Nephron最新文献

Introduction: To co-design and test the effectiveness of a tailored COmplex symptom Management intervention FOR adulTs with advanced kidney disease and their informal caregivers along with healthcare professionals who deliver care and support to both patients and informal caregivers. Methods: Informed by Symptom Management Theory, COMFORT is a program of research involving multiple studies and structured around the United Kingdom Medical Research Council's framework for developing complex interventions. The program involves building capacity of nurse researchers across three studies: first development of an intervention using mixed methods, followed by co-design workshops and prototype testing; thereafter testing of the symptom intervention through a feasibility trial. Lastly, evaluation of the intervention's effectiveness and implementation using a type two hybrid randomised control trial design, focussing on both clinical outcomes and implementation fidelity. Conclusion: This research program is expected to demonstrate that the COMFORT intervention is superior to standard care in improving symptom burden among adults with advanced kidney disease and reduce caregiver burden among informal caregivers. The COMFORT Nursing Program addresses a critical gap in clinical practice by focusing on non-pharmacological interventions tailored to individual patient needs and symptom clusters. By integrating shared decision-making and self-management support, the program aims to empower patients and caregivers, enhances clinical practice, and contributes substantial evidence to the domain of symptom management in advanced kidney disease. The involvement of stakeholders throughout the research process ensures the relevance and applicability of the findings to real-world clinical settings.

Introduction: Pulmonary hypertension and right ventricular (RV) dysfunction are associated with an increase in mortality and worse prognosis in patients with end-stage kidney disease (ESKD), but pathophysiologic mechanisms underlying the progression of RV dysfunction remain incompletely understood. The present study aimed to understand right ventricular to pulmonary artery (RV-PA) coupling, which is an early indicator of transition to RV dysfunction, to better characterize adaptive RV response to increased afterload in ESKD patients and changes in RV-PA coupling following renal transplantation.

Methods: One hundred eleven patients with ESKD, including 49 patients scheduled for renal transplantation, underwent a detailed echocardiographic examination and measurement of tricuspid annular plane excursion to pulmonary artery systolic pressure (TAPSE/PASP) ratio, and a repeat examination was performed 6 months after the baseline examination.

Results: Patients with ESKD had significantly lower TAPSE/PASP ratio at baseline (1.02 [0.71-1.63] vs. 1.29 [1.09-1.96], p < 0.001). In 40 patients that underwent transplantation, TAPSE/PASP ratio increased significantly from (0.97 [0.72-1.42] to 1.30 [1.01-1.82], p = 0.03), while in 27 patients remained on dialysis, there was a nonsignificant reduction in TAPSE/PASP ratio (1.21 [0.71-1.62] vs. 0.84 [0.61-1.38], p = 0.44). The change in TAPSE/PASP ratio correlated significantly with the change in pulmonary vascular resistance (OR: 0.61, 95% CI: 0.51-0.72, p < 0.001) and left ventricular mass index (OR: 0.97, 95% CI: 0.96-0.99, p = 0.001) after adjustment.

Conclusions: Patients with ESKD had abnormal RV-PA coupling, as indicated by a reduced TAPSE/PASP ratio, which normalizes 6 months after renal transplantation.

Introduction: Mitophagy is central to acute kidney injury (AKI) pathogenesis. Elucidating its molecular interplay with AKI is crucial for novel therapeutics.

Methods: This study is based on transcriptome sequencing combined with single-cell sequencing and applies bioinformatics analysis. Finally, it is verified by in vitro, in vivo, and clinical specimen experiments.

Results: In transcriptome analysis, combining protein-protein interaction mapping with machine intelligence algorithms, we screened out two mitophagy-related differentially expressed genes (MitoDEGs), solute carrier family 3 member 2 (SLC3A2) and thioredoxin (TXN). The immunological analysis revealed a notable rise in monocyte infiltration in the immune microenvironment of ischemia-reperfusion injury (IRI)-AKI. Spearman analysis indicated hub MitoDEGs were positively correlated with pro-inflammatory immune cell infiltration and negatively correlated with anti-inflammatory or regulatory immune cell infiltration. Based on the highest binding score, 506-26-3 CTD (gamma-linolenic acid) was determined to be the top promising therapeutic candidate. At the single-cell level, hub MitoDEGs were mainly expressed in proximal tubular. In cell experiments, mitophagy was inhibited after hypoxia-reoxygenation, SLC3A2 matched earlier results, while TXN was contrary to the previous analysis results. In the IRI-AKI rat experiments, the findings regarding hub MitoDEGs aligned with our prior analysis, revealing a decrease in the expression of genes associated with mitophagy. Consequently, we directed our attention to the expression levels of SLC3A2 in clinical cases of AKI, where we observed a notable increase.

Conclusion: Our research indicates that SLC3A2 could be a crucial target for enhancing IRI-AKI through the modulation of the mitophagy pathway.

Introduction: The number of spousal donor transplantation (SDT) has increased since the early 1990s. Although the SDT is performed successfully today, several concerns remain regarding compatibility. In particular, in husband-to-wife donations, donor-specific antibodies (DSAs) positivity may develop as a consequence of previous pregnancies, thereby posing a risk to graft survival. However, data on outcomes in recipients with a history of pregnancy and the development of DSA are limited. In this study, we aimed to compare the outcomes of transplantation between high-risk spouses and transplantation from living donors.

Methods: This study was conducted in our nephrology and transplantation department. It involved 59 spousal donors and 72 living-related donors with DSAs who were older than >18 years of age. We evaluated the consecutive patients who had kidney transplantation between 2010 and 2020.

Results: We analyzed data from 59 SDTs with 72 living-related donor transplants (LRDTs) with DSA positivity. Within the first year after transplantation, the acute rejection rate was highest in the husband-to-wife (H-to-W) group (p = 0.01). Compared with LRDT, H-to-W transplants were associated with an increased risk of acute rejection (OR [95% CI]: 4.231 [1.122-15.957], p = 0.03). Cox regression analysis demonstrated a higher risk of rejection in kidney transplants from H to W within the first year of kidney transplantation (HR: 3.734 [95% CI: 1.087-12.825], p = 0.03). There was no increase in creatinine doubling time between groups and no increase in risk of rejection in 5 years. During the follow-up period, graft loss was reported in 3 patients, comprising 2 in the LRDT group and 1 in the W-to-H group.

Conclusion: SDT, particularly when DSA has developed, appears to be associated with a higher risk of rejection during the first year compared with LRDT with similar DSA. Nevertheless, similar graft survival suggests that H-to-W spousal transplants appear to be safe in the long term.

Background: There are considerable sex and gender differences in the epidemiology of chronic kidney disease (CKD), with CKD stage 3, defined as a glomerular filtration rate (GFR) below 60, being more prevalent in women. This raises questions about whether sex differences in age-related GFR decline contribute to this paradox. Only a few studies have investigated this issue, and most of these studies used estimated GFR (eGFR) based on creatinine (eGFRcrea) or cystatin C.

Summary: This article reviews studies examining age-related GFR decline in men and women from the general population. The conflicting findings on sex differences in GFR decline are likely influenced by variations in study populations, including differences in comorbidities, as well as the methods used to assess GFR. Further research is essential to accurately address trajectories of GFR decline in men and women.

Key messages: Sex and gender differences in GFR levels and age-related GFR decline rates may influence the observed differences in CKD prevalence between men and women. Possible differences in age-related GFR decline between men and women may stem from a combination of biological factors, including sex hormones, different methods to assess GFR, and differences in the prevalence and impact of risk factors. Current eGFR equations may not accurately capture sex differences in measured GFR decline. Further research is needed to better understand these differences and their clinical implications.

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.