Effect of End-Stage Renal Disease Prospective Payment System on Utilization of Peritoneal Dialysis in Patients with Kidney Allograft Failure.

INTRODUCTION: The Center for Medicare and Medicaid Services introduced an End-Stage Renal Disease Prospective Payment System (PPS) in 2011 to increase the utilization of home dialysis modalities, including peritoneal dialysis (PD). Several studies have shown a significant increase in PD utilization after PPS implementation. However, its impact on patients with kidney allograft failure remains unknown. METHODS: We conducted an interrupted time series analysis using data from the US Renal Data System (USRDS) that include all adult kidney transplant recipients with allograft failure who started dialysis between 2005 and 2019. We compared the PD utilization in the pre-PPS period (2005-2010) to the fully implemented post-PPS period (2014-2019) for early (within 90 days) and late (91-365 days) PD experience. RESULTS: A total of 27,507 adult recipients with allograft failure started dialysis during the study period. There was no difference in early PD utilization between the pre-PPS and the post-PPS period in either immediate change (0.3% increase; 95% CI: -1.95%, 2.54%; p = 0.79) or rate of change over time (0.28% increase per year; 95% CI: -0.16%, 0.72%; p = 0.18). Subgroup analyses revealed a trend toward higher PD utilization post-PPS in for-profit and large-volume dialysis units. There was a significant increase in PD utilization in the post-PPS period in units with low PD experience in the pre-PPS period. Similar findings were seen for the late PD experience. CONCLUSION: PPS did not significantly increase the overall utilization of PD in patients initiating dialysis after allograft failure.

Study protocol of a randomized controlled trial of fistula vs. graft arteriovenous vascular access in older adults with end-stage kidney disease on hemodialysis: the AV access trial.

BACKGROUND: Treatment of end-stage kidney disease (ESKD) with hemodialysis requires surgical creation of an arteriovenous (AV) vascular access-fistula (AVF) or graft (AVG)-to avoid (or limit) the use of a central venous catheter (CVC). AVFs have long been considered the first-line vascular access option, with AVGs as second best. Recent studies have suggested that, in older adults, AVGs may be a better strategy than AVFs. Lacking evidence from well-powered randomized clinical trials, integration of these results into clinical decision making is challenging. The main objective of the AV Access Study is to compare, between the two types of AV access, clinical outcomes that are important to patients, physicians, and policy makers. METHODS: This is a prospective, multicenter, randomized controlled trial in adults ≥ 60 years old receiving chronic hemodialysis via a CVC. Eligible participants must have co-existing cardiovascular disease, peripheral arterial disease, and/or diabetes mellitus; and vascular anatomy suitable for placement of either type of AV access. Participants are randomized, in a 1:1 ratio, to a strategy of AVG or AVF creation. An estimated 262 participants will be recruited across 7 healthcare systems, with average follow-up of 2 years. Questionnaires will be administered at baseline and semi-annually. The primary outcome is the rate of CVC-free days per 100 patient-days. The primary safety outcome is the cumulative incidence of vascular access (CVC or AV access)-related severe infections-defined as access infections that lead to hospitalization or death. Secondary outcomes include access-related healthcare costs and patients' experiences with vascular access care between the two treatment groups. DISCUSSION: In the absence of studies using robust and unbiased research methodology to address vascular access care for hemodialysis patients, clinical decisions are limited to inferences from observational studies. The goal of the AV Access Study is to generate evidence to optimize vascular access care, based on objective, age-specific criteria, while incorporating goals of care and patient preference for vascular access type in clinical decision-making. TRIAL REGISTRATION: This study is being conducted in accordance with the tenets of the Helsinki Declaration, and has been approved by the central institutional review board (IRB) of Wake Forest University Health Sciences (approval number: 00069593) and local IRB of each participating clinical center; and was registered on Nov 27, 2020, at ClinicalTrials.gov (NCT04646226).

Impact of COVID-19 pandemic on hemodialysis access thrombosis.

BACKGROUND: Delay in care of suspected stenosis or thrombosis can increase the chance of losing a functioning hemodialysis access. Access to care and resources were restricted during the COVID-19 pandemic. To evaluate the impact of the pandemic on arteriovenous fistula (AVF) and arteriovenous graft (AVG) procedures we have assessed the number and success of thrombectomies done before and during the COVID-19 pandemic. METHODS: We examined all AVF and AVG angiograms with and without interventions, including thrombectomies, performed at a single center during April 2017-March 2021 (pre-COVID-19 era) and April 2020-March 2021 (COVID-19 era). RESULTS: The proportion of procedures that were thrombectomies was higher during the COVID-19 era compared to the pre-COVID-19 era (13.3% vs 8.7%, p = 0.009). The proportion of thrombectomy procedures was higher during COVID-19 for AVF (8.2% vs 3.0%, p < 0.001) but there was no difference for AVG (26.5% vs 27%, p = 0.99). There was a trend toward a higher likelihood of unsuccessful thrombectomy during COVID-19 (33.3% vs 20.4%, p = 0.08). CONCLUSIONS: More dialysis access thromboses and unsuccessful thrombectomies were noted during the COVID-19 pandemic. This difference could be due to a delay in patients getting procedures to maintain their dialysis accesses.

The Role of Peritoneal Dialysis in Different Phases of Kidney Transplantation.

The utilization of peritoneal dialysis (PD) has been increasing in the past decade owing to various government initiatives and recognition of benefits such as better preservation of residual renal function, quality of life, and lower cost. The Advancing American Kidney Health initiative aims to increase the utilization of home therapies such as PD and kidney transplantation to treat end stage kidney disease (ESKD). A natural consequence of this development is that more patients will receive PD, and many will eventually undergo kidney transplantation. Therefore, it is important to understand the effect of pretransplant PD on posttransplant outcomes such as delayed graft function (DGF), rejection, thrombosis, graft, and patient survival. Furthermore, some of these patients may develop DGF, which raises the question of the utility of PD during DGF and its risks. Although transplant is the best renal replacement therapy option, it is not everlasting, and many transplant recipients must go on dialysis after allograft failure. Can PD be a good option for these patients? This is another critical question. Furthermore, a significant proportion of nonrenal solid organ transplant recipients develop ESKD. Is PD feasible in this group? In this review, we try to address all of these questions in the light of available evidence.

Arteriovenous Access Type and Risk of Mortality, Hospitalization, and Sepsis Among Elderly Hemodialysis Patients: A Target Trial Emulation Approach.

RATIONALE & OBJECTIVE: Evidence is mixed regarding the optimal choice of the first permanent vascular access for elderly patients receiving hemodialysis (HD). Lacking data from randomized controlled trials, we used a target trial emulation approach to compare arteriovenous fistula (AVF) versus arteriovenous graft (AVG) creation among elderly patients receiving HD. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Elderly patients included in the US Renal Data System who initiated HD with a catheter and had an AVF or AVG created within 6 months of starting HD. EXPOSURE: Creation of an AVF versus an AVG as the incident arteriovenous access. OUTCOMES: All-cause mortality, all-cause and cause-specific hospitalization, and sepsis. ANALYTICAL APPROACH: Target trial emulation approach, high-dimensional propensity score and inverse probability of treatment weighting, and instrumental variable analysis using the proclivity of the operating physician to create a fistula as the instrumental variable. RESULTS: A total of 19,867 patients were included, with 80.1% receiving an AVF and 19.9% an AVG. In unweighted analysis, AVF creation was associated with significantly lower risks of mortality and hospitalization, especially within 6 months after vascular access creation. In inverse probability of treatment weighting analysis, AVF creation was associated with lower incidences of mortality and hospitalization within 6 months after creation (hazard ratios of 0.82 [95% CI, 0.75-0.91] and 0.82 [95% CI, 0.78-0.87] for mortality and all-cause hospitalization, respectively), but not between 6 months and 3 years after access creation. No association between AVF creation and mortality, sepsis, or all-cause, cardiovascular disease-related, or infection-related hospitalization was found in instrumental variable analyses. However, AVF creation was associated with a lower risk of access-related hospitalization not due to infection. LIMITATIONS: Potential for unmeasured confounding, analyses limited to elderly patients, and absence of data on actual access use during follow-up. CONCLUSIONS: Using observational data to emulate a target randomized controlled trial, the type of initial arteriovenous access created was not associated with the risks of mortality, sepsis, or all-cause, cardiovascular disease-related, or infection-related hospitalization among elderly patients who initiated HD with a catheter.

Continuation of Peritoneal Dialysis in Adult Kidney Transplant Recipients With Delayed Graft Function.

INTRODUCTION: Peritoneal dialysis (PD) has been used increasingly in past decade. Many of these patients undergo transplantation and may require dialysis for delayed graft function (DGF). The outcomes of DGF based on the post-transplantation dialysis modality are not well known. METHODS: We retrospectively reviewed all adult kidney transplant recipients (KTRs) from the University of Wisconsin School of Medicine and Public Health who developed DGF between November 2015 and April 2019. Patients were divided into those who received hemodialysis (HD) or PD during the DGF period. Immediate graft explant, DGF among living donor KTRs, or those requiring just a single dialysis treatment were excluded. RESULTS: Of 224 KTRs with DGF during the study period, 167 fulfilled our selection criteria. There were 16 patients in the PD and 151 in the HD group. Baseline characteristics were similar between the two groups, except diabetes was more prevalent in the HD group. Five of 16 PD patients had to be transitioned to HD. There was no difference in DGF duration, hospital length of stay, infectious or surgical complications, rejection at various time periods, graft function at last follow-up, or graft failure. In multivariate analysis, only rejection within the first year of transplantation (hazard ratio [HR]: 4.26; 95% confidence interval [CI]: 1.20-15.08; P = 0.02) and post-surgical complications (HR: 3.79; 95% CI: 1.03- 13.91; P = 0.04) were associated with death-censored graft failure (DCGF). The use of PD for treatment of DGF was not associated with DCGF. CONCLUSIONS: In carefully selected patients, PD can be continued safely for DGF without any effect on short-term or long-term transplant outcomes.

Mega Fistulae! A case series.

A mega fistula can be defined as generalized aneurysmal dilatation of arteriovenous fistula. Mega fistulae can lead to complications like high output cardiac failure, steal syndrome, skin ulceration and rupture. We describe a series of ten patients who were referred to our interventional nephrology practice for evaluation of mega fistula which had not been in use for a long time. Nine out of ten patients were post-transplant while one was pre dialysis. Five patients had Radiocephalic while four had Brachiocephalic and one had Brachial artery to Median Cubital vein fistula. All except one patient had severe outflow stenosis. The most common site of stenosis in Radiocepahlic and Brachiocepahlic fistula was cephalic vein at the elbow and cephalic arch respectively. Half of the patients had chronic total occlusion of the outflow vein. Successful angioplasty was done in only two patients. Seven patients underwent ligation while one had spontaneous thrombosis of the fistula. None of the patients had regular surveillance of their access for a long time as they were not on dialysis. Unrecognized and uncorrected outflow stenosis over a long time period can lead to creation of mega fistula. Once a mega fistula develops there are not many treatment options other than ligation. This leads to loss of the access which might be needed in future. Continuous access surveillance in patients who are not on dialysis is important to prevent complications like mega fistula.

A Single-Center Assessment of Delayed Graft Function in Recipients of Simultaneous Liver and Kidney Transplant.

BACKGROUND: The effects of delayed graft function on long-term kidney allograft outcomes are poorly defined among simultaneous liver and kidney transplant recipients. METHODS: We analyzed data of all simultaneous liver and kidney recipients transplanted at the University of Wisconsin between 2010 and 2017. Risk factors for the development of delayed graft function, kidney graft failure, and patient mortality were outcomes of interest. RESULTS: There were a total of 60 simultaneous liver and kidney recipients; 28 (47%) had delayed graft function. After adjustment for multiple variables, we found that pretransplant dialysis >6 weeks (hazard ratio [HR] = 5.6, 95% CI: 1.23-25.59, P = .02), pretransplant albumin <3 g/dL (HR = 5.75, 95% CI: 1.76-16.94, P = .003), and presence of pretransplant diabetes (HR = 2.5, 95% CI: 0.97-4.77, P = .05) were significantly associated with delayed graft function. Multivariate analysis showed that pretransplant albumin <3 (HR = 4.86, 95% CI: 1.07-22.02, P = .02) was associated with a higher risk of all-cause kidney allograft failure, whereas the duration of delayed graft function (HR = 1.07 per day, 95% CI: 1.01-1.14, P = .01) was associated with a higher risk of death-censored kidney allograft failure. The presence of delayed graft function was not associated with all-cause or death-censored kidney or liver allograft failure. Similarly, the presence of delayed graft function was not associated with patient mortality. CONCLUSION: The incidence of delayed graft function was high in simultaneous liver and kidney recipients. However, with appropriate management, delayed graft function may not have a negative impact on patient or kidney allograft survival.

Going Home: Access for Home Modalities.

The cost and health burden of ESRD continues to increase globally. Total Medicare expenditure on dialysis has increased from 229 million USD in 1973 to 35.4 billion USD in 2016. Dialysis access can represent almost a tenth of these costs. Central venous catheters have been recognized as a significant factor driving costs and mortality in this population. Home dialysis, which includes peritoneal dialysis and home hemodialysis, is an effective way of reducing costs related to renal replacement therapy, reducing central venous catheter usage and in many cases improving the clinical and psychosocial aspects of patients' health. Addressing access-related issues for peritoneal dialysis, urgent-start peritoneal dialysis and home hemodialysis can have impact on the success of home dialysis. This article reviews issues related to dialysis access for home therapies.

Vascular access in kidney transplant recipients.

Vascular access is an important element in the overall care provided to kidney transplant recipients. The transplanted kidney is not indestructible, and chronic kidney disease after transplantation may result in needing another transplant or beginning dialysis. Commonly used vascular accesses, like peripheral and central lines, can preclude the creation of future, permanent dialysis access. Therefore, there is urgent need to preserve vessels for the future access needs for hemodialysis among kidney transplant recipients without functional vascular access for dialysis. Moreover, the proper care of functional vascular access among kidney transplant recipients is crucial. In this review article, we will address the common vascular access procedures and complications among kidney transplant recipients.

Markers of mineral metabolism and vascular access complications: The Choices for Healthy Outcomes in Caring for ESRD (CHOICE) study.

INTRODUCTION: Vascular access dysfunction is a major cause of morbidity in patients with end-stage renal disease (ESRD) on chronic hemodialysis. The effects of abnormalities in mineral metabolism on vascular access are unclear. In this study, we evaluated the association of mineral metabolites, including 25-hydroxy vitamin D (25(OH)D) and fibroblast growth factor-23 (FGF-23), with vascular access complications. METHODS: We included participants from the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Study who were using an arteriovenous fistula (AVF; n = 103) or arteriovenous graft (AVG; n = 116). Serum levels of 25(OH)D, FGF-23, parathyroid hormone (PTH), calcium, phosphorus, C-reactive protein (CRP) and interleukin-6 (IL-6) were assessed from stored samples. Participants were followed for up to 1 year or until a vascular access intervention or replacement. FINDINGS: A total of 24 participants using an AVF and 43 participants using an AVG experienced access intervention. Those with 25(OH)D level in the lowest tertile (<11 ng/mL) had an increased risk of AVF intervention compared to those with higher 25(OH)D levels (adjusted relative hazard [aHR] = 3.28; 95% confidence interval [CI]: 1.31, 8.20). The highest tertile of FGF-23 (>3750 RU/mL) was associated with greater risk of AVF intervention (aHR = 2.56; 95% CI: 1.06, 6.18). Higher PTH was associated with higher risk of AVF intervention (aHR = 1.64 per SD of log(PTH); 95% CI: 1.02, 2.62). These associations were not observed in participants using an AVG. None of the other analytes were significantly associated with AVF or AVG intervention. DISCUSSION: Low levels of 25(OH)D and high levels of FGF-23 and PTH are associated with increased risk of AVF intervention. Abnormalities in mineral metabolism are risk factors for vascular access dysfunction and potential therapeutic targets to improve outcomes.

Association of Pre-Transplant Dialysis Modality and Post-Transplant Outcomes: A Meta-Analysis.

♦ BACKGROUND: It remains unclear whether post-transplant outcomes differ according to the pre-transplant dialysis modality (peritoneal dialysis [PD] versus hemodialysis [HD]). We performed a meta-analysis of studies that assessed either post-transplant mortality, graft survival, or delayed graft function (DGF) in both PD and HD patients. ♦ METHODS: Two independent authors searched English-language literature from January 1, 1980, through August 31, 2014, national conference proceedings, and reference lists. We used combinations of terms related to dialysis (hemodialysis, peritoneal dialysis, or renal replacement therapy), kidney transplant, and outcomes. Studies were included if they measured any of the 3 post-transplant study outcomes in both pre-transplant HD and PD. ♦ RESULTS: A total of 16 studies were included in the final analysis. Of these, 6 studies reported adjusted hazard ratio for mortality, pooled adjusted risk ratio: 0.89 (95% confidence interval [CI] 0.82 - 0.97) in favor of PD (p = 0.006). The same 6 studies reported adjusted hazard ratio for graft survival, pooled adjusted risk ratio: 0.97 (95% CI 0.92 - 1.01, p = 0.16). A total of 13 studies reported unadjusted DGF. Pooled odds ratio: 0.5 (95% CI 0.41 - 0.63) in favor of PD (p < 0.005). Significant heterogeneity observed for all outcomes: I2 = 72.7%, I2 = 59.9%, and I2 = 66.8%, respectively. ♦ CONCLUSIONS: Based on these results, pre-transplant PD is associated with better post-transplant survival than HD. Pre-transplant PD was also associated with decreased risk for DGF compared with HD, although these results were unadjusted. There was no significant difference in graft survival between pre-transplant HD and PD. These results suggest that PD may be the preferred dialysis modality for patients expected to receive a transplant.

Erosion of the Silicone Peritoneal Dialysis Catheter with the Use of Gentamicin Cream at the Exit Site.

Infection remains the leading complication of peritoneal dialysis (PD). Topical mupirocin and gentamicin are frequently used to prevent infections. Mupirocin ointment has been reported to cause damage to both polyurethane and silicone PD catheters. Gentamicin cream has not been associated with physical damage to catheters.A 64-year-old woman on PD developed relapsing peritonitis with Staphylococcus epidermidis. Because of a drainage problem and white discoloration at the exit site, which is known as " frosting," she underwent catheter exchange. The catheter was found to be fractured within the area of frosting. Four more patients with frosting of the catheter were identified. On further questioning, it was recognized that they were applying excessive amounts of gentamicin cream directly on the catheter surface rather than at the exit site. All patients in the program were educated about the correct method of topical antibiotic application. After the change in practice, no further cases of catheter frosting were identified.Polyurethane catheters can undergo oxidation, mineralization, and environmental stress cracking, leading to physical damage such frosting, ballooning, and fracture. Polyethylene glycol, a component of the mupirocin ointment base, is thought to cause plasticization of polyurethane, reducing its tensile strength. Similar damage has been observed in silicone catheters. Previous reports have not found gentamicin cream to cause that type of damage. We observed that excessive amounts of cream applied directly to the catheter surface can damage it. Damage did not recur once patients had been educated about the proper method of application.

Genetic determinants of major blood lipids in Pakistanis compared with Europeans.

BACKGROUND: Evidence is sparse about the genetic determinants of major lipids in Pakistanis. METHODS AND RESULTS: Variants (n=45 000) across 2000 genes were assessed in 3200 Pakistanis and compared with 2450 Germans using the same gene array and similar lipid assays. We also did a meta-analysis of selected lipid-related variants in Europeans. Pakistani genetic architecture was distinct from that of several ethnic groups represented in international reference samples. Forty-one variants at 14 loci were significantly associated with levels of HDL-C, triglyceride, or LDL-C. The most significant lipid-related variants identified among Pakistanis corresponded to genes previously shown to be relevant to Europeans, such as CETP associated with HDL-C levels (rs711752; P<10(-13)), APOA5/ZNF259 (rs651821; P<10(-13)) and GCKR (rs1260326; P<10(-13)) with triglyceride levels; and CELSR2 variants with LDL-C levels (rs646776; P<10(-9)). For Pakistanis, these 41 variants explained 6.2%, 7.1%, and 0.9% of the variation in HDL-C, triglyceride, and LDL-C, respectively. Compared with Europeans, the allele frequency of rs662799 in APOA5 among Pakistanis was higher and its impact on triglyceride concentration was greater (P-value for difference <10(-4)). CONCLUSIONS: Several lipid-related genetic variants are common to Pakistanis and Europeans, though they explain only a modest proportion of population variation in lipid concentration. Allelic frequencies and effect sizes of lipid-related variants can differ between Pakistanis and Europeans.

Association of the 9p21.3 locus with risk of first-ever myocardial infarction in Pakistanis: case-control study in South Asia and updated meta-analysis of Europeans.

OBJECTIVE: To examine variants at the 9p21 locus in a case-control study of acute myocardial infarction (MI) in Pakistanis and to perform an updated meta-analysis of published studies in people of European ancestry. METHODS AND RESULTS: A total of 1851 patients with first-ever confirmed MI and 1903 controls were genotyped for 89 tagging single-nucleotide polymorphisms at locus 9p21, including the lead variant (rs1333049) identified by the Wellcome Trust Case Control Consortium. Minor allele frequencies and extent of linkage disequilibrium observed in Pakistanis were broadly similar to those seen in Europeans. In the Pakistani study, 6 variants were associated with MI (P<10(-2)) in the initial sample set, and in an additional 741 cases and 674 controls in whom further genotyping was performed for these variants. For Pakistanis, the odds ratio for MI was 1.13 (95% CI, 1.05 to 1.22; P=2 x 10(-3)) for each copy of the C allele at rs1333049. In comparison, a meta-analysis of studies in Europeans yielded an odds ratio of 1.31 (95% CI, 1.26 to 1.37) for the same variant (P=1 x 10(-3) for heterogeneity). Meta-analyses of 23 variants, in up to 38,250 cases and 84,820 controls generally yielded higher values in Europeans than in Pakistanis. CONCLUSIONS: To our knowledge, this study provides the first demonstration that variants at the 9p21 locus are significantly associated with MI risk in Pakistanis. However, association signals at this locus were weaker in Pakistanis than those in European studies.

The Pakistan Risk of Myocardial Infarction Study: a resource for the study of genetic, lifestyle and other determinants of myocardial infarction in South Asia.

The burden of coronary heart disease (CHD) is increasing at a greater rate in South Asia than in any other region globally, but there is little direct evidence about its determinants. The Pakistan Risk of Myocardial Infarction Study (PROMIS) is an epidemiological resource to enable reliable study of genetic, lifestyle and other determinants of CHD in South Asia. By March 2009, PROMIS had recruited over 5,000 cases of first-ever confirmed acute myocardial infarction (MI) and over 5,000 matched controls aged 30-80 years. For each participant, information has been recorded on demographic factors, lifestyle, medical and family history, anthropometry, and a 12-lead electrocardiogram. A range of biological samples has been collected and stored, including DNA, plasma, serum and whole blood. During its next stage, the study aims to expand recruitment to achieve a total of about 20,000 cases and about 20,000 controls, and, in subsets of participants, to enrich the resource by collection of monocytes, establishment of lymphoblastoid cell lines, and by resurveying participants. Measurements in progress include profiling of candidate biochemical factors, assay of 45,000 variants in 2,100 candidate genes, and a genomewide association scan of over 650,000 genetic markers. We have established a large epidemiological resource for CHD in South Asia. In parallel with its further expansion and enrichment, the PROMIS resource will be systematically harvested to help identify and evaluate genetic and other determinants of MI in South Asia. Findings from this study should advance scientific understanding and inform regionally appropriate disease prevention and control strategies.