Utilization and clinical outcomes of kidney transplants from deceased donors with albuminuria in the UK: a national cohort study.

BACKGROUND: Urinalysis is a standard component of potential deceased kidney donor assessment in the UK. The value of albuminuria as a biomarker for organ quality is uncertain. We examined the relationship between deceased donor albuminuria and kidney utilization, survival and function. METHODS: We performed a national cohort study on adult deceased donors and kidney transplant recipients between 2016 and 2020, using data from the UK Transplant Registry. We examined the influence of donor albuminuria, defined as ≥2+ on dipstick testing, on kidney utilization, early graft function, graft failure and estimated glomerular filtration rate (eGFR). RESULTS: Eighteen percent (1681/9309) of consented donors had albuminuria. After adjustment for confounders, kidneys from donors with albuminuria were less likely to be accepted for transplantation (74% versus 82%; odds ratio 0.70, 95% confidence interval 0.61 to 0.81). Of 9834 kidney transplants included in our study, 1550 (16%) came from donors with albuminuria. After a median follow-up of 2 years, 8% (118/1550) and 9% (706/8284) of transplants from donors with and without albuminuria failed, respectively. There was no association between donor albuminuria and graft failure (hazard ratio 0.91, 95% confidence interval 0.74 to 1.11). There was also no association with delayed graft function, patient survival or eGFR at 1 or 3 years. CONCLUSIONS: Our study suggests reluctance in the UK to utilize kidneys from deceased donors with dipstick albuminuria but no evidence of an association with graft survival or function. This may represent a potential to expand organ utilization without negatively impacting transplant outcomes.

Feasibility, long-term safety, and immune monitoring of regulatory T cell therapy in living donor kidney transplant recipients.

Short-term outcomes in kidney transplantation are marred by progressive transplant failure and mortality secondary to immunosuppression toxicity. Immune modulation with autologous polyclonal regulatory T cell (Treg) therapy may facilitate immunosuppression reduction promoting better long-term clinical outcomes. In a Phase I clinical trial, 12 kidney transplant recipients received 1-10 × 106 Treg per kg at Day +5 posttransplantation in lieu of induction immunosuppression (Treg Therapy cohort). Nineteen patients received standard immunosuppression (Reference cohort). Primary outcomes were rejection-free and patient survival. Patient and transplant survival was 100%; acute rejection-free survival was 100% in the Treg Therapy versus 78.9% in the reference cohort at 48 months posttransplant. Treg therapy revealed no excess safety concerns. Four patients in the Treg Therapy cohort had mycophenolate mofetil withdrawn successfully and remain on tacrolimus monotherapy. Treg infusion resulted in a long-lasting dose-dependent increase in peripheral blood Tregs together with an increase in marginal zone B cell numbers. We identified a pretransplantation immune phenotype suggesting a high risk of unsuccessful ex-vivo Treg expansion. Autologous Treg therapy is feasible, safe, and is potentially associated with a lower rejection rate than standard immunosuppression. Treg therapy may provide an exciting opportunity to minimize immunosuppression therapy and improve long-term outcomes.

One size does not fit all: understanding individual living kidney donor risk.

Living donor kidney transplantation is the optimal treatment for end-stage kidney disease (ESKD) but confers a risk upon the donor, both in the short term and many years after donation. While perioperative mortality is low and longevity does not appear to be adversely affected, there are small increases in the risk of other important morbidities. The overall risk of ESKD among donors is low but appears to be three- to five-fold higher than among healthy non-donors, and this relative risk is even higher among donors of African ancestry. For these individuals, apolipoprotein L1 genotyping may be helpful. Kidney donors also have an increased risk of developing hypertension post-donation and a modestly increased risk of developing gout. Living kidney donation also increases the risk of gestational hypertension and preeclampsia while not affecting other important pregnancy outcomes. As our understanding of donor risk grows, it is important to counsel prospective donors according to their individual risk and so obtain better informed donor consent. As knowledge advances, it is also important that all clinicians who manage kidney transplant candidates have an up to date understanding of donor risk to inform shared decision making.

Causes of renal allograft failure in the UK: trends in UK Renal Registry and National Health Service Blood and Transplant data from 2000 to 2013.

Background: Improvement in long-term renal allograft survival is impeded by incomplete or erroneous coding of causes of allograft loss. This study reports 13-year trends in causes of graft failure across the UK. Methods: National Health Service Blood and Transplant (NHSBT) and UK Renal Registry data were linked to describe UK kidney patients transplanted in 2000-13. NHSBT graft failure categories were used, with 'other' recoded when free text was available. Adjusted analyses examined the influence of age, ethnicity and donor type on causes of graft failure. Results: In 22 730 recipients, 5389 (23.7%) grafts failed within a median follow-up of 5 years. The two most frequent causes were death with a functioning graft (40.8%) and alloimmune pathology (25.0%). Graft survival was higher in recipients who were younger (mean 47.3 versus 50.7 years), received a pre-emptive transplant (20.2% versus 10.4%), spent less time on dialysis (median 1.6 versus 2.4 years) and received a living donor transplant (36.3% versus 22.2%), with no differences by sex, ethnicity or human leucocyte antigen mismatch. Allograft failure within 2 years of transplantation fell from 12.5% (2000-4) to 9.8% (2009-13). Surgical- and alloimmune-related failures decreased over time while death with a functioning graft became more common. Age, ethnicity and donor type were factors in recurrent primary disease and alloimmune pathology. Conclusions: Since 2000 there have been reductions in surgical and alloimmune graft failures in the UK. However, graft failure codes need to be revised if they are to remain useful and effective in epidemiological and quality improvement trials.

Chronic histological changes in deceased donor kidneys at implantation do not predict graft survival: a single-centre retrospective analysis.

The use of preimplantation kidney biopsies (PIKBs) to aid deceased donor kidney utilization decisions is controversial. Outcomes of transplants that had been biopsied after the decision had been made to implant were analysed, in order to determine the association between chronic histological changes at implantation and graft outcomes. A retrospective analysis of transplants between the year range 2006-2015 was performed. Karpinski scores on biopsies were collected, and graft outcomes were analysed using univariate and multivariable techniques. Also, Karpinski scores from single and dual kidney transplants from older donors were examined to determine if knowledge of the score preoperatively would have altered utilization. Four hundred and eight single kidneys were transplanted. Although kidneys with scores >4 had lower 1- and 3-year median (IQR) estimated glomerular filtration rates (eGFRs) than those scoring 0-4 (51 (37-66) vs. 35 (26-52) ml/min/1.73 m2 , P < 0.001, and 52 (34-64) vs. 35 (24-52) ml/min/1.73 m2 , P < 0.001, respectively), there was no significant association between Karpinski score and death-censored graft survival on univariate or multivariable analyses. The utilization analysis (75 single and 25 dual kidney transplant recipients) suggested that systematic use of PIKBs would have resulted in 29% fewer patients being transplanted. This analysis does not support the systematic use of PIKBs to determine deceased donor kidney utilization.

Clinical characteristics and outcomes of HIV-associated immune complex kidney disease.

BACKGROUND: The pathogenesis and natural history of HIV-associated immune complex kidney disease (HIVICK) is not well understood. Key questions remain unanswered, including the role of HIV infection and replication in disease development and the efficacy of antiretroviral therapy (ART) in the prevention and treatment of disease. METHODS: In this multicentre study, we describe the renal pathology of HIVICK and compare the clinical characteristics of patients with HIVICK with those with IgA nephropathy and HIV-associated nephropathy (HIVAN). Poisson regression models were used to identify risk factors for each of these pathologies. RESULTS: Between 1998 and 2012, 65 patients were diagnosed with HIVICK, 27 with IgA nephropathy and 70 with HIVAN. Black ethnicity and HIV RNA were associated with HIVICK, receipt of ART with IgA nephropathy and black ethnicity and CD4 cell count with HIVAN. HIVICK was associated with lower rates of progression to end-stage kidney disease compared with HIVAN and IgA nephropathy (P < 0.0001). Patients with HIVICK who initiated ART and achieved suppression of HIV RNA experienced improvements in estimated glomerular filtration rate and proteinuria. CONCLUSIONS: These findings suggest a pathogenic role for HIV replication in the development of HIVICK and that ART may improve kidney function in patients who have detectable HIV RNA at the time of HIVICK diagnosis. Our data also suggest that IgA nephropathy should be viewed as a separate entity and not included in the HIVICK spectrum.

Renal blood flow using arterial spin labelling MRI and calculated filtration fraction in healthy adult kidney donors Pre-nephrectomy and post-nephrectomy.

OBJECTIVES: Renal plasma flow (RPF) (derived from renal blood flow, RBF) and glomerular filtration rate (GFR) allow the determination of the filtration fraction (FF), which may have a role as a non-invasive renal biomarker. This is a hypothesis-generating pilot study assessing the effect of nephrectomy on renal function in healthy kidney donors. METHODS: Eight living kidney donors underwent arterial spin labelling (ASL) magnetic resonance imaging (MRI) and GFR measurement prior to and 1 year after nephrectomy. Chromium-51 labelled ethylenediamine tetraacetic acid ((51)Cr-EDTA) with multi-blood sampling was undertaken and GFR calculated. The RBF and GFR obtained were used to calculate FF. RESULTS: All donors showed an increase in single kidney GFR of 24 - 75 %, and all but two showed an increase in FF (-7 to +52 %) after nephrectomy. The increase in RBF, and hence RPF, post-nephrectomy was not as great as the increase in GFR in seven out of eight donors. As with any pilot study, the small number of donors and their relatively narrow age range are potential limiting factors. CONCLUSIONS: The ability to measure RBF, and hence RPF, non-invasively, coupled with GFR measurement, allows calculation of FF, a biomarker that might provide a sensitive indicator of loss of renal reserve in potential donors. KEY POINTS: • Non-invasive MRI measured renal blood flow and calculated renal plasma flow. • Effect of nephrectomy on blood flow and filtration in donors is presented. • Calculated filtration fraction may be a useful new kidney biomarker.

Randomized Controlled Comparative Effectiveness Trial of Risk Model-Guided Clinical Decision Support for Suicide Screening.

Suicide prevention requires risk identification, appropriate intervention, and follow-up. Traditional risk identification relies on patient self-reporting, support network reporting, or face-to-face screening with validated instruments or history and physical exam. In the last decade, statistical risk models have been studied and more recently deployed to augment clinical judgment. Models have generally been found to be low precision or problematic at scale due to low incidence. Few have been tested in clinical practice, and none have been tested in clinical trials to our knowledge. Methods: We report the results of a pragmatic randomized controlled trial (RCT) in three outpatient adult Neurology clinic settings. This two-arm trial compared the effectiveness of Interruptive and Non-Interruptive Clinical Decision Support (CDS) to prompt further screening of suicidal ideation for those predicted to be high risk using a real-time, validated statistical risk model of suicide attempt risk, with the decision to screen as the primary end point. Secondary outcomes included rates of suicidal ideation and attempts in both arms. Manual chart review of every trial encounter was used to determine if suicide risk assessment was subsequently documented. Results: From August 16, 2022, through February 16, 2023, our study randomized 596 patient encounters across 561 patients for providers to receive either Interruptive or Non-Interruptive CDS in a 1:1 ratio. Adjusting for provider cluster effects, Interruptive CDS led to significantly higher numbers of decisions to screen (42%=121/289 encounters) compared to Non-Interruptive CDS (4%=12/307) (odds ratio=17.7, p-value <0.001). Secondarily, no documented episodes of suicidal ideation or attempts occurred in either arm. While the proportion of documented assessments among those noting the decision to screen was higher for providers in the Non-Interruptive arm (92%=11/12) than in the Interruptive arm (52%=63/121), the interruptive CDS was associated with more frequent documentation of suicide risk assessment (63/289 encounters compared to 11/307, p-value<0.001). Conclusions: In this pragmatic RCT of real-time predictive CDS to guide suicide risk assessment, Interruptive CDS led to higher numbers of decisions to screen and documented suicide risk assessments. Well-powered large-scale trials randomizing this type of CDS compared to standard of care are indicated to measure effectiveness in reducing suicidal self-harm. ClinicalTrials.gov Identifier: NCT05312437.

Incidental renal stones in potential live kidney donors: prevalence, assessment and donation, including role of ex vivo ureteroscopy.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Previously, donors with asymptomatic stones found incidentally on CT were not considered ideal donor candidates because of the presumed risk of morbidity to both the donor and recipient. Increasingly, studies show that these risks are low. This study aims to evaluate the long-term safety of using ex vivo ureteroscopy to remove the stones from the donor kidney on the bench before donation. Outcomes so far suggest that this technique can safely render a kidney stone-free before transplantation. This has led to 20 more transplants in our institution than would otherwise be possible. OBJECTIVES: To evaluate the prevalence of asymptomatic renal stones in our potential donor population. To assess the safety and success of ex vivo ureteroscopy (ExURS) to remove stones from explanted donor kidneys before transplantation. PATIENTS AND METHODS: We conducted a retrospective analysis of 377 computed tomography (CT) angiograms of potential kidney donors between October 2004 and May 2007 to assess the prevalence of asymptomatic renal stones in our donor population. Between October 2005 and October 2011, kidneys from suitable donors underwent ExURS. Stones were removed using basket extraction or were fragmented with holmium laser on bench before transplantation. Immediate and long-term complications of the transplanted recipients were recorded. Donors were followed with yearly ultrasonography of the remaining kidney in addition to standard follow-up protocol. RESULTS: Review of 377 CT angiograms between October 2004 to May 2007 showed a 5% prevalence of asymptomatic renal stones. Out of 55 potential donors (19 identified between October 2004 to May 2007 and a further 36 identified since May 2007), 20 donors with stones proceeded to donation, with stone size ranging from 2 to 12 mm. Of the patients, 17 proceeded to ExURS. Stones were removed in 10 patients; five with basket retrieval, four with laser fragmentation and one with both laser fragmentation and basket retrieval. There were no early or late allograft stone-related complications and no evidence of stones on follow-up imaging at a mean (range) of 10 (1-24) months. There has been no reported stone recurrence in any of the donors to date and no stone on ultrasonography of eight donors with >1-year follow-up (mean 26 months, range 12-49 months). CONCLUSIONS: Asymptomatic renal stones are present in 5% of our donors. ExURS can be safely used to remove stones in these kidneys before transplantation, without the risk of subjecting the donor to an additional stone-removing procedure. Continued long-term follow-up of donors and recipients is still required to ensure the safety of this approach.

UK Renal Registry 16th annual report: chapter 4 demography of patients waitlisted for renal transplantation in the UK: national and centre-specific analyses.

INTRODUCTION: For suitable patients, renal transplantation is considered the optimal modality of renal replacement therapy, with availability of donor organs limiting the number of transplants undertaken. The 2006 kidney allocation policy was developed to ensure equity of allocation to patients on the transplant waiting list, whilst still achieving a good donor/recipient match. This study aims to describe the characteristics of the kidney transplant waiting list and variations in median waiting times. METHODS: Demographics and clinical characteristics of all patients listed for a kidney only transplant in the UK on 1st January 2011 were examined. Renal unit variations were explored. Patients listed between January 2006 and December 2009 were included in analysis of waiting times to transplant. RESULTS: At the beginning of 2011, there were 6,699 patients registered active for kidney only transplant in UK; a prevalence rate of 107 pmp. The median age of prevalent listed patients was 53 years, with 8% aged 70 or above. Of the patients listed, 84% had started renal replacement therapy (RRT), 59% were male, 28% were from ethnic minorities, 50% had blood group type O, 28% were defined as difficult to HLA match and 23% were highly sensitised (calculated HLA antibody reaction frequency 85%). Median waiting time to transplant was 38 months. Waiting time was shorter for White patients (36 months) compared to Asian or Black patients (46 months), and was doubled in highly sensitised compared to un-sensitised patients. CONCLUSIONS: Intercentre variation was observed in the rate of wait-listing and in the proportion of listed patients across different ethnic groups, age, blood groups and level of sensitisation. This may reflect differences in baseline population characteristics as well as individual centre practice patterns. Median waiting times differ significantly across blood groups, degree of sensitisation and ethnic group.

A Cognitive Biotype of Depression and Symptoms, Behavior Measures, Neural Circuits, and Differential Treatment Outcomes: A Prespecified Secondary Analysis of a Randomized Clinical Trial.

Importance: Cognitive deficits in depression have been associated with poor functional capacity, frontal neural circuit dysfunction, and worse response to conventional antidepressants. However, it is not known whether these impairments combine together to identify a specific cognitive subgroup (or "biotype") of individuals with major depressive disorder (MDD), and the extent to which these impairments mediate antidepressant outcomes. Objective: To undertake a systematic test of the validity of a proposed cognitive biotype of MDD across neural circuit, symptom, social occupational function, and treatment outcome modalities. Design, Setting, and Participants: This secondary analysis of a randomized clinical trial implemented data-driven clustering in findings from the International Study to Predict Optimized Treatment in Depression, a pragmatic biomarker trial in which patients with MDD were randomized in a 1:1:1 ratio to antidepressant treatment with escitalopram, sertraline, or venlafaxine extended-release and assessed at baseline and 8 weeks on multimodal outcomes between December 1, 2008, and September 30, 2013. Eligible patients were medication-free outpatients with nonpsychotic MDD in at least the moderate range, and were recruited from 17 clinical and academic practices; a subset of these patients underwent functional magnetic resonance imaging. This prespecified secondary analysis was performed between June 10, 2022, and April 21, 2023. Main Outcomes and Measures: Pretreatment and posttreatment behavioral measures of cognitive performance across 9 domains, depression symptoms assessed using 2 standard depression scales, and psychosocial function assessed using the Social and Occupational Functioning Assessment Scale and World Health Organization Quality of Life scale were analyzed. Neural circuit function engaged during a cognitive control task was measured using functional magnetic resonance imaging. Results: A total of 1008 patients (571 [56.6%] female; mean [SD] age, 37.8 [12.6] years) participated in the overall trial and 96 patients participated in the imaging substudy (45 [46.7%] female; mean [SD] age, 34.5 [13.5] years). Cluster analysis identified what may be referred to as a cognitive biotype of 27% of depressed patients with prominent behavioral impairment in executive function and response inhibition domains of cognitive control. This biotype was characterized by a specific profile of pretreatment depressive symptoms, worse psychosocial functioning (d = -0.25; 95% CI, -0.39 to -0.11; P < .001), and reduced activation of the cognitive control circuit (right dorsolateral prefrontal cortex: d = -0.78; 95% CI, -1.28 to -0.27; P = .003). Remission was comparatively lower in the cognitive biotype positive subgroup (73 of 188 [38.8%] vs 250 of 524 [47.7%]; P = .04) and cognitive impairments persisted regardless of symptom change (executive function: ηp2 = 0.241; P < .001; response inhibition: ηp2 = 0.750; P < .001). The extent of symptom and functional change was specifically mediated by change in cognition but not the reverse. Conclusions and Relevance: Our findings suggest the presence of a cognitive biotype of depression with distinct neural correlates, and a functional clinical profile that responds poorly to standard antidepressants and instead may benefit from therapies specifically targeting cognitive dysfunction. Trial Registration: ClinicalTrials.gov Identifier: NCT00693849.

Ketamine's acute effects on negative brain states are mediated through distinct altered states of consciousness in humans.

Ketamine commonly and rapidly induces dissociative and other altered states of consciousness (ASCs) in humans. However, the neural mechanisms that contribute to these experiences remain unknown. We used functional neuroimaging to engage key regions of the brain's affective circuits during acute ketamine-induced ASCs within a randomized, multi-modal, placebo-controlled design examining placebo, 0.05 mg/kg ketamine, and 0.5 mg/kg ketamine in nonclinical adult participants (NCT03475277). Licensed clinicians monitored infusions for safety. Linear mixed effects models, analysis of variance, t-tests, and mediation models were used for statistical analyses. Our design enabled us to test our pre-specified primary and secondary endpoints, which were met: effects of ketamine across dose conditions on (1) emotional task-evoked brain activity, and (2) sub-components of dissociation and other ASCs. With this design, we also could disentangle which ketamine-induced affective brain states are dependent upon specific aspects of ASCs. Differently valenced ketamine-induced ASCs mediated opposing effects on right anterior insula activity. Participants experiencing relatively higher depersonalization induced by 0.5 mg/kg of ketamine showed relief from negative brain states (reduced task-evoked right anterior insula activity, 0.39 SD). In contrast, participants experiencing dissociative amnesia showed an exacerbation of insula activity (0.32 SD). These results in nonclinical participants may shed light on the mechanisms by which specific dissociative states predict response to ketamine in depressed individuals.

Organ Transplants From Deceased Donors With Primary Brain Tumors and Risk of Cancer Transmission.

Importance: Cancer transmission is a known risk for recipients of organ transplants. Many people wait a long time for a suitable transplant; some never receive one. Although patients with brain tumors may donate their organs, opinions vary on the risks involved. Objective: To determine the risk of cancer transmission associated with organ transplants from deceased donors with primary brain tumors. Key secondary objectives were to investigate the association that donor brain tumors have with organ usage and posttransplant survival. Design, Setting, and Participants: This was a cohort study in England and Scotland, conducted from January 1, 2000, to December 31, 2016, with follow-up to December 31, 2020. This study used linked data on deceased donors and solid organ transplant recipients with valid national patient identifier numbers from the UK Transplant Registry, the National Cancer Registration and Analysis Service (England), and the Scottish Cancer Registry. For secondary analyses, comparators were matched on factors that may influence the likelihood of organ usage or transplant failure. Statistical analysis of study data took place from October 1, 2021, to May 31, 2022. Exposures: A history of primary brain tumor in the organ donor, identified from all 3 data sources using disease codes. Main Outcomes and Measures: Transmission of brain tumor from the organ donor into the transplant recipient. Secondary outcomes were organ utilization (ie, transplant of an offered organ) and survival of kidney, liver, heart, and lung transplants and their recipients. Key covariates in donors with brain tumors were tumor grade and treatment history. Results: This study included a total of 282 donors (median [IQR] age, 42 [33-54] years; 154 females [55%]) with primary brain tumors and 887 transplants from them, 778 (88%) of which were analyzed for the primary outcome. There were 262 transplants from donors with high-grade tumors and 494 from donors with prior neurosurgical intervention or radiotherapy. Median (IQR) recipient age was 48 (35-58) years, and 476 (61%) were male. Among 83 posttransplant malignancies (excluding NMSC) that occurred over a median (IQR) of 6 (3-9) years in 79 recipients of transplants from donors with brain tumors, none were of a histological type matching the donor brain tumor. Transplant survival was equivalent to that of matched controls. Kidney, liver, and lung utilization were lower in donors with high-grade brain tumors compared with matched controls. Conclusions and Relevance: Results of this cohort study suggest that the risk of cancer transmission in transplants from deceased donors with primary brain tumors was lower than previously thought, even in the context of donors that are considered as higher risk. Long-term transplant outcomes are favorable. These results suggest that it may be possible to safely expand organ usage from this donor group.

Optimized immunosuppression to prevent graft failure in renal transplant recipients with HLA antibodies (OuTSMART): a randomised controlled trial.

Background: 3% of kidney transplant recipients return to dialysis annually upon allograft failure. Development of antibodies (Ab) against human leukocyte antigens (HLA) is a validated prognostic biomarker of allograft failure. We tested whether screening for HLA Ab, combined with an intervention to improve adherence and optimization of immunosuppression could prevent allograft failure. Methods: Prospective, open-labelled randomised biomarker-based strategy (hybrid) trial in 13 UK transplant centres [EudraCT (2012-004308-36) and ISRCTN (46157828)]. Patients were randomly allocated (1:1) to unblinded or double-blinded arms and screened every 8 months. Unblinded HLA Ab+ patients were interviewed to encourage medication adherence and had tailored optimisation of Tacrolimus, Mycophenolate mofetil and Prednisolone. The primary outcome was time to graft failure in an intention to treat analysis. The trial had 80% power to detect a hazard ratio of 0.49 in donor specific antibody (DSA)+ patients. Findings: From 11/9/13 to 27/10/16, 5519 were screened for eligibility and 2037 randomised (1028 to unblinded care and 1009 to double blinded care). We identified 198 with DSA and 818 with non-DSA. Development of DSA, but not non-DSA was predictive of graft failure. HRs for graft failure in unblinded DSA+ and non-DSA+ groups were 1.54 (95% CI: 0.72 to 3.30) and 0.97 (0.54-1.74) respectively, providing no evidence of an intervention effect. Non-inferiority for the overall unblinded versus blinded comparison was not demonstrated as the upper confidence limit of the HR for graft failure exceeded 1.4 (1.02, 95% CI: 0.72 to 1.44). The only secondary endpoint reduced in the unblinded arm was biopsy-proven rejection. Interpretation: Intervention to improve adherence and optimize immunosuppression does not delay failure of renal transplants after development of DSA. Whilst DSA predicts increased risk of allograft failure, novel interventions are needed before screening can be used to direct therapy. Funding: The National Institute for Health Research Efficacy and Mechanism Evaluation programme grant (ref 11/100/34).

Critical Care Nurses' Experiences of Caring for Patients With COVID-19: Results of a Thematic Analysis.

BACKGROUND: The COVID-19 pandemic has challenged health care professionals, especially those working in intensive care units (ICUs). OBJECTIVES: To explore critical care nurses' experiences with and perceptions of the COVID-19 pandemic during the early phases of the pandemic. METHODS: Data were from national surveys conducted during March and April 2020 to assess ICU providers' perceptions of the initial phases of the pandemic. A total of 831 responses from nurses to open-ended questions were examined by using thematic analysis. The questions assessed potentially limited resources in the ICU, adequacy of staffing, and measures used to reduce the possibility of spreading COVID-19 to family members. RESULTS: Overarching themes concerned access to equipment and preventive measures taken to reduce exposure to the virus. These themes included "sheltering the patient when I don't have enough" and "protecting those I love when I am a vector of transmission." Subthemes for the first overarching theme included not having enough personal protective equipment, not enough staff and not enough properly trained staff, and not enough institutional support. Subthemes for the second overarching theme included "isolating myself from everyone I care about" and "isolating everything I touch from everyone I care about." CONCLUSIONS: This thematic analysis identified several concerns of ICU nurses related to caring for patients in the initial phases of the COVID-19 pandemic. Ensuring adequate supplies, staffing, and administrative and emotional support are provided to frontline health care providers during the ongoing pandemic remains essential.

Sickle Cell Trait and Kidney Disease in People of African Ancestry With HIV.

Introduction: Sickle cell trait (SCT) has been associated with chronic kidney disease (CKD) in African Americans, although evidence for its impact in Africans and people with HIV is currently lacking. We conducted a cross-sectional study investigating the association between SCT and kidney disease in people of African ancestry with HIV in the UK. Methods: The primary outcome was estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2. Secondary outcomes were eGFR <90 ml/min per 1.73 m2, end-stage kidney disease (ESKD; eGFR <15 ml/min per 1.73 m2, chronic dialysis, or having received a kidney transplant), proteinuria (protein-to-creatinine ratio >50 mg/mmol), and albuminuria (albumin-to-creatinine ratio >3 mg/mmol). Multivariable logistic regression was used to estimate the associations between SCT and kidney disease outcomes. Results: A total of 2895 participants (mean age 48.1 [SD 10.3], 57.2% female) were included, of whom 335 (11.6%) had SCT and 352 (12.2%) had eGFR <60 ml/min per 1.73 m2. After adjusting for demographic, HIV, and kidney risk factors including APOL1 high-risk genotype status, individuals with SCT were more likely to have eGFR <60 ml/min per 1.73 m2 (odds ratio 1.62 [95% CI 1.14-2.32]), eGFR <90 ml/min per 1.73 m2 (1.50 [1.14-1.97]), and albuminuria (1.50 [1.09-2.05]). Stratified by APOL1 status, significant associations between SCT and GFR <60 ml/min per 1.73 m2, eGFR <90 ml/min per 1.73 m2, proteinuria, and albuminuria were observed for those with APOL1 low-risk genotypes. Conclusion: Our results extend previously reported associations between SCT and kidney disease to people with HIV. In people of African ancestry with HIV, these associations were largely restricted to those with APOL1 low-risk genotypes.

Genetic Variants of APOL1 Are Major Determinants of Kidney Failure in People of African Ancestry With HIV.

Introduction: Variants of the APOL1 gene are associated with chronic kidney disease (CKD) in people of African ancestry, although evidence for their impact in people with HIV are sparse. Methods: We conducted a cross-sectional study investigating the association between APOL1 renal risk alleles and kidney disease in people of African ancestry with HIV in the UK. The primary outcome was end-stage kidney disease (ESKD; estimated glomerular filtration rate [eGFR] of <15 ml/min per 1.73 m2, chronic dialysis, or having received a kidney transplant). The secondary outcomes included renal impairment (eGFR <60 ml/min per 1.73 m2), albuminuria (albumin-to-creatinine ratio [ACR] >30 mg/mmol), and biopsy-proven HIV-associated nephropathy (HIVAN). Multivariable logistic regression was used to estimate the associations between APOL1 high-risk genotypes (G1/G1, G1/G2, G2/G2) and kidney disease outcomes. Results: A total of 2864 participants (mean age 48.1 [SD 10.3], 57.3% female) were genotyped, of whom, 354 (12.4%) had APOL1 high-risk genotypes, and 99 (3.5%) had ESKD. After adjusting for demographic, HIV, and renal risk factors, individuals with APOL1 high-risk genotypes were at increased odds of ESKD (odds ratio [OR] 10.58, 95% CI 6.22-17.99), renal impairment (OR 5.50, 95% CI 3.81-7.95), albuminuria (OR 3.34, 95% CI 2.00-5.56), and HIVAN (OR 30.16, 95% CI 12.48-72.88). An estimated 49% of ESKD was attributable to APOL1 high-risk genotypes. Conclusion: APOL1 high-risk genotypes were strongly associated with kidney disease in people of African ancestry with HIV and accounted for approximately half of ESKD cases in this cohort.

ADAMTS-13 deficiency: can it cause chronic renal failure?

We describe a case of a 45-year-old woman with progressive chronic kidney disease (CKD), macrocytic anaemia without fragments or thrombocytopaenia, and thrombotic microangiopathy on renal biopsy. 'A disintegrin and metalloprotease, with thrombospondin-1-like domains' (ADAMTS-13) deficiency was detected, and genotyping revealed single-nucleotide polymorphisms known to be associated with reduced ADAMTS-13 secretion and activity. Congenital thrombotic thrombocytopaenic purpura was diagnosed with unusual features of late presentation and absent neurological involvement. ADAMTS-13 deficiency should be considered a cause of CKD when features of thrombotic microangiopathy are present on renal biopsy.

The epidemiology of kidney disease in people of African ancestry with HIV in the UK.

BACKGROUND: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality globally. The risk of CKD is increased in people of African ancestry and with Human Immunodeficiency Virus (HIV) infection. METHODS: We conducted a cross-sectional study investigating the relationship between region of ancestry (East, Central, South or West Africa) and kidney disease in people of sub-Saharan African ancestry with HIV in the UK between May 2018 and February 2020. The primary outcome was renal impairment (estimated glomerular filtration rate [eGFR] of <60 mL/min/1.73 m2). Secondary outcomes were stage 5 CKD (eGFR <15 ml/min/1.73 m2, on dialysis for over 3 months or who had received a kidney transplant), proteinuria (urine protein/creatinine ratio >50 mg/mmol), and biopsy-confirmed HIV-associated nephropathy (HIVAN), focal segmental glomerulosclerosis (FSGS) or arterionephrosclerosis. Multivariable robust Poisson regression estimated the effect of region of African ancestry on kidney disease outcomes. FINDINGS: Of the 2468 participants (mean age 48.1 [SD 9.8] years, 62% female), 193 had renal impairment, 87 stage 5 CKD, 126 proteinuria, and 43 HIVAN/FSGS or arterionephrosclerosis. After adjusting for demographic characteristics, HIV and several CKD risk factors and with East African ancestry as referent, West African ancestry was associated with renal impairment (prevalence ratio [PR] 2.06 [95% CI 1.40-3.04]) and stage 5 CKD (PR 2.23 [1.23-4.04]), but not with proteinuria (PR 1.27 [0.78-2.05]). West African ancestry (as compared to East/South African ancestry) was also strongly associated with a diagnosis of HIVAN/FSGS or arterionephrosclerosis on kidney biopsy (PR 6.44 [2.42-17.14]). INTERPRETATION: Our results indicate that people of West African ancestry with HIV are at increased risk of kidney disease. Although we cannot rule out the possibility of residual confounding, geographical region of origin appears to be a strong independent risk factor for CKD as the association did not appear to be explained by several demographic, HIV or renal risk factors.

Facilitating Posttraumatic Growth After Critical Illness.

The theory of posttraumatic growth arose from accounts of various trauma survivors experiencing not only distress but also growth and change. An intensive care unit admission is an unplanned, sudden, and traumatic experience, and many survivors have posttraumatic stress that can lead to posttraumatic stress disorder. Survivors leave the intensive care unit with new functional impairments that drive depression, and they frequently experience anxiety. Amidst the stress of understanding the trauma of an intensive care unit admission, survivors can grow in their world views, relationships, and sense of self. Understanding posttraumatic growth in intensive care unit survivors will inform health care providers on how to help survivors understand their new difficulties after an intensive care unit stay and facilitate growth. This article is a conceptual review of posttraumatic growth, identifiers of posttraumatic growth, and how the tenets of the posttraumatic growth theory apply to intensive care unit survivors. Health care professionals, specifically nurses, can incorporate practices into their care during and after the intensive care unit stay that encourage understanding and positive accommodation of new difficulties brought on by the intensive care unit hospitalization to support survivor growth. Opportunities for research include incorporating posttraumatic growth assessments into post-intensive care unit clinics, self-help materials, and various programs or therapies. Outcomes associated with posttraumatic growth are listed to suggest directions for research questions concerning posttraumatic growth in intensive care unit survivors.