Case ReportABSTRACT
Almost 75% of the uric acid produced by the body is eliminated by kidney while the remaining 25% is cleared by intestines. Blood levels of uric acid is maintained by balance between breakdown of purines and rate of urate excretion. Rare causes of acute hyperurice1mia include rhabdomyolysis, strenuous exercise and fits. Acute hyperuricemia can lead to acute kidney injury. This is a case of 35-year-old male with no premorbid who presented with generalized tonic clonic fits. At presentation patient was vitally stable. He had two such episodes in last 30 minutes. After controlling the seizures with intravenous antiepileptics all his baseline investigations were sent. Complete blood picture showed leukocytosis. Liver function tests, Renal function tests, C-reactive protein, Erythrocyte sedimentation rate, Serum electrolytes, Serum calcium, magnesium and phosphorus were also normal. CPK levels were 153. Serum uric acid was 20.73 mg/dl. Chest x-ray, Electrocardiography and Echocardiography were normal. After 2 days Renal function tests started deranging with maximum levels of Urea 55 mg/dl and creatinine 2.88 mg/dl. Patient was managed with intravenous hydration and allopurinol. His renal function tests and uric acid levels normalized completely after 6 days.
Keywords: Hyperuricemia; Generalized tonic clonic fits; Acute kidney injury
Background
About two third of the body uric acid is produced endogenously while the rest of one third is from dietary products containing purines. Most of the uric acid is excreted through kidneys while the remaining through intestines. Hyperuricemia occurs either due to underexcretion of urate or overproduction of urate. Factors that predominantly effect uric acid excretion include tubular fluid Ph, tubular fluid flow rate and renal blood flow. Acute hyperuricemia can lead to acute uric acid nephropathy by renal tubular obstruction by urate and uric acid crystals which can lead to significant morbidity. Seizures is an exceedingly uncommon cause of acute hyperuricemia. This is one such case of a patient with Generalized tonic clonic fits leading to acute hyperuricemia which in turn caused acute urate nephropathy.
Case Presentation
A 35-year-old man with no premorbid presented in emergency department with generalized tonic clonic fits. At presentation patient had Bp of 130/70, Pulse 96, Temperature 98.7F, Oxygen saturation 97% with room air. Blood sugar random was 126mg/dl. He had two such episodes in last 30 minutes. Abortive therapy was given to control the fits. After initial management detail examination was done. Central nervous system examination was normal with no focal neurological deficit. Chest was clear bilaterally with rest of respiratory examination normal. Cardiovascular, Gastrointestinal and musculoskeletal examination was also normal. Complete blood picture showed leukocytosis with white blood cell count 22550/microliter with 80% neutrophils. Liver function tests, Renal function tests, C-reactive protein, Erythrocyte sedimentation rate, Serum electrolytes, Fasting lipid profile, Serum calcium, magnesium and phosphorus were also normal. Urine routine examination was normal with no myoglobinuria. CPK levels were 153 and serum prolactin levels were 404. Serum uric acid was 20.73 mg/dl. Chest x-ray, Electrocardiography and Echocardiography were normal. After 2 days his Renal function tests started deranging with Urea 45 mg/dl and creatinine 1.52 mg/dl. His previous renal function tests and uric acid were completely normal. Maximum urea and creatinine levels went up to 55 and 2.88mg/dl respectively. Patient was managed with intravenous hydration and allopurinol. His renal function tests and uric acid levels started declining and normalized after 5 days.
Discussion
In previous case studies it was noted that creatinine was
deranged initially on the day of presentation. In our case unusual
was that patient’s creatinine was normal at presentation and
started rising after 2 days. So, it is important to follow patient’s
Renal function tests for at least 4-5 days post seizure so that acute
renal failure is not missed which can prove fatal if not managed
early. Secondly in previous studies maximum level of high uric acid
levels were up to 15mg/dl while in our case serum uric acid was
extremely high with levels up to 20.73 mg/dl which was managed
successfully with early intervention.
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]. 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].
Acute uric acid nephropathy is characterized by raised
creatinine levels; high uric acid levels raised urinary urate to
creatinine ratio [6]. 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].
Acute uric acid nephropathy is reversible [1]. Epileptic fits cause
skeletal muscle breakdown which in turn causes life threatening
rhabdomyolysis leading to acute kidney injury in 15% of patients [7].
Rhabdomyolysis releases high amount of myoglobin by breakdown
of muscle cells which in turn results in high serum myoglobin
levels. Raised serum myoglobin levels exceeds haptoglobin binding
capacity resulting in myoglobinuria which causes cast formation
and tubular obstruction leading to acute kidney injury [7].
Various metabolic abnormalities have been associated with
severe epileptic seizures including lactic acidosis, raised ammonia,
raised creatine phosphokinase and high prolactin levels [2].
Rare metabolic derangements associated with seizures include
electrolyte changes, hyperuricemia and osmolality changes [2]. Fits
induced hyperuricemia is one of the rarest complications described
in literature even more rare when associated with acute urate
nephropathy [2]. Seizures cause acute uric acid nephropathy by
increasing uric acid levels and provide favorable environment for
urate crystal formation [6].
It is speculated that acute hyperuricemia secondary to
seizures occurs both due to overproduction and impaired tubular
excretion of urate [1]. Muscle injury during seizures causes tissue
breakdown which release nucleosides leading to its transport
into liver and is converted into uric acid by urea cycle [6]. Factors
that lead to hyperuricemia following fits include acidification
of urine secondary to acidosis caused by lactate production and
hypoventilation making urate less soluble, dehydration secondary
to hyperthermia and profuse diaphoresis causing increase tubular
water reabsorption leading to high tubular uric acid secretion and
renal ischemia due to shunting of blood from viscera to muscles [2].
Most effective therapy to lower uric acid levels is Rasburicase
which is a recombinant form of xanthine oxidase [2]. Allopurinol
inhibits uric acid formation, but it does not remove already
existing urate in the body and may also worsen acute renal injury
by releasing xanthine [1]. Urinary alkalization can increase urate
solubility but has not yet been proven to be effective in acute urate
nephropathy [1]. Oliguria secondary to acute urate nephropathy
have excellent response to hemodialysis [1].
Conclusion
In nutshell acute hyperuricemia is an uncommon manifestation following a seizure. Immediate necessary steps should be taken to lower uric acid levels. Acute uric acid nephropathy is a reversible condition and if early management is done to lower urate levels it can prevent progression to acute renal failure with excellent fruitful outcome.
Conflict of Interest
No conflict of interest with any institution/organization.
Grant or Fellowship Supporting the Writing of Paper
Nil.
Institutional Approval
institutional approval was obtained in compliance with regulation of our institution and generally accepted guidelines governing such work.
Processing Fee
Nil.
Author’s Contribution
Author fulfilling the ICMJE criteria.
References
- Patel C, Wilson CP, Ahmed N, Hattab Y (2019) Acute Uric Acid Nephropathy following Epileptic Seizures: Case Report and Review. Case Rep Nephrol.
- Côté JM, Bérubé AA, Bollée G (2020) Association of Hyperuricemia with Acute Kidney Injury: Case Series Report Among Patients Hospitalized with General Tonic-Clonic Seizures. Can J Kidney Health Dis.
- Srivastava A, Palsson R, Leaf DE, Higuera A, Chen ME, et al. (2019) Uric Acid and Acute Kidney Injury in the Critically Ill. Kidney Med.
- Ejaz AA, Johnson RJ, Shimada M, Mohandas R, Alquadan KF, et al. (2019) The Role of Uric Acid in Acute Kidney Injury. Nephron.
- Giordano C, Karasik O, King-Morris K, Asmar A (2015) Uric Acid as a Marker of Kidney Disease: Review of the Current Literature. Dis Markers.
- Makki N, Hajj G, Schmidt GA (2013) Seizure-induced acute urate nephropathy: case report and review. Chest.
- Wang L, Hong S, Huang H, Yang M (2018) Rhabdomyolysis following status epilepticus with hyperuricemia: A case report and literature review. Medicine (Baltimore).
