Abstract Background and Aims Peritoneal dialysis (PD) patients seem to have a higher incidence of acute alithiasic pancreatitis. Though rare and with some suggested triggers described in the literature, this is still a poorly understood and potentially life-threatening complication. We present a 60 years old woman concluding antimicrobial therapy with an icodextrin night-dwell regimen for peritonitis presenting with epigastric pain. This work reviews our approach to cloudy effluent from non-infectious causes during an infection while managing acute pancreatitis in the PD setting. We report diagnostic difficulties and treatment considerations with a positive outcome. Method We present a 60 years old woman on PD for one year presenting to the emergency room in November of 2023 with severe epigastric pain, nausea and emesis. She suffered from stage 5 chronic kidney disease due to autosomal dominant polycystic kidney disease and had disease complications as anemia and secondary hyperthyroidism controlled within targets. She was on automated PD (APD) with glucose based solutions. She was on the 17th of 21 days antibiogram guided treatment (ceftazidime) for a Enterobacter ludwigii PD-related peritonitis with good clinical evolution and peritoneal effluent (PE) leukocyte count per μl from 1258 to 91 in 5 days. In the previous 3 months she had had 2 other infectious episodes. A bacteremic urinary tract infection to E. coli associated with peritonitis treated with antibiogram guided therapy (ceftazidime) followed by C. difficile colitis treated with oral vancomycin. During each infection period she transitioned from APD to continuous ambulatory peritoneal dialysis with an icodextrin night dwell. On admission she presented with normal vital signs, no fever, and abdominal distention with severe epigastric tenderness to palpation without muscular guarding. Her dwell exchange showed blood-tinged cloudy PE. She had hemoglobin of 11.3 g/dl, otherwise normal blood cell counts, and raised amylase (213 UI/l) and lipase (1467 UI/l). There was no elevation of transaminases, cholestatic enzymes, C-reactive protein or procalcitonin and lipidemia or hyperbilirubinemia were normal. PE cell count showed 213/μl leukocytes and 202/μl erythrocytes. Abdominal ultrasound showed no evidence of an obstructive cause. She was admitted in the surgical care unit for a conservative and watchful approach. Results On presentation we accounted for the peritonitis still under treatment, acute pancreatitis, drug therapy and recently introduced icodextrin solution. The acute alithiasic pancreatitis diagnosis was established but there was still a possible causative role of icodextrin or infection and refractory peritonitis could also not be promptly excluded. The literature suggests icodextrin and other drugs as causes for acute pancreatitis in some patients but also mentions the possibility of cloudy or hemorrhagic effluent due to abdominal inflammation processes. Considering the clinical stability, the multiple possible contributing causative agents and the differential diagnosis of refractory peritonitis we closely monitored PE cell count evolution keeping the icodextrin dwell and ceftazidime prescriptions and collected samples for bacterial and fungal culture. The cultures were negative and stability of leukocyte count and mononuclear cell predominance (Fig. 1) helped us exclude the peritonitis hypothesis and attribute the PE changes to the pancreatitis process. Conclusion Inpatient monitoring and identifying all possible causes are essential to ensure good outcomes in PD patients suffering from acute pancreatitis. Full anamnesis, physical examination and close attention to laboratory findings were key in allowing adequate antibiotic therapy and resolution of the abdominal inflammatory process at hand while maintaining an adequate PD prescription.