Nephrology Dialysis Transplantation最新文献

Background: ATP6V1B1 encodes a subunit of the vacuolar H+-ATPase and pathogenic variants are associated with autosomal recessive distal renal tubular acidosis (dRTA) with deafness. Heterozygous variants predicted to affect a specific amino acid, Arg394, have been recurrently reported in dRTA but their significance has been unclear. We hypothesized that these variants are associated with a dominant disease mechanism.

Methods: We conducted a retrospective analysis of cases identified in our genetic laboratories and through European nephrology organizations. Data regarding demographics, clinical presentation, laboratory findings, hearing and imaging studies of kidneys were collected from the index patient and, if available, from other family members. The potential disease mechanism was investigated through structural modelling in silico.

Results: Twenty index patients in total were included, of which 19 carried the variant c.1181G>A; p.(Arg394Gln) and one c.1180C>G; p.(Arg394Gly). In seven families, more than one member was affected and the variant segregated with the disease in those with available information (15 affected, 6 unaffected), except for the unaffected mother of 2 affected children, who was mosaic. In no patient was a second causative variant in trans identified. In eight sporadic patients and one affected parent, the variant was confirmed to be de novo. Both variants are absent in gnomAD. Sensorineural hearing loss was reported in 8 of the 22 patients with available information. Structural modelling supports a crucial role for Arg394 in nucleotide binding.

Conclusion: We provide strong evidence for the pathogenicity of heterozygous variants affecting Arg394 and thus a novel inheritance modus for ATP6V1B1-associated dRTA. Clinically, this form differs from the recessive one by the lower prevalence of hearing loss. The prominent position of Arg394 in the nucleotide binding fold of the H+-ATPase structure is consistent with a dominant negative mechanism. Our findings inform the diagnosis and management of patients with dRTA and variants of Arg394.

The phospholipase A2 receptor antibody (PLA2R-Ab) test is a valuable first-line diagnostic tool for primary membranous nephropathy (MN), helping to identify PLA2R-related MN and potentially eliminating the need for a kidney biopsy in some individuals. By reducing the reliance on biopsies, the test streamlines diagnosis and improves patient care. However, determining the optimal PLA2R measurement method and cut-off is critical to maximizing the benefits of the test and minimizing any harms. A systematic review and meta-analysis were performed to evaluate serum- and urine-based biomarkers for distinguishing between PLA2R-related MN and non-PLA2R MN. Searches were conducted in databases including Medline, Embase, Cochrane Library, Scopus, Web of Science, International HTA Database and ClinicalTrials.gov. The methodology followed Cochrane-recommended guidelines for systematic reviews and meta-analyses, and the QUADAS-2 tool was utilized to assess the overall risk of bias. Ninety-one studies met the eligibility criteria for inclusion in the review. Of these, 38 studies reporting the accuracy of the PLA2R-Ab test using the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) method and 27 using the EUROIMMUN immunofluorescence (IF) method were suitable for meta-analysis. The pooled sensitivity and specificity of EUROIMMUN ELISA at a cut-off value of 20 RU/mL were 0.64 [95% confidence interval (CI) 0.56-0.72] and 94.7% (95% CI 90.5-97.1%), respectively. The pooled sensitivity and specificity of EUROIMMUN IF at a threshold of 1:10 was 0.69 (95% CI 0.637-0.739) and 0.98 (95% CI 0.931-0.994), respectively. Risk of bias was higher for studies evaluating the IF compared with ELISA test. We also explored whether the timing of the index test had an impact on the pooled diagnostic accuracy results; no significant differences were found. By evaluating the specificity and sensitivity of EUROIMMUN ELISA PLA2R-Ab and IF, we demonstrate that at ELISA levels ≥20 RU/mL, alongside thorough secondary screening, a kidney biopsy may be unnecessary. However, lower or negative levels still warrant a biopsy.

Haemodialysis (HD) is a life-saving therapy for individuals with kidney failure. Post-filter haemodiafiltration (HDF) and high-flux HD are the most widely used treatment modalities. To date, five randomized controlled trials (RCTs) have been performed that compare all-cause and cardiovascular (CV) mortality between HDF and low- or high-flux HD in adults receiving maintenance dialysis for at least 1 year. RCTs, meta-analyses and pooled individual patient data analyses have been published on this topic. However, all of them are limited by the heterogeneity of inclusion criteria and significant methodological shortcomings, including informative selection bias and the exclusion of poorly performing patients from the HDF arm after randomization. Given this background, the European Dialysis Working Group of the European Renal Association presents a Consensus Statement on HDF and high-flux HD, addressing three key outcomes: survival, health-related quality of life, and biochemical endpoints. A separate section is dedicated to paediatric patients. We searched five large electronic databases to identify parallel or cross-over RCTs comparing HDF with high-flux HD on pre-defined outcome measures. Using a mini-Delphi method, we developed 22 key consensus points by combining meta-analyses, clinical experience, and expert opinion. They aim to inform and assist in decision making and are not intended to define a standard of care. The key summary point is that HDF appears to be associated with improved overall and CV survival, provided high convection volumes are achieved. The generalizability of these findings to the entire dialysis population depends on the patient's overall health and requires further study.

Background: It is unclear whether low birth weight (LBW), preterm birth and small for gestational age (SGA) could synergistically cause chronic kidney disease (CKD) and end-stage kidney disease (ESKD). This cohort study was conducted to examine their individual and combined impacts on the development of CKD and ESKD in childhood.

Methods: From the Taiwan Maternal and Child Health Database, we identified 1 477 128 newborns born between 1 January 2009 and 31 December 2016. We used a multivariable Cox regression model to assess the excess risk of CKD and ESKD in children with LBW/preterm/SGA. They were followed from birth until the occurrence of outcomes or until 31 December 2018, with an average follow-up of 5.78 years.

Results: This study included 1 361 071 infants with birth weight ≥2500 g (92.14%), 104 855 infants with low birth weight (1500 g to <2500 g) (7.10%), 6843 infants with very low birth weight (1000 g to <1500 g) (0.46%) and 4349 infants with extremely low birth weight (<1000 g) (0.29%). The multivariable-adjusted model showed that male infants with low birth weight were associated with an increased risk of CKD [adjusted hazard ratio (aHR) 1.20, 95% confidence interval (CI) 1.08-1.32] and ESKD (aHR 1.64, 95% CI 1.37-1.97). Female infants with LBW had an increased risk of CKD (aHR 1.18, 95% CI 1.06-1.32) and ESKD (aHR 1.31, 95% CI 1.09-1.58) than those without LBW. In addition to LBW, infants with preterm or SGA condition also had a significantly and synergistically increased risk of CKD and ESKD compared with full-term infants.

Conclusion: We found children with LBW, preterm birth or SGA had a significantly increased risk of CKD and ESKD compared with children without intrauterine growth restriction.

Background: Unlike X-linked or autosomal recessive Alport syndrome, no clear genotype/phenotype correlation has yet been demonstrated in patients carrying a single variant of COL4A3 or COL4A4.

Methods: We carried out a multicentre retrospective study to assess the risk factors involved in renal survival in patients presenting a single pathogenic variant on COL4A3 or COL4A4.

Results: A total of 97 patients presenting a single pathogenic variant of COL4A3 or COL4A4 were included. The prevalence of end-stage kidney disease (ESKD) during follow-up was 28.7% [median age 47.5 years (interquartile range 39.1-55.8). A total of 23 patients carried a 'severe' mutation (frameshift, stop gain, extensive deletion, impacting splicing) and 60 patients presented a glycine substitution in a collagenous domain. In patients with glycine missense variants, the location of the mutation in the distal exons was associated with worse renal survival with a more pronounced decline in the estimated glomerular filtration rate compared with variants in proximal exons. Conversely, the presence of a severe mutation did not impact renal survival.

Conclusion: Our results confirm that autosomal dominant Alport syndrome (ADAS) can lead to ESKD. We demonstrated that a glycine substitution involving the distal exons had a negative impact on renal survival in ADAS patients, probably due to a trimerization defect. This could help improve personalized follow-up in ADAS patients with glycine substitution and could be integrated into a future prognostic score to accurately predict renal outcomes.

Background: Haemodiafiltration (HDF) therapy improves the prognosis by reducing inflammation and oxidative stress and improving endothelial function. These factors contribute to vascular access (VA) stenosis, one of the most common complications in patients on haemodialysis (HD) or HDF. This study aimed to assess the efficacy of HDF on VA patency.

Methods: This multicentre, prospective, observational study with post hoc analysis included 612 patients among 643 who underwent VA procedures and started dialysis between April 2012 and March 2021. A total of 516 patients were on HD since starting dialysis, while 96 switched to HDF after starting dialysis. One-to-one propensity score matching was performed to compare the 24-month patency rates of VA between groups by Kaplan-Meier and logrank tests, and a Cox proportional hazards regression analysis was used to identify factors affecting patency rates.

Results: There were 87 patients in each group. The 24-month primary patency rates were 74.2% for HDF and 47.7% for HD (P < .001). A multivariate Cox proportional hazards analysis showed that a history of cardiovascular disease {hazard ratio [HR] 2.29 [95% confidence interval (CI) 1.21-4.34], P = .01} and higher haemoglobin A1c values [HR 1.37 (95% CI 1.00-1.82), P = .04] were associated with poor 24-month primary patency. However, HDF [HR 0.30 (95% CI 0.16-0.56), P < .001] and use of statins [HR 0.50 (95% CI 0.27-0.94), P = .03] were associated with better patency. A stratified analysis showed that HRs for loss of VA patency were lower in patients with HDF than in those with HD in the subgroups of ≥65 years, male sex, radiocephalic arteriovenous fistula, a history of diabetes mellitus or cardiovascular disease, haemoglobin concentrations <10 g/dl and albumin concentrations <3.5 g/dl.

Conclusions: HDF potentially improves VA patency rates compared with HD, even in patients with cardiovascular disease or diabetes, commonly associated with poor patency.

Music-based interventions (MBIs) have shown promise in enhancing cognitive and behavioural functions in patients with mild cognitive impairment (MCI). This review aims to synthesize current knowledge on the clinical application of MBIs in MCI and explore their potential use in patients with chronic kidney disease (CKD). A systematic search was conducted in the PubMed, PsycInfo, Cochrane Library and Scopus databases for studies published between January 2013 and October 2023. The search focused on MBIs applied to MCI and CKD patients. We collected data on study design, type of MBIs administered and main clinical outcomes. Sixteen studies were included in this review, ten of which were randomized controlled trials. MBIs ranged from passive music listening (four studies) to active participation in music-making (vocal or singing activities, playing instruments and improvisation, music interventions associated with physical activity, musical stimulation). While no studies specifically focused on CKD patients, cognitive improvements were generally more significant with active interventions, whereas behavioural benefits were more associated with receptive approaches. MBIs showed potential benefits in improving cognitive and depressive symptoms associated with MCI. Given the high prevalence of MCI in CKD patients, future studies should investigate the application of MBIs in this population.