Systolic dysfunction portends increased mortality among those waiting for renal transplant.

Individuals waiting for a renal transplant experience excessive cardiovascular mortality, which is not fully explained by the prevalence of ischemic heart disease in this population. Overt heart failure is known to increase the mortality of patients with ESRD, but the impact of lesser degrees of ventricular systolic dysfunction is unknown. For examination of the association between left ventricular ejection fraction(LVEF) and mortality of renal transplant candidates, the records of 2718 patients evaluated for transplantation at one institution were reviewed. During 6355 patient-years (median 27 mo) of follow-up, 681 deaths occurred. Patients with systolic dysfunction (LVEF

Bladder debris on ultrasound in the emergency department: correlation with urinalysis.

PURPOSE: To evaluate the correlation between the presence of bladder debris on ultrasound and urinalysis results in the emergency department setting. METHODS: Adult patients presenting to the emergency department with an ultrasound of the bladder and a urinalysis performed within 24 h of the ultrasound were included in this retrospective study. Two radiologists in consensus evaluated for the presence or absence of debris within the bladder. Urinalysis results were recorded including continuous variables (specific gravity and pH) and categorical variables (presence of occult blood, bilirubin, ketones, glucose, protein, urobilinogen, nitrite, leukocyte esterase, white blood cells, and red blood cells). The presence and absence of white and red blood cells were defined as > 5 cells/high-powered field. To control the experimentwise type I error rate at 0.05, a Bonferroni-corrected significance level of 0.0042 was used to determine significant associations. RESULTS: The presence of bladder debris was associated with the presence of urobilinogen, nitrite, and white blood cells (p = < 0.0001, 0.0005, and 0.0004, respectively). CONCLUSIONS: Bladder debris in the emergency department setting correlates with urinalysis laboratory values suggesting a urinary tract infection. Therefore, the presence of bladder debris should elicit the recommendation of a urinalysis in such a setting.

Impact of Willingness to Accept Hepatitis C Seropositive Kidneys Among Hepatitis C RNA-Positive Waitlisted Patients.

BACKGROUND: Kidney transplantation from hepatitis C seropositive (HCV+) donors may benefit hepatitis C RNA-positive (RNA+) candidates, but it is unclear how the willingness to be listed for and accept such kidneys affects waitlist and transplant outcomes. METHODS: In a single-center retrospective analysis, HCV+ transplant candidates (N = 169) listed from March 2004 to February 2015 were evaluated. All RNA+ candidates were offered the option to be listed for HCV+ donors. RNA- candidates were listed only for HCV- donors. RESULTS: Fifty-seven patients (51% of all RNA+ transplant candidates) willing to accept HCV+ donors were listed for both HCV+ and HCV- donor kidneys. During 6-year follow up, 43 (75%) of 57 patients accepting HCV+ versus 19 (35%) of 55 patients not accepting HCV+ received a deceased donor kidney transplant (P < 0.0001). Multivariable analysis demonstrated that willingness to be listed for and accept HCV+ kidneys was associated with receiving deceased donor kidney transplant (P = 0.0016). Fewer patients accepting HCV+ donors (7 [12%] vs 16 [29%]) were removed from the list due to death or deteriorated medical condition (P = 0.0117). Posttransplant patient and graft survival rates were not significantly different. Overall patient survival since the listing (combined waitlist and posttransplant survival) was similar among the groups. CONCLUSIONS: HCV RNA+ candidates had better access to transplantation and similar overall survival before the era of widespread use of direct-acting anti-HCV agents.

The impact of left ventricular systolic dysfunction on survival after renal transplantation.

BACKGROUND: Gated single photon emission computed tomography (SPECT) provides information on myocardial perfusion and left ventricular ejection fraction (LVEF), which correlates with risk of cardiac events in patients with known or suspected coronary artery disease (CAD). We hypothesize that decreased LVEF at time of renal transplant evaluation is an independent risk factor for cardiac death and nonfatal events after transplant. METHODS AND RESULTS: A total of 653 recipients of renal allografts between 1998 and 2005 had stress SPECT imaging before transplantation. One hundred and nineteen (18%) patients had left ventricular (LV) systolic dysfunction (LVEF

Predictors of survival in patients with end-stage renal disease evaluated for kidney transplantation.

Cardiovascular disease is the major cause of mortality in patients with end-stage renal disease (ESRD). This study examined the all-cause mortality in 3,698 patients with ESRD evaluated for kidney transplantation at our institution from 2001 to 2004. Mean age for the cohort was 48+/-12 years, and 42% were women. Stress myocardial perfusion imaging was done in 2,207 patients (60%) and coronary angiography in 260 patients (7%). There were 622 deaths (17%) during a mean follow-up period of 30+/-15 months. The presence and severity of coronary disease on angiography was not predictive of survival. Coronary revascularization did not impact survival (p=0.6) except in patients with 3-vessel disease (p=0.05). The best predictor of death was left ventricular ejection fraction, measured by gated myocardial perfusion imaging, with 2.7% mortality increase for each 1% ejection fraction decrease. In conclusion, left ventricular ejection fraction is a strong predictor of survival in patients with ESRD awaiting renal transplantation. Strategies to improve cardiac function or earlier renal transplantation deserve further studies.

Laryngotracheal transplantation: technical modifications and functional outcomes.

OBJECTIVES/HYPOTHESIS: Laryngeal transplantation offers the potential for patients without a larynx to recover their voice, which is critical in our communication age. We report clinical and functional outcomes from a laryngotracheal transplant. Widespread adoption of this technique has been slowed due to the ethical concerns of life-long immunosuppression after a nonvital organ transplant. Our patient was already on immunosuppressive medication from prior kidney-pancreas transplantation, and therefore was not exposed to added long-term risk. We describe the unique technical advances, clinical course, and rehabilitation of this patient and the implications for future laryngeal transplantation. STUDY DESIGN: Case report. METHODS: A laryngotracheal transplantation was performed in a 51-year-old prior kidney-pancreas transplant recipient presenting with complete laryngotracheal stenosis. Surgical modifications were made in the previously described technique related to retrieval, vascular supply, and reinnervation. This resulted in a robustly vascularized organ with well-perfused long-segment tracheal transplant and early return of motor reinnervation. RESULTS: A multidisciplinary approach resulted in a successful transplant without evidence of rejection to date. Postoperatively, the patient continues to rely on a tracheotomy but has had the return of an oral and nasal airway, vocalization, smell, and taste, all experienced for the first time in 11 years. CONCLUSIONS: We have demonstrated that our methods may result in a successful laryngotracheal transplant. We describe the preparation, surgical technique, rehabilitation, and interventions employed in achieving optimal outcomes. This report contributes valuable information on this rarely performed composite transplant.

Fatal transplant-associated west nile virus encephalitis and public health investigation-california, 2010.

BACKGROUND: In December 2010, a case of West Nile virus (WNV) encephalitis occurring in a kidney recipient shortly after organ transplantation was identified. METHODS: A public health investigation was initiated to determine the likely route of transmission, detect potential WNV infections among recipients from the same organ donor, and remove any potentially infected blood products or tissues. Available serum, cerebrospinal fluid, and urine samples from the organ donor and recipients were tested for WNV infection by nucleic acid testing and serology. RESULTS: Two additional recipients from the same organ donor were identified, their clinical and exposure histories were reviewed, and samples were obtained. WNV RNA was retrospectively detected in the organ donor's serum. After transplantation, the left kidney recipient had serologic and molecular evidence of WNV infection and the right kidney recipient had prolonged but clinically inapparent WNV viremia. The liver recipient showed no clinical signs of infection but had flavivirus IgG antibodies; however, insufficient samples were available to determine the timing of infection. No remaining infectious products or tissues were identified. CONCLUSIONS: Clinicians should suspect WNV as a cause of encephalitis in organ transplant recipients and report cases to public health departments for prompt investigation of the source of infection. Increased use of molecular testing and retaining pretransplantation sera may improve the ability to detect and diagnose transplant-associated WNV infection in organ transplant recipients.

QT prolongation is an independent predictor of mortality in end-stage renal disease.

BACKGROUND: Coronary artery disease (CAD) is the predominant cause of sudden cardiac death in the general population, and sudden cardiac death is the leading cause of mortality in end-stage renal disease (ESRD). HYPOTHESIS: QT-interval prolongation is an independent prognosticator in ESRD. METHODS: We reviewed clinical, electrocardiographic, stress test, and coronary angiography data on ESRD patients evaluated for transplantation at our institution between 2000 and 2004 who underwent coronary angiography. The QT interval was corrected for heart rate and QRS duration (QTc). All-cause mortality data were prospectively collected and verified against the Social Security Death Index database. RESULTS: During 40 +/- 28 months of follow-up, 132 of the 280 (47%) patients died prior to renal transplantation. Patients with a prolonged QTc (39%) had 1-, 3-, and 5-year death-rates of 12%, 36%, and 47%, respectively, vs 8%, 24%, and 36% for those with normal QTc (log-rank P = 0.03). In a multivariate Cox regression model that adjusted for age, gender, diabetes mellitus, myocardial infarction, presence and severity of CAD on angiography, left ventricular (LV) hypertrophy, LV ejection fraction (EF), and multiple other variables, QTc remained to be an independent predictor of survival (hazard ratio [HR]: 1.008, 95% confidence interval [CI]: 1.001-1.014, P = 0.016). Female gender, decreasing LVEF, and decreasing severity of CAD on angiography were independent predictors of prolonged QTc. CONCLUSIONS: QTc prolongation is an independent predictor of mortality in ESRD patients being evaluated for renal transplantation. The prognostic information gained from the QTc is additive to that provided by the LVEF and the severity of CAD.

Relation between heart rate response to adenosine and mortality in patients with end-stage renal disease.

This study examined the relation between heart rate (HR) response to adenosine and outcome in patients with end-stage renal disease (ESRD). The usual HR increase during adenosine infusion was caused by direct sympathetic stimulation. It was hypothesized that a blunted HR response, which was probably caused by sympathetic denervation, would be associated with a worse outcome in patients with ESRD. One hundred thirty-nine patients with ESRD being evaluated for renal transplantation who underwent coronary angiography and adenosine gated single-photon emission computed tomographic myocardial perfusion imaging were followed up for all-cause mortality. Percentage of change in HR (%DeltaHR) was calculated as [(peak HR during adenosine infusion - HR at rest)/HR at rest] * 100. A control group of 54 patients (normal renal function and no diabetes) was included for comparison of HR responses. Mean age of patients was 54 +/- 9 years, 30% were women, and 68% had type-2 diabetes mellitus. %DeltaHR was 19.2 +/- 18% in patients with ESRD versus 33 +/- 25% in the control group (p <0.0001). At a mean follow-up of 3.4 +/- 1.5 years, 50 patients (36%) with ESRD died. %DeltaHR was lower in nonsurvivors than survivors (12.6 +/- 14% vs 23 +/- 19%; p = 0.0017). Patients with %DeltaHR less than the median value were more likely to have lower left ventricular ejection fraction and larger end-diastolic volume (p <0.05 for each). In a multivariate logistic regression model, %DeltaHR alone was an independent predictor of all-cause mortality (adjusted odds ratio 5.5, 95% confidence interval 2.3 to 12.9, p = 0.0001). In conclusion, patients with ESRD had a blunted HR response to adenosine, and degree of blunting was strongly associated with all-cause mortality.

Late steroid withdrawal and cardiovascular events in kidney transplant recipients.

INTRODUCTION: Cardiovascular events (CVE) are the leading cause of mortality in kidney transplant recipients. The adverse effects of long-term therapy with steroids on cardiovascular risk have motivated increasing interest in steroid withdrawal (SW). The objective of this study was to compare the incidences of CVE and all-cause mortality between patients who had undergone SW at 1 year posttransplant and control patients who continued on steroids. METHODS: A cohort of 400 consecutive adult recipients of a kidney transplant between 1993 and 1998 who qualified for late SW was studied. At 1 year posttransplant 188 patients underwent SW, whereas 212 patients continued on steroids. Cox proportional-hazards analysis was used to estimate CVE (cardiac and cerebrovascular events) and all-cause mortality hazard ratios (HR) for patients who had undergone SW versus controls who continued on steroids beyond 1 year. RESULTS: The average follow-up was 61 months. There were 44 (11%) cardiac events, 18 (4.5%) cerebrovascular events, and 41 deaths (10.3%). The composite outcome of CVE and all-cause mortality was reached in 26 (13.8%) subjects who had undergone SW and 50 (23.6%) controls (P=0.013). In adjusted analyses, SW was associated with decreased risk for the composite outcome (HR 0.46, 95% confidence interval [CI] 0.28-0.76), cardiac events (HR 0.48, 95% CI 0.28-0.84), and all-cause mortality (HR 0.27, 95% CI 0.12-0.59). There was no association of SW with the risk for cerebrovascular events (HR 1.76, 95% CI 0.45-7.01). CONCLUSION: In this retrospective analysis, SW at 1 year posttransplant was associated with decreased risk for future CVE and all-cause mortality.

Role of myocardial perfusion imaging in patients with end-stage renal disease undergoing coronary angiography.

Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular events. This study examined the prognostic power of stress myocardial perfusion imaging (MPI) in 150 patients with ESRD (mean age 53 +/- 9 years; 30% women; 66% with diabetes mellitus) being evaluated for renal transplantation with known coronary anatomy using angiography. Baseline data in addition to perfusion and angiographic parameters were compared between survivors and nonsurvivors. All-cause mortality was defined as the outcome measure. An abnormal MPI result was present in 85% of patients, 30% had left ventricular (LV) ejection fraction (EF) < or =40%, and 40% had multivessel coronary artery disease using angiography. At a mean follow-up of 3.4 +/- 1.5 years, 53 patients died (35%). LVEF < or =40%, LV dilatation (LV end-diastolic volume >90 ml), and diabetes mellitus were associated with higher mortality (all p <0.05). Both total perfusion defect size and mean number of narrowed coronary arteries using angiography were significantly higher in those who died (p <0.05). In a multivariate model, abnormal MPI results (low LVEF or abnormal perfusion) and diabetes alone were independent predictors of death, whereas number of narrowed arteries using coronary angiography was not. Thus, MPI was a strong predictor of all-cause mortality in patients with ESRD. In conclusion, abnormal MPI results independently predicted worse survival and provided more powerful prognostic data than coronary angiography.

Increasing referral for renal transplant evaluation in recipients of nonrenal solid-organ transplants: a single-center experience.

The use of cyclosporine and tacrolimus therapy in nonrenal (heart, heart/lung, lung, and liver) transplantation has resulted in improved patient and graft survival. Nephrotoxicity is one of the major side effects of tacrolimus and cyclosporine therapy and may lead to ESRD. The trend of referral of nonrenal solid-organ transplant recipients for kidney transplant evaluation at a large multiorgan transplant center was examined. Records of all patients who were referred for renal transplantation at the University of Alabama between January 1, 1993, and June 30, 2004, were reviewed. Eighty (0.96%) of 8318 individuals had previously undergone a nonrenal solid-organ transplant and were included in the study. The majority (72%) of patients had their nonrenal transplants performed at the University of Alabama. Twenty-two patients had their nonrenal transplant performed elsewhere and had fewer data available for analysis. From the period 1993-1996 to 2001-2004, an 11-fold increase in the absolute number of referrals of patients with nonrenal transplants was noted. Of patients who were referred for transplant evaluation, 25 became recipients of kidney transplants with a predominance of living-donor transplants. Referral for kidney transplant evaluation among nonrenal solid-organ transplant recipients is increasing and will exacerbate the existing shortage of deceased-donor kidneys that are available for transplantation. There was a trend for liver transplant recipients compared with other solid-organ recipients to develop ESRD at a greater rate.

Autosomal-dominant polycystic kidney disease as a risk factor for diabetes mellitus following renal transplantation.

BACKGROUND: Posttransplant diabetes mellitus is an important complication of renal transplantation that is associated with a significant impact on quality of life and an increase in long-term morbidity and mortality. Autosomal-dominant polycystic kidney disease (ADPKD) is a hereditary disease that commonly leads to end-stage renal disease (ESRD) in adulthood. The association between ADPKD and posttransplant diabetes mellitus has not been previously studied in a large cohort of patients. METHODS: To address this question, we studied a cohort of 135 patients with ADPKD who received a first renal-only transplant between January 1985 and December 1999. An age, race, and date of transplant-matched cohort of 135 non-ADPKD subjects were used as the control population. RESULTS: The cohorts were similar at baseline for gender distribution, body mass index (BMI), proportion of obese subjects (BMI greater than 30 kg/m(2)), family history of diabetes mellitus, and type of donor (deceased or living). At 12 months, the incidence of posttransplant diabetes mellitus was significantly higher in patients with ADPKD when compared to the controls (17% vs. 7.4%) (P= 0.016), despite no significant differences in the BMI, percent increase in BMI, number of acute rejections, prednisone dose at 3 and 6 months, use of diuretics or beta blockers, delayed graft function, or serum creatinine levels. The proportion of subjects requiring insulin was significantly higher in the ADPKD group (11.1% vs. 3%) (P= 0.009). Variables significantly associated with posttransplant diabetes mellitus at 1 year by bivariate analyses were the diagnosis of ADPKD (P= 0.02), BMI at transplant (P= 0.04), obesity at 12 months (P= 0.01), and delayed graft function (P= 0.02). Gender of recipient (P= 0.9), family history of diabetes (P= 0.3), prednisone dose at 3 months (P= 0.9) and 6 months (P= 0.7), acute rejection (P= 0.9), use of beta blockers or tacrolimus (P= 0.8), deceased donor transplant (P= 0.2), and serum creatinine at 1 year (P= 0.5) were not associated with posttransplant diabetes mellitus. A trend toward increased incidence of posttransplant diabetes mellitus was found with the use of diuretics post transplant (P= 0.054). By multivariable analyses, in patients with ADPKD, the adjusted (by all the variables listed above) relative risk for development of posttransplant diabetes mellitus was 2.87 (95% CI = 1.24-6.65) (P= 0.014). Only the diagnosis of ADPKD (RR = 2.9) (P= 0.01), obesity at 1 year (RR 2.5) (P= 0.017), and delayed graft function (RR 2.4) (P= 0.03) contributed significantly to the fit of a stepwise logistic regression model. Patient survival was significantly worse in the cohort of patients who developed posttransplant diabetes mellitus (median survival 109.3 vs. 121 months) (P= 0.008). CONCLUSION: In our study patients with ADPKD were at a threefold increased risk for development of posttransplant diabetes mellitus within the first year following renal transplantation. Development of posttransplant diabetes mellitus was associated with a significant detrimental impact on patient survival. Further studies are needed to provide insight into the mechanisms of the association between ADPKD and posttransplant diabetes mellitus.

Living unrelated donor renal transplantation: a single center experience.

PURPOSE: Living, genetically unrelated donor renal transplantation (LURT) is being performed with increasing frequency. We evaluated our single center experience with LURT and compared this to a cohort of living related donor renal transplants (LRT) to evaluate the short-term success of LURT at our center. MATERIALS AND METHODS: We identified 99 consecutive patients who underwent LURT at our center and had at least 1 year of followup data. A control cohort of 99 patients who underwent LRT at our center matched for age, number of transplants and date of transplant was also identified. One-year graft and patient survival, and serum creatinine levels at 1, 3, 6 and 12 months were compared between the groups. Our data were compared with national and international data. RESULTS: At our center 1-year graft survival was 95% in the LURT and LRT cohorts. One-year LURT patient survival was 99% compared with 97% in the LRT group and the serum creatinine levels were not significantly different. CONCLUSIONS: Patients undergoing LURT at our center have excellent 1-year graft and patient survival compared with LRT performed at our center, and national and international LURT. Genetically unrelated kidney donors should continue to be used to expand the kidney donor pool.

Renal transplantation at Oregon Health and Science University: recent results and protocols.

Renal transplants have been performed at the University Hospital, Portland, OR since 1959. In the 5-year period between January 1997 and December 2001, 736 kidney-only transplants were performed at our institution. Living donor transplants comprise an increasing proportion of the transplants performed. Our patient and graft survival rates, both short- and long-term reflect the close collaboration between the transplantation medicine and transplantation surgery faculties, and the excellent support from nurse-coordinators, histocompatibility laboratory specialists and the organ procurement organization. Since September 2001, we have used a risk-based immunosuppression algorithm. The incidence of acute rejection within the first 3 months following transplantation ranged from 7-18% in the different risk groups. We have incorporated surveillance renal allograft biopsies into our standard of care and biopsies are performed at 3 months and one year after transplantation. The incidence of subclinical rejection was 15% on the 3-month surveillance biopsies and 4% on the one-year biopsies. The majority of these rejection episodes were CCTT type I acute rejection, which responded to treatment with pulse steroids. Since 1991, we have been transplanting kidneys from blood group A2 donors into blood group B or O recipients. Graft survival is similar to that in patients receiving an ABO compatible transplant. We have recently adopted the use of intravenous immune globulin to abrogate a positive crossmatch and allow transplantation of a kidney from a living donor. Six patients have been successfully transplanted using this protocol. In an effort to speed up the work-up of recipients waiting for a deceased donor kidney transplant, we have implemented a computer-driven algorithm. By generating a list of patients who should be crossmatched, and by automating generation of work sheets and reports, this computer-driven program has expedited deceased donor workups.