The latest medical research on Transplant Nephrology

Chronic kidney disease (CKD) presents a significant clinical and economic burden to healthcare systems worldwide, which increases considerably with progression towards kidney failure. The DAPA-CKD trial demonstrated that patients with or without type 2 diabetes (T2D) who were treated with dapagliflozin experienced slower progression of CKD versus placebo. Understanding the effect of long-term treatment with dapagliflozin on the timing of kidney failure beyond trial follow-up can assist informed decision-making by healthcare providers and patients. The study objective was therefore to extrapolate the outcome-based clinical benefits of treatment with dapagliflozin in patients with CKD via a time-to-event analysis using trial data.

Patient-level data from the DAPA-CKD trial were used to parameterise a closed cohort-level partitioned survival model that predicted time-to-event for key trial endpoints (kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure). Data were pooled with a subpopulation of the DECLARE-TIMI 58 trial to create a combined CKD population spanning a range of CKD stages; a parallel survival analysis was conducted in this population.

In the DAPA-CKD and pooled CKD populations, treatment with dapagliflozin delayed time to first event for kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure. Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years (dapagliflozin: 25.2, 95%CI: 19.0-31.5; standard therapy: 18.5, 95%CI: 14.7-23.4) in the DAPA-CKD population. A similar result was observed in the pooled CKD population with an estimated delay of 6.3 years (dapagliflozin: 36.0, 95%CI: 31.9-38.3; standard therapy: 29.6, 95%CI: 25.5-34.7).

Treatment with dapagliflozin over a lifetime time horizon may considerably delay the mean time to adverse clinical outcomes for patients who would go on to experience them, including those at modest risk of progression.

National and international policies on parental leave for physician trainees are inconsistent. Physician trainees, including nephrology fellows, may be at higher risk of pregnancy complications. Physician trainees face barriers in meeting their breastfeeding goals and in finding childcare due to nontraditional work hours with extended or unpredictable shifts. Here, we examine awareness of current policies in United States (US) nephrology fellowship programs regarding parental leave, pregnancy/breastfeeding accommodations, and fellows' perspectives on family planning.

An anonymous, on-line survey of US nephrology fellows was undertaken from June 9 to August, 24, 2023.

One hundred twenty nephrology fellows submitted the survey. A majority of fellow respondents were unaware of parental leave policies of their training programs (63%), Accreditation Council for Graduate Medical Education (ACGME) (75%), and/or American Board of Medical Specialties(ABMS) (75%). Forty two percent were unaware of the duration of parental leave at their program. Nearly 45% of all respondents were unsure if their program limited night shifts or shifts greater than 24 hours for pregnant trainees. Forty three percent reported they were unsure of lactation accommodations, and 40% were unsure of access to subsidized childcare. When fellows received work accommodations for pregnancy or parenthood, their work obligations were largely covered by co-fellows (60%) or attendings (38%). Over 60% of fellows agreed or strongly agreed that they would avoid a pregnancy in fellowship due to concern they would have to extend their training. Of the 40 fellows who chose to pursue pregnancy or parenthood during medical training, 75% did not change their career plans as a result.

Most nephrology fellows were unaware of parental leave policies and pregnancy/lactation accommodations. While the topic itself has a broad impact to all physician trainees, there is need for improved awareness about national and local program policies among trainees across individual nephrology programs.

Cognitive dysfunction is a well-known complication of chronic kidney disease, but it is less known whether cognitive decline occurs in survivors after acute kidney injury (AKI). We hypothesized that an episode of AKI is associated with poorer cognitive function, mediated, at least in part, by persistent systemic inflammation.

ASSESS-AKI enrolled patients surviving three months after hospitalization with and without AKI matched based on demographics, comorbidities, and baseline kidney function. A subset underwent cognitive testing using the modified mini-mental status examination (3MS) at 3, 12, and 36 months. We examined the association of AKI with 3MS scores using mixed linear models and assessed the proportion of risk mediated by systemic inflammatory biomarkers.

Among 1538 participants in ASSESS-AKI, 1420 (92%) completed the 3MS assessment at 3 months and had a corresponding matched participant. Participants with AKI had lower 3MS scores at three years (difference -1.1 (95% CI: -2.0, -0.3) P=0.009) compared to participants without AKI. A higher proportion of AKI participants had a clinically meaningful (≥ 5 point) reduction in 3MS scores at three years compared to participants without AKI (14% vs. 10%, P=0.04). In mediation analyses, plasma soluble tumor necrosis factor receptor-1 (sTNFR-1) at three months after AKI mediated 35% (P=0.02) of the AKI related risk for 3MS scores at three years.

AKI was associated with lower 3MS scores and sTNFR-1 concentrations appeared to mediate a significant proportion of the risk of long-term cognitive impairment. Further work is needed to determine if AKI is causal or a marker for cognitive impairment.

Understanding plasma metabolome patterns in relation to changing kidney function in pediatric chronic kidney disease (CKD) is important for continued research for identifying novel biomarkers, characterizing biochemical pathophysiology, and developing targeted interventions. There is a limited number of studies of longitudinal metabolomics, and virtually none in pediatric CKD.

The Chronic Kidney Disease in Children (CKiD) study is a multi-institutional, prospective cohort that enrolled children aged six-months to 16-years with estimated glomerular filtration rate (eGFR) 30-90ml/min/1.73m2. Untargeted metabolomics profiling was performed on plasma samples from the baseline, two-, and four-year study visits. There were technologic updates in the metabolomic profiling platform used between the baseline and follow-up assays. Statistical approaches were adopted to avoid direct comparison of baseline and follow-up measurements.To identify metabolite associations with eGFR or urine protein:creatinine (UPCR) among all three timepoints, we applied linear mixed effects (LME) models. To identify metabolites associated with time, we applied LME models to the two- and four-year follow-up data. We applied linear regression analysis to examine associations between change in metabolite level over time (∆level) and change in eGFR (∆eGFR) and UPCR (∆UPCR). We reported significance based on both the False Discovery Rate (FDR) <0.05 and p<0.05.

There were 1156 person-visits (N: baseline=626, 2-year=254, 4-year=276) included. There were 622 metabolites with standardized measurements at all three timepoints. In LME modeling, 406 and 343 metabolites associated with eGFR and UPCR at FDR<0.05 respectively. Among 530 follow-up person-visits, 158 metabolites showed differences over time at FDR<0.05. For participants with complete data at both follow-up visits (N=123), we report 35 metabolites with ∆level∼∆eGFR associations significant at FDR<0.05. There were no metabolites with significant ∆level∼∆UPCR associations at FDR<0.05. We report 16 metabolites with ∆level∼∆UPCR associations at p<0.05 and associations with UPCR in LME modeling at FDR<0.05.

We characterized longitudinal plasma metabolomic patterns associated with eGFR and UPCR in a large pediatric CKD population. Many of these metabolite signals have been associated with CKD progression, etiology, and proteinuria in previous CKD Biomarkers Consortium studies. There were also novel metabolite associations with eGFR and proteinuria detected.

Iron deficiency is common in children with kidney failure, but current guidelines are based on biomarkers of iron stores that may be influenced by inflammation. This is the first study that examined which serum iron indices were associated with stainable marrow iron stores (the gold standard) in this population with kidney failure who underwent bone biopsies.

This cross-sectional study enrolled 71 clinically stable children and young adults receiving dialysis who underwent bone biopsy for chronic kidney disease-mineral bone disorder between 2007 through 2011. Bone biopsies were stained with Perls' Prussian blue and independently interpreted by a pathologist blinded to participants' iron parameters and clinical status. Marrow staining was scored absent vs. present to facilitate receiver operator curve (ROC) analysis. In ROC analysis, the ability of serum ferritin to detect stainable marrow iron stores was compared with that of transferrin saturation (TSAT), serum hepcidin, and clinical guideline-based iron deficiency cut-offs for serum iron, TSAT, and their combinations.

Mean age was 17.2 ± 4.4 years (range 2-28), and 30% of patients were female. Median dialysis vintage was 1.2 (IQR 0.7, 2.0) years, and 56% were supported by peritoneal dialysis. Mean hemoglobin was 12.4 ± 1.7 g/dl, and 35% were receiving iron supplementation at the time of biopsy. Based on the gold standard of depleted marrow iron stores, 46.5% of patients were iron-deficient. As an indicator of marrow iron staining, serum ferritin provided a higher area under the ROC curve than serum hepcidin, TSAT, or clinical guidelines-based evaluation of TSAT + ferritin.

In this cohort of children and young adults with kidney failure, serum ferritin provided the best indication of stainable marrow iron stores, followed by transferrin saturation.