BACKGROUND Morphology changes of the peritoneal membrane after long-term peritoneal dialysis (PD) consist of denudation of peritoneal mesothelial cells, interstitial sclerosis, and hyalinizing vasculopathy. Those changes are considered to be the result of uremia and bioincompatible effects of conventional acidic lactate-buffered dialysate with glucose degradation products (GDPs). In the last decade, biocompatible dialysate with neutral pH and low GDPs has become widely used. Clinical practice has been modified in Japan, especially for anuric patients, and now includes the use of hybrid therapy. The impact on peritoneal morphology has not been well reported. OBJECTIVE The aim of the present study was to investigate the long-term effect on peritoneal morphology and function of biocompatible fluid use and current clinical practice in Japan, including hybrid dialysis therapy. METHODS We evaluated peritoneal biopsy specimens from patients who had undergone PD for more than 3 years. We used the average peritoneal thickness (APT) of the submesothelial compact zone as a marker of interstitial sclerosis and the lumen/vessel diameter ratio (L/V ratio) at postcapillary venules as a marker of hyalinizing vasculopathy. Demography and other data for the patients, including dialysate-to-plasma (D/P) ratio of creatinine, were obtained at baseline and every 6 months by peritoneal equilibration test. RESULTS Between 2002 and 2009, 110 patients started PD therapy with biocompatible dialysate at Tokyo University Hospital. Among them, 11 patients (8 men, 3 women; age: 54.2 ± 11.8 years; 1 with diabetes mellitus) were enrolled into this morphology study. The mean duration of PD in this group was 61 ± 11.3 months, and the mean time to peritoneal biopsy was 58 ± 15.1 months. The median APT was 180 μm (96 - 1424 μm), and the median L/V ratio was 0.66 (0.46 - 0.74). No obvious correlations between APT, L/V ratio, and PD duration were detected. The D/P creatinine of the 11 patients was maintained at a favorably low value, comparable with that of the other 99 patients. CONCLUSIONS Peritoneal dialysis therapy using biocompatible dialysate in conjunction with modification of clinical practice may minimize the progression of peritoneal interstitial sclerosis and hyalinizing vasculopathy, preserving favorable peritoneal function for more than 3 years.