Enteric hyperoxaluria, recurrent urolithiasis, and systemic oxalosis in patients with Crohn’s disease

Hueppelshaeuser, Renate; Unruh, Gerd E. Von; Habbig, Sandra; Beck, Bodo B.; Buderus, Stephan; Hesse, Albrecht; Höppe, Bernd

doi:10.1007/s00467-012-2126-8

Cited by 73 publications

(53 citation statements)

References 32 publications

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“…IBD patients have a 10-to 100-fold increased risk of kidney stones (69), with enteric hyperoxaluria, which is commonly seen in these patients (9,17,43), being the major risk factor. This hyperoxaluria has been largely attributed to malabsorption of fat and bile acids (16).…”

Section: Discussionmentioning

confidence: 99%

Extracellular nucleotides inhibit oxalate transport by human intestinal Caco-2-BBe cells through PKC-δ activation

Amin

Sharma

Ratakonda

et al. 2013

American Journal of Physiology-Cell Physiology

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Nephrolithiasis remains a major health problem in Western countries. Seventy to 80% of kidney stones are composed of calcium oxalate, and small changes in urinary oxalate affect risk of kidney stone formation. Intestinal oxalate secretion mediated by the anion exchanger SLC26A6 plays an essential role in preventing hyperoxaluria and calcium oxalate nephrolithiasis, indicating that understanding the mechanisms regulating intestinal oxalate transport is critical for management of hyperoxaluria. Purinergic signaling modulates several intestinal processes through pathways including PKC activation, which we previously found to inhibit Slc26a6 activity in mouse duodenal tissue. We therefore examined whether purinergic stimulation with ATP and UTP affects oxalate transport by human intestinal Caco-2-BBe (C2) cells. We measured [¹⁴C]oxalate uptake in the presence of an outward Cl⁻ gradient as an assay of Cl⁻/oxalate exchange activity, ≥50% of which is mediated by SLC26A6. We found that ATP and UTP significantly inhibited oxalate transport by C2 cells, an effect blocked by the PKC inhibitor Gö-6983. Utilizing pharmacological agonists and antagonists, as well as PKC-δ knockdown studies, we observed that ATP inhibits oxalate transport through the P2Y₂ receptor, PLC, and PKC-δ. Biotinylation studies showed that ATP inhibits oxalate transport by lowering SLC26A6 surface expression. These findings are of potential relevance to pathophysiology of inflammatory bowel disease-associated hyperoxaluria, where supraphysiological levels of ATP/UTP are expected and overexpression of the P2Y₂ receptor has been reported. We conclude that ATP and UTP inhibit oxalate transport by lowering SLC26A6 surface expression in C2 cells through signaling pathways including the P2Y₂ purinergic receptor, PLC, and PKC-δ.

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Section: Discussionmentioning

confidence: 99%

Extracellular nucleotides inhibit oxalate transport by human intestinal Caco-2-BBe cells through PKC-δ activation

Amin

Sharma

Ratakonda

et al. 2013

American Journal of Physiology-Cell Physiology

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“…1 Enteric hyperoxaluria due to excessive absorption of dietary oxalate can also result in oxalate nephropathy with renal failure, and has been reported in a wide variety of disorders including chronic pancreatitis, 2 cystic fibrosis, 3 celiac disease, 4 Crohn’s disease, 5, 6 and ingestion of a high oxalate load. 7 Malabsorptive bariatric surgery is an increasingly common cause of enteric hyperoxaluria, which can cause oxalate nephropathy.…”

Section: Introductionmentioning

confidence: 99%

NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy

Knauf

Asplin

Granja

et al. 2013

Kidney International

198

186

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Oxalate nephropathy with renal failure is caused by multiple disorders causing hyperoxaluria due to either overproduction of oxalate (primary hyperoxaluria) or excessive absorption of dietary oxalate (enteric hyperoxaluria). To study the etiology of renal failure in crystal-induced kidney disease, we created a model of progressive oxalate nephropathy by feeding mice a diet high in soluble oxalate (high oxalate in the absence of dietary calcium). Renal histology was characterized by intratubular calcium-oxalate crystal deposition with an inflammatory response in the surrounding interstitium. Oxalate nephropathy was not found in mice fed a high oxalate diet that also contained calcium. NALP3, also known as cryopyrin, has been implicated in crystal-associated diseases such as gout and silicosis. Mice fed the diet high in soluble oxalate demonstrated increased NALP3 expression in the kidney. Nalp3-null mice were completely protected from the progressive renal failure and death that occurred in wild-type mice fed the diet high in soluble oxalate. NALP3-deficiency did not affect oxalate homeostasis, thereby excluding differences in intestinal oxalate handling to explain the observed phenotype. Thus, progressive renal failure in oxalate nephropathy results primarily from NALP3-mediated inflammation.

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“…The intestinal absorption of oxalate was significantly higher in CD patients; (0.92 ± 0.57 mmol/1.73 m 2 per 24 h) compared with those without the disease (0.53 ± 0.13 mmol/1.73 m 2 per 24 h) respectively ( P < 0.05); this also correlated with hyperoxaluria and risk of developing urolithiasis[24]. …”

Section: Resultsmentioning

confidence: 99%

Urolithiasis in inflammatory bowel disease and bariatric surgery

Gkentzis¹,

Kimuli²,

Cartledge³

et al. 2016

WJN

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AIMTo analyse current literature focusing on pathogenesis and therapeutic aspects of urolithiasis with inflammatory bowel disease (IBD) and following bariatric surgery.METHODSA systematic literature search was performed using PubMed, supplemented with additional references. Studies assessing the association of IBD or bariatric surgery with renal stones in both paediatric and adulthood were included.RESULTSCertain types of stones are seen more frequently with IBD. Hyperoxaluria and hypocitraturia are the main metabolic changes responsible for urolithiasis. The incidence of renal stones in malabsorptive types of bariatric surgery such as gastric bypass is high; this is not as common in modern restrictive surgical methods. Preventative methods and urine alkalinisation have been shown to be beneficial.CONCLUSIONBoth conditions are associated with renal stones. Patients’ counselling and prevention strategies are the mainstay of urolithiasis management in these patients.

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Enteric hyperoxaluria, recurrent urolithiasis, and systemic oxalosis in patients with Crohn’s disease

Abstract: As UL/oxalosis has major implications for the general health in patients with Crohn's disease (ESRF and systemic oxalosis), new medication, e.g. to reduce intestinal oxalate absorption, is definitely needed.

Cited by 73 publications

References 32 publications

Extracellular nucleotides inhibit oxalate transport by human intestinal Caco-2-BBe cells through PKC-δ activation

Extracellular nucleotides inhibit oxalate transport by human intestinal Caco-2-BBe cells through PKC-δ activation

NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy

Urolithiasis in inflammatory bowel disease and bariatric surgery

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