The latest medical research on Transplant Nephrology
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about transplant nephrology gathered by our medical AI research bot.
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Protective effect of sacubitril/valsartan (Entresto®) on kidney function and filtration barrier injury in a porcine model of partial nephrectomy.Nephrol Dial Transplant
Kidney surgery often includes organ ischemia with risk of acute kidney injury. The present study tested if treatment with combined angiotensin II-A...
Design of the COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using an UACR Endpoint study (CONFIDENCE).Nephrol Dial Transplant
Despite available interventions, people with type 2 diabetes (T2D) remain at risk of chronic kidney disease (CKD). Finerenone, a potent and selective nonsteroidal mineralocorticoid receptor antagonist, and sodium-glucose co-transporter 2 inhibitors (SGLT2is) can reduce both kidney and cardiovascular risks in people with CKD and T2D. Here we outline the design of a study to investigate whether dual therapy with finerenone and a SGLT2i is superior to either agent alone.
CONFIDENCE (NCT05254002) is a randomized, controlled, double-blind, double-dummy, international, multicentre, three-armed, parallel-group, 7.5-8.5-month, Phase 2 study in approximately 807 adults with T2D, stage 2-3 CKD and a urine albumin-to-creatinine ratio (UACR) from ≥ 300-<5000 mg/g. The primary objective is to demonstrate that 6 months' dual therapy comprising finerenone and the SGLT2i empagliflozin is superior for reducing albuminuria versus either agent alone. Interventions will be once-daily finerenone 10 mg or 20 mg (target dose) plus empagliflozin 10 mg, or empagliflozin 10 mg alone, or finerenone 10 mg or 20 mg (target dose) alone.
The primary outcome is relative change from baseline in UACR among the three groups. Secondary outcomes will further characterize efficacy and safety, including change in eGFR and incident hyperkalaemia.
CONFIDENCE is evaluating the safety, tolerability and efficacy of dual use of finerenone and a SGLT2i in adults with CKD and T2D. Should an additive effect be shown, early and efficient intervention with dual finerenone and SGLT2i therapy could slow disease progression and provide long-term benefits for people with CKD and T2D.
Salivary potassium measured by genetically encoded potassium ion indicators as a surrogate for plasma potassium levels in hemodialysis patients - a proof-of-concept study.Nephrol Dial Transplant
Hyperkalemia is a common complication in cardiorenal patients treated with agents interfering with renal potassium (K+) excretion. It frequently leads to discontinuation of potentially life-saving medication, which has increased the importance of K+-monitoring. Non-invasive means to detect hyperkalemia are currently unavailable, but would be of potential use for therapy guidance. The aim of the present study was to assess the analytical performance of genetically-encoded potassium-ion indicators (GEPIIs) in measuring salivary K+ ([K+]Saliva) and to determine whether changes of [K+]Saliva depict those of [K+]Plasma.
We conducted this proof-of-concept study: saliva samples from 20 healthy volunteers as well as plasma and saliva from 29 patients on hemodialysis (HD) before and after three consecutive HD treatments were collected. We compared [K+]Saliva as assessed by the gold standard ion-selective electrode (ISE) with GEPII measurements.
The Bland-Altmann analysis showed a strong agreement (Bias 0.71; 95% limits of agreement from -2.79 to 4.40) between GEPII and ISE. Before treatment, patients on HD showed significantly higher [K+]Saliva compared to healthy controls (median 37.7 [30.85; 48.46] vs. 23.8 [21.63; 25.23] mmol/L; p < 0.05). [K+]Plasma in HD patients decreased significantly after dialysis. This was paralleled by a significant decrease in [K+]Saliva, and both parameters increased until the subsequent HD session. Despite similar kinetics, we found weak or no correlation between [K+]Plasma and [K+]Saliva.
GEPIIs have shown an excellent performance in determining [K+]Saliva. [K+]Plasma and [K+]Saliva exhibited similar kinetics. To determine whether saliva could be a suitable sample type to monitor [K+]Plasma, further testing in future studies are required.
Removing race from the CKD-EPI equation and its impact on prognosis in a predominantly White European population.Nephrol Dial Transplant
While American nephrology societies recommend using the 2021 CKD-EPI eGFR equation without a Black race coefficient, it is unknown how this would impact disease distribution, prognosis and kidney failure risk prediction in predominantly White non-US populations.
We studied 1.6 million Stockholm adults with serum/plasma creatinine measurements between 2007-2019. We calculated changes in eGFR and reclassification across KDIGO GFR categories when changing from the 2009 to 2021 CKD-EPI equation; estimated associations between eGFR and the clinical outcomes kidney failure with replacement therapy (KFRT), (cardiovascular) mortality and major adverse cardiovascular events using Cox regression; and investigated prognostic accuracy (discrimination and calibration) of both equations within the Kidney Failure Risk Equation.
Compared with the 2009 equation, the 2021 equation yielded a higher eGFR by a median (IQR) of 3.9 (2.9-4.8) ml/min/1.73m2, which was larger at older age and for men. Consequently, 9.9% of the total population and 36.2% of the population with CKD G3a-G5 was reclassified to a higher eGFR category. Reclassified individuals exhibited a lower risk of KFRT, but higher risks of all-cause/cardiovascular death and major adverse cardiovascular events, compared with non-reclassified participants of similar eGFR. eGFR by both equations strongly predicted study outcomes, with equal discrimination and calibration for the Kidney Failure Risk Equation.
Implementing the 2021 CKD-EPI equation in predominantly White European populations would raise eGFR by a modest amount (larger at older age and men) and shift a major proportion of CKD patients to a higher eGFR category. eGFR by both equations strongly predicted outcomes.
Association of coronary artery calcium with adverse cardiovascular outcomes and death in patients with chronic kidney disease: results from the KNOW-CKD.Nephrol Dial Transplant
In East Asian countries, patients with chronic kidney disease (CKD) have lower cardiovascular risk profiles and experience fewer cardiovascular events (CVEs) than those in Western countries. Thus, the clinical predictive performance of well-known risk factors warrants further testing in this population.
The KoreaN cohort study for Outcome in patients with CKD (KNOW-CKD) is a multicenter, prospective observational study. We included 1579 participants with CKD G1-G5 without kidney replacement therapy between 2011 and 2016. The main predictor was coronary artery calcium score (CACS). The primary outcome was a composite of non-fatal CVEs or all-cause mortality. Secondary outcomes included 3-point major adverse cardiovascular events (MACE; the composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke), all CVEs, and all-cause mortality.
During a median follow-up of 5.1 years, a total of 123 primary outcome events occurred (incidence rate, 1.6/100 person-years). In the multivariable Cox model, a 1-SD log increase in CACS was associated with a 1.67-fold (95% confidence interval [CI]; 1.37-2.04) higher risk of the primary outcome. Compared to CACS of 0, the hazard ratio associated with CACS > 400 was 4.89 (95% CI, 2.68-8.93) for the primary outcome. This association was consistent for secondary outcomes. Moreover, the inclusion of CACS led to modest improvements in prediction indices of the primary outcome compared to well-known conventional risk factors.
In Korean patients with CKD, CACS was independently associated with adverse cardiovascular outcomes and all-cause death. CACS also showed modest improvements in prediction performance over conventional cardiovascular risk factors.
Measuring Quality of Life in Trials Including Patients on Hemodialysis: Methodological Issues Surrounding use of the Kidney Disease Quality of Life Questionnaire. A Systematic Review.Nephrol Dial Transplant
Hemodialysis treatment causes significant reductions in quality of life (QoL). When enrolled in a clinical trial, some patients are lost prior to follow-up either because they die or receive a kidney transplant. It is unclear how these patients are dealt with in the analysis of QoL data. There are questions surrounding the consistency of how QoL measures are used, reported and analysed.
A systematic search of electronic databases for trials measuring QoL in hemodialysis patients using any variation of the Kidney Disease Quality of Life (KDQoL) Questionnaire. The review was conducted in Covidence version2. Quantitative analysis was conducted in STATA version16.
We included 61 trials in the review, of which 82% reported dropouts. The methods to account for missing data due to dropouts include imputation (7%) and complete case analysis (72%). Few trials (7%) conducted sensitivity analysis to assess the impact of missing data on the study results. Single imputation techniques were used which are only valid under strong assumptions regarding the type and pattern of missingness. There was inconsistency in the reporting of the KDQoL, with many papers (54%) amending the validated questionnaires or reporting only statistically significant results.
Missing data are not dealt with according to the missing data mechanism, which may lead to biased results. Inconsistency in the use of patient reported outcome measures raises questions about the validity of these trials. Methodological issues in nephrology trials could be a contributing factor to why there are limited effective interventions to improve QoL in this patient group.
Outcomes of kidney transplantation in patients with myeloma and amyloidosis in the US.Nephrol Dial Transplant
Recent improvement in treatment and patient survival has opened the eligibility of kidney transplantation for patients who developed end-stage kidney disease (ESKD) from plasma cell dyscrasias (PCD). Data on clinical outcomes in this population is lacking.
We conducted a retrospective study of UNOS/OPTN dataset (2006-2018) to compare patient and graft outcomes of kidney transplant recipients with ESKD due to PCD vs other causes.
Among 168 369 first kidney transplant adult recipients, 0.22-0.43% per year had PCD as the cause of ESKD. The PCD group had worse survival than the non-PCD group for both living and deceased donor types, (adjusted hazard ratio [aHR]: 2.24 [95% CI: 1.67, 2.99]) and (aHR: 1.40 [1.08, 1.83), respectively. The PCD group had worse survival than the diabetes group, but only among living donor type (aHR: 1.87 [1.37, 2.53]) vs (aHR: 1.16, [0.89, 1.2]). Graft survival in patients with PCD were worse than non-PCD in both living and deceased donor type (aHR 1.72 [1.91, 2.56], aHR 1.30 [1.03, 1.66]). Patient and graft survival were worse in amyloidosis but not statistically different in multiple myeloma, compared to non-PCD group.
The study data is crucial when determining kidney transplant eligibility and when discussing transplant risk in patients with PCD.
Machine Learning-Derived Integer-Based Score and Prediction of Tertiary Hyperparathyroidism among Kidney Transplant Recipients: An Integer-Based Score to Predict Tertiary Hyperparathyroidism.Clinical Journal of the American
Tertiary hyperparathyroidism in kidney allograft recipients is associated with bone loss, allograft dysfunction, and cardiovascular mortality. Accurate pretransplant risk prediction of tertiary hyperparathyroidism may support individualized treatment decisions. We aimed to develop an integer score system that predicts the risk of tertiary hyperparathyroidism using machine learning algorithms.
We used two separate cohorts: a derivation cohort with the data of kidney allograft recipients (n=669) who underwent kidney transplantation at Severance Hospital, Seoul, Korea between January 2009 and December 2015 and a multicenter registry dataset (the Korean Cohort Study for Outcome in Patients with Kidney Transplantation) as an external validation cohort (n=542). Tertiary hyperparathyroidism was defined as post-transplant parathyroidectomy. The derivation cohort was split into 75% training set (n=501) and 25% holdout test set (n=168) to develop prediction models and integer-based score.
Tertiary hyperparathyroidism requiring parathyroidectomy occurred in 5% and 2% of the derivation and validation cohorts, respectively. Three top predictors (dialysis duration, pretransplant intact parathyroid hormone, and serum calcium level measured at the time of admission for kidney transplantation) were identified to create an integer score system (dialysis duration, pretransplant serum parathyroid hormone level, and pretransplant calcium level score [DPC]; 0-15 points) to predict tertiary hyperparathyroidism. The median DPC score was higher in participants with post-transplant parathyroidectomy than in those without (13 versus three in derivation; 13 versus four in external validation; P<0.001 for all). Pretransplant dialysis duration, pretransplant serum parathyroid hormone level, and pretransplant calcium level score predicted post-transplant parathyroidectomy with comparable performance with the best-performing machine learning model in the test set (area under the receiver operating characteristic curve: 0.94 versus 0.92; area under the precision-recall curve: 0.52 versus 0.47). Serial measurement of DPC scores (≥13 at least two or more times, 3-month interval) during 12 months prior to kidney transplantation improved risk classification for post-transplant parathyroidectomy compared with single-time measurement (net reclassification improvement, 0.28; 95% confidence interval, 0.02 to 0.54; P=0.03).
A simple integer-based score predicted the risk of tertiary hyperparathyroidism in kidney allograft recipients, with improved classification by serial measurement compared with single-time measurement.
Korean Cohort Study for Outcome in Patients with Kidney Transplantation (KNOW-KT), NCT02042963 PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_06_10_CJN15921221.mp3.
Evolution of humoral lesions on follow-up biopsy stratifies the risk for renal graft loss after antibody-mediated rejection treatment.Nephrol Dial Transplant
Standard-of-care protocol, based on plasma exchanges, high dose IVIg, and optimization of maintenance immunosuppression can slow down the evolution...
Availability of assisted peritoneal dialysis in Europe: call for increased and equal access.Nephrol Dial Transplant
Availability of assisted PD (asPD) increases access to dialysis at home, particularly for the increasing numbers of older and frail people with advanced kidney disease. Although asPD has been widely used in some European countries for many years, it remains unavailable or poorly utilised in others. A group of leading European nephrologists have therefore formed a group to drive increased availability of asPD in Europe and in their own countries.
Members of the group filled in a proforma with the following headings: personal experience, country experience, who are the assistants, funding of asPD, barriers to growth, what is needed to grow, and their top 3 priorities.
Only 5 of the 13 countries surveyed provided publicly funded reimbursement for asPD. The use of asPD depends on overall attitudes to PD with all respondents mentioning need for nephrology team education and/or patient education and involvement in dialysis modality decision making.
Many people with advanced kidney disease would prefer to have their dialysis at home, yet if the frail patient chooses PD most healthcare systems cannot provide their choice. AsPD should be available in all countries in Europe and for all renal centres. The top priorities to make this happen are education of renal healthcare teams about the advantages of PD, education of and discussion with patients and their families as they approach the need for dialysis, and engagement with policy makers and healthcare providers to develop and support assistance for PD.
Treatment Decision Making for Older Kidney Patients during COVID-19.Clinical Journal of the American
Coronavirus disease 2019 (COVID-19) disrupted medical care across health care settings for older patients with advanced CKD. Understanding how shared decision making for kidney treatment decisions was influenced by the uncertainty of an evolving pandemic can provide insights for supporting shared decision making through the current and future public health crises.
We performed thematic and narrative analyses of semistructured interviews with patients (CKD stages 4 and 5, age 70+), care partners, and clinicians from Boston, Portland (Maine), San Diego, and Chicago from August to December 2020.
We interviewed 76 participants (39 patients, 17 care partners, and 20 clinicians). Among patient participants, 13 (33%) patients identified as Black, and seven (18%) had initiated dialysis. Four themes with corresponding subthemes emerged related to treatment decision making and the COVID-19 pandemic: (1) adapting to changed educational and patient engagement practices (patient barriers to care and new opportunities for telemedicine); (2) reconceptualizing vulnerability (clinician awareness of illness severity increased and limited discussions of patient COVID-19 vulnerability); (3) embracing home-based dialysis but not conservative management (openness to home-based modalities and limited discussion of conservative management and advanced care planning); and (4) satisfaction and safety with treatment decisions despite conditions of uncertainty.
Although clinicians perceived greater vulnerability among older patients CKD and more readily encouraged home-based modalities during the COVID-19 pandemic, their discussions of vulnerability, advance care planning, and conservative management remained limited, suggesting areas for improvement. Clinicians reported burnout caused by the pandemic, increased time demands, and workforce limitations, whereas patients remained satisfied with their treatment choices despite uncertainty.Clinical Trial registry name and registration number: Decision Aid for Renal Therapy (DART), NCT03522740.
Automated Determination of Left Ventricular Function Using Electrocardiogram Data in Patients on Maintenance Hemodialysis.Clinical Journal of the American
Left ventricular ejection fraction is disrupted in patients on maintenance hemodialysis and can be estimated using deep learning models on electrocardiograms. Smaller sample sizes within this population may be mitigated using transfer learning.
We identified patients on hemodialysis with transthoracic echocardiograms within 7 days of electrocardiogram using diagnostic/procedure codes. We developed four models: (1) trained from scratch in patients on hemodialysis, (2) pretrained on a publicly available set of natural images (ImageNet), (3) pretrained on all patients not on hemodialysis, and (4) pretrained on patients not on hemodialysis and fine-tuned on patients on hemodialysis. We assessed the ability of the models to classify left ventricular ejection fraction into clinically relevant categories of ≤40%, 41% to ≤50%, and >50%. We compared performance by area under the receiver operating characteristic curve.
We extracted 705,075 electrocardiogram:echocardiogram pairs for 158,840 patients not on hemodialysis used for development of models 3 and 4 and n=18,626 electrocardiogram:echocardiogram pairs for 2168 patients on hemodialysis for models 1, 2, and 4. The transfer learning model achieved area under the receiver operating characteristic curves of 0.86, 0.63, and 0.83 in predicting left ventricular ejection fraction categories of ≤40% (n=461), 41%-50% (n=398), and >50% (n=1309), respectively. For the same tasks, model 1 achieved area under the receiver operating characteristic curves of 0.74, 0.55, and 0.71, respectively; model 2 achieved area under the receiver operating characteristic curves of 0.71, 0.55, and 0.69, respectively, and model 3 achieved area under the receiver operating characteristic curves of 0.80, 0.51, and 0.77, respectively. We found that predictions of left ventricular ejection fraction by the transfer learning model were associated with mortality in a Cox regression with an adjusted hazard ratio of 1.29 (95% confidence interval, 1.04 to 1.59).
A deep learning model can determine left ventricular ejection fraction for patients on hemodialysis following pretraining on electrocardiograms of patients not on hemodialysis. Predictions of low ejection fraction from this model were associated with mortality over a 5-year follow-up period.
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_06_06_CJN16481221.mp3.