Nephrology Dialysis Transplantation最新文献

Background: Intradialytic hypotension (IDH) is a common complication of haemodialysis that is associated with adverse patient outcomes. We have developed a new non-invasive approach to continuously estimate systolic blood pressure (SBP) in real time during haemodialysis using pressure wave sensors in the extracorporeal circuit. We sought to compare the performance of our continuous real-time SBP estimator against brachial cuff SBP measurements.

Methods: Single-centre, observational study conducted in 21 participants receiving haemodialysis with a functioning arteriovenous fistula, studied throughout two 4-h haemodialysis sessions. Time-averaged real-time SBP estimator values from the 5-s period immediately prior to each cuff measurement were compared with matched brachial cuff SBP values.

Results: Mean age was 71 ± 11 years and median dialysis vintage was 20.0 months (interquartile range 12.5-63.5). Across 522 SBP comparison data points, mean brachial cuff SBP and real-time SBP estimate were 121.8 ± 27.1 mmHg and 123.7 ± 27.9 mmHg, respectively. Brachial cuff SBP and real-time SBP estimate were significantly associated (r = 0.825; P < .001). There was a low absolute mean difference between the brachial cuff SBP and the real-time SBP estimate of -1.9 ± 16 mmHg, and no evidence of systematic bias between measurements. Across all comparison points, 95% of estimator values were within 30% of the matched brachial cuff value, and 66% within 10% of the cuff value.

Conclusions: A blood pressure estimator that runs in real time during haemodialysis using pressure wave sensors in the extracorporeal circuit and avoiding additional sensor-burden on patients has good performance in tracking intradialytic SBP when compared against brachial cuff measurements, supporting its further development and larger scale testing.

Clustering of traditional and kidney-specific risk factors leads to elevated cardiovascular disease (CVD) risk across the trajectory of chronic kidney disease (CKD) and transplantation. As kidney function declines, the prevalence of CVD, cardiovascular events, and mortality increases. This review considers recent evidence for the association between physical activity (PA) and exercise and cardiorenal health, and the effectiveness of interventions for the prevention and management of cardiorenal decline across the CKD spectrum. Evidence supports a beneficial dose-response effect of PA in the prevention of incident CKD, and growing evidence in prevalent CKD patients for the attenuation of kidney function decline, and a reduction in CVD risk, morbidity, and mortality. Broadly speaking, across the trajectory of CKD, the literature supports the efficacy of exercise interventions for improving cardiorespiratory fitness and aspects of cardiorenal health. The mechanisms underlying improvements indicate differential effects on traditional and non-traditional risk factors for CKD progression and CVD. To date, there is limited transfer of these findings into clinical care, although the evaluation of available evidence has led to the development of the first detailed clinical practice guideline for exercise and lifestyle in CKD. There is a lack of large-scale multicentre randomized controlled trials, and trials exploring hard clinical outcomes and long-term effects of exercise on cardiorenal outcomes. However, research should also address the challenges of implementing programmes of exercise and PA as part of routine care in combination with addressing the shortfall in literature to improve cardiorenal outcomes in all patients with CKD.

Background and hypothesis: Recent advances in membranous nephropathy treatment have focused on B cell depletion, which is incompletely effective, potentially due to persistent autoantibody-producing plasma cells or alternative pathways of injury. T cell costimulatory blockade [cytotoxic-T-lymphocyte-associated antigen 4 (CTLA4)-Ig] to prevent T cell-dependent B cell activation and short-course proteasome inhibition (bortezomib) to deplete plasma cells may represent a complementary form of treatment.

Methods: Lewis rats were immunized with Fx1A and complete Freund's adjuvant to induce experimental membranous nephropathy (Heymann nephritis or HN) and treated with CTLA4-Ig alone or CTLA4-Ig plus a short-course of bortezomib. Serum creatinine, proteinuria, kidney histology, serum anti-Fx1A levels, kidney and spleen messenger RNA expression, and flow cytometry on splenocytes were evaluated at 12 weeks.

Results: CTLA4-Ig-treated and CTLA4-Ig plus bortezomib-treated rats had significant and similar reductions in serum creatinine and proteinuria, with less histological kidney injury compared with untreated HN rats. Glomerular IgG deposition was reduced in CTLA4-Ig-treated and CTLA4-Ig plus bortezomib-treated rats compared with untreated HN rats but there were no significant differences in serum anti-Fx1A levels. CTLA4-Ig-treated and CTLA4-Ig plus bortezomib-treated rats exhibited significantly reduced T helper (Th)-17 cell cytokines (interleukin-6, -17, -21) and regulatory T cell (Foxp3, TGF-β) expression in the kidney but not the spleen. Immunohistochemical staining of CD4+ and intracellular STAT3+ cells was reduced in CTLA4-Ig plus bortezomib-treated and CTLA4-Ig-treated compared with untreated HN rats. On flow cytometry, CTLA4-Ig reduced B cells and plasma cells but not T cell subsets.

Conclusions: CTLA4-Ig ameliorated induction of experimental membranous nephropathy, potentially through suppression of Th17 cells in the kidney, and may represent an effective adjunct treatment in membranous nephropathy.

Background: After kidney transplantation adherence to immunosuppressive medication is crucial for graft survival and its assessment requires valid measurements. The Basel Assessment of Adherence-to Immunosuppressive Medications Scale (BAASIS) is a validated self-report tool to detect non-adherence, however, its ability to predict clinically relevant outcomes remains to be established.

Methods: In this prospective cohort study including 226 consecutive kidney graft recipients transplanted at the Medical University of Vienna between 2018 and 2019 the adherence toward immunosuppressive medication was monitored for 2 years after transplantation. The BAASIS was applied at the first outpatient visit and at months 3, 6, 9, 12, and 24 post-transplant to assess the implementation and persistence phase of adherence. Non-adherence was defined by any positive response to one of the BAASIS-items. The primary endpoint was biopsy-proven allograft rejection defined by the Banff meeting report during a maximum follow-up of 4 years.

Results: Of the total study cohort [median age 56 years (IQR 46-63), 75 (33%) female], 125 recipients (55%) reported non-adherence at least once. Self-reported non-adherence increased within the first 3 months from 11% to 31% and remained between 27% and 32% at months 6 to 24 post-transplant. Non-adherent recipients experienced more allograft rejections than adherent patients (24%, n = 30 vs. 7%, n = 7; P < .001) during a median follow-up of 3.7 years (IQR 1.0-4.0). Using a time-dependent Cox regression model, the adjusted hazard ratio for allograft rejection associated with previously reported non-adherence was 2.90 (95% confidence interval (CI) 1.51-5.58; P = .001) accounting for recipient sex, age at transplantation, and history of previous transplantation.

Conclusion: Our findings support the clinical value of the BAASIS. Its implementation into routine post-transplant care may facilitate the identification of clinically relevant medication non-adherence, enabling timely interventions.

Background: Previous evidence showed that while first-time kidney transplants (KT) typically yield better outcomes, repeat and subsequent transplants were associated with increased risks of graft failure and adverse patient outcomes, yet conflicting findings exist. The aim of this meta-analysis is to compare graft survival and delayed graft function (DGF) outcomes in first-time KT, repeat KT (regrafts) and subsequent KT.

Methods: Relevant studies were identified through comprehensive searches in PubMed, Web of Science, Cochrane Library, MEDLINE (Ovid) and Scopus until 8 October 2024. Primary outcomes include graft survival and DGF, compared with repeat and subsequent KT.

Results: The meta-analysis included a total of 16 studies. Analysis on long-term graft survival revealed that patients who underwent a first KT had significantly better graft survival compared with those who received a second transplant [86.7% versus 77.6%; odds ratio (OR) 1.40, 95% confidence interval (CI) 1.14-1.71, P = .001]. At 5 years post-transplant, first KT recipients continued to demonstrate superior graft survival (OR 1.41, 95% CI 1.13-1.77, P = .003), although this difference diminished by 10 years, with no significant disparity observed (OR 1.26, 95% CI 0.88-1.81, P = .20). Graft survival at 5 years was also significantly higher in second KT recipients compared with those undergoing a third transplant (OR 2.66, 95% CI 1.86-3.80, P < .00001). Patient survival outcomes were largely comparable between first and second KT groups, with no statistically significant differences in overall survival (OR 1.25, 95% CI 0.87-1.81, P = .23). At specific time points, the 5-year survival rate showed a borderline non-significant trend favoring first KT recipients (OR 1.63, 95% CI 0.97-2.73, P = .06), while the 10-year survival rate showed no difference (OR 0.94, 95% CI 0.67-1.32, P = .71). Survival rates between second and subsequent retransplants (e.g. third or fourth KT) showed no significant variation, including at 5 years (P = .37 and P = .90, respectively). DGF rates did not differ significantly between first and second KT recipients (P = .11).

Conclusion: These findings underscore the superior graft survival associated with first and second KT compared with subsequent retransplants, particularly in the early post-transplant period, while highlighting the lack of significant differences in overall patient survival across groups; however, variability in outcomes due to study heterogeneity and patient-specific factors warrants cautious interpretation and tailored clinical approaches.

Kidney amyloidosis encompasses a spectrum of heterogeneous conditions in which damage is caused by the deposition of various misfolded proteins that aggregate into fibrils. The main form of renal amyloidosis in Western countries is immunoglobulin light chain (AL) amyloidosis, which is usually secondary to a plasma cell clone or less frequently a B-cell clone, while rarer causes include AA amyloidosis, ALECT2 and hereditary amyloidoses. The main renal manifestations include nephrotic syndrome and kidney dysfunction with modest or absent proteinuria. The course is progressive and renal and overall survival is reduced in many patients. While biopsies are usually positive by Congo Red staining in all types of amyloidosis, precise identification of the amyloid fibril protein is essential and is best achieved with immunohistochemistry or proteomic studies, such as mass spectrometry. This method also allows the discovery of novel amyloidogenic proteins and has contributed to expand the list of amyloid types. The current treatment strategy is based on suppressing new amyloid fibril production through chemotherapy in AL amyloidosis, control of inflammation in AA amyloidosis and 'gene silencing' therapies in hereditary forms, such as the one linked with transthyretin. Novel approaches aim at enhancing natural amyloid clearance in order to reduce the rate of organ failure. Kidney transplantation in patients who achieved response has shown outcomes comparable to the general transplant population. In this review, we present the key aspects of renal amyloidosis and discuss novel concepts in this evolving field.

Background: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)ASR-NB2009 estimated glomerular filtration rate (eGFR) equation has shown substantial overestimation of GFR in Europeans, hence new equations have been developed. We examined the effect of introducing the European Kidney Function Consortium (EKFC) or Lund-Malmö revised (LMR) eGFR equations on KDIGO eGFR category classification in a large cohort. We compared the EKFC and LMR equations with the CKD-EPIASR-NB2009 formula in view of discriminative ability of all-cause mortality, kidney failure with replacement therapy (KFRT) and acute kidney injury (AKI) risks across eGFR categories.

Methods: Individuals aged ≥18 years with a serum creatinine measurement (December 2006-July 2024) at University Medical Center Utrecht, were included. Hazard ratios (HRs) were analysed for all outcomes per eGFR category, per equation. Harrell's Concordance index (C-index) was used to assess the ability of risk discrimination across eGFR categories. Whether reclassification between eGFR categories was justified by the occurrence of events, was assessed with net reclassification improvement analysis.

Results: In total, 285 686 individuals were included. Compared with the CKD-EPIASR-NB2009 equation, the EKFC and LMR estimated GFR lower [mean -6.3 (standard deviation, SD 5.3) and -10.7 (SD 6.5) mL/min/1.732, respectively]. The number of individuals with eGFR <60 mL/min/1.73 m2 increased 29.0% (EKFC) and 36.4% (LMR). The EKFC predominantly reclassified older individuals, and the LMR older men, to worse eGFR categories. HRs of reclassified individuals to worse eGFR categories were mainly higher compared with the non-reclassified. The EKFC and LMR equations showed equal/improved C-index for mortality (EKFC 0.584/LMR 0.588/CKD-EPIASR-NB2009 0.570), KFRT (0.895/0.900/0.897) and AKI (0.606/0.609/0.599). The LMR equation reclassified more individuals without an event to worse eGFR categories.

Conclusion: eGFR category classification was substantially different when using the EKFC or LMR equation compared with the CKD-EPIASR-NB2009 formula. Both equations showed equal to improved ability of risk stratification across eGFR categories. Shifts in eGFR category classification might significantly impact clinical decisions. Given that we have identified variation between equations, a careful consideration of the advantages and disadvantages of different eGFR equations is essential.

Background and hypothesis: While the primary treatment for minimal change disease (MCD) is prednisolone, the immunosuppressive treatment at relapse is less well defined. More treatment options for MCD have become available and concerns about the adverse effects of prednisolone have been raised. It is unclear to what extent this has influenced the treatment of relapsing disease. Thus, the objective of this study is to characterize the changes in the immunosuppressive treatment of relapse in MCD over the past 35 years.

Methods: A multicentre, retrospective cohort including adult patients with biopsy-proven MCD from 13 hospitals in Denmark and the Netherlands between 1985 and 2022. Patients were identified from pathology registers. Information on treatment and clinical outcomes was retrieved from health records. Treatment before and after 2010 was compared.

Results: The study included 239 patients with a median age of 46 years, 55% female and 64% being diagnosed before 2010. A first relapse was identified in 50% and a second relapse in 28%. The most frequently prescribed treatment at first relapse was prednisolone monotherapy before and after 2010 (67% and 44% of patients, respectively), while the use of calcineurin inhibitors (CNI) increased 3-fold after 2010 compared with before 2010. At second relapse CNI was the most frequently prescribed treatment after 2010, while the use of both cyclophosphamide and prednisolone decreased when compared with before 2010. A similar trend was observed at the 3rd to 14th relapse with CNI (44% of patients) and rituximab (35% of patients) being the most frequently prescribed treatments after 2010 while the use of cyclophosphamide and prednisolone decreased (0% and 21% of patients, respectively). Regardless of treatment, remission rates remained high.

Conclusion: The treatment of relapses in MCD has changed since 2010 with reduced use of prednisolone monotherapy and cyclophosphamide, and increased use of CNI and rituximab.