Urine 6-Bromotryptophan: Associations with Genetic Variants and Incident End-Stage Kidney Disease.
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SUBMITTER: Sekula P
PROVIDER: S-EPMC7308283 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
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Urine 6-Bromotryptophan: Associations with Genetic Variants and Incident End-Stage Kidney Disease.
Sekula Peggy P Tin Adrienne A Schultheiss Ulla T UT Baid-Agrawal Seema S Mohney Robert P RP Steinbrenner Inga I Yu Bing B Luo Shengyuan S Boerwinkle Eric E Eckardt Kai-Uwe KU Coresh Josef J Grams Morgan E ME Kӧttgen Anna A
Scientific reports 20200622 1
Higher serum 6-bromotryptophan has been associated with lower risk of chronic kidney disease (CKD) progression, implicating mechanisms beyond renal clearance. We studied genetic determinants of urine 6-bromotryptophan and its association with CKD risk factors and incident end-stage kidney disease (ESKD) in 4,843 participants of the German Chronic Kidney Disease (GCKD) study. 6-bromotryptophan was measured from urine samples using mass spectrometry. Patients with higher levels of urine 6-bromotry ...[more]
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Project description:BackgroundChronic kidney disease (CKD) progression can be a cause and potentially a consequence of anemia. Previous studies suggesting that anemia is associated with CKD progression have not utilized methodologic approaches to address time-dependent confounding.MethodsWe evaluated the association of anemia (defined using World Health Organization criteria of hemoglobin <12 g/dL in women and <13 g/dL in men) with incident ESRD and all-cause death in individuals with CKD using data from the Chronic Renal Insufficiency Cohort Study. Marginal structural models were used to account for time-dependent confounding.ResultsAmong 3919 participants, 1859 (47.4%) had anemia at baseline. Over median follow up of 7.8 years, we observed 1,010 ESRD events and 994 deaths. In multivariable analyses, individuals with anemia had higher risk for ESRD compared to those without (HR 1.62, 95% CI 1.24-2.11). In stratified analyses, the increased risk for incident ESRD with anemia was observed in males (HR 2.15, 95% CI: 1.53-3.02) but not females (HR 1.20, 95% CI 0.82-1.78. The association between anemia and ESRD was significant among all racial/ethnic groups except non-Hispanic blacks (non-Hispanic white, HR 2.16, 95% CI 1.53-3.06; Hispanic, HR 1.92, 1.04-3.51; others, HR 2.94; 95% CI 1.16-7.44; non-Hispanic black, HR 1.39; 95% CI 0.95-2.02). There was no association between anemia and all-cause death.ConclusionsIn this cohort, anemia was independently associated with increased risk for incident ESRD. Future work is needed to evaluate the mechanisms by which anemia leads to CKD progression as well as the impact of novel therapeutic agents to treat anemia.
| S-EPMC7591144 | biostudies-literature
Project description:BackgroundMutations in the complement factor H gene (CFH) region associate with renal-limited mesangial proliferative forms of glomerulonephritis including IgA nephropathy (IgAN), dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). Lack of kidney biopsies could lead to under diagnosis of CFH-associated end-stage kidney disease (ESKD) in African Americans (AAs), with incorrect attribution to other causes. A prior genome-wide association study in AAs with non-diabetic ESKD implicated an intronic CFH single nucleotide polymorphism (SNP).MethodsThirteen CFH SNPs (8 exonic, 2 synonymous, 2 3'UTR, and the previously associated intronic variant rs379489) were tested for association with common forms of non-diabetic and type 2 diabetes-associated (T2D) ESKD in 3770 AAs (1705 with non-diabetic ESKD, 1305 with T2D-ESKD, 760 controls). Most cases lacked kidney biopsies; those with known IgAN, DDD or C3GN were excluded.ResultsAdjusting for age, gender, ancestry and apolipoprotein L1 gene risk variants, single SNP analyses detected 6 CFH SNPs (5 exonic and the intronic variant) as significantly associated with non-diabetic ESKD (P = 0.002-0.01), three of these SNPs were also associated with T2D-ESKD. Weighted CFH locus-wide Sequence Kernel Association Testing (SKAT) in non-diabetic ESKD (P = 0.00053) and T2D-ESKD (P = 0.047) confirmed significant evidence of association.ConclusionsCFH was associated with commonly reported etiologies of ESKD in the AA population. These results suggest that a subset of cases with ESKD clinically ascribed to the effects of hypertension or glomerulosclerosis actually have CFH-related forms of mesangial proliferative glomerulonephritis. Genetic testing may prove useful to identify the causes of renal-limited kidney disease in patients with ESKD who lack renal biopsies.
| S-EPMC4081633 | biostudies-literature
Project description:Chronic kidney disease (CKD) is a global health problem with a genetic component. Genome-wide association studies have identified variants associated with specific CKD etiologies, but their genetic overlap has not been well studied. This study examined SNP associations across different CKD etiologies and CKD stages using data from 5,034 CKD patients of the German Chronic Kidney Disease study. In addition to confirming known associations, a systemic lupus erythematosus-associated risk variant at TNXB was also associated with CKD attributed to type 1 diabetes (p?=?2.5?×?10-7), a membranous nephropathy-associated variant at HLA-DQA1 was also associated with CKD attributed to systemic lupus erythematosus (p?=?5.9?×?10-6), and an IgA risk variant at HLA-DRB1 was associated with both CKD attributed to granulomatosis with polyangiitis (p?=?2.0?×?10-4) and to type 1 diabetes (p?=?4.6?×?10-11). Associations were independent of additional risk variants in the respective genetic regions. Evaluation of CKD stage showed a significant association of the UMOD risk variant, previously identified in population-based studies for association with kidney function, for advanced (stage ?G3b) compared to early-stage CKD (?stage G2). Shared genetic associations across CKD etiologies and stages highlight the role of the immune response in CKD. Association studies with detailed information on CKD etiology can reveal shared genetic risk variants.
| S-EPMC5655008 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVES:We investigated the incidence of ESKD after surgical management of kidney cancer in the Australian state of Queensland, and described patterns in the initiation of kidney replacement therapy resulting from kidney cancer across Australia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:All newly diagnosed cases of kidney cancer in the Australian state of Queensland between January of 2009 and December of 2014 were ascertained through the Queensland Cancer Registry. There were 2739 patients included in our analysis. Patients who developed ESKD were identified using international classification of disease-10-coded hospital administrative data. Incidence rate and 3-year cumulative incidence were calculated, and multivariable Cox proportional hazards models were used to identify factors associated with ESKD. Additional descriptive analysis was undertaken of Australian population data. RESULTS:The incidence rate of ESKD in all patients was 4.9 (95% confidence interval [95% CI], 3.9 to 6.2) per 1000 patient-years. The 3-year cumulative incidence was 1.7%, 1.9%, and 1.0% for all patients, and patients managed with radical or partial nephrectomy, respectively. Apart from preoperative kidney disease, exposures associated with increased ESKD risk were age?65 years (adjusted hazard ratio [aHR], 2.0; 95% CI, 1.2 to 3.2), male sex (aHR, 2.3; 95% CI, 1.3 to 4.3), preoperative diabetes (aHR, 1.8; 95% CI, 1.0 to 3.3), American Society of Anesthesiologists classification ?3 (aHR, 4.0; 95% CI, 2.2 to 7.4), socioeconomic disadvantage (aHR, 1.6; 95% CI, 0.9 to 2.7), and postoperative length of hospitalization ?6 days (aHR, 2.1; 95% CI, 1.4 to 3.0). Australia-wide trends indicate that the rate of kidney replacement therapy after oncologic nephrectomy doubled between 1995 and 2015, from 0.3 to 0.6 per 100,000 per year. CONCLUSIONS:In Queensland between 2009 and 2014, one in 53 patients managed with radical nephrectomy and one in 100 patients managed with partial nephrectomy developed ESKD within 3 years of surgery. PODCAST:This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_09_28_CJASNPodcast_18_1_.mp3.
| S-EPMC6237064 | biostudies-literature
Project description:African Americans (AAs) are at higher risk for developing end-stage kidney disease (ESKD) compared to European Americans. Genome-wide association studies have identified variants associated with diabetic and non-diabetic kidney diseases. Nephropathy loci, including SLC7A9, UMOD, and SHROOM3, have been implicated in the maintenance of normal glomerular and renal tubular structure and function. Herein, 47 genes important in podocyte, glomerular basement membrane, mesangial cell, mesangial matrix, renal tubular cell, and renal interstitium structure were examined for association with type 2 diabetes (T2D)-attributed ESKD in AAs. Single-variant association analysis was performed in the discovery stage, including 2041 T2D-ESKD cases and 1140 controls (non-diabetic, non-nephropathy). Discrimination analyses in 667 T2D cases-lacking nephropathy excluded T2D-associated SNPs. Nominal associations were tested in an additional 483 T2D-ESKD cases and 554 controls in the replication stage. Meta-analysis of 4218 discovery and replication samples revealed three significant associations with T2D-ESKD at CD2AP and MMP2 (P corr < 0.05 corrected for effective number of SNPs in each locus). Removal of APOL1 renal-risk genotype carriers revealed additional association at five loci, TTC21B, COL4A3, NPHP3-ACAD11, CLDN8, and ARHGAP24 (P corr < 0.05). Genetic variants at COL4A3, CLDN8, and ARHGAP24 were potentially pathogenic. Gene-based associations revealed suggestive significant aggregate effects of coding variants at four genes. Our findings suggest that genetic variation in kidney structure-related genes may contribute to T2D-attributed ESKD in the AA population.
| S-EPMC5053912 | biostudies-literature
Project description:Background and objectivesDiet soda consumption is common in the United States and is associated with impaired glucose metabolism, diabetes, and metabolic syndrome.Design, setting, participants, & measurementsWe prospectively analyzed diet soda consumption, assessed by food frequency questionnaire at baseline (1987-1989) and a follow-up examination (1993-1995), and incident ESRD through December 31, 2012 in the Atherosclerosis Risk in Communities study (n=15,368).ResultsBaseline mean age of participants was 54 years, 55% were female, and 27% were black. The majority of participants (43.5%) consumed <1 glass/wk of diet soda; 17.8% consumed 1-4 glasses/wk; 25.3% consumed 5-7 glasses/wk; and 13.5% consumed >7 glasses/wk. Over a median follow-up of 23 years, 357 incident ESRD cases were observed. Relative to <1 glass/wk of diet soda, consuming 1-4 glasses/wk, 5-7 glasses/wk, and >7 glasses/wk, respectively, was associated with 1.08-times (95% confidence interval [95% CI], 0.75 to 1.55), 1.33-times (95% CI, 1.01 to 1.75), and 1.83-times (95% CI, 1.01 to 2.52) higher risk of ESRD after adjusting for age, sex, race-center, education level, smoking status, physical activity, total caloric intake, eGFR, body mass index category, diabetes, systolic BP, and serum uric acid (P value for trend <0.001). Results were similar after additional adjustment for dietary acid load, diet quality, dietary sodium, dietary fructose, sugar-sweetened beverages, and dietary phosphorus. Risk estimates were similar by body mass index category (P value for interaction = 0.82), but the association between diet soda and ESRD was only significant for those who were overweight or obese at baseline. Sugar-sweetened beverage consumption was not significantly associated with ESRD in the fully adjusted model.ConclusionsDiet soda consumption was associated with higher ESRD risk in this general population sample. Further research is necessary to validate these findings in other study populations and to examine potential mechanisms through which diet soda could impact kidney disease.
| S-EPMC5220651 | biostudies-literature
Project description:Purpose of reviewThis review evaluates current recommendations for pain management in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) with a specific focus on evidence for opioid analgesia, including the partial agonist, buprenorphine.Recent findingsRecent evidence supports the use of physical activity and other nonpharmacologic therapies, either alone or with pharmacological therapies, for pain management. Nonopioid analgesics, including acetaminophen, topical analgesics, gabapentinoids, serotonin-norepinephrine reuptake inhibitors, and TCA may be considered based on pain cause and type, with careful dose considerations in kidney disease. NSAIDs may be used in CKD and ESKD for short durations with careful monitoring. Opioid use should be minimized and reserved for patients who have failed other therapies. Opioids have been associated with increased adverse events in this population, and thus should be used cautiously after risk/benefit discussion with the patient. Opioids that are safer to use in kidney disease include oxycodone, hydromorphone, fentanyl, methadone, and buprenorphine. Buprenorphine appears to be a promising and safer option due to its partial agonism at the mu opioid receptor.SummaryPain is poorly managed in patients with kidney disease. Nonpharmacological and nonopioid analgesics should be first-line approaches for pain management. Opioid use should be minimized with careful monitoring and dose adjustment.
| S-EPMC7753951 | biostudies-literature
Project description:BACKGROUND/AIMS:Decision-making in elderly patients considering dialysis is highly complex. With the increasing number of elderly with end-stage kidney disease (ESKD), it may be important to assess geriatric impairments in this population. The aim of the Geriatric assessment in OLder patients starting Dialysis (GOLD) study was to assess the prevalence of geriatric impairments and frailty in the elderly ESKD population by means of a geriatric assessment (GA), which is a comprehensive tool for overall health assessment. METHODS:This study included 285 patients ≥65 years: 196 patients at the time of dialysis initiation and 89 patients who chose maximal conservative management (MCM). The GA assessed cognition, mood, nutritional status, (instrumental) activities of daily living (ADL), mobility, comorbidity burden, quality of life and overall frailty. RESULTS:The mean age of the participants was 78 years and 36% were women. Of the incident dialysis patients, 77% started haemodialysis and 23% started peritoneal dialysis. Geriatric impairments were highly prevalent in both dialysis and MCM patients. Most frequently impaired geriatric domains in the dialysis group were functional performance (ADL 29%, instrumental ADL (iADL) 79%), cognition (67%) and comorbidity (41%). According to the GA, 77% in the dialysis group and 88% in the MCM group had 2 or more geriatric impairments. In the MCM group, functional impairment (ADL 45%, iADL 85%) was highly prevalent. CONCLUSIONS:Geriatric impairments are highly prevalent in the elderly ESKD population. Since impairments can be missed when not searched for in regular (pre)dialysis care, the first step of improving nephrologic care is awareness of the extensiveness of geriatric impairment.
| S-EPMC6381867 | biostudies-other
Project description:OBJECTIVES:Higher SBP visit-to-visit variability (SBPV) has been associated with increased risk of adverse events in patients with chronic kidney disease, but the association of SBPV in advanced nondialysis-dependent chronic kidney disease with mortality after the transition to end-stage renal disease (ESRD) remains unknown. METHODS:Among 17?729 US veterans transitioning to dialysis between October 2007 and September 2011, we assessed SBPV calculated from the SD of at least three intraindividual outpatient SBP values during the last year prior to dialysis transition (prelude period). Outcomes included factors associated with higher prelude SBPV and post-transition all-cause, cardiovascular, and infection-related mortality, assessed using multivariable linear regression and Cox and competing risk regressions, respectively, adjusted for demographics, comorbidities, medications, cardiovascular medication adherence, SBP, BMI, estimated glomerular filtration rate, and type of vascular access. RESULTS:Modifiable clinical factors associated with higher prelude SBPV included higher SBP, use of antihypertensive medications and erythropoiesis-stimulating agents, inadequate cardiovascular medication adherence, and catheter use. After multivariable adjustment, higher prelude SBPV was significantly associated with higher post-ESRD all-cause and infection-related mortality, but not cardiovascular mortality [hazard/subhazard ratios (95% confidence interval) for the highest (vs. lowest) quartile of SBPV, 1.08 (1.01-1.16), 1.02 (0.89-1.15), and 1.41 (1.10-1.80) for all-cause, cardiovascular, and infection-related mortality, respectively]. CONCLUSION:High pre-ESRD SBPV is potentially modifiable and associated with higher all-cause and infection-related mortality following dialysis initiation. Further studies are needed to test whether modification of pre-ESRD SBPV can improve clinical outcomes in incident ESRD patients. VIDEO ABSTRACT:.
| S-EPMC5708539 | biostudies-literature
Project description:BackgroundControversy remains whether white coat hypertension (WCH) is associated with renal prognosis in patients with chronic kidney disease (CKD).MethodsIn the present multicenter, prospective study, we analyzed data of participants with CKD stage 1–4 from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE). WCH was defined according to two criteria as follows: A, clinical blood pressure (BP)???140/90 mm Hg and average 24-h ambulatory BP?<?130/80 mm Hg; B, clinical BP???130/80 mm Hg and daytime ambulatory BP?<?130/80 mm Hg. Renal outcome was defined as initiation of renal replacement therapy. The association of WCH with renal events was evaluated by Cox regression model.ResultsA total of 1714 patients with CKD were included in the present analysis. The mean age of the population was 48.9?±?13.8 years and 56.8% were men. The mean baseline estimated glomerular filtration rate (eGFR) was 52.2?±?30.1 ml/min/1.73 m2 and urinary protein was 1.0 (0.4, 2.4) g/day. The overall prevalence of WCH was 4.7% and 16.6% according to criteria A and B, respectively. Incidence rates of renal events were 49.58 and 26.51 according to criteria A and B, respectively, per 1000 person-years during a median follow-up of 4.8 years. After full adjustment, WCH was associated with an increased risk of renal event (criterion A: hazard ratio 2.36, 95% confidence interval 1.29–4.34; for criterion B: hazard ratio 1.90, 95% confidence interval 1.04–3.49) compared with patients with normal BP.ConclusionsWCH is associated with a greater risk for renal events in non-dialysis dependent Chinese patients with CKD.
| S-EPMC7296682 | biostudies-literature