Endogenously-Produced Hyaluronan and Its Potential to Regulate the Development of Peritoneal Adhesions

Formation of peritoneal adhesions (PA) is one of the major complications following intra-abdominal surgery. It is primarily caused by activation of the mesothelial layer and underlying tissues in the peritoneal membrane resulting in the transition of mesothelial cells (MCs) and fibroblasts to a pro-fibrotic phenotype. Pro-fibrotic transition of MCs—mesothelial-to-mesenchymal transition (MMT), and fibroblasts activation to myofibroblasts are interconnected to changes in cellular metabolism and culminate in the deposition of extracellular matrix (ECM) in the form of fibrotic tissue between injured sides in the abdominal cavity. However, ECM is not only a mechanical scaffold of the newly synthetized tissue but reciprocally affects fibrosis development. Hyaluronan (HA), an important component of ECM, is a non-sulfated glycosaminoglycan consisting of N-acetyl-D-glucosamine (GlcNAc) and D-glucuronic acid (GlcUA) that can affect the majority of processes involved in PA formation. This review considers the role of endogenously produced HA in the context of different fibrosis-related pathologies and its overlap in the development of PA.

Assessing Mechanical Catheter Dysfunction in Peritoneal Dialysis Patients: A Case Control, Proof-of-Concept Study

New guidelines on evaluation of peritoneal membrane function recommend ruling out catheter dysfunction when evaluating patients with low ultrafiltration capacity. We introduce the use of a combination of parameters obtained from daily measurements of the cycler software for predicting catheter dysfunction in automated peritoneal dialysis patients. Out of 117 patients treated between 2015 and 2021, all patients with verified catheter dysfunction (n=14) were identified and compared to controls (n=19). We retrieved cycler data for seven days each and tested parameters predictive capability of catheter dysfunction. Total number of alarms/week >7 as single predictive parameter of catheter dislocation identified 85.7% (sensitivity) of patients with dislocated catheter and 31.6% (1-specificity) of control patients. A combination of parameters (number of alarms/week >7, drain time >22 min, ultrafiltration of last fill <150 mL) where at least two of three parameters appeared identified the same proportion of patients with catheter dislocation, but was more accurate in identifying controls (21% false positive). An easily applicable combination of daily cycler readout parameters, also available in remote monitoring platforms can be used as predictor of inadequate catheter function during routine follow-up with potential for earlier diagnosis of this frequent complication in the future.

COVID 19 Pneumonia and a Rare Form of Fungal Peritonitis in a Patient Survivor on Peritoneal Dialysis

Peritoneal dialysis (PD) related peritonitis is usually caused by bacteria, but viruses and fungi could also affect the peritoneal membrane and cause cloudy effluent with negative bacterial cultures. We present a case of a PD patient who survived fungal peritonitis caused by Geotrichum klebahnii (March 2015) and COVID-19 pneumonia (April 2021) with peritonitis probably caused by the SARS-CoV-2 virus. The fungal peritonitis followed one episode of exit-site infection and two episodes of bacterial peritonitis treated with a wide-spectrum antibiotic. The patient’s PD catheter was removed immediately upon the diagnosis of fungal peritonitis, and an antifungal treatment was continued for 3 weeks after catheter removal. The new peritoneal catheter was reinserted 8 weeks after complete resolution of peritonitis, and the patient continued treatment with PD. The patient developed severe Covid-19 pneumonia with a sudden appearance of cloudy peritoneal effluent. There was no bacterial or fungal growth on the effluent culture. A PCR test for SARS-CoV-2 in peritoneal effluent was not performed. The peritoneal effluent became transparent with the resolution of the severe symptoms of Covid-19 pneumonia.

The Role of Monocytes in Gouty Arthritis

<p>Gout is one of the most painful forms of arthritis characterised by the deposition of monosodium urate crystals (MSU) in the joint synovium and the subsequent acute influx of circulating leukocytes. This study investigated the contribution of the inflammatory microenvironment in driving recruited monocyte differentiation and function in acute gouty inflammation. Using the murine peritoneal model of MSU-induced inflammation, the differentiation and functional phenotypes of MSU-recruited monocytes were compared in normal acute inflammation and in an inflammatory environment depleted of resident macrophages and infiltrating neutrophils. In addition, the role of the local environment in producing monocyte chemoattractant protein-1 (MCP-1) was investigated. Furthermore, the effect of transmigration on the suppressor phenotype of recruited monocytes was also explored. The pro-inflammatory environment was shown to play a key role in the differentiation and function of recruited monocytes in MSU-induced acute inflammation. In addition, infiltrating neutrophils suppressed the pro-inflammatory abilities of recruited monocytes, which may contribute to the resolution of inflammation. Using both whole peritoneal membrane preparations and in vitro culture techniques, results showed that mesothelial cells lining the peritoneal membrane were a source of MCP-1 production, which contributed to monocyte recruitment. Finally no differences were observed in either the differentiation or functional phenotypes of MSU-recruited monocytes isolated from Glatiramer acetate (GA) treated or non-treated mice. These findings suggest that the inflammatory microenvironment plays a key role in driving the recruitment, differentiation and function of circulating monocytes in the MSU-induced model of acute inflammation.</p>

The Role of Monocytes in Gouty Arthritis

<p>Gout is one of the most painful forms of arthritis characterised by the deposition of monosodium urate crystals (MSU) in the joint synovium and the subsequent acute influx of circulating leukocytes. This study investigated the contribution of the inflammatory microenvironment in driving recruited monocyte differentiation and function in acute gouty inflammation. Using the murine peritoneal model of MSU-induced inflammation, the differentiation and functional phenotypes of MSU-recruited monocytes were compared in normal acute inflammation and in an inflammatory environment depleted of resident macrophages and infiltrating neutrophils. In addition, the role of the local environment in producing monocyte chemoattractant protein-1 (MCP-1) was investigated. Furthermore, the effect of transmigration on the suppressor phenotype of recruited monocytes was also explored. The pro-inflammatory environment was shown to play a key role in the differentiation and function of recruited monocytes in MSU-induced acute inflammation. In addition, infiltrating neutrophils suppressed the pro-inflammatory abilities of recruited monocytes, which may contribute to the resolution of inflammation. Using both whole peritoneal membrane preparations and in vitro culture techniques, results showed that mesothelial cells lining the peritoneal membrane were a source of MCP-1 production, which contributed to monocyte recruitment. Finally no differences were observed in either the differentiation or functional phenotypes of MSU-recruited monocytes isolated from Glatiramer acetate (GA) treated or non-treated mice. These findings suggest that the inflammatory microenvironment plays a key role in driving the recruitment, differentiation and function of circulating monocytes in the MSU-induced model of acute inflammation.</p>

NEPRHOGENIC ASCITES: A CASE OF POORLY UNSTATED SYNDROME

Nephrogenic ascites is a controversial and very rare entity; it was described for the first time in 1970.It is often described as an antites of ascites in patients undergoing renal transplant therapy with end-stage renal disease (ESRD). This condition is thought to be multifactorial in origin resulting from including amalgamation of malnutrition, inadequate dialysis and ultra-filtration with resultant uraemia and increased peritoneal membrane permeability. Prognosis is often grave particularly if timely diagnosis is not done with ensuing treatment. We are talking about the story of a 40-year-old man with no medical history who once reported to us the discomfort, nausea and vomiting that lasted for two days. He was found to have multiple ascites. A diagnostic paracentesis was performed and it was revealed that the patient had Hepatic, cardiovascular, infectious and dangerous causes of ascites were not excluded after a thorough examination. The cause of ascites was determined to be phrogenic. Patient showed excellent renal recovery and disappearance of ascites which makes this case quite unusual given the setting of absence of chronic disease of kidney as well as liver.

Peritoneal-Membrane Characteristics and Hypervolemia Management in Peritoneal Dialysis: A Randomized Control Trial

Excessive bodily-fluid retention is the major cause of hypertension and congestive heart failure in patients with end-stage renal disease. Compared to hemodialysis, peritoneal dialysis (PD) uses the abdominal peritoneum as a semipermeable dialysis membrane, providing continuous therapy as natural kidneys, and having fewer hemodynamic changes. One major challenge of PD treatment is to determine the dry weight, especially considering that the speed of small solutes and fluid across the peritoneal membrane varies among individuals; considerable between-patient variability is expected in both solute transportation and ultrafiltration capacity. This study explores the influence of peritoneal-membrane characteristics in the hydration status in patients on PD. A randomized control trial compares the bioimpedance-assessed dry weight with clinical judgment alone. A high peritoneal membrane D/P ratio was associated with the extracellular/total body water ratio, dialysate protein loss, and poor nutritional status in patients on PD. After a six-month intervention, patients with monthly bioimpedance analysis (BIA) assistance had better fluid (−1.2 ± 0.4 vs. 0.1 ± 0.4 kg, p = 0.014) and blood-pressure (124.7 ± 2.7 vs. 136.8 ± 2.8 mmHg, p < 0.001) control; however, hydration status and blood pressure returned to the baseline after we prolonged BIA assistance to a 3-month interval. The dry-weight reduction process had no negative effect on residual renal function or peritoneal-membrane function. We concluded that peritoneal-membrane characteristics affect fluid and nutritional status in patients on PD, and BIA is a helpful objective technique for fluid assessment for PD.