<b><i>Background:</i></b> Long-term peritoneal dialysis (PD), especially with nonphysiological solutions, is afflicted with the severe complication of encapsulating peritoneal sclerosis (EPS). Physiologic PD solutions have been introduced to reduce pH trauma. Data on peritoneal biopsies in pediatrics with long-term PD using physiological solutions are scant. <b><i>Case Report:</i></b> We report an adolescent who had been on 10-h continuous hourly cycles using mostly 2.27% Physioneal™ for 5 years. There were two episodes of peritonitis in October 2017 (<i>Klebsiella oxytoca</i>) and May 2018 (<i>Klebsiella pneumoniae</i>), which were treated promptly. This adolescent, who lost two kidney transplants from recurrent focal and segmental glomerulosclerosis, underwent a peritoneal membrane biopsy at the time of a third PD catheter placement, 16 months after the second renal transplant. Laparoscopically, the peritoneum appeared grossly normal, but fibrosis and abundant hemosiderin deposition were noted on histology. The thickness of the peritoneum was 200–900 (mean 680) µm; normal for age of 14 years is 297 [IQR 229, 384] μm. The peritoneum biopsy did not show specific EPS findings, as the mesothelial cells were intact, and there was a lack of fibrin exudation, neo-membrane, fibroblast proliferation, infiltration, or calcification. <b><i>Conclusions:</i></b> While the biopsy was reassuring with respect to the absence of EPS, significant histopathological changes suggest that avoiding pH trauma may not ameliorate the effects of glucose exposure in long-term PD.