Association of Hyperuricemia With Acute Kidney Injury: Case Series Report Among Patients Hospitalized With General Tonic-Clonic Seizures

Abstract

Background: Urate nephropathy is a rare cause of acute kidney injury. Although most risk factors are associated with chemotherapy, tumor lysis syndrome or rhabdomyolysis, occurrence following severe seizure has also been reported. Uric acid measurement following convulsion is rarely performed and, therefore, the incidence of hyperuricemia in this context is unknown. Objective: The objective is to present a case of urate nephropathy following generalized tonic-clonic seizure (GTCS) and to investigate the kinetics of serum uric acid and creatinine levels in a series of patients admitted for severe seizures. Design: Retrospective case report and prospective case series. Setting: Emergency room department and neurology unit of a tertiary care hospital. Patients: The study included 13 hospitalized patients for severe GTCS. Measurements: Type, timing, and duration of seizure episodes were documented. Demographic data, weight, hypouricemic therapy, and baseline serum creatinine were recorded. Blood samples (uric acid, creatinine, blood gas, lactate, and creatinine kinase) and urine samples (uric acid, creatinine, and dipstick) were prospectively collected at Day 0, 1, 2, and 3 following the GTCS episode. Methods: We identified and described one rare case of urate nephropathy following GTCS. Then, we presented the kinetic of uric acid and creatinine levels and the acute kidney injury incidence over the follow-up period. All analyses were using descriptive statistics. Results: During the study period, 13 patients with a median tonic-clonic seizure duration of 5.0 minutes (interquartile range [IQR], 2.0–12.5) were included. From day 0 to day 3, the median serum uric acid level decreased from 346.0 µmol/L (IQR, 155.0–377.5) to 178.0 µmol/L (IQR, 140.0–297.5) and median serum creatinine from 73.0 µmol/L (IQR, 51.0–80.0) to 57.0 µmol/L (IQR, 44.0–70.0). Acute kidney injury occurred in four patients. Limitations: This is a single-center observational study with small sample size, which does not allow us to demonstrate causality between the increase of uric acid levels observed and the occurrence of acute kidney injury. A delay between the first sampling and seizure episodes was observed and could explain the limited increase of uric acid levels captured. Conclusions: There is a signal for an acute increase of uric acid levels following a severe seizure before returning to baseline within 3 days. During that period, there might be an increased risk of acute kidney injury, although these changes seem to be usually mild and reversible. Our findings suggest that routine serum uric acid measurement in patients presenting with GTCS could help to identify those patients at risk of developing acute kidney injury as a result of acute hyperuricemia. Further larger studies are required to confirm the effectiveness of such screening in acute kidney injury prevention. Trial Registration: As an observational noninterventional study, no registration was required.

"Acute Hyperuricemia Secondary to Epileptic Seizures Leading to Acute Urate Nephropathy: A Case report"

“…Uric acid is the final insoluble waste product of purine breakdown [1]. Uricase enzyme which allows converts insoluble uric acid to soluble allantoin in absent in humans because of which it accumulates in the distal part of nephron particularly in acidic environment leading to toxicity [1,2]. Multiple studies have proven that high uric acid level is linked with many systemic illnesses including hypertension, chronic kidney disease, cardiovascular disease, diabetic nephropathy, stroke and acute kidney injury [3,4].…”

“…Multiple studies have proven that high uric acid level is linked with many systemic illnesses including hypertension, chronic kidney disease, cardiovascular disease, diabetic nephropathy, stroke and acute kidney injury [3,4]. Tumor lysis syndrome is the most common cause of acute hyperuricemia through high cell turnover and cell lysis following aggressive chemotherapy for cancer particularly lymphoma [1,2]. When urinary uric acid surpasses solubility threshold, it is deposited and accumulated as crystals in renal tubule leading to acute renal failure [2].…”

“…Tumor lysis syndrome is the most common cause of acute hyperuricemia through high cell turnover and cell lysis following aggressive chemotherapy for cancer particularly lymphoma [1,2]. When urinary uric acid surpasses solubility threshold, it is deposited and accumulated as crystals in renal tubule leading to acute renal failure [2]. High uric acid levels have been implicated to change the basic architecture of renal histology and have an important role in acute and chronic renal injury [5].…”

“…High uric acid causes acute urate nephropathy by various mechanisms including uric acid crystal formation and non-crystal mediated pathway [6]. Acute urate nephropathy must be suspected in high risk patients who develop acute renal failure with high serum uric acid levels and presence of urate crystals in urinary sediment [2]. Various mechanisms proposed in the development of acute kidney injury secondary to hyperuricemia include uric acid crystal formation in tubules, renal vasoconstriction, endothelial dysfunction, stimulation of inflammatory response, oxidative stress, antiangiogenic changes and direct microvascular injury [6].…”

“…Various metabolic abnormalities have been associated with severe epileptic seizures including lactic acidosis, raised ammonia, raised creatine phosphokinase and high prolactin levels [2].…”