The latest medical research on Nephrology

Kidney transplant recipients are at higher risk of fractures compared to the general population. The use of bisphosphonates has been shown to increase bone mineral density after transplantation but has not been shown to lower fracture rates. Here, we aim to determine if exposure to bisphosphonates associates with lower incidence of non-vertebral fractures after kidney transplantation.

We conducted a retrospective review for all Southern California Kaiser Permanente kidney transplant recipients with osteoporosis transplanted between 2000 and 2019. Baseline variables were collected. Those prescribed an oral bisphosphonate were compared to those who were not. The primary outcome was non-vertebral fracture. Chi square was used to evaluate categorical variables and Wilcoxson rank sum test for continuous variables. Propensity scores were generated to balance covariates in the bisphosphonate and non-bisphosphonate groups. Cause-specific hazard and sub distribution (Fine-Gray) methods were performed for competing risk analysis. Death censored graft survival was evaluated as a secondary outcome using standard Cox regression.

There were 489 patients included in the study, 203 of which were in the bisphosphonate group. The cause specific hazard model suggested a 64% lower risk of non-vertebral fracture in the bisphosphonate group (p=0.02). The Fine-Gray hazard model treating death as a competing risk did not show lower relative incidence of non-vertebral fracture. Bisphosphonate treatment was associated with lower death censored graft failure (p=0.002).

Bisphosphonate use after kidney transplantation may associate with lower risk of non-vertebral fracture after transplant. Bisphosphonate use in this study was also associated with lower death censored graft failure. Caution is advised when interpreting these results given the retrospective nature of the study.

Social determinants of health shape a child's transplant course. We describe the association between neighborhood socioeconomic deprivation, transplant characteristics, and graft survival in US pediatric kidney transplant recipients.

US recipients <18 years of age at listing transplanted January 1st, 2010, to May 31st, 2022 (N=9,178) were included from the Scientific Registry of Transplant Recipients. Recipients were stratified into three groups according to Material Community Deprivation Index score, with greater score representing higher neighborhood socioeconomic deprivation. Outcomes were modeled using multivariable logistic regression and Cox proportional hazards models.

Twenty-four percent (N=110) of recipients from neighborhoods of high socioeconomic deprivation identified as being of Black race, versus 12% (N=383) of recipients from neighborhoods of low socioeconomic deprivation. Neighborhoods of high socioeconomic deprivation had a much greater proportion of recipients identifying as being of Hispanic ethnicity (67%, N=311), versus neighborhoods of low socioeconomic deprivation (17%, N=562). The hazard of graft loss was 55% higher (aHR 1.55, 95% CI: 1.24, 1.94) for recipients from neighborhoods of high versus recipients from low socioeconomic deprivation neighborhoods when adjusted for base covariates, race and ethnicity, and insurance status, with 59% lower odds (aOR 0.41, 95% CI: 0.30, 0.56) of living donor transplantation and, although not statistically significant, 8% lower odds (aOR 0.92, 95% CI: 0.72, 1.19) of preemptive transplantation. The hazard of graft loss was 41% higher (aHR 1.41, 95% CI: 1.25, 1.60) for recipients from neighborhoods of intermediate versus recipients from low socioeconomic deprivation neighborhoods when adjusted for base covariates, race and ethnicity, and insurance status, with 27% lower odds (aOR 0.73, 95% CI: 0.66, 0.81) of living donor transplantation and 11% lower odds (aOR 0.89, 95% CI: 0.80, 0.99) of preemptive transplantation.

Children from neighborhoods of high socioeconomic deprivation have worse graft survival and lower utilization of preemptive and living donor transplantation. These findings demonstrate inequities in pediatric kidney transplantation that warrant further intervention.

The onset of diabetic kidney disease (DKD) in youth with type 2 diabetes mellitus often occurs early, leading to complications in young adulthood. Risk biomarkers associated with the early onset of DKD are urgently needed in youth with type 2 diabetes.

We conducted an in-depth analysis of 6596 proteins (SomaScan 7K) in 374 baseline plasma samples from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study to identify multi-protein signatures associated with the onset of albuminuria (urine albumin-to-creatinine ratio [UACR] ≥30 mg/g), a rapid decline in estimated glomerular filtration rate (eGFR) [annual eGFR decline >3 mL/min/1.73m2 and/or ≥3.3% at two consecutive visits], and hyperfiltration (≥135 mL/min/1.73m2 at two consecutive visits). Elastic net Cox regression with 10-fold cross-validation was applied to the top 100 proteins (ranked by p-value) to identify multi-protein signatures of time to development of DKD outcomes.

Participants in the TODAY study (14±2 years old, 63% female, 7±6 months diabetes duration) experienced high rates of early DKD: 43% developed albuminuria, 48% hyperfiltration, and 16% rapid eGFR decline. Increased levels of seven and three proteins were predictive of shorter time to develop albuminuria and rapid eGFR decline, respectively; 118 proteins predicted time to development of hyperfiltration. Elastic net Cox proportional hazards model identified multi-protein signatures of time to incident early DKD with concordance for models with clinical covariates and selected proteins between 0.81 and 0.96, while the concordance for models with clinical covariates only was between 0.56 and 0.63.

Our research sheds new light on proteomic changes early in the course of youth-onset type 2 diabetes that associate with DKD. Proteomic analyses identified promising risk factors that predict DKD risk in youth with type 2 diabetes and could deepen our understanding of DKD mechanisms and potential interventions.

Cause-specific mortality data from the United States Renal Data System (USRDS) form the basis for identifying cardiovascular disease (CVD), specifically sudden cardiac death (SCD), as the leading cause of death for patients on dialysis. Death certificate data from the National Death Index (NDI) is the epidemiological standard for assessing causes of death for the United States population. The cause of death has not been compared between the USRDS and the NDI.

Among 39,507 adults starting dialysis in the US, we identified 6436 patients who died between 2003-2009. We classified the cause of death as SCD, non-SCD CVD, cancer, infection, and others; and compared the USRDS to the NDI.

Median age at the time of death was 70 years, 44% were female, and 30% were non-Hispanic Black individuals. The median time from dialysis initiation to death was 1.2 years. Most deaths occurred in-hospital (N=4681, 73%). The overall concordance in cause of death between the two national registries was 42% (κ=0.23, 95% confidence interval 0.22 to 0.24). CVD, including SCD and non-SCD CVD, accounted for 67% of deaths per the USRDS but only 52% per the NDI; this difference was mainly driven by the larger proportion of SCD in the USRDS (42%) versus the NDI (22%). Of the 2962 deaths reported as SCD by the USRDS, only 35% were also classified as SCD by the NDI. Out-of-hospital deaths were more likely to be classified as SCD in the USRDS (60%) versus the NDI (29%), compared to in-hospital deaths (41% in the USRDS; 25% in the NDI).

Significant discordance exists in the causes of death for patients on dialysis reported by the USRDS and the NDI. Our findings underscore the urgent need to integrate NDI data into the USRDS registry and enhance the accuracy of cause-of-death reporting.