In a recent article published in the American Journal of Kidneys Diseases, Barreto et al reviewed the literature on potential clinical uses of peritoneal fluid effluent biomarkers. Evaluation of peritoneal membrane status in patients on long-term peritoneal dialysis has mainly focused on solute transport. Only recently have peritoneal fluid effluent biomarkers been considered as a clinically useful tool. Following biomarker levels in the peritoneal fluid effluent on a longitudinal basis may be useful in detecting early morphological changes that occur in the peritoneal membrane that precede functional changes (i.e., ultrafiltration failure). The ideal biomarker should be 1) derived from intraperitoneal production and readily measurable in peritoneal fluid effluent, 2) involved in membrane pathology, and 3) have a high sensitivity and specificity for the clinical outcome of interest, such as encapsulating peritoneal sclerosis (EPS). Among the best studied peritoneal effluent biomarkers are cancer antigen 125 (CA125) and IL-6. CA125 is solely produced by human peritoneal mesothelial cells. Sudden drops in CA125 levels are indicative of severe mesothelial cell damage, which is a risk factor for future EPS. IL-6 is a cytokine produced by various cell types including mesothelial cells. IL-6 is a well-known acute phase reactant. IL-6 levels in peritoneal fluid markedly increase during an episode of peritonitis, but an association between effluent IL-6 levels and peritoneal solute transport has also been described in patients without peritonitis. A case-control study showed that an appearance rate of CA125 less than 33 U/min combined with an appearance rate of IL-6 above 350 pg/min has a sensitivity of 70% and a specificity of 89% to detect EPS. Other significant biomarkers that have been studied include plasminogen activator inhibitor-1 (PAI-1) and matrix metalloproteinase-2 (MMP-2), which have been associated with intraperitoneal fibrosis. Barreto et al illustrated their review with a clinical vignette of a patient with end-stage renal disease on peritoneal dialysis who developed intermittent small bowel obstruction due to encapsulating peritoneal sclerosis. The patient had five episodes of peritonitis in the past. Peritoneal fluid effluent was collected at 1 month after initiation of peritoneal dialysis and annually thereafter. The patient developed ultrafiltration failure by 3 years. Ultrafiltration failure was preceded by a gradual and marked decline in CA125 levels, especially after 1 year of peritoneal dialysis initiation. PAI-1 and MMP-2 effluent levels were found to be elevated. With the help of the right biomarker(s), nephrologists may anticipate poor clinical outcomes and intervene before severe complications such as EPS occur.
Helbert Rondon, MD
Assistant Professor of Medicine
University of Pittsburgh School of Medicine