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Practitioner - Enteric Hyperoxaluria Overview
 

Enteric Hyperoxaluria Overview


What is enteric hyperoxaluria?


Enteric HOx refers to excessive excretion of oxalate in the urine that is a metabolic complication of increased gastrointestinal (GI) oxalate absorption. Enteric HOx is most commonly a complication of bariatric surgical procedures, such as Roux-en-Y gastric bypass (RYGB), and can also be a consequence of inflammatory bowel diseases (IBDs), such as Crohn’s disease or other conditions associated with GI malabsorption including cystic fibrosis (and other conditions associated with pancreatic insufficiency) or short bowel syndrome following ileal resection for any reason.1


How does malabsorption result in enteric hyperoxaluria?

 

The mechanisms potentially contributing to excessive GI absorption of oxalate and subsequent HOx in these settings include fat malabsorption (unabsorbed fat and bile acids react with calcium in the intestinal lumen, limiting the amount of calcium that can bind oxalate, leaving more free oxalate to be absorbed) and increased concentration of fatty acid and bile salts causing increased GI permeability2. This is illustrated by one study using radiolabeled oxalate, which reported that subjects who had undergone jejunoileal bypass had substantially increased oxalate absorption, with 36.8% of the isotope detected in their urine, compared with 14.4% in idiopathic stone formers and 13.6% in normal controls.3

There is an extensive epidemiologic literature describing enteric HOx, some reporting severe HOx. In bariatric surgery patients who have had a kidney stone, UOx excretion frequently exceeds 80 mg/24 hr, and some subjects may even have > 150 mg/24 hr4. Other disease states that lead to fat malabsorption such as pancreatic insufficiency, cystic fibrosis, and small bowel resection can also result in pronounced HOx.5

In post-bariatric surgery patients and patients with other malabsorptive conditions, HOx is a well-described cause of nephrolithiasis and nephrocalcinosis.6 In addition, enteric HOx is increasingly recognized as contributing to chronic kidney disease (CKD) and ESRD as a consequence of oxalate nephropathy.7

A number of studies have identified higher UOx as a significant factor associated with kidney stones after bariatric surgery.8

What FDA or EMA approved pharmacological therapies are available to treat enteric hyperoxaluria?

 

There is no approved pharmacologic therapy specifically directed at reducing the absorption of oxalate from the GI tract. Current management consists of recommendations to reduce dietary oxalate intake and increase calcium intake, and to drink large volumes of fluid, aimed at decreasing oxalate absorbed from food and decreasing urinary CaOx crystalluria, to minimize the risk of subsequent kidney stone formation and/or oxalate nephropathy due to CaOx crystals.9 However, many subjects with enteric HOx may be unable to consistently ingest the quantities of fluid required to maintain adequate urine volume. Furthermore, recommendations for a low-oxalate diet are somewhat in conflict with general recommendations that patients follow a healthy diet composed of largely plant-based foods, as many plants are high in oxalate. In conclusion, there remains a significant unmet need for improved management of patients with enteric HOx.

REFERENCES
  1. Earnest DL. Perspectives on incidence, etiology, and treatment of enteric hyperoxaluria. J Am Clin Nutr. 1977;39(1):72-75.
  2. Kumar R, Lieske JC, Collazo-Clavell ML, Sarr MG, Olson ER, Vrtiska TJ, Bergstralh EJ, Li X. Fat malabsorption and increased intestinal oxalate absorption are common after Roux-en-Y gastric bypass surgery. Surgery. 2011;149(5):654-661.
  3. Tiselius HG, Ahlstrand C, Lundstrom B, Nilsson MA. [14C]Oxalate absorption by normal persons, calcium oxalate stone formers, and patients with surgically disturbed intestinal function. Clin Chem. 1981;27(10):1682-1685.
  4. Asplin J. Hyperoxaluria and bariatric surgery. AIP Conference Procedings. 2007;900(1):82-87.
  5. Cartery C, Faguer S, Karras A, Cointault O, Buscail L, Modesto A, Ribes D, Rostaing L, Chauveau D, Giraud P. Oxalate nephropathy associated with chronic pancreatitis. Clin J Am Soc Nephrol. 2011;6(8):1895-1902.
  6. Canales BK, Gonzalez RD. Kidney stone risk following Roux-en-Y gastric bypass surgery. Transl Androl Urol. 2014a;3(3):242-249. Canales BK, Hatch M. Kidney stone incidence and metabolic urinary changes after modern bariatric surgery: review of clinical studies, experimental models, and prevention strategies. Surg Obes Relat Dis. 2014b;10(4):734-742.
  7. Nasr SH, D'Agati VD, Said SM, Stokes MB, Largoza MV, Radhakrishnan J, Markowitz GS. Oxalate nephropathy complicating Roux-en-Y Gastric Bypass: an underrecognized cause of irreversible renal failure. Clin J Am Soc Nephrol. 2008;3(6):1676-1683.
  8. Gonzalez RD, Canales BK. Kidney stone risk following modern bariatric surgery. Curr Urol Rep. 2014;15(5):401.
  9. Hoppe B, Leumann E, von Unruh G, Laube N, Hesse A. Diagnostic and therapeutic approaches in patients with secondary hyperoxaluria. Front Biosci. 2003;8(1-3):e437-443.

 
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