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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Renal events in patients receiving Neprilysin inhibitors: a systematic review and meta-analysis.

Nephrol Dial Transplant

While it is well known that angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs) increase the risk of acute renal failure1,2, the role of neprilysin inhibition (NEPi) is unclear and some physicians are reluctant to prescribe Sacubitril/Valsartan because of safety concerns. This meta-analysis aimed to examine the risk for renal events, progression of chronic kidney disease (CKD) or progression to dialysis on combined NEPi and ACEi/ARBs compared to ACEi or ARBs.

We performed a systematic meta-analysis including 17 randomized controlled trials (study drug Sacubitril/Valsartan or Omapatrilat), involving a total of 23,569 patients, after searching PubMed, Cochrane, and Embase for eligible studies. From the included trials, all renal endpoints, including long- and short-term outcomes and hyperkalemia were extracted. Pooled odds ratios were calculated using the DerSimonian and Laird-method. The study was registered at PROSPERO.

Overall, treatment with Sacubitril/Valsartan or Omapatrilat showed a slightly lower risk of any renal event (OR 0.82, [0.7-0.97]) compared to treatment with an ACEi or ARB alone. Also, there was a decreased risk of severe acute renal events (OR 0.8, [0.69-0.93]) and a decrease in estimated glomerular filtration rate (eGFR) decline (mean difference -0.58 ml/min, [-0.83--0.33 ml/min]). There was no difference in chronic renal events (OR 0.92, [0.8-1.05]) or hyperkalemia (OR 1.02, [0.84-1.23]).

NEPi + ACEi/ARBs are safe in terms of renal adverse events. Longer trials focusing on CKD are needed to evaluate the effect of neprilysin inhibition on lowering progression of CKD.

Overcoming barriers in the design and implementation of clinical trials for Acute Kidney Injury: a report from the 2020 Kidney Disease Clinical Trialists meeting.

Nephrol Dial Transplant

Acute Kidney Injury (AKI) is a growing epidemic and is independently associated with increased risk of death, chronic kidney disease, and cardiovas...

Lifelong Effect of Therapy in Young Patients with the COL4A5 Alport Missense Variant p.(Gly624Asp): a Prospective Cohort Study.

Nephrol Dial Transplant

Angiotensin-converting enzyme inhibitors (ACEis) have evolved as a first-line therapy for delaying end-stage renal failure (ESRF) in Alport syndrome. The present study tested the hypothesis of a superior nephroprotective potential of an early ACEi intervention, examining a cohort with the COL4A5 missense variant p.(Gly624Asp).

In this observational cohort study (NCT02378805), 114 individuals with the identical gene-variant were explored for "age at ESRF" and "life-expectancy" in correlation with treatment as endpoints.

All 13 untreated hemizygous patients developed ESRF (mean age 48.9+/-13.7 years) as did three very late treated hemizygotes (51.7+/-4.2 years), with a mean life-expectancy of 59.2+/-9.6 years. All 28 earlier (eGFR 60 ml/min or higher) treated hemizygous patients were still alive and still had not reached ESRF. Therapy minimized the annual loss of their glomerular filtration rate, similar to the annual loss in healthy individuals. Out of 65 heterozygotes, 4 untreated individuals developed ESRF at an age of 53.3+/-20.7 years. None of the treated heterozygous females developed ESRF.

For the first time, this study shows that in Alport syndrome, early therapy in individuals with missense variants might have the potential to delay renal failure for their lifetime and thus to improve life-expectancy and quality of life without the need for renal replacement therapy. Some treated patients have reached retirement age with still-functioning kidneys whereas untreated relatives have already reached ESRF at the same or younger age. Thus, in children with glomerular hematuria, early testing for Alport-related gene variants could lead to timely nephroprotective intervention.

Barriers to conservative care from patients' and nephrologists' perspectives: The CKD-REIN Study.

Nephrol Dial Transplant

Conservative care is increasingly considered an alternative to kidney replacement therapy for kidney failure management, mostly among the elderly. We investigated its status and the barriers to its implementation from patients' and providers' perspectives.

We analyzed data from 1204 patients with advanced CKD (eGFR < 30 mL/min/1.73 m2) enrolled at 40 nationally representative nephrology clinics (2013-2016) who completed a self-administered questionnaire about the information they received and their preferred treatment option, including conservative care, if their kidneys failed. Nephrologists (N = 137) also reported data about their clinics' resources and practices regarding conservative care.

All participating facilities reported they were routinely able to offer conservative care, but only 37% had written protocols and only 5% a person or team primarily responsible for it. Overall 6% of patients were estimated to use conservative care. Among nephrologists, 82% reported they were fairly or extremely comfortable discussing conservative care, but only 28% usually or always offered this option for older (>75 years) patients approaching kidney failure. They used various terminology for this care, conservative management and non-dialysis care mentioned most often. Among patients, 5% of those >75 years reported receiving information about this option, and 2% preferring it.

Although reported by nephrologists to be widely available and easily discussed, conservative care is only occasionally offered to older patients, most of whom report they were not informed of this option. The lack of a person or team responsible for conservative care and unclear information appear to be key barriers to its implementation.

Dissecting the genotype-phenotype correlation of COL4A5 gene mutation and its response to renin-angiotensin-aldosterone system blockers in Chinese male patients with Alport syndrome.

Nephrol Dial Transplant

Alport syndrome (AS) is an inherited type IV collagen-related disorder with an irreversible tendency to progress to end-stage renal disease (ESRD). X-linked AS (XLAS) is caused by mutations in the COL4A5 gene. The aim of this study was to investigate the effects of underlying mutations on clinical manifestations and the response to therapy in XLAS.

We conducted a retrospective cohort study of 187 Chinese male patients with XLAS confirmed by pathological examination and genetic analysis. The Kaplan-Meier method and Cox proportional hazards model were used to assess the age and risk of progression to ESRD under different genotypes and treatment conditions.

A strong relationship between transcript type and renal outcome was observed, with the median age of ESRD onset being 22 years for truncating mutations and 39 years for nontruncating mutations. The response of affected patients to renin-angiotensin-aldosterone system (RAAS) blockers was genotype-associated. This therapy delayed the onset of ESRD by 16 years in patients with nontruncating mutations and 3 years in patients with truncating mutations. The efficacy of RAAS blockers functioned in a time-dependent manner, with a 7% reduction in the risk of progression to ESRD per each 6-month increase in treatment duration (HR 0.93; 95% CI 0.89-0.96) (P < 0.001).

Clinical features and response to RAAS blockers were observed to be strongly correlated with the genotypes of male XLAS patients. Genotyping of COL4A5 gene mutations is essential and is a useful tool to assess the prognosis of AS patients.

RtNet: a deep hybrid neural networks for the identification of acute rejection and chronic allograft nephropathy after renal transplantation using multiparametric MRI.

Nephrol Dial Transplant

Reliable diagnosis of the cause of renal allograft dysfunction is of clinical importance. The aim of this study is to develop a hybrid deep learning approach for determining acute rejection (AR), chronic allograft nephropathy (CAN) and renal function in kidney-allografted patients by multimodality integration.

Clinical and MRI data of 252 kidney-allografted patients who underwent post-transplantation MRI between Dec 2014 and Nov 2019 were retrospectively collected. An end-to-end convolutional neural network, namely RtNet, was designed to discriminate between AR, CAN and stable renal allograft recipient (SR), and secondary, to predict the impaired renal graft function (eGFR ≤ 50 mL/min/1.73 m2). Specially, clinical variables and MRI radiomics features were integrated into the RtNet, resulting a hybrid network (RtNet+). The performance of the conventional radiomics model RtRad, RtNet, and RtNet+ was compared to test effect of multimodality interaction.

Out of 252 patients, AR, CAN and SR was diagnosed in 20/252 (7.9%), 92/252 (36.5%) and 140/252 (55.6%) patients, respectively. Of all MRI sequences, T2-weighted imaging and diffusion-weighted imaging with stretched exponential analysis showed better performance than other sequences. On pairwise comparison of resulting prediction models, RtNet+ produced significantly higher macro-area-under-curve (macro-AUC) (0.733 vs 0.745; p = 0.047) than RtNet in discriminating between AR, CAN and SR. RtNet+ performed similarly with the RtNet (macro-AUC, 0.762 vs 0.756; p > 0.05) in discriminating between eGFR ≤ 50 mL/min/1.73 m2 and > 50 mL/min/1.73 m2. With decision curve analysis, adding RtRad and RtNet to clinical variables resulted in more net benefits in diagnostic performance.

Our study revealed that the proposed RtNet+ model owned a stable performance in revealing the cause of renal allograft dysfunction, thus might afford important references for individualized diagnostics and treatment strategy.

Rapidly progressive iga nephropathy: clinicopathological characteristics and outcomes assessed according to the revised definition of the KDIGO 2021 guideline.

Nephrol Dial Transplant

Rapidly progressive IgA nephropathy (RPIgAN) is a severe clinical phenotype of IgAN, associated with a poor outcome. The recently published KDIGO 2021 Guideline for the Management of Glomerular Diseases has proposed a new definition for RPIgAN, which is based simply on a ≥ 50% decline in eGFR ≤ 3 months.

In 1,677 IgAN patients followed at a single centre in China, we evaluated the utility of this new definition to identify the highest risk IgAN patients who might be suitable for combination immunosuppressive therapy.

The proportion of a ≥ 50% decline in eGFR ≤ 3 months was 5.2%. The majority of these patients had reversible causes, only 2.3% (39/1,677) meeting the KDIGO 2021 criteria for RPIgAN. These patients had a significantly higher risk for ESKD than non-RPIgAN patients (log rank P < 0.001). RPIgAN was an independent risk factor for ESKD (hazard ratio [HR] 3.99; 95% confidence interval [CI] 2.25 - 7.09; P < 0.001). A minority of the RPIgAN patients (25.6%) had ≥ 50% crescents. There was no significant difference in the risk for ESKD between patients in the RPIgAN group with ≥ 50% crescents and ˂ 50% crescents (log rank P = 0.27). Patients with RPIgAN and ≥ 50% crescents had a higher risk for ESKD than patients with non-RPIgAN and ≥ 50% crescents (log rank P = 0.04).

These data support the validity of the KDIGO 2021 definition but require independent validation in other non-Chinese cohorts.

Cannabinoids for Symptom Management in Patients with Kidney Failure.

Clinical Journal of the American

People with kidney failure can experience a range of symptoms that lead to suffering and poor quality of life. Available therapies are limited, and...

Assessing Global Kidney Nutrition Care.

Clinical Journal of the American

Nutrition intervention is an essential component of kidney disease management. This study aimed to understand current global availability and capacity of kidney nutrition care services, interdisciplinary communication, and availability of oral nutrition supplements.

The International Society of Renal Nutrition and Metabolism (ISRNM), working in partnership with the International Society of Nephrology (ISN) Global Kidney Health Atlas Committee, developed this Global Kidney Nutrition Care Atlas. An electronic survey was administered among key kidney care stakeholders through 182 ISN-affiliated countries between July and September 2018.

Overall, 160 of 182 countries (88%) responded, of which 155 countries (97%) answered the survey items related to kidney nutrition care. Only 48% of the 155 countries have dietitians/renal dietitians to provide this specialized service. Dietary counseling, provided by a person trained in nutrition, was generally not available in 65% of low-/lower middle-income countries and "never" available in 23% of low-income countries. Forty-one percent of the countries did not provide formal assessment of nutrition status for kidney nutrition care. The availability of oral nutrition supplements varied globally and, mostly, were not freely available in low-/lower middle-income countries for both inpatient and outpatient settings. Dietitians and nephrologists only communicated "sometimes" on kidney nutrition care in ≥60% of countries globally.

This survey reveals significant gaps in global kidney nutrition care service capacity, availability, cost coverage, and deficiencies in interdisciplinary communication on kidney nutrition care delivery, especially in lower-income countries.

A Core Outcome Set for Trials in Glomerular Disease: A Report of the Standardized Outcomes in Nephrology-Glomerular Disease (SONG-GD) Stakeholder Workshops.

Clinical Journal of the American

Outcomes reported in trials in adults with glomerular disease are often selected with minimal patient input, are heterogeneous, and may not be relevant for clinical decision making. The Standardized Outcomes in Nephrology-Glomerular Disease (SONG-GD) initiative aimed to establish a core outcome set to help ensure that outcomes of critical importance to patients, care partners, and clinicians are consistently reported.

We convened two 1.5-hour workshops in Melbourne, Australia, and Washington, DC, United States. Attendees were identified purposively with 50 patients/care partners and 88 health professionals from 19 countries; 51% were female. Patients and care partners were from the United States, Australia, and Canada, and had experience of a glomerular disease with systemic features (n=9), kidney-limited nephrotic disease (n=9), or other kidney-limited glomerular disease (n=8). Attendees reviewed the results of the SONG-GD Delphi survey and aims of the workshop and then discussed potential core outcomes and their implementation in trials among moderated breakout groups of eight to 12 people from diverse backgrounds. Transcripts of discussions were analyzed thematically.

Three themes were identified that supported the proposed core outcomes: limiting disease progression, stability and control, and ensuring universal relevance (i.e., applicable across diverse populations and settings). The fourth theme, preparedness for implementation, included engaging with funders and regulators, establishing reliable and validated measures, and leveraging existing endorsements for patient-reported outcomes.

Workshop themes demonstrated support for kidney function, disease activity, death, life participation, and cardiovascular disease, and these were established as the core outcomes for trials in adults with glomerular disease. Future work is needed to establish the core measures for each domain, with funders and regulators central to the uptake of the core outcome set in trials.

Kidney Failure Risk Equation and Cost of Care in Patients with Chronic Kidney Disease.

Clinical Journal of the American

Patients with CKD exhibit heterogeneity in their rates of progression to kidney failure. The kidney failure risk equation (KFRE) has been shown to accurately estimate progression to kidney failure in adults with CKD. Our objective was to determine health care utilization patterns of patients on the basis of their risk of progression.

We conducted a retrospective cohort study of adults with CKD and eGFR of 15-59 ml/min per 1.73 m2 enrolled in multidisciplinary CKD clinics in the province of Saskatchewan, Canada. Data were collected from January 1, 2004 to December 31, 2012 and followed for 5 years (December 31, 2017). We stratified patients by eGFR and risk of progression and compared the number and cost of hospital admissions, physician visits, and prescription drugs.

In total, 1003 adults were included in the study. Within the eGFR of 15-29 ml/min per 1.73 m2 group, the costs of hospital admissions, physician visits, and drug dispensations over the 5-year study period comparing high-risk patients with low-risk patients were (Canadian dollars) $89,265 versus $48,374 (P=0.008), $23,423 versus $11,231 (P<0.001), and $21,853 versus $16,757 (P=0.01), respectively. Within the eGFR of 30-59 ml/min per 1.73 m2 group, the costs of hospital admissions, physician visits, and prescription drugs were $55,944 versus $36,740 (P=0.10), $13,414 versus $10,370 (P=0.08), and $20,394 versus $14,902 (P=0.02) in high-risk patients in comparison with low-risk patients, respectively, for progression to kidney failure.

In patients with CKD and eGFR of 15-59 ml/min per 1.73 m2 followed in multidisciplinary clinics, the costs of hospital admissions, physician visits, and drugs were higher for patients at higher risk of progression to kidney failure by the KFRE compared with patients in the low-risk category. The high-risk group of patients with CKD and eGFR of 15-29 ml/min per 1.73 m2 had stronger association with hospitalizations costs, physician visits, and drug utilizations.

Waiting Time for Second Kidney Transplantation and Mortality.

Clinical Journal of the American

The median kidney transplant half-life is 10-15 years. Because of the scarcity of donor organs and immunologic sensitization of candidates for retransplantation, there is a need for quantitative information on if and when a second transplantation is no longer associated with a lower risk of mortality compared with waitlisted patients treated by dialysis. Therefore, we investigated the association of time on waiting list with patient survival in patients who received a second transplantation versus remaining on the waiting list.

In this retrospective study using target trial emulation, we analyzed data of 2346 patients from the Austrian Dialysis and Transplant Registry and Eurotransplant with a failed first graft, aged over 18 years, and waitlisted for a second kidney transplantation in Austria during the years 1980-2019. The differences in restricted mean survival time and hazard ratios for all-cause mortality comparing the treatment strategies "retransplant" versus "remain waitlisted with maintenance dialysis" are reported for different waiting times after first graft loss.

Second kidney transplantation showed a longer restricted mean survival time at 10 years of follow-up compared with remaining on the waiting list (5.8 life months gained; 95% confidence interval, 0.9 to 11.1). This survival difference was diminished in patients with longer waiting time after loss of the first allograft; restricted mean survival time differences at 10 years were 8.0 (95% confidence interval, 1.9 to 14.0) and 0.1 life months gained (95% confidence interval, -14.3 to 15.2) for patients with waiting time for retransplantation of <1 and 8 years, respectively.

Second kidney transplant is associated with patient survival compared with remaining waitlisted and treatment by dialysis, but the survival difference diminishes with longer waiting time.