Nephrology最新文献

Aim: Recently, substantial studies have been accumulated to indicate the important role of gut microbiota in diabetic kidney disease (DKD). The abnormal change of bacterial-derived products could imply specific injuries or play beneficial or harmful roles in DKD progression. In this study, we examined the presence and contribution of the Klebsiella oxytoca gene in the circulation of patients with DKD.

Method: We enrolled a total of 16 healthy participants, 17 patients with DKD, 5 patients with DKD requiring haemodialysis (HD), and 7 patients with CKD without diabetes. Bacterial-derived DNA (16S rDNA and a specific K. oxytoca gene) in the blood was detected using droplet digital PCR, then investigated the relationship with clinical characteristics.

Results: We identified an increase in K. oxytoca genes in the blood of DKD patients. Interestingly, blood K. oxytoca copies and K. oxytoca/ 16S DNA ratio correlated with higher blood creatinine and BUN levels together with lower eGFR in DKD patients. K. oxytoca levels were also associated with higher neutrophil percentage, lower lymphocyte frequency, and increased neutrophil-to-lymphocyte ratio.

Conclusion: Collectively, the presence of the K. oxytoca gene in the circulation could serve as a biomarker reflecting reduced renal function in DKD patients.

Aim: Acute kidney injury (AKI) is a severe condition in hospitalized patients and carries high mortality. The influence of statin use on the outcomes of AKI patients remains inconsistent. We aimed to discover the association between statin use and in-hospital mortality.

Methods: This retrospective study screened all adult admissions in Peking University First Hospital between 1 January 2018 and 31 December 2020, and patients with AKI during hospitalization were included. Exposure was defined as any statin prescription prior to AKI onset. Patients were followed up until death or discharge. The primary outcome was in-hospital all-cause mortality; secondary outcomes included cardiovascular- and sepsis-related mortality, elevated transaminases, rhabdomyolysis and kidney nonrecovery at discharge.

Results: A total of 2034 AKI patients were included. 551 (27%) patients were statin users. During a median of 10 days of follow-up, we documented 283 (14%) in-hospital deaths. Compared with statin nonusers, statin users experienced a significantly lower risk in in-hospital all-cause mortality (adjust hazard ratio [aHR], 0.54; 95% CI, 0.35-0.84) and cardiovascular-related mortality (aHR, 0.48; 95% CI, 0.24-0.97) after covariate adjustment. The survival benefit of statin use was consistent across subgroups, that is, age, sex, initial AKI stage and major surgery (all P for heterogeneity >.05). For sepsis-related mortality, elevated transaminases, rhabdomyolysis and kidney nonrecovery, the association was no longer significant in the fully adjusted model. For any type of statins, a statistically significant association was only observed in atorvastatin (aHR, 0.49; 95% CI, 0.30-0.81).

Conclusions: Statin use may improve survival, and atorvastatin may be preferred in patients with AKI.

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.

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.

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.

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.

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.

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.