Kidney Transplant Status Research Articles

The EKFC equation outperforms the CKD-EPI and CKiD equations for GFR estimation in adolescent and young adult kidney transplant patients.

This study evaluated the bias and accuracy of the CKD-EPI/CKiD and EKFC equations compared with the reference exogenous tracer-based assessment of glomerular filtration rate (GFR) in adult and pediatric patients according to their renal transplant status. We assessed the bias and P30 accuracy of the CKD-EPI/CKiD and EKFC equations compared with iohexol-based GFR measurement. In the overall population (n = 59), the median age was 29 years (IQR, 16.0-46.0) and the median measured GFR was 73.9 mL/min/1.73m2 (IQR, 57.3-84.6). Among non-kidney transplant patients, the median was 77.7 mL/min/1.73m2 (IQR, 59.3-86.5), while among kidney transplant patients, it was 60.5 mL/min/1.73m2 (IQR, 54.2-66.8). The bias associated with the EKFC and CKD-EPI/CKiD equations was significantly higher among kidney transplant patients than among non-kidney transplant patients, with a difference between medians (Hodges-Lehmann) of +10.4 mL/min/1.73m2 (95% CI, 2.2-18.9; p = .02) for the EKFC and +12.1 mL/min/1.73m2 (95% CI, 4.2-21.4; p = .006) for the CKD-EPI/CKiD equations. In multivariable analysis, kidney transplant status emerged as an independent factor associated with a bias of >3.4 mL/min/1.73m2 (odds ratio, 7.7; 95% CI, 1.4-43.3; p = .02) for the EKFC equation and a bias of >13.4 mL/min/1.73m2 (odds ratio, 15.0; 95% CI, 2.6-85.7; p = .002) for the CKD-EPI/CKiD equations. In our study, which included adolescent and young adult kidney transplant patients, both the CKD-EPI/CKiD and EKFC equations tended to overestimate the measured glomerular filtration rate, with the EKFC equation exhibiting less bias. Renal transplant status significantly influenced the degree of estimation bias.

#2859 Clinical and morphological characteristics of biopsy-proven kidney graft rejection in Latvia

Abstract Background and Aims Kidney transplantation is a treatment for many patients with end stage renal disease leading to increased quality of life. In last decades results in kidney transplantation have been improving, but allograft rejection remains an important clinical problem. Graft biopsy remains the gold standard to assess the cause of kidney transplant status. This study aimed to determine clinical and histopathological characteristics, treatment and short-term outcomes of biopsy-proved kidney graft rejection in Latvia. Method In this retrospective observational study all kidney allograft biopsies performed in Pauls Stradins Clinical University Hospital from January 2014 till December 2022 was reviewed. Biopsies with rejection, ≥7 glomeruli, patients ≥18 years old were included. Acute rejection was diagnosed according to clinical, laboratory and biopsy-proven acute rejection (BPAR) histological criteria. BPAR was classified and subdivided using Banff criteria. All recipients universally received either depleting or non-depleting induction therapy. Most of the patient (82%) for maintenance immunosuppression (MI) received triple therapy with calcineurin inhibitor, mycophenolate mofetil, and prednisone, others—in different combinations with above and mammalian target of rapamycin (mTOR), azathioprine. Graft function was evaluated according to glomerular filtration rate (GFR), calculated with the CKD-EPI Creatinine, 2021 equation. Treatment strategies, laboratory data at the time of biopsy and after 1 year follow-up were analysed. Repeated-control biopsies after receiving therapy were excluded. Data were analysed using descriptive statistics and T-test. Results From all 523 biopsies, further included and analysed were 153 (total 146 patients). 58% were males, average patient age was 45.5 years. Most 84% of the grafts were from deceased, 8%—living donors. Mean time from transplantation to biopsy was 32 months. Acute antibody-mediated rejection (AAMR) was diagnosed in 41% cases, chronic-active antibody mediated (CAAMR)—25%, followed by mixed 16%, acute cellular (ACR) 10% and borderline 8% rejection. Besides augmented MI for almost all patients, pulse steroids (GCS) were the most commonly 70% administered treatment, followed by plasma exchange 59% (PEX), rituximab (RTX) 50%, immunoglobulins (IG) 24% and anti-thymocyte globulin (ATG) 10% in different, mostly non-homogenous combinations. Non adherence, advanced fibrotic changes in biopsy and serious comorbidities were the main reasons patients did not receive specific treatment besides intensified MI. The most favourable outcomes were in ACR where mean allograft GFR increased +20.7 ml/min after one year, compared to the worst outcome CAAMR group where GFR decreased −4.7 ml/min (p = 0.03). In ACR group 92% graft function stayed the same or improved, moreover 54% graft function increased ≥20% from baseline; similarly in mixed and AAMR group GFR increase ≥20% were for 45% and 48%, compared to CAAMR where it was only for 6% of patient. Furthermore, the CAAMR group was with the most patients (48%) who returned to dialysis or died. In AAMR and mixed rejection groups mean GFR changes were close +13.4 ml/min and +12.9 ml/min (p = 0.95). There were no statistically significant associations between treatment outcomes in PEX+RTX+GCS vs PEX+RTX+GCS+IG in the AAMR group (p = 0.382). Overall, 3.9% of patients died. Conclusion Overall BPAR prevalence between kidney graft biopsies was high (29%). Antibody mediated rejection was diagnosed most often with least favourable short-term outcomes in CAAMR group. Despite various improvements in immunosuppression, CAAMR remains a serious cause of transplant dysfunction or loss.

“Acute urinary antibiotics”—A simple metric to identify outpatient antibiotic stewardship opportunities in renal transplant

Background:International Classification of Diseases, Tenth Edition (ICD-10) data help track outpatient antibiotic prescribing but lack validation in immunocompromised populations or subspecialty clinics for this purpose. Asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) are important stewardship targets in renal transplant (RT) patients, but they may require alternative metrics to best monitor prescribing patterns. We describe ICD-10 utilization for RT clinic encounters in which antibiotics were prescribed. We developed a metric classifying “acute urinary antibiotics” (AUA) to track antibiotic use for ASB and UTI, and we validated systematic identification of AUA to enable practical implementation. Methods: We examined RT clinic visit and telemedicine encounters from 2018 to 2021 conducted 1 month after transplant. This project was deemed non–human-subjects research by the Stanford Panel on Human Subjects in Medical Research. Results: The analytic cohort included 420 antibacterial prescriptions from 408 encounters (Fig. 1). Of 238 patients, 136 (57%) were male and 112 (47%) were Hispanic or Latino. The most common primary ICD-10 code was Z94.0 (kidney transplant status) (N = 302 of 408 encounters, 75%); 26 encounters (6%) were coded for UTI (eg, N39.0, urinary tract infection, site not specified); and 214 encounters (53%) had multiple ICD-10 codes. The R82.71 code (bacteriuria) was never used. However, 215 prescriptions (51%) were classified as AUA (Fig. 2). The validation cohort included 130 prescriptions; 59 (45%) were classified as AUA and 51 (39%) had documented intent to treat ASB or UTI (positive percent agreement, 83%; negative percent agreement, 97%) (Table 1). For patients >1 month after transplant, the positive percent agreement was 95% and the negative percent agreement was 98%. Of 51 patients receiving AUA, 32 (63%) were asymptomatic despite frequently having a code for UTI (Fig. 3). Conclusions: ICD-10 coding may not be helpful in monitoring antibiotic prescribing in RT patients. The AUA metric offers a practical alternative to track antibiotic prescribing for urinary syndromes and reliably correlates with physician intent. Monitoring AUA prescribing rates could help identify opportunities to optimize antibiotic use in this complex outpatient setting.Disclosures: None

314.5: The Difference Between Delta and Omicron Variants in Solid Organ Transplant Recipients

Introduction: Solid Organ Transplant (SOT) recipients are vulnerable to SARS-CoV-2 infection. Delta variant has been reported to have worse outcomes as compared to other variants to date. The Omicron variant has been reported more transmissible but less virulent in general population. However, this phenomenon has not been validated in SOT recipients. Method: This is a retrospective cohort study, conducted in two phases, between July 1st and December 10th, 2021(Delta dominant phase), and January 1st and January 31st, 2022 (Omicron dominant phase) in one of the biggest SOT centers in the United States. Patient demographics including transplanted organ, immunosuppressive medication, vaccination status, and treatment modalities were obtained. We also compared clinical outcomes including hospitalization, ICU admission rate and mortality between two groups. Chi squared or fisher’s exact test were performed for categorical variables, whichever appropriate. For continuous variables, Mann Whitney U-test was performed. Multiple logistic regression model with stepwise backward elimination was developed to identify the risk factors for mortality. We put variables whose p value was less than 0.2. Of note, the institutional treatment protocol has not changed during the study period. Result: We identified 64 and 95 SOT recipients while delta and omicron variants were dominant, respectively. The rate of kidney transplant, age, gender, African American race, and the rate of at least received one dose vaccination were not significantly different between two groups. Of note, the hospital admission rate (68.8% vs 36.2%, p<0.001), ICU admission rate (20.3% vs. 6.3%, p=0.012), and mortality (20.9% vs. 4.2%) were higher during the delta variant versus omicron variant phase. For the risk factor analysis for mortality, we put age, African American race, COVID-19 variant, kidney transplant and vaccination status into multiple logistic regression model. Finally, delta variant was the only statistical significant risk factor for mortality (p<0.001, Odds ratio 9.35, 95% confidence interval 2.52-34.5). Conclusion: This is the first study comparing the outcomes between Delta variant dominant and Omicron variant dominant phase in SOT recipients. Even though there was no treatment protocol changed, the identified risk factor for mortality was delta variant dominant phase. However, still, the hospital admission rate (36.2%) should have been observed while Omicron variant phase and required significant aggressive treatment. Thus, we should prepare and may need to change the treatment protocol based on the variant in the future.

A Propensity-Matched Analysis of COVID-19 in Kidney Transplant Recipients Compared With Non-Kidney Transplant Patients: A Single-Center Report From India.

Comparisons of COVID-19 incidence between kidney transplant recipients and patients who did not receive kidney transplant are underexplored in various geographic regions. This Indian, single-center, retrospective study analyzed COVID-19 data of patients hospitalized between May 12, 2020, and January 11, 2021. A propensity matching score was used to compare outcomes between the 2 groups. We also used multivariable Cox proportional hazard analyses to assess association of kidney transplantation with mortality. Of the 1627 COVID-19 cases, 179 were kidney transplant recipients and 1448 were not kidney transplant patients (control group). Ofthe 436 reported in-hospital deaths, 20 (11.1%) were in the kidney transplant group and 416 (28.7%) were in the control group. Propensity matching identified 98 kidney transplantrecipients and167 controlpatients. InKaplanMeier survival plots for these patients, there was no statistical difference in mortality (log-rank, Mantel Cox test; P = .07) or severity (log-rank, Mantel Cox test; P = .07) with regard to COVID-19. In Cox analysis, age groups from 61 to 70 years (hazard ratio = 1.5; 95% CI, 1.0-2.2; P = .04), 71 to 80 years (hazard ratio = 1.64; 95% CI, 1.0-2.5; P = .02), and >80 years (hazard ratio = 1.91; 95% CI, 1.1-3.1; P = .01)were associatedwith statistically significant greater mortality.Having a kidney transplant (hazard ratio = 0.43; 95% CI, 0.3-0.7; P = 0.001) was not associated with mortality. In our analysis, age was the most important predictor of mortality. Kidney transplant status was not found to have an independent association with mortality and severity.

Sequential Organ Failure Assessment (SOFA) and 90-day mortality in patients with kidney transplant status at first ICU admission: a cohort study of 428 patients.

We investigated the prognostic accuracy of scores of SOFA for 90-day mortality in patients with kidney transplant status identified from the public Medical Information Mart for Intensive Care III databank. A total of 428 participants with kidney transplant status who were admitted for the first time to the ICU were included. The target-independent and target-dependent variables were the SOFA scores in the first 3 days of ICU admission and 90-day mortality, respectively. Fully adjusted binary logistic regression indicated that the day-2 and day-3 SOFA scores were positively associated with a risk of 90-day mortality after adjustment for confounders (odds ratio: 1.196, 95% confidence interval: 1.052-1.360; odds ratio: 1.233, 95% confidence interval: 1.062-1.432). The receiver operating characteristic curve showed areas under the curve for the prediction of 90-day mortality from SOFA scores on days 1, 2and 3 were 0.524, 0.654, and 0.727, respectively. Further analysis using Kaplan-Meier survival curves and multivariate regression models of 90-day survival showed that patients with low SOFA scores survived longer than those with high scores. The SOFA scores in the early days of ICU admission were positively associated with 90-day outcomes although the first-day score showed no significant correlation.

Incidence and Outcome of Acute Kidney Injury in Patients Hospitalized With Coronavirus Disease-19 at a Tertiary Care Medical Center in Saudi Arabia.

IntroductionThe systemic acute respiratory syndrome coronavirus (SARS-CoV-2) has been associated with acute kidney injury (AKI). We retrospectively studied the incidence and outcome of AKI in patients hospitalized with COVID-19 at King Abdulaziz Medical City (KAMC) Riyadh, Kingdom of Saudi Arabia.MethodsA retrospective cohort study was conducted after ethical approval from the institutional review board of King Abdullah International Medical Research Center (KAIMRC). Subjects were identified by Data Management Office of KAIMRC. The data were extracted from electronic medical records using a customized data collection sheet.The study included all adult patients (>18 years) who tested positive for COVID-19 by polymerase chain reaction and were admitted at KAMC from March 2020 until the end of September 2020. Patients with a history of end-stage kidney diseases and patients where adequate data were not available to establish diagnosis of AKI were excluded.Patient demographics, comorbid conditions, medications, use of mechanical ventilation, and 30-day mortality were recorded.ResultsDuring the study period (01 March 2020 to 30 September 2020) 1293 patients were hospitalized at KAMC with the diagnosis of COVID-19. After excluding the patients who met the exclusion criteria, data were collected for 1025 patients [male 582 (56.8%); female 443 (43.2%)]. On univariate analysis, increasing age, male gender, use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, diuretics, and vasopressors, presence of chronic kidney disease, coronary artery disease, chronic obstructive pulmonary disease, dyslipidemia, diabetes mellitus, heart failure, and hypertension, kidney transplant status, and mechanical ventilation were associated with development of AKI.On multivariate logistic regression analysis, independent predictors of AKI were restricted to increasing age, presence of chronic kidney disease, hypertension, kidney transplant status, use of vasopressors, and mechanical ventilation.For patients who developed AKI, 30-day mortality was 40.7% compared to 3.7% for those who did not develop AKI (p<0.001).ConclusionFor hospitalized patients with COVID-19, we observed an incidence of AKI of 36%. Increasing age, presence of chronic kidney disease and hypertension, kidney transplant status, use of vasopressors, and mechanical ventilation were independently associated with development of AKI. Presence of AKI was associated with higher 30-day mortality (40.7% vs 3.7%).

Is COVID-19 infection more severe in kidney transplant recipients?

There are no studies which have compared the risk of severe COVID‐19 and related mortality between transplant recipients and nontransplant patients. We enrolled two groups of patients hospitalized for COVID‐19, that is, kidney transplant recipients (KTR) from the French Registry of Solid Organ Transplant (n = 306) and a single‐center cohort of nontransplant patients (n = 795). An analysis was performed among subgroups matched for age and risk factors for severe COVID‐19 or mortality. Severe COVID‐19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death. Transplant recipients were younger and had more comorbidities compared to nontransplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30‐day cumulative incidence of severe COVID‐19 did not differ between KTR and nontransplant patients; however, 30‐day COVID‐19‐related mortality was significantly higher in KTR (17.9% vs 11.4%, respectively, p = .038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C‐reactive protein (CRP) were associated with severe COVID‐19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR = 1.55), and creatinine level >115 µmol/L (HR = 2.32) were associated with COVID‐19‐related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. KTR had a higher COVID‐19‐related mortality compared to nontransplant hospitalized patients.

COVID-19 in kidney transplant recipients.

There is minimal information on coronavirus disease 2019 (COVID‐19) in immunocompromised individuals. We have studied 10 patients treated at 12 adult care hospitals. Ten kidney transplant recipients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by polymerase chain reaction, and 9 were admitted. The median age was 57 (interquartile range [IQR] 47‐67), 60% were male, 40% Caucasian, and 30% Black/African American. Median time from transplant to COVID‐19 testing was 2822 days (IQR 1272‐4592). The most common symptom was fever, followed by cough, myalgia, chills, and fatigue. The most common chest X‐ray and computed tomography abnormality was multifocal patchy opacities. Three patients had no abnormal findings. Leukopenia was seen in 20% of patients, and allograft function was stable in 50% of patients. Nine patients were on tacrolimus and a mycophenolic antimetabolite, and 70% were on prednisone. Hospitalized patients had their antimetabolite agent stopped. All hospitalized patients received hydroxychloroquine and azithromycin. Three patients died (30%), and 5 (50%) developed acute kidney injury. Kidney transplant recipients infected with COVID‐19 should be monitored closely in the setting of lowered immunosuppression. Most individuals required hospitalization and presenting symptoms were similar to those of nontransplant individuals.

Association of Sleep Apnea with Mortality in Patients with Advanced Kidney Disease.

In the general population, sleep disorders are associated with mortality. However, such evidence in patients with CKD and ESKD is limited and shows conflicting results. Our aim was to examine the association of sleep apnea with mortality among patients with CKD and ESKD. In this prospective cohort study, 180 patients (88 with CKD stage 4 or 5, 92 with ESKD) underwent in-home polysomnography, and sleep apnea measures such as apnea hypopnea index (AHI) and nocturnal hypoxemia were obtained. Mortality data were obtained from the National Death Index. Cox proportional hazard models were used for survival analysis. Among the 180 patients (mean age 54 years, 37% women, 39% with diabetes, 49% CKD with mean eGFR 18±7 ml/min per 1.73 m2), 71% had sleep apnea (AHI>5) and 23% had severe sleep apnea (AHI>30). Median AHI was 13 (range, 4-29) and was not significantly different in patients with advanced CKD or ESKD. Over a median follow-up of 9 years, there were 84 (47%) deaths. AHI was not significantly associated with mortality after adjusting for age, sex, race, diabetes, body mass index, CKD/ESKD status, and kidney transplant status (AHI>30: hazard ratio [HR], 1.5; 95% confidence interval [95% CI], 0.6 to 4.0; AHI >15 to 30: HR, 2.3; 95% CI, 0.9 to 5.9; AHI >5 to 15: HR, 2.1; 95% CI, 0.8 to 5.4, compared with AHI≤5). Higher proportion of sleep time with oxygen saturation <90% and lower mean oxygen saturation were significantly associated with higher mortality in adjusted analysis (HR, 1.4; 95% CI, 1.1 to 1.7; P=0.007 for every 15% higher proportion, and HR, 1.6; 95% CI, 1.2 to 2.1; P=0.003 for every 2% lower saturation, respectively). Sleep duration, sleep efficiency, or periodic limb movement index were not associated with mortality. Hypoxemia-based measures of sleep apnea are significantly associated with increased risk of death among advanced CKD and ESKD.

Atherosclerotic vascular disease and its correlates in stable black South African kidney transplant recipients.

BackgroundDespite remarkable improvement in renal function attributable to kidney transplantation, the burden of cardiovascular disease (CVD) among kidney transplant recipients (KTRs) remains high in the post-transplant period. Aggressive use of statins in KTRs may make lipoprotein ratios correlate better with atherosclerotic vascular disease (AsVD) when compared with traditional lipid profile parameters. We therefore evaluated the clinical and echocardiographic correlates of AsVD among non-diabetic, stable, black KTRs in South Africa.MethodsThis was a cross-sectional study of 41 adult (18–65 years), non-diabetic, stable KTRs and 41 age- and sex-matched healthy controls. An interviewer-administered questionnaire was used to obtain information on participants’ sociodemographic and cardiovascular risk factors. Anthropometric parameters were measured. Urine and blood samples were obtained and analyzed. Echocardiography was performed and carotid intima media thickness (CIMT) was assessed in both right and left carotid arteries. Spearman’s rank correlation and binary logistic regression were performed to determine the relationship between CVD risk factors and AsVD.ResultsAsVD was present in 46.3% of KTRs compared to 17.1% of healthy controls (p = 0.004). Left ventricular hypertrophy was present in 92.7% of the KTRs. There were statistically significant differences in waist–hip ratio, systolic blood pressure, mean arterial pressure, urine albumin–creatinine ratio, serum fibrinogen, serum creatinine, estimated glomerular filtration rate, left atrial diameter, left ventricular mass (LVM), and left ventricular mass index (LVMI) between KTRs and controls. A positive relationship was seen between CIMT and certain risk factors for CVD including LVM, LVMI, and mitral valve deceleration time, (p < 0.001). Castelli index 2 and lipoprotein combine index (LCI) showed positive correlation with CIMT. On multivariate analysis, increasing age and kidney transplant status were independent predictors of AsVD after controlling for other risk factors.ConclusionAsVD was common among KTRs. Older age and kidney transplant status independently predicted AsVD. Castelli index 2 and LCI correlated with AsVD better than serum lipid parameters.

Brain Magnetic Resonance Imaging Findings in Children and Young Adults With CKD

The neuroanatomic basis for cognitive impairment in chronic kidney disease (CKD) is incompletely characterized. We performed advanced quantitative structural magnetic resonance imaging (MRI) to determine whether CKD affects brain structure and whether poorer neurocognitive performance in CKD is associated with structural brain differences. Cross-sectional. 85 individuals with CKD stages 2 to 5 and 63 healthy controls, aged 8 to 25 years PREDICTORS: CKD versus control, estimated glomerular filtration rate (eGFR), and kidney transplant status were analyzed as predictors of MRI findings. MRI volumes in 19 prespecified regions of gray matter (GM), white matter (WM), and cerebrospinal fluid were analyzed as predictors of neurocognitive performance (median z scores) in 7 prespecified domains. 19 prespecified brain regions of interest (ROIs) in 7 prespecified domains. Neurocognitive performance in 7 prespecified domains. ROI volumes were compared in CKD versus controls using unadjusted t tests and analysis of covariance (ANCOVA). Associations of ROI volumes with eGFR and kidney transplant status in participants with CKD were analyzed using ANCOVA and linear regression. Associations of neurocognitive performance and ROI volumes were analyzed by linear regression. Participants with CKD had lower whole-brain, cortical, and left parietal GM volumes than controls in unadjusted analyses, but no differences were found in adjusted analysis. In participants with CKD, lower eGFR was associated with higher WM volume in whole-brain (P=0.05) and frontal (P=0.04) ROIs, but differences were not significant after multiple comparisons correction. Kidney transplant recipients had lower GM volumes in whole-brain (P=0.01; Q=0.06), frontal (P=0.02; Q=0.08), and left and right parietal (P=0.01; Q=0.06; and P=0.03; Q=0.1) ROIs and higher whole-brain WM volume (P=0.04; Q=0.1). Neurocognitive performance in the CKD group was not associated with ROI volumes. Unable to assess changes in brain structure and kidney function over time; analysis limited to prespecified ROIs and neurocognitive domains. CKD in children and young adults may be associated with lower GM and higher WM volumes in some ROIs. Differences were relatively subtle in the CKD group as a whole, but were more prominent in recipients of a kidney transplant. However, neurocognitive performance was not explained by differences in brain ROI volumes, suggesting a functional rather than structural basis for neurocognitive impairment in CKD.

Influence of Kidney Transplant Status on Warfarin Dose, Anticoagulation Control, and Risk of Hemorrhage.

To assess whether warfarin dose requirement, anticoagulation control, and risk of hemorrhage differ in kidney transplant recipients (KTRs) compared with patients without kidney transplants (non-KTRs). Analysis of data from the Warfarin Pharmacogenetics Cohort, a prospective cohort of first-time warfarin users followed at two anticoagulation clinics. Two outpatient anticoagulation clinics at two large, academic, tertiary care hospitals. Adults aged 20years or older starting warfarin for anticoagulation with a therapeutic international normalized ratio (INR) goal of 2-3 who were KTRs (n=65) or non-KTRs (n=1630). Warfarin dose requirement, anticoagulation control, and risk of hemorrhage were assessed in each group. KTRs required an approximately 20% lower warfarin dose (4.7 vs 5.6mg/day, p=0.0005) compared with non-KTRs. Genetic variants had similar effects on dose in both groups. Mean percentage of time in therapeutic range (PTTR) was similar among KTRs and non-KTRs. Although the proportion of patients achieving good anticoagulation control (PTTR≥60%) was low in both groups, it was similar among KTRs and non-KTRs. KTRs had a higher risk of major hemorrhage (hazard ratio 2.1, p=0.0081), but this difference was not statistically significant after controlling for kidney function, clinical, and genetic factors. KTRs initiating warfarin require lower doses and closer monitoring to optimize anticoagulation therapy. Additional studies are needed to confirm these findings.

Severe chronic norovirus diarrheal disease in transplant recipients: Clinical features of an under-recognized syndrome.

Norovirus (NV) infection has been reported as a cause of severe chronic diarrhea in transplant recipients, but this entity remains under-recognized in clinical practice, leading to diagnostic delays. Transplant clinicians should become familiar with this syndrome in order to facilitate early detection and management. Demographic, clinical, and outcomes variables were summarized from a series of transplant recipients with positive stool NV reverse transcription polymerase chain reaction (RT-PCR) assays at Johns Hopkins in 2013-2014. Factors associated with longer duration of symptoms were compared using random forest analysis. Thirty-one of 193 (16%) transplant recipients who were tested for NV had positive stool RT-PCRs. Symptoms included diarrhea (100%), nausea/vomiting (58%), abdominal pain (52%), and wasting (35%). Acute kidney injury occurred in 23%, and persisted in 21% after 6months. Median duration of diarrheal symptoms was 4months (range, <1-20) and 11/31 (35.4%) patients had relapses after improvement. Wasting, incompatible kidney transplant status, and plasmapheresis were associated with longer diarrhea durations. Treatments included nitazoxanide (in 74%), reduction of immunosuppression (58%), and intravenous immunoglobulin (32%). Six patients died, but no deaths were attributed to NV. It is important for clinicians to recognize that NV can cause severe chronic diarrhea in transplant recipients. In this series, receipt of a human leukocyte antigen- and/or blood type-incompatible kidney transplant, and plasmapheresis were associated with longer symptom duration.

Impact of Cognitive Function Change on Mortality in Renal Transplant and End-Stage Renal Disease Patients

Background: Limited evidence from small-scale studies, mainly involving end-stage renal disease (ESRD) patients, suggests that kidney transplantation may improve cognitive function. We examined changes in cognitive function after a kidney transplant and its association with survival in advanced chronic kidney disease (CKD)/ESRD patients. Methods: In a prospective study design, cognitive performance of 90 patients (50.6 ± 13.1 years, 66.7% men, 27.8% blacks, 76% CKD stages 4-5) was assessed at the respective patients' residences using established neurocognitive tests. Results: Among the 90 patients, 44 received a kidney transplant (KTx group) while 46 did not (no-KTx group). After a mean follow-up of ∼19 months, there was no significant change in scores for majority of cognitive tests in either group. Older age, but not diabetes or renal function status (CKD vs. ESRD), was a determinant of poor follow-up cognitive performance. Additionally, poor attention/psychomotor speed and executive performance (as measured by Trails A and Stroop test, respectively) was associated with higher mortality over a mean follow-up of 4.7 years, even after adjustment for age, sex, diabetes, CKD or ESRD status and kidney transplant status. Conclusion: Overall, cognitive function does not significantly improve after kidney transplant or significantly decline in non-transplanted, advanced CKD/ESRD patients. Poor attention, psychomotor speed and executive performance independent of transplant status were associated with higher mortality over time.

Eculizumab Prevents Thrombotic Microangiopathy: Long-Term Follow-up Study of Patients with Atypical Hemolytic Uremic Syndrome

▪Background: Eculizumab was demonstrated to effectively treat and prevent thrombotic microangiopathy (TMA) and to improve renal function and hematologic parameters for up to 2 years in4 previous prospective clinical trials and in 1 retrospective study of patients with atypical hemolytic uremic syndrome (aHUS). Patients in these studies enrolled in a long-term follow-up study, in which rates of TMA were evaluated during eculizumab treatment and during discontinuation from eculizumab.Methods: Data were gathered from an ongoing, observational, multicenter study of aHUS patients treated with eculizumab in 5 prior clinical studies. The primary endpoint was TMA event rate post-parent study during on-treatment (ON; among patients receiving eculizumab) and off-treatment (OFF; among patients who discontinued eculizumab) periods.Results: As of March 28, 2015, 87 patients, including 35 children <18 years of age (40%) and 52 adults ≥18 years of age (60%), enrolled in the study (Table). Of these, 76 patients had ON and 39 patients had OFF treatment periods with median follow-up of 26.1 and 20.1 months, respectively. A reduced dosage of eculizumab was received by 33 of 87 patients (38%). Seventeen of 39 patients (44%) reinitiated eculizumab after therapy discontinuation. The TMA event rates were 7.3 and 19.9 per 100 patient-years for ON and OFF patients, respectively. The rate of TMA in ON patients was greater in those receiving reduced dosing compared with label recommendations (Table). OFF patients had higher estimated glomerular filtration rates at time of discontinuation than ON patients. Age, frequencies of higher-risk complement factor mutations (CFH, C3, or CFB) and kidney transplant status were not different between ON and OFF patients. Factors that independently predicted TMA events included: ON treatment status (compared with OFF; hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.07‒0.49; P<0.001), higher-risk mutations (compared with no mutation; HR, 5.51; 95% CI, 1.61‒18.84; P =0.007), and lower-risk mutations (compared with no mutation; HR, 3.70; 95% CI, 1.05‒13.02; P =0.04).Conclusions: The TMA event rate was 2.7-fold higher after eculizumab discontinuation compared with patients receiving ongoing eculizumab therapy. TMA event rates were lowest during on-label dosing, higher during reduced dosing, and highest during off-treatment periods. These findings suggest that patients with aHUS have a progressive increase in the risk of TMA events during periods of reduced dosing and after discontinuation of eculizumab, compared with on-label eculizumab dosing. [Display omitted] DisclosuresGreenbaum:Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Fakhouri:Alexion Pharmaceuticals: Consultancy. Kincaid:Alexion Pharmaceuticals: Employment, Equity Ownership. Licht:Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Achillon: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Mix:Alexion Pharmaceuticals: Employment, Equity Ownership. Provôt:Alexion Pharmaceuticals: Honoraria. Rondeau:Alexion Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sheerin:Alexion Pharmaceuticals: Honoraria. Wang:Alexion Pharmaceuticals: Employment, Equity Ownership. Menne:Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees.

An alternative approach to estimate age-related mortality of kidney transplant recipients compared to the general population: results in favor of old-to-old transplantations

Compared to dialysis, kidney transplantation appears to be the best treatment for chronic kidney failure, even for older aged patients. Nevertheless, the individual benefit of transplanting elderly patients has to be balanced against the corresponding increase in the number of patients awaiting grafts. We analyzed the excess mortality related to kidney transplant recipients by taking into account the expected mortality of the general population (additive regression model for relative survival). We applied this method to a cohort of patients who received a first deceased-donor kidney transplant between 1998 and 2009 in France (DIVAT, n = 3641). Overall 10-year mortality was 13%. As expected, recipient age was the main risk factor associated with overall mortality. In contrast, recipient age was no longer significantly associated with the excess of mortality related to kidney transplant status by subtracting the expected mortality of the general population. Delayed graft function (DGF), pretransplantation immunization, and past history of diabetes appeared as the main risk factors of this higher mortality rate. Our results constitute a strong argument in favor of kidney transplantation, regardless of the patient's age. Preventing DGF may be more effective for decreasing the risk of death specifically attributable to the disease.

The quality of cardiovascular disease care for adolescents with kidney disease: a Midwest Pediatric Nephrology Consortium study

Cardiovascular disease is the leading cause of increased mortality for adolescents with advanced kidney disease. The quality of preventive cardiovascular care may impact long-term outcomes for these patients. We reviewed the records of 196 consecutive adolescents from eight centers with pre-dialysis chronic kidney disease, on dialysis or with a kidney transplant, who transferred to adult-focused providers. We compared cardiovascular risk assessment and therapy within and across centers. Predictors of care were assessed using multilevel models. Overall, 58 % (range 44-86 %; p = 0.08 for variance) of five recommended cardiovascular risk assessments were documented. Recommended therapy for six modifiable cardiovascular risk factors was documented 57 % (26-76 %; p = 0.09) of the time. Of these patients, 30 % (n = 59) were reported to go through formal transition which was independently associated with a 21 % increase in composite cardiovascular risk assessment (p < 0.001). Transfer after 2006 and kidney transplant status were also associated with increased cardiovascular risk assessment (p < 0.01 and p = 0.045, respectively). Adolescents with kidney disease receive suboptimal preventive cardiovascular care, that may contribute to their high risk of future cardiovascular mortality. A great opportunity exists to improve outcomes for children with kidney disease by improving the reliability of preventive care that may include formal transition programs.

The relationship between social networks and pathways to kidney transplant parity: Evidence from black Americans in Chicago

Research has shown that black dialysis patients in the United States are significantly less likely than their white peers to be evaluated and listed for a kidney transplant. Extrapolating from social-network theory, I hypothesize that a lack of access to social contacts with information about kidney transplantation may hinder information transaction regarding the benefits of, and pathway to, transplantation. In 2007–2008, the following research questions were addressed in an investigation in Chicago, USA: (1) What is the role of social networks in providing information about kidney transplantation to black hemodialysis patients? (2) What is the relationship between social networks and a patient’s likelihood of being seen at a kidney transplant center? From a stratified sample of dialysis units in the area, a purposive sample of 228 black patients was surveyed while they received treatment about their social networks and kidney transplant status. It was found that the odds of black hemodialysis patients being seen at a kidney transplant center increase with income, and patients who have people in their social network with information about kidney transplant were significantly more likely to be seen at a kidney transplant center. Specifically, black dialysis patients who get informational social support from their dialysis team and social networks were significantly more likely to be seen at kidney transplant centers. I conclude that considering black dialysis patients’ social milieu can be complementary to the existing research regarding this public health crisis.

Cardioprotective Medication Use After Acute Myocardial Infarction in Kidney Transplant Recipients

Limited data are available on the use of potentially cardioprotective medications among U.S. kidney transplant recipients. We constructed a database wherein Organ Procurement and Transplant Network identifiers for kidney transplant recipients were linked to billing records of a private health insurer (2003-2006 claims). Transplant recipients and general beneficiaries with acute myocardial infarction (AMI) events were identified by diagnosis codes. The healthcare process measures of interest comprised prescription fills for beta-blockers, antiplatelet drugs, angiotensin-converting enzyme inhibitors/angiotensin-2 receptor blockers, and β-hydroxy-β-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) within 60 days after AMI. Medication use was compared in transplant and general patients by multivariable regression and by one-to-one matching for demographic and clinical factors including comorbidities and revascularization status. We identified 192 kidney transplant recipients and 52,021 general patients who survived with insurance benefits more than or equal to 60 days after AMI diagnosis. In multiple logistic regression, transplant status was independently associated with increased likelihood of beta-blocker (adjusted odds ratio, 2.50; 95% confidence interval, 1.70-3.68; P<0.0001) and statin (adjusted odds ratio, 1.78; 95% confidence interval, 1.28-2.48; P=0.0006) use after AMI. Similarly kidney transplant recipients with AMI more commonly received beta-blockers (83.0% vs. 65.9%; P=0.0001) and statins (72.0% vs. 62.6%; P=0.04) compared with matched controls. Use of antiplatelet agents and angiotensin-converting enzyme inhibitors/angiotensin-2 receptor blockers did not differ significantly by transplant status. Although kidney transplant status does not seem to be a barrier to medication use after AMI, there may be opportunities for improving cardiovascular risk management in high-risk transplant recipients. Administrative records offer a practical tool for monitoring cardiovascular complications and healthcare delivery not tracked in national registries.