Nephrology Dialysis Transplantation最新文献

Background and hypothesis: Organ transplantation reverses cognitive impairment in chronic kidney disease (CKD), indicating that cognitive impairment driven by CKD is therapeutically amendable. We recently demonstrated that impaired cognition in CKD is linked to IL-1β-release from microglia and IL-1R1-signaling in neuronal cells, thereby identifying a signaling pathway that can be exploited therapeutically. However, the mechanism of IL-1β-maturation in microglia in CKD remains unknown. We hypothesized that microglia cells require caspase-1 for CKD-driven cognitive impairment.

Methods: We used a combination of single cell analyses, in situ analyses, genetically modified mouse models (including newly generated Cre-LoxP mouse models) and in vitro models. The current study builds on a recently identified intercellular crosstalk between microglia and neurons that impairs cognition in chronic kidney disease (CKD).

Results: Here, we show that despite NLRP3 inflammasome activation in the brain and protection of mice with constitutive NLRP3 deficiency from CKD-induced cognitive impairment, (i) caspase-1 is not required for IL-1β maturation in microglia and (ii) targeted caspase-1 deficiency in microglia does not improve cognition in CKD mice. These data indicate that IL-1β maturation in microglia is independent of the NLRP3-caspase-1 interaction in CKD. Indeed, microglia activation in CKD induces noncanonical, cathepsin C-caspase-8 mediated IL-1β maturation. Depletion of cathepsin C or caspase-8 blocks IL-1β maturation in microglia. Preliminary analyses suggest that noncanonical microglia IL-1β maturation occurs also in diabetes mellitus.

Conclusion: These results identify a noncanonical IL-1β-maturation pathway as a potential therapeutic target to combat microglia-induced neuronal dysfunction in CKD and possible other peripheral diseases.

The kidneys fulfil several essential homeostatic functions for the body. One of them is the maintenance of sufficient oxygen supply to the organs. For this purpose, the kidneys control the formation of red blood cells by the production of the hormone erythropoietin. This control of red cell formation is not only relevant to prevent states of oxygen deficiency but also to prevent an unwanted increase of red cell numbers causing thromboembolic risks. The adequate production of erythropoietin requires a sensing of the arterial oxygen content and transduction to hormone production. This oxygen sensing is a two-step process which includes a translation of the arterial oxygen content to respective oxygen tension in the tubulointerstitium and a perception of the resulting local interstitial oxygen tension to translate them into specific cellular responses such as the production of erythropoietin. This contribution will describe these steps of oxygen sensing for the healthy kidney and for the changes occurring during states of chronic renal disease, which are commonly associated with anemia. In this context a special focus will also be set on intrarenal hypoxia and oxygen sensing in the diabetic kidney including the treatment with tubular glucose transport (SGLT-2) inhibitors which might influence the oxygen sensing in the kidney. Finally, we will consider the effects of prolylhydroxylase inhibitors (PHD-I), which fundamentally interfere with the cellular oxygen sensing and which are meanwhile treatment options in renal anemia.

Background: Accurate estimation of glomerular filtration rate (GFR) is crucial in living kidney donation. While most estimated GFR (eGFR) equations are based on plasma creatinine, its levels are strongly influenced by muscle mass. Application of cystatin C (cysC)-based estimates before donation may improve both estimation of current GFR and prediction of post-donation GFR.

Methods: We assessed the performance of Chronic Kidney Disease Epidemiology Collaboration equations based on creatinine (eGFRcreat-2009, eGFRcreat-2021), cysC (eGFRCysC-2012) or both (eGFRcombined-2012, eGFRcombined-2021) for estimating pre- and post-donation (mGFR) GFR in 486 living kidney donors. We subsequently focused on a subgroup of individuals with high/low muscle mass (25% highest/lowest 24-hour urinary creatinine excretion, sex stratified and height indexed).

Results: Pre-donation eGFRcombined-2012 and eGFRcombined-2021 showed the strongest associations with pre- and post-donation mGFR. Pre-donation eGFRcombined-2021 was most accurate for estimating both pre-donation (bias 0.01 ± 11.9 ml/min/1.73 m2) and post-donation mGFR (bias 1.3 ± 8.5 ml/min/1.73 m2). In donors with high/low muscle mass, cysC-based equations (with or without creatinine) performed better compared with equations based on only creatinine.

Conclusions: Combined eGFR equations yielded a better estimate of pre- and post-donation mGFR compared with estimates based on creatinine or cysC only. The added value of cysC seems particularly pronounced in donors with high or low muscle mass.

Kidney diseases have become a global epidemic with significant public health impact. Chronic kidney disease (CKD) is set to become the fifth largest cause of death by 2040, with major impacts on low-resource countries. This review is based on a recent report of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) which uncovered gaps in key vehicles of kidney care delivery assessed using World Health Organization building blocks for health systems (financing, services delivery, workforce, access to essential medicines, health information systems and leadership/governance). High-income countries had more centres for kidney replacement therapies (KRT), higher KRT access, higher allocation of public funds to KRT, larger workforces, more health information systems, and higher government recognition of CKD and KRT as health priorities than low-income nations. Evidence identified from the current ISN-GKHA initiative should serve as template for generating and advancing policies and partnerships to address the global burden of kidney disease. The results provide opportunities for kidney health policymakers, nephrology leaders and organizations to initiate consultations to identify strategies for improving care delivery and access in equitable, resource-sensitive manners. Policies to increase use of public funding for kidney care, lower the cost of KRT and increase workforces should be a high priority in low-resource nations, while strategies that expand access to kidney care and maintain current status of care should be prioritized in high-income countries. In all countries, the perspectives of people with CKD should be exhaustively explored to identify core kidney care priorities.

Background: The aim of this study was to quantify hypertension control and evaluate concordance between all commonly available blood pressure (BP) modalities in kidney transplant recipients (KTRs).

Methods: For this prospective cross-sectional study, 89 stable KTRs were recruited at the Charité Transplant Outpatient Clinic. For each study participant office [manual office BP (MOBP) and automated office BP (AOBP)], 7-day home (HBPM) and 24-hour ambulatory BP (24h-ABPM) measurements were performed.

Results: 80 of the 89 patients recruited had sufficient BP recordings. The mean BP for MOBP, AOBP, HBPM and 24h-ABPM was 129/73, 126/71, 131/85 and 130/81 mmHg, respectively. Uncontrolled hypertension, as defined by 24h-ABPM (mean ≥130/80 mmHg), was present in 53 (66%) patients. MOBP, AOBP and HBPM classified 19 (24%), 22 (28%) and 41 (51%) patients, respectively, as 'uncontrolled hypertensive'. The Bland-Altman plot showed good agreement between systolic MOBP, AOBP, HBPM and daytime-ABPM (mean bias: -1 ± 13 mmHg, -4 ± 13 mmHg, 1 ± 10 mmHg, respectively). Uncontrolled night-time hypertension was present in 74 (93%) KTRs, with 71 (89%) patients showing a non-physiological dipping pattern. Moderate positive correlation between daytime-ABPM/HBPM and night-time-ABPM (Pearson correlation coefficients: 0.62-0.73), followed by MOBP/AOBP (Pearson correlation coefficients: 0.49-0.59) was noted. Estimated eGFR and proteinuria displayed weak correlation with 24h-, daytime- and night-time-ABPM (absolute values of Pearson correlation coefficients: 0.04-0.41). No robust association with either 24h-, daytime- or night-time-ABPM was observed for volume status exams.

Conclusions: Masked hypertension is highly prevalent in KTRs, especially due to high rates of uncontrolled night-time hypertension. HBPM shows the narrowest limits of agreement with daytime-ABPM. Daytime-ABPM and HBPM show the highest, albeit clinically insufficient, correlation with night-time-ABPM. Systematic integration of 24h-ABPM into clinical practice, as proposed by the 2023 ESH guidelines for the management of arterial hypertension, should not be withheld for the KTR population. Clinical trials evaluating the treatment of hypertension in KTRs are urgently needed.

Background: A low-protein diet (LPD) is recommended to patients with advanced chronic kidney disease (CKD), whereas geriatric guidelines recommend a higher amount of protein. The aim of this study was to evaluate the safety of LPD treatment in older adults with advanced CKD.

Methods: The EQUAL study is a prospective, observational study including patients ≥65 years of age with an incident estimated glomerular filtration rate <20 ml/min/1.73 m2 in six European countries with follow-up through 6 years. Nutritional status was assessed by a 7-point subjective global assessment (SGA) every 3-6 months. Prescribed diet (g protein/kg of bodyweight) was recorded on every study visit; measured protein intake was available in three countries. Time to death and decline in nutritional status (SGA decrease of ≥2 points) were analysed using marginal structural models with dynamic inverse probability of treatment and censoring weights.

Results: Of 1738 adults (631 prescribed LPD at any point during follow-up), there were 1319 with repeated SGA measurements, of which 267 (20%) decreased in SGA ≥2 points and 565 (32.5%) who died. There was no difference in survival or decrease in nutritional status for patients prescribed a LPD ≤0.8 g/kg ideal bodyweight {odds ratio [OR] for mortality 1.15 [95% confidence interval (CI) 0.86-1.55)] and OR for decrease in SGA 1.11 [95% CI 0.74-1.66]} in the adjusted models. In patients prescribed a LPD <0.6 g/kg ideal bodyweight, the results were similar. There was a significant interaction with LPD and older age >75 years, lower SGA and higher comorbidity burden for both mortality and nutritional status decline.

Conclusions: In older adults with CKD approaching end-stage kidney disease, a traditional LPD prescribed and monitored according to routine clinical practice in Europe appears to be safe.

Background: In 2020, the coronavirus disease 2019 (COVID-19) pandemic caused disruptions in kidney replacement therapy (KRT) services worldwide. The aim of this study was to assess the effect of the COVID-19 pandemic in 2020 on the incidence of KRT, kidney transplantation activity, mortality and prevalence of KRT across Europe.

Methods: Patients receiving KRT were included from 17 countries providing data to the European Renal Association Registry. The epidemiology of KRT in 2020 was compared with average data from the period 2017-2019. Changes occurring during the first and second waves of the pandemic were also explored.

Results: The incidence of KRT was 6.2% lower in 2020 compared with 2017-2019, with the lowest point (-22.7%) during the first wave in April. The decrease varied across countries, was smaller in males (-5.2%) than in females (-8.2%) and was moderate for peritoneal dialysis (-3.7%) and haemodialysis (-5.4%) but substantial for pre-emptive kidney transplantation (-23.6%). The kidney transplantation rate decreased by 22.5%, reaching a nadir of -80.1% during the first wave, and was greatest for living donor kidney transplants (-30.5%). While in most countries the kidney transplantation rate decreased, in the Nordic/Baltic countries and Greece there was no clear decrease. In dialysis patients, mortality increased by 11.4% and was highest in those 65-74 years of age (16.1%), in those with diabetes as the primary renal disease (15.1%) and in those on haemodialysis (12.4%). In transplant recipients, the mortality was 25.8% higher, but there were no subgroups that stood out. In contrast to the rising prevalence of KRT observed over the past decades across Europe, the prevalence at the end of 2020 (N = 317 787) resembled that of 2019 (N = 317 077).

Conclusion: The COVID-19 pandemic has had a substantial impact on the incidence of KRT, kidney transplant activity, mortality of KRT and prevalence of KRT in Europe with variations across countries.