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Longitudinal uric acid has nonlinear association with kidney failure and mortality in chronic kidney disease.

ABSTRACT: We investigated the shape of the relationship between longitudinal uric acid (UA) and the hazard of kidney failure and death in chronic kidney disease (CKD) patients, and attempted to identify thresholds associated with increased hazards. We included CKD stage 3-5 patients from the CKD-REIN cohort with one serum UA measurement at cohort entry. We used cause-specific multivariate Cox models including a spline function of current values of UA (cUA), estimated from a separate linear mixed model. We followed 2781 patients (66% men, median age, 69 years) for a median of 3.2 years with a median of five longitudinal UA measures per patient. The hazard of kidney failure increased with increasing cUA, with a plateau between 6 and 10 mg/dl and a sharp increase above 11 mg/dl. The hazard of death had a U-shape relationship with cUA, with a hazard twice higher for 3 or 11 mg/dl, compared to 5 mg/dl. In CKD patients, our results indicate that UA above 10 mg/dl is a strong risk marker for kidney failure and death and that low UA levels below 5 mg/dl are associated with death before kidney failure.

SUBMITTER: Prezelin-Reydit M

PROVIDER: S-EPMC9998636 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Longitudinal uric acid has nonlinear association with kidney failure and mortality in chronic kidney disease.

Prezelin-Reydit Mathilde M Combe Christian C Fouque Denis D Frimat Luc L Jacquelinet Christian C Laville Maurice M Massy Ziad A ZA Lange Céline C Ayav Carole C Pecoits-Filho Roberto R Liabeuf Sophie S Stengel Bénédicte B Harambat Jérôme J Leffondré Karen K

Scientific reports 20230309 1

We investigated the shape of the relationship between longitudinal uric acid (UA) and the hazard of kidney failure and death in chronic kidney disease (CKD) patients, and attempted to identify thresholds associated with increased hazards. We included CKD stage 3-5 patients from the CKD-REIN cohort with one serum UA measurement at cohort entry. We used cause-specific multivariate Cox models including a spline function of current values of UA (cUA), estimated from a separate linear mixed model. We ...[more]

PMID: 36894586

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Project description:ImportanceUric acid is a waste metabolite produced from the breakdown of purines, and elevated serum uric acid levels are associated with higher risk of hypertension, cardiovascular disease, and mortality and progression of chronic kidney disease (CKD). Treatment of hyperuricemia in patients with preexisting CKD has not been shown to improve kidney outcomes, but the associations of uric acid-lowering therapies with the development of new-onset kidney disease in patients with estimated glomerular filtration rate (eGFR) within reference range and no albuminuria is unclear.ObjectiveTo examine the association of initiating uric acid-lowering therapy with the incidence of CKD.Design, setting, and participantsThis cohort study included patients with eGFR of 60 mL/min/1.73 m2 or greater and no albuminuria treated at US Department of Veterans Affairs health care facilities from 2004 to 2019. Clinical trial emulation methods, including propensity score weighting, were used to minimize confounding. Data were analyzed from 2020 to 2022.ExposureNewly started uric acid-lowering therapy.Main outcomes and measuresThe main outcomes were incidences of eGFR less than 60 mL/min/1.73 m2, new-onset albuminuria, and end-stage kidney disease.ResultsA total of 269 651 patients were assessed (mean [SD] age, 57.4 [12.5] years; 252 171 [94%] men). Among these, 29 501 patients (10.9%) started uric acid-lowering therapy, and 240 150 patients (89.1%) did not. Baseline characteristics, including serum uric acid level, were similar among treated and untreated patients after propensity score weighting. In the overall cohort, uric acid-lowering therapy was associated with higher risk of both incident eGFR less than 60 mL/min/1.73 m2 (weighted subhazard ratio [SHR], 1.15 [95% CI, 1.10-1.20; P < .001) and incident albuminuria (SHR, 1.05 [95% CI, 1.01-1.09; P < .001) but was not associated with the risk of end-stage kidney disease (SHR, 0.96 [95% CI, 0.62-1.50]; P = .87). In subgroup analyses, the association of uric acid-lowering therapy with worse kidney outcomes was limited to patients with baseline serum uric acid levels of 8 mg/dL or less.Conclusions and relevanceThese findings suggest that in patients with kidney function within reference range, uric acid-lowering therapy was not associated with beneficial kidney outcomes and may be associated with potential harm in patients with less severely elevated serum uric acid levels.

Project description:BackgroundIncreasing evidence supports the association between hyperuricemia and incident chronic kidney disease (CKD); however, there are conflicting data regarding the role of hyperuricemia in the progression of CKD. This study retrospectively assessed the longitudinal association between uric acid (UA) level and CKD progression in a Chinese population lived in Taiwan.MethodsPatients with physician diagnosis of hyperuricemia or receiving urate-lowering therapy between 2003 and 2005 were identified in the electronic medical records (EMR) of a tertiary medical center and were followed up until December 31, 2011. Patients were divided into four UA categories at the cut-off 6, 8, and 10 mg/dL. CKD progression was estimated by the change of estimated glomerular filtration rate (eGFR) in the linear mixed models. Kidney failure was defined as an eGFR less than 15 mL/min/1.73 m2 or requiring renal replacement therapy.ResultsA total of 739 patients were analyzed. In the full-adjusted model, patients with a baseline UA level ≥6 mg/dL had greater decline in eGFR ((β = -9.6, 95% CI -16.1, -3.1), comparing to those with a UA level less than 6 mg/dL. When stratifying patients into four UA categories, all three hyperuricemia categories (UA6-8, 8-10, ≥10 mg/dL) associated with a greater decline in eGFR over the follow-up period with an increasing dose-response, comparing to the lowest UA category. The risk of progression to renal failure increased 7% (hazard ratio 1.07, 95% CI 1.00, 1.14) for each 1mg/dL increase in baseline UA level. The influences of hyperuricemia on eGFR decline and the risk of kidney failure were more prominent in patients without proteinuria than those with proteinuria.ConclusionOur study showed a higher uric acid level is associated with a significant rapid decline in eGFR and a higher risk of kidney failure, particularly in patients without proteinuria. Our findings suggest hyperuricemia is a potential modifiable factor of CKD progression.

Project description:ObjectiveThe ratio of uric acid to high-density lipoprotein cholesterol (UHR) was related to the risk of chronic kidney disease (CKD), we aimed to investigate the association of cumulative UHR (cumUHR) with incidence and progression of CKD.MethodsOur study included a total of 49,913 participants (mean age 52.57 years, 77% males) from the Kailuan Study conducted between 2006 and 2018. Participants who completed three consecutive physical examinations were included. Cumulative UHR (cumUHR) was computed as the summed average UHR between two consecutive physical examinations, multiplied by the time between the two examinations. Participants were then categorized into four groups based on cumUHR quartiles. Subsequently, participants were further divided into a CKD group and a non-CKD group. The associations between cumUHR and CKD and it's progression were assessed by Cox proportional hazards regression models. The cumulative incidence of endpoint events was compared between the cumUHR groups using the log-rank test. The C-index, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated to assess the predictive performance of cumUHR.ResultsAfter a mean follow-up of 8.0 ± 1.7 years, there were 4843 cases of new-onset CKD, 2504 of low eGFR, and 2617 of proteinuria in the non-CKD group. Within the CKD group, there were 1952 cases of decline in eGFR category, 1465 of >30% decline in eGFR, and 2100 of increased proteinuria. In the non-CKD group, the adjusted hazard ratios (HRs) and confidence intervals (CIs) in the fourth quartile were 1.484 (1.362-1.617), 1.643 (1.457-1.852), and 1.324 (1.179-1.486) for new-onset CKD, low eGFR, and proteinuria, respectively. In the CKD group, the adjusted HRs in the fourth quartile were 1.337 (1.164-1.534), 1.428 (1.216-1.677), and 1.446 (1.267-1.651) for decline in eGFR category, >30% decline in eGFR, and increase in proteinuria, respectively. In addition, we separately added a single UHR measurement and cumUHR to the CKD base prediction model and the CKD progression base prediction model, and found that the models added cumUHR had the highest predictive value.ConclusionHigh cumUHR exposure was an independent risk factor for the incidence and progression of CKD, and it was a better predictor than a single UHR measurement.

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Longitudinal uric acid has nonlinear association with kidney failure and mortality in chronic kidney disease.

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Longitudinal uric acid has nonlinear association with kidney failure and mortality in chronic kidney disease.

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