Background: Pasireotide is a second generation, pan-somatostatin analogue with higher receptor affinity, broader action and longer half-life than octreotide and lanreotide. While it is known to impair insulin secretion, it also results in pancreatic exocrine dysfunction, hypothesised to result from high affinity binding of somatostatin receptors 1, 2, 3 and 5 [1,2]. We report a case of interstital nephritis, likely secondary to oxalate nephropathy after commencing pasireotide.
Case: A 73-year-old woman was diagnosed with acromegaly in 2020 in the setting of newly-diagnosed type 2 diabetes. She had persistent IGF-1 elevation despite two surgical resections of an invasive mammosomatotroph pituitary tumour, cabergoline and maximal dose lanreotide treatment (figure 1). The tumour expressed SSTR5, but not SSTR2, predicting good response from pasireotide, which was commenced at 40mg 4 weekly in place of lanreotide. IGF-1 rapidly normalised. She rapidly developed significant nausea and lethargy, soon followed by an acute kidney injury (serum creatinine 425µmol/L, baseline 100µmol/L). Serum cortisol was 374nmol/L. There was no haematuria and low-level proteinuria. Renal imaging was unremarkable and glomerulonephritis screen was negative. She was treated presumptively for acute drug-induced interstitial nephritis with pulsed methylprednisolone. Subsequent renal biopsy showed acute-on-chronic interstitial nephritis with numerous oxalate crystals, raising the possibility of secondary hyperoxaluria contributing to interstitial injury. Increased faecal fat globules were noted on fat stain (3+). Shortly after drug withdrawal, urine oxalate excretion was high-normal (0.498mmol/day, RR <0.500). She continues prednisolone 37.5mg with down-trending creatinine.
Conclusion: We hypothesise that development of interstitial nephritis after three doses of pasireotide was secondary to oxalate nephropathy due to pancreatic exocrine insufficiency, or direct drug induced interstitial nephritis. A previous case of oxalate nephritis has been described with octreotide therapy, albeit with other complicating factors [3]. Hyperoxaluria should be considered in patients who develop renal dysfunction in the setting of pasireotide therapy.