Amarpali Brar

Hypertension in Chronic Kidney Disease: Navigating the Evidence

Hypertension is both an important cause and consequence of chronic kidney disease. Evidence from numerous clinical trials has demonstrated the benefit of blood pressure control. However, it remains unclear whether available results could be extrapolated to patients with chronic kidney diseases because most studies on hypertension have excluded patients with kidney failure. In addition, chronic kidney disease encompasses a large group of clinical disorders with heterogeneous natural history and pathogenesis. In this paper, we review current evidence supporting treatment of hypertension in various forms of chronic kidney disease and highlight some of the gaps in the extant literature.

Practice Patterns in Evaluation of Living Kidney Donors in United Network for Organ Sharing-Approved Kidney Transplant Centers

Introduction: The current pattern of evaluation for living kidney donors was investigated. Methods: We designed a 37-question electronic survey to collect information about living kidney donor evaluation. Of the 181 United Network for Organ Sharing (UNOS)-approved centers, 72 responded. Survey responses were coded and downloaded into SPSS. Data was expressed as means and standard deviations or the percentage of centers with specific responses. Results: 66% of the centers used a cut-off of <80 ml/min for exclusion of living kidney donors. 24-hour urine measuring creatinine clearance (CrCl) was the most common screening method for glomerular filtration rate (GFR) assessment in potential living donors. 56% of the centers excluded donors with blood pressure (BP) >140/90, whereas 22.7 and 7.1% excluded patients with pre-hypertension with a cut-off BP of 130/85 and 120/80, respectively. 66% of the centers used 24-hour urine creatinine to assess for proteinuria. 20% of the centers accepted living kidney donors with microalbuminuria and 84% accepted patients with a history of nephrolithiasis. 24% of the centers reported use of formal cognitive testing of potential living donors. Discussion: There were significant variations in exclusion criteria based on GFR, history of kidney stones, body mass index, BP and donors with urinary abnormalities. The definitions for hematuria and proteinuria were variable. There is a need for uniformity in selection and for a living donor registry. We also recommend raising the cut-off for estimated GFR to 90 ml/min to account for 10–15% overestimation when CrCl is used.

Effect of peripheral vascular disease on kidney allograft outcomes: a study of U.S. Renal data system.

Background The U.S. Renal Data System was used to analyze renal allograft outcomes in patients with peripheral vascular disease (PVD) at the time of transplant listing. Methods We used an incident cohort of patients who underwent renal transplantation between June 2004 and September 2009. We defined PVD as symptomatic PVD at wait-listing. Comorbid conditions were diabetes mellitus, ischemic heart disease, cerebrovascular disease, hypertension, and smoking. Chi-square test, Student’s t test, and Cox regression were used for statistical associations. Results The mean graft survival was 55.3±0.40 months in patients with PVD versus 60.8±0.06 months in patients without PVD. There was an increased risk of graft failure with PVD (hazard ratio, 2.01; 95% confidence interval, 1.83–2.21; P=0.0001). After adjusting for other variables, PVD remained an independent risk factor for graft failure. Patients with PVD had lower death-censored graft survival versus patients without PVD at 1 year (93.3% vs. 96.6%), 2 years (89.7% vs. 95%), and 3 years (87.2% vs. 93.7%). All-cause mortality was higher in PVD versus without PVD (6.2% vs. 3.0%). In African Americans, the mean allograft survival was 54.8±0.98, months with PVD versus 59.7±0.135 months without PVD (P=0.0001). In non–African Americans, the mean allograft survival was 55.4±0.44 months with PVD versus 61.1±0.069 months without PVD (P=0.0001). There were no differences in survival between African Americans with PVD and non–African Americans with PVD. Conclusions Patients with PVD have inferior allograft and patient survival versus those without PVD. Caution should be exercised when placing patients with symptomatic PVD or amputation on the wait-list.

Evaluation of Non-adherence in Patients Undergoing Dialysis and Kidney Transplantation: United States Transplantation Practice Patterns Survey

INTRODUCTION We performed a survey of United States transplantation centers to evaluate practice patterns in the assessment of nonadherence before and after kidney transplantation. METHODS An electronically administered, anonymous survey was sent to 181 United Network for Organ Sharing (UNOS) approved transplantation centers in 2012. RESULTS Seventy-nine centers completed our survey. Of them, 51.3% had a protocol to evaluate medication/dialysis adherence before the listing; most common (36.4%) was the Simplified Medication Adherence Questionnaire. As an alternative to a questionnaire, the most common measure of nonadherence was the number of missed hemodialysis sessions (77.0%). The most common reason for poor adherence to dialysis regimens was difficulty with transportation (81.3%). Also, 94.4% noted the lack of a questionnaire to evaluate adherence to medications but relied on drug levels (73.4%) and self report. Only 12.9% used a questionnaire for the measurement of quality of life (Karnofsky performance scale). Of the participating centers, 27.1% used a formal cognitive testing for potential living donors. A social worker was used by most centers for nonadherent patients. Respondents indicated that patients (in the pretransplantation state) were more compliant with dialysis than with medication regimens. Finally, 37.7% of respondents noted graft failure due to medication nonadherence in 15% to 29% of their patients. CONCLUSIONS There was a significant variability in the methods of screening for nonadherence while the patient was on dialysis, during pretransplantation work up, and during post-transplantation follow-up examinations. We recommend that there should be a standardized technique to evaluate nonadherence to facilitate focused clinical trials to improve adherence.

Intravenous immunoglobulin in kidney transplantation.

Purpose of reviewAntibody-mediated injury of renal allografts has assumed increasing importance with the availability of potent immunosuppressants directed against T-lymphocytes. Intravenous immunoglobulin (IVIG) has been used for prevention and treatment of antibody-mediated rejection. The review summarizes recent advances that shed light on mechanisms of action of IVIG and outlines current roles of IVIG in kidney transplantation. Recent findingsObservational studies support the use of IVIG for desensitization and treatment of acute rejection. Most studies are small and uncontrolled, but a matched case–control study reported a better survival with incompatible live-donor kidney transplant after desensitization using IVIG-containing regimens compared with dialysis or waiting for compatible transplant. Recent data indicate that variations in glycosylation and amino acid sequence cause the crystallizable fragment of immunoglobulin G to assume specific conformations that have high affinity for canonical crystallizable fragment receptors (FcR) or a newly discovered class of FcRs, labelled type II FcRs. Signaling through type II FcRs appears to trigger anti-inflammatory pathways. SummaryRecent discoveries expand our understanding of the mechanism of action of IVIG. Future research is expected to clarify the relevance of these findings to humans and could lead to the development of novel immunomodulatory agents.

Poor kidney allograft survival associated with positive B cell - Only flow cytometry cross matches: a ten year single center study.

The presence of donor specific antibody (DSA) to class 1 or class 2 HLA as detected respectively in T cell or B cell - only flow cytometry cross matches (FCXMs) are risk factors for renal allograft survival, though the comparative risk of these XMs has not been definitively established. Allograft survival and FCXM data in 624 microcytotoxicity (CDC) XM negative kidney transplants were evaluated. Short and long term allograft survival was significantly less in recipients with T(-) B(+) FCXMs (1 year, 74%, 10 year, 58%) compared to T(+) B(+) FCXMs (1 year, 84%, 10 year, 68%) and to T(-) B(-) FCXM (1 year, 90%, 10 year, 85%). Risk factors were positive FCXM, deceased donor (DD) transplantation and donor age, but not race, gender, recipient age or previous transplant. Recipients with T(-) B(+) and T(+) B(+) FCXMs were at 4.5 and 2.5 fold greater risk, respectively, of DD allograft failure compared to patients with T(-) B(-) FCXMs. The quantitative value of FCXM did not correlate with the duration of graft survival. We conclude that patients with DSA to class 2 HLA have a greater risk of early and late allograft failure compared to patients with DSA to class 1 HLA.

Risk of transmission of human T-lymphotropic virus through transplant.

Keywords: editorial / personal viewpoint; infectious disease; kidney transplantation / nephrology; infection and infectious agents; infection and infectious agents; viral: human T-lymphotropic virus (HTLV); kidney transplantation: living donor

Mortality after Renal Allograft Failure and Return to Dialysis

Introduction: The outcomes of patients who fail their kidney transplant and return to dialysis (RTD) has not been investigated in a nationally representative sample. We hypothesized that variations in management of transplant chronic kidney disease stage 5 leading to kidney allograft failure (KAF) and RTD, such as access, nutrition, timing of dialysis, and anemia management predict long-term survival. Methods: We used an incident cohort of patients from the United States Renal Data System who initiated hemodialysis between January 1, 2003 and December 31, 2008, after KAF. We used Cox regression analysis for statistical associations, with mortality as the primary outcome. Results: We identified 5,077 RTD patients and followed them for a mean of 30.9 ± 22.6 months. Adjusting for all possible confounders at the time of RTD, the adjusted hazards ratio (AHR) for death was increased with lack of arteriovenous fistula at initiation of dialysis (AHR 1.22, 95% CI 1.02-1.46, p = 0.03), albumin <3.5 g/dL (AHR 1.33, 95% CI 1.18-1.49, p = 0.0001), and being underweight (AHR 1.30, 95% CI 1.07-1.58, p = 0.006). Hemoglobin <10 g/dL (AHR 0.96, 95% CI 0.86-1.06, p = 0.46), type of insurance, and zip code-based median household income were not associated with higher mortality. Glomerular filtration rate <10 mL/min/1.73 m2 at time of dialysis initiation (AHR 0.83, 95% CI 0.75-0.93, p = 0.001) was associated with reduction in mortality. Conclusions: Excess mortality risk observed in patients starting dialysis after KAF is multifactorial, including nutritional issues and vascular access. Adequate preparation of patients with failing kidney transplants prior to resuming dialysis may improve outcomes.

Mortality on the Kidney Waiting List and After Transplantation in Patients With Peripheral Arterial Disease: An Analysis of the United States Renal Data System

BACKGROUND Reports from the United States Renal Data System (USRDS) indicated that kidney transplantation, whether from a living donor (LD) or deceased donor (DD), offers survival advantage over being on the waiting list. Whether this is true for patients with peripheral arterial disease (PAD) is unknown given that patients with PAD have significant comorbidities. METHODS We used a cohort of USRDS incident dialysis patients from 2001 to 2007, with follow-up through 2008. Patients with PAD younger than the age of 70 were included and divided into 3 groups; PAD waitlisted, PAD patients who received a first transplant from a DD, or PAD patients who received a first transplant from a LD. Time-dependent Cox regression models were used to compare differences in mortality. RESULTS In this study, 23,699 incident dialysis patients met inclusion criteria; only 16.7% (n = 3964) were waitlisted, of which 8.9 % (n = 2121) underwent transplantation. Patient survival in the LD group at any time point was significantly better than being on the waiting list (P < .001). For DD, mortality was higher in the first year compared with waitlisted patients (P < .001), however, after 1 year survival did not differ as compared with remaining on the waiting list. After adjusting for confounders, the relative risk (RR) of dying was significantly higher for patients with history of severe vascular disease requiring amputation (RR, 1.45; 95% confidence interval [CI], 1.15-1.84) in the DD group. CONCLUSIONS Kidney transplantation from a DD did not offer survival advantage over being on the waiting list, in part due to a higher rate of severe vascular disease. Careful patient selection may improve outcomes in the DD group.

Impact of renal posttransplantation amputation on allograft outcomes: a study of United States renal data system.

Background The prevalence of renal posttransplantation amputation and its impact on allograft and patient survival have not been widely reported. Methods We used an incident cohort of patients who underwent renal transplantation between June 2004 and September 2009. Amputation data were obtained using Medicare institutional claim forms. Baseline demographics and comorbidities, such as peripheral vascular disease (PVD), diabetes, ischemic heart disease, cerebrovascular disease, hypertension, and smoking, were captured. The chi-square and t tests were used for statistical associations. Kaplan–Meier survival curves were plotted for renal allograft and patient survival. Independent associations between patient factors and amputation were examined using multivariable Cox regression analysis. Results Of the 85,873 renal transplant recipients, 1062 patients had amputation. The prevalence of amputation was higher in those with PVD versus those without PVD at listing (5.6% vs. 1%; P=0.0001). Mean allograft survival was 55.5±0.55 months in patients with amputation versus 60.6±0.06 months in patients without amputation (P=0.0001). All-cause mortality was higher in patients with amputation versus those without amputation (19.9% vs. 7.3%; P=0.0001). Mean allograft survival was 60.97±0.67 months in non–African Americans without amputation versus 55.7±0.65 months in non–African Americans with amputation. Allograft survival was 59.73±0.13 months in African Americans without amputation versus 54.9±1.06 months in African Americans with amputation. In patients with amputation, race did not have any impact. Infectious complications were noted in 39 patients leading to death. Conclusions Amputation is associated with decreased allograft and patient survival. Early detection and preventive strategies for PVD may decrease amputation rate and improve survival.