteinuria greater than100 mg/dl and had had a kidney biopsy. Results. The incidence of atopic disease, increased IgE levels, and positive RAST results in children with HSPN did not differ from findings in children with IgAN, non-IgAGN, or microhematuria. Conclusion. Our results in Japanese children do not support the idea (suggested by the two European studies) that IgE may play an important role in the pathogenesis of HSPN.

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.

Renal tubular calcification in six nephrotic children with acute renal insufficiency

Summary: A review of 42 primary nephrotic children who underwent kidney biopsies found that six patients had calcification of the renal tubules (aged 2‐9 years). These six patients showed significant increases in weight gain, blood pressure, urinary protein, serum urea nitrogen and urinary calcium/creatinine, and significant decreases in serum phosphate, % tubular reabsorption of phosphate and creatinine clearance as compared with 36 nephrotic patients without tubular calcification. Furthermore, these patients received high dose furosemide, and five of six patients received methylprednisolone pulse therapy to treat progressive renal dysfunction. the interval before the first kidney biopsy and after both the onset of the nephrotic syndrome, and the start of glucocorticoid therapy, including methylprednisolone pulse therapy and furosemide, ranged from 1 to 5 months excluding one patient (33 months). Although one patient received haemodialysis, renal insufficiency was resolved from 10 to 18 days after its onset. Glucocorticoid therapy, including methylprednisolone pulse therapy and high dose furosemide in primary nephrotic children with acute renal insufficiency, induced calcification of the renal tubules.

Saireito-induced cystitis in children: Two new cases and a review of the literature

We describe 2 children with sterile cystitis caused by Saireito, a traditional Chinese herbal medicine. A diagnosis of cystitis was made for 1 child at 8 months and for the other at 11 months after Saireito treatment for renal disease was initiated. Clinical symptoms were resolved 1 and 6 weeks after Saireito treatment was withdrawn. We also reviewed the first report written in the English language on 8 additional patients with Saireito-induced cystitis. We found that Saireito-induced cystitis occurred mainly in children and developed 6 months or more after Saireito treatment was initiated. The incidence is not uncommon, and the cause may be an allergic reaction, because eosinophilic cell infiltration was noted on histopathologic examination, and the challenge test was positive. We recommend that, when sterile cystitis develops during treatment with Saireito, Saireito should be immediately withdrawn.

Chronic Idiopathic Thrombocytopenic Purpura in a Patient with Membranous Glomerulonephritis

Accessible online at: www.karger.com/journals/nef Dear Sir, We read with great interest the article by Tamura et al. [1] describing a case of idiopathic thrombocytopenic purpura (ITP) associated with nephrotic syndrome (NS) due to membranous glomerulonephritis. We have observed a similar case in a female patient. A 14-year-old girl was found to have 2+ proteinuria by the dipstick method on a routine school screening examination in 1993. In July 1994, she developed facial edema, and was admitted to Oyama City Hospital. A 24-hour urine sample contained 8 g protein. Blood analysis revealed: serum total protein 3.7 g/dl; albumin 1.9 g/ dl; total cholesterol 357 mg/dl, and platelet count 244,000/mm3. Although the patient was treated with 80 mg/day prednisolone, 3 courses of pulse methylprednisolone and cyclophosphamide, the NS did not improve. Therefore, she was transferred to Dokkyo University School of Medicine Hospital in September 1994, and renal biopsy was performed. Light microscopy of the first renal biopsy sample showed diffuse membranous glomerulonephritis associated with mild hypercellularity (stage II). The patient was treated with a combination of prednisolone, pravastatin, mizoribine and heparin for 4 weeks, followed by warfarin potassium. Proteinuria gradually decreased, and the serum total protein, albumin and total cholesterol values normalized 6 months after start of therapy. The combination therapy was stopped after 12 months, and proteinuria disappeared in June 1996. A second renal biopsy was performed in July 1996. At that time the patient showed a decreased platelet count of 104,000/mm3 and a slightly prolonged bleeding time of 4 min, but serum CH50, C3, C4, LE test and dsDNA antibody showed normal values. Light microscopy of the second renal biopsy sample showed membranous glomerulonephritis (stage III). Purpura on both legs appeared transiently when the platelet count fell to 44,000/mm3 in April 1997. Bone marrow aspiration in August 1997 showed a normal number of megakaryocytes, and the serum platelet-associated IgG level was 93.8 ng/10 cells (normal value 9–25.0), consistent with ITP. No splenomegaly was recognized by echography. The platelet count remained between 44,000 and 92,000/mm3 for 2 years after the second renal biopsy. The platelet count in April 1999 was 113,000/mm3 without treatment. Repeated examinations of serum complement components, LE test and antinuclear antibody gave normal results, and no signs of systemic lupus erythematosus were recognized. Proteinuria has been negative since June 1996. To our knowledge, our case of membranous glomerulonephritis associated with ITP is the third to have been reported [1, 2]. Renal impairment associated with primary ITP seems to be rare [1–3], but the difficulty in explaining a mechanism that can cause both ITP and renal disease may explain the low number of previous reports. The common pathogenic mechanism that underlies these two entities should be evaluated by further studies of many patients. Three of the four previously reported patients were Japanese, and were found to have mild proteinuria on routine school health check-ups. If school screening programs like that in Japan could also be performed in other countries, more patients with both ITP and renal disease would be found.

Effect of prednisone on the amount of epidural fat as measured on magnetic resonance imaging in children with nephrotic syndrome

BackgroundThis study was designed to investigate whether steroid-induced epidural lipomatosis or an increase in epidural fat developed, and whether there was a difference in the amount of epidural fat in the epidural area, in steroid-sensitive children with nephrotic syndrome who were treated with prednisone.MethodsMagnetic resonance imaging (MRI) from the cervical area to the lumbosacral area was performed in 8 steroid-sensitive patients with nephrosis (aged 7 to 10 years, 4 boys and 4 girls) at intervals of 2 to 4 weeks, and at 2 to 3 months, after starting prednisone treatment. A final MRI was performed at 7 to 11 months after the start of treatment, which was 2 to 6 months after the withdrawal of prednisone. The study was performed prospectively and consecutively.ResultsThese 8 patients with nephrotic syndrome did not show any symptoms of steroid-induced epidural lipomatosis (i.e., back pain or paresthesia), but the mean amount of thoracic epidural fat in these patients 2 to 3 months after starting prednisone treatment showed a significant increase compared to that in 8 age-matched control patients.ConclusionsIt is not necessary to perform MRI in steroid-sensitive, nonrelapsing patients with nephrotic syndrome who are treated with prednisone for less than 1 year. However, it may be necessary to monitor the thoracic area by MRI in renal transplant recipients treated with prednisone over a prolonged period, or frequently relapsing nephrotic patients treated with frequent high doses of prednisone.