Changing landscape of dialysis withdrawal in patients with kidney failure: Implications for clinical practice.

Dialysis withdrawal has become an accepted treatment option for patients with kidney failure and is one of the leading causes of death in patients receiving dialysis in high-income countries. Despite its increasing acceptance, dialysis withdrawal currently lacks a clear, consistent definition. The processes and outcomes of dialysis withdrawal have wide temporal and geographical variability, attributed to dialysis patient selection, influence from cultural, religious and spiritual beliefs, and availability of kidney replacement therapy and conservative kidney management. As a complex, evolving process, dialysis withdrawal poses an enormous challenge for clinicians and healthcare teams with various limitations precluding a peaceful and smooth transition between active dialysis and end-of-life care. In this review, we examine the current definitions of dialysis withdrawal, the temporal and geographical patterns of dialysis withdrawal, international barriers in the decision-making process (including dialysis withdrawal during the COVID-19 pandemic), and gaps in the current dialysis withdrawal recommendations for clinical consideration and future studies.

Allograft and Patient Outcomes Between Indigenous and Nonindigenous Kidney Transplant Recipients.

BACKGROUND: Kidney transplant outcomes of indigenous Australians are poorer compared with nonindigenous Australians, but it is unknown whether the type of acute rejection differs between these patient groups or whether rejection mediates the effect between ethnicity, death-censored graft failure (DCGF), and death with a functioning graft (DWFG). METHODS: Biopsy-proven acute rejection (BPAR) rates and types were compared between indigenous and nonindigenous recipients. The associations between ethnicity, BPAR, DCGF, and DWFG were examined using adjusted competing risk analyses, and mediation analysis was conducted to determine whether BPAR mediated the adverse effects between ethnicity and outcomes. RESULTS: Fifty-seven (9.3%) of 616 patients who have received kidney-only transplants between 2000 and 2010 in Western Australia were indigenous. Compared with nonindigenous recipients, BPAR rates were higher in indigenous recipients (42 versus 74 episodes/100 recipients, P < 0.01), with an excess of antibody-mediated rejections. During a median follow-up of 8 years, indigenous recipients were more likely to experience BPAR, DCGF, and DWFG compared with nonindigenous recipients, with adjusted subdistribution hazard ratio of 1.94 (1.39-2.70), 1.53 (0.85-2.76; P = 0.159), and 2.14 (1.13-4.06; P = 0.020), respectively. Although 70% of the effect between ethnicity and DCGF was mediated by BPAR, no similar association was found for DWFG. CONCLUSIONS: Indigenous recipients experienced poorer allograft and patient outcomes compared with nonindigenous recipients, with BPAR an important determinant for DCGF. Future research identifying other risk factors and mediators associated with patient survival in indigenous recipients should be considered a priority.

Cytomegalovirus burden improves a predictive model identifying measures of vascular risk in renal transplant recipients and healthy adults.

Cytomegalovirus (CMV) has been implicated in vascular pathologies and may warrant inclusion in cardiovascular predictive algorithms. We addressed this in healthy older adults and renal transplant recipients (RTR) as they retain a high burden of CMV. RTR (n = 45) stable more than 2 years after transplantation and 58 age-matched healthy adults were assessed. Plasma inflammatory biomarkers (soluble isoform of the interferon-ß receptor [sIFNAR2], soluble tumour necrosis factorreceptor-1 [sTNFR1], soluble cluster of differentiation 14 [sCD14], C reactive protein, P-selectin, intracellular cell adhesion molecule-1, vascular cell adhesion molecule-1), and measures of CMV burden (antibodies, saliva CMV DNA, and interferon γ responses to CMV) were assessed in 2014 and evaluated in 2017 as predictors of vascular health-defined using flow-mediated dilatation (FMD), pulse wave velocity (PWV), and augmentation indices (Aix@ 75). Linear regression models adjusted for age, sex, and body mass index (BMI) were optimized to identify risk factors. In 2017, RTR had inferior vascular health marked by impaired FMD and PWV. Detectable CMV DNA (P = .02) was associated with impaired FMD, whilst CMV glycoprotein B (gB) antibody attenuated this effect (P = .03) (adjusted R2 = .42). In healthy adults, the optimal model for predicting FMD (R2 =.22) incorporated high P-selectin (P = .03) and low ICAM-1 (P = .03) levels with no significant impact of CMV. Elevated sIFNAR2 (P = .04) and gB antibody (P = .06) levels predicted increasing Aix@ 75 (poor vascular health) in healthy adults (R2 = .4), whilst optimal models for RTR (R2 = .37) linked low sIFNAR2 and CMV IE-1 antibody levels with lower Aix@ 75 (better vascular health). CMV IE-1 antibody was also protective in relation to PWV in healthy adults (R2 = .55). Overall, measures of active CMV replication were more predictive of impaired FMD in RTR than standard biomarkers, but increased CMV gB antibodies may be protective.

Deciphering Effects of Uncontrolled Cytomegalovirus Replication on Immune Responses in Cytomegalovirus DNA-Positive Renal Transplant Recipients.

Cytomegalovirus (CMV) is a highly prevalent virus and a common cause of morbidity in solid organ transplant patients. It is also known for its long-lasting imprint on the immune system, expanding populations of highly differentiated T cells and natural killer (NK) cells with novel phenotypes. However, it is unclear whether these cells mark success or failure in the management of an active infection. We assessed CMV reactivation in 54 renal transplant recipients (RTRs) by measuring CMV DNA in plasma samples. Function and phenotype of T cells and NK cells were then assessed in seven RTR with detectable CMV DNA. The patient with highest CMV viral load (P1) displayed increased NK cell function and abundant highly differentiated T cells. We compare P1 with the other six patients and review possible scenarios of cross-regulation between NK cells and T cells.

A high burden of cytomegalovirus marks poor vascular health in transplant recipients more clearly than in the general population.

OBJECTIVES: Meta-analyses have now confirmed that persistent infections with cytomegalovirus (CMV) can accelerate the onset of diseases of ageing, notably cardiovascular pathologies. We address the circumstances in which the association may be strong enough to warrant intervention to reduce the viral burden. RESULTS: We compare markers of the burden of CMV with established indices of vascular pathology in healthy adults (n = 82) and in renal transplant recipients (RTR; n = 81). Levels of all inflammatory and vascular biomarkers and CMV antibodies were higher in RTR, and flow-mediated dilation (FMD) values were lower indicating inferior endothelial function. In multivariable regression models without adjustment for estimated glomerular filtration rate (eGFR), CMV antibody levels, age and gender were independently associated with FMD in RTR, whilst only CRP associated with FMD in healthy adults. After adjustment for eGFR, associations between CMV antibody and FMD in RTR were reduced. METHODS: Carotid intima-media thickness, FMD, eGFR and plasma levels of CMV antibodies (reactive with a lysate, CMV IE-1 or CMV gB), ICAM-1, VCAM-1, P-selectin, sIFNαR2, sTNFR1, sCD14 and CRP were determined. CONCLUSION: Levels of CMV antibody predict declining endothelial health in RTR and not in healthy adults, presumably by reflecting a high burden of CMV. The levels of CMV antibodies were a poor reflection of plasma biomarkers thought to reflect 'inflammaging' or vascular damage.

The Relationship Between Presentation and the Time of Initial Administration of Antibiotics With Outcomes of Peritonitis in Peritoneal Dialysis Patients: The PROMPT Study.

INTRODUCTION: The impact of time to treatment on clinical outcome is an established precept in infectious disease but is not established in peritoneal dialysis-related peritonitis (PDRP). METHODS: In a prospective multicenter study of PDRP, symptom-to-contact time (SC), contact-to-treatment time (CT), defined as the time from health care presentation to initial antibiotic, and symptom-to-treatment time (ST) were determined. RESULTS: One hundred sixteen patients had 159 episodes of PDRP. Median SC for all episodes was 5.0 hours (first to third quartile [Q1-Q3]: 1.3-13.9); CT, 2.3 hours (Q1-Q3: 1.2-4.0); and ST, 9.0 hours (Q1-Q3: 4.7-25.3). Thirty-eight (23.9%) patient episodes (28 catheter removals and 10 deaths) met the primary composite outcome of PD failure at 30 days (PD-fail). The risk of PD-fail increased by 5.5% for each hour of delay of administration of antibiotics (odds ratio [OR] for CT: 1.055; 95% confidence interval [CI]: 1.005-1.109; P = 0.032). Neither SC (OR: 1.00; 95% CI: 0.99-1.01; P = 0.74) nor ST (OR: 1.00; 95% CI: 0.99-1.01; P = 0.48) was associated with PD-fail. In a multivariable analysis, only CT for presentation to a hospital-based facility compared with a community facility (OR: 1.068; 95% CI: 1.013-1.126; P = 0.015) and female sex (OR: 2.4; 95% CI: 1.1-5.4; P = 0.027) were independently associated with PD-fail. Each hour of delay in administering antibacterial therapy from the time of presentation to a hospital facility increased the risk of PD failure or death by 6.8%. DISCUSSION: Strategies targeted to expedited antibiotic treatment should be implemented to improve outcomes from PDRP.