Concurrent acute kidney injury and pancreatitis in a female patient: Answers

The differential diagnosis of her acute kidney injury (AKI) includes hypovolemia secondary to decreased kidney perfusion and increased vascular permeability. During pancreatitis, the release of pancreatic amylase from the injured pancreas can lead to increased vascular permeability, and to the hypovolemic state [1]. In addition, intra-abdominal hypertension increases the risk of AKI during acute pancreatitis (AP). Furthermore, inflammatory endotoxins and reactive oxygen species can directly act on the kidney to cause inflammation and a nephrotoxic effect [2].

In a recent study, the mortality rate among AP hospitalizations with AKI was 2.5%, and AKI almost doubled the risk of mortality among pediatric patients with AP [3].

AP as a cause of hemolytic uremic syndrome (HUS) is rare and reported in few case reports in both adults and pediatrics [4, 5]. Multiple mechanisms have been suggested, with the most common one that pancreatic inflammation can cause changes in the von Willebrand factor and ADAMTS13 which stimulate spontaneous binding of platelets, leading to platelet aggregation [5, 6].

Our patient had sudden onset of microangiopathic hemolytic anemia (hemoglobin < 10 g/dL), thrombocytopenia (platelets < 150,000/mm³), high serum LDH, and AKI. Those are classical manifestations of HUS. However, she did not have preceding diarrhea which ruled out typical HUS. AP rarely occurs with atypical hemolytic uremic syndrome (aHUS) [7‐9]. Since there was no diarrhea or fever, no infectious workup such as a stool PCR was done. She had no neurological symptoms and a normal ADAMTS-13 level, which ruled out thrombotic thrombocytopenic purpura (TTP). Her genetic workup revealed a heterozygous missense mutation (c355G>A, p. Gly119Arg) in exon 3 of the CFI gene. This mutation has been published several times in association with aHUS [10, 11]. In addition, she had a heterozygous missense variant (c2669G>T, p. Ser890lle) in exon 17 of CFH (which was determined to be a benign polymorphism since no functional defect was detected) and another heterozygous, missense variant (c3019G>T, p. Val1007Leu) in exon 19 of CFH which is also a benign polymorphism. However, this variant mutation has been associated with aHUS in the literature [12]. Our patient had a normal C3 level of 119 (normal range 82–173), we did not get a level of CFI during her admission. Per literature review, plasma C3 and CFI concentrations decreased in only 30% of patients with CFI mutations and a normal level does not rule out the diagnosis of aHUS [12]. The penetrance of the disease is low and only 50% of family members carrying the same complement mutation will have the disease. For that reason, genetic screening is not recommended for parents/siblings and other family members of a patient with a heterozygous complement mutation [12, 13].

How would you further manage this patient?

The clinical presentation and management of aHUS are the same whether the disease is genetic, acquired, or caused by an unknown mechanism [13]. Given that our patient had pancreatitis, IV hydration and gradual return to a regular diet were key to improvement. As the patient’s pancreatitis resolved, her AKI then resolved, along with increases in hemoglobin and platelet count. Likewise, the management of HUS is mostly supportive with strict laboratory monitoring to prevent worsening of AKI and systemic complications [13]. These measures include packed cell transfusion for severe anemia (Hb < 8 g/dL), platelet transfusion when the count is < 10,000/mm³, correction of electrolyte disturbances, and avoidance of nephrotoxic medications. Dialysis is required for patients who develop anuria, significant fluid overload, or become symptomatic with uremia/azotemia. Additionally, outpatient monitoring of kidney and hematologic function should persist on a scheduled basis to monitor for late worsening of anemia or kidney function.