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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. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information., Author(s): Kenichiro Miura [sup.1] , Naoto Kaneko [sup.1] , Taeko Hashimoto [sup.1] [sup.2] , Kiyonobu Ishizuka [sup.1] , Yoko Shirai [sup.1] , Masataka Hisano [sup.3] , Hiroko Chikamoto [sup.1] , [...]

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. Graphical abstract, Author(s): Hideki Ban [sup.1] [sup.2] , Kenichiro Miura [sup.1] , Naoto Kaneko [sup.1] , Yoko Shirai [sup.1] , Tomoo Yabuuchi [sup.1] , Kiyonobu Ishizuka [sup.1] , Hiroko Chikamoto [sup.1] , [...]

This article examines the long-term kidney function of individuals with Lowe syndrome, a genetic disorder characterized by ocular disease, central nervous system disorder, and kidney disease. The study analyzed a large group of pediatric and adult patients with Lowe syndrome and found that all patients had congenital cataracts, CNS involvement, and Fanconi syndrome. The study also investigated the estimated glomerular filtration rate (eGFR) and clinical prognostic factors in these patients. The results indicate that kidney disease is a significant prognostic factor in Lowe syndrome, and further research is necessary to understand the progression of chronic kidney disease in adult patients with this syndrome. Another study analyzed the progression of chronic kidney disease (CKD) in individuals with Lowe syndrome, a rare genetic disorder. The study discovered that CKD progressed rapidly after the age of 10, with 84% of patients developing severe CKD after the age of 20. Nephrocalcinosis and hypercalciuria did not have a significant impact on kidney function. The study also found that age was the only factor significantly associated with kidney function. These findings suggest that the majority of individuals with Lowe syndrome develop end-stage kidney disease by their fourth decade of life. [Extracted from the article]

Background Circulating factor(s) has been thought to be the underlying cause of focal segmental glomerulosclerosis (FSGS), and recent studies foster this idea by demonstrating increased soluble urokinase receptor (suPAR) levels in the serum of FSGS patients. Methods To explore the possible contribution of suPAR in FSGS pathogenesis, we analyzed serum suPAR levels in 17 patients with FSGS and compared them with those in patients with steroid-sensitive nephrotic syndrome, chronic glomerulonephritis, or non-glomerular kidney diseases. Results Serum suPAR levels in patients with FSGS were higher than those in patients with steroid-sensitive nephrotic syndrome or chronic glomerulonephritis, but not higher than those in patients with non-glomerular kidney diseases. suPAR levels negatively correlate with estimated glomerular filtration rate and were decreased after renal transplantation in patients with FSGS as well as in those with non-glomerular kidney diseases. Furthermore, 6 FSGS patients with post-transplant recurrence demonstrated that suPAR levels were not high during the recurrence. Conclusions Based on our results, elevated suPAR levels in FSGS patients were attributed mainly to decreased glomerular filtration. These data warrant further analysis for involvement of possible circulating factor(s) in FSGS pathogenesis. Keywords Soluble urokinase receptor * Focal segmental glomerulosclerosis * Post-transplant recurrence, Introduction Focal segmental glomerulosclerosis (FSGS) is a common pattern of histopathological findings seen in children with nephrotic syndrome, and it is one of the leading causes of end-stage renal disease [...]

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. [ABSTRACT FROM AUTHOR]

WDR19 has been reported as a causative gene of nephronophthisis-related ciliopathies. Patients with WDR19 mutations can show various extrarenal manifestations such as skeletal disorders, Caroli disease, and retinal dystrophy, and typically display nephronophthisis as a renal phenotype. However, there is limited information on the renal phenotypes of patients with WDR19 mutations. We report two Japanese infants with Sensenbrenner syndrome caused by WDR19 mutations who demonstrated different features in renal ultrasound and histopathological results, despite several common extrarenal manifestations. Patient 1 had normal sized and hyperechogenic kidneys with several small cysts and histopathological findings compatible with infantile nephronophthisis. Renal ultrasound of Patient 2 showed enlarged kidneys with diffuse microcysts resembling those of autosomal recessive polycystic kidney disease. Her renal histopathology revealed dysplastic kidney with diffuse glomerular cysts. Genetic testing identified compound heterozygous mutations in WDR19 in both patients (Patient 1: c.953delA, c.3533G > A, Patient 2: c.2645 + 1G > T, c.3533G > A). Our patients suggest that WDR19 mutations can cause dysplastic kidney in addition to nephronophthisis pathologically. In addition, differences in pathology of the kidneys from WDR19 mutations may result in heterogeneous features in renal ultrasound findings. Renal phenotypes from WDR19 mutations may thus be more diverse than previously reported. Extrarenal manifestations and genetic testing can therefore help to diagnosis this disease more precisely. [ABSTRACT FROM AUTHOR]