BACKGROUND: Solute and water transport by peritoneal membrane has significant variation between patients; the function changes significantly over time. This affects treatment outcomes and requires individual approaches. AIM: To evaluate the influence of the baseline peritoneal transport state, its dynamics during peritoneal dialysis and the possibility of long-term outcomes modification. MATERIALS AND METHODS: The dynamics of peritoneal transport of solutes (in peritoneal equilibrium test, PET) and water (in mini-PET) was evaluated in a prospective interventional open-label study with historical control among 96 unselected consecutive patients admitted in three dialysis centers with unified program of peritoneal membrane monitoring and protection. RESULTS: Compared to the matched standard arm, the increase in peritoneal solute transport was significantly slower (by 9.5%) in the observation group. Ultrafiltration in classical PET decreased more slowly (by 28%). At baseline ultrafiltration was satisfactory (the proportion of the patients with ultrafiltration less 400 ml was 7.6%); water transport by small pores did not decrease (−1.1 ± 5.9 ml/year), and the decrease in total ultrafiltration (by 32.1 ± 8.2 ml/year) was due to a decrease in free water transport (by 29.9 ± 7.6 ml/year). Negative dynamics of free water transport was associated with total glucose load and with monthly glucose load greater than 2.68 kg/month. More than one case of peritonitis was associated with a more rapid decline in free water transport. The comorbidity increased in 34 of 96 patients, with median first/last scores of 5 (4–6) and 6 (4–7) points; (Wilcoxon Z = −5.423; p 0.001). When analyzed separately by peritoneal transport category, a significant worsening of the comorbidity index was observed only for high average and high transporters (Z = −2.754, p = 0.006 and Z = −3.357, p = 0.001, respectively). CONCLUSIONS: The interaction between peritoneal transport, primarily free water transport, and cardiovascular disease is certainly two-way: deterioration of water balance due to loss of effective ultrafiltration leads to volume overload and progression of cardiovascular disease. On the other hand, cardiovascular disease contributes to peritoneal membrane damage. The most sensitive monitoring of interventions effectiveness in membrane protection and preventing cardiovascular disease progression is the separate measuring of water transport through small pores and ultrapores, which simultaneously reveals a feature of progressive peritoneal fibrosis, a potential precursor of encapsulating peritoneal sclerosis.