Peritoneal sclerosis (PS) is a severe complication of long-term peritoneal dialysis (PD). We therefore investigated whether longitudinal analysis of solute and fluid transport preceding a diagnosis of PS could predict its development. We reviewed all standard peritoneal permeability analyses (SPAs) performed with 3.86% glucose and completed before a diagnosis of PS in all patients (n = 11) in whom that diagnosis was made in our center between 1995 and 2006. Most patients had 4 SPAs available. A linear mixed-model procedure was used to analyze the trends. Transport of small-solutes showed significant inverse U-shaped trends before a diagnosis of PS. This trend held for the mass transport area coefficients of creatinine, urea, and urate (all p < 0.05) and for their dialysate-to-plasma ratios (all p < 0. 001). Net ultrafiltration and free water transport at 60 minutes showed significant downward linear trends (both p < or = 0. 01). This U-shaped trend in small-solute transport combined with an ongoing decrease in net ultrafiltration and free water transport might be a warning sign of the development of PS. It underlines the importance of regular assessment of peritoneal function with 3.86% peritoneal equilibration tests in every PD patient-not only those at risk for peritoneal membrane failure.