Nephron最新文献

Introduction: Treatment conditions and progression of chronic kidney disease (CKD) are factors for work incapacity, related with physical limitations and social and emotional distress, affecting quality of life (QOL).

Methods: In a cross-sectional study, 343 patients with CKD were included: chronic kidney disease non-dialysis (CKD G3-G5ND) (n = 98), hemodialysis (HD) (n = 95), peritoneal dialysis (PD) (n = 96), and kidney transplant (KT) (n = 54). A clinical and nutritional assessment was carried out using the Subjective Global Assessment instrument. QOL was assessed using the Kidney Disease Quality of Life Short Form instrument.

Results: Employed patients (44%) were younger (40 ± 14 vs. 51 ± 16 years, p < 0.0001), had >9 years of schooling (49 vs. 29%, p < 0.0001), lower diabetes frequency (21 vs. 47%, p < 0.0001), hypertension (71 vs. 87%, p < 0.0001), cardiovascular disease (5 vs. 16%, p = 0.002), and better nutritional status score (6 ± 1 vs. 5 ± 1, p < 0.0001) than unemployed. Employed patients with KT had better QOL than employed patients on CKD G3-G5ND, HD, and PD (76 ± 6, 68 ± 13, 68 ± 12, and 67 ± 7, respectively, p < 0.05). In multivariate analysis, employment predicted QOL in all kidney replacement therapies (KRTs): HD (B = 10.1, 95% CI: 5.5-14.6), PD (B = 4.5, 95% CI: 0.08-8.9) and KT (B = 13.3, 95% CI: 6.1-20.5). Nutritional status predicted QOL in all groups: CKD G3-G5ND (B = 3.6, 95% CI: 1.24-5.97), HD (B = 2.44, 95% CI: 0.4-4.4), PD (B = 3.73, 95% CI: 2.1-5.3), and KT (B = 4.4, 95% CI: 0.05-8.8).

Conclusion: Only 44% of patients had employment. Employed patients had better QOL, were younger, more educated, had fewer comorbidities and better nutritional status than unemployed patients. Employment predicted QOL in all three KRTs but not in CKD G3-G5ND patients, and nutritional status was a predictor QOL in all groups.

Introduction: The aetiology of congenital nephrotic syndrome (CNS) is heterogenous with genetic and more rarely infectious or maternal allo-immune disease causes. In resource-replete settings, 60-80% of CNS is attributable to monogenic causes, with other causes much more rarely diagnosed. The relative prevalence of these aetiologies and differences in clinical presentation are understudied in southern Africans. We describe the aetiology, clinical presentation, outcomes, and genetic testing results in black African infants with CNS.

Methods: We enrolled 36 children with CNS from a tertiary referral centre in KwaZulu-Natal, South Africa. Chart reviews were performed to identify aetiology, clinical features, and outcomes. Genetic testing for variants in NPHS1, NPHS2, WT1, LAMB2, and PLCE1 was performed for a subset of 9 children with CNS without infection.

Results: Of the 36 CNS cases, 15 (41.7%) children were diagnosed with infection-associated CNS: 11 (30.6%) with cytomegalovirus (CMV) and 4 (11.1%) with human immunodeficiency virus (HIV). Twenty-one (58.3%) of the cases had unknown aetiology after the exclusion of other non-genetic causes, nine of whom underwent genetic testing, yielding a genetic diagnosis for 3 (33.3%) of the 9: 2 (22.2%) children were homozygous for NPHS1 p.R460Q and one for NPHS2 p.V260E. There were no statistically significant differences in age of diagnosis, age at kidney failure, age of death or kidney function markers between the group of infants with CNS attributed to infection and those without infection (p > 0.05). Infants with monogenic CNS experienced, on average, an earlier diagnosis (mean age 28 days, SD 11) than those with infection-associated CNS (43 days, SD 19.11).

Conclusion: South African black children are diagnosed with high rates of CNS attributed to untreated maternal CMV and HIV infections likely resulting from limited prenatal maternal care in this population. The diagnostic genetic yield was much less than expected, most likely due to the small number of patients tested compared to larger studies in Western settings, indicating a need for further investigation of the genetic landscape of CNS in African populations.

Introduction: Recent studies have identified an association between regional citrate anticoagulation (RCA) and subsequent infectious complications during continuous renal replacement therapy (CRRT). We aimed to determine if RCA was associated with infectious complications in children and young adults receiving CRRT.

Methods: A secondary analysis of the multinational Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry (34 centers, 9 countries), was performed, including patients from 2015 to 2018. Patients were excluded if they (1) died within 72 h of CRRT initiation, had minor trauma or were postsurgical (analysis 1), or (2) met an exclusion in analysis 1 or had sepsis prior to CRRT initiation or chronic immunosuppression (analysis 2). Multivariable mixed-effects logistic (analysis 1) and mixed-effects Cox regression (analysis 2) were used to determine the associations between anticoagulant type and culture-positive infection after CRRT initiation.

Results: A total of 874 patients were included in analysis 1 and 283 in analysis 2. Culture-positive infection occurred in 25% and 17% of each analysis. In analysis 1, culture-positive infection was higher in RCA (29%) vs. heparin (23%) and other (15%); p = 0.008. There was no association between RCA and infection in multivariable analysis. In analysis 2, there was no difference in the frequency of infection by anticoagulation type. A longer time to achieve the first negative fluid balance was associated with culture-positive infection.

Conclusion: RCA was not associated with culture-positive infection after CRRT initiation in this study. The systemic effects of AKI and longer time to first negative fluid balance may be inciting factors for an infection and represent a potentially modifiable factor that warrants future studies in this high-risk population.

Background: Mitochondria are central regulators of cellular metabolism, redox signaling, and apoptosis. Their dysfunction plays a pivotal role in the pathogenesis of kidney diseases, including acute kidney injury and diabetic nephropathy.

Summary: Recent advances have unveiled horizontal mitochondrial transfer as a novel intercellular communication by which renal cells exchange mitochondria to promote tissue repair through the modulation of metabolic processes, oxidative stress, apoptosis, and fibrosis.

Key findings: Horizontal mitochondrial transfer, mediated by tunneling nanotubes and extracellular vesicles, has emerged as a potential homotypic rescue mechanism between injured tubular and glomerular cells. In addition, heterotypic mitochondrial transfer from mesenchymal stromal cells to renal cells has been described. These findings open new perspectives for exploring therapeutic mitochondrial transplantation in both acute and chronic kidney diseases. Nonetheless, significant challenges remain, including elucidating the poorly characterized biological mechanisms underlying mitochondrial transfer, optimizing delivery strategies, and defining the long-term safety and efficacy of mitochondrial-based therapies.

Introduction: Coenzyme Q8B (COQ8B) nephropathy is an autosomal recessive hereditary disorder caused by primary coenzyme Q10 (CoQ10) deficiency. It manifests as a genetic steroid-resistant nephrotic syndrome (SRNS), typically of childhood-onset. CoQ10 supplementation is a treatment option; however, it is not always effective in an entire patient population, leading to end-stage kidney disease. Kidney transplantation (KTx) is an effective treatment option for genetic SRNS; however, living KTx within biologically related members is associated with increased risk of allograft failure in recipients and future kidney dysfunction in donors. Here, we present two successful cases of living kidney donations from heterozygous carrier parents to their siblings with COQ8B nephropathy.

Case presentation: The family comprised two parents and three siblings. Two of the daughters were diagnosed with proteinuria at 11 and 8 years of age, respectively. COQ8B nephropathy diagnosis was confirmed by next-generation and Sanger sequencing analysis, which revealed a novel compound heterozygous mutation in the COQ8B gene (c.737G>A and c.1468C>T). An older sister missed an opportunity for CoQ10 supplementation due to late diagnosis, whereas a younger sister did not respond to CoQ10 supplementation. Living kidney donation from father to the older sister and from mother to the younger sister was successfully performed without post-transplant recurrence in recipients or kidney dysfunction in donors within 5 and 2 years of follow-up.

Conclusion: Parent-to-child KTx may be an effective treatment option within family members affected with COQ8B nephropathy.

Background: Acute kidney injury (AKI) pathophysiology and repair are heterogenous processes, and clinical outcomes are difficult to predict. As a result, promising treatments in preclinical models have failed to translate to human subjects, and treatment options for AKI are primarily supportive.

Summary: To address this, one of the AKI and CRRT 2025 preconference symposium plenary sessions showcased cutting-edge translational work to guide the scientific community of AKI investigators. Topics included those focused on stratifying risk for AKI reflected in the concept of kidney fitness, characterizing the molecular phenotypes of AKI, improving diagnostics, and identifying novel therapeutic targets.

Key messages: This article provides a review of these topics and a summary of how they address challenges to translating new therapies in AKI from bench to bedside.

Introduction: Left ventricular hypertrophy (LVH) is a common cardiovascular complication in chronic kidney disease (CKD), driven by anemia and nutritional deficiencies. The hemoglobin-to-red cell distribution width ratio (HRR) reflects these factors, but its association with LVH in CKD remains unclear. This study aimed to investigate the relationship between HRR and LVH in non-dialysis CKD stage 3-5 patients.

Methods: In this cross-sectional study, 195 patients were included. HRR was calculated from hemoglobin and red cell distribution width. LVH was diagnosed by echocardiography (LV mass index >115 g/m2 in men, >95 g/m2 in women). Logistic regression assessed HRR-LVH association, including subgroup and restricted cubic spline analyses. Mediation analysis explored the role of intact parathyroid hormone (iPTH) and N-terminal pro-brain natriuretic peptide (NT-proBNP).

Results: Patients with LVH (n = 40) had significantly lower HRR (median 0.62 vs. 0.81, p < 0.001). HRR was inversely associated with LVH (adjusted OR 0.41 per SD increase, p = 0.005), with the highest HRR tertile showing the lowest LVH risk (adjusted OR 0.23, p = 0.044). Subgroup analyses showed consistent associations. Mediation analysis indicated iPTH and NT-proBNP explained 37% and 21.1% of the HRR-LVH relationship.

Conclusion: HRR may be a simple marker for cardiovascular risk stratification in CKD. Prospective studies should assess whether interventions targeting HRR reduce LVH incidence.

Background: Kidney transplantation and dialysis are the two main modalities of kidney replacement therapy, and both are increasingly challenged by the current climate emergency landscape. Dialysis has long been scrutinised for its high energy and water demands, but transplantation, while generally more sustainable over the long term, also warrants critical evaluation concerning environmental accountability, equity, and resilience.

Summary: In this review, we compare the environmental and structural dimensions of dialysis and transplantation, while examining how climate change uniquely affects transplant recipients and grafts. We highlight the vulnerabilities of immunosuppressed recipients to heat stress and infectious diseases, the risks of cold chain disruption for organ preservation and shipment, and the impact of graft failure necessitating return to dialysis. We then consider how green nephrology principles can be applied to transplantation, drawing on emerging UK data, global policy frameworks such as the European Green Deal, and lessons from low- and middle-income countries. Digital healthcare solutions such as hybrid virtual clinics are explored as tangible strategies to reduce the carbon footprint of follow-up care. Recent life-cycle analyses also provide comparative estimates of dialysis and transplantation emissions, underscoring the importance of nuanced evaluation of both modalities.

Key messages: We conclude with a forward-looking agenda for clinicians and policymakers to embed environmental and social responsibility into both dialysis and transplantation, ensuring that kidney replacement therapy as a whole is resilient and sustainable in a warming world.

Background: Acute kidney injury (AKI) represents a multifaceted clinical syndrome marked by precipitous loss of kidney function, high morbidity and mortality, and a strong propensity for progression to chronic kidney disease. Collectively, these challenges underscore the imperative to delineate conserved molecular and signaling networks that are uniformly engaged across diverse AKI etiologies.

Summary: Herein, we survey five emerging research domains poised to transform AKI pathophysiology and therapeutic paradigms. First, lymphatic network remodeling has been implicated as a critical determinant of renal immunodynamics and interstitial fluid homeostasis, whereby modulation of VEGF-C/D signaling reshapes immune cell trafficking and fibrogenic responses. Second, we will cover emerging evidence that positions macrophage ferritin heavy chain as a key regulator of macrophage phenotype and subsequent kidney ferroptosis susceptibility via coordinated regulation of synuclein-⍺, and Spic. Third, we will emphasize incorporating development as a biological variable into experimental design based on evidence that identifies age-dependent divergences in injury susceptibility, and progression of disease. Fourth, we cover mechanosensitive ion channels that are activated by therapeutic ultrasound offering novel opportunities to harness the cholinergic anti-inflammatory pathway for nephroprotection. Finally, targeting tubular epithelial cell senescence and mitochondrial bioenergetics as a promising approach to limit progression of kidney disease will be discussed.

Key messages: Collectively, these emerging mechanisms deepen our understanding of AKI pathophysiology and unveil novel therapeutic targets with the potential to transform the treatment landscape.

Introduction: Nephronophthisis (NPHP) is an autosomal recessive kidney disease resulting mainly from primary cilium defects, with unspecific and variable symptoms that can progress to kidney failure needing replacement therapy at a young age. Currently, up to 64% of likely NPHP cases can be diagnosed by assessing known genes. Therefore, there is a need to gain more insight in what genes can cause this disease.

Methods: In a diagnostic setting, we performed broad genetic testing in patients with advanced kidney disease. We carried out in silico and in vitro analyses for TMEM72, including immunohistochemistry and affinity proteomics, and in vivo experiments to further interpret our findings.

Results: We identified biallelic TMEM72 variants in 9 patients from six families with a phenotype suggestive for NPHP. Five families presented with kidney failure at a (young) adult age. One family had a different phenotype with prenatal onset of kidney failure and neurological symptoms. The phenotypes of the patients correspond to TMEM72 expression mainly in the kidney. In silico analyses indicate that homozygous loss-of-function variants are likely not tolerated in TMEM72. Immunohistochemistry staining of kidney biopsies revealed altered localization and expression of TMEM72 in cases compared to controls. In human-derived tubuloids, we showed that TMEM72 localizes to the cilium. Furthermore, using an affinity proteomics approach, we found an association of TMEM72 and ciliary function, more specifically in selective ciliary cholesterol transport.

Conclusion: We present the first genetic evidence, underlined by immunohistochemistry and protein binding assays, linking TMEM72 variants to kidney disease and ciliary function. We conclude that TMEM72 is a candidate gene for NPHP. Future work is needed to further characterize TMEM72 variants and unravel its disease mechanism.