tacrolimus and Hyperuricemia

Although hyperuricemia is a well-known adverse effect of cyclosporine (CsA) treatment, there are contradictory data regarding the effect of tacrolimus on uric acid levels. The aim of this study was to examine the influences of CsA and tacrolimus-based treatment regimens on serum uric acid levels in 155 renal transplant recipients with normal allograft function who underwent renal transplantation between 1999 and 2002. Serum uric acid levels were recorded at 1, 6, 12, 18, and 24 months follow-up. The patients were treated with CsA-based (n = 73), tacrolimus-based (n = 47), or conversion from CsA-based to tacrolimus-based (n = 35) immunosuppressive regimens. Serum uric acid levels for patients in the CsA and tacrolimus groups were 6.3 +/- 1.6 versus 7.9 +/- 1.9 mg/dL and 6.5 +/- 1.8 versus 8.0 +/- 1.8 mg/dL at the study outset and 24 months, respectively. Both of the treatment regimens showed progressively increasing serum uric acid levels (P < .001). Serum uric acid levels of patients with treatment conversion from CsA to tacrolimus were 8.6 +/- 2.8 mg/dL before conversion and 8.1 +/- 1.9 mg/dL after conversion. There was no alteration in serum uric acid levels after the change of treatment (P > .05). These findings indicate that, compared with CsA, tacrolimus offers no advantage for serum uric acid levels in renal transplant recipients.

Topics: Adult; Cyclosporine; Female; Humans; Hyperuricemia; Immunosuppressive Agents; Kidney Transplantation; Male; Postoperative Complications; Tacrolimus; Uric Acid

The prevalence of hyperuricemia shows an increasing trend among kidney transplant recipients. The association between metabolic syndrome and hyperuricemia among the recipients of kidney transplants may consequently lead to reduction in graft survival. In this regard, the present study aimed at comparing the kidney transplant recipients with and without metabolic syndrome in terms of the prevalence of hyperuricemia.. This cross-sectional study was carried out on kidney transplant recipients who were referred to the Kidney Transplant Clinic of Montaserieh Organ Transplant Hospital, Mashhad University of Medical Sciences, from 2019 to 2020. The serum uric acid, anthropometric data, renal function, glucose levels, and lipid profile of the study participants were evaluated.. According to our findings, higher mean uric acid levels were reported in recipients with metabolic syndrome (6.9 ± 1.51 mg/dL), compared to recipients without metabolic syndrome (6.11 ± 1.47 mg/dL; P < .001). It was also found that 55.6 and 38.5% of the cases with and without metabolic syndrome had hyperuricemia, respectively (P < .05). Additionally, the results showed no significant association between hyperuricemia and the number of metabolic syndrome criteria (P > .05). A comparison between recipients with and without hyperuricemia revealed significantly lower levels of tacrolimus in the hyperuricemia group (P < .05). Regarding serum Tacrolimus levels, no significant difference was found between recipients with and without metabolic syndrome (P > .05). Moreover, there was no significant difference between recipients with and without hyperuricemia (P > .05) or metabolic syndrome (P > .05) in terms of serum cyclosporine level.. The findings of the current study indicate that kidney transplant recipients suffering from metabolic syndrome have higher mean serum levels of uric acid than those without metabolic syndrome.  DOI: 10.52547/ijkd.7141.

Topics: Cross-Sectional Studies; Humans; Hyperuricemia; Kidney Transplantation; Metabolic Syndrome; Tacrolimus; Uric Acid

The use of calcineurin inhibitors is a well-known risk factor for hyperuricemia in kidney transplant recipients. We evaluated the effect of febuxostat (Fx), a new uric acid-lowering drug, on hyperuricemia and renal injury in an experimental model of chronic tacrolimus (Tac)-induced nephropathy.. Chronic Tac nephropathy was induced by administering Tac (1.5 mg/kg/day) to rats on a low-salt diet (0.05%) with oxonic acid (OA, 2%, 0.2 g/kg/day) for 28 days. Two doses of Fx (5 and 10 mg/kg) were concomitantly administered with Tac or vehicle (Vh). We evaluated the effect of Fx on hyperuricemia by measuring serum uric acid (SUA) levels, fractional excretion of uric acid (FEUA), and urate transporters in Tac-induced nephropathy. The effects of Fx on Tac-induced renal injury were evaluated in terms of renal function and arteriolopathy, tubulointerstitial fibrosis, inflammation, and apoptosis. We evaluated oxidative stress as a protective mechanism via xanthine oxidase (XO) activity, and as a marker of oxidative stress (via evaluation of levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxy-2-hexenal (4-HHE)).. The Tac group showed higher SUA levels and lower FEUA than did the Vh group, but Fx treatment significantly decreased SUA levels in a dose-dependent manner, with an increase of FEUA at a high dose (10 mg/kg). Tac treatment increased urate-anion exchanger 1 and decreased organic anion transporter type 1 expression in renal tubular cells, but Fx treatment reversed the effects on those transporters. Impaired renal function and histological injury (interstitial fibrosis, inflammation, and arteriolopathy) in the Tac group were markedly improved by Fx administration. Increases in apoptotic cell death and activation of proapoptotic caspase-3 by Tac were remarkably decreased by Fx treatment. Tac administration increased the activity of XO in kidney tissue and serum, and the levels of 8-OHdG in urine and 8-OHdG and 4-HHE of kidney tissue, but combined treatment with Fx decreased the levels of these parameters.. Fx is effective in controlling hyperuricemia and in preventing Tac-induced renal injury, via a reduction of oxidative stress. Therefore, a targeted therapy aimed at inhibiting uric acid by Fx may be a useful approach in the management of the progression of nephropathy in renal transplant patients treated with Tac.

Topics: Animals; Anion Transport Proteins; Apoptosis; Calcineurin Inhibitors; Disease Models, Animal; Febuxostat; Gout Suppressants; Humans; Hyperuricemia; Kidney; Kidney Transplantation; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Tacrolimus

Cardiovascular disease (CVD) is the second major cause of death in kidney-transplanted children. Cardiovascular risk factors (CVRF) prevalence after transplant may increase. The effect of immunosuppressive therapy has not been fully studied in children. The objective of the study was to measure and compare CVRF prevalence in kidney-transplanted children, depending of immunosuppressive therapy.. The study was an observational, transversal, retrospective, comparative study of pediatric patients transplanted at UMAE Hospital General Centro Medico La Raza. All patients were treated with prednisone and mycophenolic acid and any of cyclosporine, tacrolimus, or sirolimus. Demographic, clinical, and biochemical variables and immunosuppressive therapy were evaluated. We used analysis of variance, χ(2), and Fisher tests with the SPSS 18.0 statistical program.. One hundred fifteen patients were studied. Sixty-five (56.5%) were male, and median age was 18.5 ± 2.3 years. Seventy-eight (67.2%) were transplanted from a living related donor. Prevalence of anemia and nephrotic proteinuria was significantly less in patients treated with tacrolimus. Those treated with cyclosporine had a significantly greater prevalence of increased LDL-cholesterol, increased serum phosphorus, and increased calcium-phosphorus. Those treated with tacrolimus had lower, not significant, prevalence of hypertension, hyperuricemia, hypoalbuminemia, hypercholesterolemia, hypertriglyceridemia, and low serum HDL-cholesterol than those treated with sirolimus and cyclosporine. In multivariate analysis, patients treated with cyclosporine had significantly more probability of increased phosphorus (OR, 10.65; 95% CI, 2.75-41.16, P = .001) and calcium-phosphorus (OR, 37.94; 95% CI, 3.45-416.17, P = .003) than those treated with tacrolimus.. Patients treated with tacrolimus had less prevalence of CVRF than those treated with cyclosporine or sirolimus. Tacrolimus is the best immunosuppressive option to diminish CVRF in children after kidney transplantation.

Topics: Adolescent; Adult; Cardiovascular Diseases; Child; Cyclosporine; Female; Humans; Hypertension; Hypertriglyceridemia; Hyperuricemia; Immunosuppressive Agents; Immunotherapy; Kidney Failure, Chronic; Kidney Transplantation; Male; Mycophenolic Acid; Postoperative Complications; Prednisone; Prevalence; Retrospective Studies; Risk Factors; Sirolimus; Tacrolimus; Young Adult

We sought to evaluate the prevalence and confounding clinical variables of hyperuricemia in pediatric kidney transplant patients.. We retrospectively evaluated the medical records of 151 pediatric renal transplant recipients who received their grafts at Akdeniz University Medical Faculty in Antalya, Turkey, with a follow-up longer than 6 months. This retrospective, single-center study included 117 pediatric renal transplant recipients, after we had excluded the patients with changes in immunosuppressive treatment and graft loss, who were receiving therapy with allopurinol and furosemide. Patient information and laboratory data were obtained from patient charts and an electronic hospital database.. Mean uric acid levels of patients were 311 ± 74 μmol/L, and 24 of all of the patients (20%) had high uric acid levels. Fifteen patients taking tacrolimus (16%), and 9 of patients taking cyclosporine (39%) had hyperuricemia. The hyperuricemia rate of patients taking cyclosporine was significantly higher than it was for those patients taking tacrolimus (P = .014). Mean levels of uric acid in patients taking cyclosporine were higher than those of patients taking tacrolimus (344 ± 62 μmol/L and 303 ± 75 μmol/L; P = .006). There was a significant positive correlation between mean uric acid concentrations, and both serum creatinine (P = .000; r=0.487) and cystatin C (P = .000; r=0.433). There was negative correlation between mean uric acid concentration and estimated glomerular filtration rate (P = .000; r=-0.417). Mean uric acid levels of patients with intact graft function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m²) was lower than the patients with a low estimated glomerular filtration rate (291 ± 67 μmol/L and 353 ± 71 μmol/L; P = .000). Mean uric acid level of patients with normal body mass index was significantly lower than that of patients who were obese-overweight (301 ± 64 μmol/L vs 343 ± 94 μmol/L; P = .045).. We found 20% of our patient group had high uric acid levels. We also found that lower glomerular filtration rate, higher serum creatinine, cystatin c, obesity, and being overweight were risk factors for hyperuricemia in pediatric renal transplant recipients.

Topics: Adolescent; Child; Child, Preschool; Creatinine; Cyclosporine; Cystatin C; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hyperuricemia; Immunosuppressive Agents; Kidney Transplantation; Male; Obesity; Overweight; Prevalence; Retrospective Studies; Risk Factors; Tacrolimus; Transplantation

Cardiovascular disease (CVD) accounts for 35% to 50% of deaths among renal transplant recipients. Beside the atherogenic risk factors related to hemodialysis, renal function, and use of immunosuppressive agents, other relevant risk factors for CVD include acute rejection episodes, microalbuminuria (muAlb), diabetes, arterial hypertension, lipid disorders, inflammatory triggers, hyperhomocysteinemia, anemia, erythrocytosis, obesity, and hyperuricemia. We studied the prevalence of risk factors and the impact of various drugs on CVD among 103 renal transplant recipients with measured glomerular filtration rates showing values >45 mL/min. We measured uric acid, triglycerides (TG), low-density lipoprotein (LDL)/high-density lipoprotein (HDL) LDL/HDL ratio, homocysteine (HOMO), insulin resistance, muAlb, C-reactive protein (CRP), and fibrinogen. Subsequently, patients were divided into 8 groups based on the immunosuppressive protocol to evaluate its impact on CVD risk factors. Insulin resistance and hyperhomocysteinemia were present in >2/3 of patients. Considering the impact of protocols, the combination of cyclosporine (CsA) + everolimus (EVL) resulted in the most favorable profile in terms of reduction of hyperuricemia, hyperlipidemia, and hyperhomocysteinemia. Insulin resistance tended to be more frequent among patients treated with protocols including calcineurin inhibitors (CNI) and steroids. The prevalence of hyperhomocyteinemia was similar among patients on CsA and on tacrolimus (Tac). Sirolimus (SRL) was associated with higher levels of HOMO. The combination of CNI and proliferative signal inhibitors (PSI) seemed to be the most promising one to reduce the impact of CVD risk factors. The reduction in CVD morbidity can improve expectancy and quality of life, as well as graft function and survival among renal transplant patients.

Topics: Calcineurin Inhibitors; Cardiovascular Diseases; Cyclosporine; Drug Therapy, Combination; Everolimus; Female; Glomerular Filtration Rate; Humans; Hyperhomocysteinemia; Hyperlipidemias; Hyperuricemia; Immunosuppressive Agents; Kidney Transplantation; Lipoproteins, HDL; Middle Aged; Risk Factors; Sirolimus; Tacrolimus; Transplant Recipients

Hyperuricemia is common after renal and cardiac transplantations, but it is rarely reported after liver transplantations. The aim of this study is to determine the frequency of hyperuricemia in children following orthotopic liver transplantation and the effects of calcineurin inhibitors tacrolimus and cyclosporine) on blood uric acid levels. Between September 1997 to January 2004, 76 liver transplantations were performed in 70 children (male/female; 39/31) at Ege University, Organ Transplantation Center (37 deceased donation and 39 live donors). Patients who had been transplanted within the last three months and patients who died within six months after liver transplantation were excluded from the study. Finally 59 patients were included in this study. Uric acid levels were measured before transplantation and after transplantation within six months intervals for two yr. In these series 17 cases had increased uric acid levels after liver transplantation (28.8%). Serum uric acid levels in both groups (tacrolimus or cyclosporine) were detected to be significantly higher than initial values at 12th months (p < 0.05). Hyperuricemia developed in eight patients receiving cyclosporine (eight of 11; 72%) whereas nine patients receiving tacrolimus developed hyperuricemia (nine of 48; 18%). However, the rate of having high uric acid levels was significantly higher in cyclosporine group compared tacrolimus group (p = 0.001, OR: 11.5, CI 95% 2.5-52.4). Uric acid levels were also significantly higher in cyclosporine group in 12th and 18th months (respectively, p = 0.003 and p = 0.003). Serum creatinine levels at 12th, 18th and 24th months were significantly higher in cyclosporine group than tacrolimus group (respectively, p = 0.009, p = 0.04 and p = 0.02). Hyperuricemia is a common complication after liver transplantation in children. Cyclosporine may cause hyperuricemia more often in respect to tacrolimus and this may be related to the impairment of renal functions. Complications developing because of hyperuricemia such as gout disease or renal calculi are quite rare in children.

Topics: Adolescent; Chi-Square Distribution; Child; Child, Preschool; Creatinine; Cyclosporine; Female; Humans; Hyperuricemia; Immunosuppressive Agents; Infant; Liver Transplantation; Male; Postoperative Complications; Tacrolimus; Treatment Outcome; Uric Acid

Although cyclosporine use has been associated with an increased risk of new-onset gout after renal transplantation, the incidence and risk factors for new-onset gout have not been reported in the era of modern immunosuppression.. We conducted a retrospective cohort study of Medicare primary renal transplant patients reported in the United States Renal Data System (USRDS), using Medicare claims data to determine the incidence of new-onset gout. Cox regression analysis was used to calculate adjusted hazard ratios (AHR) for cyclosporine (including separate analysis of Neoral) compared directly with tacrolimus, for the risk of new-onset gout, adjusted for baseline demographic factors and posttransplant renal function.. The cumulative incidence of new-onset gout was 7.6% at 3 years posttransplant. The following factors were independently associated with an increased risk of new-onset gout: use of Neoral (vs. tacrolimus, AHR 1.25, 95% CI 1.07-1.47) at discharge, recipient male sex (AHR 1.44, 95% CI 1.25-1.67), older age, higher body mass index, and more recent year of transplant. No other immunosuppressive medications were associated with new-onset gout. Diabetes was associated with a significantly lower risk of new-onset gout. The development of new-onset gout was independently associated with decreased patient survival (AHR 1.26, 95% CI 1.08-1.47) as well as death-censored graft survival.. Cyclosporine is an independent risk factor for new-onset gout after transplantation. The incidence of new-onset gout appears to be increasing even while the use of cyclosporine is decreasing, and the development of new-onset gout was an independent predictor for death and graft loss in this population.

Topics: Body Mass Index; Cyclosporine; Female; Gout; Humans; Hyperuricemia; Incidence; Kidney Transplantation; Male; Middle Aged; Regression Analysis; Risk Factors; Tacrolimus; United States