|Year : 2012 | Volume
| Issue : 4 | Page : 280-284
Hyperuricemia beyond 1 year after kidney transplantation in pediatric patients: Prevalence and risk factors
B Einollahi, H Einollahi, Z Rostami
Department of Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
|Date of Web Publication||22-Sep-2012|
Ground Floor of Baqiyatallah Hospital, Baqiyatallah Medical University, Mollasdra Ave., Vanak Squ., Tehran
Source of Support: None, Conflict of Interest: None
Hyperuricemia is frequent among adult renal transplant recipients; however, data among pediatric kidney recipients are scarce. This study is designed to estimate the prevalence and risk factors of late post-transplant hyperuricemia in pediatric recipients. A retrospective observational multicenter study on 179 pediatric renal recipients (5-18 years) was conducted between April 2008 and January 2011 from five kidney transplant centers of Tehran, Iran. All recipients were followed up for more than 1 year (5.9 ±3.3 years) after transplantation. A total of 17686 blood samples were obtained for serum uric acid (SUA). The normal range of SUA was defined as SUA 1.86-5.93 mg/dl for children between 2 and 15 years in both genders; 2.40-5.70 mg/dl for girls aged >15 years; 3.40-7.0 mg/dl for boys aged >15 and more than 6 and 7 mg/dl in boys and girls older than 15 years old. The median age of the children was 13 years. Male recipients were more popular than female (male/female 59/41%). Hyperuricemia was detected in 50.2% of patients. Mean SUA concentration was 5.9±1.7 mg/dl and mean SUA concentration in hyperuricemic patients was 7.7±1.2 mg/dl. While at multivariate logistic regression elevated serum creatinine concentration (P>0.001) and the time span after renal transplantation (P=0.02) had impact on late post-transplant hyperuricemia. High cyclosporine level (C0 and C2) was not risk factor for huperuricemia. Late post-transplant hyperuricemia was found in about half of pediatric renal recipients, and was associated with impaired renal allograft function.
Keywords: Hyperuricemia, pediatric renal recipients, renal allograft impairment
|How to cite this article:|
Einollahi B, Einollahi H, Rostami Z. Hyperuricemia beyond 1 year after kidney transplantation in pediatric patients: Prevalence and risk factors. Indian J Nephrol 2012;22:280-4
|How to cite this URL:|
Einollahi B, Einollahi H, Rostami Z. Hyperuricemia beyond 1 year after kidney transplantation in pediatric patients: Prevalence and risk factors. Indian J Nephrol [serial online] 2012 [cited 2020 Aug 15];22:280-4. Available from: http://www.indianjnephrol.org/text.asp?2012/22/4/280/101248
| Introduction|| |
Hyperuricemia is a frequent among adult renal transplant recipients , and it is also a frequent metabolic disorder after liver  and heart transplantations.  During puberty, there is increase in fractional excretion rate of uric acid, reducing the likelihood of development of this complication.  Moreover, several studies have shown a correlation between plasma uric acid concentration and body mass index in adolescents. , In pediatric recipients, however, published data in literature on hyperuricemia after transplantation are scarce. ,, In a retrospective study from Edvardsson et al.,  hyperuricemia was seen in 23% of children after renal transplantation. Hoyer et al.  described an increased net tubular absorption of uric acid in 28 cyclosporine (CsA) treated pediatric renal transplant recipients.
In the current study, our aim was to evaluate the prevalence and confounding variables of hyperuricemia in pediatric kidney transplant recipients.
| Materials and Methods|| |
A retrospective observational multicenter study on 179 children and adolescents renal recipients younger than 18 years old was performed between April 2008 and January 2011 from five Kidney Transplant Centers of Tehran, Iran to estimate the prevalence of late post-transplant hyperuricemia and its risk factors. They received kidney allograft for the first time and followed more than 1 year after transplantation (5.9±3.3 years). Both living and deceased kidney transplant recipients were included. All laboratory tests such as serum uric acid (SUA) were done in a single laboratory. In this period, a total of 17686 blood samples were obtained. This study was approved by the Local Ethics Committee of the Baqiyatallah University of Medical Sciences.
All patients treated with CsA (targeting trough level (C0) of 200 to 300 ng/ml for first 3 months, 100 to 250 ng/ml for 4 to 12 months, and 100 to 150 ng/ml thereafter; while we used 2 h post-dose (C2) target levels of 800 to 1000 ng/mL in the first 3 months after transplantation and C2 targets of 400 to 600 ng/mL for subsequent months); mycophenolate mofetil or azathioprine and prednisolone, except those who withdrew these drugs due to their side effects.
Clinical and biochemical data collection
The clinical and biochemical parameters collected for all patients were age and sex of recipients and donors, donor source (living or deceased), serum creatinine (Cr) concentration, fasting blood sugar (FBS), CsA levels (C0 and C2), hemoglobin (Hb) value and lipid profile including triglycerides (TG), cholesterols (Chol), low-density lipoprotein (LDL), and high-density lipoprotein (HDL).
Definition of hyperuricemia after renal transplantation
The normal range of SUA was defined according to age and sex: For children between 2 and 15 years in both genders: 1.86-5.93 mg/dl; for girls aged more than 15 years: 2.40-5.70 mg/dl; for boys aged more than 15 years: 3.40-7.0 mg/dl (9). Thus, we considered hyperuricemia if SUA concentration of ≥6 mg/dl in boys younger than 15 years old and all girls, as well as SUA level of ≥7 mg/dl in boys older than 15 years old on at least two successive determinations during follow up.
Statistical analyses were performed using SPSS for Windows, versions 17.0. Quantitative variables were expressed as means±SD, while qualitative variables were shown by number and percentage. The Kolmogorov-Smirnov test showed that uric acid levels were distributed normally (P=0.5); therefore, parametric tests were used to comparisons of qualitative and qualitative data. Linear regression model and multivariate logistic regression analyses were used to examine the influence of the potential predisposing factors for hyperuricemia. All tests were two tailed, and P-values of less than 0.05 were considered statistically significant.
| Results|| |
The patient demographic and laboratory information are shown in [Table 1]. The median age of the children was 13 years (range: 5-18 years) and the median time since of transplantation was 6 years (5.9±3.3 years). The majority of cases were male (59 vs 41%) and received the grafts from living donors (88.7% unrelated and 8.3% related), while 7.3% of them came from deceased donors. Mean SUA and serum Cr were 6.2±1.8 and 1.5±1 mg/dl, respectively.
Comparison between normouricemic and hyperuricemic groups is shown in [Table 2]. Low hemoglobin level as well as high serum Cr, high TG level and longer transplantation duration were significantly associated with post-transplant hyperuricemia (P=0.001, P=0.000, P=0.03, P=0.000) [Table 2].
Hyperuricemia was detected in 90 (50.2%) children 1 year after renal transplantation. Females were more likely to be hyperuricemic with no significant value (52% vs 45% in boys, P=0.08).
Univariate correlation analysis between SUA concentration and other possible affecting factors are demonstrated in [Table 3]. There were a negative and significant correlation between hyperuricemia and age of recipients, hemoglobin level, FBS, and HDL [Table 3]. Conversely, positive and significant correlation were seen between hyperuricemia and serum Cr, cyclosporine levels (through and 2 h postdoes), Chol, LDL, and TG [Table 3].
At linear regression analysis [Table 4], we found the renal allograft impairment and time since transplantation were only risk factors for late post-transplant hyperuricemia in pediatric renal recipients (P=0.000 and P=0.02, respectively). Anemia and hypertriglyceridemia were not risk factors for elevated SUA concentration (P=0.1 and P=0.4, respectively). At multivariate logistic regression analysis after adjustment for categorical and continuous variables, elevated serum creatinine concentration (P=0.000) and the time span after renal transplantation (P=0.02) had only impact on late post-transplant hyperuricemia. High cyclosporine level (C0 and C2) was not risk factor for hyperuricemia (P=0.7, P=0.6).
| Discussion|| |
This study demonstrates that as in adults, nearly one-half of pediatric kidney transplant recipients suffer from late post-transplant hyperuricemia.  This result is consistent with a previous report, which hyperuricemia occurred in 47% of 32 pediatric kidney recipients.  However, Edvardsson et al. in a retrospective study showed that the prevalence of hyperuricemia in pediatric kidney transplants was lower than our reports; it accounted for 23% of all patients at 30 months of transplantation.  This difference may be due to differences in race, age distribution, renal impairment, post-transplant duration, and other confounding factors. However, published data in the literature on post-transplant hyperuricemia especially late onset post-transplant hyperuricemia among these patients are scarce and a few studies have addressed the issue of hyperuricemia following pediatric kidney transplantation. ,, Moreover, our finding is consistent with reports in adult kidney transplantation. ,, Hyperuricemia is also a frequent complication after liver and cardiac transplantation. , Tumgor et al.  reported that hyperuricemia occurred in 29% of 70 pediatric liver transplant recipients. In adult kidney transplantation, males developing hyperuricemia than females, , which is opposite of our observation that the prevalence of hyperuricemia was higher in girls, but with no significant differences.
Consistent with previous studies, impaired renal allograft function was a major risk factor for post-transplant hyperuricemia. ,,,,, One small study showed that post-transplant hyperuricemia had a significantly adverse effect on renal graft survival after 5 years in adult patients, with a lower survival rate (69%) in hyperuremic recipients compared to those with normouricemia (83%).  In addition, another report suggested that hyperuricemia was a risk factor for graft loss.  On the other hand, Meier-Kriesche et al. had results different from our findings, suggesting a lack of any significant association between SUA levels and deterioration of renal allograft function in the first three post-transplant years.  In addition, prospective and controlled clinical trials are required to determine if SUA lowering therapies may lead to reducing the development of chronic allograft injury.
In this study, post-transplant hyperuricemia was a time-dependent variable and SUA was increasing over time, which matches with a previous report.  Conversely, Edvardsson et al. showed a peak SUA level in pediatric recipients at 6 months following kidney transplantation, with a hyperuricemia rate of 39% versus of 23% at 30 months after transplantation. 
CsA plays a key role in post-transplant hyperuricemia among adult kidney transplant recipients. , All of our pediatric patients received CsA as a major immunosuppression agent; however, the hyperuricemic effect of CsA appears to be less significant in terms of the drug doses and blood levels. Our study did not find any correlation between CsA blood levels and SUA concentration. This result is consistent with that of two previous studies. , Hyperuricemia is also a common complication among CsA-treated liver , and cardiac  recipients. There are several experimental , and clinical evidence , suggested that SUA may contribute to CsA nephrotoxicity. An animal study showed that SUA may have a role in aggravation of CsA vasculopathy and interstitial injury.  In a series of 53 children with steroid-dependent nephrotic syndrome, higher SUA concentration was associated with CsA-induced nephropathy. 
Although our study was clearly limited by its retrospective nature and uncontrolled of the study design, the data of this study may be more reliable because of the relatively higher number of our pediatric renal recipients compared to the previous studies. Additional prospective randomized trials with a larger cohort of renal transplant patients are required to determine the cause and effect correlation of SUA and graft dysfunction.
| Conclusion|| |
We found that hyperuricemia is a frequent metabolic problem in pediatric kidney transplant recipients. It is correlated with the time since transplantation and is a consequence of renal allograft impairment.
| References|| |
|1.||Clive DM. Renal transplant-associated hyperuricemia and gout. J Am Soc Nephrol 2000;11:974-9. |
|2.||Abbott KC, Kimmel PL, Dharnidharka V, Oglesby RJ, Agodoa LY, Caillard S. New-onset gout after kidney transplantation: Incidence, risk factors and implications. Transplantation 2005;80:1383-91. |
|3.||Neal DA, Tom BD, Gimson AE, Gibbs P, Alexander GJ. Hyperuricemia, gout, and renal function after liver transplantation. Transplantation 2001;72:1689-91. |
|4.||Burack DA, Griffith BP, Thompson ME, Kahl LE. Hyperuricemia and gout among heart transplant recipients receiving cyclosporine. Am J Med 1992;92:141-6. |
|5.||Baldree LA, Stapleton FB. Uric acid metabolism in children. Pediatr Clin North Am 1990;37:391-418. |
|6.||Invitti C, Guzzaloni G, Gilardini L, Morabito F, Viberti G. Prevalence and concomitants of glucose intolerance in European obese children and adolescents. Diabetes Care 2003;26:118-24. |
|7.||Denzer C, Muche R, Mayer H, Heinze E, Debatin KM, Wabitsch M. Serum uric acid levels in obese children and adolescents: Linkage to testosterone levels and pre-metabolic syndrome. J Pediatr Endocrinol Metab 2003;16:1225-32. |
|8.||Edvardsson VO, Kaiser BA, Polinsky MS, Palmer JA, Quien R, Baluarte HJ. Natural history and etiology of hyperuricemia following pediatric renal transplantation. Pediatr Nephrol 1995;9:57-60. |
|9.||Sparta G, Kemper MJ, Neuhaus TJ. Hyperuricemia and gout following pediatric renal transplantation. Pediatr Nephrol 2006;21:1884-8. |
|10.||Laine J, Holmberg C. Mechanisms of hyperuricemia in cyclosporine-treated renal transplanted children. Nephron 1996;74:318-23. |
|11.||Hoyer PF, Lee IJ, Oemar BS, Krohn HP, Offner G, Brodehl J. Renal handling of uric acid under cyclosporin A treatment. Pediatr Nephrol 1988;2:18-21. |
|12.||Kalantar E, Khalili N, Hossieni MS, Rostami Z, Einollahi B. Hyperuricemia after renal transplantation. Transplant Proc 2011;43:584-5. |
|13.||Vijayanagar R, Bognolo DA, Eckstein PF, Jeffery DL, Harrison E, Natarajan P, et al. Advantages of superior approach for mitral valve surgery. J Cardiovasc Surg (Torino) 1985;26:426-32. |
|14.||Min SI, Yun IJ, Kang JM, Park YJ, Min SK, Ahn C, et al. Moderate-to-severe early-onset hyperuricaemia: A prognostic marker of long-term kidney transplant outcome. Nephrol Dial Transplant 2009;24:2584-90. |
|15.||Harambat J, Dubourg L, Ranchin B, Hadj-Aïssa A, Fargue S, Rivet C, et al. Hyperuricemia after liver transplantation in children. Pediatr Transplant 2008;12:847-53. |
|16.||Tumgor G, Arikan C, Kilic M, Aydogdu S. Frequency of hyperuricemia and effect of calcineurin inhibitors on serum uric acid levels in liver transplanted children. Pediatr Transplant 2006;10:665-8. |
|17.||Bandukwala F, Huang M, Prasad GV. Role of uric acid in post-renal transplantation hypertension. Transplant Proc 2009;41:1634-6. |
|18.||Marcén R, Gallego N, Orofino L, Gámez C, Estepa MR, Sabater J, et al. Impairment of tubular secretion of urate in renal transplant patients on cyclosporine. Nephron 1995;70:307-13. |
|19.||Armstrong KA, Johnson DW, Campbell SB, Isbel NM, Hawley CM. Does uric acid have a pathogenetic role in graft dysfunction and hypertension in renal transplant recipients? Transplantation 2005;80:1565-71. |
|20.||Gerhardt U, Grosse Huttmann M, Hohage H. Influence of hyperglycemia and hyperuricemia on long-term transplant survival in kidney transplant recipients. Clin Transplant 1999;13:375-9. |
|21.||Haririan A, Nogueira JM, Zandi-Nejad K, Aiyer R, Hurley H, Cooper M, et al. The independent association between serum uric acid and graft outcomes after kidney transplantation. Transplantation 2010;89:573-9. |
|22.||Meier-Kriesche HU, Schold JD, Vanrenterghem Y, Halloran PF, Ekberg H. Uric acid levels have no significant effect on renal function in adult renal transplant recipients: Evidence from the symphony study. Clin J Am Soc Nephrol 2009;4:1655-60. |
|23.||Delaney V, Sumrani N, Daskalakis P, Hong JH, Sommer BG. Hyperuricemia and gout in renal allograft recipients. Transplant Proc 1992;24:1773-4. |
|24.||Kang DH, Nakagawa T, Feng L, Watanabe S, Han L, Mazzali M, et al. A role for uric acid in the progression of renal disease. J Am Soc Nephrol 2002;13:2888-97. |
|25.||Mazzali M, Kim YG, Suga S, Gordon KL, Kang DH, Jefferson JA, et al. Hyperuricemia exacerbates chronic cyclosporine nephropathy. Transplantation 2001;71:900-5. |
|26.||Kengne-Wafo S, Massella L, Diomedi-Camassei F, Gianviti A, Vivarelli M, Greco M, et al. Risk factors for cyclosporin A nephrotoxicity in children with steroid-dependant nephrotic syndrome. Clin J Am Soc Nephrol 2009;4:1409-16. |
[Table 1], [Table 2], [Table 3], [Table 4]