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Apolipoprotein L1 and Chronic Kidney Disease Risk in Young Potential Living Kidney Donors.

ABSTRACT: OBJECTIVE:The aim of this study was to develop a novel chronic kidney disease (CKD) risk prediction tool for young potential living kidney donors. SUMMARY OF BACKGROUND DATA:Living kidney donor selection practices have evolved from examining individual risk factors to a risk calculator incorporating multiple characteristics. Owing to limited long-term data and lack of genetic information, current risk tools lack precision among young potential living kidney donors, particularly African Americans (AAs). METHODS:We identified a cohort of young adults (18-30 years) with no absolute contraindication to kidney donation from the longitudinal cohort study Coronary Artery Risk Development in Young Adults. Risk associations for CKD (estimated glomerular filtration rate <60?mL/min/1.73?m) were identified and assigned weighted points to calculate risk scores. RESULTS:A total of 3438 healthy adults were identified [mean age 24.8 years; 48.3% AA; median follow-up 24.9 years (interquartile range: 24.5-25.2)]. For 18-year olds, 25-year projected CKD risk varied by ethnicity and sex even without baseline clinical and genetic abnormalities; risk was 0.30% for European American (EA) women, 0.52% for EA men, 0.52% for AA women, 0.90% for AA men. Among 18-year-old AAs with apolipoprotein L1 gene (APOL1) renal-risk variants without baseline abnormalities, 25-year risk significantly increased: 1.46% for women and 2.53% for men; among those with 2 APOL1 renal-risk variants and baseline abnormalities, 25-year risk was higher: 2.53% to 6.23% for women and 4.35% to 10.58% for men. CONCLUSIONS:Young AAs were at highest risk for CKD, and APOL1 renal-risk variants drove some of this risk. Understanding the genetic profile of young AA potential living kidney donors in the context of baseline health characteristics may help to inform candidate selection and counseling.

SUBMITTER: Locke JE

PROVIDER: S-EPMC5805656 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Apolipoprotein L1 and Chronic Kidney Disease Risk in Young Potential Living Kidney Donors.

Locke Jayme E JE Sawinski Deirdre D Reed Rhiannon D RD Shelton Brittany B MacLennan Paul A PA Kumar Vineeta V Mehta Shikha S Mannon Roslyn B RB Gaston Robert R Julian Bruce A BA Carr John J JJ Terry James G JG Kilgore Meredith M Massie Allan B AB Segev Dorry L DL Lewis Cora E CE

Annals of surgery 20180601 6

<h4>Objective</h4>The aim of this study was to develop a novel chronic kidney disease (CKD) risk prediction tool for young potential living kidney donors.<h4>Summary of background data</h4>Living kidney donor selection practices have evolved from examining individual risk factors to a risk calculator incorporating multiple characteristics. Owing to limited long-term data and lack of genetic information, current risk tools lack precision among young potential living kidney donors, particularly Af ...[more]

PMID: 28187045

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Project description:Cardiovascular disease (CVD) is an evolving process that begins in the early stages of chronic kidney disease (CKD) in children. Several surrogate markers, such as ambulatory blood pressure monitoring (ABPM), left ventricular (LV) mass, and arterial stiffness assessment, allow for the early detection of subclinical CVD in pediatric CKD. Four groups of plasma samples (n = 3/group) from congenital anomalies of the kidney and urinary tract (CAKUT), as well as non-CAKUT patients with or without BP abnormalities, were studied to screen differentially expressed proteins using isobaric tags for relative and absolute protein quantification (iTRAQ)-based proteomics. As a result, 20 differentially expressed proteins associated with hypertension in children with CKD were discovered. Among them, apolipoprotein C-II (apoC-II) was found to have the highest abundance among the CKD patients with hypertension. As such, we hypothesized that apoC-II and apolipoprotein C-III (apoC-III) levels were related to BP abnormalities and CVD in children suffering from mild-to-moderate CKD. We examined their associations with surrogate markers of CV risk in 88 pediatric patients with CKD stages G1-G4. Children with CKD stages G2-G4 had a higher plasma apoC-II level than G1 patients (6.35 vs. 5.05 mg/dl, p < 0.05). We observed that ABPM abnormalities, LV mass, and arterial stiffness parameters were greater in CKD children who had stages G2-G4 than in those who had stage G1 (all p < 0.05). Plasma levels of apoC-II and apoC-III were positively correlated with total cholesterol, triglyceride, and low-density lipoprotein (LDL) (all p < 0.001). In multivariate linear regression analyses, apoC-II was correlated with a high LV mass index and an abnormal ABPM profile, and apoC-III was correlated with 24-h hypertension (r = 0.303, p = 0.003) and asleep hypertension (r = 0.379, p < 0.001). Early evaluations of apoC-II and apoC-III, ABPM, and surrogate markers of CV risk will aid in early preventative interventions to reduce the risk of CV in youths suffering from CKD.

Project description:ImportanceLiving kidney donors may have an increased risk of fractures due to reductions in kidney mass, lower concentrations of serum 1,25-dihydroxyvitamin D, and secondary increases in serum parathyroid hormone.ObjectiveTo compare the overall and site-specific risk of fractures among living kidney donors with strictly matched controls from the general population who would have been eligible to donate a kidney but did not do so.Design, setting, and participantsThis survey study was conducted between December 1, 2021, and July 31, 2023. A total of 5065 living kidney donors from 3 large transplant centers in Minnesota were invited to complete a survey about their bone health and history of fractures, and 16 156 population-based nondonor controls without a history of comorbidities that would have precluded kidney donation were identified from the Rochester Epidemiology Project and completed the same survey. A total of 2132 living kidney donors and 2014 nondonor controls responded to the survey. Statistical analyses were performed from May to August 2023.ExposureLiving kidney donation.Main outcomes and measuresThe rates of overall and site-specific fractures were compared between living kidney donors and controls using standardized incidence ratios (SIRs).ResultsAt the time of survey, the 2132 living kidney donors had a mean (SD) age of 67.1 (8.9) years and included 1245 women (58.4%), and the 2014 controls had a mean (SD) age of 68.6 (7.9) years and included 1140 women (56.6%). The mean (SD) time between donation or index date and survey date was 24.2 (10.4) years for donors and 27.6 (10.7) years for controls. The overall rate of fractures among living kidney donors was significantly lower than among controls (SIR, 0.89; 95% CI, 0.81-0.97). However, there were significantly more vertebral fractures among living kidney donors than among controls (SIR, 1.42; 95% CI, 1.05-1.83).Conclusions and relevanceThis survey study found a reduced rate of overall fractures but an excess of vertebral fractures among living kidney donors compared with controls after a mean follow-up of 25 years. Treatment of excess vertebral fractures with dietary supplements such as vitamin D3 may reduce the numbers of vertebral fractures and patient morbidity.

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Apolipoprotein L1 and Chronic Kidney Disease Risk in Young Potential Living Kidney Donors.

Publications

Apolipoprotein L1 and Chronic Kidney Disease Risk in Young Potential Living Kidney Donors.

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