Uric acid: association with rate of renal function decline and time until start of dialysis in incident pre-dialysis patients

BMC Nephrology

Friedo W Dekker²  Joris I Rotmans¹  Moniek CM de Goeij²  Merel van Diepen²  Hakan Nacak² 

[1] Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands;Department of Clinical Epidemiology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands

关键词: Prospective cohort;    Pre-dialysis;    CKD progression;    Uric acid;   

Others  :  1082671
DOI  :  10.1186/1471-2369-15-91

 received in 2014-02-05, accepted in 2014-06-11,  发布年份 2014

【 摘 要 】

Background

In patients with chronic kidney disease (CKD) hyperuricemia is common. Evidence that hyperuricemia might also play a causal role in vascular disease, hypertension and progression of CKD is accumulating. Therefore, we studied the association between baseline uric acid (UA) levels and the rate of decline in renal function and time until start of dialysis in pre-dialysis patients.

Methods

Data from the PREPARE-2 study were used. The PREPARE-2 study is an observational prospective cohort study including incident pre-dialysis patients with CKD stages IV-V in the years between 2004 and 2011. Patients were followed for a median of 14.9 months until start of dialysis, kidney transplantation, death, or censoring. Main outcomes were the change in the rate of decline in renal function (measured as estimated glomerular filtration rate (eGFR)) estimated using linear mixed models, and time until start of dialysis estimated using Cox proportional hazards models.

Results

In this analysis 131 patients were included with a baseline UA level (mean (standard deviation (SD)) of 8.0 (1.79) mg/dl) and a mean decline in renal function of -1.61 (95% confidence interval (CI), -2.01; -1.22) ml/min/1.73 m²/year. The change in decline in GFR associated with a unit increase in UA at baseline was -0.14 (95% CI -0.61;0.33, p = 0.55) ml/min/1.73 m²/year. Adjusted for demography, comorbidities, diet, body mass index (BMI), blood pressure, lipids, proteinuria, diuretic and/or allopurinol usage the change in decline in eGFR did not change. The hazard ratio (HR) for starting dialysis for each mg/dl increase in UA at baseline was 1.08 (95% CI, 0.94;1.24, p = 0.27). After adjustment for the same confounders the HR became significant at 1.26 (95% CI, 1.06;1.49, p = 0.01), indicating an earlier start of dialysis with higher levels of UA.

Conclusion

Although high UA levels are not associated with an accelerated decline in renal function, a high serum UA level in incident pre-dialysis patient is a risk factor for an earlier start of dialysis.

【 授权许可】

   
2014 Nacak et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Zoccali C, Mallamaci F: Uric Acid, hypertension, and cardiovascular and renal complications. Curr Hypertens Rep 2013, 15:531-537.
• [2]Bose B, Badve SV, Hiremath SS, Boudville N, Brown FG, Cass A, de Zoysa JR, Fassett RG, Faull R, Harris DC, Hawley CM, Kanellis J, Palmer SC, Perkovic V, Pascoe EM, Rangan GK, Walker RJ, Walters G, Johnson DW: Effects of uric acid-lowering therapy on renal outcomes: a systematic review and meta-analysis. Nephrol Dial Transplant 2014, 29:406-413.
• [3]Tomita M, Mizuno S, Yamanaka H, Hosoda Y, Sakuma K, Matuoka Y, Odaka M, Yamaguchi M, Yosida H, Morisawa H, Murayama T: Does hyperuricemia affect mortality? A prospective cohort study of Japanese male workers. J Epidemiol 2000, 10:403-409.
• [4]Iseki K, Ikemiya Y, Inoue T, Iseki C, Kinjo K, Takishita S: Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis 2004, 44:642-650.
• [5]Sonoda H, Takase H, Dohi Y, Kimura G: Uric acid levels predict future development of chronic kidney disease. Am J Nephrol 2011, 33:352-357.
• [6]Zoppini G, Targher G, Chonchol M, Ortalda V, Abaterusso C, Pichiri I, Negri C, Bonora E: Serum uric acid levels and incident chronic kidney disease in patients with type 2 diabetes and preserved kidney function. Diabetes Care 2012, 35:99-104.
• [7]Siu YP, Leung KT, Tong MK, Kwan TH: Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis 2006, 47:51-59.
• [8]Kanbay M, Ozkara A, Selcoki Y, Isik B, Turgut F, Bavbek N, Uz E, Akcay A, Yigitoglu R, Covic A: Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearence, and proteinuria in patients with normal renal functions. Int Urol Nephrol 2007, 39:1227-1233.
• [9]Grayson PC, Kim SY, LaValley M, Choi HK: Hyperuricemia and incident hypertension: a systematic review and meta-analysis. Arthritis Care Res (Hoboken) 2011, 63:102-110.
• [10]Feig DI, Soletsky B, Johnson RJ: Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. JAMA 2008, 300:924-932.
• [11]Agarwal V, Hans N, Messerli FH: Effect of allopurinol on blood pressure: a systematic review and meta-analysis. J Clin Hypertens (Greenwich) 2013, 15:435-442.
• [12]Bellomo G, Venanzi S, Verdura C, Saronio P, Esposito A, Timio M: Association of uric acid with change in kidney function in healthy normotensive individuals. Am J Kidney Dis 2010, 56:264-272.
• [13]Obermayr RP, Temml C, Gutjahr G, Knechtelsdorfer M, Oberbauer R, Klauser-Braun R: Elevated uric acid increases the risk for kidney disease. J Am Soc Nephrol 2008, 19:2407-2413.
• [14]Kuo CF, Luo SF, See LC, Ko YS, Chen YM, Hwang JS, Chou IJ, Chang HC, Chen HW, Yu KH: Hyperuricaemia and accelerated reduction in renal function. Scand J Rheumatol 2011, 40:116-121.
• [15]Zhang L, Wang F, Wang X, Liu L, Wang H: The association between plasma uric acid and renal function decline in a Chinese population-based cohort. Nephrol Dial Transplant 2012, 27:1836-1839.
• [16]Park JT, Kim DK, Chang TI, Kim HW, Chang JH, Park SY, Kim E, Kang SW, Han DS, Yoo TH: Uric acid is associated with the rate of residual renal function decline in peritoneal dialysis patients. Nephrol Dial Transplant 2009, 24:3520-3525.
• [17]Tattersall J, Martin-Malo A, Pedrini L, Basci A, Canaud B, Fouque D, Haage P, Konner K, Kooman J, Pizzarelli F, Tordoir J, Vennegoor M, Wanner C, ter Wee P, Vanholder R: EBPG guideline on dialysis strategies. Nephrol Dial Transplant 2007, 22(Suppl 2):ii5-ii21.
• [18]Dutch Federation of Nephrology: Multidisciplinary guidelines pre-dialysis. 2011.
• [19]K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification Am J Kidney Dis 2002, 39:S1-S266.
• [20]Section I: Measurement of renal function, when to refer and when to start dialysis. Nephrol Dial Transplant 2002, 17(Suppl 7):7-15.
• [21]Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF III, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J: A new equation to estimate glomerular filtration rate. Ann Intern Med 2009, 150:604-612.
• [22]FitzMaurice GM: Laird NM. Hoboken, New Jersey: John Wiley & Sons, Inc; 2011.
• [23]Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958, 53(282):457-481.
• [24]Cox DR: Regression models and life-tables. J Royal Stat Soc 1972, 34(2):187-220. Series B (Methodological)
• [25]de Goeij MC, Van DM, Jager KJ, Tripepi G, Zoccali C, Dekker FW: Multiple imputation: dealing with missing data. Nephrol Dial Transplant 2013, 28(2):2415-2420.
• [26]Sanchez-Lozada LG, Tapia E, Santamaria J, Avila-Casado C, Soto V, Nepomuceno T, Rodriguez-Iturbe B, Johnson RJ, Herrera-Acosta J: Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int 2005, 67:237-247.
• [27]Sanchez-Lozada LG, Tapia E, Lopez-Molina R, Nepomuceno T, Soto V, Avila-Casado C, Nakagawa T, Johnson RJ, Herrera-Acosta J, Franco M: Effects of acute and chronic L-arginine treatment in experimental hyperuricemia. Am J Physiol Renal Physiol 2007, 292:F1238-F1244.
• [28]Sanchez-Lozada LG, Soto V, Tapia E, Avila-Casado C, Sautin YY, Nakagawa T, Franco M, Rodriguez-Iturbe B, Johnson RJ: Role of oxidative stress in the renal abnormalities induced by experimental hyperuricemia. Am J Physiol Renal Physiol 2008, 295:F1134-F1141.
• [29]Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL, Lan HY, Kivlighn S, Johnson RJ: Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension 2001, 38:1101-1106.
• [30]Nakagawa T, Mazzali M, Kang DH, Kanellis J, Watanabe S, Sanchez-Lozada LG, Rodriguez-Iturbe B, Herrera-Acosta J, Johnson RJ: Hyperuricemia causes glomerular hypertrophy in the rat. Am J Nephrol 2003, 23:2-7.
• [31]Weiner DE, Tighiouart H, Elsayed EF, Griffith JL, Salem DN, Levey AS: Uric acid and incident kidney disease in the community. J Am Soc Nephrol 2008, 19:1204-1211.
• [32]Sturm G, Kollerits B, Neyer U, Ritz E, Kronenberg F: Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The Mild to Moderate Kidney Disease (MMKD) Study. Exp Gerontol 2008, 43:347-352.
• [33]Madero M, Sarnak MJ, Wang X, Greene T, Beck GJ, Kusek JW, Collins AJ, Levey AS, Menon V: Uric acid and long-term outcomes in CKD. Am J Kidney Dis 2009, 53:796-803.
• [34]John R, Webb M, Young A, Stevens PE: Unreferred chronic kidney disease: a longitudinal study. Am J Kidney Dis 2004, 43:825-835.