Key Points Question What are the humoral immune response rates and risk factors associated with diminished response after COVID-19 vaccination in recipients of solid organ transplant? Findings In this systematic review and meta-analysis of 29 studies and 11 713 recipients of solid organ transplant, seroconversion rates increased with progressively increased numbers of mRNA COVID-19 vaccine doses. Older age, recent transplantation, deceased donor status, active use of antimetabolites, and recent exposure to antithymocyte globulin or rituximab were risk factors associated with diminished humoral immune response after receiving 2 doses of mRNA vaccines. Meaning These findings suggest that more efforts are needed to modulate the risk factors associated with reduced humoral responses among recipients of solid organ transplant.

Background and objectivesIn 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, & measurementsWe 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.ResultsOut 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.ConclusionsIn 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.

Proteinuric kidney diseases are a group of disorders with diverse pathological mechanisms associated with significant losses of protein in the urine. The glomerular filtration barrier (GFB), comprised of the three important layers, the fenestrated glomerular endothelium, the glomerular basement membrane (GBM), and the podocyte, dictates that disruption of any one of these structures should lead to proteinuric disease. Podocytes, in particular, have long been considered as the final gatekeeper of the GFB. This specialized visceral epithelial cell contains a complex framework of cytoskeletons forming foot processes and mediate important cell signaling to maintain podocyte health. In this review, we will focus on slit diaphragm proteins such as nephrin, podocin, TRPC6/5, as well as cytoskeletal proteins Rho/small GTPases and synaptopodin and their respective roles in participating in the pathogenesis of proteinuric kidney diseases. Furthermore, we will summarize the potential therapeutic options targeting the podocyte to treat this group of kidney diseases.

AIMTo investigate the prevalence and association of Helicobacter pylori (H. pylori) with end-stage renal disease (ESRD).METHODSSA comprehensive literature search was completed from inception until October 2016. Studies that reported prevalence, relative risks, odd ratios, hazard ratios or standardized incidence ratio of H. pylori among ESRD patients were included. Participants without H. pylori were used as comparators to assess the association between H. pylori infection and ESRD. Pooled risk ratios and 95%CI was calculated using a random-effect model. Adjusted point estimates from each study were combined by the generic inverse variance method of DerSimonian and Laird.RESULTSOf 4546 relevant studies, thirty-seven observational studies met all inclusion criteria. Thirty-five cross-sectional studies were included in the analyses to assess the prevalence and association of H. pylori with ESRD. The estimated prevalence of H. pylori among ESRD patients was 44% (95%CI: 40%-49%). The pooled RR of H. pylori in patients with ESRD was 0.77 (95%CI: 0.59-1.00) when compared with the patients without ESRD. Subgroup analysis showed significantly reduced risk of H. pylori in adult ESRD patients with pooled RR of 0.71 (95%CI: 0.55-0.94). The data on the risk of ESRD in patients with H. pylori were limited. Two cohort studies were included to assess the risk of ESRD in patients with H. pylori. The pooled risk RR of ESRD in patients with H. pylori was 0.61 (95%CI: 0.03-12.20).CONCLUSIONThe estimated prevalence of H. pylori in ESRD patients is 44%. Our meta-analysis demonstrates a decreased risk of H. pylori in adult ESRD patients.

ObjectiveAdvanced kidney disease is associated with a high risk of morbidity and mortality. Consequently, invasive treatments such as dialysis may not yield survival benefits. Advance care planning has been encouraged. However, whether such discussions are acceptable when done earlier, before end-stage kidney treatment decision-making occurs, is unclear. This pilot study aimed to explore whether use of the Serious Illness Conversation Guide to aid early advance care planning is acceptable, and to evaluate the information gained from these conversations.MethodsPatients with advanced kidney disease (stage 3B and above) and high mortality risk at 2 years were enrolled in this mixed-methods study from an academic nephrology clinic. Semi-structured interviews were conducted using the adapted Serious Illness Conversation Guide. Thematic analysis was used to assess patients’ perceptions of the conversation. Participants completed a questionnaire assessing conversation acceptability.ResultsTwenty-six patients participated, 50% were female. Participants felt that the conversation guide helped them reflect on their prognosis, goals of care and treatment preferences. Most did not feel that the conversation provoked anxiety (23/26, 88%) nor that it decreased hopefulness (24/26, 92%). Some challenges were elicited; patients expressed cognitive dissonance with the kidney disease severity due to lack of symptoms; had difficulty conceptualising their goals of care; and vocalised fear of personal failure without attempting dialysis.ConclusionsPatients in this pilot study found the adapted Serious Illness Conversation Guide acceptable. This guide may be used with patients early in the course of advanced kidney disease to gather information for future advanced care planning.

The estimated prevalence of H. pylori in patients with non-dialysis-dependent kidney diseases is 53%. This study does not support the association between H. pylori infection and non-dialysis-dependent kidney diseases nor CKD.

Background: Acute kidney injury (AKI) is a significant complication of Coronavirus Disease 2019 (COVID-19), with no effective therapy. Niacinamide, a vitamin B3 analog, has some evidence of efficacy in non-COVID-19-related AKI. The objective of this study is to evaluate the association between niacinamide therapy and outcomes in patients with COVID-19-related AKI. Methods: We implemented a quasi-experimental design with non-random, prospective allocation of niacinamide in 201 hospitalized adult patients, excluding those with baseline estimated glomerular filtration rate <15 ml/min/1.73m2 on or off dialysis, with COVID-19-related AKI by Kidney Disease Improving Global Outcomes (KDIGO) criteria, in two hospitals with identical COVID-19 care algorithms, one of which additionally implemented treatment with niacinamide for COVID-19-related AKI. Patients on the niacinamide protocol (B3 patients) were compared against patients at the same institution before protocol commencement and contemporaneous patients at the non-niacinamide hospital (collectively, non-B3 patients). The primary outcome was a composite of death or renal replacement therapy (RRT). Results: 38/90 B3 patients and 62/111 non-B3 patients died or received RRT. Using multivariable Cox proportional hazard modeling, niacinamide was associated with a lower risk of RRT or death (HR 0.64, 95% CI 0.40 to 1.00, p=0.05), an association driven by patients with KDIGO stage 2/3 AKI (HR 0.29, 95% CI 0.13 to 0.65, p=0.03; p interaction with KDIGO stage 0.03). Total mortality also followed this pattern (HR 0.17, 95% CI 0.05-0.52 in KDIGO 2/3 patients, p=0.002). Serum creatinine following AKI increased by 0.20 (SE 0.08) mg/dL/day among non-B3 patients with KDIGO 2/3 AKI but was stable among comparable B3 patients (+0.01 (SE 0.06) mg/dL/day; p interaction 0.03). Conclusions: Niacinamide was associated with lower risk of RRT/death and improved creatinine trajectory among patients with severe COVID-19-related AKI. Larger randomized studies are necessary to establish a causal relationship.

AIMTo investigate the association between hepatitis C virus (HCV) infection and risk of renal cell carcinoma (RCC).METHODSA 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.RESULTSSeven 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).CONCLUSIONOur study demonstrated a potential association between HCV infection and RCC. Further studies of RCC surveillance in patients with HCV are required.