Hyperoxaluria results from inherited disorders of glyoxylate metabolism (primary hyperoxaluria) or increased intestinal oxalate absorption (secondary hyperoxaluria) [1]. Primary hyperoxaluria types 1, 2 and 3 are caused by pathogenic variants in AGXT, GRHPR or HOGA1. Secondary hyperoxaluria can be due either to increased intake of oxalate or oxalate precursor(s), or fat malabsorption, or decreased intestinal oxalate degradation. It often results from a combination of these factors, and acute dehydration, diuretic use, inflammation and antibiotic use may further increase the urinary oxalate concentration [1]. In our case, although the intermittent diarrhea and diuretic treatment (both potentially causing hypovolemia), as well as pantoprazole treatement may have played some role in the lesions of acute tubular necrosis and interstitial nephritis, the kidney biopsy pointed to the key cause of acute kidney injury, by showing numerous oxalate crystals in the kidney, despite the absence of oxalate crystals at urinalysis. The underlying pathophysiology is clear: there was no history of gastric bypass, orlistat use of small bowel disease (Crohn’s disease of post-surgical short bowel), but pancreatectomy caused an abrupt exocrine pancreatic insufficiency, leading to fat malabsorption (Fig. 3). As a result, free fatty acids bind in the bowel lumen to calcium. There is thus less calcium available to bind oxalate in the bowel, resulting in increased absorption of free oxalate. In our patient hyperoxaluria also resulted from daily intake of ascorbic acid, a precursor of oxalate: circulating ascorbic acid is converted to dehydroascorbate then to diketogluconic acid, that breaks down to oxalate [2]. Hyperoxaluria may then lead to urinary supersaturation of calcium oxalate and crystal formation, contributing to nephrolithiasis and deposition of oxalate crystals in renal tissue (oxalate nephropathy). The latter causes tubulo-interstitial injury and fibrosis, acute kidney injury and/or chronic kidney disease [1]. It may be worth mentioning here that the sensitivity of urinary oxalate level may be decreased in case of kidney failure, precisely because of the lower urinary elimination of oxalate, as a result of tissue deposition.

Pathophysiology of hyperoxaluria and oxalate deposition in the kidney in the reported case

Oxalate nephropathy caused by exocrine pancreatic insufficiency is well-documented [3, 4]; the review of 2265 native kidney biopsies identified ON as the cause of kidney injury in 1% of cases, with chronic pancreatitis being the cause in 24% of them [4].

Oxalate nephropathy following pancreatic surgery has received hitherto little attention. A single retrospective study of pancreatectomies for adenocarcinoma performed between 2010 and 2017, identified oxalate nephropathy in 1% of patients but this was based on 3 cases only [3]. The risk was higher after pancreaticoduodenectomy than after splenopancreatectomy.

Cases of vitamin C induced oxalate nephropathy have been reported after oral and IV use of vitamin C in the intensive care unit as an adjunctive therapy for sepsis [5]. Interestingly, the COVID-19 pandemic prompted greater use of vitamin C supplements and was accompanied by an increase of cases of oxalate nephropathy secondary to high-dose vitamin [6]. The dose and duration of vitamin C therapy associated with oxalate nephropathy is variable.

Also, a multifactorial origin of ON, including an association with both vitamin C intake and malabsorption has already been described [7,8,9] but to the best of our knowledge, this is the first case reporting a combination of pancreatectomy and intake of vitamin C leading to acute oxalate nephropathy.

The prognosis of oxalate nephropathy associated with secondary hyperoxaluria is variable, with about 50% of patients reaching kidney failure [1, 4]. Treatment includes high fluid intake, calcium supplements to limit the bioavailability of intestinal oxalate, and management of the underlying cause of hyperoxaluria.

In conclusion, oxalate nephropathy should be considered among the causes of acute kidney injury following pancreatectomy, with important therapeutic implications.