Recurrence of membranous nephropathy after kidney transplantation: A multicenter retrospective cohort study.

Membranous nephropathy (MN) is a leading cause of kidney failure worldwide and frequently recurs after transplant. Available data originated from small retrospective cohort studies or registry analyses; therefore, uncertainties remain on risk factors for MN recurrence and response to therapy. Within the Post-Transplant Glomerular Disease Consortium, we conducted a retrospective multicenter cohort study examining the MN recurrence rate, risk factors, and response to treatment. This study screened 22,921 patients across 3 continents and included 194 patients who underwent a kidney transplant due to biopsy-proven MN. The cumulative incidence of MN recurrence was 31% at 10 years posttransplant. Patients with a faster progression toward end-stage kidney disease were at higher risk of developing recurrent MN (hazard ratio [HR], 0.55 per decade; 95% confidence interval [CI], 0.35-0.88). Moreover, elevated pretransplant levels of anti-phospholipase A2 receptor (PLA2R) antibodies were strongly associated with recurrence (HR, 18.58; 95% CI, 5.37-64.27). Patients receiving rituximab for MN recurrence had a higher likelihood of achieving remission than patients receiving renin-angiotensin-aldosterone system inhibition alone. In sum, MN recurs in one-third of patients posttransplant, and measurement of serum anti-PLA2R antibody levels shortly before transplant could aid in risk-stratifying patients for MN recurrence. Moreover, patients receiving rituximab had a higher rate of treatment response.

Distinct phenotypes of kidney transplant recipients aged 80 years or older in the USA by machine learning consensus clustering.

Objectives: This study aimed to identify distinct clusters of very elderly kidney transplant recipients aged ≥80 and assess clinical outcomes among these unique clusters. Design: Cohort study with machine learning (ML) consensus clustering approach. Setting and participants: All very elderly (age ≥80 at time of transplant) kidney transplant recipients in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database database from 2010 to 2019. Main outcome measures: Distinct clusters of very elderly kidney transplant recipients and their post-transplant outcomes including death-censored graft failure, overall mortality and acute allograft rejection among the assigned clusters. Results: Consensus cluster analysis was performed in 419 very elderly kidney transplant and identified three distinct clusters that best represented the clinical characteristics of very elderly kidney transplant recipients. Recipients in cluster 1 received standard Kidney Donor Profile Index (KDPI) non-extended criteria donor (ECD) kidneys from deceased donors. Recipients in cluster 2 received kidneys from older, hypertensive ECD deceased donors with a KDPI score ≥85%. Kidneys for cluster 2 patients had longer cold ischaemia time and the highest use of machine perfusion. Recipients in clusters 1 and 2 were more likely to be on dialysis at the time of transplant (88.3%, 89.4%). Recipients in cluster 3 were more likely to be preemptive (39%) or had a dialysis duration less than 1 year (24%). These recipients received living donor kidney transplants. Cluster 3 had the most favourable post-transplant outcomes. Compared with cluster 3, cluster 1 had comparable survival but higher death-censored graft failure, while cluster 2 had lower patient survival, higher death-censored graft failure and more acute rejection. Conclusions: Our study used an unsupervised ML approach to cluster very elderly kidney transplant recipients into three clinically unique clusters with distinct post-transplant outcomes. These findings from an ML clustering approach provide additional understanding towards individualised medicine and opportunities to improve care for very elderly kidney transplant recipients.

Immunogenicity of SARS-CoV-2 vaccines in patients with multiple myeloma: a systematic review and meta-analysis.

Patients with multiple myeloma (MM) have a diminished immune response to coronavirus disease 2019 (COVID-19) vaccines. Risk factors for an impaired immune response are yet to be determined. We aimed to summarize the COVID-19 vaccine immunogenicity and to identify factors that influence the humoral immune response in patients with MM. Two reviewers independently conducted a literature search in MEDLINE, Embase, ISI Web of Science, Cochrane library, and Clinicaltrials.gov from existence until 24 May 24 2022. (PROSPERO: CRD42021277005). A total of 15 studies were included in the systematic review and 5 were included in the meta-analysis. The average rate (range) of positive functional T-lymphocyte response was 44.2% (34.2%-48.5%) after 2 doses of messenger RNA (mRNA) COVID-19 vaccines. The average antispike antibody response rates (range) were 42.7% (20.8%-88.5%) and 78.2% (55.8%-94.2%) after 1 and 2 doses of mRNA COVID-19 vaccines, respectively. The average neutralizing antibody response rates (range) were 25% (1 study) and 62.7% (53.3%-68.6%) after 1 and 2 doses of mRNA COVID-19 vaccines, respectively. Patients with high-risk cytogenetics or receiving anti-CD38 therapy were less likely to have a humoral immune response with pooled odds ratios of 0.36 (95% confidence interval [95% CI], 0.18, 0.69), I2 = 0% and 0.42 (95% CI, 0.22, 0.79), I2 = 14%, respectively. Patients who were not on active MM treatment were more likely to respond with pooled odds ratio of 2.42 (95% CI, 1.10, 5.33), I2 = 7%. Patients with MM had low rates of humoral and cellular immune responses to the mRNA COVID-19 vaccines. Further studies are needed to determine the optimal doses of vaccines and evaluate the use of monoclonal antibodies for pre-exposure prophylaxis in this population.

Protocol-based donor-derived cell-free DNA surveillance in kidney transplant recipients: A single-center experience.

AIMS: Donor-derived cell-free DNA (dd-cfDNA) surveillance testing has never been studied in comparison with other surveillance tests. In this study we aim to describe our center's clinical experience with routine dd-cfDNA monitoring and to assess whether monitoring dd-cfDNA by protocol provides additional information that aids in detection of acute rejection. MATERIALS AND METHODS: We implemented the dd-cfDNA (Allosure) surveillance protocol in addition to measurements of serum creatinine, proteinuria, and donor-Specific antibody. We retrospectively reviewed all kidney recipients transplanted from July 2018 to April 2020. 366 dd-cfDNA test results were reviewed from 82 patients. RESULTS: There were 13/366 positive dd-cfDNA tests in 8/82 patients. Five of the 8 patients had kidney biopsy which showed: 3 rejections (1 antibody-mediated rejection, 1 T-cell-mediated rejection, and 1 mixed), 1 acute tubular necrosis, and 1 transplant glomerulopathy. The remaining 3 patients did not undergo a biopsy and repeat dd-cfDNA testing improved without intervention. In the 353/366 negative dd-cfDNA tests in 74 patients: 7 patients underwent a biopsy: 1 patient with increased creatinine showed borderline cellular rejection, 3 had recurrent disease (membranoproliferative glomerulonephritis, diabetes mellitus, immunoglobulin A nephropathy), and 3 showed interstitial fibrosis and tubular atrophy. dd-cfDNA levels were not elevated in recipients with infection (BK viruria/viremia, CMV viremia, or urinary tract infection (UTI). CONCLUSION: The addition of surveillance dd-cfDNA testing resulted in marginal added benefit. Whether this offsets the cost of testing needs to be further explored. In our cohort of low-risk patients, the cost of protocol dd-cfDNA testing may not be justified by its limited benefits.

Recurrence of IgA Nephropathy after Kidney Transplantation in Adults.

BACKGROUND AND OBJECTIVES: In patients with kidney failure due to IgA nephropathy, IgA deposits can recur in a subsequent kidney transplant. The incidence, effect, and risk factors of IgA nephropathy recurrence is unclear, because most studies have been single center and sample sizes are relatively small. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a multicenter, international, retrospective study to determine the incidence, risk factors, and treatment response of recurrent IgA nephropathy after kidney transplantation. Data were collected from all consecutive patients with biopsy-proven IgA nephropathy transplanted between 2005 and 2015, across 16 "The Post-Transplant Glomerular Disease" study centers in Europe, North America, and South America. RESULTS: Out of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients; cumulative incidence of recurrence was 23% at 15 years (95% confidence interval, 14 to 34). Multivariable Cox regression revealed a higher risk for recurrence of IgA deposits in patients with a pre-emptive kidney transplant (hazard ratio, 3.45; 95% confidence interval, 1.31 to 9.17) and in patients with preformed donor-specific antibodies (hazard ratio, 2.59; 95% confidence interval, 1.09 to 6.19). After kidney transplantation, development of de novo donor-specific antibodies was associated with subsequent higher risk of recurrence of IgA nephropathy (hazard ratio, 6.65; 95% confidence interval, 3.33 to 13.27). Immunosuppressive regimen was not associated with recurrent IgA nephropathy in multivariable analysis, including steroid use. Graft loss was higher in patients with recurrence of IgA nephropathy compared with patients without (hazard ratio, 3.69; 95% confidence interval, 2.04 to 6.66), resulting in 32% (95% confidence interval, 50 to 82) graft loss at 8 years after diagnosis of recurrence. CONCLUSIONS: In our international cohort, cumulative risk of IgA nephropathy recurrence increased after transplant and was associated with a 3.7-fold greater risk of graft loss.

ANCA and IgA glomerulonephritis all in one: prognosis and complications.

We present the case of a 75-year-old Hispanic woman with known stage 3 chronic kidney disease, long-standing hypertension and type 2 diabetes mellitus who presented with right-sided abdominal pain and acute kidney injury, nephrotic range proteinuria with positive antimyeloperoxidase antibody. A renal biopsy revealed IgA nephropathy with superimposed pauci-immune antineutrophilic cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis. The patient was treated with pulse intravenous methylprednisolone, cyclophosphamide and plasmapheresis. One week after her second dose of cyclophosphamide, she was readmitted for infectious complications including influenza A respiratory infection, Rothia bacteraemia associated with diarrhoea and herpes zoster of the trunk. In this report, we review the prevalence, treatment and prognosis of coexistent IgA nephropathy and pauci-immune ANCA-associated crescentic glomerulonephritis. We propose that a reduced-dose treatment regimen should be considered in elderly patients due to their higher risk of infectious complications. Current literature suggests that this treatment approach may reduce infectious complications without compromising therapeutic efficacy.

Hepatitis C infection and renal cell carcinoma: A systematic review and meta-analysis.

AIM: To investigate the association between hepatitis C virus (HCV) infection and risk of renal cell carcinoma (RCC). METHODS: A literature search was performed from inception until February 2016. Studies that reported relative risks, odd ratios, hazard ratios or standardized incidence ratio comparing the risk of RCC among HCV-infected participants vs those without HCV infection were included. Participants without HCV infection were used as comparators. Pooled odds ratios and 95%CI were calculated using a random-effect, generic inverse variance method. RESULTS: Seven observational studies were with 196826 patients were included in the analysis to assess the risk of RCC in patients with HCV. A significantly increased risk of RCC among participants with HCV infection was found with a pooled RR of 1.86 (95%CI: 1.11-3.11). The association between RCC and HCV was marginally insignificant after a sensitivity analysis limited only to studies with adjusted analysis, with a pooled RR of 1.50 (95%CI: 0.93-2.42). CONCLUSION: Our study demonstrated a potential association between HCV infection and RCC. Further studies of RCC surveillance in patients with HCV are required.