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Erschienen in: Pediatric Nephrology 8/2018

16.03.2018 | Original Article

Effect of allopurinol on the glomerular filtration rate of children with chronic kidney disease

verfasst von: Fatemeh Ghane Sharbaf, Farahnak Assadi

Erschienen in: Pediatric Nephrology | Ausgabe 8/2018

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Abstract

Background

Hyperuricemia is a leading risk factor for the development of chronic kidney disease (CKD). We hypothesized that lowering serum uric acid (SUA) with allopurinol in hyperuricemic children with CKD may reduce the risk of CKD progression.

Methods

A total of 70 children, aged 3–15 years, with elevated serum uric acid level (SUA) > 5.5 mg/dL and CKD stages 1–3 were prospectively randomized to receive allopurinol 5 mg/kg/day (study group, n = 38) or no treatment (control group, n = 32) for 4 months. The primary and secondary outcomes were changes in estimated glomerular filtration rate (eGFR) (> 10 mL/min/1.73m2) and the SUA (> 1.0 mg/dL) from baseline values, respectively.

Results

Baseline age, gender, blood pressure (BP), body mass index (BMI), SUA, high-sensitive C-reactive protein (hsCRP), and eGFR were similar in allopurinol and control subjects. Allopurinol treatment resulted in a decrease in SUA, a decrease in systolic and diastolic BP, a decrease in hsCRP, and an increase in eGFR compared with the baseline values (p < 0.05 for all). No significant difference was observed in the control hyperuricemic subjects. In multiple regression analysis after incorporating variables (age, gender, BMI, systolic and diastolic BP, CRP, and SUA), eGFR was independently related to SUA both before and after treatments (p = 0.03 vs. p = 0.02, respectively). All patients in the study group tolerated allopurinol, and there were no adverse reactions observed by physical examination or reported by patients.

Conclusion

Urate-lowering therapy with allopurinol, over a 4-month period, can improve renal function in children with CKD stages 1–3.
Literatur
1.
Zurück zum Zitat Levey AS, Atkins R, Coresh J, Cohen EP, Collins AJ, Ekardt KU, Nahas ME, Jaber BL, Jadoul M, Levin A, Powe NR, Rossert J, Wheeler DC, Lameire N, Eknoyan G (2007) Chronic kidney disease as a global public health problem: approaches and initiatives—a position statement from kidney disease improving global outcomes. Kidney Int 72(3):247–259CrossRefPubMed Levey AS, Atkins R, Coresh J, Cohen EP, Collins AJ, Ekardt KU, Nahas ME, Jaber BL, Jadoul M, Levin A, Powe NR, Rossert J, Wheeler DC, Lameire N, Eknoyan G (2007) Chronic kidney disease as a global public health problem: approaches and initiatives—a position statement from kidney disease improving global outcomes. Kidney Int 72(3):247–259CrossRefPubMed
2.
Zurück zum Zitat Kuwabara M, Bjornstad P, Hisatome I, Niwa K, Roncal-Jimenez CA, Andres-Hemando A (2017) Elevated serum uric acid level predicts rapid decline in kidney function. Am J Nephrol 45:330–337CrossRefPubMedPubMedCentral Kuwabara M, Bjornstad P, Hisatome I, Niwa K, Roncal-Jimenez CA, Andres-Hemando A (2017) Elevated serum uric acid level predicts rapid decline in kidney function. Am J Nephrol 45:330–337CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Wu AH, Gladden JD, Ahmed M, Ahmed A, Filippatos G (2016) Relation of serum uric acid to cardiovascular disease. Int J Cardiol 213:4–7CrossRefPubMed Wu AH, Gladden JD, Ahmed M, Ahmed A, Filippatos G (2016) Relation of serum uric acid to cardiovascular disease. Int J Cardiol 213:4–7CrossRefPubMed
4.
Zurück zum Zitat Kuwabara M (2016) Hyperuricemia, cardiovascular disease, and hypertension. Pulse (Basel) 3:242–252CrossRef Kuwabara M (2016) Hyperuricemia, cardiovascular disease, and hypertension. Pulse (Basel) 3:242–252CrossRef
5.
Zurück zum Zitat Hisatome I, Kuwabara M (2016) Hyperuricemia plays pivotal role in progression of kidney disease. Circ J 80:1710–1711CrossRefPubMed Hisatome I, Kuwabara M (2016) Hyperuricemia plays pivotal role in progression of kidney disease. Circ J 80:1710–1711CrossRefPubMed
6.
Zurück zum Zitat Rodenbach KE, Schneider MF, Furth SL, Moxey-Mims MM, Mitsnefes MM, Weaver DI, Weaver DJ, Warady BA, Schwartz GJ (2015) Hyperuricemia and progression of CKD in children and adolescents: the Chronic Kidney Disease in Children (CKiD) Cohort Study. Am J Kidney Dis 66:984–992CrossRefPubMedPubMedCentral Rodenbach KE, Schneider MF, Furth SL, Moxey-Mims MM, Mitsnefes MM, Weaver DI, Weaver DJ, Warady BA, Schwartz GJ (2015) Hyperuricemia and progression of CKD in children and adolescents: the Chronic Kidney Disease in Children (CKiD) Cohort Study. Am J Kidney Dis 66:984–992CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Assadi F (2014) Allopurinol enhances the blood pressure lowering effect of enalepril in children with hyperuricemic essential hypertension. J Nephrol 27:51–56CrossRefPubMed Assadi F (2014) Allopurinol enhances the blood pressure lowering effect of enalepril in children with hyperuricemic essential hypertension. J Nephrol 27:51–56CrossRefPubMed
8.
Zurück zum Zitat Feig DI, Soleteky B, Johnson RJ (2008) Effect of allopurinol on the blood pressure of adolescents with newly diagnosed essential hypertension. JAMA 300:922–930CrossRef Feig DI, Soleteky B, Johnson RJ (2008) Effect of allopurinol on the blood pressure of adolescents with newly diagnosed essential hypertension. JAMA 300:922–930CrossRef
9.
Zurück zum Zitat Goicoechea M, de Vinuesa SG, Verdalles U, Ruiz-Caro C, Ampuero J, Rincon A, Arroyo D, Luño J (2010) Effect of allopurinol in chronic kidney disease progression of renal disease and cardiovascular risk. Clin J Am Soc Nephrol 5:1388–1393CrossRefPubMedPubMedCentral Goicoechea M, de Vinuesa SG, Verdalles U, Ruiz-Caro C, Ampuero J, Rincon A, Arroyo D, Luño J (2010) Effect of allopurinol in chronic kidney disease progression of renal disease and cardiovascular risk. Clin J Am Soc Nephrol 5:1388–1393CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Siu YP, Leung KT, Tong MK, Kwan TH (2006) Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis 47:51–59CrossRefPubMed Siu YP, Leung KT, Tong MK, Kwan TH (2006) Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis 47:51–59CrossRefPubMed
11.
Zurück zum Zitat Mercuro G, Vitale C, Cerquetani E, Zoncu S, Deidda M, Fini M, Rosano GM (2004) Effect of hyperuricemia upon endothelial function in patients at increased cardiovascular risk. Am J Cardiol 94:932–935CrossRefPubMed Mercuro G, Vitale C, Cerquetani E, Zoncu S, Deidda M, Fini M, Rosano GM (2004) Effect of hyperuricemia upon endothelial function in patients at increased cardiovascular risk. Am J Cardiol 94:932–935CrossRefPubMed
12.
Zurück zum Zitat Toyama T, Furuichi K, Shimizu M, Hara A, Iwata Y, Sakai N, Perkovic V, Kobayashi M, Mano T, Kaneko S, Wada T (2015) Relationship between serum uric acid levels and chronic kidney disease in a Japanese cohort with normal or mildly reduced kidney function. PLoS One 10:e0137449CrossRefPubMedPubMedCentral Toyama T, Furuichi K, Shimizu M, Hara A, Iwata Y, Sakai N, Perkovic V, Kobayashi M, Mano T, Kaneko S, Wada T (2015) Relationship between serum uric acid levels and chronic kidney disease in a Japanese cohort with normal or mildly reduced kidney function. PLoS One 10:e0137449CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Zhu P, Liu Y, Han L, Xu G, Ran JM (2014) Serum uric acid is associated with incident chronic kidney disease in the middle-aged populations: a meta-analysis of 15 cohort studies. PLoS One 9:e100801CrossRefPubMedPubMedCentral Zhu P, Liu Y, Han L, Xu G, Ran JM (2014) Serum uric acid is associated with incident chronic kidney disease in the middle-aged populations: a meta-analysis of 15 cohort studies. PLoS One 9:e100801CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Crom WR, Webster SL, Bobo L, Teresi ME, Relling MV, Evans WE (1987) Simultaneous administration of multiple model substrates to assess hepatic drug clearance. Clin Pharmacol Ther 41:645–650CrossRefPubMed Crom WR, Webster SL, Bobo L, Teresi ME, Relling MV, Evans WE (1987) Simultaneous administration of multiple model substrates to assess hepatic drug clearance. Clin Pharmacol Ther 41:645–650CrossRefPubMed
15.
Zurück zum Zitat Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, de Ferranti SD, Dionne JM, Falkner B, Flinn SK, Gidding SS, Goodwin C, Leu MG, Powers ME, Rea C, Samuels J, Simasek M, Thaker VV, Urbina EM, Subcommittee on Screening and Management of High Blood Pressure in Children (2017) Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics e20171904:140 Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, de Ferranti SD, Dionne JM, Falkner B, Flinn SK, Gidding SS, Goodwin C, Leu MG, Powers ME, Rea C, Samuels J, Simasek M, Thaker VV, Urbina EM, Subcommittee on Screening and Management of High Blood Pressure in Children (2017) Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics e20171904:140
16.
Zurück zum Zitat Inker LA, Astor BC, Fox CH, Isakova T, Lash JP, Peralta CA, Kurella Tamura M, Feldman HI (2014) KDOQI US commentary on the 2012 clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis 63:713–735CrossRefPubMed Inker LA, Astor BC, Fox CH, Isakova T, Lash JP, Peralta CA, Kurella Tamura M, Feldman HI (2014) KDOQI US commentary on the 2012 clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis 63:713–735CrossRefPubMed
17.
Zurück zum Zitat Schwatz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRef Schwatz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRef
18.
Zurück zum Zitat De Souza CV, Rabilloud M, Cochat P, Seilstre L, Hadi-Aissa A, Kassai B, Ranchin B, Berg U, Herthelius M, Dubourg L (2012) Schwatz formula: is one k-coefficient adequate for all children? PLoS One 7:e53439CrossRefPubMedPubMedCentral De Souza CV, Rabilloud M, Cochat P, Seilstre L, Hadi-Aissa A, Kassai B, Ranchin B, Berg U, Herthelius M, Dubourg L (2012) Schwatz formula: is one k-coefficient adequate for all children? PLoS One 7:e53439CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Ogden CL, Kuczmarski RJ, Flegal KM, Mei Z, Guo S, Wei R, Grummer-Strawn LM, Curtin LR, Roche AF, Johnson CL (2000) lefts for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National left for Health Statistics version. Pediatrics 109:45–60CrossRef Ogden CL, Kuczmarski RJ, Flegal KM, Mei Z, Guo S, Wei R, Grummer-Strawn LM, Curtin LR, Roche AF, Johnson CL (2000) lefts for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National left for Health Statistics version. Pediatrics 109:45–60CrossRef
20.
21.
Zurück zum Zitat Bellamo G, Venanzi S, Verdura C, Saronio P, Esposito A, Timio M (2010) Association of uric acid with changes in kidney function in healthy normotensive individuals. Am J Kidney Dis 56:264–272CrossRef Bellamo G, Venanzi S, Verdura C, Saronio P, Esposito A, Timio M (2010) Association of uric acid with changes in kidney function in healthy normotensive individuals. Am J Kidney Dis 56:264–272CrossRef
22.
Zurück zum Zitat Leski K, Ikemiya Y, Inoue T, Leski C, Kinjo K, Takishita S (2004) Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis 44:642–650CrossRef Leski K, Ikemiya Y, Inoue T, Leski C, Kinjo K, Takishita S (2004) Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis 44:642–650CrossRef
23.
Zurück zum Zitat Weiner DE, Tighiouart H, Elsayed EF, Griffith JL, Salem DN, Levey AS (2008) Uric acid and incident kidney disease in the community. J Am Soc Nephrol 19:1204–1211CrossRefPubMedPubMedCentral Weiner DE, Tighiouart H, Elsayed EF, Griffith JL, Salem DN, Levey AS (2008) Uric acid and incident kidney disease in the community. J Am Soc Nephrol 19:1204–1211CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Kanaby M, Ozkara A, Selcoki Y, Lsik B, Turgut F, Bavbek N, Uz E, Akcay A, Yigitoglu R, Covic A (2007) Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearance, and proteinuria in patients with normal renal function. Int Urol Nephrol 39:1227–1233CrossRef Kanaby M, Ozkara A, Selcoki Y, Lsik B, Turgut F, Bavbek N, Uz E, Akcay A, Yigitoglu R, Covic A (2007) Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearance, and proteinuria in patients with normal renal function. Int Urol Nephrol 39:1227–1233CrossRef
25.
Zurück zum Zitat Assadi F (2007) C-reactive protein and incident left ventricular hypertrophy in essential hypertension. Pediatr Cardiol 28:280–285CrossRefPubMed Assadi F (2007) C-reactive protein and incident left ventricular hypertrophy in essential hypertension. Pediatr Cardiol 28:280–285CrossRefPubMed
26.
Zurück zum Zitat Kanbay MK, Huddam B, Azak A, Solak Y, Kadioglu GK, Kirbas I, Duranay M, Covic A, Johnson RJ (2011) Randomized study of allopurinol on endothelial function and estimated glomerular filtration rate in asymptomatic hyperuricemic subjects with normal renal function. Clin J Am Soc Nephrol:1887–1894 Kanbay MK, Huddam B, Azak A, Solak Y, Kadioglu GK, Kirbas I, Duranay M, Covic A, Johnson RJ (2011) Randomized study of allopurinol on endothelial function and estimated glomerular filtration rate in asymptomatic hyperuricemic subjects with normal renal function. Clin J Am Soc Nephrol:1887–1894
27.
28.
Zurück zum Zitat Sanchez-Lozada LG, Soto V, Tapia E, Avila-Casado C, Sautin YY, Nakagawa T, Franco M, Rodríguez-Iturbe B, Johnson RJ (2008) Role of oxidative stress in the renal abnormalities induced by experimental hyperuricemia. Am J Physiol Renal Physiol 295:F1134–F1141CrossRefPubMedPubMedCentral Sanchez-Lozada LG, Soto V, Tapia E, Avila-Casado C, Sautin YY, Nakagawa T, Franco M, Rodríguez-Iturbe B, Johnson RJ (2008) Role of oxidative stress in the renal abnormalities induced by experimental hyperuricemia. Am J Physiol Renal Physiol 295:F1134–F1141CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Yu MA, Sanchez-Lozada LG, Johnson RJ, Kang DH (2010) Oxidative stress with activation of the renin-angiotensin system in human vascular endothelial cells as a novel mechanism of uric acid-induced endothelial dysfunction. J Hypertens 28:1234–1242PubMed Yu MA, Sanchez-Lozada LG, Johnson RJ, Kang DH (2010) Oxidative stress with activation of the renin-angiotensin system in human vascular endothelial cells as a novel mechanism of uric acid-induced endothelial dysfunction. J Hypertens 28:1234–1242PubMed
30.
Zurück zum Zitat Sanchez-Lozada LG, Tapia E, Santamaria J, Avila-Casado C, Soto V, Nepomuceno T, Rodríguez-Iturbe B, Johnson RJ, Herrera-Acosta J (2005) Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int 67:237–247CrossRefPubMed Sanchez-Lozada LG, Tapia E, Santamaria J, Avila-Casado C, Soto V, Nepomuceno T, Rodríguez-Iturbe B, Johnson RJ, Herrera-Acosta J (2005) Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int 67:237–247CrossRefPubMed
31.
Zurück zum Zitat Uedono H, Tsuda A, Ishimura E, Yasumoto M, Ichii M, Ochi A, Ohno Y, Nakatani S, Mori K, Uchida J, Nakatani T, Inaba M (2015) Relationships between serum uric acid levels and intrarenal hemodynamic parameters. Kidney Blood Press Re 40:315–322CrossRef Uedono H, Tsuda A, Ishimura E, Yasumoto M, Ichii M, Ochi A, Ohno Y, Nakatani S, Mori K, Uchida J, Nakatani T, Inaba M (2015) Relationships between serum uric acid levels and intrarenal hemodynamic parameters. Kidney Blood Press Re 40:315–322CrossRef
32.
Zurück zum Zitat Corry DB, Eslami P, Yamamoto K, Nyby MD, Makino H, Tuck ML (2008) Uric acid stimulates vascular smooth cell proliferation and oxidative stress via the vascular renin-angiotensin system. Hypertension 26:269–275CrossRef Corry DB, Eslami P, Yamamoto K, Nyby MD, Makino H, Tuck ML (2008) Uric acid stimulates vascular smooth cell proliferation and oxidative stress via the vascular renin-angiotensin system. Hypertension 26:269–275CrossRef
33.
Zurück zum Zitat Jalad DI, Chonchol M, Chen McInnes GT, Lawson DH, Jick H (1981) Acute adverse reactions attributed to allopurinol in hospitalized patients. Ann Rheum Dis 40:245–249CrossRef Jalad DI, Chonchol M, Chen McInnes GT, Lawson DH, Jick H (1981) Acute adverse reactions attributed to allopurinol in hospitalized patients. Ann Rheum Dis 40:245–249CrossRef
Metadaten
Titel
Effect of allopurinol on the glomerular filtration rate of children with chronic kidney disease
verfasst von
Fatemeh Ghane Sharbaf
Farahnak Assadi
Publikationsdatum
16.03.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 8/2018
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-018-3943-1

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