Skip to main content
Top
Published in: BMC Nephrology 1/2014

Open Access 01-12-2014 | Research article

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

Authors: Hakan Nacak, Merel van Diepen, Moniek CM de Goeij, Joris I Rotmans, Friedo W Dekker, the PREPARE-2 study group

Published in: BMC Nephrology | Issue 1/2014

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Zoccali C, Mallamaci F: Uric Acid, hypertension, and cardiovascular and renal complications. Curr Hypertens Rep. 2013, 15: 531-537.CrossRefPubMed Zoccali C, Mallamaci F: Uric Acid, hypertension, and cardiovascular and renal complications. Curr Hypertens Rep. 2013, 15: 531-537.CrossRefPubMed
2.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
3.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
4.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
5.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
6.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
7.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
8.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
9.
go back to reference 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.CrossRef 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.CrossRef
10.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
11.
go back to reference 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.CrossRef 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.CrossRef
12.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
13.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
14.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
16.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
17.
go back to reference 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.PubMed 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.PubMed
18.
go back to reference Dutch Federation of Nephrology: Multidisciplinary guidelines pre-dialysis. 2011 Dutch Federation of Nephrology: Multidisciplinary guidelines pre-dialysis. 2011
19.
go back to reference K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002, 39: S1-S266. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002, 39: S1-S266.
20.
go back to reference Section I: Measurement of renal function, when to refer and when to start dialysis. Nephrol Dial Transplant. 2002, 17 (Suppl 7): 7-15. Section I: Measurement of renal function, when to refer and when to start dialysis. Nephrol Dial Transplant. 2002, 17 (Suppl 7): 7-15.
21.
go back to reference Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, 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.CrossRefPubMedPubMedCentral Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, 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.CrossRefPubMedPubMedCentral
22.
go back to reference FitzMaurice GM: Laird NM. 2011, Hoboken, New Jersey: John Wiley & Sons, Inc FitzMaurice GM: Laird NM. 2011, Hoboken, New Jersey: John Wiley & Sons, Inc
23.
go back to reference Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958, 53 (282): 457-481.CrossRef Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958, 53 (282): 457-481.CrossRef
24.
go back to reference Cox DR: Regression models and life-tables. J Royal Stat Soc. 1972, 34 (2): 187-220. Series B (Methodological) Cox DR: Regression models and life-tables. J Royal Stat Soc. 1972, 34 (2): 187-220. Series B (Methodological)
25.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
26.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
27.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
28.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
29.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
30.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
31.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
32.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
33.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
34.
go back to reference John R, Webb M, Young A, Stevens PE: Unreferred chronic kidney disease: a longitudinal study. Am J Kidney Dis. 2004, 43: 825-835.CrossRefPubMed John R, Webb M, Young A, Stevens PE: Unreferred chronic kidney disease: a longitudinal study. Am J Kidney Dis. 2004, 43: 825-835.CrossRefPubMed
Metadata
Title
Uric acid: association with rate of renal function decline and time until start of dialysis in incident pre-dialysis patients
Authors
Hakan Nacak
Merel van Diepen
Moniek CM de Goeij
Joris I Rotmans
Friedo W Dekker
the PREPARE-2 study group
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2014
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/1471-2369-15-91

Other articles of this Issue 1/2014

BMC Nephrology 1/2014 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.