Oxalate, inflammasome, and progression of kidney disease

Abstract

Purpose of review Oxalate is an end product of metabolism excreted via the kidney. Excess urinary oxalate, whether from primary or enteric hyperoxaluria, can lead to oxalate deposition in the kidney. Oxalate crystals are associated with renal inflammation, fibrosis and progressive renal failure. It has long been known that as glomerular filtration rate (GFR) becomes reduced in chronic kidney disease (CKD), there is striking elevation of plasma oxalate. Taken together, these findings raise the possibility that elevation of plasma oxalate in CKD may promote renal inflammation and more rapid progression of CKD independent of primary etiology. Recent findings The inflammasome has recently been identified to play a critical role in oxalate-induced renal inflammation. Oxalate crystals have been shown to activate the nucleotide-binding domain, leucine-rich repeat inflammasome 3 (also known as NALP3, NLRP3 or cryopyrin), resulting in release of Interleukin-1β and macrophage infiltration. Deletion of inflammasome proteins in mice protects from oxalate-induced renal inflammation and progressive renal failure. Summary The findings reviewed in this article expand our understanding of the relevance of elevated plasma oxalate levels leading to inflammasome activation. We propose that inhibiting oxalate-induced inflammasome activation, or lowering plasma oxalate, may prevent or mitigate progressive renal damage in CKD, and warrants clinical trials.

A randomised Phase II/III study to evaluate the efficacy and safety of orally administered Oxalobacter formigenes to treat primary hyperoxaluria

“…Calcium oxalate crystals can provoke parenchymal inflammation, interstitial fibrosis and nephrocalcinosis [11, 12, 31]. This crystal-induced damage in combination with renal obstruction can lead to progressive decline in kidney function.…”

72-Year-Old Woman With Fatigue, Confusion, and Severe Acute Renal Failure

“…1 Excessive urinary oxalate excretion can be due to primary endogenous overproduction of oxalate, excess exogenous oxalate intake and/or absorption, or decreased renal clearance. 1,3,10 Serum oxalate levels in adults vary below 1 to 3 mmol/L but can be elevated up to 45 mmol/L in patients undergoing hemodialysis patients. 3 Malabsorptive bariatric surgeries, such as RYGB, can cause secondary oxalate nephropathy due to intestinal oxalate absorption.…”

“…1,3,10 Serum oxalate levels in adults vary below 1 to 3 mmol/L but can be elevated up to 45 mmol/L in patients undergoing hemodialysis patients. 3 Malabsorptive bariatric surgeries, such as RYGB, can cause secondary oxalate nephropathy due to intestinal oxalate absorption. The incidence of hyperoxaluria after RYGB has been reported to be as high as 42% to 67% at 1 to 3.5 years postoperatively.…”

“…Magnesium and calcium supplementation have found to decrease gastrointestinal oxalate absorption by binding to intestinal oxalate. 3 Our patient met with the hospital nutrition service regarding education for a low-oxalate diet and appropriate nutrition in the setting of acute and chronic kidney disease. In general, patients with hyperoxaluria are advised to avoid foods containing high levels of oxalate, for example, pomegranate, rhubarb, star fruit, spinach, almonds, and soy products.…”

“…Unbound oxalate is more readily absorbed in the remaining small intestine and colon instead of excreted. 1,3,5,6 Post-RYGB renal diseases include calcium oxalate nephrolithiasis and oxalate nephropathy associated with interstitial oxalate deposits. 7 This patient developed oxalate nephropathy manifesting as acute kidney injury on a background of chronic kidney disease approximately 18 months after RYGB.…”