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Revisiting the association between human leukocyte antigen and end-stage renal disease.

ABSTRACT: Multiple works have studied possible associations between human leukocyte antigen (HLA) alleles and end stage renal disease (ESRD) showing, however, contradictory and inconsistent results. Here, we revisit the association between ESRD and HLA antigens, comparing HLA polymorphism (at HLA-A, -B, -C, -DRB1, -DQB1 and DQA1 loci) in ESRD patients (n = 497) and controls (n = 672). Our data identified several HLA alleles that displayed a significant positive or negative association with ESRD. We also determined whether heterozygosity or homozygosity of the ESRD-associated HLA alleles at different loci could modify the prevalence of the disease. Few HLA allele combinations displayed significant associations with ESRD, among which A*3_26 combination showed the highest strength of association (OR = 4.488, P? 0.05) with ESRD. Interestingly, the age of ESRD onset was not affected by HLA allele combinations at different loci. We also performed an extensive literature analysis to determine whether the association of HLA to ESRD can be similar across different ethnic groups. Our analysis showed that at least certain HLA alleles, HLA-A*11, HLA-DRB1*11, and HLA-DRB1*4, display a significant association with ESRD in different ethnic groups. The findings of our study will help in determining possible protective or susceptible roles of various HLA alleles in ESRD.

SUBMITTER: Noureen N

PROVIDER: S-EPMC7485852 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Revisiting the association between human leukocyte antigen and end-stage renal disease.

Noureen Naila N Shah Farhad Ali FA Lisec Jan J Usman Hina H Khalid Mohammad M Munir Rimsha R Zaidi Nousheen N

PloS one 20200911 9

Multiple works have studied possible associations between human leukocyte antigen (HLA) alleles and end stage renal disease (ESRD) showing, however, contradictory and inconsistent results. Here, we revisit the association between ESRD and HLA antigens, comparing HLA polymorphism (at HLA-A, -B, -C, -DRB1, -DQB1 and DQA1 loci) in ESRD patients (n = 497) and controls (n = 672). Our data identified several HLA alleles that displayed a significant positive or negative association with ESRD. We also d ...[more]

PMID: 32915858

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Project description:Alterations in autonomic nervous function are common in hemodialysis (HD) patients. Sympathetic as well as parasympathetic activation may be associated with immune and inflammatory responses. We intended to confirm a role of autonomous dysregulation for inflammation in HD patients.30 HD patients (including 15 diabetics) and 15 healthy controls were studied for heart rate variability (HRV) using 5 min ECG recordings. Heart rate variability was estimated by time-domain parameters (the standard deviation of the RR intervals (SDNN) and the percentage of pairs of adjacent RR intervals differing by >50 ms (pNN50)) and frequency-domain-analysis (high- and low-frequency variation of RR intervals, HF and LF). Inflammation was detected as serum C-reactive Protein (CRP), IL-6 and circulating monocyte subpopulation numbers. Immune cells were characterized by ACh receptor expression.Patients differed from controls in terms of age (68.0 [14.8] yrs vs. 58.0 [13.0] yrs, p?<?0.001; Median [IQR]) and sex. However, HRV parameters were different in controls and HD patients (SDNN controls 34.0 [14.0] ms, HD patients 15.5 [14.8] ms, p?<?0.01). This finding was not restricted to patients with diabetes mellitus (diab), although diabetes is an important cause of autonomous dysfunction (SDNN, diab 13.0 [14.0] ms, non-diab 18.0 [15.3] ms, p?=?0.8). LF and HF were reduced by the same magnitude to 1/3 of those in controls. Patients suffered from chronic inflammation (CRP 9.4 [12.9] mg/l, controls 1.6 [2.4] mg/l, p?<?0.001) and expanded proinflammatory monocyte subpopulations (CD14++/CD16+ cells: patients 41 [27]/?l, controls 24 [18]/?l, p?<?0.01). ECG parameters did not correlate with inflammation in patients, but monocyte ACh receptor expression was enhanced, indicating potentially elevated responsiveness of this cell type to parasympathetic regulation.HD patients have strongly impaired HRV. Chronic inflammation is not related to autonomous dysfunction, although monocytes express the ACh receptor at enhanced density making them potentially more sensitive to parasympathetic effects.This study was listed with ClinicalTrials.gov ( NCT00878033 ).

Project description:BackgroundDevelopment of vascular calcification is accelerated in patients with end-stage renal disease. In addition to traditional risk factors of cardiovascular disease (CVD) abnormal bone and mineral metabolism together with many other factors contribute to the excess cardiovascular burden in patients on dialysis. Aortic calcification score and coronary calcification score are predictive of CVD and mortality. The aim of this study was to evaluate the possible relationship between arterial calcification and bone metabolism.MethodsThirty two patients on dialysis were included. All patients underwent a bone biopsy to assess bone histomorphometry and a 18F-NaF PET scan. Fluoride activity was measured in the lumbar spine (L1 - L4) and at the anterior iliac crest. Arterial calcification scores were assessed by computerized tomography for quantification of coronary artery calcification score and lateral lumbar radiography for aortic calcification score.ResultsThis study group showed high prevalence of arterial calcification and 59% had verified CVD. Both CAC and AAC were significantly higher in patients with verified CVD. Only 22% had low turnover bone disease. There was a weak association between fluoride activity, which reflects bone turnover, measured in the lumbar spine, and CAC and between PTH and CAC. There was also a weak association between erosion surfaces and AAC. No significant association was found between calcification score and any other parameter measured.ConclusionsThe results in this study highlight the complexity, when evaluating the link between bone remodeling and vascular calcification in patients with multiple comorbidities and extensive atherosclerosis. Several studies suggest an impact of bone turnover on development of arterial calcification and there is some evidence of reduced progression of vascular calcification with improvement in bone status. The present study indicates an association between vascular calcification and bone turnover, even though many parameters of bone turnover failed to show significance. In the presence of multiple other factors contributing to the development of calcification, the impact of bone remodeling might be diminished.Trial registrationThe study is registered in ClinicalTrials.gov protocol registration and result system, ID is NCT02967042 . Date of registration is 17/11/2016.

Project description:OBJECTIVE:Serum albumin is a marker of malnutrition and inflammation and has been demonstrated as a strong predictor of mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. Yet, whether serum albumin levels in late-stage CKD are associated with adverse outcomes after the transition to ESRD is unknown. We hypothesize that lower levels and a decline in serum albumin in late-stage CKD are associated with higher risk of mortality and hospitalization rates 1 year after transition to ESRD. DESIGN AND METHODS:This retrospective cohort study included 29,124 US veterans with advanced CKD transitioning to ESRD between 2007 and 2015. We evaluated the association of pre-ESRD (91 days before transition) serum albumin with 12-month post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates as well as the association of 1-year pre-ESRD albumin slope and 12-month post-ESRD mortality using hierarchical multivariable adjustments. RESULTS:There was a negative linear association between serum albumin and all-cause mortality, such that risk doubled (hazard ratio [HR]: 2.07, 95% confidence interval [CI]: 1.87, 2.28) for patients with the lowest serum albumin <2.8 g/dL (ref: ?4.0 g/dL) after full adjustment. A consistent relationship was observed between serum albumin and cardiovascular and infection-related mortality, and hospitalization outcomes. An increase in serum albumin of >0.25 g/dL/year was associated with reduced mortality risk (HR: 0.76, 95% CI: 0.63, 0.91) compared with a slight decline in albumin (ref: >-0.25 to 0 g/dL/year), whereas a decline more than 0.5 g/dL/year was associated with a 55% higher risk in mortality (HR: 1.55, 95% CI: 1.43, 1.68) in fully adjusted models. CONCLUSIONS:Lower pre-ESRD serum albumin was associated with higher post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates. Declining serum albumin levels in the pre-ESRD period were also associated with worse 12-month post-ESRD mortality.

Project description:BackgroundPrevious studies have demonstrated that early pre-end-stage renal disease (ESRD) nephrology care could improve postdialysis prognosis. However, less is known about the specific types of interventions responsible for the improved outcomes. We hypothesized that more frequent predialysis laboratory testing is associated with better postdialysis outcomes in incident ESRD patients.MethodsIn all, 23?089 patients with available outpatient laboratory tests performed during the 2-year predialysis (i.e. prelude) period were identified from a total of 52?172 American veterans with chronic kidney disease (CKD) transitioning to dialysis between October 2007 and September 2011. The associations between the frequency of combined laboratory tests, including serum creatinine, serum potassium and hemoglobin (test trio), with postdialysis mortality and hospitalization were examined in multivariable adjusted Cox and logistic regression models.ResultsWhen entering the 2-year prelude period, the mean age (Standard Deviation) of the patients was 66.2 (SD 11.3)?years and the mean estimated glomerular filtration rate was 46.8 (SD 23.9)?mL/min/1.73 m2. In all, 14% of patients had the test trio performed less than twice in 24?months and 8.9% had the trio measured more often than every other month. Over a 2.5-year median postdialysis follow-up period, 15?303 (66.3%) patients died (mortality rate 260/1000 patient-years). The adjusted hazard ratio of all-cause mortality and adjusted odds ratio of the composite of hospitalization or death associated with lab testing done >12/24?months compared with 2-?4/24 months were 0.68 [95% confidence interval (CI) 0.65-0.73] and 0.70 (95% CI 0.62-0.79), respectively.ConclusionsMore frequent laboratory testing in patients with advanced CKD is associated with better clinical outcomes after dialysis. Further examination in clinical trials is needed before the implementation of more frequent laboratory testing in clinical practice.

Project description:ImportanceHypertension is a leading risk factor of cardiovascular morbidity and mortality. The role of nonmalignant hypertension as the sole initiating factor of end-stage renal disease (ESRD) in non-African American populations has recently been questioned.ObjectiveTo investigate the association between hypertension and future ESRD in otherwise healthy adolescents.Design, setting, and participantsThis retrospective cohort study examined the data of 16- to 19-year-old healthy candidates for military service in the Israel Defense Forces between January 1, 1967, and December 31, 2013. Data were obtained from the central conscription registry of the Israel Defense Forces and the ESRD registry of the Israel Ministry of Health. Participants underwent a comprehensive medical assessment prior to their military service. Individuals with evidence of renal damage or kidney-related risk factors were excluded. The data analysis was conducted from February 12, 2017, to October 16, 2018.Main outcomes and measuresEnd-stage renal disease as recorded by the Israeli ESRD registry, including hemodialysis, peritoneal dialysis, renal transplant diagnosed between January 1, 1990, and December 31, 2014.ResultsThe cohort included 2 658 238 adolescents (1 596 709 [60.1%] male with a mean [SD] age of 17.4 [0.5] years), of whom 7997 (0.3%) had an established hypertension diagnosis. Half of the individuals in the hypertensive group were overweight (1559 [20.1%]) or obese (2243 [28.9%]), and most (7235 [90.5%]) were male. During a median follow-up of 19.6 years (52 287 945 person-years), 2189 individuals developed ESRD, with an incidence rate of 3.9 per 100 000 person-years. Adolescent hypertension was found to be associated with future ESRD (crude hazard ratio [HR], 5.07; 95% CI, 3.73-6.88). In a multivariable model adjusted for sex, age, years of education, body mass index, and other sociodemographic variables, the HR was 1.98 (95% CI, 1.42-2.77). When excluding participants with severe hypertension, the association with ESRD remained statistically significant (HR, 1.93; 95% CI, 1.37-2.70). In the subanalysis of nonoverweight adolescents, the association between hypertension and ESRD was statistically significant as well (HR, 2.11; 95% CI, 1.05-4.24).Conclusions and relevanceHypertension appears to be associated with a doubling of the risk of future ESRD in an otherwise healthy adolescent population.

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Revisiting the association between human leukocyte antigen and end-stage renal disease.

Publications

Revisiting the association between human leukocyte antigen and end-stage renal disease.

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