Novel Colorimetric and Light Scatter Methods to Identify and Manage Peritoneal Dialysis-Associated Peritonitis at the Point-of-Care.

Introduction: Peritoneal dialysis (PD)-related peritonitis (PDRP) is a common cause of transfer to hemodialysis, patient morbidity, and is a risk factor for mortality. Associated patient anxiety can deter selection of PD for renal replacement therapy. Diagnosis relies on hospital laboratory tests; however, this might be achieved earlier if such information was available at the point-of-care (POC), thereby significantly improving outcomes. The presence of culturable microbes and the concentration of leukocytes in effluent both aid peritonitis diagnosis, as specified in the International Society for Peritoneal Dialysis (ISPD) diagnostic guidelines. Here, we report the development of 2 new methods providing such information in simple POC tests. Methods: One approach uses a tetrazolium-based chemical reporting system, primarily focused on detecting bacterial contamination and associated vancomycin-sensitivity. The second approach uses a novel forward light-scatter device (QuickCheck) to provide an instant quantitative cell count directly from PD patient effluent. Results: The tetrazolium approach detected and correctly distinguished laboratory isolates, taking 10 hours to provide non-quantitative results. We compared the technical performance of the light scatter leukocyte counting approach with spectrophotometry, hemocytometer counting and flow cytometry (Sysmex) using patient effluent samples. QuickCheck had high accuracy (94%) and was the most precise (coefficient of variation <4%), showing minimal bias, overall performing similarly to flow cytometry. Conclusion: These complementary new approaches provide a simple means to obtain information to assist diagnosis at the POC. The first provides antibiotic sensitivity following 10 hours incubation, whereas the second optical approach (QuickCheck), provides instant accurate total leukocyte count.

Human mesenchymal stromal cells broadly modulate high glucose-induced inflammatory responses of renal proximal tubular cell monolayers.

BACKGROUND: Renal proximal tubular epithelial cells (RPTEC) are dysfunctional in diabetic kidney disease (DKD). Mesenchymal stromal cells (MSC) may modulate DKD pathogenesis through anti-inflammatory mediators. This study aimed to investigate the pro-inflammatory effect of extended exposure to high glucose (HG) concentration on stable RPTEC monolayers and the influence of MSC on this response. METHODS: Morphologically stable human RPTEC/TERT1 cell monolayers were exposed to 5 mM and 30 mM (HG) D-glucose or to 5 mM D-glucose + 25 mM D-mannitol (MAN) for 5 days with sequential immunoassays of supernatants and end-point transcriptomic analysis by RNA sequencing. Under the same conditions, MSC-conditioned media (MSC-CM) or MSC-containing transwells were added for days 4-5. Effects of CM from HG- and MAN-exposed RPTEC/MSC co-cultures on cytokine secretion by monocyte-derived macrophages were determined. RESULTS: After 72-80 h, HG resulted in increased RPTEC/TERT1 release of interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and neutrophil gelatinase-associated lipocalin (NGAL). The HG pro-inflammatory effect was attenuated by concentrated (10×) MSC-CM and, to a greater extent, by MSC transwell co-culture. Bioinformatics analysis of RNA sequencing data confirmed a predominant effect of HG on inflammation-related mediators and biological processes/KEGG pathways in RPTEC/TERT1 stable monolayers as well as the non-contact-dependent anti-inflammatory effect of MSC. Finally, CM from HG-exposed RPTEC/MSC transwell co-cultures was associated with attenuated secretion of inflammatory mediators by macrophages compared to CM from HG-stimulated RPTEC alone. CONCLUSIONS: Stable RPTEC monolayers demonstrate delayed pro-inflammatory response to HG that is attenuated by close proximity to human MSC. In DKD, this MSC effect has potential to modulate hyperglycemia-associated RPTEC/macrophage cross-talk.

Granulomatous interstitial nephritis secondary to adalimumab therapy.

Tumour necrosis factor α (TNF-α) inhibitors are frequently used for the treatment of immune-mediated diseases. Conversely, cytokine therapy has the potential to paradoxically induce autoimmunity. A number of case reports have emerged concerning sarcoid-like granulomatosis secondary to TNF-α therapy, an adverse effect that typically affects the pulmonary and cutaneous systems. Granulomatous interstitial nephritis (GIN) is a relatively unknown, relatively under-reported consequence of adalimumab therapy that can have important clinical implications. To our knowledge, this is the first case report of GIN secondary to anti-TNF-α therapy necessitating a prolonged period of dialysis and the first report demonstrating the successful use of secukinumab as an alternative immunomodulatory agent.

Hemodialysis Session Duration, Ultrafiltration Rate, Interdialytic Weight Gain and their Association with Albumin in Patients on Intermittent Hemodialysis in a Regional Dialysis Unit: A Cross-sectional Study.

Aim Several studies suggest that a low pre-dialysis serum albumin level (<40g/L) is associated with increased mortality in dialysis patients. The objective of this study was to assess if hemodialysis session duration (HSD), ultrafiltration rate (UFR) and interdialytic weight gain percentage (IDWG%) are associated with pre-dialysis serum albumin levels (markers of all-cause mortality), thus influencing mortality.  Method  This is a cross-sectional analytical study in which data were collected from a regional cohort of 59 prevalent chronic hemodialysis patients using a national electronic database (eMED). Continuous data were analyzed using a regression model to assess for an association between HSD, IDWG% and UFR with albumin levels. Results Fifty-six patients were included in the study. Multiple linear regression models demonstrated a cross-sectional association between longer HSD and higher serum albumin levels and a statistically significant positive correlation (r = 0.353; p < 0.05). No significant association of UFR (p = 0.169) and IDWG% (p = 0.549) with albumin was observed. Mean albumin was 38.07 ± 3.96 g/L in the HSD <240 min group compared to 40.50 ± 2.83g/L in the HSD ≥240 min group which was statistically significant (p < 0.05). Conclusion Longer HSD has a cross-sectional association with higher pre-dialysis serum albumin with patients having HSD ≥240 min demonstrating the highest levels of serum albumin. Our study suggests longer HSD may improve mortality in the dialysis population.