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.

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.

Cardiovascular, metabolic and kidney disease: crosscutting science and best practice in multimorbidity - a multispecialty conference at the Royal College of Physicians.

Patients with multimorbidity are increasingly encountered, especially with an ageing population and the co-segregation of lifestyle diseases such as diabetes, obesity and hypertension, but the care of these patients is fragmented and research rarely undertaken within this group. Research into genetic biomarkers and the evolution of crosscutting multiorgan science, resulting in collaboration between specialties for the treatment of patients with multimorbidity, should be the next major step change in medicine. Evolving technology is making this possible. However, there is a necessity to instigate more collaborative multispecialty research efforts to provide the evidence needed to move treatment possibilities forward, leading to the capability for a major redesign of clinical practice. The patient must be at the centre of a new, radically changed and holistic journey and collaborative research with primary care is essential, as general practitioners and primary care colleagues are the experts dealing with common multimorbidities, including those due to long-term poor lifestyle.

Prevalence and outcomes of proton pump inhibitor associated hypomagnesemia in chronic kidney disease.

BACKGROUND: Proton pump inhibitors (PPIs) are one of the most widely prescribed medications across the world. PPIs have been associated with significant electrolyte abnormalities including hypomagnesaemia. We explored the prevalence of PPI associated hypomagnesaemia (PPIH) in different Chronic Kidney Disease (CKD) stages, in different PPI agents, and the impact of PPIH on survival in CKD. METHODS: This was a subgroup analysis of the Salford Kidney Study, a prospective, observational, longitudinal study of non-dialysis CKD patients. Patients with outpatient magnesium samples obtained between 2002 and 2013 were included in the analysis. The prevalence hypomagnesaemia based on mean values over 12 months as well as 'ever' hypomagnesaemia were investigated. RESULTS: 1,230 patients were included in this analysis, mean age 64.3± 32.3 years and mean eGFR 29.2±15.8 ml/min/1.73m2. Mean serum magnesium in those on PPI was significantly lower than those not on PPI overall (0.85±0.10 mmolL-1 versus 0.79±0.12 mmolL-1 respectively, p<0.001). This finding was maintained at all CKD stages. The adjusted odds ratio (OR) for mean hypomagnesaemia in PPI use was 1.12 (95% CI 1.06-1.18) p = <0. 'Ever hypomagnesaemia' had an OR of 1.12 (95% CI 1.07-1.16) p = <0.001. The expected rise in serum magnesium with declining eGFR was not observed in those on a PPI but was seen in those not on PPI. There was no difference in serum magnesium between PPI drugs. Thiazide diuretics were also associated with hypomagnesaemia independent of PPI use. Cox regression analysis demonstrated no reduction in survival in patients with PPI associated hypomagnesaemia. CONCLUSION: No specific PPI drugs show a favourable profile in regards of risk for hypomagnesaemia in CKD. Avoiding concurrent use of PPI and thiazide may be of value in patients with hypomagnesaemia.