Post-Transplant Cardiovascular Disease in Kidney Transplant Recipients: Incidence, Risk Factors, and Outcomes in the Era of Modern Immunosuppression.

Introduction: Post-transplant cardiovascular disease (PTCVD) poses a significant challenge in kidney transplantation, potentially impacting graft outcomes and patient survival. This retrospective study aimed to investigate the incidence, risk factors, and consequential impact of PTCVD in kidney transplant recipients (KTRs) devoid of pre-existing cardiovascular disease (CVD). Method: The cohort comprised 1114 KTRs, with 749 individuals included after excluding those with pre-existing CVD and early graft loss. PTCVD encompasses ischemic heart disease, myocardial infarction, arrhythmias, heart failure, stroke, peripheral vascular disease, and valvular heart disease. Competing risk regression analysis was performed to identify predictors of PTCVD, while Cox proportional hazards analysis assessed the impact of PTCVD on graft and recipient survival. Results: The cumulative incidence of PTCVD at 5, 10, and 20 years was 5.4%, 14.3%, and 22.5%, respectively. Competing risk regression identified increased age (sub-hazard ratio [SHR], 1.22; p = 0.036) per decade, duration of dialysis (SHR, 1.07; p = 0.048) per year on dialysis, and the slope of the estimated glomerular filtration rate (SHR, 1.08; p = 0.008) mL/min/year decline as independent predictors of higher-risk PTCVD. A higher baseline estimated glomerular filtration rate (eGFR) was protective (SHR, 0.98; p = 0.032). PTCVD was not significantly associated with death-censored graft loss (adjusted hazard ratio [aHR] 1.31; p = 0.48) but was correlated with higher all-cause graft loss (aHR, 1.71; p = 0.011) and recipient mortality (aHR, 1.97; p = 0.004). Conclusion: This study provides insights into PTCVD predictors. Although not directly associated with graft loss, PTCVD significantly correlates with heightened mortality in kidney transplant recipients, emphasizing the need for enhanced clinical management and surveillance strategies.

Incidence, Risk Factors, and Outcomes of De Novo Malignancy following Kidney Transplantation.

Introduction: Post-transplant malignancy is a significant cause of morbidity and mortality following kidney transplantation often emerging after medium- to long-term follow-up. To understand the risk factors for the development of de novo post-transplant malignancy (DPTM), this study aimed to assess the incidence, risk factors, and outcomes of DPTM at a single nephrology centre over two decades. Methods: This retrospective cohort study included 963 kidney transplant recipients who underwent kidney transplantation between January 2000 and December 2020 and followed up over a median follow-up of 7.1 years (IQR 3.9-11.4). Cox regression models were used to identify the significant risk factors of DPTM development, the association of DPTM with graft survival, and mortality with a functioning graft. Results: In total, 8.1% of transplant recipients developed DPTM, and the DPTM incidence rate was 14.7 per 100 patient-years. There was a higher mean age observed in the DPTM group (53 vs. 47 years, p < 0.001). The most affected organ systems were genitourinary (32.1%), gastrointestinal (24.4%), and lymphoproliferative (20.5%). Multivariate Cox analysis identified older age at transplant (aHR 9.51, 95%CI: 2.60-34.87, p < 0.001) and pre-existing glomerulonephritis (aHR 3.27, 95%CI: 1.10-9.77, p = 0.03) as significant risk factors for DPTM. Older age was significantly associated with poorer graft survival (aHR 8.71, 95%CI: 3.77-20.20, p < 0.001). When age was excluded from the multivariate Cox model, DPTM emerged as a significant risk factor for poor survival (aHR 1.76, 95%CI: 1.17-2.63, p = 0.006). Conclusion: These findings underscore the need for tailored screening, prevention, and management strategies to address DPTM in an aging and immunosuppressed kidney transplant population.

The Birth and Beyond (BABY) study: protocol for a birth cohort study investigating the social and environmental determinants of pregnancy-related outcomes in Black American families.

INTRODUCTION: In the USA, Black birthing people and infants experience disproportionately worse pregnancy-related health outcomes. The causes for these disparities are unknown, but evidence suggests that they are likely socially and environmentally based. Efforts to identify the determinants of these racial disparities are urgently needed to elucidate the highest priority targets for intervention. The Birth and Beyond (BABY) study evaluates how micro-level (eg, interpersonal and family) and macro-level (eg, neighbourhood and environmental) risk and resiliency factors transact to shape birth person-infant health, and underlying psychobiological mechanisms. METHODS AND ANALYSIS: The BABY study will follow 350 Black families (birthing parents, non-birthing parents and infants) from pregnancy through the first postpartum year, with research visits during pregnancy and at infant ages 6 and 12 months. Research visits comprise a combination of interview about a range of recent and life course stress and resiliency exposures and supports, psychophysiological (sympathetic, parasympathetic and adrenocortical) assessment and behavioural observations of parent-infant coregulatory behaviours. Spatial analyses are completed by mapping parent current and past residential addresses onto archival public data (eg, about neighbourhood quality and racial segregation). Finally, EMRs are abstracted for information about birthing parent relevant medical history, pregnancy conditions and infant birth outcomes. Analyses will evaluate the risk and resiliency mechanisms that contribute to pregnancy and birth-related outcomes for Black birthing people and their infants, and the protective role of individual, familial, cultural, and community supports. ETHICS AND DISSEMINATION: The BABY study has been approved by the Institutional Review Board at Albany Medical Centre. The study team consulted with local organisations and groups comprised of stakeholders and community leaders and continues to do so throughout the study. Research results will be disseminated with the scientific and local community as appropriate.

The effect of primary renal disease upon outcomes after renal transplant.

BACKGROUND: This study investigated whether nature of primary renal disease affects clinical outcomes after renal transplantation at a single center in the United Kingdom. METHODS: This was a retrospective cohort study of 961 renal transplant recipients followed up at a large renal center from 2000 to 2020. Separation of diseases responsible for end-stage kidney disease included glomerulonephritis, diabetic kidney disease, hypertensive nephropathy, autosomal dominant polycystic kidney disease, unknown cause, other causes and chronic pyelonephritis. Outcome data included graft loss, cardiovascular events, malignancy, post-transplant diabetes mellitus and death, analyzed according to primary disease type. RESULTS: The mean age at transplantation was 47.3 years. During a mean follow-up of 7.6 years, 18% of the overall cohort died corresponding to an annualised mortality rate of 2.3%. Death with a functioning graft occurred at a rate of 2.1% per annum, with the highest incidence observed in in patients with diabetic kidney disease (4.1%/year). Post-transplant cardiovascular events occurred in 21% of recipients (2.8% per year), again highest in recipients with diabetic kidney disease (5.1%/year) and hypertensive nephropathy (4.5%/year). Post-transplant diabetes mellitus manifested in 19% of the cohort at an annualized rate of2.1% while cancer incidence stood at 9% with an annualized rate of 1.1% . Graft loss occurred in 6.8% of recipients at the rate of1.2% per year with chronic allograft injury, acute rejection and recurrent glomerulonephritis being the predominant causative factors. Median + IQR dialysis-free survival of the whole cohort was 16.2 (9.9 - > 20) years, being shortest for diabetic kidney disease (11.0 years) and greatest for autosomal dominant polycystic kidney disease (18.2 years) .The collective mean decline in eGFR over time was -1.14ml/min/year. Recipients with Pre-transplant diabetic kidney disease exhibited the fastest rate of decline(-2.1ml/min/year) a statistically significant difference in comparison to the other native kidney diseases with Autosomal dominant polycystic kidney disease exhibiting the lowest rate of decline(-0.05ml/min/year) CONCLUSION: Primary renal disease can influence the outcome after renal transplantation, with patients with prior diabetic kidney disease having the poorest outcome in terms of dialysis-free survival and loss of transplant function. Autosomal polycystic kidney disease, other cause and unknown cause had the best outcomes compared to other primary renal disease groups.

Clinical and histopathologic predictors of recurrent glomerulonephritis after kidney transplantation.

INTRODUCTION: We evaluated the long-term outcomes of recurrent glomerulonephritis (RGN) using clinical, histopathological, and demographic predictors. METHODS: A retrospective cohort study of kidney transplant recipients (KTR) in two renal centers between 2005 and 2020. Clinical and native kidney histological data were analyzed. The risk factors and outcomes of each primary glomerulonephritis subtype were assessed using Cox methods. RESULT: 336 recipients with primary glomerulonephritis were analyzed. RGN was diagnosed in 17%, 20%, 25%, and 13% of recipients with IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and membranoproliferative glomerulonephritis (MPGN), respectively. Median time to recurrence was shortest in FSGS (.6 years IQR .2-2.9) and longest in MN (6.3 years IQR 3.3-8.0) whereas time to graft loss after diagnosis was shortest in MPGN (.3 years IQR .1-1.7) and longest in IgAN (2.9 year IQR 1.3-4.3). Recipients with recurrent IgAN were likely to be younger, have higher proteinuria at diagnosis, receive living donor allografts, receive cyclosporine treatment, have a history of acute rejection, and have segmental sclerosis in native glomeruli. Younger age of the donors, higher proteinuria at diagnosis, alemtuzumab, proteinuria within the first 12 months, acute rejection, low baseline eGFR, mesangial proliferation, and IgG and IgA deposits were associated with FSGS recurrence. MPGN recurrence was predicted by lower BMI at transplantation, and crescentic native disease. Death-censored graft survival at 5-, 10-, and 15-years was 83%, 51%, and 29% in the RGN group and 95%, 93%, and 84%, respectively in the non-RGN group. Over 15 years, recipients with RGN are nine times more likely than those without RGN to lose their grafts, regardless of donor type, acute rejection, and baseline eGFR. Transplant recipients of related donor allograft were not more likely to have recurrent GN than non-related donors.

Kidney Transplant-Associated Viral Infection Rates and Outcomes in a Single-Centre Cohort.

BACKGROUND: Opportunistic infections remain a significant cause of morbidity and mortality after kidney transplantation. This retrospective cohort study aimed to assess the incidence and predictors of post-transplant DNA virus infections (CMV, EBV, BKV and JCV infections) in kidney transplant recipients (KTR) at a single tertiary centre and evaluate their impact on graft outcomes. METHODS: KTR transplanted between 2000 and 2021 were evaluated. Multivariate logistic regression analysis and Cox proportional hazard analyses were used to identify factors associated with DNA virus infections and their impact on allograft outcomes respectively. A sub-analysis of individual viral infections was also conducted to describe the pattern, timing, interventions, and outcomes of individual infections. RESULTS: Data from 962 recipients were evaluated (Mean age 47.3 ± 15 years, 62% male, 81% white). 30% of recipients (288/962) had infection(s) by one or more of the DNA viruses. Individually, CMV, EBV, BKV and JCV viruses were diagnosed in 13.8%. 11.3%, 8.9% and 4.4% of recipients respectively. Factors associated with increased risk of post-transplant DNA virus infection included recipient female gender, higher number of HLA mismatch, lower baseline estimated glomerular filtration rate (eGFR), CMV seropositive donor, maintenance with cyclosporin (rather than tacrolimus) and higher number of maintenance immunosuppressive medications. The slope of eGFR decline was steeper in recipients with a history of DNA virus infection irrespective of the virus type. Further, GFR declined faster with an increasing number of different viral infections. Death-censored graft loss adjusted for age, gender, total HLA mismatch, baseline eGFR and acute rejection was significantly higher in recipients with a history of DNA virus infection than those without infection (adjusted hazard ratio (aHR, 1.74, 95% CI, 1.08-2.80)). In contrast, dialysis-free survival did not differ between the two groups of recipients (aHR, 1.13, 95% CI, 0.88-1.47). CONCLUSION: Post-transplant DNA viral infection is associated with a higher risk of allograft loss. Careful management of immunosuppression and close surveillance of at-risk recipients may improve graft outcomes.

Increasing Uptake of COVID-19 Vaccination and Reducing Health Inequalities in Patients on Renal Replacement Therapy-Experience from a Single Tertiary Centre.

BACKGROUND: COVID-19 vaccination has changed the landscape of the COVID-19 pandemic; however, decreased uptake due to vaccine hesitancy has been observed, particularly in patients from minority ethnic backgrounds and socially deprived areas. These patient characteristics are common in patients on Renal Replacement Therapy (RRT), a population at extremely high risk of developing serious illness from COVID-19 and who would thus benefit the most from the vaccination programme. We designed a bespoke COVID-19 vaccination programme for our RRT population with the aim of decreasing health inequalities and increasing vaccination uptake. METHODS: Key interventions included addressing vaccine hesitancy by deploying the respective clinical teams as trusted messengers, prompt eligible patient identification and notification, the deployment of resources to optimise vaccine administration in a manner convenient to patients, and the timely collection and analysis of local safety and efficacy data. First, COVID-19 vaccination data in relation to ethnicity and social deprivation in our RRT population, measured by the multiple deprivation index, were analysed and compared to uptake data in the total regional adult clinically extremely vulnerable (CEV) population in Greater Manchester (GM). Univariate logistic regression analysis was used to explore the factors associated with not receiving a vaccine. RESULTS: Out of 1156 RRT patients included in this analysis, 96.7% received the first dose of the vaccination compared to 93% in the cohort of CEV patients in the GM. Age, gender, ethnicity, and a lower index of multiple deprivation were not identified as significant risk factors for poor first dose vaccine uptake in our cohort. Vaccine uptake in Asian and Black RRT patients was 94.9% and 92.3%, respectively, compared to 93% and 76.2% for the same ethnic groups in the reference CEV GM. Vaccine uptake was 96.1% for RRT patients in the lowest quartile of the multiple deprivation index, compared to 90.5% in the GM reference population. CONCLUSION: Bespoke COVID-19 vaccination programmes based on local clinical teams as trusted messengers can improve negative attitudes towards vaccination and reduce health inequalities.

Resilience predicts positive mental health outcomes during the COVID-19 pandemic in New Yorkers with and without obsessive-compulsive disorder.

There has been substantial concern about the mental health effects of the COVID-19 pandemic, particularly for those with obsessive-compulsive disorder (OCD) given the overlap between OCD symptoms (e.g., excessive handwashing) and appropriate disease prevention measures. However, the pandemic has demonstrated heterogeneous mental health effects, suggesting that individual-level factors could play a role in buffering or exacerbating its deleterious impact. This study aimed to understand how individual differences in resilience were associated with trajectories of obsessive-compulsive, depression, and anxiety symptoms among healthy adults and those with OCD residing in New York City, considered the epicenter of the pandemic in the United States at its onset. The sample consisted of healthy individuals (n = 30) and people with OCD (n = 33) who completed clinical interviews and self-report questionnaires that assessed baseline resilience, OCD symptoms, depression, anxiety, and perceived positive effects of the pandemic at four assessment timepoints: baseline (April 2020) and one, two, and six months later. Linear mixed-effects growth models revealed that greater resilience was associated with stable trajectories of symptoms over time. Conversely, less resilience was associated with worsening obsessive-compulsive symptoms from the two-month to six-month assessment timepoints and worsening depressive symptoms at six months across both groups, and with worsening anxiety symptoms in individuals with OCD at six months. Resilience was correlated with the ability to appreciate "silver linings" of the pandemic. These findings highlight resilience as a potential treatment target for bolstering mental health outcomes among individuals with and without psychopathology during sustained and unprecedented periods of stress.

Evaluating the antibody response to SARS-COV-2 vaccination amongst kidney transplant recipients at a single nephrology centre.

BACKGROUND AND OBJECTIVES: Kidney transplant recipients are highly vulnerable to the serious complications of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infections and thus stand to benefit from vaccination. Therefore, it is necessary to establish the effectiveness of available vaccines as this group of patients was not represented in the randomized trials. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 707 consecutive adult kidney transplant recipients in a single center in the United Kingdom were evaluated. 373 were confirmed to have received two doses of either the BNT162b2 (Pfizer-BioNTech) or AZD1222 (Oxford-AstraZeneca) and subsequently had SARS-COV-2 antibody testing were included in the final analysis. Participants were excluded from the analysis if they had a previous history of SARS-COV-2 infection or were seropositive for SARS-COV-2 antibody pre-vaccination. Multivariate and propensity score analyses were performed to identify the predictors of antibody response to SARS-COV-2 vaccines. The primary outcome was seroconversion rates following two vaccine doses. RESULTS: Antibody responders were 56.8% (212/373) and non-responders 43.2% (161/373). Antibody response was associated with greater estimated glomerular filtration (eGFR) rate [odds ratio (OR), for every 10 ml/min/1.73m2 = 1.40 (1.19-1.66), P<0.001] whereas, non-response was associated with mycophenolic acid immunosuppression [OR, 0.02(0.01-0.11), p<0.001] and increasing age [OR per 10year increase, 0.61(0.48-0.78), p<0.001]. In the propensity-score analysis of four treatment variables (vaccine type, mycophenolic acid, corticosteroid, and triple immunosuppression), only mycophenolic acid was significantly associated with vaccine response [adjusted OR by PSA 0.17 (0.07-0.41): p<0.001]. 22 SARS-COV-2 infections were recorded in our cohort following vaccination. 17(77%) infections, with 3 deaths, occurred in the non-responder group. No death occurred in the responder group. CONCLUSION: Vaccine response in allograft recipients after two doses of SARS-COV-2 vaccine is poor compared to the general population. Maintenance with mycophenolic acid appears to have the strongest negative impact on vaccine response.

Alemtuzumab in renal transplantation. Reviews of literature and usage in the United Kingdom.

Kidney transplantation has evolved over the years from transplants between identically matched donors and recipients to successfully transplanting allografts across virtually any degree of donor-recipient human leukocyte antigen mismatch and ABO-incompatibility. Integral to these improved outcomes has been the development and deployment of a range of immunosuppressive agents. The addition of monoclonal and polyclonal antibodies as a standard part of overall immunosuppression has led to the improved outcomes by providing a robust and focused protection during the first few months of transplantation when allografts are most vulnerable to immune-mediated injury. Alemtuzumab is a recombinant anti-CD52 pan-lymphocyte depleting monoclonal antibody that has been in use for kidney transplantation since the late 1990s. Despite the many years of experience with alemtuzumab, its utilisation in the UK has remained relatively restrained. This may be due to a lack of high-level evidence to support its safety and efficacy in transplantation. Also, long-term outcomes have not been addressed by existing studies. Nevertheless, available evidence suggests that alemtuzumab is associated with a lower risk of acute rejection within the first year of transplantation while exhibiting a comparable safety profile to non-lymphocyte depleting agents. Despite the current economic advantages of alemtuzumab (available free of cost on a named transplant recipient basis), its use in UK transplant centres has remained limited, variating from non-use, through usage in selected high immunologic risk subjects, to use as routine induction immunosuppression. This review discusses the current use of alemtuzumab for immunosuppression induction in kidney transplantation. It describes its evolution from development to its present application in kidney transplantation and reviews the evidence underpinning its utilisation. The role of alemtuzumab in the immunosuppressive protocols individual UK kidney transplant centres is also described.

Maintenance of Wellness in Patients With Obsessive-Compulsive Disorder Who Discontinue Medication After Exposure/Response Prevention Augmentation: A Randomized Clinical Trial.

IMPORTANCE: Serotonin reuptake inhibitors (SRIs) are the only medications approved for obsessive-compulsive disorder (OCD), yet most patients taking SRIs exhibit significant symptoms. Adding exposure/response prevention (EX/RP) therapy improves symptoms, but it is unknown whether patients maintain wellness after discontinuing SRIs. OBJECTIVE: To assess whether patients with OCD who are taking SRIs and have attained wellness after EX/RP augmentation can discontinue their SRI with noninferior outcomes compared with those who continue their SRI therapy. DESIGN, SETTING, AND PARTICIPANTS: A 24-week, double-blind, randomized clinical trial was performed from May 3, 2013, to June 25, 2018. The trial took place at US academic medical centers. Participants included 137 adults with a principal diagnosis of OCD (≥1 year) who were taking an SRI (≥12 weeks), had at least moderate symptoms (defined as Yale-Brown Obsessive-Compulsive Scale [Y-BOCS] score ≥18 points), and received as many as 25 sessions of EX/RP therapy. Those who attained wellness (Y-BOCS score ≤14 points; 103 patients [75.2%]) were study eligible. Data were analyzed from June 29, 2019, to October 2, 2021. INTERVENTION: Participants were randomly assigned either to receive taper to placebo (taper group) or to continue their SRI (continuation group) and monitored for 24 weeks. MAIN OUTCOME AND MEASURES: The Y-BOCS score (range, 0-40 points) was the primary outcome; the Hamilton Depression Rating Scale (HDRS; range, 0-52 points) and the Quality-of-Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF; range, 0%-100%) scores were secondary outcomes. Outcomes were assessed at 8 time points by independent evaluators who were blinded to randomization. The taper regimen was hypothesized to be noninferior to continuation at 24 weeks using a 1-sided α value of .05. RESULTS: A total of 101 patients (mean [SD] age, 31.0 [11.2] years; 55 women [54.5%]) participated in the trial: 51 patients (50.5%) in the taper group and 50 patients (49.5%) in the continuation group. At 24 weeks, patients in the taper group had noninferior results compared with patients in the continuation group (mean [SD] Y-BOCS score: taper group, 11.47 [6.56] points; continuation group: 11.51 [5.97] points; difference, -0.04 points; 1-sided 95% CI, -∞ to 2.09 points [below the noninferiority margin of 3.0 points]; mean [SD] HDRS score: taper group, 5.69 [3.84] points; continuation group, 4.61 [3.46] points; difference, 1.08 points; 1-sided 95% CI, -∞ to 2.28 points [below the noninferiority margin of 2.5 points]; mean [SD] Q-LES-Q-SF score: taper group, 68.01% [15.28%]; continuation group, 70.01% [15.59%]; difference, 2.00%; 1-sided 95% CI, -∞ to 6.83 [below the noninferiority margin of 7.75]). However, the taper group had higher rates of clinical worsening (23 of 51 [45%] vs 12 of 50 [24%]; P = .04). CONCLUSIONS AND RELEVANCE: Results of this randomized clinical trial show that patients with OCD who achieve wellness after EX/RP therapy could, on average, discontinue their SRI with noninferior outcomes compared with those who continued their SRI. Those who tapered the SRI had higher clinical worsening rates. Future research should evaluate if SRI half-life alters these rates. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01686087.

Managing recurrent urinary tract infections in kidney transplant recipients using smartphone assisted urinalysis test.

BACKGROUND: Urinary tract infection is the most frequent infectious complication in allograft recipients with poor outcomes. The study aimed to assess the effect of self-testing urine dipsticks at home, with the assistance of smartphone technology, on the occurrence of urinary tract infection (UTI)-associated complications and frequency and length of hospital admissions. METHOD: We performed a retrospective cohort study of kidney transplant recipients with a history of recurrent UTI who used a newly introduced smartphone-assisted dipsticks urinalysis test for self-monitoring. Participants self-administered the home urinalysis test with symptom onset. Antibiotics were prescribed if an infection was suspected, and home urinalysis was positive. The incidence of urinary infections, hospitalisations, and complications was evaluated before and during the home urinalysis period. Remote and face-to-face interactions with healthcare personnel were also assessed (cases acted as their controls). RESULTS: Nineteen participants were included in the study. A total of 89.5% were females. Ninety home urinalysis tests were conducted over a mean period of 7 months. Sixty-one of these were pre-antibiotic. A total of 42.2% of all tests and 47.5% of the pre-antibiotic tests were positive. UTI-related hospitalisations were lower by 75% during the home urinalysis period; mean 1.26 (0.8-1.6) versus 0.32 (-0.01-0.6). The incidence of infection-related complications was also 65% lower; mean 1.52 (0.8-2.2) versus 0.52 (-0.2-1.2) during the same period. The number of face-to-face interactions was slightly lower; mean 1.9 (1.1-2.2) versus 1.7 (0.6-2.8), with more remote interactions; mean 6.0 (3.7-8.5) versus 10.4 (6.5-14.3), during smartphone urinalysis. Fifty per cent of antibiotic-treated UTI episodes had antibiotics within 24 h, rising to 82% within 48 h of a test. CONCLUSION: Smartphone-assisted home urinalysis enabled remote management of UTI in a high-risk population. Outcomes point to a reduction in UTI complications and hospitalisations.

Longitudinal change in c-terminal fibroblast growth factor 23 and outcomes in patients with advanced chronic kidney disease.

BACKGROUND: Fibroblast growth factor23 (FGF23) is elevated in CKD and has been associated with outcomes such as death, cardiovascular (CV) events and progression to Renal Replacement therapy (RRT). The majority of studies have been unable to account for change in FGF23 over time and those which have demonstrate conflicting results. We performed a survival analysis looking at change in c-terminal FGF23 (cFGF23) over time to assess the relative contribution of cFGF23 to these outcomes. METHODS: We measured cFGF23 on plasma samples from 388 patients with CKD 3-5 who had serial measurements of cFGF23, with a mean of 4.2 samples per individual. We used linear regression analysis to assess the annual rate of change in cFGF23 and assessed the relationship between time-varying cFGF23 and the outcomes in a cox-regression analysis. RESULTS: Across our population, median baseline eGFR was 32.3mls/min/1.73m2, median baseline cFGF23 was 162 relative units/ml (RU/ml) (IQR 101-244 RU/mL). Over 70 months (IQR 53-97) median follow-up, 76 (19.6%) patients progressed to RRT, 86 (22.2%) died, and 52 (13.4%) suffered a major non-fatal CV event. On multivariate analysis, longitudinal change in cFGF23 was significantly associated with risk for death and progression to RRT but not non-fatal cardiovascular events. CONCLUSION: In our study, increasing cFGF23 was significantly associated with risk for death and RRT.

Integrating Exposure and Response Prevention With a Mobile App to Treat Obsessive-Compulsive Disorder: Feasibility, Acceptability, and Preliminary Effects.

Many individuals with obsessive-compulsive disorder (OCD) do not receive evidence-based care (specifically exposure and ritual prevention; EX/RP) due to barriers such as a lack of EX/RP-trained clinicians, geographic obstacles, and the cost and time associated with the treatment. Offering an integrated treatment model consisting of brief in-person therapy coupled with a mobile application (app) might be one way to increase access to and reduce the time burden (to clinicians and patients) of EX/RP. This pilot trial evaluated the feasibility, acceptability, and clinical effects of such a treatment program for adults with OCD. Thirty-three participants enrolled in the 8-week open trial. The integrated treatment program consisted of 3 to 5 in-person sessions followed by weekly phone calls supported by a mobile app (nOCD). Participants were evaluated by trained raters and completed self-report measures at baseline, midtreatment, posttreatment and 2-month follow-up; the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was the primary outcome. This integrated treatment program was feasible and acceptable to participants. Of the 33 study entrants, 14 (42%) responded to treatment (Y-BOCS decrease ≥35% with CGI- of 1 or 2), and 8 (24%) achieved minimal symptoms (i.e., Y-BOCS ≤12). At 2-month follow-up (n=20), 7/20 (35%) met criteria for treatment response, and 3/20 (15.0%) met criteria for treatment remission. Although preliminary, this model warrants further study as an efficacious and resource-efficient way to deliver EX/RP for some patients with OCD.

Safely reducing haemodialysis frequency during the COVID-19 pandemic.

BACKGROUND: Patients undergoing haemodialysis (HD) are at higher risk of developing worse outcomes if they contract COVID-19. In our renal service we reduced HD frequency from thrice to twice-weekly in selected patients with the primary aim of reducing COVID 19 exposure and transmission between HD patients. METHODS: Dialysis unit nephrologists identified 166 suitable patients (38.4% of our HD population) to temporarily convert to twice-weekly haemodialysis immediately prior to the peak of the COVID-19 pandemic in our area. Changes in pre-dialysis weight, systolic blood pressure (SBP) and biochemistry were recorded weekly throughout the 4-week project. Hyperkalaemic patients (serum potassium > 6.0 mmol/L) were treated with a potassium binder, sodium bicarbonate and received responsive dietary advice. RESULTS: There were 12 deaths (5 due to COVID-19) in the HD population, 6 of which were in the twice weekly HD group; no deaths were definitively associated with change of dialysis protocol. A further 19 patients were either hospitalised and/or developed COVID-19 and thus transferred back to thrice weekly dialysis as per protocol. 113 (68.1%) were still receiving twice-weekly HD by the end of the 4-week project. Indications for transfer back to thrice weekly were; fluid overload (19), persistent hyperkalaemia (4), patient request (4) and compliance (1). There were statistically significant increases in SBP and pre-dialysis potassium during the project. CONCLUSIONS: Short term conversion of a large but selected HD population to twice-weekly dialysis sessions was possible and safe. This approach could help mitigate COVID-19 transmission amongst dialysis patients in centres with similar organisational pressures.

Task-based fMRI predicts response and remission to exposure therapy in obsessive-compulsive disorder.

Exposure and ritual prevention (EX/RP) is an effective first-line treatment for obsessive-compulsive disorder (OCD), but only some patients achieve minimal symptoms following EX/RP. Herein, we investigate whether task-based neural activity can predict who responds best to EX/RP. Unmedicated adult patients with OCD (n = 36) and healthy participants (n = 33) completed the Simon Spatial Incompatibility Task during high-resolution, multiband functional MRI (fMRI); patients were then offered twice-weekly EX/RP (17 sessions). Linear mixed-effects models were used to identify brain regions where conflict-related activity moderated the slope of change in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores across treatment. Conflict-related activity in the left pallidum and 35 cortical parcels/regions significantly predicted symptom improvement with EX/RP for patients with OCD (false discovery rate-corrected P < 0.05). Significant parcels/regions included cingulo-opercular and default mode network regions, specifically the anterior insula and anterior and posterior cingulate. Summarizing across these parcels/regions, greater conflict-related activity predicted greater EX/RP response and which patients achieved remission (Y-BOCS score ≤ 12; Cohen's d = 1.68) with >80% sensitivity and specificity. The association between brain activity and treatment response was partially mediated by patient EX/RP adherence (b = -2.99; 43.61% of total effect; P = 0.02). Brain activity and adherence together were highly predictive of remission. Together, these findings suggest that cingulo-opercular and default mode regions typically implicated in task control and introspective processes, respectively, may be targets for novel treatments that augment the ability of persons with OCD to resolve cognitive conflict and thereby facilitate adherence to EX/RP, increasing the likelihood of remission.

Utilizing Exposure and Response Prevention to Address Poor Insight in Obsessive-Compulsive Disorder.

Studies indicate that approximately 9%-30% of adults diagnosed with obsessive-compulsive disorder have poor insight into their symptoms. That is, they fail to recognize the excessiveness or irrationality of the obsessive thoughts or their compulsive behaviors. Poor insight in OCD is associated with more severe symptoms, earlier age of illness onset, longer illness duration, and higher rates of comorbid depression. Moreover, some studies have also reported that patients with poor insight are less likely than are those with good or fair insight to respond to first-line treatments such as exposure and response prevention (ERP). Despite the clinical relevance of poor insight, very little research has focused on how to enhance therapy with strategies specifically used to target it. In this report, we use a case study to demonstrate how different techniques can be emphasized or integrated with standard ERP to improve treatment outcomes for this subset of patients.

Outcomes in dialysis versus conservative care for older patients: A prospective cohort analysis of stage 5 Chronic Kidney Disease.

BACKGROUND: The benefits of dialysis in older people with ESKD are not clear. We prospectively evaluated whether dialysis has survival advantage compared to conservative care (CC) in older people who were medically suitable for dialysis therapy. METHODS: This was a prospective observational study of CKD patients aged ≥75 years when eGFR first reached ≤15ml/min/1.73m2. Hazard ratios (HR) for death were compared between patients who chose dialysis versus conservative care (CC) from when first seen in pre-dialysis clinic (eGFR ≤15ml/min/1.73m2), and when initiation of dialysis was first considered (eGFR ≤10ml/min/1.73m2). Patients with co-morbidities likely to significantly reduce life expectancy such as advanced heart failure, advanced dementia, and malignancy, were excluded. RESULTS: There were 204 patients (123 dialysis, 81 CC). 115 went on to record eGFR of ≤10ml/min/1.73m2 (73 dialysis, 42 CC). The median survival from eGFR first ≤15ml/min/1.73m2 for the dialysis and CC groups were 42 (33-50) months and 31 (21-41) months. The adjusted hazard ratio (HR) for death in the dialysis group compared to CC was 0.61 (0.41-0.61, p = 0.01). The median survival from eGFR first ≤10ml/min/1.73m2 for dialysis and CC group were 36 (25-47) months and 12 (0-5) months. The adjusted HR for death in the dialysis group compared to CC was 0.36 (0.21-0.62, p <0.001). CONCLUSION: Dialysis confers a survival benefit in older patients medically suitable for dialysis. This study is novel in being both prospective and in excluding patients with co-morbidities which may limit suitability for dialysis and life expectancy. A future focus on quality of life is needed to establish the true benefits of dialysis in older people.

Comparing the impact of older age on outcome in chronic kidney disease of different etiologies: a prospective cohort study.

BACKGROUND: In older patients with chronic kidney disease (CKD), the risk of progression to end stage renal disease and cardiovascular death both differ compared to younger patients. This likely reflects differences in case mix and co-morbid burdens. We sought to establish the extent to which age itself is an independent biomarker of adverse outcome in CKD. METHODS: This was an analysis of the Salford Kidney Study, a prospective, longitudinal, observational study of 2,667 patients with eGFR < 60 ml/min/1.73 m2. Patients were divided into four age groups (< 55, 55-65, 65-75 and > 75 years). Within group adjusted hazard ratios for death in older compared to younger patients were calculated for different primary renal diseases. A competing risk model of death and renal replacement therapy (RRT) as outcomes was performed. RESULTS: The median age of the cohort was 67.1 years [interquartile range (IQR): 55.6-75.3] and median eGFR 30.8 ml/min/1.73 m2 (IQR: 20.6-43.2). Follow up was 3.5 ± 2.9 years. Overall, the adjusted HR for death in patients aged > 75 years compared to those < 55 years was 4.4 (95% CI 3.4-5.9), p < 0.001. The HR for death differed between primary renal diseases and CKD stages. In diabetic nephropathy, the HR was 3.0 (1.8-5.3, p < 0.001), in glomerulonephritis the HR was 12.2 (5.6-25.5, p < 0.001). The cumulative incidence of RRT was < 0.1 at 10 years for patients > 75 years, compared with 0.50 in those < 55 years. Death was more likely at 20 months in those aged 75 years or older (0.17) than at 10 years in those aged < 55 years (0.10). CONCLUSION: This study demonstrates that the risk associated with older age shows significant variability between primary renal diseases. This is whilst acknowledging that observational studies carry the risk of hidden bias not adjusted for in the statistical model.