Hyperuricemia beyond 1 year after kidney transplantation in pediatric patients: Prevalence and risk factors

Introduction

Hyperuricemia is a frequent among adult renal transplant recipients[12] and it is also a frequent metabolic disorder after liver[3] and heart transplantations.[4] During puberty, there is increase in fractional excretion rate of uric acid, reducing the likelihood of development of this complication.[5] Moreover, several studies have shown a correlation between plasma uric acid concentration and body mass index in adolescents.[67] In pediatric recipients, however, published data in literature on hyperuricemia after transplantation are scarce.[8–10] In a retrospective study from Edvardsson et al.,[8] hyperuricemia was seen in 23% of children after renal transplantation. Hoyer et al.[11] 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

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.

Table 1 Demographic and laboratory data of recipients and donors

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].

Table 2 Comparison between normouricemic and hyperuricemic groups

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].

Table 3 Univariate correlation between SUA and other parameters

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).

Table 4 Multivariate correlation between SUA and other parameters

Discussion

This study demonstrates that as in adults, nearly one-half of pediatric kidney transplant recipients suffer from late post-transplant hyperuricemia.[12] This result is consistent with a previous report, which hyperuricemia occurred in 47% of 32 pediatric kidney recipients.[9] 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.[8] 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.[8–10] Moreover, our finding is consistent with reports in adult kidney transplantation.[11314] Hyperuricemia is also a frequent complication after liver and cardiac transplantation.[415] Tumgor et al.[16] reported that hyperuricemia occurred in 29% of 70 pediatric liver transplant recipients. In adult kidney transplantation, males developing hyperuricemia than females,[1417] 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.[8111318–20] 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%).[20] In addition, another report suggested that hyperuricemia was a risk factor for graft loss.[21] 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.[22] 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.[15] 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.[8]

CsA plays a key role in post-transplant hyperuricemia among adult kidney transplant recipients.[123] 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.[89] Hyperuricemia is also a common complication among CsA-treated liver[1516] and cardiac[4] recipients. There are several experimental[2425] and clinical evidence[325] 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.[25] In a series of 53 children with steroid-dependent nephrotic syndrome, higher SUA concentration was associated with CsA-induced nephropathy.[26]

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.