Clinical Course of Nonresponders With Recurrent Focal Segmental Glomerulosclerosis After Pediatric Kidney Transplantation: A Retrospective Multicenter Study.

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation and is associated with poor graft survival. Patients who do not achieve remission (nonresponders) have an especially poor graft survival. However, the characteristics that may affect graft survival in nonresponders are unknown. This study aimed to determine the clinical characteristics associated with graft survival in nonresponders. METHODS: We retrospectively collected the clinical records of patients with FSGS and an age at onset <16 years who experienced posttransplant recurrence of FSGS at six hospitals in Japan from 1993 to 2018. RESULTS: Eight nonresponders with recurrent FSGS were enrolled in this study. The median time to recurrence after kidney transplantation was 1 day (interquartile range, 1-2 days). All patients received therapeutic plasma exchange and methylprednisolone pulse therapy. Rituximab was used as an add-on therapy in three patients. Five patients lost their graft within 2 years after kidney transplantation (rapid group). In contrast, three patients had much longer graft survival (nonrapid group). We compared the clinical characteristics of the rapid and nonrapid groups. Proteinuria tended to be lower in the nonrapid group at the third and subsequent months of therapy. The rapid group had persistent nephrotic syndrome. The rate of reduction in proteinuria was lower in the rapid group than in the nonrapid group. CONCLUSIONS: Our study suggests that persistent nephrotic syndrome and a low rate of reduction in proteinuria may predict rapid progression to graft failure in nonresponders.

En bloc kidney transplantation from pediatric donors to teenage recipients: Two case reports.

Introduction: Since the implementation of the new selection criteria in 2018, kidney donations from pediatric patients have been prioritized for pediatric recipients and kidney donations from pediatric donors have increased in Japan. Herein, we present two cases of en bloc kidney transplantation. Case presentation: Case 1: A 19-year-old male patient who had been on hemodialysis for 5 years due to end-stage renal disease. After brain death, a graft from a 5-year-old boy was transplanted into the right iliac fossa. Case 2: A 19-year-old male patient, who had previously undergone a living kidney transplantation at the age of 3, received a secondary cadaveric kidney transplantation in the left iliac fossa. The graft was procured from a 17-month-old girl following cardiac death. Conclusion: This report will help surgeons perform en bloc kidney transplantation in the growing number of pediatric kidney donations, such as those in Japan.

A multi-institutional study found a possible role of anti-nephrin antibodies in post-transplant focal segmental glomerulosclerosis recurrence.

Possible roles of anti-nephrin antibodies in post-transplant recurrent focal segmental glomerulosclerosis (FSGS) have been reported recently. To confirm these preliminary results, we performed a multi-institutional study of 22 Japanese pediatric kidney transplant recipients with FSGS including eight genetic FSGS and 14 non-genetic (presumed primary) FSGS. Eleven of the 14 non-genetic FSGS patients had post-transplant recurrent FSGS. Median (interquartile range) plasma levels of anti-nephrin antibodies in post-transplant recurrent FSGS measured using ELISA were markedly high at 899 (831, 1292) U/mL (cutoff 231 U/mL) before transplantation or during recurrence. Graft biopsies during recurrence showed punctate IgG deposition co-localized with nephrin that had altered localization with increased nephrin tyrosine phosphorylation and Src homology and collagen homology A expressions. Graft biopsies after remission showed no signals for IgG and a normal expression pattern of nephrin. Anti-nephrin antibody levels decreased to 155 (53, 367) U/mL in five patients with samples available after remission. In patients with genetic FSGS as in those with non-genetic FSGS without recurrence, anti-nephrin antibody levels were comparable to those of 30 control individuals, and graft biopsies had no signals for IgG and a normal expression pattern of nephrin. Thus, our results suggest that circulating anti-nephrin antibodies are a possible candidate for circulating factors involved in the pathogenesis of post-transplant recurrent FSGS and that this may be mediated by nephrin phosphorylation. Larger studies including other ethnicities are required to confirm this finding.

Successful administration of eltrombopag in preparation for peritoneal dialysis catheter placement in a girl with MYH9-related disease.

MYH9-related disease is an autosomal dominant disorder characterized by macrothrombocytopenia, nephropathy, inclusion bodies in leukocytes, sensorineural hearing loss, and cataract. Severe cases require kidney replacement therapy in the patient's second decade of life; thrombocytopenia constitutes a major risk factor for hemorrhagic complications during dialysis initiation or kidney transplantation. Prophylactic platelet transfusion prior to surgery is commonly administered to affected patients in these cases. However, transfusion in such patients has limitations other than the general risk of allergic reactions and blood-borne infections; it may also trigger alloimmunization, leading to platelet transfusion resistance or the development of anti-donor antibodies in potential kidney transplant recipients. Here, we describe prophylactic administration of eltrombopag, an oral thrombopoietin receptor agonist, prior to laparoscopic peritoneal dialysis catheter placement in a 15-year-old girl with MYH9-related disease. Her platelet count was approximately 30 × 103/µL at baseline; it increased to 61 × 103/µL on the day before surgery, thereby avoiding the need for platelet transfusions. There were no major bleeding or adverse events associated with eltrombopag administration. Thus, eltrombopag may be a safe and effective alternative to prophylactic platelet transfusions in patients with MYH9-related disease.

Precise clinicopathologic findings for application of genetic testing in pediatric kidney transplant recipients with focal segmental glomerulosclerosis/steroid-resistant nephrotic syndrome.

BACKGROUND: Establishing a molecular genetic diagnosis of focal segmental glomerulosclerosis (FSGS)/steroid-resistant nephrotic syndrome (SRNS) can be useful for predicting post-transplant recurrence. Monogenic causes are reportedly present in approximately 20-30% of patients with FSGS/SRNS. However, the characteristics of patients who are likely to have a monogenic cause remain to be determined. METHODS: Pediatric recipients with SRNS and/or biopsy-proven FSGS who underwent their first kidney transplantation at our center between 1999 and 2019 were analyzed. Patients with secondary FSGS/SRNS were excluded. The recipients were divided into three groups: familial/syndromic, presumed primary, and undetermined FSGS/SRNS. Patients who met all of the following criteria were categorized as having presumed primary FSGS/SRNS: (i) nephrotic syndrome, (ii) complete or partial remission with initial steroid therapy and/or additional immunosuppressive therapies, and (iii) diffuse foot process effacement on electron microscopy in the native kidney biopsy. All patients underwent genetic testing using next-generation sequencing. RESULTS: Twenty-four patients from 23 families were analyzed in this study. Pathogenic or likely pathogenic variants in FSGS/SRNS-related genes were identified in four of four families, zero of eight families, and 10 of 11 families with familial/syndromic, presumed primary, and undetermined FSGS/SRNS, respectively. Post-transplant recurrence only occurred in patients with presumed primary FSGS/SRNS. CONCLUSIONS: Our systematic approach based on precise clinicopathological findings including nephrotic syndrome, treatment responses, and diffuse foot process effacement might be useful to differentiate pediatric kidney transplant recipients with FSGS/SRNS who are likely to have a monogenic cause from patients who are not, and to predict post-transplant recurrence. A higher resolution version of the Graphical abstract is available as Supplementary information.

Cumulative Dialytic Glucose Exposure is a Risk Factor for Peritoneal Fibrosis and Angiogenesis in Pediatric Patients Undergoing Peritoneal Dialysis Using Neutral-pH Fluids.

Introduction: Neutral-pH dialysate has been reported to be beneficial to prevent the peritoneal pathological changes in adult peritoneal dialysis (PD) patients, but its use is controversial in pediatric PD patients. In addition, the impact of cumulative dialytic glucose exposure has not been examined. Methods: Pediatric PD patients using conventional fluids (conventional group, n = 31) or those using neutral-pH fluids (neutral-pH group, n = 33) were compared. Clinical risk factors for peritoneal pathological changes in the neutral-pH group were analyzed using generalized linear modeling. Furthermore, the mechanisms of peritoneal pathological changes were explored using immunohistochemical studies and cultured cells. Results: The median (interquartile range) duration of dialysis was 3.2 (1.7-5.3) years in overall patients. After propensity score matching, the conventional group showed increased thickening of the submesothelial compact (SMC) zone and lower luminal-to-vessel diameter (L/V) ratio than the neutral-pH group. In the neutral-pH group, the cumulative dialytic glucose exposure was an independent risk factor for greater thickness of the SMC zone (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.16-2.05) and higher submesothelial microvessel density (OR, 1.29; 95% CI, 1.01-1.64). Immunohistochemical study showed that cumulative dialytic glucose exposure correlated with the proportion of the tissue expressing hypoxia inducible factor -1α (HIF-1α) and vascular endothelial growth factor-α (VEGF-α). In human peritoneal mesothelial cells, high glucose significantly increased HIF-1α and VEGF-α expressions. Conclusion: Cumulative dialytic glucose exposure is an independent risk factor for peritoneal fibrosis and angiogenesis in pediatric patients undergoing PD using neutral-pH fluids, which might be associated with greater VEGF-α production by myofibroblasts implying a hypoxic response.

Safe Renal Transplantation to the Extraperitoneal Cavity in Children Weighing Less Than 15 kg.

Pediatric renal transplantation is associated with various surgical complications due to the complexity of the technique and the often-fragile condition of patients with end-stage renal disease. We evaluated the surgical complications associated with renal transplantation via the extraperitoneal approach in pediatric recipients. This retrospective study enrolled 280 patients younger than 16 years old who underwent renal transplantation via the extraperitoneal approach: 216 patients underwent transplant placement in the iliac fossa like in adults, and 64 underwent transplant placement in the distal part of the original renal lower pole (the extraperitoneal cavity). On the basis of the Clavien-Dindo classification, 30 patients (10.7%) showed grade 2 complications and 12 patients (4.3%) showed grade 3 or higher complications. None of the patients showed gastrointestinal complications. In a Cox regression analysis, grade 2 or higher complications were significantly associated with weight less than 15 kg (P = .027) and operative times longer than 245 minutes (P = .029). Among the 49 patients weighing less than 15 kg with an allograft placed in a distal portion of the original renal lower pole, only 3 patients (6.1%) developed surgical complications. Thus, allograft placement in the extraperitoneal cavity can be performed safely in children weighing less than 15 kg.

Response to steroid and immunosuppressive therapies may predict post-transplant recurrence of steroid-resistant nephrotic syndrome.

BACKGROUND: Recurrence of SRNS is a major challenge in KT. Several clinical factors, including initial steroid sensitivity, have been associated with increased post-transplant SRNS recurrence risk. However, conflicting data have been reported, possibly due to the heterogeneous pathophysiology of SRNS and the lack of genetic testing of SRNS patients. Furthermore, the response to immunosuppressive therapies has not been evaluated. METHODS: Seventy patients aged 1-15 years at SRNS onset who underwent KT between 2002 and 2018 were enrolled. Patients with secondary, familial, syndromic, and genetic forms of SRNS and those who were not treated with steroid were excluded. This study aimed to assess the risk factors for post-transplant recurrence, including treatment responses to initial steroid therapy and additional therapies with immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A. RESULTS: Data from 36 kidney transplant recipients were analyzed. Twenty-two (61%) patients experienced post-transplant SRNS recurrence, while 14 patients did not. The proportion of patients who achieved complete or partial remission with initial steroid therapy and/or additional therapies with immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A was significantly higher in the SRNS recurrence group (19/22, 86%) than in the group without SRNS recurrence (6/14, 43%; p = .01). CONCLUSION: This study suggests that the response to steroid treatment, other immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A may predict post-transplant SRNS recurrence.

Analysis of water and electrolyte imbalance in a patient with adipsic hypernatremia associated with subfornical organ-targeting antibody.

Patients with adipsic hypernatremia present with chronic hypernatremia because of defects in thirst sensation and dysregulated salt appetite, without demonstrable hypothalamic structural lesions. The involvement of autoantibodies directed against the sodium channel, Nax in the subfornical organ (SFO) has recently been reported. However, the pathophysiology of water and electrolyte imbalance underlying the disease has yet to be elucidated. We describe the case of a 5-year-old boy who complained of headaches and vomiting that gradually worsened. Brain magnetic resonance imaging detected no abnormal lesions. Blood laboratory testing revealed a serum sodium (Na) concentration of 152 mmol/L and a serum osmolarity of 312 mOsm/L. His body weight had slightly decreased, and his thirst sensation was absent. His plasma vasopressin concentration was 0.9 pg/mL, despite the high serum osmolarity. He was encouraged to drink water, and oral 1-deamino-8-D-arginine-vasopressin was administered. When serum sodium concentrations were normalized, plasma vasopressin concentrations were apparently normal and ranged from 0.8 to 2.0 pg/mL. He did not present with polyuria at any time. Immunohistochemical study using mouse brain sections and the patient's serum revealed the deposition of human immunoglobulin G (IgG) antibody in the mouse SFO. In conclusion, our observations suggested that water and electrolyte imbalance in adipsic hypernatremia is characterized by a certain amount of vasopressin release regardless of serum sodium concentrations with no response to hyperosmolarity.

A novel de novo truncating TRIM8 variant associated with childhood-onset focal segmental glomerulosclerosis without epileptic encephalopathy: a case report.

BACKGROUND: Heterozygous truncating variants in the Tripartite motif containing 8 (TRIM8) gene have been reported to cause epileptic encephalopathy, both with and without proteinuria. A recent study showed a lack of TRIM8 protein expression, with suppressor of cytokine signaling 1 (SOCS1) overexpression, in podocytes and tubules from a patient with a TRIM8 variant, who presented with epileptic encephalopathy and focal segmental glomerulosclerosis (FSGS). To date, no patients with TRIM8 variants who presented with nephrotic syndrome but without neurological manifestations have been described. CASE PRESENTATION: An 8-year-old girl presented with nephrotic syndrome, without epilepsy or developmental delay. Her kidney biopsy specimens showed FSGS and cystic dilatations of the distal tubules. Whole-exome sequencing identified a novel de novo heterozygous variant in the C-terminal encoding portion of TRIM8 (c.1461C > A), resulting in a premature stop codon (p.Tyr487*). Reverse transcription-polymerase chain reaction using peripheral blood mononuclear cells identified the mRNA sequence of the mutant allele, which confirmed an escape from nonsense-mediated mRNA decay. Immunofluorescence studies showed a lack of TRIM8 expression in glomerular and tubular cells and cystic dilatation of distal tubules. Immunohistochemical studies showed overexpression of SOCS1 in glomerular and tubular cells. CONCLUSIONS: We reported a patient with FSGS, associated with a de novo heterozygous TRIM8 variant, without any neurological manifestations. Our results expanded the clinical phenotypic spectrum of TRIM8 variants.

The Japanese Society for Apheresis clinical practice guideline for therapeutic apheresis.

Most of the diseases for which apheresis therapy is indicated are intractable and rare, and each patient has a different background and treatment course prior to apheresis therapy initiation. Therefore, it is difficult to conduct large-scale randomized controlled trials to secure high-quality evidence. Under such circumstances, the American Society for Apheresis (ASFA) issued its guidelines in 2007, which were repeatedly revised until the latest edition in 2019. The ASFA guidelines are comprehensive. However, in the United States, a centrifugal separation method is mainly used for apheresis, whereas the mainstream procedure in Japan is the membrane separation method. The target diseases and their backgrounds are different from those in Japan. Due to these differences, the direct adoption of the ASFA guidelines in Japanese practice creates various problems. One of the features of apheresis in Japan is the development of treatment methods using hollow-fiber devices such as double filtration plasmapheresis (DFPP) and selective plasma exchange and adsorption-type devices such as polymyxin B-immobilized endotoxin adsorption columns. Specialists in emergency medicine, hematology, collagen diseases/rheumatology, respiratory medicine, cardiovascular medicine, gastroenterology, neurology, nephrology, and dermatology who are familiar with apheresis therapy gathered for this guideline, which covers 86 diseases. In addition, since apheresis therapy involves not only physicians but also clinical engineers, nurses, dieticians, and many other medical professionals, this guideline was prepared in the form of a worksheet so that it can be easily understood at the bedside. Moreover, to the clinical purposes, this guideline is designed to summarize apheresis therapy in Japan and to disseminate and further develop Japanese apheresis technology to the world. As diagnostic and therapeutic techniques are constantly advancing, the guidelines need to be revised every few years. In order to ensure the high quality of apheresis therapy in Japan, both the Japanese Society for Apheresis Registry and the guidelines will be inseparable.

Cancer After Pediatric Kidney Transplantation: A Long-term Single-center Experience in Japan.

BACKGROUND: The cancer incidence, types, and risk factors after pediatric kidney transplantation (KT) have been reported in the United States, Canada, Europe, Australia, and New Zealand. However, no information is available about cancer in pediatric KT recipients in Asian countries. METHODS: Children aged <20 y who underwent initial KT from 1983 to 2016 were analyzed. We compared the cancer incidence with that in the general Japanese population using standardized incidence ratio and examined posttransplant cancer risk using Cox proportional hazards models. RESULTS: A total of 356 children (median age, 11.7 y; interquartile range, 5.0-17.6) received KT with a follow-up period of 4466 person-years. The median age of cancer onset was 18.5 y (interquartile range, 8.0-32.3), and 13 cancers occurred in 12 patients (3.4%). Two patients died from cancer. The most common cancers were posttransplant lymphoproliferative disorders (PTLDs) (38.5%). The median time to PTLD and non-PTLD diagnosis after KT was 0.6 and 16.4 y, respectively. There was no occurrence of skin cancer. The posttransplant cancer incidence was 9.9 times higher than that in the general age-matched population (standardized incidence ratio = 9.9; 95% confidence interval, 4.80-18.39). The cumulative cancer incidence was 5.3% in 20 y after KT, which is lower than that reported in previous studies. We could not identify any risk factors for all cancer after KT in all patients, whereas subgroup analysis in 264 patients with available data of recipient Epstein-Barr virus serological status showed that recipient Epstein-Barr virus-negative serology was an independent risk factor for cancer development. CONCLUSIONS: The incidence of cancer is higher in Japanese pediatric KT recipients than in the general population. The cumulative incidence of cancer after KT was lower in our population than that previously reported. This may be because there was no skin cancer observed in the Japanese pediatric KT recipients in our study.

Degree of foot process effacement in patients with genetic focal segmental glomerulosclerosis: a single-center analysis and review of the literature.

Determining the cause of focal segmental glomerulosclerosis (FSGS) has crucial implications for evaluating the risk of posttransplant recurrence. The degree of foot process effacement (FPE) on electron micrographs (EM) of native kidney biopsies can reportedly differentiate primary FSGS from secondary FSGS. However, no systematic evaluation of FPE in genetic FSGS has been performed. In this study, percentage of FPE and foot process width (FPW) in native kidney biopsies were analyzed in eight genetic FSGS patients and nine primary FSGS patients. All genetic FSGS patients showed segmental FPE up to 38% and FPW below 2000 nm, while all primary FSGS patients showed diffuse FPE above 88% and FPW above 3000 nm. We reviewed the literature which described the degree of FPE in genetic FSGS patients and identified 38 patients with a description of the degree of FPE. The degree of FPE in patients with mutations in the genes encoding proteins associated with slit diaphragm and cytoskeletal proteins was varied, while almost all patients with mutations in other FSGS genes showed segmental FPE. In conclusion, the present study suggests that the degree of FPE in native kidney biopsies may be useful for differentiating some genetic FSGS patients from primary FSGS patients.

Amount and selectivity of proteinuria may predict the treatment response in post-transplant recurrence of focal segmental glomerulosclerosis: a single-center retrospective study.

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation and is associated with poor graft survival. To date, few studies have investigated predictive factors for treatment responses in recurrent FSGS. METHODS: We retrospectively analyzed 16 patients who were < 16 years at the age of onset and had post-transplant recurrence of FSGS from 1993 to 2018. Patients who achieved complete remission or partial remission after initiating therapy for recurrent FSGS were defined as responders. We compared several clinical characteristics between responders and non-responders. Time to remission was also analyzed. RESULTS: Ten patients were responders, and six patients were non-responders. Univariate analysis showed that responders had a significantly lower amount of maximum proteinuria at the time of recurrence (P = 0.015) and more highly selective proteinuria (P = 0.013) than non-responders. The time to remission from initiation of therapy was 2 months (interquartile range 0.2-4.4). In all responders, except for one patient, remission was achieved within 6 months. CONCLUSIONS: Therapeutic responses may be predicted by examining the amount and selectivity of proteinuria at the time of recurrence. Further studies with larger numbers of patients are clearly required to validate these findings.

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.

Any modality of renal replacement therapy can be a treatment option for Joubert syndrome.

Joubert syndrome (JS) is an inherited ciliopathy characterized by a distinctive cerebellar and brain stem malformation which is known as the "molar tooth sign" on axial brain images, hypotonia, and developmental delay. Approximately 25-30% of patients with JS have kidney disease and many of them progress to end-stage kidney disease (ESKD). However, there are few reports on the outcomes of renal replacement therapy (RRT) in patients with JS and ESKD. In this study, we clarified the clinical features, treatment, and outcomes of patients with JS who underwent RRT. We retrospectively analyzed the medical records and clinical characteristics of 11 patients with JS who underwent RRT between June 1994 and July 2019. Data are shown as the median (range). Gene analysis was performed in 8 of the 11 cases, and CEP290 mutations were found in four patients, two had TMEM67 mutations, one had a RPGRIP1L mutation, and one patient showed no mutation with the panel exome analysis. Complications in other organs included hydrocephalus in two cases, retinal degeneration in eight cases, coloboma in one case, liver diseases in four cases, and polydactyly in one case. Peritoneal dialysis (PD) was introduced in seven cases, with a median treatment duration of 5.4 (3.4-10.7) years. Hemodialysis was performed using arteriovenous fistula in two cases, and kidney transplantation was performed 9 times in eight cases. Only one of the grafts failed during the observation period of 25.6 (8.2-134.2) months. The glomerular filtration rate at the final observation was 78.1 (41.4-107.7) mL/min/1.73 m2. The median age at the final observation was 13.4 (5.6-25.1) years, and all patients were alive except one who died of hepatic failure while on PD. Any type of RRT modality can be a treatment option for patients with JS and ESKD.

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.

Chronic Active Antibody-Mediated Rejection with Linear IgG Deposition on Glomerular Capillaries in a Kidney Transplant Recipient.

Glomerular IgG deposition is rarely observed in antibody-mediated rejection. Here, we report chronic active antibody-mediated rejection with linear IgG deposition on glomerular capillary walls in a pediatric kidney transplant recipient. A 6-year-old boy with bilateral renal hypoplasia underwent preemptive deceased-donor kidney transplantation. Five years after the transplantation, an allograft biopsy revealed chronic active antibody-mediated rejection with diffuse linear IgG deposition on glomerular capillaries. Anti-glomerular basement membrane antibody, donor-specific anti-human leukocyte antigen (HLA) antibodies, and anti-angiotensin II type 1 receptor antibody were negative. A multiplex antibody assay identified anti-major histocompatibility complex class I chain-related molecule A antibody. Additionally, a single-antigen bead assay identified autoantibodies to 12 non-HLA antigens, including vimentin and glutathione S-transferase theta-1. To investigate whether IgG autoantibodies in the patient's serum bind to antigens on glomerular capillaries, we incubated the patient's serum with 0-h biopsy specimens of tissue donated to the patient and a control subject, both obtained immediately after nephrectomy from respective donors. IgG signals were observed in neither patient nor control samples. Nevertheless, linear IgG deposition may be explained by the binding of autoantibodies to non-HLA antigens that are usually hidden and only exposed via severe endothelial cell injury. Further studies are needed to confirm the significance of non-HLA antibodies in glomerular IgG deposition.