Skip to main content

Advertisement

SpringerLink
Log in

Uric Acid Lowering to Prevent Kidney Function Loss in Diabetes: The Preventing Early Renal Function Loss (PERL) Allopurinol Study

  • Microvascular Complications-Nephropathy (B Roshan, Section Editor)
  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Diabetic kidney disease causes significant morbidity and mortality among people with type 1 diabetes (T1D). Intensive glucose and blood pressure control have thus far failed to adequately curb this problem and therefore a major need for novel treatment approaches exists. Multiple observations link serum uric acid levels to kidney disease development and progression in diabetes and strongly argue that uric acid lowering should be tested as one such novel intervention. A pilot of such a trial, using allopurinol, is currently being conducted by the Preventing Early Renal Function Loss (PERL) Consortium. Although the PERL trial targets T1D individuals at highest risk of kidney function decline, the use of allopurinol as a renoprotective agent may also be relevant to a larger segment of the population with diabetes. As allopurinol is inexpensive and safe, it could be cost-effective even for relatively low-risk patients, pending the completion of appropriate trials at earlier stages.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Marshall SM. Diabetic nephropathy in type 1 diabetes: has the outlook improved since the 1980s? Diabetologia. 2012;55:2301–6.

    Article  PubMed  CAS  Google Scholar 

  2. Nathan DM, Zinman B, Cleary PA, et al. Modern-day clinical course of type 1 diabetes mellitus after 30 years’ duration: the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983-2005). Arch Intern Med. 2009;169:1307–16.

    Article  PubMed  Google Scholar 

  3. • Krolewski AS, Bonventre JV. High risk of ESRD in type 1 diabetes: new strategies are needed to retard progressive renal function decline. Semin Nephrol. 2012;32:407–14. Review highlighting the need for new strategies and novel therapeutics to prevent renal function decline.

    Article  PubMed  Google Scholar 

  4. Maahs DM, Rewers M. Editorial: mortality and renal disease in type 1 diabetes mellitus—progress made, more to be done. J Clin Endocrinol Metab. 2006;91:3757–9.

    Article  PubMed  Google Scholar 

  5. • de Boer I, Rue TC, Hall YN, Heagerty PJ, Weiss NS, Himmelfarb J. Temporal trends in the prevalence of diabetic kidney disease in the United States. JAMA. 2011;305:2532–9. Overview of prevalence of DKD in the US and demonstrates continued burden of diabetic kidney disease on individuals and its public health importance.

    Article  PubMed  Google Scholar 

  6. • Rosolowsky ET, Skupien J, Smiles AM, et al. Risk for ESRD in type 1 diabetes remains high despite renoprotection. J Am Soc Nephrol. 2011;22:545–53. Demonstrates persistence of ESRD risk despite advances in diabetes care in past decades.

    Article  PubMed  CAS  Google Scholar 

  7. •• Jalal DI, Rivard CJ, Johnson RJ, et al. Serum uric acid levels predict the development of albuminuria over 6 years in patients with type 1 diabetes: findings from the Coronary Artery Calcification in Type 1 Diabetes. Study. Nephrol Dial Transplant. 2010;25:1865–9. One of 3 epidemiologic studies from the PERL Consortium in which uric acid is associated with development of albuminuria over 6 years in young adults with type 1 diabetes.

    Article  PubMed  CAS  Google Scholar 

  8. •• Hovind P, Rossing P, Tarnow L, Johnson RJ, Parving HH. Serum uric acid as a predictor for development of diabetic nephropathy in type 1 diabetes: an inception cohort study. Diabetes. 2009;58:1668–71. One of 3 epidemiologic studies from the PERL Consortium in which uric acid is associated with development of diabetic nephropathy over 18 years in an inception cohort of adults with type 1 diabetes.

    Article  PubMed  CAS  Google Scholar 

  9. •• Ficociello LH, Rosolowsky ET, Niewczas MA, et al. High-normal serum uric acid increases risk of early progressive renal function loss in type 1 diabetes: results of a 6-year follow-up. Diabetes Care. 2010;33:1337–43. One of 3 epidemiologic studies from the PERL Consortium in which uric acid is associated with progressive renal function loss over 6 years in adults with type 1 diabetes.

    Article  PubMed  CAS  Google Scholar 

  10. Kang DH, Nakagawa T, Feng L, et al. A role for uric acid in the progression of renal disease. J Am Soc Nephrol. 2002;13:2888–97.

    Article  PubMed  CAS  Google Scholar 

  11. Mazzali M, Hughes J, Kim YG, et al. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension. 2001;38:1101–6.

    Article  PubMed  CAS  Google Scholar 

  12. Johnson RJ, Segal MS, Srinivas T, et al. Essential hypertension, progressive renal disease, and uric acid: a pathogenetic link? J Am Soc Nephrol. 2005;16:1909–19.

    Article  PubMed  CAS  Google Scholar 

  13. Mazzali M, Kanellis J, Han L, et al. Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism. Am J Physiol Ren Physiol. 2002;282:F991–7.

    CAS  Google Scholar 

  14. Desco MC, Asensi M, Marquez R, et al. Xanthine oxidase is involved in free radical production in type 1 diabetes: protection by allopurinol. Diabetes. 2002;51:1118–24.

    Article  PubMed  CAS  Google Scholar 

  15. Pacher P, Nivorozhkin A, Szabo C. Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev. 2006;58:87–114.

    Article  PubMed  CAS  Google Scholar 

  16. 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;47:51–9.

    Article  PubMed  CAS  Google Scholar 

  17. • Goicoechea M, de Vinuesa SG, Verdalles U, et al. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol. 2010;5:1388–93. Clinical trial using allopurinol to lower uric acid to slow kidney and cardiovascular disease progression.

    Article  PubMed  CAS  Google Scholar 

  18. Krolewski AS, Warram JH. Epidemiology of late complications of diabetes: a basis for the development and evaluation of preventive program. In: Kahn CR, Weir GC, King GL, Jacobson AM, Moses AC, Smith RJ, editors. Joslin’s diabetes mellitus. New York: Lippincott, Williams & Wilkins; 2005.

    Google Scholar 

  19. • Groop PH, Thomas MC, Moran JL, et al. The presence and severity of chronic kidney disease predicts all-cause mortality in type 1 diabetes. Diabetes. 2009;58:1651–8. Large epidemiologic cohort study from Finland in which people with type 1 diabetes without evidence of diabetic kidney disease have similar standardized mortality rates compared with the general Finnish population.

    Article  PubMed  CAS  Google Scholar 

  20. • Orchard TJ, Secrest AM, Miller RG, Costacou T. In the absence of renal disease, 20 year mortality risk in type 1 diabetes is comparable to that of the general population: a report from the Pittsburgh Epidemiology of Diabetes. Complications Study. Diabetologia. 2010;53:2312–9. Extends the findings from the FinnDiane study [19] over 20 years in a US cohort with type 1 diabetes.

    Article  PubMed  CAS  Google Scholar 

  21. •• de Boer I, Sun W, Cleary PA, et al. Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. N Engl J Med. 2011;365:2366–76. Demonstrates that intensive diabetes therapy reduces the risk to develop GFR <60 mL/min/1.73 m 2 in the DCCT-EDIC study.

    Article  PubMed  Google Scholar 

  22. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993;329:1456–62.

    Article  PubMed  CAS  Google Scholar 

  23. Hoerger TJ, Segel JE, Gregg EW, Saaddine JB. Is glycemic control improving in U.S. adults? Diabetes Care. 2008;31:81–6.

    Article  PubMed  Google Scholar 

  24. Wood J, Miller K, Maahs D, et al. Most youth with type 1 diabetes in the T1D exchange clinic registry do not meet ADA or ISPAD clinical guidelines. Diabetes Care. (in press).

  25. Mauer M, Zinman B, Gardiner R, et al. Renal and retinal effects of enalapril and losartan in type 1 diabetes. N Engl J Med. 2009;361:40–51.

    Article  PubMed  CAS  Google Scholar 

  26. Bilous R, Chaturvedi N, Sjolie AK, et al. Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials. Ann Intern Med. 2009;151:11–4.

    Article  PubMed  Google Scholar 

  27. Mathiesen ER, Hommel E, Giese J, Parving HH. Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria. BMJ. 1991;303:81–7.

    Article  PubMed  CAS  Google Scholar 

  28. •• Parving HH, Brenner BM, McMurray JJ, et al. Cardiorenal end points in a trial of Aliskiren for Type 2 Diabetes. N Engl J Med. 2012. In Press. Recent clinical trial highlighting the need for novel therapeutics to improve cardiorenal health in people with diabetes.

  29. Mancia G, Schumacher H, Redon J, et al. Blood pressure targets recommended by guidelines and incidence of cardiovascular and renal events in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET). Circulation. 2011;124:1727–36.

    Article  PubMed  Google Scholar 

  30. • Rodrigues TC, Maahs DM, Johnson RJ, et al. Serum uric acid predicts progression of subclinical coronary atherosclerosis in individuals without renal disease. Diabetes Care. 2010;33:2471–3. Epidemiologic study in which uric acid is associated with progression of subclinical coronary atherosclerosis in young adults with type 1 diabetes.

    Article  PubMed  CAS  Google Scholar 

  31. Libman IM, Pietropaolo M, Arslanian SA, LaPorte RE, Becker DJ. Changing prevalence of overweight children and adolescents at onset of insulin-treated diabetes. Diabetes Care. 2003;26:2871–5.

    Article  PubMed  Google Scholar 

  32. McGill M, Molyneaux L, Twigg SM, Yue DK. The metabolic syndrome in type 1 diabetes: does it exist and does it matter? J Diabetes Complications. 2008;22:18–23.

    Article  PubMed  Google Scholar 

  33. Thorn LM, Forsblom C, Fagerudd J, et al. Metabolic syndrome in type 1 diabetes: association with diabetic nephropathy and glycemic control (the FinnDiane study). Diabetes Care. 2005;28:2019–24.

    Article  PubMed  Google Scholar 

  34. Tsouli SG, Liberopoulos EN, Mikhailidis DP, Athyros VG, Elisaf MS. Elevated serum uric acid levels in metabolic syndrome: an active component or an innocent bystander? Metabolism. 2006;55:1293–301.

    Article  PubMed  CAS  Google Scholar 

  35. Godsland IF, Johnston DG. Co-associations between insulin sensitivity and measures of liver function, subclinical inflammation, and hematology. Metabolism. 2008;57:1190–7.

    Article  PubMed  CAS  Google Scholar 

  36. Cirillo P, Sato W, Reungjui S, et al. Uric acid, the metabolic syndrome, and renal disease. J Am Soc Nephrol. 2006;17(12 Suppl 3):S165–8.

    Article  PubMed  CAS  Google Scholar 

  37. Jalal DI, Maahs DM, Hovind P, Nakagawa T. Uric acid as a mediator of diabetic nephropathy. Semin Nephrol. 2011;31:459–65.

    Article  PubMed  CAS  Google Scholar 

  38. Edwards NL. The role of hyperuricemia and gout in kidney and cardiovascular disease. Cleve Clin J Med. 2008;75 Suppl 5:S13–6.

    Article  PubMed  Google Scholar 

  39. Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med. 2008;359:1811–21.

    Article  PubMed  CAS  Google Scholar 

  40. Zoppini G, Targher G, Chonchol M, et al. 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.

    Article  PubMed  CAS  Google Scholar 

  41. • Miao Y, Ottenbros SA, Laverman GD, et al. Effect of a reduction in uric acid on renal outcomes during losartan treatment: a post hoc analysis of the reduction of endpoints in non-insulin-dependent diabetes mellitus with the Angiotensin II Antagonist Losartan Trial. Hypertension. 2011;58:2–7. Post-hoc analysis suggesting losartan lowers uric acid as a mechanism of improving renal outcomes.

    Article  PubMed  CAS  Google Scholar 

  42. 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;44:642–50.

    PubMed  Google Scholar 

  43. Domrongkitchaiporn S, Sritara P, Kitiyakara C, et al. Risk factors for development of decreased kidney function in a southeast Asian population: a 12-year cohort study. J Am Soc Nephrol. 2005;16:791–9.

    Article  PubMed  Google Scholar 

  44. Zhang L, Zuo L, Xu G, et al. Community-based screening for chronic kidney disease among populations older than 40 years in Beijing. Nephrol Dial Transplant. 2007;22:1093–9.

    Article  PubMed  Google Scholar 

  45. Kuo CF, Luo SF, See LC, et al. Hyperuricaemia and accelerated reduction in renal function. Scand J Rheumatol. 2011;40:116–21.

    Article  PubMed  CAS  Google Scholar 

  46. Yu MA, Sanchez-Lozada LG, Johnson RJ, Kang DH. Oxidative stress with an activation of the renin-angiotensin system in human vascular endothelial cells as a novel mechanism of uric acid-induced endothelial dysfunction. J Hypertens. 2010;28:1234–42.

    PubMed  Google Scholar 

  47. Zharikov S, Krotova K, Hu H, et al. Uric acid decreases NO production and increases arginase activity in cultured pulmonary artery endothelial cells. Am J Physiol Cell Physiol. 2008;295:C1183–90.

    Article  PubMed  CAS  Google Scholar 

  48. Kang DH, Park SK, Lee IK, Johnson RJ. Uric acid-induced C-reactive protein expression: implication on cell proliferation and nitric oxide production of human vascular cells. J Am Soc Nephrol. 2005;16:3553–62.

    Article  PubMed  CAS  Google Scholar 

  49. Gersch C, Palii SP, Kim KM, Angerhofer A, Johnson RJ, Henderson GN. Inactivation of nitric oxide by uric acid. Nucleosides Nucleotides Nucleic Acids. 2008;27:967–78.

    Article  PubMed  CAS  Google Scholar 

  50. Kanbay M, Yilmaz MI, Sonmez A, et al. Serum uric acid level and endothelial dysfunction in patients with nondiabetic chronic kidney disease. Am J Nephrol. 2011;33:298–304.

    Article  PubMed  CAS  Google Scholar 

  51. Khosla UM, Zharikov S, Finch JL, et al. Hyperuricemia induces endothelial dysfunction. Kidney Int. 2005;67:1739–42.

    Article  PubMed  Google Scholar 

  52. Perlstein TS, Gumieniak O, Hopkins PN, et al. Uric acid and the state of the intrarenal renin-angiotensin system in humans. Kidney Int. 2004;66:1465–70.

    Article  PubMed  CAS  Google Scholar 

  53. Myllymaki J, Honkanen T, Syrjanen J, et al. Uric acid correlates with the severity of histopathological parameters in IgA nephropathy. Nephrol Dial Transplant. 2005;20:89–95.

    Article  PubMed  Google Scholar 

  54. Netea MG, Kullberg BJ, Blok WL, Netea RT, Van der Meer JW. The role of hyperuricemia in the increased cytokine production after lipopolysaccharide challenge in neutropenic mice. Blood. 1997;89:577–82.

    PubMed  CAS  Google Scholar 

  55. Talaat KM, el-Sheikh AR. The effect of mild hyperuricemia on urinary transforming growth factor beta and the progression of chronic kidney disease. Am J Nephrol. 2007;27:435–40.

    Article  PubMed  CAS  Google Scholar 

  56. Roncal CA, Mu W, Croker B, et al. Effect of elevated serum uric acid on cisplatin-induced acute renal failure. Am J Physiol Ren Physiol. 2007;292:F116–22.

    Article  CAS  Google Scholar 

  57. Doria A, Niewczas MA, Fiorina P. Can existing drugs approved for other indications retard renal function decline in patients with type 1 diabetes and nephropathy? Semin Nephrol. 2012;32:437–44.

    Article  PubMed  CAS  Google Scholar 

  58. Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. JAMA. 2008;300:924–32.

    Article  PubMed  CAS  Google Scholar 

  59. Becker MA, Schumacher Jr HR, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005;353:2450–61.

    Article  PubMed  CAS  Google Scholar 

  60. Schumacher Jr HR, Becker MA, Wortmann RL, et al. Effects of febuxostat vs allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum. 2008;59:1540–8.

    Article  PubMed  CAS  Google Scholar 

  61. Noman A, Ang DS, Ogston S, Lang CC, Struthers AD. Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomized, placebo controlled crossover trial. Lancet. 2010;375:2161–7.

    Article  PubMed  CAS  Google Scholar 

  62. Dogan A, Yarlioglues M, Kaya MG, et al. Effect of long-term and high-dose allopurinol therapy on endothelial function in normotensive diabetic patients. Blood Press. 2011;20:182–7.

    Article  PubMed  CAS  Google Scholar 

  63. Butler R, Morris AD, Belch JJ, Hill A, Struthers AD. Allopurinol normalizes endothelial dysfunction in type 2 diabetics with mild hypertension. Hypertension. 2000;35:746–51.

    Article  PubMed  CAS  Google Scholar 

  64. Watanabe S, Kang DH, Feng L, et al. Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity. Hypertension. 2002;40:355–60.

    Article  PubMed  CAS  Google Scholar 

  65. Roujeau JC, Kelly JP, Naldi L, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med. 1995;333:1600–7.

    Article  PubMed  CAS  Google Scholar 

  66. Jung JW, Song WJ, Kim YS, et al. HLA-B58 can help the clinical decision on starting allopurinol in patients with chronic renal insufficiency. Nephrol Dial Transplant. 2011;26:3567–72.

    Article  PubMed  CAS  Google Scholar 

  67. Lonjou C, Borot N, Sekula P, et al. A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics. 2008;18:99–107.

    Article  PubMed  CAS  Google Scholar 

  68. • Tassaneeyakul W, Jantararoungtong T, Chen P, et al. Strong association between HLA-B*5801 and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a Thai population. Pharmacogenet Genomics. 2009;19:704–9. Pharmacogenetic data in which the association of HLA-B*5801 is identified as an important risk factor for SJS.

    Article  PubMed  CAS  Google Scholar 

  69. Chohan S, Becker MA, MacDonald PA, Chefo S, Jackson RL. Women with gout: efficacy and safety of urate-lowering with febuxostat and allopurinol. Arthritis Care Res. 2012;64:256–61.

    Article  CAS  Google Scholar 

  70. Eknoyan G, Hostetter T, Bakris GL, et al. Proteinuria and other markers of chronic kidney disease: a position statement of the National Kidney Foundation (NKF) and the National Institute Of Diabetes and Digestive and Kidney Diseases (NIDDK). Am J Kidney Dis. 2003;42:617–22.

    Article  PubMed  Google Scholar 

  71. Caramori ML, Fioretto P, Mauer M. Low glomerular filtration rate in normoalbuminuric type 1 diabetic patients: an indicator of more advanced glomerular lesions. Diabetes. 2003;52:1036–40.

    Article  PubMed  CAS  Google Scholar 

  72. Perkins BA, Ficociello LH, Ostrander BE, et al. Microalbuminuria and the risk for early progressive renal function decline in type 1 diabetes. J Am Soc Nephrol. 2007;18:1353–61.

    Article  PubMed  CAS  Google Scholar 

  73. Premaratne E, Macisaac RJ, Finch S, Panagiotopoulos S, Ekinci E, Jerums G. Serial measurements of cystatin C are more accurate than creatinine-based methods in detecting declining renal function in type 1 diabetes. Diabetes Care. 2008;31:971–3.

    Article  PubMed  CAS  Google Scholar 

  74. Molitch ME, Steffes M, Sun W, et al. Development and progression of renal insufficiency with and without albuminuria in adults with type 1 diabetes in the diabetes control and complications trial and the epidemiology of diabetes interventions and complications study. Diabetes Care. 2010;33:1536–43.

    Article  PubMed  CAS  Google Scholar 

  75. Fioretto P, Mauer M, Brocco E, et al. Patterns of renal injury in NIDDM patients with microalbuminuria. Diabetologia. 1996;39:1569–76.

    Article  PubMed  CAS  Google Scholar 

  76. Mauer M, Drummond K. The early natural history of nephropathy in type 1 diabetes: I. Study design and baseline characteristics of the study participants. Diabetes. 2002;51:1572–9.

    Article  PubMed  CAS  Google Scholar 

  77. Gaspari F, Perico N, Matalone M, et al. Precision of plasma clearance of iohexol for estimation of GFR in patients with renal disease. J Am Soc Nephrol. 1998;9:310–3.

    PubMed  CAS  Google Scholar 

  78. O'Reilly PH, Brooman PJ, Martin PJ, Pollard AJ, Farah NB, Mason GC. Accuracy and reproducibility of a new contrast clearance method for the determination of glomerular filtration rate. BMJ (Clin Res Ed). 1986;293:234–6.

    Article  Google Scholar 

  79. Gaspari F, Perico N, Remuzzi G. Measurement of glomerular filtration rate. Kidney Int Suppl. 1997;63:S151–4.

    PubMed  CAS  Google Scholar 

  80. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.

    Article  PubMed  Google Scholar 

  81. Stevens LA, Coresh J, Schmid CH, et al. Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3418 individuals with CKD. Am J Kidney Dis. 2008;51:395–406.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Dr. Maahs was supported by a grant from NIDDK (DK075360). Dr. Caramori is supported by a Career Development Award from the Juvenile Diabetes Research Foundation. This project was supported by NIH grants R03 DK094484 and R34 DK097808, and by grant 17-2012-377 from the Juvenile Diabetes Research Foundation (JDRF). Its contents are the authors’ sole responsibility and do not necessarily represent official NIH or JDRF views.

Other PERL Consortium members

University of Colorado: Marian Rewers, Richard Johnson, Satish Garg.

University of Michigan: Frank Brosius.

Steno Diabetes Center: Maria Lajer, Morten Kofod Lindhardt, and Bernt Johan Illum Horten von Scholten.

University of Minnesota: John Eckfeldt, Trudy Strand.

Joslin Diabetes Center: Andrzej Krolewski, Robert Stanton, Allison Goldfine.

Conflicts of Interest

David M. Maahs declares that he has no conflict of interest.

M. Luiza Caramori declares that she has no conflict of interest.

David Z.I. Cherney declares that he has no conflict of interest.

Andrzej T. Galecki declares that he has no conflict of interest.

Chuanyun Gao declares that she has no conflict of interest.

Diana Jalal has received ASN honoraria for speaking on the role of uric acid in kidney and cardiac disease in the elderly.

Bruce A. Perkins is a Senior Advisory Board Member for Neurometrix Inc.; and has been a Site investigator for a sponsored clinical trial for Medtronic Inc.; a Co-PI for a sponsored clinical trial by Boehringer Ingelheim; and has received speaker honoraria from Medtronic Inc., Roche, GlaxoSmithKline, Johnson & Johnson, Novo Nordisk, and Eli Lilly.

Rodica Pop-Busui declares that she has no conflict of interest.

Peter Rossing serves on the board for Astra Zeneca/BMS, Eli Lilly, Janssen, Novo Nordisk, and Astellas; has received grant support from Novo Nordisk, Novartis, and Abbott; has received payment for lectures including service on speaker’s bureaus from Astra Zeneca/BMS, Novartis, and Sanofi-Aventis; and has stock/stock options with Novo Nordisk.

Michael Mauer declares that he has no conflict of interest.

Alessandro Doria has received research grant support from Sanofi-Aventis; has received travel/accommodations expenses covered or reimbursed from the American Society of Nephrology and the Italian Society of Diabetology.

Author information

Authors and Affiliations

  1. Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, USA

    David M. Maahs

  2. Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, USA

    David M. Maahs & Diana Jalal

  3. Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, MN, USA

    Luiza Caramori & Michael Mauer

  4. Department of Medicine and Division of Nephrology, University of Toronto, Toronto, ON, Canada

    David Z. I. Cherney

  5. Division of Geriatrics/Institute of Gerontology, Medical School, and Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA

    Andrzej T. Galecki

  6. Joslin Clinic, Joslin Diabetes Center, Boston, MA, USA

    Chuanyun Gao

  7. Department of Medicine and Division of Endocrinology, University of Toronto, Toronto, ON, Canada

    Bruce A. Perkins

  8. Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA

    Rodica Pop-Busui

  9. Steno Diabetes Center, Gentofte, Denmark

    Peter Rossing

  10. HEALTH, University of Aarhus, Aarhus, Denmark

    Peter Rossing

  11. NNF CBMR University of Copenhagen, Copenhagen, Denmark

    Peter Rossing

  12. Section on Genetics and Epidemiology, Joslin Diabetes Center, One Joslin Place, Boston, MA, 02215, USA

    Alessandro Doria

  13. Department of Medicine, Harvard Medical School, Boston, MA, USA

    Alessandro Doria

Authors
  1. David M. Maahs
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luiza Caramori
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David Z. I. Cherney
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrzej T. Galecki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chuanyun Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Diana Jalal
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bruce A. Perkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rodica Pop-Busui
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Peter Rossing
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Michael Mauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Alessandro Doria
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the PERL Consortium

Corresponding author

Correspondence to Alessandro Doria.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maahs, D.M., Caramori, L., Cherney, D.Z.I. et al. Uric Acid Lowering to Prevent Kidney Function Loss in Diabetes: The Preventing Early Renal Function Loss (PERL) Allopurinol Study. Curr Diab Rep 13, 550–559 (2013). https://doi.org/10.1007/s11892-013-0381-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11892-013-0381-0

Keywords

Search

Navigation