Representation of Low- and Middle-Income Countries in CKD Drug Trials: A Systematic Review.

RATIONALE & OBJECTIVE: Almost 80% of individuals with chronic kidney disease (CKD) reside in low- and middle-income countries (LMICs) and are potentially under-represented in randomized controlled clinical trials (RCTs). We assessed the global distribution of RCTs comparing pharmacological treatments for CKD over the past two decades, as well as the magnitude and evolution of participation by LMICs. STUDY DESIGN: Systematic review. SETTING & STUDY POPULATIONS: RCTs evaluating pharmacological interventions in adults with CKD. SELECTION CRITERIA FOR STUDIES: RCTs published between 2003-2023 and indexed in MEDLINE. DATA EXTRACTION: Each trial was reviewed and extracted independently by two investigators. Disagreements were settled by consensus or a third reviewer. ANALYTICAL APPROACH: RCT participation of World Bank-defined income groups and geographic regions were described and the representation indices (RI) according to RCT participants and estimated CKD prevalences were calculated. RCTs were also categorized as global, regional, or national in scope. RESULTS: Among 7,760 identified studies, we included 1,366 RCTs conducted in 84 countries with 301,158 participants. National, regional, and global RCTs represented 85.4%, 3.5%, and 11.1% of studies, respectively. LMICs were included in 34.7% of RCTs. No RCTs included participants from low-income countries, and lower-middle-income countries participated in 13.2%. Of participants from RCTs with available information, 25.4% (n=64,843/255,237) were from LMICs. According to the RI, six LMICs were over-represented (>1.25), seven adequately represented (0.75-1.25), and 26 under-represented (<0.75). Most (80.2%) global CKD RCTs included LMICs; however, LMIC participants constituted only 32.9% of the global trial population. We observed a positive trend in LMIC inclusion over time, rising from 22.9% (n=71/310) in 2003-2007 to 45.5% (n=140/308) in 2018-2023. LIMITATIONS: The use of an income-group dichotomy, exclusion of non-randomized studies of intervention, and studies identified in one database. CONCLUSIONS: Despite an increase in participation over the past two decades, individuals with CKD from LMICs remain significantly under-represented in RCTs. These findings suggest that increased efforts are warranted to increase LMIC representation in pharmacological CKD RCTs.

Impact of hyperparathyroidism on allograft histology and function after kidney transplantation: Rethinking its causal role in graft dysfunction.

INTRODUCTION: The causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford-Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time-zero graft biopsies. METHODS: Retrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre-transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post-transplant hyperparathyroidism by iPTH >1× and >2× the URL 1 year after transplantation. RESULTS: We included 325 KTRs (56% female, age 38 ± 13 years, follow-up 4.2 years [IQR: 2.7-5.8]). Based on pre-transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of >25% IF/TA between KTRs with pre-transplant iPTH levels above and within target range according to KDIGO (53% vs. 62%, P = .16, HR.94 [95% CI:.67-1.32]) and KDOQI (60% vs. 60%, P = 1.0, HR 1.19 [95% CI:.88-1.60]) criteria. Similarly, there were no differences when using 1 year post-transplant iPTH cut-offs > 88 pg/mL (58% vs. 64%, P = .33) and > 176 pg/mL (55% vs. 62%, P = .19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata. CONCLUSION: In young KTRs who received a healthy graft, no association was found between increased pre- and post-transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation.

What Did We Learn about Coronavirus Disease-19-Associated Acute Kidney Injury During the Pandemic?

ABSTRACT Initial reports suggested that kidney involvement after coronavirus disease 19 (COVID-19) infection was uncommon, but this premise appears to be incorrect. Acute kidney injury can occur through various mechanisms and complicate the course of up to 25% of patients with COVID-19 hospitalized in our Institution, and of over 50% of those on invasive mechanical ventilation. Mechanisms of injury include direct kidney injury and predominantly tubular, although glomerular injury has been reported, and resulting from severe hypoxic respiratory failure, secondary infection, and exposure to nephrotoxic drugs. The mainstay of treatment remains the prevention of progressive kidney damage and, in some cases, the use of renal replacement therapy. Although the use of blood purification techniques has been proposed as a potential treatment, results to date have not been conclusive. In this manuscript, the mechanisms of kidney injury by COVID-19, risk factors, and the mainstays of treatment are reviewed.

Diseño de estudios clínicos y causalidad: ¿la vacuna oral contra rotavirus causa invaginación intestinal? / Clinical research design and causality: does oral rotavirus vaccine cause intussusception?

ResumenLos diseños de investigación clínica, cuyo propósito es responder preguntas sobre causalidad, se pueden clasificar en relación con cuatro ejes: el número de grupos de estudio, la aplicación de una maniobra experimental, la direccionalidad causa-efecto y la fuente de la que se recaban los datos. Los diseños básicos más utilizados en epidemiología son el ensayo clínico, el estudio de cohortes, el estudio de casos y controles y la encuesta transversal. Este texto pretende facilitar la identificación y comprensión de cada uno de estos diseños mediante ejemplos relacionados con la asociación entre la vacunación con rotavirus y la invaginación intestinal.

AbstractDesign of clinical research whose purpose is to answer questions about causality can be classified in relation to four axes: the number of study groups, the implementation of an experimental maneuver, cause-effect directionality and source from which the data are collected. The basic designs used in epidemiology are the clinical trial, the cohort study, the case-control study and the cross-sectional survey. This text aims to facilitate the identification and understanding of each of these designs through examples related to the association between rotavirus vaccination and intussusception.

Riesgo precoz de recidiva bioquímica en prostatectomizados radicales (T1c): aplicación de una ecuación predictiva validada / Precocious risk of biochemical recurrence in radical prostatectomy (Rp): application of a validated predictive equation

Muchos modelos predictivos de recidiva para cáncer de próstata (CaP) post prostatectomía radical (PR)son difíciles de aplicar y la tendencia es a encontrar modelos que consideren datos clínicos y patológicosde fácil y rápida obtención. El grupo de trabajo del Johns Hopkins Hospital desarrolló una ecuación deriesgo validada para identificar pacientes de alto riesgo de recidiva precoz de CaP (etapa clínica T1c),después de PR.Realizamos una revisión retrospectiva de pacientes sometidos a PR retropúbica por CaP etapa clínica T1,con un seguimiento mínimo de 6 meses. En estos pacientes aplicamos la ecuación Rw.De un total de 190 pacientes sometidos a PR en los últimos 7 años, encontramos 60 pacientes analizablesen etapa T1c. El promedio de seguimiento fue de 25,4 meses. Al aplicar la ecuación Rw encontramos unasensibilidad de 29 porciento, especificidad de 98 porciento, VPP de 83 porciento y VPN de 78 porciento. En nuestra serie la ecuación RWtiene una pobre sensibilidad pero una buena especificidad.