Hyperoxaluria: a gut–kidney axis?

Abstract

Hyperoxaluria leads to urinary calcium oxalate (CaOx) supersaturation, resulting in the formation and retention of CaOx crystals in renal tissue. CaOx crystals may contribute to the formation of diffuse renal calcifications (nephrocalcinosis) or stones (nephrolithiasis). When the innate renal defense mechanisms are suppressed, injury and progressive inflammation caused by these CaOx crystals, together with secondary complications such as tubular obstruction, may lead to decreased renal function and in severe cases to end-stage renal failure. For decades, research on nephrocalcinosis and nephrolithiasis mainly focused on both the physicochemistry of crystal formation and the cell biology of crystal retention. Although both have been characterized quite well, the mechanisms involved in establishing urinary supersaturation in vivo are insufficiently understood, particularly with respect to oxalate. Therefore, current therapeutic strategies often fail in their compliance or effectiveness, and CaOx stone recurrence is still common. As the etiology of hyperoxaluria is diverse, a good understanding of how oxalate is absorbed and transported throughout the body, together with a better insight in the regulatory mechanisms, is crucial in the setting of future treatment strategies of this disorder. In this review, the currently known mechanisms of oxalate handling in relevant organs will be discussed in relation to the different etiologies of hyperoxaluria. Furthermore, future directions in the treatment of hyperoxaluria will be covered.

Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies

“…[23][24][25] However, the precise molecular mechanisms that result in hyperoxaluria as a consequence of defective 4-hydroxyproline catabolism due to HOGA1 mutations remain unknown, as much as the pathogenesis and the significance of hypercalciuria. Riedel and colleagues 22 demonstrated that in contrast to related bacterial enzymes termed DHDPS human HOGA1 favours forward cleavage of 4-hydroxy-2-oxo-glutarate to glyoxylate and pyruvate.…”

Enteric Oxalate Nephropathy in the Renal Allograft: An Underrecognized Complication of Bariatric Surgery

“…Oxalate nephropathy is a rare cause of acute and chronic renal failure (1)(2)(3)(4). Oxalate accumulation in renal allografts may arise de novo, or as "recurrence" of native kidney disease if underlying hyperoxalosis remains uncorrected.…”

“…Primary hyperoxaluria is a hereditary condition with at least three different genetic enzymatic defects ( Table 1) (1). Currently, liver or combined liver-kidney transplantation is recommended for patients with primary hyperoxaluria, with liver transplantation serving to correct the enzymatic deficiency (1). Secondary hyperoxaluria can arise from a variety of different processes (Table 1), including iatrogenic causes.…”

“…Secondary hyperoxaluria can arise from a variety of different processes (Table 1), including iatrogenic causes. Gastrointestinal surgery is a known cause of hyperoxaluria, most notably in situations of fat malabsorption and diarrhea (1)(2)(3)(4).…”

“…The presence of high levels of free fatty acids and bile are also said to increase colonic mucosal permeability to oxalate. (1,2) Cystic fibrosis patients with lung transplants are at particular risk of oxalate (native) nephropathy due to fat malabsorption, diabetes, antibiotic exposure which alters bowel flora including Oxalobacter formigenes, and a role for CTFR in reciprocal regulation of oxalate transporters in renal tubular epithelial cells (1,21,22). weight loss.…”