Comparison of antibody response to SARS-CoV-2 after two doses of inactivated virus and BNT162b2 mRNA vaccines in kidney transplant.

BACKGROUND: Antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after mRNA or adenoviral vector-based vaccines is weak in kidney transplant (KT) patients. However, few studies have focused on humoral response after inactivated virus-based vaccines in KT. Here, we compare antibody response following vaccination with inactivated virus (CoronaVac®) and BNT162b2 mRNA. METHODS: A national multicentre cross-sectional study was conducted. The study group was composed of patients from all KT centres in Uruguay, vaccinated between 1 and 31 May 2021 (CoronaVac®, n = 245 and BNT162b2, n = 39). The control group was constituted of 82 healthy individuals. Participants had no prior confirmed coronavirus disease 2019 (COVID-19) test. Blood samples were collected between 30 and 40 days after the second dose. Serum-specific immunoglobulin G (IgG) antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 Spike protein were determined using the COVID-19 IgG QUANT ELISA Kit. RESULTS: Only 29% of KT recipients showed seroconversion (36.5% BNT162b2, 27.8% inactivated virus, P = 0.248) in comparison with 100% in healthy control with either vaccine. Antibody levels against RBD were higher with BNT162b mRNA than with inactivated virus [median (interquartile range) 173 (73-554) and 29 (11-70) binding antibody units (BAU)/mL, P < 0.034] in KT and 10 times lower than healthy control [inactivated virus: 308 (209-335) and BNT162b2: 2638 (2608-3808) BAU/mL, P < 0.034]. In multivariate analysis, variables associated with negative humoral response were age, triple immunosuppression, estimated glomerular filtration rate and time post-KT. CONCLUSION: Seroconversion was low in KT patients after vaccination with both platforms. Antibody levels against SARS-CoV-2 were lower with inactivated virus than BNT162b mRNA. These findings support the need for strategies to improve immunogenicity in KT recipients after two doses of either vaccine.

Is Chronic Kidney Disease Progression Influenced by the Type of Renin-Angiotensin-System Blocker Used?

INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce proteinuria and slow renal disease progression more effectively than other therapies in patients with chronic kidney disease (CKD). However, differences regarding efficacy and safety between these therapies remain controversial. OBJECTIVES: Aim of this study was to analyze the different treatment effect of ACEI, ARB, and non-ACEI/ARB in CKD progression. The primary outcome was survival to end-stage renal disease (ESRD) and/or death and to ESRD censored by all-cause death, secondary outcomes were proteinuria reduction and hyperkalemia. METHODS: We analyzed data from 1,120 patients extracted from the National Renal Healthcare Program cohort, which included 17,238 CKD nondialysis subjects who were successively monitored between -September 1, 2004 and August 31, 2016. Inclusion criteria were at least a 1-year follow-up, 3 clinical visits, and no previous treatment with ACEI or ARB. From the baseline visit onward, patients continued with 3 different treatment schemes: no ACEI/ARB, started on ACEI or ARB, but while avoiding both treatments in combination. Chi2, t test, binary logistic regression, and multivariate regression models (Cox proportional Hazard model and competing risk Fine and Gray model were used for statistical analysis. RESULTS: Mean age and follow-up were 67.9 (± 15) and 3.8 (± 2) years, respectively. Estimated glomerular filtration rate averaged 42.1 ± 23 mL/min/1.73 m2 and 300 (27%) patients were diabetics. Progression to ESRD was significantly worse in the no ACEI/ARB group (hazard ratio [HR] 4.23, 95% CI 1.28-13.92) versus ACEI (reference group; p = 0.01). The analysis by competing-risks' regression showed significantly higher risk of ESRD in the no ACEI/ARB group (HR 3.63, 95% CI 1.34-9.85) versus ACEI (p = 0.01). There were no significant differences between ACEI and ARB groups (HR 1.31, 95% CI 0.37-4.66) regarding the risk of progression to ESRD. Survival was similar in all 3 groups (p = 0.051). Statistically significantly more patients experienced reductions in proteinuria/albuminuria in ACEI and ARB groups (together) versus no ACEI/ARB group (p = 0.016, OR 1.82, 95% CI 1.12-2.94). No difference in hyperkalemia frequency was found between them (p = 0.17). CONCLUSIONS: In patients with CKD, treatment with ACEI or ARB had a superior effect than no ACEI or ARB treatment on slowing kidney disease progression and on proteinuria reduction. Efficacy of ACEI and ARB was comparable.

Impacto de la acidosis en la evolución de la cohorte de pacientes del Programade Salud Renal del Uruguay / Impact of acidosis in the evoluton of the patients cohort in the renal health program of Uruguay

Objetivo: evaluar la frecuencia de acidosis metabólica en la enfermedad renal crónica (ERC) y su impacto en la evolución. Material y método: se realizó un estudio retrospectivo de pacientes del Programa de Salud Renal del Uruguay (octubre de 2004 a octubre de 2011) con dos controles separados porseis o más meses y al menos un dato de bicarbonatemia. Se analizaron: creatininemia, proteinuria, bicarbonatemia venosa y tratamiento alcalinizante. Se consideró evento final el ingreso a diálisis o trasplante y/o fallecimiento. Análisis estadístico: test de t, chi2, ANOVA, Kaplan-Meier y análisis multivariado de Cox (significativo p < 0,05). Resultados: se analizaron 921 pacientes con al menos un dato de bicarbonatemia (232 pacientes con dos o más datos). La creatininemia fue mayor en las nefropatías túbulo intersticiales y en los grupos con bicarbonatemia menor a 23 mEq/l(acidosis) o mayor a 32 mEq/l versus grupo intermedio. La bicarbonatemia fue menor en los estadios IV-V versus I-II de ERC. En estadios I-II, la bicarbonatemia fue menor si teníaproteinuria. Recibían alcalinizantes al inicio 7,3% y al final 31%. En el grupo con acidosis, el aumento de creatininemia/año (n = 232) fue mayor y la sobrevida (combinada) fue menor. Los niveles de bicarbonatemia, creatininemia y proteinuria se correlacionaron independientemente con el evento final combinado (ingreso a tratamiento de sustitución renal /muerte). Conclusiones: la acidosis metabólica se puede observardesde estadios iniciales de ERC y es un factor independiente de progresión y muerte, por lo que se recomienda sudetección precoz y corrección.

Objective: to evaluate the prevalence of metabolic acidosis in chronic kidney disease and its impact on the evolution of the condition. Method:we conducted a retrospective study of patients in the Renal Health Program of Uruguay (from October, 2004 through October, 2011) with two controlgroups six months or longer apart, and at least one bicarbonatemia datum. We analysed: creatininemia, proteinuria, venous bicarbonatemia and alcalinizing treatment. The start of dialysis, transplant and/or death wereconsidered final events. Statistical analysis: t test, chi2, ANOVA, Kaplan-Meier and multivariate analysis usingCox method (meaningful p < 0,05).Results: we analyzed 921 patients with at least one bicarbonatemia datum (232 patients with two or more data). Creatininemia was greater in the tubulo-interstitial nephritis and in the groups with bicarbonatemia lower than 23 mEq/l (acidosis) or greater than 32 mEq/l, rather than in the intermediate group. Bicarbonatemia was lower in the IV-V stages than in the I-II stages ofchronic kidney disease. In stages I-II bicarbonatemia was lower in the presence of proteinuria. Seven pointthree percent of patients received alkalinizers at the start, and 31% at the end. In the group with acidosis, increase of creatininemia/year (n = 232) was greater and survival (combined) was lower. Bicarbonatemia, creatininemia and proteinuria levels were independentlycorrelated with the combined final event (entering the renal substitution treatment/death). Conclusions:metabolic acidosis may be observedsince initial stages of the chronic kidney disease and it constitutes an independent factor of progression anddeath. Thus, early detection and correction are advisable.

Objetivo: avaliar a frequência da acidose metabólica na doença renal crônica (DRC) e o impacto desta na evolução dessa patologia. Material e método: um estudo retrospectivo de pacientes do Programa de Saúde Renal do Uruguai no período outubro de 2004 a outubro de 2011, como dois controles separados por seis ou mais meses e com pelo menos um dado de bicarbonatemia foi realizado. Foram analisados: creatininemia, proteinuria, bicarbonatemia venosa e tratamento alcalinizante. Foram consideradoscomo evento final a entrada a tratamento de substituição da função renal (diálise ou transplante) ou morte. A analise estatística foi realizada empregando teste de t, chi-quadrado, ANOVA, Kaplan-Meier e análisemultivariado de Cox (significativo p < 0,05). Resultados: foram analisados 921 pacientes compelo menos uma bicarbonatemia, dos quais 232 tinham dois ou mais resultados. A creatininemia foi maior nasnefropatias túbulo intersticiales e nos grupos com bicarbonatemia menor a 23 mEq/l (acidose) ou maior a 32mEq/l comparado com o grupo intermediário. A bicarbonatemia foi menor nos estádios IV-V quando comparados com I-II de DRC. Nos estádios I-II a bicarbonatemia foi menor se havia proteinuria. No inicio 7,3 % receberam alcalinizantes e 31% ao final. No grupo com acidose, o aumento da creatininemia/ano (n=232) foi maiore a sobrevida (combinada) foi menor. Os níveis de bicarbonatemia, creatininemia e proteinuria estavam correlacionados de forma independente com o evento final combinado (ingresso a tratamento de substituição renal/morte). Conclusões: a acidose metabólica pode ser observada desde estádios iniciais da DRC e é um fator independente de progressão e morte, por essa razão se recomenda sua detecção precoce e correção.