Summary: A chance post on a global CBBLE creates intrigue in a critical realist heutagogue (aka CRH where H is more often used to mean heutagogy) and leads the CRH human user to search and share more on this topic.
Conversational participatory medical cognition aka Web 2.0:
[19/08, 19:01]gm:
[19/08, 19:25]cm:
Thanks for sharing.
Was also stimulated to find out more.
As far as the patient data here is concerned, it appears to be a real patient experience although it's mentioned as case scenario so can't be sure. The case narrative indicates certain highlights around his exercise induced AKI that was later suspected to be due to RHUC.
Found another real case from Hyderabad, Telangana here: https://pmc.ncbi.nlm.nih.gov/
And another from Kolkata here: https://journals.sagepub.com/
Till 2020 the Hyderabad case report was the second to report this condition from India along with the genomic analysis.
AI driven medical cognition offering further structured summary and analysis
Online Clinical Biochemistry Learning Session: Renal Hypouricemia (RHUC)
Core Concept: Renal Hypouricemia (RHUC) is a rare genetic disorder characterized by a defect in the renal tubular reabsorption of uric acid, leading to abnormally low serum uric acid levels (< 2.0 mg/dL) and increased urinary uric acid excretion. It is a significant, though often overlooked, cause of exercise-induced acute kidney injury (AKI).
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1. Pathophysiology: How the Kidney Handles Uric Acid
To understand RHUC, one must first understand normal urate handling (as depicted in Figure 1 of the Hyderabad case report).
· Filtration: Uric acid is freely filtered at the glomerulus.
· Reabsorption: ~90% of the filtered load is reabsorbed in the proximal tubule. This is the key process disrupted in RHUC.
· URAT1 (SLC22A12): The primary apical (luminal) transporter responsible for urate reabsorption from the urine into the tubular cell.
· GLUT9 (SLC2A9): The major basolateral transporter that moves urate from the tubular cell into the blood.
· Secretion: A smaller portion is secreted back into the tubule via other transporters (e.g., OAT1, OAT3).
Genetic Defects:
· RHUC Type 1: Caused by loss-of-function mutations in the SLC22A12 gene encoding URAT1. This is the most common type, especially in Japanese and Korean populations.
· RHUC Type 2: Caused by mutations in the SLC2A9 gene encoding GLUT9. This is rarer and often leads to more severe hypouricemia, as it blocks the final exit step from the cell into the blood.
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2. Clinical Presentation: The Case Studies as Examples
The shared cases illustrate the classic and a variant presentation.
A. The Classic Case (Hyderabad Report):
· Patient: 15-year-old boy.
· Precipitant: Strenuous anaerobic exercise (sprint run).
· Symptoms: Severe bilateral loin pain, extreme fatigue, oliguria/anuria.
· Key Biochemical Findings:
· During AKI: Serum Creatinine 7.4 mg/dL, Uric Acid low (noted as "extremely low").
· After Recovery: Confirmed hypouricemia. Fractional Excretion of Uric Acid (FEUA) = 52% (Normal <10%). This is diagnostic.
· Notable Absence: No significant rise in Creatine Kinase (CK=280 IU/L), ruling out rhabdomyolysis as the primary cause.
· Genetics: Compound heterozygous mutation in SLC2A9 (GLUT9), confirming RHUC Type 2.
· Family History: Mother also had hypouricemia (1.8 mg/dL), suggesting a hereditary pattern.
B. The Variant Case (Kolkata Report):
· Patient: 19-year-old man.
· Precipitant: Rigorous gym exercise.
· Symptoms: Muscular pain, weakness, dark urine.
· Key Biochemical Findings:
· During AKI: Markedly elevated Creatinine (736 μmol/L) and, crucially, CK was very high (10,127 U/L) indicating rhabdomyolysis. His uric acid was normal (243 μmol/L) at this time.
· After Recovery: Profound hypouricemia (17 μmol/L) with high FEUA (151%) was discovered.
· Family History: Brother also had hypouricemia and exercise intolerance.
· Key Learning Point: This case demonstrates that RHUC and rhabdomyolysis are not mutually exclusive. A patient with RHUC can also develop rhabdomyolysis from extreme exercise. The initial normal uric acid during AKI is a red herring and highlights why follow-up testing is essential.
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3. Why Does Exercise Cause AKI in RHUC? (The Proposed Mechanism)
The exact mechanism is not fully proven but is thought to be a multi-hit model involving loss of antioxidant protection:
1. Exercise-Induced Renal Vasoconstriction: Strenuous exercise shunts blood away from the kidneys, causing transient ischemia.
2. Oxidative Stress: Upon reperfusion, a burst of oxygen-free radicals is generated.
3. Lack of Antioxidant Defense: Uric acid is a potent intracellular antioxidant. Tubular cells in RHUC patients have a depleted uric acid pool due to their reabsorption defect, making them uniquely vulnerable to this oxidative stress.
4. Result: Severe acute tubular necrosis (ATN) and AKI, often with the characteristic symptom of severe loin pain.
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4. Diagnostic Approach (Answering the Original Question)
Yes, if serum uric acid is ≤2.0 mg/dL, you should absolutely investigate hypouricemia. The investigation is simple and non-invasive.
Step-by-Step Workup:
1. Confirm Hypouricemia: Repeat the test on a fresh sample when the patient is well and hydrated.
2. Check 24-hour Urinary Uric Acid Excretion or Fractional Excretion (FEUA):
· Expected in RHUC: Normal or high total urinary uric acid excretion, with a FEUA > 10% (often >50%, as seen in the cases). A high FEUA confirms a renal cause (over-excretion) as opposed to reduced production (e.g., Wilson's disease, SIADH).
3. Exclude Other Causes: Rule out generalized proximal tubular dysfunction (Fanconi syndrome) by checking for glycosuria, phosphaturia, and aminoaciduria.
4. Genetic Testing: The gold standard for confirming and typing RHUC (SLC22A12 or SLC2A9 gene sequencing). This was elegantly done in the Hyderabad case.
5. Family Screening: As shown in both cases, screening first-degree relatives can reveal an inherited pattern and identify other asymptomatic affected individuals.
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5. Management & Counselling
· There is no cure. Management is preventive.
· Patient Education: This is the cornerstone. Patients must be counseled to avoid strenuous anaerobic exercise (e.g., sprinting, repetitive weightlifting, competitive swimming).
· Hydration: Maintain excellent hydration, especially before any physical activity.
· Avoid Nephrotoxins: Be cautious with NSAIDs and other potentially nephrotoxic drugs.
· Antioxidants?: Some case reports suggest a potential benefit from vitamin C and E supplementation due to their antioxidant properties, but this is not proven.
· Allopurinol?: Paradoxically, there are reports of allopurinol (a xanthine oxidase inhibitor) being used to raise serum urate levels and potentially prevent AKI, but evidence is anecdotal.
Take-Home Messages
1. Think Beyond Rhabdo: Not all exercise-induced AKI is due to rhabdomyolysis. RHUC is an important differential diagnosis.
2. Check the Uric Acid: Always include uric acid in the initial workup of AKI. A low or normal uric acid in the context of AKI is unusual and should prompt further investigation.
3. Follow Up: The diagnostic hallmark (hypouricemia) may only be visible after the AKI has resolved.
4. FEUA is Key: The fractional excretion of uric acid is a simple, crucial calculation to confirm renal wasting.
5. Genetic & Family Impact: RHUC is a genetic disorder. Identifying a case has implications for genetic counselling and screening of family members.
These cases from India highlight that while RHUC is most reported in East Asian populations, it is a global condition and likely underdiagnosed. A high index of suspicion is required.
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