Nephrology Dialysis Transplantation最新文献

Acute kidney injury (AKI) is a critical complication in patients with chronic lung diseases (CLD), particularly during acute exacerbations. This review focuses on the pathophysiological mechanisms linking CLD to AKI and highlights key clinical strategies to mitigate its impact. CLD patients with pre-existing kidney dysfunction face an increased risk of AKI due to impaired gas exchange, systemic inflammation, and neurohormonal activation. Hypoxemia and hypercapnia contribute to kidney hypoperfusion, endothelial dysfunction, and sodium-water imbalances, exacerbating renal injury. Current management strategies prioritize minimizing mechanical ventilation-related damage, optimizing hemodynamics, and preventing AKI progression. A multidisciplinary approach is essential to improving outcomes, emphasizing early identification and targeted interventions for CLD-associated AKI.

HLA-matching between donor (D) and recipient (R) is routinely performed in kidney allocation to optimize allograft survival but explains only a moderate variability of these outcomes. Recent findings suggest that donor-to-recipient mismatches outside the HLA region contribute to alloimmunity and graft loss, but the extent varies in different publications. We therefore conducted a systematic review of publications on this subject using a broad search string in our literature review in accordance with current guidelines for systematic reviews. The effect sizes were analyzed by a meta-analysis. A total of 1890 publications from 2019-25 within three different repositories (465 Medline, 1408 Embase, 17 Central) were systematically screened using the PICOTS (Population, Intervention, Comparator, Outcome, Time and Setting) system, which resulted in 12 eligible papers that met the inclusion criteria. Cohort studies that investigated the association of D-R non-HLA SNP mismatch and graft rejection/loss in renal transplant patients were included. We found that overall SNP mismatch between D-R pairs outside the HLA region was independently numerically associated with rejection hazard ratio (HR) 1.26 [95% confidence interval (CI) 0.97-1.65] and graft loss HR 1.35 (95% CI 0.86-2.12). Furthermore, loss of function mutation of the gene LIMS1 in the recipient who received a transplant organ with at least one functioning copy (collision genotype) was numerically associated with rejection HR 1.23 (95% CI 0.68-2.23) and graft loss HR 1.43 (95% CI 0.61-3.36). The exact quantification of the effect size of these mismatches varied by publication and needs further investigation. Based on these data, the strength of immunosuppression may be guided by the load of D-R mismatches in the future.

Kidney stone disease (KSD) affects >10% of the global population and has a high likelihood of recurrence. Its prevalence has risen significantly in recent decades, posing a substantial economic burden. Moreover, KSD is linked to several comorbidities, amplifying its impact on general health and well-being. Environmental factors play a critical role in KSD development, acting upon an underlying genetic substratum. These genetic factors affect the regulation of stone-forming elements and natural inhibitors of crystallization within the kidney. Understanding the interplay between genetic and environmental factors is essential for improving KSD management. Tailored dietary interventions and targeted therapies can address individual risk profiles, reducing the burden of this complex disease. We believe that the common form of KSD, which is the one observed in the general population, is indeed a heterogeneous condition characterized by significant variability in the influence of environmental and genetic factors among patients as well as distinct biological pathways involved in lithogenesis for each individual. The aim of this review is to describe the relevant biology of nephrolithiasis, leveraging 'experiments of nature', specifically the known genetic associations of KSD and the resulting biological and physiological derangements. We hypothesize that the carriers, molecular pathways and physiological processes identified in this manner play a major role in the biology of lithogenesis, not only in rare genetic nephrolithiasis, but also in 'common' KSD.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic necrotizing vasculitis with significant cardiovascular involvement, primarily manifesting in granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. AAV patients face a 65% higher cardiovascular event risk, with common manifestations such as myocardial infarction, stroke and myocarditis, and less frequently, aortitis. Pathophysiology includes endothelial dysfunction, vascular inflammation, and direct inflammatory infiltration of cardiac tissue, exacerbated by traditional risk factors such as hypertension and dyslipidemia, and non-traditional factors like immunosuppressive therapies. Management emphasizes cardiovascular risk reduction through traditional methods alongside cautious use of glucocorticoids and immunosuppressants to control disease activity and minimize cardiovascular impact. Despite therapeutic advancements, long-term cardiovascular morbidity and mortality risks persist, underscoring the need for enhanced predictive tools and individualized therapeutic strategies. We aim to review current literature on the incidence, clinical manifestations and outcomes of cardiovascular involvement in AAV, with a focus on pathophysiology, risk factors, predictive models, and strategies for prevention and management.

Inhibitors of the sodium-glucose cotransporter 2 (SGLT2i) were originally developed to treat diabetes mellitus but have shown important renoprotective benefits independently from blood glucose levels. SGLT2i have thus become an important addition to the therapeutic armamentarium to treat patients with chronic kidney disease. However, specific patient populations were excluded from the pivotal trials, for instance patients with very low eGFR, patients on dialysis, kidney transplant recipients, and patients with autosomal dominant polycystic kidney disease (ADPKD), the most common genetic kidney disorder. Considering the lack of potent treatment modalities in ADPKD, the use of SGLT2i in this patient population would be of major interest. However, the combination of inconclusive results from preclinical models with the lack of clinical efficacy data and potential disease-specific safety concerns currently exclude patients with ADPKD from this promising therapeutic opportunity. This results in an urgent need for adequately powered clinical trials examining SGLT2i in ADPKD. This review summarizes the current knowledge on SGLT2i in this specific patient population and outlines running and upcoming clinical trial programs in different geographic regions aiming to make SGLT2i accessible to patients with ADPKD.

Cholinergic synapses are widespread throughout the human central nervous system. Their high density in the thalamus, neocortex, limbic system and striatum suggests that cholinergic transmission plays a vital role in memory, attention, learning and other higher cognitive functions. As a result, the brain's cholinergic system occupies a central position in research on normal cognition and age-related cognitive decline, including dementias such as Alzheimer's disease. In addition to its role in the brain, neuronal cholinergic pathways are essential for the physiological regulation of the body's organs, including the kidneys, through the parasympathetic branch of the peripheral nervous system. Chronic kidney disease (CKD) is a non-communicable disease with a global prevalence of ≈10%. Cognitive impairment is common among patients with CKD, with reported prevalence rates ranging from 30% to 60%, depending on the definitions and assessment methods used. Given the importance of the cholinergic system in cognitive processes, it may be a key area of focus for evaluating cognitive function in this population. In this current narrative review, we will first examine evidence linking the cholinergic system to cognitive functions and then we will discuss the potential implications of cholinergic function in patients with CKD.

Background and hypothesis: We assessed disease progression among patients with immunoglobulin A nephropathy (IgAN) and characterized factors associated with risk for adverse outcomes.

Methods: A retrospective longitudinal cohort (2000-2022) study of adults with biopsy-confirmed IgAN within Kaiser Permanente Southern California was performed. The outcome of interest was a composite of ≥50% estimated glomerular filtration rate (eGFR) decline, kidney failure, or mortality. Cox proportional hazards regression modeling was used to estimate hazard ratios (HR) for the eGFR decline/kidney failure with adjustment for potential confounders.

Results: Among 655 patients with primary IgAN (31% Asian/Pacific Islander, 3% Black, 40% Hispanic/Latino, 24% White), 234 (36%) reached the composite outcome of ≥50% eGFR decline (17%), kidney failure (16%), or mortality (3%). The composite outcome occurred at a rate of 79.4 events (95% confidence intervals (CI) 69.6, 90.7) per 1000 patient-years, with a median time to event of 2.7 years. Compared to urine protein creatinine ratio (UPCR) <0.5 vs 0.5-<1 g/g, 1-2, and >2 g/g, the HR (95% CI) for ≥50% eGFR decline/kidney failure were 2.4 (1.1, 5.1), 3.2 (1.5, 6.6), and 5.1 (2.5, 10.4) for baseline UPCR and 5.4 (2.3, 13.0), 14.4 (16.5, 32.2), and 41.2 (17.9, 94.5) for time-averaged UPCR. Lower baseline eGFR and diabetes were also associated with higher risk, while age ≥30 years was associated with lower risk for ≥50% eGFR decline/kidney failure. There were no clear trends differentiating risk by race/ethnicity.

Conclusion: In this large, diverse cohort, high rates of kidney outcomes occurred within a relatively short follow-up duration. Our findings suggest that IgAN carries elevated risk for kidney outcomes starting at proteinuria levels ≥0.5 g/g, in contrast to earlier perceptions that levels below 1 g/g are associated with low risk.

Secondary thrombotic microangiopathies (TMAs) represent a heterogeneous group of diseases associated with a high risk of kidney failure and death despite available therapeutic strategies. Strong evidence implicates complement activation in the pathogenesis of secondary TMA, and emerging data increasingly suggest that pharmacological blockade of the complement improves the outcomes in patients with secondary TMA. Certain forms of secondary TMA, including postpartum TMA, TMA with coexisting hypertensive emergency and de novo TMA after kidney transplantation exhibit a high prevalence of pathogenic variants in complement genes, similar to those observed in primary atypical haemolytic uraemic syndrome. These conditions should be considered as complement-mediated TMA triggered by pregnancy or transplantation or in which severe hypertension represents a symptom rather than the aetiology of TMA. Their optimal management relies on early initiation of complement inhibition. Other aetiologies of secondary TMA (i.e. autoimmune diseases, haematopoietic stem cell transplantation, drugs, infections) are typically not linked with complement gene variants and their management primarily focuses on removal of the culprit trigger or treatment of the underlying condition. While well-designed trials are still awaited, a growing body of evidence suggests that complement activation is also involved in the pathophysiology of these diseases. Complement inhibitors, which have been associated with better outcomes, should be considered in patients with severe (life- or organ-threatening TMA) or refractory secondary TMA despite adequate management of the underlying condition. This review summarizes the current understanding and future directions in the management of secondary TMA, emphasizing the potential of complement inhibition as a therapeutic strategy.

Background: High glomerular filtration rate (GFR) is generally regarded as beneficial but has been associated with cardiovascular disease (CVD) and all-cause mortality in epidemiological studies. However, these investigations may have been biased by the non-GFR determinants of estimated GFR (eGFR). We compared the risk of high baseline iohexol clearance [measured GFR (mGFR)] and eGFR based on creatinine or cystatin C in a prospective longitudinal population-based study of the Renal Iohexol Clearance Survey (RENIS) cohort.

Methods: The cohort consists of a representative sample of the general population of persons 50-64 years of age without baseline CVD, diabetes or kidney disease in the municipality of Tromsø, Norway. We investigated non-linear associations in general additive Cox regression models adjusted for CVD risk factors.

Results: During a median follow-up of 14.1 years, 232 CVD outcomes and 117 deaths occurred in a study population of 1552 persons. For all-cause mortality, no association was found for mGFR, but the previously reported association between high eGFR with creatinine (eGFRcrea) and increased risk was confirmed. For the CVD outcome, the best fitting model included interactions between mGFR or eGFR and the urine albumin:creatinine ratio (ACR). An mGFR or eGFR with cystatin C (eGFRcys) >85 ml/min/1.73 m2 was associated with an elevated hazard ratio for CVD in participants with high-normal urine ACR (>10 mg/g) only.

Conclusions: A high mGFR or eGFRcys is not associated with an increased risk of CVD or all-cause mortality in the general non-diabetic population with normal urine ACR. Previous findings of an association with high eGFRcrea were most likely caused by non-GFR confounders. In persons with high-normal ACR, high mGFR or eGFRcys is associated with an increased risk of CVD.

Clonal hematopoiesis of indeterminate potential (CHIP) is a non-malignant state characterized by hematopoietic stem cells exhibiting clonality driven by acquired mutations during aging. Using next-generation sequencing, it has been reported that the prevalence of CHIP increases exponentially with age. Thus far, epigenetic mutations including DNMT3A, TET2 and ASXL1 are the most common mutations identified in driving CHIP. CHIP is considered a pre-malignant state, however with reports of its associations with non-malignant disease states, the clinical impact of CHIP has been of great interest, in particular its effect on the renal and cardiac systems. CHIP has been associated with a higher rate of estimated glomerular filtration rate decline and increased risk of acute kidney injury. CHIP and its driver mutations have also been shown to increase cardiovascular disease and atherosclerosis through various inflammatory pathways. In this review, we discuss the pathophysiology of CHIP through aging, its impact on kidney disease and implications on cardiovascular health. We also compare CHIP to another pre-malignant clonal disorder, monoclonal gammopathy of undetermined significance (MGUS).