The Seattle Heart Failure Model in Kidney Transplant Recipients.

Cardiovascular disease is the leading cause of mortality following kidney transplantation. Heart failure affects 17-21% of patients with chronic kidney disease and increases along with time receiving dialysis. The Seattle Heart Failure Model (SHFM) is a validated mortality risk model for heart failure patients that incorporates clinical, therapeutic, and laboratory parameters but does not include measures of kidney function. We applied the SHFM to patients with end-stage renal disease (ESRD) who were being evaluated for kidney transplantation to determine if the model was associated with post-transplant mortality. This retrospective single-center study analyzed survival among 360 adult deceased-donor kidney transplant recipients. Cox regression was used to model post-transplant patient survival. Our findings indicated that a 1.0-point increase in the adapted SHFM score was significantly associated with post-transplant mortality (HR 1.76, 95% CI = 1.10-2.83, p = 0.02), independently of the Kidney Donor Profile Index and Estimated Post-Transplant Survival. Individual covariates of the SHFM were evaluated in univariate analyses, and age, sodium, cholesterol, and lymphocyte count were significantly related to mortality. This study provides preliminary evidence that an adapted SHFM score could be a useful tool in evaluating mortality risk post-transplant in patients with ESRD.

The demise of islet allotransplantation in the United States: A call for an urgent regulatory update.

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and "more than minimally manipulated" human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as "minimally manipulated tissue" and not regulated as a drug, which has led to islet allotransplantation (allo-ITx) becoming a standard-of-care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo-ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States.

Prostate Cancer Outcomes Following Solid-Organ Transplantation: A SEER-Medicare Analysis.

BACKGROUND: Immunosuppressive regimens associated with organ transplantation increase the risk of developing cancer. Transplant candidates and recipients with prostate cancer are often treated, even if low-risk features would ordinarily justify active surveillance. METHODS: Using SEER-Medicare, we identified 163 676 men aged 66 years and older diagnosed with nonmetastatic prostate cancer. History of solid organ transplant was identified using diagnosis or procedure codes. A propensity score-matched cohort was identified by matching transplanted men to nontransplanted controls by age, race, region, year, T-stage, grade, comorbidity, and cancer therapy. Fine-Gray competing risk models assessed associations between transplant status and prostate cancer-specific mortality (PCSM) and overall mortality (OM). RESULTS: We identified 620 men (0.4%) with transplant up to 10 years before (n = 320) or 5 years after (n = 300) prostate cancer diagnosis and matched them to 3100 men. At 10 years, OM was 55.7% and PCSM was 6.0% in the transplant cohort compared with 42.4% (P < .001) and 7.6% (P = .70) in the nontransplant cohort, respectively. Adjusted models showed no difference in PCSM for transplanted men (hazard ratio = 0.88, 95% confidence interval = 0.61 to 1.27, P = .70) or differences by prostate cancer therapy. Among 334 transplanted men with T1-2N0, well or moderately differentiated "low-risk" prostate cancer, PCSM was similar for treated and untreated men (hazard ratio = 0.92, 95% confidence interval = 0.47 to 1.81). CONCLUSIONS: Among men aged 66 years and older with prostate cancer, an organ transplant is associated with higher OM but no observable difference in PCSM. These findings suggest men with prostate cancer and previous or future organ transplantation should be managed per usual standards of care, including consideration of active surveillance for low-risk cancer characteristics.

Hemoperitoneum in a Peritoneal Dialysis Patient: Ruptured Ectopic Pregnancy.

Hemoperitoneum is a well-recognized complication in female peritoneal dialysis (PD) patients of childbearing age. Bloody effluent is commonly of minor nature, presenting during menstruation or midcycle, resolving after a few rapid exchanges without a need for further intervention. One must remain vigilant, however, and consider a broader differential diagnosis when hemoperitoneum is persistent or severe, as it indicates a serious and potentially life-threatening etiology. We report 2 episodes of hemoperitoneum in a PD patient occurring more than 1.5 years apart, with different underlying etiologies. The more dramatic second episode was due to a ruptured ectopic pregnancy, a condition which had not been reported as a cause of hemoperitoneum in dialysis patients to date and requires a high index of suspicion and prompt surgical intervention.

Frequency of In-Home Internet Use Among Prekidney and Postkidney Transplant Patients-Facilitators and Barriers to Use and Trends Over Time.

BACKGROUND: As health-related communications become digitized, strategies to increase adoption of these Web-based platforms are needed. The purpose of this study was to assess facilitators and barriers to in-home Internet use among prekidney and postkidney transplant patients. METHODS: A single center, cross-sectional survey of 240 consecutive patients of all levels of technological proficiency who presented to an urban transplant center in the United States. The Patient Information and Technology Assessment consists of 6 demographic questions, 3 disease-related questions, and 8 technology-related questions. RESULTS: Much of the sample was African American, male with a mean age of 51 years, and median income of $53 800/year. Logistic regression analysis was undertaken, and after adjusting for covariates, we found Smartphone ownership (odds ratio [OR], 4.94; 95% confidence interval [CI], 2.32-10.52), a higher number of Internet users in the home (OR, 2.00; 95% CI, 1.11-3.62), and having college education and beyond (OR, 4.88; 95% CI, 2.03-11.74) increased the likelihood of being a frequent Internet user. African American or Hispanic/Latino patients were less likely to be frequent Internet users compared with white patients (OR, 0.26 and 0.24, respectively, compared with whites, all P < 0.05). As the total number of people in the household increased, frequent Internet use decreased (OR, 0.52; 95% CI, 0.29-0.92). As age increased, reports of frequent Internet use decreased. CONCLUSIONS: Lower rates of Internet use among African Americans and Hispanic/Latinos in urban areas in the United States remains a problem despite a significant increase in access to the Internet and Smartphone ownership. The finding that Internet use increases as the number of Internet users in the household increases indicates that leveraging the patient's social support network and/or the development of patient information champion programs may aid with patient's adoption of health technology and patient engagement in self-care.

Patient-Reported Barriers to the Prekidney Transplant Evaluation in an At-Risk Population in the United States.

BACKGROUND: Despite our knowledge of barriers to the early stages of the transplant process, we have limited insight into patient-reported barriers to the prekidney transplant medical evaluation in populations largely at-risk for evaluation failure. METHODS: One-hundred consecutive adults were enrolled at an urban, Midwestern transplant center. Demographic, clinical, and quality of life data were collected prior to patients visit with a transplant surgeon/nephrologist (evaluation begins). Patient-reported barriers to evaluation completion were collected using the Subjective Barriers Questionnaire 90-days after the initial medical evaluation appointment (evaluation ends), our center targeted goal for transplant work-up completion. RESULTS: At 90 days, 40% of participants had not completed the transplant evaluation. Five barrier categories were created from the 85 responses to the Subjective Barriers Questionnaire. Patient-reported barriers included poor communication, physical health, socioeconomics, psychosocial influences, and access to care. In addition, determinants for successful evaluation completion included being of white race, higher income, free of dialysis, a lower comorbid burden, and reporting higher scores on the Kidney Disease Quality of Life subscale role-emotional. CONCLUSION: Poor communication between patients and providers, and among providers, was the most prominent patient-reported barrier identified. Barriers were more prominent in marginalized groups such as ethnic minorities and people with low income. Understanding the prevalence of patient-reported barriers may aid in the development of patient-centered interventions to improve completion rates.

Urine Metabolite Profiles Predictive of Human Kidney Allograft Status.

Noninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may help realize the full benefits of kidney transplantation. To investigate whether urine metabolites predict kidney allograft status, we determined levels of 749 metabolites in 1516 urine samples from 241 kidney graft recipients enrolled in the prospective multicenter Clinical Trials in Organ Transplantation-04 study. A metabolite signature of the ratio of 3-sialyllactose to xanthosine in biopsy specimen-matched urine supernatants best discriminated acute cellular rejection biopsy specimens from specimens without rejection. For clinical application, we developed a high-throughput mass spectrometry-based assay that enabled absolute and rapid quantification of the 3-sialyllactose-to-xanthosine ratio in urine samples. A composite signature of ratios of 3-sialyllactose to xanthosine and quinolinate to X-16397 and our previously reported urinary cell mRNA signature of 18S ribosomal RNA, CD3ε mRNA, and interferon-inducible protein-10 mRNA outperformed the metabolite signatures and the mRNA signature. The area under the receiver operating characteristics curve for the composite metabolite-mRNA signature was 0.93, and the signature was diagnostic of acute cellular rejection with a specificity of 84% and a sensitivity of 90%. The composite signature, developed using solely biopsy specimen-matched urine samples, predicted future acute cellular rejection when applied to pristine samples taken days to weeks before biopsy. We conclude that metabolite profiling of urine offers a noninvasive means of diagnosing and prognosticating acute cellular rejection in the human kidney allograft, and that the combined metabolite and mRNA signature is diagnostic and prognostic of acute cellular rejection with very high accuracy.

Use of leflunomide in renal transplant recipients with ganciclovir-resistant/refractory cytomegalovirus infection: a case series from the University of Chicago.

INTRODUCTION: Although antiviral prophylaxis for cytomegalovirus (CMV) is widely used, CMV infection remains common in renal transplant recipients with adverse consequences. METHODS: We report 5 cases of renal transplant recipients with resistant CMV infection who were successfully managed with leflunomide at the University of Chicago Medical Center. RESULTS: Five renal transplant recipients (2 simultaneous pancreas/kidney transplants, 3 deceased donor kidney transplants) were diagnosed with GCV-resistant CMV infection from 2003 to 2011. Of the 4 patients who had resistance genotype testing, 3 showed a UL97 mutation and 1 patient had a clinically resistant CMV infection. All patients received CMV prophylaxis with valganciclovir for 3 months. The number of days from the date of transplant to viremia ranged from 38 to 458 days (median 219). All 5 patients received other antiviral agents (e.g. ganciclovir, foscarnet), and in 4 patients, viremia was cleared before leflunomide was initiated as consolidation (or maintenance) therapy. CONCLUSION: Leflunomide was well tolerated and successful in preventing recurrence of viremia in renal transplant recipients with resistant CMV infection. The beneficial effect of leflunomide in this setting warrants further investigation.

Determinants of frequent Internet use in an urban kidney transplant population in the United States: characterizing the digital divide.

CONTEXT: The Internet is a staple of electronic communication and is essential to the emerging telemonitoring and health information technology interventions for adults with chronic diseases. OBJECTIVE: To identify determinants of frequent Internet use in an urban kidney transplant population in the United States. DESIGN: A single center, cross-sectional survey study. SETTING: An urban Midwestern transplant center. PARTICIPANTS: 78 pretransplant and 177 posttransplant patients. MAIN OUTCOME MEASURES: Frequent Internet use, defined as using the Internet more than 5 hours per week. RESULTS: Only 38% of participants reported being frequent Internet users. Non-Hispanic blacks and participants who reported their race/ethnicity as "other" were significantly less likely than whites to report being frequent Internet users. Women were 59% less likely than men to be frequent users of the Internet. Those who reported having kidney disease for more than 3 years were more likely to report being frequent Internet users. As education increased, Internet use increased. As age increased, Internet use decreased. CONCLUSION: Alternatives to electronic information sources and/or additional resources should be considered for those who may fall in the so-called digital divide.

Kidney transplant and the digital divide: is information and communication technology a barrier or a bridge to transplant for African Americans?

CONTEXT: Barriers to kidney transplant for African Americans are well documented in the literature. Little information on ownership of information and communication technology and use of such technology in transplant populations has been published. OBJECTIVE: To characterize racial differences related to ownership and use of information and communication technology in kidney transplant patients. DESIGN: A single-center, cross-sectional survey study. SETTING: An urban Midwestern transplant center. PARTICIPANTS: 78 pretransplant patients and 177 transplant recipients. MAIN OUTCOMES MEASURES: The survey consisted of 6 demographic questions, 3 disease-related questions, and 9 technology-related questions. Dichotomous (yes/no) and Likert-scale items were the basis for the survey. RESULTS: Cell phone use was high and comparable between groups (94% in African Americans, 90% in whites, P= .22). A vast majority (75% of African Americans and 74% of whites) reported being "comfortable" sending and receiving text messages. Computer ownership (94.3% vs 79.3%) and Internet access (97.7% vs 80.7%) were greater among whites than African Americans (both P< .01). Fewer African Americans were frequent users of the Internet (27.1% vs 56.3%) and e-mail (61.6% vs 79.3%) than whites (both P<.01). More African Americans than whites preferred education in a classroom setting (77% vs 60%; P< .005) and educational DVDs (66% vs 46%; P< .002). CONCLUSION: The use of cell phone technology and text messaging was ubiquitous and comparable between groups, but computer and Internet access and frequency of use were not. Reaching out to the African American community may best be accomplished by using cell phone/text messaging as opposed to Internet-based platforms.

Urinary-cell mRNA profile and acute cellular rejection in kidney allografts.

BACKGROUND: The standard test for the diagnosis of acute rejection in kidney transplants is the renal biopsy. Noninvasive tests would be preferable. METHODS: We prospectively collected 4300 urine specimens from 485 kidney-graft recipients from day 3 through month 12 after transplantation. Messenger RNA (mRNA) levels were measured in urinary cells and correlated with allograft-rejection status with the use of logistic regression. RESULTS: A three-gene signature of 18S ribosomal (rRNA)-normalized measures of CD3ε mRNA and interferon-inducible protein 10 (IP-10) mRNA, and 18S rRNA discriminated between biopsy specimens showing acute cellular rejection and those not showing rejection (area under the curve [AUC], 0.85; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 by receiver-operating-characteristic curve analysis). The cross-validation estimate of the AUC was 0.83 by bootstrap resampling, and the Hosmer-Lemeshow test indicated good fit (P=0.77). In an external-validation data set, the AUC was 0.74 (95% CI, 0.61 to 0.86; P<0.001) and did not differ significantly from the AUC in our primary data set (P=0.13). The signature distinguished acute cellular rejection from acute antibody-mediated rejection and borderline rejection (AUC, 0.78; 95% CI, 0.68 to 0.89; P<0.001). It also distinguished patients who received anti-interleukin-2 receptor antibodies from those who received T-cell-depleting antibodies (P<0.001) and was diagnostic of acute cellular rejection in both groups. Urinary tract infection did not affect the signature (P=0.69). The average trajectory of the signature in repeated urine samples remained below the diagnostic threshold for acute cellular rejection in the group of patients with no rejection, but in the group with rejection, there was a sharp rise during the weeks before the biopsy showing rejection (P<0.001). CONCLUSIONS: A molecular signature of CD3ε mRNA, IP-10 mRNA, and 18S rRNA levels in urinary cells appears to be diagnostic and prognostic of acute cellular rejection in kidney allografts. (Funded by the National Institutes of Health and others.).

Simultaneous pancreas and kidney (SPK) retransplantation in prior SPK recipients.

INTRODUCTION: We have performed 113 renal and 28 isolated pancreas retransplants in our cohort of more than 1200 prior simultaneous pancreas and kidney (SPK) recipients. On the basis of these experiences, we began performing repeat SPK in prior SPK recipients (n = 9). METHODS: This retrospective review summarizes our experience with repeat SPK transplantation in prior SPK recipients. Mean age at retransplant was 39 yr; mean interval to retransplant was 7.8 yr. Thirty-three percent were pre-dialysis. Eighty-nine percent of patients underwent transplant nephrectomy (five during the repeat SPK and three prior to it), and 78% underwent transplant pancreatectomy (four during the repeat SPK and three prior to it). Enteric drainage was performed in all repeat SPKs. RESULTS: Median length of stay was 11 d. Perioperative complications included the following: renal artery thrombosis (1), pancreatic portal venous thrombosis (1), enteric leak (1), and hematoma (2). Overall pancreatic allograft survival was 78% at one yr and 67% at two yr. Overall renal allograft survival was 89% at one yr and 78% at two yr. Patient survival at one and three yr was 100%. CONCLUSIONS: Survival of repeat SPK allografts is acceptable despite the increased technical and immunologic demands of retransplantation. Graftectomy prior to or at the time of retransplantation is often necessary.

"Venopathy" at work: recasting neointimal hyperplasia in a new light.

Hemodialysis vascular access is a unique form of vascular anastomosis. Although it is created in a unique disease state, it has much to offer in terms of insights into venous endothelial and anastomotic biology. The development of neointimal hyperplasia (NH) has been identified as a pathologic entity, decreasing the lifespan and effectiveness of hemodialysis vascular access. Subtle hints and new data suggest a contrary idea-that NH, to some extent an expected response, if controlled properly, may play a beneficial role in the promotion of maturation to a functional access. This review attempts to recast our understanding of NH and redefine research goals for an evolving discipline that focuses on a life-sustaining connection between an artery and vein.

One thousand simultaneous pancreas-kidney transplants at a single center with 22-year follow-up.

OBJECTIVE: Simultaneous pancreas-kidney transplantation (SPK) is a procedure which frees the diabetic patient with end-stage nephropathy from dialysis and daily insulin injections. The purpose of this study is to report long-term outcomes of this procedure, and describe surgical and medical complications. METHODS: The analysis includes 1000 consecutive SPKs performed between 1985 and 2007. Bladder drainage was used in 390 patients and enteric drainage in 610 patients. In 362 patients, SPK transplantation was performed before initiation of dialysis. RESULTS: Patient survival at 1, 10, and 20 years is 97%, 80%, and 58%; kidney survival is 91%, 63%, and 38%; and pancreas survival is 88%, 63%, and 36%, respectively. There was no difference (P > 0.19) for patient, kidney, and pancreas survival between bladder and enteric drainage. Major surgical complications for bladder-drained patients were anastomotic leaks, urological complications, and infections. For enteric-drained patients, major surgical complications were infection, bleeding, and enzyme leak. Principal causes of death were myocardial infarction (n = 23), cerebrovascular accident (n = 18), and renal failure (n = 15). Graft failure for the kidney was due to acute rejection (n = 48), chronic rejection (n = 146), and death with a functioning graft (n = 99). Graft failure for the pancreas was caused by chronic graft loss (n = 44), thrombosis (n = 31), rejection (n = 80), and death with a functioning graft (n = 125). A total of 113 patients were retransplanted with either living related or unrelated donor kidneys (n = 64) or deceased donor kidneys (n = 42). Survival for retransplanted kidneys is 84% at 1 year and 68% at 5 years. Surviving bladder-drained patients underwent enteric conversion (>50%) for severe recalcitrant metabolic or urologic complications, most commonly enzyme leaks, hematuria, and recurrent urinary tract infection. CONCLUSIONS: Diabetic patients with end-stage renal failure have a poor prognosis without transplantation. Transplantation with SPK provides a marked extension of the patient's life and freedom from insulin injections. Enteric drainage is currently the surgical technique of choice. SPK transplantation should be considered the treatment of choice in this patient population.

Alemtuzumab induction and antibody-mediated kidney rejection after simultaneous pancreas-kidney transplantation.

BACKGROUND: The best induction agent for simultaneous pancreas-kidney transplantation (SPKT) remains the subject of debate. Alemtuzumab is effective in preventing acute cellular rejection (ACR) in SPK recipients and has been used to prevent antibody-mediated rejection (AMR) in sensitized kidney transplant candidates. METHODS: A retrospective cohort study was performed including 136 SPK recipients receiving maintenance immunosuppression with tacrolimus, mycophenolic acid prodrugs, and prednisone. Two groups were compared: those who received induction with alemtuzumab (n=97) and those induced with basiliximab (n=39). RESULTS: Kidney ACR was more frequent in SPKT induced with basiliximab (2-year 12.8% vs. 3.1%, P=0.04), but the incidence of AMR was similar (2-year 18% with basiliximab vs. 13.8% with alemtuzumab, P=NS). Kidney rejection was associated with clinical pancreas rejection in 70% of cases, without differences between the groups. Postrejection kidney graft survival was similar in both groups (2-year basiliximab/alemtuzumab 94.7%/91.2%), but death-censored kidney graft survival was lower with alemtuzumab (100%/91.2%, P=0.056). In the basiliximab group, the predominant cause of kidney loss was death-with-function, whereas in the alemtuzumab group AMR accounted for all losses. Pancreas graft survival was similar in both groups, yet more pancreas losses due to acute rejection occurred in alemtuzumab-treated patients (4 vs. 1). CONCLUSIONS: Kidney AMR is more common than ACR in SPKT recipients treated with alemtuzumab, tacrolimus, mycophenolic acid, and steroids. ACR is better prevented by alemtuzumab than basiliximab, but no relevant difference is found in prevention of AMR. Despite the high incidence of AMR, survival rates are excellent in both groups.

Obesity as a predictor of vascular access outcomes: analysis of the USRDS DMMS Wave II study.

Arteriovenous fistulae (AVF) are widely regarded as the preferred vascular access in hemodialysis patients due to their primary patency and patient survival benefits. While the obesity paradox has been associated with improved cardiovascular morbidity and all-cause mortality in dialysis patients, its long-term vascular access outcomes are less clear. Recent literature has suggested that obese patients may have increased early and late fistula failure. The purpose of this study was to explore the relationships between obesity and vascular access outcomes. We performed a retrospective cohort analysis using the USRDS DMMS Wave 2 data set. All incident dialysis patients as of January 1, 1996, over the age of 18, receiving only hemodialysis as mode of renal replacement therapy were eligible for inclusion. Among other variables, data collected for the DMMS Wave 2 included: type and location of vascular access, AVF maturity, vascular access revision, and failure. Logistic regression analyses were used to examine the relationships between obesity and vascular access outcomes, adjusting for important covariates. In all, 1486 hemodialysis patients were included. Using body mass index (BMI) <30 kg/m(2) as reference, obesity did not emerge as a factor in predicting vascular access revisions or failures. An increased risk of AVF failure to mature was found only in the highest BMI quartile (>or=35 kg/m(2)) (aOR 3.66 [95% CI 1.27-10.55], p = 0.017). Peripheral vascular disease was independently associated with an increased risk of AVF failure (aOR 2.78 [95% CI 1.01-7.63], p = 0.047) and arteriovenous graft (AVG) failure (aOR 1.65 [95% CI 1.03-2.64], p = 0.036). Obesity was not associated with increased AVF or AVG revision rates or failure and only associated with poorer AVF maturity at highest BMI quartile. We conclude that obesity should not preclude placement of AVF as vascular access of choice, except in the very obese where assessment should be individually based.