The anti-CD52 monoclonal antibody, alemtuzumab, is used as induction therapy for renal transplantation. Its use has been associated with autoimmune manifestations, particularly autoimmune cytopenias (AICs). Here, we report a single-center, retrospective analysis of patients who developed AICs after an alemtuzumab-induced renal transplant. Over a period of 8 years, 40 renal transplant patients developed immune thrombocytopenia (ITP) (n=28), autoimmune hemolytic anemia (AIHA) (n=7) or Evans syndrome (ES) (n=5), with two peaks of incidence, at 18 and 36 months after alemtuzumab. Response and relapse rates to standard first-line ITP and AIHA therapy were comparable to primary forms, with two thirds requiring second-line agents. Most patients with ITP who failed to go into remission after steroids or IVIG received either rituximab or a thrombopoietin receptor agonist (TPO-RA). Compared to primary ITP, a higher response rate (91.6%) and median duration of response (56 months) were achieved with rituximab; and a higher proportion of patients were able to discontinue TPO-RAs and maintain remission (50%). Most patients experienced one or more adverse events, most commonly, infections (62.5%), cardiovascular diseases (27.5%) and deep vein thrombosis (25%). In conclusion, AICs are a significant complication following alemtuzumab-induced renal transplantation, typically occurring within the 5-year period of immune reconstitution. Both rituximab and TPO-RAs show good efficacy, a few patients develop multi refractory disease, and the majority go into sustained remission off-treatment. Given that treatment is complicated by high rates of infections and thrombosis, supportive measures using antimicrobials as well as quick re-introduction of antiplatelet or anticoagulants in ITP and addition of anticoagulation in AIHA is recommended.

BACKGROUND:Solid organ transplant (SOT) recipients face elevated tuberculosis risk, yet optimal prevention strategies in low- to medium-incidence regions remain unclear. METHODS:We conducted a multicenter retrospective cohort study of adult SOT recipients transplanted between 2007 and 2012 at 15 European centers, with follow-up through 2018. The primary outcome was microbiologically confirmed post-transplant tuberculosis. Incidence rates were calculated per 100,000 person-years; standardized incidence ratios (SIRs) used World Health Organization country-specific background rates. Cox models assessed risk factors. RESULTS:Among 5805 patients (median age 51; 62.7% male; 73.9% renal transplants), 33.8% were tested for tuberculosis infection and 10.3% received tuberculosis preventive therapy (TPT). Over 33,785 person-years, 23 patients (0.4%) developed tuberculosis (68.0/100,000 person-years). Highest incidence occurred in patients with positive screening but no TPT (233.8/100,000). Incidence was higher in Southern vs. Central Europe (251.9 vs. 28.7/100,000), with pooled SIRs of 12.8 and 3.1, respectively. Tuberculosis risk was elevated among Southern European recipients (HR 22.9) and those with migration history (HR 2.7). CONCLUSION:Tuberculosis risk is increased in European SOT recipients. Regionally adapted prevention strategies, including targeted screening in low-incidence areas and universal screening in higher-incidence regions, are warranted.

BACKGROUND:Living donor kidney transplantation (LDKT) is considered the gold standard for treating end-stage kidney disease. Previous studies have highlighted the impact of donor and recipient demographics in influencing post-transplant outcomes. We believe that patient and graft outcomes in a tertiary university hospital setting will have no difference between pairs of standard criteria vs pairs of extended criteria (EC) donors and recipients in LDKT. AIM:To investigate the outcomes of allocating EC donation (ECD) kidneys to EC recipients (ECR) in LDKT and compare them to standard and mixed standard and EC pair counterparts. METHODS:We collected data from adult LDKTs conducted between April 2017 and April 2022. Donor-recipient pairs were grouped based on criteria as follows: (1) Group 1: Standard criteria donor (SCD) to standard criteria recipient (SCR); (2) Group 2: SCD to ECR; (3) Group 3: ECD to SCR; and (4) Group 4: ECD to ECR. RESULTS:A total of 149 living donor transplants were analysed over a 5-year period. Graft survival, patient survival, and graft function were similar across all four groups. The incidence of common postoperative complications was as follows: (1) Perioperative bleeding (5.6%); (2) Surgical site infection (6.8%); and (3) Incisional hernia (7.4%). No statistically significant differences were found in patient or graft outcomes amongst the four groups. Multivariate analysis showed that group 4 recipients might experience inferior 5-year graft function (β = -11.8, P = 0.037) when compared with group 1. CONCLUSION:In LDKT, long-term patient and graft outcomes are comparable amongst different combinations of standard vs EC donors and recipients. These findings show the primary potential of living donor ECD to ECR kidney transplantation with satisfying outcomes.

ABSTRACT Background Light chain proximal tubulopathy (LCPT) is a rare form of paraprotein-related disease, occurring in two main histopathological forms: crystalline and non-crystalline. The clinicopathological features, treatment strategies and outcomes, especially of the non-crystalline form, are not well described. Methods We conducted a single-centre retrospective case series of 12 LCPT patients, 5 crystalline and 7 non-crystalline, between 2005 and 2021. Results The median age was 69.5 years (range 47–80). Ten patients presented with CKD and significant proteinuria (median estimated glomerular filtration rate of 43.5 ml/min/1.73 m2; urine protein:creatinine ratio 328 mg/mmol). Only six patients had known haematological disease at the time of renal biopsy. Multiple myeloma (MM) was diagnosed in seven patients cases and monoclonal gammopathy of renal significance (MGRS) in five patients. A clone was detected in all cases combining serum/urine electrophoresis and free light chain (LC) assays. Crystalline and non-crystalline variants had similar clinical presentations. For the non-crystalline variant, a diagnosis was reached based on a combination of CKD without another cause, haematological workup, LC restriction on immunofluorescence and abnormalities on electron microscopy (EM). Nine of 12 patients received clone-directed treatment. Patients who achieved haematological response (including all non-crystalline LCPT) had improved renal outcomes over a median follow-up of 79 months. Conclusions The non-crystalline variant may go unrecognised because of its subtle histopathological features and requires EM to distinguish it from ‘excessive LC resorption without tubular injury’. Clone-directed treatment with good haematological response improves renal outcomes in both variants but limited data exist in MGRS. Multicentre prospective studies are needed to better define the clinicopathological characteristics associated with poor outcomes and optimize treatment strategies in patients with MGRS.

Urinary tract infections(UTI) are the most common cause of infection in kidney transplant recipients1. Recurrent UTIs are not only a significant cause of morbidity and mortality in renal transplant recipients2, but are associated with loss of graft function3. Independent risk factors for recurrent UTIs are age, gender, urological abnormalities, and a pre-transplant history of recurrent UTIs4. Prophylactic antibiotics predispose to antibiotic resistance2, while D-mannose5 and faecal microbiota transplantation(FMT) are not a resolution6.

Background Latent TB infection (LTBI) remains an important reservoir of TB even in low incidence countries. The prevalence of latent infection is higher in patients with chronic kidney disease and those receiving dialysis.1 Those with LTBI on renal replacement therapy (RRT) are known to have higher risks of reactivation to active disease.2 Our centre data has shown risk is highest within the first 24 months of initiating RRT. At present there is no uniform TB screening and with ad hoc testing by clinicians. Aim Feasibility and yield of screening new dialysis starters for LTBI with a QuantiFERON blood test. Methods This analysis is between the period 1st May 2021 and 30th April 2022 at our group of West London based dialysis centres as we started to implement this new pathway. Within the first three months of dialysis initiation a QuantiFERON blood test is included as part of routine initiation or monthly infection screening. Positive and recurrent indeterminate results are referred to the TB service. Comorbidities and individual risk factors are collected through electronic patient records. Results 464 patients have started dialysis during this time. 371 haemodialysis patients, 93 peritoneal dialysis. There has been a gradual increase in monthly QuantiFERON testing as awareness of the pilot has increased (6–17 tests performed per month). 107/464 (23%) patients have now had a QuantiFERON test. A schematic of the results are shown in the figure below. Conclusions Our pilot has shown routine testing for LTBI can be implemented in this high risk group and has allowed a significant proportion (14%) of high risk individuals to be assessed by a TB clinician and the multi-disciplinary team. Suitable patients are offered latent TB treatment or may be investigated for active infection. References Getahun, H., Matteelli, A., Chaisson, R.E., Raviglione, M., 2015. Latent Mycobacterium tuberculosis Infection. New England Journal of Medicine 372, 2127–2135. doi:10.1056/nejmra1405427 Horsburgh CR Jr, Rubin EJ. Clinical practice. Latent tuberculosis infection in the United States. N Engl J Med. 2011 Apr 14;364(15):1441–8. doi: 10.1056/NEJMcp1005750. PMID: 21488766.

BACKGROUND AND OBJECTIVES:In patients with chronic kidney disease the risk of developing Tuberculosis is increased, while the presentation is often atypical making the diagnosis more difficult. The aim of this study is to describe the presentation of Tuberculosis in dialysis and kidney transplant patients, including the range of diagnostic approaches and the utility of different sample types.DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS:In this retrospective study, case records of dialysis and kidney transplant patients were reviewed, including all those treated for Tuberculosis between January 2009 and December 2020.RESULTS:Over 12 years, there were 143 cases of Tuberculosis in 141 patients (aged 17-86, 50.4% male). Tuberculosis was most common in Asian patients (64%) and those receiving hemodialysis (82%), particularly during the first year after dialysis initiation (54% of dialysis cases). Non-pleural/pulmonary disease accounted 40% of cases, and non-organ-specific presenting features were prominent including fever, lymphadenopathy, and weight loss. The diagnosis was confirmed microbiologically or histologically in 87 cases (61%), with low sensitivity observed for many types of samples including sputum (18%) and pleural fluid (12%). Higher sensitivity was observed with tissue samples including bronchoscopic lymph node aspiration (75%) and other lymph node sampling (92%). In the 52 cases where drug sensitivities were available, resistance to a first line treatment, most commonly isoniazid, was seen in 12 cases (23%). Furthermore, 1- and 5-year survival from diagnosis were 78% and 61%, respectively. Baseline variables independently associated with poorer survival were age (OR 1.8 per decade, 95% CI 1.4-2.3), weight loss over 10% (OR 1.9, 95% CI 1.0-3.5), and a non-confirmed diagnosis (OR 1.6, 95% CI 1.2-2.1).CONCLUSIONS:Tuberculosis is common in dialysis and kidney transplant patients, particularly during the first year of dialysis. Short-term mortality is high, but the diagnostic sensitivity of many types of samples is low, so that diagnosis is difficult, with treatment often initiated without confirmation. These data highlight the importance of judgment and clinical experience with this complex patient group.

The incidence of active tuberculosis (TB) post renal transplantation is much higher than the general population. This has previously been described as presenting in the first year following solid organ transplantation and is predominantly due to reactivation of latent TB infection (LTBI)(1). Diagnosis can be challenging in this patient group who may present with atypical presentations or extra-pulmonary infection. Our aim was to assess the active TB incidence in our post renal transplant population. In our London based renal transplant centre, retrospective data was collected including demographic data, site of disease and culture positivity. Electronic patient records and our TB database was analysed for case details for rates of active TB. A total of 2311 patients received renal or simultaneous pancreas kidney transplantation between November 2005 and July 2019. At the time of analysis all patients had at least one year follow up post renal transplantation. In total, 8 patients were treated for active TB. Of these patients the median time to TB diagnosis was 4.35 years (IQR 1.125–6.2). None were screened for latent TB but 4 were on prophylactic isoniazid 150 mg od at the time of diagnosis; of which 2 developed isoniazid resistant disease. A total of 3 cases were culture confirmed tuberculosis. 6/8 cases were extra-pulmonary TB. There was 1 graft rejection and 2 graft losses, none were attributed to TB. In our cohort, the rate of TB remains comparable to historic data (cumulative rate of 0.36%) however the time to diagnosis was longer than expected, suggesting possible re-exposure. Within our patients who received chemoprophylaxis, there was a high rate of isoniazid resistance. We have worked towards improving pre-transplant screening, appropriate interferon gamma release assay (IGRA) assessment in addition to standardising latent TB treatment. Patients with previous TB or at high risk due to ethnic or geographical background receive TB prophylaxis with isoniazid 300 mg OD and pyridoxine 50 mg once a week for 1 year post transplant. Reference Abad CLR, Razonable RR. Mycobacterium tuberculosis after solid organ transplantation: A review of more than 2000 cases. Clin Transplant. 2018;32(6):e13259. doi:10.1111/ctr.13259

Patients with end stage kidney disease receiving in-center hemodialysis (ICHD) have had high rates of SARS-CoV-2 infection. Following infection, patients receiving ICHD frequently develop circulating antibodies to SARS-CoV-2, even with asymptomatic infection. Here, we investigated the durability and functionality of the immune responses to SARS-CoV-2 infection in patients receiving ICHD. Three hundred and fifty-six such patients were longitudinally screened for SARS-CoV-2 antibodies and underwent routine PCR-testing for symptomatic and asymptomatic infection. Patients were regularly screened for nucleocapsid protein (anti-NP) and receptor binding domain (anti-RBD) antibodies, and those who became seronegative at six months were screened for SARS-CoV-2 specific T-cell responses. One hundred and twenty-nine (36.2%) patients had detectable antibody to anti-NP at time zero, of whom 127 also had detectable anti-RBD. Significantly, at six months, 71/111 (64.0%) and 99/116 (85.3%) remained anti-NP and anti-RBD seropositive, respectively. For patients who retained antibody, both anti-NP and anti-RBD levels were reduced significantly after six months. Eleven patients who were anti-NP seropositive at time zero, had no detectable antibody at six months; of whom eight were found to have SARS-CoV-2 antigen specific T cell responses. Independent of antibody status at six months, patients with baseline positive SARS-CoV-2 serology were significantly less likely to have PCR confirmed infection over the following six months. Thus, patients receiving ICHD mount durable immune responses six months post SARS-CoV-2 infection, with fewer than 3% of patients showing no evidence of humoral or cellular immunity.

The incidence of active tuberculosis (TB) post renal transplantation is much higher than the general population. This has previously been described as presenting in the first year following solid organ transplantation and is predominantly due to disease reactivation. Diagnosis can be challenging in this patient group who may present with atypical presentations or extra-pulmonary infection. In a London based renal transplant centre, retrospective data was collected including demographic data, site of disease and culture positivity. Electronic patient records and our TB database was analysed for case details for rates of active TB. A total of 2199 patients received renal transplantation between November 2005 to December 2018 of which, 8 patients were treated for active TB. Of these patients the median time to TB diagnosis was 4.35 years (IQR 1.125-6.2). None were screened for latent TB but 4 were on prophylactic isoniazid 150mg od at the time of diagnosis; of which 2 developed isoniazid resistant disease. A total of 3 cases were culture confirmed. 6/8 cases were extrapulmonary TB. There was 1 graft rejection and 2 graft losses. In our cohort, the rate of TB remains comparable to historic data however the time to diagnosis was longer than expected, suggesting possible re-exposure. Within our patients who received chemoprophylaxis, there was a high rate of isoniazid resistance and hence isoniazid use and a higher dose needs to be considered.

Introduction: There are limited data pertaining to comparative outcomes of remaining on dialysis versus kidney transplantation as the threat of coronavirus disease 2019 (COVID-19) remains. In this study we delineate the differential risks involved using serologic methods to help define exposure rates. Methods: From a cohort of 1433 patients with end-stage kidney disease (ESKD), we analyzed COVID-19 infection rates and outcomes in 299 waitlist patients compared with 237 transplant recipients within their first year post-transplant. Patients were followed over a 68-day period from the time our transplant program closed due to COVID-19. Results: The overall mortality rates in waitlist and transplant populations were equivalent (P = 0.69). However, COVID-19 infection was more commonly diagnosed in the waitlist patients (P= 0.001), who were more likely to be tested by reverse transcriptase polymerase chain reaction (P= 0.0004). Once infection was confirmed, mortality risk was higher in the transplant patients (P = 0.015). The seroprevalence in dialysis and transplant patients with undetected infection was 18.3% and 4.6%, respectively (P = 0.0001). After adjusting for potential screening bias, the relative risk of death after a diagnosis of COVID-19 remained higher in transplant recipients (hazard ratio = 3.36 [95% confidence interval = 1.19-9.50], P= 0.022). Conclusions: Although COVID-19 infection was more common in the waitlist patients, a higher COVID-19- associated mortality rate was seen in the transplant recipients, resulting in comparable overall mortality rates.

Background: An intrathoracic kidney is a very rare form of ectopic kidney. Though increasingly recognized in the literature, impact on renal function is less well described. We report the case of a 67-year-old South Asian gentleman who presented with intrathoracic kidney and chronic kidney disease. We carried out a systematic review of the available literature on intrathoracic kidney, in order to characterize the typical clinical features, and describe likely clinical course and possible renal and extra-renal complications associated with this form of ectopia. Materials and methods: A structured search using PubMed identified all relevant published case reports from 1988 to 2018, with search restricted to papers in English, and to adult cases only (> 18 years of age). 124 records were identified, and after screening for eligibility, 34 case reports were analyzed. Results: Median age was 53.5 years, with no gender predominance. 68% (27/34) of cases were symptomatic. 29% (10/34) had a significant complication associated with their intrathoracic kidney, with 3 cases with either documented chronic or end-stage kidney disease. 26% (9/34) required surgical intervention. Conclusion: Though previously regarded as a benign entity, results from our systematic review, bearing in mind susceptibility to publication bias, suggests an appreciable risk of symptoms, complications, and in the minority a risk to kidney function. We recommend close biochemical and imaging surveillance of affected patients, with low threshold for intervention in those with renovascular stenosis, reflux, or hydronephrosis.