MO427SAFE USE OF ALLOPURINOL TO TREAT ACUTE URIC ACID NEPHROPATHY IN PREGNANCY: A CASE REPORT

Introduction Acute uric acid nephropathy (UAN) is characterized by acute kidney injury (AKI) due to uric acid crystal precipitation within the distal tubules and collecting ducts. We present a young woman, with a history of hyperuricaemia, who was treated with allopurinol for acute UAN during her first pregnancy. She also continued allopurinol treatment during her second pregnancy for prevention of further acute UAN. To the author’s knowledge, this is the first case report of biopsy-confirmed acute UAN during pregnancy. Case report A 20 year old woman, who was 13 weeks pregnant, was admitted with AKI. Past medical history included chronic kidney disease (CKD) and gout since the age of 17. She had an extensive family history of CKD and gout (without diagnosis, despite genetic testing). She had been on daily allopurinol 300mg, but this was stopped 8 weeks prior by her rheumatology team due to concerns about teratogenicity. At that time serum creatinine was at her baseline of 100 μmol/L (normal range 50-120 μmol/L) and serum uric acid had been 740 μmol/L (normal range 140-360 μmol/L). On admission, she felt well and was euvolemic. Serum creatinine was now 352 μmol/L and her serum uric acid level was 1720 μmol/L, with an elevated urine uric acid to creatinine ratio of 1.1. She underwent renal biopsy, which showed significant deposition of uric acid crystals in the renal tubules, confirming a diagnosis of acute UAN. She was given intravenous fluids. The uncertainties of allopurinol use in pregnancy were discussed with her, and she was restarted on allopurinol 200 mg daily. Over the next 3 weeks, serum uric acid decreased to 470 μmol/L and serum creatinine to 116 μmol/L. She was maintained on allopurinol during her pregnancy and delivered a healthy baby girl. She was advised against further pregnancies due to increased risk of maternal and fetal complications. However, three years later she presented at 15 weeks’ gestation. After a discussion regarding the potential teratogenic effects of allopurinol versus the risk of recurrent severe AKI due to acute UAN if it was again discontinued, she chose to continue allopurinol. The pregnancy proceeded without complication. Her daughters are now 8 and 5 years old. They do not have any congenital malformations, though both have mild to moderate learning difficulties. Discussion Allopurinol is approved for the treatment of hyperuricaemia outside of pregnancy, but given it interrupts purine synthesis there is a biologically plausible concern regarding teratogenicity. However, in our patient with long-standing hyperuricaemia it was the discontinuation of allopurinol that precipitated AKI due to the resultant crystal formation when serum uric acid reached very high levels. Biopsy confirmation of acute UAN was vital in this case, given the possibility of missing an alternative diagnosis and the risks of giving empirical allopurinol therapy. Once the diagnosis for her severe AKI was confirmed, it was clear our patient would benefit from uric acid lowering therapy. Our patient had two healthy girls despite using allopurinol from week 16 in her first pregnancy and throughout her second pregnancy. Unfortunately, both girls have mild to moderate learning needs, though it is unprovable whether allopurinol was causative as no study has followed up long term outcomes after foetal exposure during pregnancy.

Acute Uric Acid Nephropathy following Epileptic Seizures: Case Report and Review

Acute hyperuricemia most commonly occurs in patients who experience tumor lysis syndrome. Hyperuricemia along with other electrolyte abnormalities like hyperkalemia, hypocalcemia, and hyperphosphatemia leads to acute kidney injury (AKI) due to acute uric acid nephropathy which is associated with significant morbidity. High risk patients are thus closely monitored for signs of these laboratory abnormalities. Extreme exercise, rhabdomyolysis, and seizures are rare causes of acute hyperuricemia. Serum uric acid level is not routinely monitored as a part of postictal labs. We report an unusual case of AKI in a young male with recurrent seizures and no associated rhabdomyolysis who was found to have acute uric acid nephropathy. Timely administration of Rasburicase prevented the need for dialysis in this patient and led to complete renal recovery. This case illustrates the importance of doing a urine microscopy and checking uric acid level in patients with recurrent seizures who develop unexplainable AKI, as timely management helps improve outcome. We also briefly review the pathophysiology of seizure related hyperuricemia and acute uric acid nephropathy.

Disposable Nonenzymatic Uric Acid and Creatinine Sensors Using μPAD Coupled with Screen-Printed Reduced Graphene Oxide-Gold Nanocomposites

Uric acid (UA) and creatinine are the imperative biological substance for clinical monitoring and diagnosis. Measuring the ratio between uric acid and creatinine in urine helps differentiate acute uric acid nephropathy from the hyperuricemia that secondarily occurs to renal failure. In general, the ratio is greater than 0.9 in acute uric acid nephropathy and less than 0.7 in hyperuricemia. In this work, disposable nonenzymatic screen-printed reduced graphene oxide-gold nanocomposites electrodes were firstly developed for the quantitative analysis of uric acid. Our sensors were also coupled with the paper-based colorimetric sensor of the determination of creatinine. Hence, an alternative high-throughput screening test for the uric acid to creatinine ratio with high sensitivity, specificity, simplicity, and rapidity was developed. Under the optimum conditions, our disposable nonenzymatic screen-printed electrode for the determination of uric acid shows the acceptable analytical performance in a wide range of linearity (2.5-1,000 μM) with a low detection limit of 0.74 μM. Our electrodes also showed no interference from common physiologic compound in urine. The determination of creatinine has been developed using Jaffé reaction between the creatinine and picric acid in alkaline condition. The alkaline picrate color on μPAD changed from yellow to orange in the presence of creatinine and the orange intensity is directly proportional to the creatinine amount in a linearity range of 0.20-6.0 mM as a detection limit of 180 μM. Finally, our device has been utilized to determine uric acid and creatinine simultaneously in control urine samples with acceptable result.