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. 2023 Mar 9;13(1):3952.
doi: 10.1038/s41598-023-30902-7.

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

Mathilde Prezelin-Reydit  1   2   3 , Christian Combe  4   5 , Denis Fouque  6 , Luc Frimat  7   8 , Christian Jacquelinet  9   10 , Maurice Laville  11   12 , Ziad A Massy  9   13 , Céline Lange  9 , Carole Ayav  14 , Roberto Pecoits-Filho  15   16 , Sophie Liabeuf  9   17   18 , Bénédicte Stengel  9 , Jérôme Harambat  19   20   21 , Karen Leffondré  19   20 ; CKD-REIN study group
Collaborators, Affiliations

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

Mathilde Prezelin-Reydit et al. Sci Rep. .

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.

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Conflict of interest statement

CKD-REIN is supported by a public–private partnership with funding from seven pharmaceutical companies as listed above. The partners did not participate in this work nor in the writing of the manuscript. CKD-REIN is funded by the ‘Agence Nationale de la Recherche’ through the 2010 ‘Cohortes-Investissements d’Avenir’ programme and by the 2010 national ‘Programme Hospitalier de Recherche Clinique’. CKD-REIN is also supported through a public–private partnership with Amgen, Baxter, Fresenius Medical Care, GlaxoSmithKline (GSK), Merck Sharp & Dohme-Chibret (MSD France) since 2012, Lilly France since 2013, Otsuka Pharmaceutical since 2015 and Sanofi-Genzyme from 2012 to 2015. Inserm Transfert set up and has managed this partnership since 2011. The remaining authors do not have any conflict of interest to declare.

Figures

Figure 1
Figure 1
Included population, CKD-REIN, France, 2013–2018.
Figure 2
Figure 2
(A) Estimated effect of current uric acid value on the hazard of kidney failure in all patients (n = 2344 including 382 KRT, Model 1 in Table 3). (B) Estimated effect of baseline uric acid value on the hazard of kidney failure in all patients (n = 2344, Model 3 in Table 3). Results from cause-specific Cox models using a spline function for uric acid, adjusted for age, sex, primary kidney disease, hypertension, diabetes, cardiovascular disease, dyslipidemia, body mass index, albuminuria, medication adherence, use of renin-angiotensin system inhibitors and urate lowering therapy, all at baseline. The reference value of uric acid for the HR indicated in the y-axis was arbitrarily chosen at 5 mg/dl, which corresponds to the midpoint of the normal range of uric acid (uric acid in mg/dl to µmol/l: × 59.48). CKD-REIN cohort, France, 2013–2018.
Figure 3
Figure 3
Estimated effect of current uric acid value on the hazard of death before kidney failure, Panel (A) Estimated effect of current uric acid value on the hazard of death before kidney failure adjusted for age, sex, primary kidney disease, hypertension, diabetes, cardiovascular disease, dyslipidemia, body mass index, albuminuria, CKD stage, medication adherence, use of renin-angiotensin system inhibitors, urate lowering therapy, spironolactone and anti-platelet agents, all at baseline (Model 1 in Table 3); Panel (B) Estimated effect of baseline uric acid value on the hazard of death before kidney failure, adjusted for the same factors as in (A) (Model 3 in Table 3). The reference value of uric acid for the HR indicated in the y-axis was arbitrarily chosen at 5 mg/gl, which corresponds to the midpoint of the normal range of uric acid (uric acid in mg/dl to µmol/l: × 59.48). Results from cause-specific Cox models using a spline function for uric acid. CKD-REIN cohort, France, 2013–2018 (n = 2344, including 218 death before kidney failure).
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References

    1. Modification of Diet in Renal Disease Study Group, Hunsicker LG, Adler S, Caggiula A, England BK, Greene T, et al. Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study. Kidney Int.51(6), 1908–1919 (1997). - PubMed
    1. Sturm G, Kollerits B, Neyer U, Ritz E, Kronenberg F, MMKD Study Group. Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The mild to Moderate Kidney Disease (MMKD) Study. Exp. Gerontol.43(4), 347–352 (2008). - PubMed
    1. Madero M, Sarnak MJ, Wang X, Greene T, Beck GJ, Kusek JW, et al. Uric acid and long-term outcomes in CKD. Am. J. Kidney Dis. 2009;53(5):796–803. doi: 10.1053/j.ajkd.2008.12.021. - DOI - PMC - PubMed
    1. Liu WC, Hung CC, Chen SC, Yeh SM, Lin MY, Chiu YW, et al. Association of hyperuricemia with renal outcomes, cardiovascular disease, and mortality. Clin. J. Am. Soc. Nephrol. 2012;7(4):541–548. doi: 10.2215/CJN.09420911. - DOI - PubMed
    1. Nacak H, van Diepen M, Qureshi AR, Carrero JJ, Stijnen T, Dekker FW, et al. Uric acid is not associated with decline in renal function or time to renal replacement therapy initiation in a referred cohort of patients with Stage III, IV and V chronic kidney disease. Nephrol. Dial. Transpl. 2015;30(12):2039–2045. doi: 10.1093/ndt/gfv225. - DOI - PMC - PubMed

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