Use of rasburicase to improve kidney function in children with hyperuricemia and acute kidney injury.

BACKGROUND: Hyperuricemia contributes to decrease in kidney function and induces additional renal damage in children with acute kidney injury (AKI). Rasburicase oxidizes uric acid (UA), decreasing its serum quantities in less than 24 h. METHODS: This is a retrospective study involving hospitalized patients under 18 years of age with underlying pathology diagnosed with AKI and severe hyperuricemia treated with rasburicase over a 4-year period. RESULTS: We describe 15 patients from 4 days of life to 18 years (median: 4.4 years). Seventy-three percent had known underlying pathologies. All presented worsening of basal renal function or AKI data. All received the usual medical treatment for AKI without response. Twenty percent received an extrarenal depuration technique. All had hyperuricemia with a mean (± SD) of 13.1 (± 2.19) mg/dl. After rasburicase administration UA levels fell to a mean (± SD) of 0.76 (± 0.62) mg/dl (p < 0.001) in less than 24 h. In parallel, a decrease in the mean plasma creatinine was observed (2.92 mg/dl to 1.93 mg/dl (p = 0.057)) together with a significant improvement of the mean glomerular filtration rate (16.3 ml/min/1.73 m2 to 78.6 ml/min/1.73 m2) (p = 0.001)). No side effects were recorded. Kidney function normalized in all cases or returned to baseline levels. CONCLUSIONS: Although the use of rasburicase is not routinely approved in pediatric patients with severe hyperuricemia and AKI, it has been used successfully without complications, and helped prevent progressive kidney damage. This study could serve as a basis for suggesting the off-label use of rasburicase for the management of complex pediatric patients in whom UA plays an important role in the development of AKI.

Secondary Immunosuppression in Pediatric Kidney Transplant Recipients.

OBJECTIVES: Currentimmunosuppressive treatments for kidney transplant recipients have improved graft viability at the expense of impaired immune surveillance. The tools for monitoring immune status in pediatric kidney transplant recipients have not been widely investigated. Better knowledge could help recognize over immunosuppression and allow implementation of individualized preventive strategies. MATERIALS AND METHODS: This retrospective and observational study included 28 pediatric kidney transplant recipients treated at a tertiary hospital. We measured peripheral blood lymphocyte subpopulations, immunoglobulins, immunosuppressivedrug levels, and viral loads. Reference analytical values for different age ranges were used to determine immune status. We recorded overall hospitalizations due to opportunistic infections and positive viral loads posttransplant. RESULTS: We found hypogammaglobulinemia and lymphopenia in 19% and 41% of the patients, respectively. Peripheral blood lymphocyte subpopulations were below normal limits in one-third of the sample. These parameters were not related to the current number or plasma levels of immunosuppressive drugs. During follow-up, cytomegalovirus, Epstein-Barr virus, and BK virus viremias were detected in 60.7% of the patients. Admissions due to opportunistic infections happened in 57.1%, mainly related to severe viral disease (30%) or gastrointestinal infections (26.7%). Most occurred in younger transplant recipients and during the first 2 years posttransplant (73.3%). We found no significant relation between peripheral blood lymphocyte subpopulations and hospital admissions for opportunistic infections or positive viral loads during follow-up. CONCLUSIONS: Recurrent hospitalizations for opportunistic infections and analytical disorders in the immune system suggested that secondary immunosuppression in pediatric kidney transplant recipients was frequent. Immunosuppression was not directly related to plasma drug levels or the number of immunosuppressive drugs. Thus, immune monitoring might be helpful in combination with immunosuppressant levels to assess immunosuppression status and to establish individualized preventive measures.

URAT1 and GLUT9 mutations in Spanish patients with renal hypouricemia.

BACKGROUND: Renal hypouricemia (RHUC), a rare inherited disorder characterized by impaired uric acid (UA) reabsorption in the proximal tubule, is caused by mutations in SLC22A12 or SLC2A9. Most mutations have been identified in Japanese patients, and only a few have been detected in Europeans. METHODS: We report clinical, biochemical and genetics findings of fourteen Spanish patients, six Caucasians and eight of Roma ethnia, diagnosed with idiopathic RHUC. Two of the patients presented exercise-induced acute renal failure and another one had several episodes of nephrolithiasis and four of them had progressive deterioration of renal function, while the rest were asymptomatic. RESULTS: Molecular analysis revealed SLC22A12 mutations in ten of the patients, and SLC2A9 mutations in the other four. A new heterozygous SLC22A12 missense mutation, c.1427C>A (p.A476D), was identified in two affected members of the same family. The rest of the patients presented homozygous, heterozygous or compound heterozygous mutations that have been previously identified in patients with RHUC; SLC22A12 p.T467M and p.L415_G417del, and SLC2A9 p.T125M. Expression studies in Xenopus oocytes revealed that c.1427C>A reduced UA transport but did not alter the location of URAT1 protein on the plasma membrane. CONCLUSIONS: The biochemical and clinical features of our patients together with the genetic analysis results confirmed the diagnosis of RHUC. This is the first report describing SLC22A12 and SLC2A9 mutations in Spanish patients.