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 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.

Factors Governing the Erythropoietic Response to Intravenous Iron Infusion in Patients with Chronic Kidney Disease: A Retrospective Cohort Study.

BACKGROUND: Limited knowledge exists about factors affecting parenteral iron response. A study was conducted to determine the factors influencing the erythropoietic response to parenteral iron in iron-deficient anaemic patients whose kidney function ranged from normal through all stages of chronic kidney disease (CKD) severity. METHODS: This retrospective cohort study included parenteral iron recipients who did not receive erythropoiesis-stimulating agents (ESA) between 2017 and 2019. The study cohort was derived from two groups of patients: those managed by the CKD team and patients being optimised for surgery in the pre-operative clinic. Patients were categorized based on their kidney function: Patients with normal kidney function [estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2] were compared to those with CKD stages 3-5 (eGFR < 60 mL/min/1.73 m2). Patients were further stratified by the type of iron deficiency [absolute iron deficiency (AID) versus functional iron deficiency (FID)]. The key outcome was change in hemoglobin (∆Hb) between pre- and post-infusion haemoglobin (Hb) values. Parenteral iron response was assessed using propensity-score matching and multivariate linear regression. The impact of kidney impairment versus the nature of iron deficiency (AID vs. FID) in response was explored. RESULTS: 732 subjects (mean age 66 ± 17 years, 56% females and 87% White) were evaluated. No significant differences were observed in the time to repeat Hb among CKD stages and FID/AID patients. The Hb rise was significantly lower with lower kidney function (non-CKD and CKD1-2; 13 g/L, CKD3-5; 7 g/L; p < 0.001). When groups with different degrees of renal impairment were propensity-score matched according to whether iron deficiency was due to AID or FID, the level of CKD was found not to be relevant to Hb responses [unmatched (∆Hb) 12.1 vs. 8.7 g/L; matched (∆Hb) 12.4 vs. 12.1 g/L in non-CKD and CKD1-2 versus CKD3-5, respectively]. However, a comparison of patients with AID and FID, while controlling for the degree of CKD, indicated that patients with FID exhibited a diminished Hb response regardless of their level of kidney impairment. CONCLUSION: The nature of iron deficiency rather than the severity of CKD has a stronger impact on Hb response to intravenous iron with an attenuated response seen in functional iron deficiency irrespective of the degree of renal impairment.

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.

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.

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.

Recurrent glomerulonephritis after renal transplantation.

PURPOSE OF REVIEW: The current understanding of the incidence, predisposing factors, pathophysiology and effective treatment of recurrent glomerulonephritis (RGN) in renal transplants remains at best patchy and at worst, completely lacking. Current reports have been limited by inconsistencies in study design, sample populations and lengths of follow-up. Making sense of the available evidence will provide the tools to support transplant nephrologists in their management of allograft donors and recipients. RECENT FINDINGS: With better survival of renal allografts, RGN has become a dominant factor influencing allograft survival. Evidently, the risk of recurrence is proportional to the incremental time posttransplantation. The proposed risk factors for RGN include but are not limited to the severity of primary glomerulonephritis (PGN), younger recipient age, live-related donor allograft, minimal HLA mismatch, steroid avoidance and nonuse of induction therapy. Unfortunately, these findings are derived from retrospective cohort and registry studies; hence, true causality for RGN is hard to prove. SUMMARY: The management of RGN is improving, as we gain greater understanding of its pathophysiology, including the genetic, alloimmune and autoimmune contributions to recurrence. With better pretransplant risk stratification, posttransplant surveillance, novel biomarkers and new treatment strategies, we hope the transplant community will eventually have the tools to predict risk, prevent recurrence and personalise treatment of RGN.

Heart failure and acute renal dysfunction in the cardiorenal syndrome.

Just under 1 million people in the UK have symptomatic heart failure. Decompensated heart failure is associated with a particularly poor prognosis with in-hospital mortality at around 10%. Over the last 30 years renin-angiotensin-aldosterone system antagonists have been shown to have incremental benefit on improved quality of life, reduced hospitalisation and mortality rates in those with heart failure with reduced ejection fraction. Concomitant chronic kidney disease and 'acute kidney injury' are common and associated with adverse outcomes.In patients with decompensated heart failure, congestion is a key driver of deterioration in renal function. Decongestion is fundamental to successful management. Yet it is not uncommon to see prognostically important medication (such as angiotensin converting enzyme inhibitors and mineralocorticoid antagonists) inappropriately stopped, along with under-diuresis of the patient. This leaves the patient still in a state of congestion without the prognostic medication at discharge, with resultant adverse outcome. The British Society for Heart Failure and the Renal Association have produced consensus guidance to help guide management in a more consistent fashion based on heart failure classification, whether the patient is congested and the degree of renal impairment. Early heart failure specialist review is associated with improved patient outcomes.