Renal Hypouricemia: Causes, Risk Factors, Symptoms, Diagnosis, Treatment, Prognosis, Complications
Renal Hypouricemia is a metabolic disease that results in lower uric acid level in blood. The disease is caused by impaired or malabsorption of uric acid in the kidney. In this article, we will discuss about the various causes, symptoms, and treatments for Renal Hypouricemia.
How Do We Define Renal Hypouricemia?
- Uric Acid Reabsorption- Renal Hypouricemia is a medical condition caused by impairment of reabsorption of uric acid at apical membrane of proximal renal tubular cells.
- Excretion of Uric Acid- Uric acid is excreted in renal tubule and reabsorbed. Most of the uric acid is reabsorbed. Disease is caused following excessive uric acid excretion in urine.A
- Hypouricemia- Disease is diagnosed when blood uric acid level is below 2 mg/dl (119 micromol/L).
- Idiopathic Renal Hypouricemia (iRHUC)- iRHUC is an autosomal recessive hereditary disorder.CiRHUC is characterized by following impairment-
- Impaired tubular uric acid transport
- Re-absorption insufficiency and/or
- Acceleration of uric acid secretions.
- Asymptomatic Disease- Hypouricemia or low serum uric acid is an asymptomatic benign disease.
- Renal Stone (Nephrolithiasis)- Disease is often associated with renal stone.C
- Symptoms- Symptoms often results following obstruction of urine flow and blockade of ureter. Ureter or renal pelvis is blocked or obstructed by renal stone resulting in symptoms.
- Hypercalciuria- In some instances, hypouricemia is associated with higher urine calcium level (hypercalciuria).
- Exercise Induced Hypouricemia- Exercise may cause severe renal complication and renal failure in patient suffering with hypouricemia.D
Causes Of Renal Hypouricemia
- Genetic Disease-
- Hypouricemia is considered a genetic disorder.B, D
- Genetic mutations were found in several human studies. Most of the mutations were observed in SLC22A12 Gene.E
- There are two kinds of genetic mutations that may cause hypouricemia, one in which there is Xanthine oxidase deficiency, which results in reduced production of uric acid in the body and the second one in which there is impaired renal function resulting in increased excretion of uric acid.B
- Disorders of Purine Metabolism and Transport-
- Abnormal metabolism of purine and protein may cause hypouricemia.B
- Low Protein Diet-
- Diet containing low uric acid may result in hypouricemia.
- Disease is often seen in vegetarian with low protein diet.
- Protein diet or meat contains purine, which metabolizes to uric acid. Hypouricemia is rarely observed in non-vegetarian individuals.B
- Ingestion of toxins often causes hypouricemia. Toxin increases excretion of uric acid and decreases reabsorption.
- Increased excretion of uric acid- Certain medications and diuretics causes increases excretion of uric acid, which results in low serum uric acid level.
- Rasburicase or Sevelamer causes less production of uric acid.
Risk Factors Involved In Renal Hypouricemia
- Vegetarian diet.
- Following diseases may be associated with hypouricemia-
Symptoms of Renal Hypouricemia
- Most of the hypouricemia (85%) are asymptomatic.
- Disease is diagnosed during routine urine examination.
- Disease is benign.
- Abdominal colic pain mostly felt in right or left flank when upper ureter or pelvic ureter is obstructed
- Pelvic pain is caused by blockade of lower ureter by ureter stone.
- Pain is often radiated to lower back.
Diagnosis of Renal Hypouricemia
- Routine blood examination may suggest low serum (blood uric acid) level.
- Blood examination to evaluate cause of pelvic or flank pain may indicate low serum uric acid level.
- Normal range of blood uric acid is 2 mg/dl to 4 mg/dl.
- Uric acid clearance test- Normal or reduced clearance is caused by abnormal xanthine oxidase.
- Glomerular Filtration Rate is normal.
- Elevated levels of calcitriol
Treatment For Renal Hypouricemia
- Asymptomatic Hypouricemia-
- No treatment
- Observe any abnormal symptoms and frequent blood examination.
- Increased protein in diet.
- Symptomatic Hypouricemia-
- Low blood uric acid may be caused by increased excretion of uric acid in urine known as ‘hyperuricosuria’.
- Higher uric acid in urine may result in uric acid stone, which may cause symptoms.
- Hyperuricosuria (higher excretion of uric acid) is treated by maintaining urine pH at 6 to 6.5 by drinking excessive water. Excess water is excreted in urine and maintains low ph. Low urine pH increases reabsorption of uric acid.
- Potassium citrate is prescribed to be taken every day or alternate day.A
Prognosis Of Renal Hypouricemia
- Hypouricemia is a benign condition and its prognosis is usually quite good.
- Elevated levels increase the risk for gout and renal failure.
- Exercise-induced acute renal failure.
1. Renal hypouricemia due to enhanced tubular secretion of urate associated with urolithiasis: successful treatment of urolithiasis by alkalization of urine K+, Na(+)-citrate.
Hisatome I1, Tanaka Y, Kotake H, Kosaka H, Hirata N, Fujimoto Y, Yoshida A, Shigemasa C, Mashiba H, Sato R, et al.
2. Recurrent exercise-induced acute kidney injury by idiopathic renal hypouricemia with a novel mutation in the SLC2A9 gene and literature review.
Shen H, Feng C, Jin X, Mao J1, Fu H, Gu W, Liu A, Shu Q, Du L.
BMC Pediatr. 2014 Mar 14;14:73. doi: 10.1186/1471-2431-14-73.
3. Recurrent exercise-induced acute renal failure in a young Pakistani man with severe renal hypouricemia and SLC2A9 compound heterozygosity.
Jeannin G, Chiarelli N, Gaggiotti M, Ritelli M, Maiorca P, Quinzani S, Verzeletti F, Possenti S, Colombi M1, Cancarini G.
BMC Med Genet. 2014 Jan 7;15:3.
4. Purine disorders with hypouricemia.
Sebesta I1, Stiburkova B2.
5. Diagnostic tests for primary renal hypouricemia.
Sebesta I1, Stiburkova B, Bartl J, Ichida K, Hosoyamada M, Taylor J, Marinaki A.
Nucleosides Nucleotides Nucleic Acids. 2011 Dec;30(12):1112-6. doi: 10.1080/15257770.2011.611483.