A 64-Year-Old Woman with Diabetes Mellitus Associated with Increased Urinary Oxalate Excretion Presenting with Acute Kidney Injury Due to Acute Oxalate Nephropathy

Introduction

Acute oxalate nephropathy (AON) is an uncommon condition distinguished by the excessive accumulation of calcium oxalate crystals in the renal tubules, resulting in compromised renal function. Disturbances at any stage of the oxalate pathway, including increased production, increased absorption, decreased degradation, and diminished renal excretion, contribute to a disruption in oxalate homeostasis. Oxalate crystals supersaturate, precipitate, aggregate, and deposit within tubule interstitium [1]. Hyperoxaluria can progress to the development of nephrocalcinosis, nephrolithiasis, or oxalate nephropathy [2]. This can clinically manifest as acute kidney injury (AKI), chronic kidney disease (CKD), or end-stage renal disease (ESRD) [3]. A large majority of the cases reported have been due to increased intake of oxalate-containing foods. AON as a consequence of diabetes mellitus (DM) is rare. This report describes the case of a 64-year-old woman with DM associated with increased urinary oxalate excretion presenting with AKI due to AON.

Case Report

A 64-year-old woman with a medical history of recently diagnosed diabetes mellitus, hypertension on amlodipine and losartan-hydrochlorothiazide, presented to the hospital with a 4-day history of right-sided flank pain, anuria, nausea, and vomiting. She additionally experienced an episode of emesis followed by transient right-sided chest pain. She reported having no urine output in the past 2 days and noted accompanying shortness of breath. She weighed 94 kg and was 160 cm tall. Her body temperature was 37.3°C (99.1°F), blood pressure was 170/71 mmHg, and all other vital signs were within normal limits. Systemic examination was unremarkable except for right-sided flank tenderness and bilateral non-pitting pedal edema. There was no past medical history of celiac disease, Crohn disease, chronic pancreatitis, or Clostridium difficile colitis. There was also no history of ileal resection or gastric bypass surgery. The exact duration of her diabetes was unknown, but a diagnosis of diabetic retinopathy on ophthalmic examination 5 years ago suggests a duration of at least 5 years. Blood work was significant for elevated white blood cell (WBC) count of 25 000 cells/mm3, blood urea nitrogen (BUN) of 68.6 mg/dL, and serum creatinine of 9.0 mg/dL. Earlier records from a month ago showed a baseline serum creatinine of 1.5 mg/dL. Imaging showed a small atrophic left kidney with asymmetric perinephric stranding. Based on the physical examination finding of flank tenderness, elevated WBC count, and perinephric stranding on imaging, pyelonephritis was suspected and antibiotics were started. She remained anuric on day 2 of hospitalization, with worsening renal failure requiring initiation of hemodialysis. An autoimmune workup for the cause of renal failure, including serum ANCA and ANA antibodies, was negative, with normal complement levels. Urine protein electrophoresis (UPEP) and serum protein electrophoresis (SPEP) were also unremarkable. Subsequently, she underwent a random renal biopsy, which showed moderate diabetic nephrosclerosis and the presence of birefringent calcium oxalate crystals in numerous tubules (Figure 1). Evidence of an associated acute tubular injury with widespread flattening of the tubule epithelial cells, marked distention of the tubules, and focal interstitial inflammation probably in response to the oxalate deposition was also seen. Urinalysis was not feasible as the patient was anuric at presentation and remained anuric until discharge. Based on the renal biopsy report, we concluded that the acute renal failure was due to the acute oxalate nephropathy (Figure 2).

Dietary causes of hyperoxaluria were ruled out by inquiring about the consumption of several oxalate-rich dietary sources, including rhubarb, spinach, starfish fruit, black tea, chocolate, peanuts, and chaga mushrooms, all of which have been associated with elevated oxalate levels. Additionally, we considered asking about orlistat consumption, as it can interfere with fat absorption and increase the oxalate absorption from the gastrointestinal tract. Diabetes can lead to increased oxalate excretion. Given her history of DM and absence of other gastrointestinal causes, we thought that increased gastrointestinal transit time, as a result of diabetic gastroparesis, could have further precipitated AON by increasing oxalate absorption. Hence, we conducted a gastric emptying scintigraphy (Figure 3), which confirmed delayed emptying (Table 1). Her renal function did not improve thereafter, and she was placed on maintenance hemodialysis for end-stage renal failure.

Discussion

We have described the case of a 64-year-old woman with diabetes mellitus associated with increased urinary oxalate excretion presenting with acute kidney injury due to acute oxalate nephropathy. The clinical spectrum of oxalate nephropathy ranges from AKI, AKI on CKD, to CKD requiring hemodialysis [4]. Enzymatic defects in the glyoxylate cycle can lead to primary hyperoxaluria, which is characterized by an hyperoxaluric state [5]. Secondary causes of hyperoxaluria encompass increased intake of dietary oxalate or precursors and conditions that result in increased intestinal oxalate absorption. These include: Crohn’s disease, celiac disease, diabetic gastroenteropathy, small bowel resection, orlistat use, Roux-en-Y gastric bypass, and cystic fibrosis [6]. For every 100 mg of dietary oxalate ingested, there is a 1.7 mg rise in 24-hour urinary oxalate [7]. Green leafy vegetables like rhubarb and spinach are oxalate-rich dietary sources. In people eating a normal serving of spinach daily, their intake could surpass 1000 mg per day [8]. Vitamin C is a precursor to oxalate and can potentially convert into it. Consuming more than 1000 mg daily is considered as a risk factor [9]. Hyperoxaluria has also been linked to decreased intestine bacterial oxalate breakdown brought on by antibiotic use [10]. Acute dehydration, renin-angiotensin system inhibitor use, nonsteroidal anti-inflammatory medicines (NSAIDs), and diuretics can act as triggers for an underlying hyperoxaluria, which can progress to renal failure [11]. All of these contributing factors were excluded in our patient.

Our patient with underlying diabetes presented with acute oxalate nephropathy, ultimately precipitating end-stage renal disease. Diabetes has been linked to higher oxalate excretion, probably due to elevated levels of oxalate precursors like glyoxylate and glyoxal, as observed in diabetic individuals [9,12]. Additionally, diabetes can cause gastroparesis [13], increasing the risk of volume depletion and calcium oxalate supersaturation [14]. The Chronic Renal Insufficiency Cohort (CRIC) study reported that diabetic individuals had 11% higher 24-hour urinary oxalate than non-diabetic individuals [15]. Janga et al documented a case of oxalate nephropathy in a patient with long-standing diabetes, where renal hypoperfusion from diabetes ketoacidosis triggered renal failure [16]. Polarizable calcium crystals in tubular lumen, tubular epithelial cells, and infrequently in the interstitium, are the main pathological findings in cases of oxalate nephropathy. In addition to underlying glomerulosclerosis, different degrees of acute tubular injury with necrosis, interstitial nephritis, and fibrosis are observed [6].

Secondary hyperoxaluria is usually managed with: (a) low-oxalate and high-calcium diet, and (b) increasing fluid intake (>3 L/1.73 m2), (c) supplemented with bile acid sequestrants and calcium or other oxalate binders to reduce oxalate permeability in the intestines, and (d) consuming probiotics that include oxalate-degrading bacteria [17]. Although uncommon, secondary oxalate nephropathy can be fatal. Over half of such patients need renal replacement therapy, and most still depend on dialysis [4].

Conclusions

This report highlights a rare but important complication of DM and that patients who present with AKI should be investigated for the presence of AON. In individuals with inexplicable renal failure, it is critical to rule out oxalate nephropathy since early detection and treatment may improve prognosis. AON presents a significant risk, leading to both acute and chronic renal failure. It is crucial to evaluate predisposing factors in patients experiencing sudden and persistent renal failure, and a renal biopsy should be promptly done in such cases. In cases where AON is secondary to another systemic disease, addressing the primary disorder is paramount to prevent irreversible renal damage. The outcome of AON depends on the underlying cause, the oxalate burden, and the expediency of the intervention.