A 78-Year-Old Man with Chronic Kidney Disease and Monoclonal Gammopathy Who Developed Post-Transplant C3 Glomerulopathy - Recurrence or De Novo? A Case Report and Literature Review.

BACKGROUND The incidence of glomerular disease recurrence in kidney transplant patients varies according to type of glomerulopathy; therefore, it is important to know the primary chronic kidney disease etiology. C3 glomerulopathy (C3G) is characterized by deposits of C3 in immunofluorescence and its pathogeny is based on the dysregulation of the alternative complement pathway. C3G has a high recurrence rate and, given its low prevalence, only case series have been published. A higher rate of recurrence and a more aggressive course have been described in association with monoclonal gammopathy (MG). CASE REPORT We describe the case of a 78-year-old man with chronic kidney disease of unknown etiology (no significant proteinuria) and monoclonal IgGl gammopathy with low risk of progression, who received a kidney transplant, presenting accelerated deterioration of kidney function. Histopathology showed predominant C3 deposits in immunofluorescence, compatible with C3 glomerulonephritis (C3GN). He was treated with eculizumab during 4 weeks while the study was completed. The response to treatment was not favorable and the patient remained in the dialysis program. CONCLUSIONS Further studies are needed to explain the pathogenic mechanisms of complement alternative pathway dysregulation mediated by monoclonal component in patients with C3GN and MG. Patients older than 50 years who are on a waiting list for kidney transplantation should have an MG detection study. The information provided to patients with MG on a waiting list for kidney transplantation should include not only the possibility of hematologic progression but also the recurrence/de novo appearance of associated kidney pathology.

Evolving spectrum but persistent high mortality of COVID-19 among patients on kidney replacement therapy in the vaccine era: the Spanish COVID-19 KRT Registry.

Background: Kidney replacement therapy (KRT) conferred a high risk for coronavirus disease 2019 (COVID-19) related mortality early in the pandemic. We evaluate the presentation, treatment and outcomes of COVID-19 in patients on KRT over time during the pandemic. Methods: This registry-based study involved 6080 dialysis and kidney transplant (KT) patients with COVID-19, representing roughly 10% of total Spanish KRT patients. Epidemiology, comorbidity, infection, vaccine status and treatment data were recorded, and predictors of hospital admission, intensive care unit (ICU) admission and mortality were evaluated. Results: Vaccine introduction decreased the number of COVID-19 cases from 1747 to 280 per wave. Of 3856 (64%) COVID-19 KRT patients admitted to the hospital, 1481/3856 (38%) were admitted during the first of six waves. Independent predictors for admission included KT and the first wave. During follow-up, 1207 patients (21%) died, 500/1207 (41%) during the first wave. Among vaccinated patients, mortality was 19%, mostly affecting KT recipients. Overall, independent predictors for mortality were older age, disease severity (lymphopaenia, pneumonia) and ICU rejection. Among patient factors, older age, male sex, diabetes, KT and no angiotensin receptor blockers (ARB) were independent predictors of death. In KT recipients, individual immunosuppressants were independent predictors of death. Over time, patient characteristics evolved and in later pandemic waves, COVID-19 was mainly diagnosed in vaccinated KT recipients; in the few unvaccinated dialysis patients, ICU admissions increased and mortality decreased (28% for the first wave and 16-22% thereafter). Conclusions: The clinical presentation and outcomes of COVID-19 during the first wave no longer represent COVID-19 in KRT patients, as the pandemic has become centred around vaccinated KT recipients. Vaccines lowered the incidence of diagnosed COVID-19 and mortality. However, mortality remains high despite increased access to ICU care.

The role of relief, perceived control, and prospective intolerance of uncertainty in excessive avoidance in uncertain-threat environments.

Excessive avoidance is a key feature of pathological anxiety. However, the precise mechanisms underlying the development of excessive avoidance are still unknown. In the present study, we tested the hypothesis that excessive avoidance, especially in individuals with high Intolerance of Uncertainty (IU) is aimed at distress reduction via the enhancement of subjective perceived control in uncertain-threat environments. In our experiment, participants learned to avoid an uncertain aversive sound through a discriminated free operant procedure. In a later test phase in extinction, we manipulated the amount of avoidance responses available per trial by creating a limited and an unrestricted response condition. Nonetheless, the aversive sound could be effectively avoided in both conditions. We measured response frequency, avoidance confidence ratings and anxiety-predisposing traits such as intolerance of uncertainty, trait anxiety and distress tolerance. The degree of distress suffered during trials was inferred from post-trial relief ratings that were requested after trials in which the aversive sound had been omitted. In the avoidance acquisition phase, we found a positive association between prospective intolerance of uncertainty (P-IU) and the decline rate of distress. This relationship was not significant, however, when inhibitory intolerance of uncertainty (I-IU) was controlled for. At test, we found that the increase in avoidance responses led to distress reduction through the enhancement of avoidance confidence. Finally, we found a significant modulating role of P-IU in the effect of response limit on distress reduction that lends further support to our hypothesis. Specifically, P-IU was positively associated with the effect of response limit on distress. However, such modulating role was not significant when controlling for trait anxiety or I-IU.

Breakthrough Infections Following mRNA SARS-CoV-2 Vaccination in Kidney Transplant Recipients.

BACKGROUND: The clinical effectiveness of coronavirus disease 2019 (COVID-19) vaccination in kidney transplant (KT) recipients is lower than in the general population. METHODS: From April to October 2021, 481 KT recipients with COVID-19, included in the Spanish Society of Nephrology COVID-19 Registry, were analyzed. Data regarding vaccination status and vaccine type were collected, and outcomes of unvaccinated or partially vaccinated patients (n = 130) were compared with fully vaccinated patients (n = 351). RESULTS: Clinical picture was similar and survival analysis showed no differences between groups: 21.7% of fully vaccinated patients and 20.8% of unvaccinated or partially vaccinated died (P = 0.776). In multivariable analysis, age and pneumonia were independent risk factors for death, whereas vaccination status was not related to mortality. These results remained similar when we excluded patients with partial vaccination, as well as when we analyzed exclusively hospitalized patients. Patients vaccinated with mRNA-1273 (n = 213) showed a significantly lower mortality than those who received the BNT162b2 vaccine (n = 121) (hazard ratio: 0.52; 95% confidence interval, 0.31-0.85; P = 0.010). CONCLUSIONS: COVID-19 severity in KT patients has remained high and has not improved despite receiving 2 doses of the mRNA vaccine. The mRNA-1273 vaccine shows higher clinical effectiveness than BNT162b2 in KT recipients with breakthrough infections. Confirmation of these data will require further research taking into account the new variants and the administration of successive vaccine doses.

Use and Safety of Remdesivir in Kidney Transplant Recipients With COVID-19.

INTRODUCTION: Remdesivir has demonstrated antiviral activity against coronavirus, shortening the time to recovery in adults hospitalized with moderate/severe COVID-19. Severe adverse events such as acute kidney injury have been reported. Scant data are available on the use and safety of remdesivir in kidney transplant recipients. METHODS: We present a multicenter cohort study of 51 kidney transplant recipients with COVID-19 treated with remdesivir. Outcomes and safety were assessed. RESULTS: Mean age at diagnosis was 60 years, with a median time since kidney transplant of 4.5 years. Mean time since admission to remdesivir was 2 days. Twenty-eight patients (54.9%) required mechanical ventilation (19 noninvasive). Mortality was 18.9% and markedly higher if aged ≥65 years (45% vs. 3.2% in younger patients). Acute kidney injury was present in 27.7% of patients, but was diagnosed in 50% before treatment. No patients required remdesivir discontinuation because of adverse events. We did not find significant hepatoxicity or systemic symptoms resulting from the drug. CONCLUSION: In our cohort of kidney transplant recipients, remdesivir was well tolerated and safe in renal and hepatic toxicity, but randomized trials are needed to assess its efficacy.

COVID-19 in Solid Organ Transplant Recipients in Spain Throughout 2020: Catching the Wave?

BACKGROUND: Few studies have analyzed differences in clinical presentation and outcomes in solid organ transplant (SOT) recipients with coronavirus disease 2019 (COVID-19) across different pandemic waves. METHODS: In this multicenter, nationwide, prospective study, we compared demographics and clinical features, therapeutic management, and outcomes in SOT recipients diagnosed with COVID-19 in Spain before (first wave) or after (second wave) 13 July 2020. RESULTS: Of 1634 SOT recipients, 690 (42.2%) and 944 (57.8%) were diagnosed during the first and second periods, respectively. Compared with the first wave, recipients in the second were younger (median: 63 y [interquartile range, IQR: 53-71] versus 59 y [IQR: 49-68]; P < 0.001) and less likely to receive anti-severe acute respiratory syndrome coronavirus 2 drugs (81.8% versus 8.1%; P < 0.001), with no differences in immunomodulatory therapies (46.8% versus 47.0%; P = 0.931). Adjustment of immunosuppression was less common during the second period (76.4% versus 53.6%; P < 0.001). Hospital admission (86.7% versus 58.1%; P < 0.001), occurrence of acute respiratory distress syndrome (34.1% versus 21.0%; P < 0.001), and case-fatality rate (25.8% versus 16.7%; P < 0.001) were lower in the second period. In multivariate analysis, acquiring COVID-19 during the first wave was associated with an increased risk of death (OR: 1.47; 95% confidence interval [CI], 1.12-1.93; P = 0.005), although this impact was lost in the subgroup of patients requiring hospital (OR: 0.97; 95% CI, 0.73-1.29; P = 0.873) or intensive care unit admission (OR: 0.65; 95% CI, 0.35-1.18; P = 0.157). CONCLUSIONS: We observed meaningful changes in demographics, therapeutic approaches, level of care, and outcomes between the first and second pandemic waves. However, outcomes have not improved in the more severe cases of posttransplant COVID-19.

Predictors of severe COVID-19 in kidney transplant recipients in the different epidemic waves: Analysis of the Spanish Registry.

SARS-CoV-2 infection has produced high mortality in kidney transplant (KT) recipients, especially in the elderly. Until December 2020, 1011 KT with COVID-19 have been prospectively included in the Spanish Registry and followed until recovery or death. In multivariable analysis, age, pneumonia, and KT performed ≤6 months before COVID-19 were predictors of death, whereas gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups according to recipient age and time after KT (age <65 years and posttransplant time >6 months, age <65 and time ≤6, age ≥65 and time >6 and age ≥65 and time ≤6): mortality rates were, respectively, 11.3%, 24.5%, 35.4%, and 54.5% (p < .001). Patients were significantly younger, presented less pneumonia, and received less frequently specific anti-COVID-19 treatment in the second wave (July-December) than in the first one (March-June). Overall mortality was lower in the second wave (15.1 vs. 27.4%, p < .001) but similar in critical patients (66.7% vs. 58.1%, p = .29). The interaction between age and time post-KT should be considered when selecting recipients for transplantation in the COVID-19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination.

Use of tocilizumab in kidney transplant recipients with COVID-19.

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed.

Plasma Cell-Rich Acute Rejection in Renal Transplantation: A Case Report.

Plasma cell-rich acute rejection (PCAR) is a rare type of allograft rejection in renal transplantation. It is characterized by the presence of mature plasma cells that compromise more than 10% of inflammatory cells infiltrating the renal graft. The pathogenesis of PCAR is unknown, appears late, and has been related mainly to insufficient immunosuppression or infections. The treatment is not clearly defined, and the graft survival is poor. Here, we report a case series of 3 Spanish patients diagnosed with PCAR accompanied by donor-specific antibodies (DSA) after kidney transplantation. Mean to diagnosis was 2-12 years post-transplantation, and they began with abrupt deterioration of renal function. All patients were women and had preceding viral infection. In addition, two of the three patients recognize a doubtful adherence to immunosuppression. About treatment, 2 of the 3 patients, because the biopsy of the renal graft showed signs suggestive of incipient antibody-mediated rejection (ABMR) (glomerulitis, capilaritis, transplant glomerulopathy), were started with corticosteroids, anti-thymoglobulin, plasmapheresis, and intravenous immunoglobulins. The last patient, who only showed PCAR at biopsy, was treated with corticosteroids and anti-thymoglobulin. After treatment, graft function improved in all of them, but one patient developed an ABMR and another required a dialysis program, all of which indicates the difficulty in management and treatment of PCAR.

El paciente trasplantado renal en urgencias / Renal transplant patient in emergency department

No disponible