Distribution of serum adiponectin isoforms in pediatric patients with steroid-sensitive nephrotic syndrome.

BACKGROUND: Serum adiponectin circulates in three multimeric isoforms: high-molecular-weight (HMW), middle-molecular-weight (MMW), and low-molecular-weight (LMW) isoforms. Potential change in the circulating adiponectin levels in patients with nephrotic syndrome (NS) remain unknown. This study aimed to assess the levels of total adiponectin and the distribution of its isoforms in pediatric patients with NS. METHODS: We sequentially measured total adiponectin and each adiponectin isoform levels at the onset of NS, initial remission, and during the remission period of the disease in 31 NS patients. We also calculated the ratios of HMW (%HMW), MMW (%MMW), and LMW (%LMW) to total adiponectin incuding 51 control subjects. RESULTS: The median of total serum adiponectin levels in patients were 36.7, 36.7, and 20.2 µg/mL at the onset, at initial remission, and during the remission period of NS, respectively. These values were significantly higher than those in control subjects. The median values of %HMW, %MMW, and %LMW values were 56.9/27.0/14.1 at the onset, 62.0/21.8/13.4 at the initial remission, and 58.1/21.7/17.5 at during the remission period of NS, respectively. Compared with control subjects, %HMW at initial remission and %MMW at the onset were high, and the %LMW values at the onset and at initial remission were low. CONCLUSIONS: In patients with NS, total serum adiponectin levels increase at the onset of the disease, and the ratio of adiponectin isoforms changes during the course of the disease. Further studies are needed to delineate the mechanisms between proteinuria and adiponectin isoforms change.

Valganciclovir prophylaxis for cytomegalovirus infection in pediatric kidney transplant recipients: a single-center experience.

BACKGROUND: There are two approaches for treating cytomegalovirus (CMV) infection occurring after kidney transplantation (KTx). One is preemptive therapy in which treatment is started after confirming positive CMV antigenemia using periodic antigenemia assay. The other approach is prophylactic therapy in which oral valganciclovir (VGCV) is started within 10 days after KTx and continued for 200 days. The Transplantation Society guidelines recommend prophylactic therapy for high-risk (donor's CMV-IgG antibody positive and recipient's negative) pediatric recipients. However, the adequate dose and side effects of VGCV are not clear in children, and there is no sufficient information about prophylaxis for Japanese pediatric recipients. METHODS: A single-center retrospective analysis was conducted on case series of high-risk pediatric patients who underwent KTx and received oral VGCV prophylaxis at the Department of Pediatric Nephrology, Tokyo Women's Medical University, between August 2018 and March 2019. Data were collected using medical records. RESULTS: The dose of administration was 450 mg in all the study patients (n = 5). Reduction or discontinuation was required in four of five patients due to adverse events, which included neutropenia in one patient, anemia in two patients, and neutropenia and digestive symptoms in one patient. Late-onset CMV disease occurred in all patients. No seroconversion was observed during prophylaxis. CONCLUSIONS: Our preliminary study suggests that the dosage endorsed by The Transplantation Society may be an overdose for Japanese pediatric recipients. Further studies are required to examine the safety and efficacy of VGCV prophylaxis in Japanese pediatric recipients.

Morphologic Analysis of Urinary Podocytes in Focal Segmental Glomerulosclerosis.

Background: The development of glomerulosclerosis in FSGS is associated with a reduction in podocyte number in the glomerular capillary tufts. Although it has been reported that the number of urinary podocytes in FSGS exceeds that of minimal-change nephrotic syndrome, the nature of events that promote podocyte detachment in FSGS remains elusive. Methods: In this study, we provide detailed, morphologic analysis of the urinary podocytes found in FSGS by examining the size of the urinary podocytes from patients with FSGS, minimal-change nephrotic syndrome, and GN. In addition, in urinary podocytes from patients with FSGS and minimal-change nephrotic syndrome, we analyzed podocyte hypertrophy and mitotic catastrophe using immunostaining of p21 and phospho-ribosomal protein S6. Results: The size of the urinary podocytes was strikingly larger in samples obtained from patients with FSGS compared with those with minimal-change nephrotic syndrome and GN (P=0.008). Urinary podocytes from patients with FSGS had a higher frequency of positive immunostaining for p21 (P<0.001) and phospho-ribosomal protein S6 (P=0.02) than those from patients with minimal-change nephrotic syndrome. Characteristic features of mitotic catastrophe were more commonly observed in FSGS than in minimal-change nephrotic syndrome urinary samples (P=0.001). Conclusions: We posit that the significant increase in the size of urinary podocytes in FSGS, compared with those in minimal-change nephrotic syndrome, may be explained by hypertrophy and mitotic catastrophe.

A pediatric patient with hyponatremic hypertensive syndrome without persistent hypertension in acute phase: A case report and review of literature.

Hyponatremic hypertensive syndrome is characterized by hypertension, hyponatremia, and hypokalemia due to unilateral renal artery stenosis. We herein report a 1-year-old hyponatremic hypertensive syndrome infant without persistent hypertension in the acute phase. On the ninth hospital day, his systolic and diastolic blood pressure increased up to 154-160 and 70-84 mmHg, respectively. Acute gastroenteritis and dehydration might transiently mask his hypertension. By percutaneous transluminal balloon angioplasty for right renal artery, his blood pressure finally normalized without antihypertensive drugs. We reviewed 23 previously reported pediatric patients with hyponatremic hypertensive syndrome under the age of 15 years. Including our patient, there are only three reports on hyponatremic hypertensive syndrome without persistent hypertension in the acute phase. Hyponatremic hypertensive syndrome is curable with proper diagnosis and timely intervention. Therefore, pediatricians should pay attention to the signs and symptoms associated with hyponatremic hypertensive syndrome, even if persistent hypertension was absent in the acute phase.

Difficult Renal Pathological Classification in a Case of Pediatric Nephrotic Syndrome.

The underlying histopathology is very important in determining patient management, as the histopathology usually has direct repercussions on the treatment response and clinical course. However, the impact of the method used to assess renal biopsies, i.e., light microscopy (LM), immunofluorescence (IF), and electron microscopy (EM), on the occurrence of a difficult biopsy classification in the native kidneys of pediatric nephrotic patients is unknown. A 12-month-old Japanese boy was diagnosed with nephrotic syndrome (NS); he was administered prednisolone (60 mg/m2/day), and a continuous albumin infusion was started. A renal biopsy using LM revealed minimal change. However, an IF study showed granular staining for immunoglobulin G along the glomerular basement membrane. Therefore, he was diagnosed with membranous nephropathy (MN). As his proteinuria was so severe, we started immunosuppressant therapy and continued the albumin infusion for more than 2 months. However, he did not attain complete remission. A month later, EM examination of his renal biopsy showed extensive foot process fusion without electron-dense deposits. Although the result of the IF study suggested MN, the results of the LM and EM studies indicated minimal change. We finally diagnosed the patient with minimal change NS, in consideration of his clinical condition and course. Because of the failure of previous treatments, pulse steroid therapy was started. After five rounds of therapy the patient attained complete remission. A difficult renal biopsy finding classification, dependent on the diagnostic method used, might occur in the native kidneys of pediatric nephrotic patients. Therefore, a diagnosis should be made after considering all renal biopsy findings and the clinical course.

Efficacy of rituximab therapy against intractable steroid-resistant nephrotic syndrome.

BACKGROUND: Some cases of childhood steroid-resistant nephrotic syndrome (SRNS) are intractable. We examined the cases of three patients with SRNS resistant to various treatment, but who achieved complete remission after being treated with rituximab (RTX) followed by methylprednisolone pulse (MP) therapy. METHODS: A retrospective chart review of all new-onset SRNS in the period from January 1997 to December 2013 was performed. Three of the 13 patients who received conventional treatment continued to have NS for >6 months, despite also being treated with immunosuppressants and receiving frequent albumin treatment. In addition, two of the patients received plasma exchange therapy, but it was ineffective. Therefore, RTX was used once a week for 4 weeks, followed by several courses of MP therapy. RESULTS: Two of the three intractable SRNS patients achieved complete remission after treatment with RTX followed by MP therapy, and the remaining patient achieved incomplete remission after the first round of this treatment. That patient subsequently achieved complete remission after the second round of the treatment. RTX did not cause any serious side-effects, and all three patients had normal renal function at the final observation. CONCLUSIONS: Complete remission was achieved in all 13 SRNS patients. RTX followed by MP therapy might be effective against SRNS refractory to conventional treatments and requiring frequent albumin treatment. Prospective clinical study examining the effectiveness and safety of this approach is required.