Sebastian Schwab

Background: Immune checkpoint inhibitors and tyrosine kinase inhibitors have transformed cancer therapy also for patients with end-stage-kidney-disease. Case presentation: We here report hemoperitoneum and peritonitis in a peritoneal dialysis patient after therapies with both drug classes. The differential diagnosis included peritoneal dialysis associated peritonitis, immune checkpoint inhibitor -associated colitis, viral reactivation as well as an unrelated gastrointestinal process. Colonic resection revealed perforation, granulocytic and lymphocytic inflammation together with cytomegalovirus DNA. Symptoms responded to systemic Ganciclovir therapy. Conclusions: The case highlights the need for clinical vigilance and repeated diagnostics in the care of multimorbid individuals with unusual presentations and multidisciplinary state of the art therapies.

Background: We analyzed the performance of a multiplex PCR application (Unyvero IAI) in comparison to culture in a cohort of peritonitis patients undergoing peritoneal dialysis or with liver cirrhosis. Methods: We performed a single-center study of 47 patients with clinically suspected peritonitis and compared pathogen detection rates of culture and PCR. The main outcome of interest was a comparison of accuracy and time to final positive result. Results: In the total cohort, the pathogen detection rate in culture was 58.14% versus 34.88% in PCR (p = 0.03). Detection rates of bacteria in peritoneal dialysis patients were even higher by culture (70.83%) but comparably low by PCR (37.50%; p = 0.04). The majority of discordant results were in the Gram-positive spectrum (81.82%). Differential time to final positive result was 37.39 ± 16.75 h. Conclusion: Time gains by using PCR diagnostic have to be weighed against lower detection rates, mainly in Gram-positive infections.

Background: Urinary Dickkopf 3 (DKK3) excretion is a recently established biomarker of renal functional development. Its excretion into the peritoneal cavity has not been reported. We here studied DKK3 in peritoneal dialysis. Methods: DKK3 was assessed in serum, urine and dialysate in a prevalent adult peritoneal dialysis cohort and its concentration analyzed in relation to creatinine and clinical characteristics. Results: Highest DKK3 concentrations were found in serum, followed by urine. Dialysate concentrations were significantly lower. Dialysate DKK3 correlated with both other compartments. Serum, dialysate and urine values were stable during three months of follow-up. Continuous ambulatory dialysis (CAPD) but not cycler-assisted peritoneal dialysis (CCPD) volume-dependently increased peritoneal DKK3 in relation to creatinine. RAAS blockade significantly decreased urinary, but not serum or peritoneal DKK3. Conclusion: Our data provide a detailed characterization of DKK3 in peritoneal dialysis. They support the notion that the RAAS system is essential for renal DKK3 handling.

Kidney transplantation improves quality of life and prolongs survival of patients with end-stage kidney disease. However, kidney transplant recipients present a higher risk for cardiovascular events compared to the general population. Risk assessment for graft failure as well as cardiovascular events is still based on invasive procedures. Biomarkers in blood and urine, but also new diagnostic approaches like genetic or molecular testing, can be useful tools to monitor graft function and to identify patients of high cardiovascular risk. Many biomarkers have been introduced, whereas most of these biomarkers have not been implemented in clinical routine. Here, we discuss recent developments in biomarkers and diagnostic models in kidney transplant recipients. Because many factors impact graft function and cardiovascular risk, it is most likely that no biomarker will meet the highest demands and standards. We advocate to shift focus to the identification of patients benefitting from molecular and genetic testing as well as from analysis of more specific biomarkers instead of finding one biomarker fitting to all patients.

Background: For the improvement of outcome after renal transplantation it is important to predict future risk of major adverse cardiac events as well as all-cause mortality. We aimed to determine the relationship of pre-transplant NT-proBNP with major adverse cardiac events and all-cause mortality after transplant in patients on the waiting-list with preserved left ventricular ejection fraction. Patients and methods: We included 176 patients with end-stage renal disease and preserved left ventricular ejection fraction who received a kidney transplant. MACE was defined as myocardial infarction (ST-segment elevation [STEMI] or non-ST-segment elevation [NSTEMI]), stroke or transient ischemic attack), coronary artery disease requiring intervention or bypass or death from cardiovascular causes. Results: MACE occurred in 28/176 patients. Patients with NT-proBNP levels above 4350 pg/ml had 1- and 5-year survival rates of 90.67% and 68.20%, whereas patients with NT-proBNP levels below 4350 pg/ml had 1- and 5-year survival rates of 100% and 90.48% (p < 0.01). 1- and 5-year MACE-free survival rates were calculated as 78.82% and 74.68% for patients with NT-proBNP > 4350 pg/ml and 93.33% and 91.21% for patients with NT-proBNP < 4350 pg/ml (p < 0.01). Conclusions: Pre-transplant NT-proBNP might identify renal transplant candidates at risk for MACE after transplant.

Background: Beta Trace Protein (BTP) is a biomarker for residual kidney function which has been linked to cardiovascular and all‐cause mortality in haemodialysis patients. Following renal transplantation, recipients remain at increased risk for cardiovascular events compared with the general population. We aimed to determine the relationship of pre‐transplant BTP to major adverse cardiac events (MACE) in patients following kidney transplantation.Methods: We included 384 patients with end‐stage renal disease who received a kidney transplant. MACE was defined as myocardial infarction (ST‐segment elevation or non‐ST‐segment elevation, stroke or transient ischemic attack), coronary artery disease requiring intervention or bypass or death for cardiovascular reason. The association between pre‐transplant serum BTP concentration and post‐transplant MACE was evaluated by Kaplan–Meier and Cox regression analyses.Results: Post‐transplant MACE occurred in 70/384 patients. Pre‐transplant BTP was significantly higher in patients with post‐transplant MACE (14.36 ± 5.73 mg/l vs. 11.26 ± 5.11 mg/l; p < .01). Next to smoking (HR 1.81), age > 56.38 years (HR 1.97) and pre‐existing coronary heart disease (HR 8.23), BTP above the cut off value of 12.7 mg/l was confirmed as independent risk factor for MACE (HR 2.02, all p < .05). MACE‐free survival inversely correlated with pre‐transplant BTP levels.Conclusions: Pre‐transplant serum BTP concentration may identify renal transplant recipients with higher risk of post‐transplant MACE.

Background: Residual renal function is closely linked to quality of life, morbidity and mortality in dialysis patients. Beta-trace protein (BTP), a low molecular weight protein, has been suggested as marker of residual renal function, in particular in patients on hemodialysis. We hypothesized that BTP also serves as a marker of residual renal function in pertioneal dialysis patients.Methods: In this study 34 adult patients on peritoneal dialysis were included. BTP, creatinine, cystatin C and urea concentrations were analyzed simultaneously in serum and dialysate to calculate renal and peritoneal removal of the analytes.Results: In peritoneal dialysis patients with residual diuresis, mean serum BTP was 8.16 mg/l (SD ± 4.75 mg/l). BTP correlated inversely with residual diuresis (r_s = − 0.58,p < 0.001), residual creatinine clearance (Cl_Cr) (r_s = − 0.69,p < 0.001) and total urea clearance (Cl_urea) (r_s = − 0.56,p < 0.001). Mean peritoneal removal of BTP was 3.36 L/week/1.73m²(SD ± 1.38) and mean renal removal 15.14 L/week/1.73m²(SD ± 12.65) demonstrating a significant renal contribution to the total removal. Finally, serum BTP inversely correlated with alterations in residual diuresis (r = − 0.41,p = 0.035) and renal creatinine clearance over time (r = − 0.79,p = p < 0.001).Conclusion: BTP measurement in the serum may be a simple tool to assess residual renal function in peritoneal dialysis patients.

Conjunctiva-associated tissue (CALT) is assumed to play a crucial role in the immune system of the ocular surface. Its function in several ocular surface diseases (OSD) is still not fully understood. This study investigates the function of CALT in mouse models of dry-eye disease and ocular allergy. Since antigen-presentation is the central similarity in the pathologies, this study focuses on antigen-presentation in CALT Morphology and the expression of CALT, which was investigated in mice after induction of dry-eye, ocular allergy, topical antigen-stimulation, and after local depletion of phagocytic cells. Antigen uptake was investigated after the application of fluorescent ovalbumin (OVA). OSD influences the appearance and morphology of CALT in a disease-dependent manner. Ocular allergy leads to an increase and dry-eye disease to a decrease in number and size of CALT. The development of CALT is dependent on the presence of APCs. Professional APCs are present in CALT, and soluble antigen is transported into the follicle. CALT appearance is disease-specific and indicative of differing functions. Although the specific involvement of CALT in OSD needs further study, the existence of functional APCS and antigen-uptake supports the hypothesis that CALT is an immunological key player at the ocular surface.