NPHP3-Related Disease: A Possible Risk Factor for Developing Encapsulating Peritoneal Sclerosis

Introduction

Encapsulating peritoneal sclerosis (EPS) presents a rare but serious complication of chronic peritoneal dialysis (PD) which is associated with significant morbidity and mortality (Stefanidis CJ et al., Pediatr Nephrol 2014; 29: 2093–2103). In paediatric patients, there are only several previously published studies (Vidal E et al., Nephrol Dial Transplant 2013; 28: 1603–1609; Ekim M et al., Nephrology (Carlton) 2005; 10: 341–343), but the prevalence (8.7 per 1000 patient-years on PD) seems similar as in the adult population (Shroff R et al., Nephrol Dial Transplant 2013; 28: 1908–1914). On the other hand, the general outcome of paediatric patients is better with lower mortality compared to adults (Shroff R et al., Nephrol Dial Transplant 2013; 28: 1908–1914).

The pathogenesis of EPS is multifactorial, not fully elucidated, with various initiating and accelerating factors at different stages of the disease. The chronic exposure of the peritoneum during PD can activate inflammatory and angiogenic cytokines and lead to peritoneal fibrosis. There is a strong linear correlation between the duration of PD and frequency of EPS (Jagirdar RM et al., Int J Mol Sci 2019; 20: 5765). Exposure to bioincompatible PD solutions that contain supraphysiological concentrations of glucose result in peritoneal mesothelial cell loss, submesothelial fibrosis, and vasculopathy. Chronic uremia associated pro-inflammatory and oxidative stress may further accelerate these mechanisms (Jagirdar RM et al., Int J Mol Sci 2019; 20: 5765).

In peritoneal biopsies of patients with EPS, there is a loss of normal mesothelial cells, expansion of the submesothelial tissue and increased vascularisation. The histological finding includes the abnormal mucoprotein, podoplanin, which plays a crucial role in lymphangiogenesis and the overall immune response. Podoplanin expression is enhanced by inflammation and cancer. Abnormal podoplanin results in the downregulation of Wnt-signalling activity (Quintanilla M et al., Int J Mol Sci 2019; 20: 707). The Wnt signalling pathway regulates crucial aspects of cell determination, cell migration, polarity, and organogenesis.

In summary, the main risk factors to develop EPS include longer dialysis duration, high glucose concentration in PD solutions, and frequent episodes of peritonitis. EPS may also develop in patients with autoimmune diseases, peritoneal malignancies, intraperitoneal exposure to disinfectant (e. g. chlorhexidine, povidone iodine), abdominal surgery or intra-peritoneal infections. EPS can clinically manifest by ultrafiltration failure, bowel obstruction (vomiting, abdominal distension, altered bowel habits) and malnutrition. Treatment is based on immuno-suppressants (mainly corticosteroids) (Shroff R et al., Nephrol Dial Transplant 2013; 28: 1908–1914).

This case report may help increase awareness of EPS as a potentially life-threatening complication of PD in paediatric patients with NPHP3-related disease. Data were collected from medical reports only and were anonymized. Informed consent and consent for publication from parents were obtained.

Publication History

Article published online:
17 March 2023