Urinary oxalate as a potential mediator of kidney disease in diabetes mellitus and obesity

Abstract

Purpose of review: Hyperoxaluria can cause kidney disease through multiple mechanisms, including tubular obstruction from calcium oxalate crystals, sterile inflammation, and tubular epithelial cell injury. Hyperoxaluria is also observed in individuals with diabetes mellitus and obesity, which are in turn risk factors for chronic kidney disease. Whether hyperoxaluria is a potential mediator of increased risk of chronic kidney disease in diabetes mellitus and obesity is unknown. Recent Findings: Individuals with diabetes have increased levels of plasma glyoxal (a protein glycation product) and glyoxylate, both of which are precursors for oxalate. Increased gut absorption of oxalate in obesity may be due to obesity-associated inflammation. A recent study in individuals with chronic kidney disease found that higher 24h urinary oxalate excretion was independently associated with increased risk of kidney disease progression, especially in individuals with diabetes and obesity. Summary: Both diabetes mellitus and obesity are associated with higher urinary oxalate excretion through distinct mechanisms. Hyperoxaluria could be a mechanism by which kidney disease develops in individuals with diabetes mellitus or obesity and could also contribute to progressive loss of renal function. Future research on pharmacologic or dietary measures to limit oxalate absorption or generation are required to test whether lowering urinary oxalate excretion is beneficial in preventing kidney disease development and progression in diabetes mellitus and obesity.

Oxalate nephropathy: a review

“…To some extent, this could be because the population was older (mean age 60 years), and diabetes is more common with aging. Diabetes has also been associated with increased oxalate excretion, perhaps via an increase in oxalate precursors such as glyoxylate and glyoxal that has been observed in diabetes [ 67 ]. Furthermore, diabetes is associated with dysfunction of the gastrointestinal tract, including gastroparesis and diabetes-related enteropathy [ 68 ], which would make these patients prone to volume depletion and an increase in urine supersaturation of calcium oxalate.…”

A Sodium Oxalate-Rich Diet Induces Chronic Kidney Disease and Cardiac Dysfunction in Rats

“…Importantly, the observed evolution of human health demographics, with an increasing number of obese, hypertensive and diabetic individuals, is a major issue; thus, a rat model allows us to consider rat species that naturally develop these pathologies (such as: Zucker rat, spontaneously hypertensive rat, Brattleboro rat and biobreeding diabetes-prone rat) and may also be confronted with oxalate-rich diets. Indeed, both diabetes mellitus and obesity are associated with higher urinary oxalate excretion, both of which are mediators of severe kidney disease [13]. This study investigates the impact of a high sodium oxalate diet on rats by assessing both renal structure and function and cardiovascular complications.…”

Sodium Oxalate-Induced Acute Kidney Injury Associated With Glomerular and Tubulointerstitial Damage in Rats

“…Intestinal oxalate absorption is predominantly passive and paracellular. In addition, transcellular transport of oxalate is mediated by SLC26 anion exchangers expressed on both apical and basolateral membranes of intestinal epithelial cells ( Efe et al, 2019 ; Knauf et al, 2019 ). In healthy humans, the plasma oxalate levels are fairly low (1–6 μmol/L) ( Kasidas and Rose, 1986 ; Hoppe et al, 2009 ).…”

“…During the acute supersaturation phase, CaOx complexes are the most common type of kidney stone, which was initially referred to as type 2 crystalline nephropathy ( Mulay et al, 2018 ). Under this condition, tubular injury is associated with crystals and/or Tamm–Horsfall protein (THP) complexes, apoptotic and inflammatory responses consistent with acute kidney injury (AKI), in addition to the risk for recurrence and/or chronic kidney disease (CKD) progression ( Lorenz et al, 2014 ; Pfau and Knauf, 2016 ; Fox et al, 2018 ; Mulay et al, 2018 ; Efe et al, 2019 ). However, clinical evidence and experimental models of ischemia-reperfusion have revealed that frequently, the recovery of renal function after AKI is incomplete and accompanied by proteinuria, tubular injury and glomerular filtration rate (GFR) decline, leading to end-stage renal disease (ESRD) ( Hingorani et al, 2009 ; Basile et al, 2012 ).…”