Interstitial nephritis and nephrogenic diabetes insipidus in a patient treated with pemetrexed

Abstract

We present a case of interstitial nephritis and nephrogenic diabetes insipidus (NDI) in a patient treated with pemetrexed (500 mg/m 2 ) for non-small cell lung cancer. Renal impairment and diabetes insipidus appeared after the first treatment cycle while he totally received four cycles of chemotherapy. There was not any significant myelosuppression and the patient was on regular supplementation with folic acid and vitamin B 12 . He was not on any other medications and he did not receive any nephrotoxic agents. Kidney biopsy showed acute tubular necrosis together with interstitial inflammatory infiltrate of mononuclear cells and interstitial fibrosis occupying 25% of the cortex. There was not any improvement of renal function after a 2-week trial of oral prednisone. In the present case report, we review the literature for pemetrexed-induced renal toxicity and the possible mechanisms involved.

Pemetrexed-induced acute kidney failure following irreversible renal damage: two case reports and literature review

“…Michels et al (12) and Stavroupoulos et al (13) published one case report each, in which both patients underwent kidney biopsy. The first developed acute tubular necrosis and interstitial nephritis after six cycles, the latter interstitial nephritis and diabetes insipidus after only four cycles.…”

Pemetrexed-Induced Nephrogenic Diabetes Insipidus

“…One case described a patient with non–small cell lung cancer who showed AKI beginning with the first cycle of pemetrexed therapy, with serum creatinine rising and ultimately peaking at 3.4 mg/dL (eGFR, 19ml/min/1.73 m 2 ). 10 After 3 cycles of pemetrexed therapy, he developed nephrogenic diabetes insipidus, based on hypernatremia, low specific gravity, and urine sodium, normal hypothalamic-pituitary MRI, and only partial response to polyuria with desmopressin. Kidney biopsy specimen showed interstitial fibrosis and acute tubular necrosis.…”

“…5–9 In 2 such cases, accompanying nephrogenic diabetes insipidus was also noted, with the authors suggesting that the modest to severe AKI may have led to distal tubular injury sufficient to explain the nephrogenic diabetes insipidus. 10,11 …”

Néphrotoxicité du pemetrexed

“…Les lésions rénales et cutanées ne semblent pas être en rapport avec la carence en folates, d'autant que les patients étaient correctement supplémentés. Revue des cas rapportés dans la littérature Douze cas d'IRA (incluant 2 cas personnels non publiés) suite à l'administration de pemetrexed ont été rapportés [40][41][42][43][44][45][46] [44], une IRA irréversible après un traitement par pemetrexed (500 mg/m 2 ) est apparue en dépit d'une supplémentation vitaminique adé-quate et d'une corticothérapie orale de 2 semaines, nécessitant l'épuration extrarénale itérative. Dix patients ont fait l'objet d'un traitement séquentiel (platine + pemetrexed, suivie de pemetrexed seul).…”

“…Un diabète insipide néphrogénique et une acidose tubulaire rénale distale ont été signalés respectivement chez 3 patients [41,44] (un cas personnel) et 1 patient [41]. D'autres anomalies électrolytiques ont également été rapportées suite à l'administration de pemetrexed : hypokaliémie 3,1 %, l'hypocalcémie 1,5 %, hyponatrémie 1,3 %, hypomagnésémie 0,8 %, hypernatrémie chez 0,2 %, et une hypophosphatémie 0,4 %, probablement en rapport avec une atteinte tubulaire.…”