Nephrology最新文献

Aim: The global prevalence of overweight/obesity has been rising, and this trend is apparent in US and European incident end-stage kidney disease (ESKD) populations. We aimed to examine temporal trends in the prevalence of overweight/obesity and underweight among adult incident ESKD patients in Japan by year of dialysis initiation between 2006 and 2019 in comparison with those observed in the Japanese adult population during the same period.

Methods: Using data from the Japanese Society of Dialysis Therapy Renal Data Registry and the National Health and Nutrition Survey, the sex-specific prevalence of overweight/obesity and that of underweight (BMI ≥ 25 kg/m² and <18.5 kg/m², respectively) were calculated, adjusted for age according to the 2019 Population Census via the direct method. Average annual percentage changes (AAPCs) and corresponding 95% confidence intervals (CIs) were calculated to examine trends.

Results: From 2006 to 2019, the age-adjusted prevalence of overweight/obesity in the incident ESKD population increased for males (AAPC 3.36 [95% CI, 2.70 to 4.09]) and females (AAPC 2.86 [95% CI, 1.65 to 4.19]). The age-adjusted prevalence of overweight/obesity in the general population increased for males (AAPC 0.87 [95% CI, 0.26 to 1.42]) but not for females (AAPC 0.01 [95% CI, -0.55 to 0.57]). The age-adjusted prevalence of underweight in the incident ESKD population significantly decreased but was higher than that in the general population for both sexes.

Conclusion: An increasing trend of overweight/obesity was observed in the incident ESKD population in Japan. There is a pressing need to address both underweight and overweight/obesity in the incident ESKD population.

Aim: Several studies have shown that the progression of proteinuria and renal tissue injury is associated with activation of the intrarenal renin-angiotensin system (RAS). CCCTC-binding factor (CTCF) is a DNA-binding factor that plays an essential role in the regulation of gene expression. In the present study, we aimed to investigate the phenotypic effects of CTCF deficiency in podocytes.

Methods: Angiotensin II type 1 receptor blockers (ARBs) were administered to the podocyte-specific Ctcf knockout mice, and histological and biochemical analyzes were performed. We also investigated the changes in the expression of podocin in podocyte cell cultures with or without stimulation with angiotensin II from glomeruli isolated using magnetic beads from podocyte-specific Ctcf knockout mice.

Results: Mice in which Ctcf was deleted from podocytes developed glomerulopathy and mice developed severe progressive proteinuria, and impaired renal function. Moreover, ARBs suppressed the development of glomerulopathy in podocyte-specific Ctcf knockout mice. Both real-time polymerase chain reaction and western blotting showed that podocin expression was decreased in cell cultures stimulated with angiotensin II. Furthermore, RAS components gene expressions in podocyte cell cultures isolated from podocyte-specific Ctcf knockout mice were significantly increased.

Conclusion: These results suggest that RAS is involved in the development of glomerulopathy in podocyte-specific Ctcf knockout mice. Elucidation of the pathophysiology of podocyte-specific Ctcf knockout mice may provide new insights into the relationship between podocyte injury and chronic glomerulonephritis.

Herbaspirillum spp. is a common environmental bacterium usually found in soil, plant roots, and water. It is rarely associated with infection in immunocompromised patients, and rarely reported infections in immunocompetent patients. We report the first case of a Herbaspirillum huttiense bacteraemia in a non-neutropenic home haemodialysis patient. A 57-year-old male presented to our hospital with a 3-day history of malaise, fevers, rigours, and anorexia following dialysis through his central line. On examination, he was pyrexic (temperature 38.7°C) with splinter haemorrhages noted, but no other signs of infection were present. Blood cultures revealed a polymicrobial infection, with Serratia liquefaciens and Corynebacterium jeikeium isolated from the central line and Herbaspirillum sp. was isolated from both the central line and a peripheral culture. A later peripheral blood culture following central line removal isolated Herbaspirillum huttiense. Regular biological testing of his home water supply and dialysate detected no colony forming units of non-fermenting gram-negative bacilli. He was initially treated with ceftriaxone and vancomycin initially, followed by ertapenem and vancomycin. Intravenous antibiotics were ceased following 5 days after central line removal and he made an uneventful recovery.

Aim: In India, 85% of organ donations are from living donors and 15% are from deceased donors. One-third of living donors were rejected because of ABO or HLA incompatibility. Kidney exchange transplantation (KET) is a cost-effective and legal strategy to increase living donor kidney transplantation (LDKT) by 25%-35%.

Methods: We report our experience with 539 KET cases and the evolution of a single-centre program to increase the use of LDKT.

Results: Between January 2000 and 13 March, 2024, 1382 deceased donor kidney transplantations and 5346 LDKT were performed at our centre, including 10% (n = 539) from KET. Of the 539 KET, 80.9% (n = 436) were ABO incompatible pairs, 11.1% (n = 60) were compatible pairs, and 8% (n = 43) were sensitized pairs. There were 75% 2-way (n = 2 × 202 = 404), 16.2% 3-way (n = 3 × 29 = 87), 3% 4-way (n = 4 × 4 = 16), 1.8% 5-way (n = 5 × 2 = 10), 2.2% 6-way (n = 6 × 2 = 12), and 1.8% 10-way KET (n = 10 × 1 = 10). Of the recipients 81.2% (n = 438) were male and 18.8% (n = 101) were female, while of the donors, 78.5% (n = 423) were female and 21.5% (n = 116) were male. All donors were near relatives; wives (54%, n = 291) and mothers (20%, n = 108) were the most common donors. At a median follow-up of 8.2 years, patient survival, death censored graft survival, acute rejection, and median serum creatinine levels of functioning grafts were 81.63% (n = 440), 91% (n = 494), 9.8% (n = 53) and 1.3 mg/dL respectively. We credited the success to maintaining a registry of incompatible pairs, high-volume LDKT programs, non-anonymous allocation and teamwork.

Conclusion: This is the largest single-centre KET program in Asia. We report the challenges and solutions to replicate our success in other KET programs.

Introduction: Autosomal recessive polycystic kidney disease (ARPKD) ranks among the most severe chronic kidney diseases (CKD). Its primary cause is variants in the Polycystic Kidney and Hepatic Disease 1 gene (PKHD1). The clinical spectrum of ARPKD varies widely, ranging from mild late-onset symptoms to severe perinatal mortality. However, achieving an early genetic diagnosis in ARPKD patients before clinical symptoms appear proves challenging.

Case presentation: This case is a 4-year-old boy who experienced a convulsion characterized by a generalized tonic attack lasting approximately 3-5 minutes and later sought treatment to our hospital. However, routine abdominal ultrasound examination accidentally detected that he had diffuse liver lesions, splenomegaly, and bilateral renal enlargement with renal pelvis dilation. Given the uncertainty regarding the underlying cause of the patient's structural abnormalities and convulsions, karyotyping, whole exome sequencing (WES), structural variant analysis (SV analysis) of whole genome sequencing (WGS) were recommended. The result of SV analysis revealed that he has an RBT impacting PKHD1 and the precise location of breakpoints was confirmed through Long-Range Polymerase Chain Reaction (LR-PCR). However, WES did not screen out pathogenic variants initially, the WES data was reviewed subsequently based on SV analysis results.

Conclusion: We identified an infrequent variant combination, c.2507T>C (p.V836A) in PKHD1 and an RBT with broken PKHD1, which extends the genetic spectrum of ARPKD, and provide a basis for further genetic counselling to the family.

Mercury contained in beauty-enhancing cosmetics can cause chronic poisoning and membranous nephropathy (MN). We report two cases of nephrotic syndrome caused by MN with evidence of mercury poisoning due to the application of fairness cream in a short duration of a few months. The individuals were positive for neural epidermal growth factor-like 1 [NELL-1]. Discontinuation of the use of cosmetic products and modified Ponticelli regimen improved the nephrotic state in these individuals. We suggest that mercury poisoning should be considered in NELL-1-positive individuals with a history of application of beauty products.

Alport syndrome (AS) is one of the most common inherited kidney disorders, involving pathogenic variants of COL4A3, COL4A4 and COL4A5 genes that lead to disruption of the normal structure of collagen IV protein through improper chain or heterotrimer folding or degradation of heterotrimer components. Lipoprotein glomerulopathy (LPG) is an autosomal dominant disease involving APOE gene mutations disturbing lipoprotein metabolism. We report the first case with both AS and LPG in an 11-year-old girl. The patient presented with blepharedema, and decreased vision. Laboratory examinations showed hematemesis, proteinuria, hypoproteinemia, hyperlipidemia and progressive renal failure. Renal biopsy showed the changes of LPG and AS. Whole-exome sequencing (WES) identified two pathogenic variants, c.127C > T in exon 3 of APOE gene, and c.930 + 1G > A in exon 15 of COL4A4 gene. We emphasize the importance of early completion of renal biopsy and WES for early diagnosis of LPG and AS.

Aim: This study aimed to describe the epidemiology of kidney replacement therapy (KRT) in Aotearoa New Zealand and assess the impact of residential location on access to kidney transplantation.

Methods: AcceSS and Equity in Transplantation (ASSET), a health-linked data platform, was used to identify people commencing KRT in New Zealand from 2006 to 2019 and analyse regional epidemiology. Health services were classified as 'transplanting', 'intermediate' or 'remote' depending on their degree of separation from a transplant centre. Multiple logistic regression modelling was used to assess the predictors of deceased donor waitlisting or living donor transplantation within 6 months after starting KRT. Web-based mapping software was used to develop interactive geospatial maps.

Results: The cohort was 7704 people newly starting KRT. Living in an intermediate [odds ratio (OR): 0.73 (95% confidence interval (CI): 0.61-0.88)] or remote [OR: 0.38 (95% CI: 0.27-0.54)) region and Māori (OR: 0.35 (95% CI: 0.28-0.44)], Pacific [OR: 0.32 (95% CI: 0.24-0.42)) and Asian (OR: 0.66 (95% CI: 0.50-0.87)] ethnicity were associated with a decreased likelihood of timely waitlisting or transplantation. Regional maps can be explored here.

Conclusion: There is marked geospatial and ethnic variation in the epidemiology of kidney failure and access to kidney transplantation across New Zealand. Geospatial mapping of kidney failure epidemiology and transplantation outcomes can provide opportunities to direct resources towards populations at greatest need.

Aim: Determining specific causes of allograft failure allows a focus on understanding and treating these conditions. Previous studies highlight chronic antibody-mediated rejection as a leading cause of late allograft failure. We sought to define causes of allograft failure in a large cohort of kidney transplant recipients across multiple centres in Australia and New Zealand, including cases previously attributed to chronic allograft nephropathy (CAN).

Methods: All death-censored allograft failures at 9 participating centres between 1 January 2014 to 31 December 2018 were included. Available clinical and biopsy data were reviewed and the "most likely" cause assigned.

Results: There were 642 death-censored allograft failures in the study period. Of these, 495 (77.1%) had an informative biopsy performed a median of 13.4 months (IQR 2.5-39.1 months) prior to allograft failure. Rejection of any type was the leading cause of allograft failure (47.5%), comprised chiefly of chronic antibody-mediated rejection (37.4%) and chronic T-cell mediated rejection (6.4%). Other leading causes were undifferentiated interstitial fibrosis and tubular atrophy (10.8%), late medical and surgical complications (8.1%) and recurrent or de novo glomerulonephritis (7.0%). Polyoma viral nephropathy and calcineurin inhibitor toxicity each contributed to <2%. Causes of allograft failure previously attributed to CAN (n = 419, 65.3%) had a similar distribution to the overall cohort, with 43.9% attributed to chronic antibody-mediated rejection.

Conclusion: To prolong allograft survival, improved strategies are needed to curtail alloimmune responses. Greater understanding of the causes of undifferentiated interstitial fibrosis and tubular atrophy and potential treatments would also be of considerable benefit.

Background: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD) is the predominant isoform of the catalytic subunit of PI3K in lymphocytes. Based on comprehensive bioinformatics, this study explores the functions of PIK3CD in diabetic kidney disease (DKD) progression in mice and B lymphocyte activity.

Methods: Non-obese diabetic (NOD) mice that spontaneously develop DKD were applied as animal models. Lentiviral vector-mediated PIK3CD silencing was introduced in mice, followed by histological staining and biomarker assessments to evaluate DKD-associated symptoms. The activity of the Akt/mTOR signalling pathway was determined by western blot analysis. Following bioinformatics analyses, the interaction between POU class 2 homeobox 2 (POU2F2) and PIK3CD in B lymphocytes was determined by chromatin immunoprecipitation and luciferase reporter assays. Their functions in B cell function were identified by MTT, flow cytometry and IgG deposition assessment.

Results: PIK3CD was found to be highly expressed in the kidney of DKD mice. Knockdown of PIK3CD inactivated the Akt/mTOR signalling, thus ameliorating tissue injury and fibrosis, enhancing the expression of AQP1 and decreasing urinary NGAL contents, UACR, BUN and β-NAG/creatinine ratio. These effects were negated by the Akt-specific activator SC79. POU2F2 was found to promote PIK3CD transcription by binding to its promoter, thus activating the Akt/mTOR pathway. Knockdown of POU2F2 suppressed B cell proliferation in vitro and decreased B cell population and IgG deposition in the mouse kidney. However, these trends were reversed upon additional PIK3CD overexpression.

Conclusion: This study demonstrates that POU2F2 mediates PIK3CD-dependent Akt/mTOR signalling activation, thus enhancing B lymphocyte function and promoting DKD progression.