Safety and effectiveness of COVID-19 SPUTNIK V vaccine in dialysis patients.

INTRODUCTION: Given the vulnerability of chronic kidney disease individuals to SARS-CoV-2, nephrology societies have issued statements calling for prioritization of these patients for vaccination. It is not yet known whether COVID-19 vaccines grant the same high level of protection in patients with kidney disease compared to the non-dialysis population. The aims of this study were to evaluate the safety - measured by the adverse events potentially attributed to vaccines (ESAVI) - and the effectiveness - evaluated by the presence of antibodies - in dialysis patients immunized with the COVID-19 Sputnik V vaccine. METHODS: multicenter, observational and analytical study of a prospective cohort of hemodialysis patients from the Ciudad Autónoma de Buenos Aires participating in an official vaccination program. Dialysis requiring individuals older than 18 years, who received both components of the COVID-19 vaccine were included. RESULTS: Data from 491 patients were included in the safety analysis. ESAVI with either the first or second component was detected in 186 (37.9%, 95% CI 33.6%-42.3%). Effectiveness analysis measuring antibodies levels against SARS-CoV-2 were performed in 102 patients; 98% presented these IgG antibodies at day 21 after the second component. In patients with COVID-19 prior to vaccination, antibodies at day 21 after the first component reached almost the highest levels compared to patients without previous COVID-19, but IgG rise among patients with previous COVID-19 was lower than in those without this previous disease. CONCLUSION: The Sputnik V vaccine has been shown to be safe and effective in this patient's population.

Introducción: Dada la vulnerabilidad al SARS-CoV-2 de las personas con enfermedad renal crónica, las sociedades de nefrología han emitido declaraciones pidiendo priorizar a estos pacientes para la vacunación. Aún no se sabe si las vacunas COVID-19 confieren el mismo nivel de protección en pacientes con enfermedad renal. Los objetivos de este estudio fueron evaluar la seguridad, medida por eventos supuestamente atribuidos a las vacunas (ESAVI) y la efectividad, evaluada por la presencia de anticuerpos en pacientes en diálisis inmunizados con la vacuna COVID-19 Sputnik V. Métodos: estudio multicéntrico, observacional y analítico de una cohorte prospectiva de pacientes en hemodiálisis, en la Ciudad Autónoma de Buenos Aires, con plan de vacunación. Se incluyeron pacientes mayores de 18 años en diálisis que recibieron ambos componentes de la vacuna COVID-19. Resultados: 491 pacientes fueron incluidos en el análisis de seguridad. Se detectó ESAVI con el primer o el segundo componente en 186 (37.9% IC 95%: 33.6%-42.3%). La efectividad medida por presencia de anticuerpos IgG contra SARS-Cov-2 se realizó en 102 pacientes, 98% presentaba IgG contra SARS-CoV-2, 21 días después del segundo componente. En pacientes con COVID-19 previo a la vacunación, los anticuerpos al día 21 del primer componente alcanzaron niveles casi mayores que en aquellos que no habían sufrido COVID-19, aunque el aumento de los niveles a los 21 días del segundo componente fue menor que en los pacientes sin COVID-19 previo. Conclusión: Los pacientes en diálisis constituyen una población vulnerable para la infección por SARS-CoV-2, por lo tanto, más allá de las recomendaciones implementadas por las unidades de diálisis, la vacunación completa es mandatoria. Se ha demostrado que la vacuna Sputnik V es segura y eficaz en esta población de pacientes.

Safety and effectiveness of COVID-19 SPUTNIK V vaccine in dialysis patients / Seguridad y efectividad de vacuna COVID-19 SPUTNIK V en pacientes en diálisis

Abstract Introduction: Given the vulnerability of chronic kidney disease individuals to SARS-CoV-2, nephrology societies have issued statements calling for prioritization of these patients for vaccination. It is not yet known whether COVID-19 vaccines grant the same high level of protection in patients with kidney disease compared to the non-dialysis population. The aims of this study were to evaluate the safety - measured by the adverse events potentially attributed to vaccines (ESAVI) - and the effectiveness - evaluated by the presence of antibodies - in dialysis patients immunized with the COVID-19 Sputnik V vaccine. Methods: multicenter, ob servational and analytical study of a prospective cohort of hemodialysis patients from the Ciudad Autónoma de Buenos Aires participating in an official vaccination program. Dialysis requiring individuals older than 18 years, who received both components of the COVID-19 vaccine were included. Results: Data from 491 patients were included in the safety analysis. ESAVI with either the first or second component was detected in 186 (37.9%, 95% CI 33.6%-42.3%). Effectiveness analysis measuring antibodies levels against SARS-CoV-2 were performed in 102 patients; 98% presented these IgG antibodies at day 21 after the second component. In patients with COVID-19 prior to vaccination, antibodies at day 21 after the first component reached almost the highest levels compared to patients without previous COVID-19, but IgG rise among patients with previous COVID-19 was lower than in those without this previous disease. Conclusion: The Sputnik V vaccine has been shown to be safe and effective in this patient's population.

Resumen Introducción: Dada la vulnerabilidad al SARS-CoV-2 de las personas con enfermedad renal crónica, las sociedades de nefrología han emitido declaraciones pidiendo priorizar a estos pacientes para la vacunación. Aún no se sabe si las vacunas COVID-19 confieren el mismo nivel de protección en pacientes con enfermedad renal. Los objetivos de este estudio fueron evaluar la seguridad, medida por eventos supuestamente atribuidos a las vacunas (ESAVI) y la efectividad, evaluada por la presencia de anticuerpos en pacientes en diálisis inmuniza dos con la vacuna COVID-19 Sputnik V. Métodos: estudio multicéntrico, observacional y analítico de una cohorte prospectiva de pacientes en hemodiálisis, en la Ciudad Autónoma de Buenos Aires, con plan de vacunación. Se incluyeron pacientes mayores de 18 años en diálisis que recibieron ambos componentes de la vacuna COVID-19. Resultados: 491 pacientes fueron incluidos en el análisis de seguridad. Se detectó ESAVI con el primer o el segundo componente en 186 (37.9% IC 95%: 33.6%-42.3%). La efectividad medida por presencia de anticuerpos IgG contra SARS-Cov-2 se realizó en 102 pacientes, 98% presentaba IgG contra SARS-CoV-2, 21 días después del segundo componente. En pacientes con COVID-19 previo a la vacunación, los anticuerpos al día 21 del primer componente alcanzaron niveles casi mayores que en aquellos que no habían sufrido COVID-19, aunque el aumento de los niveles a los 21 días del segundo componente fue menor que en los pacientes sin COVID-19 previo. Conclusión: Los pacientes en diálisis constituyen una población vulnerable para la infección por SARS-CoV-2, por lo tanto, más allá de las recomendaciones implementadas por las unidades de diálisis, la vacunación completa es mandatoria. Se ha demostrado que la vacuna Sputnik V es segura y eficaz en esta población de pacientes.

N-acethyl-cysteine reduces the occurrence of contrast-induced acute kidney injury in patients with renal dysfunction: a single-center randomized controlled trial.

BACKGROUND: The occurrence of contrast-induced acute kidney injury (CIAKI) has paralleled the increased number of diagnostic interventions requiring radiographic contrast media (CM). Several strategies aimed at preventing renal injury following iodine have been carried out over the last several years. The aim of this study was to evaluate the impact of three different strategies aimed at preventing CIAKI in patients with renal dysfunction (serum creatinine >1.25 mg/dl or estimated creatinine clearance <45 ml/min) receiving low osmolar CM for diagnostic-therapeutic procedures. METHODS: Candidates received 154 mmol NaHCO3 solution (B0) at a rate of 3 ml/kg/h from at least 2 h before the procedure and at 1 ml/kg/h during and for the next 6-12 h; the same schedule plus N-acethyl-cysteine (NAC) 600 mg twice daily the day before and the day of the procedure (BN) or NAC as above plus 154 mmol NaCl solution at a rate of 3 ml/kg/h from at least 2 h before the procedure and at 1 ml/kg/h during and for the next 6-12 h (SN). Serum creatinine (SCr) was measured at baseline and on days 2 or occasionally 3 after CM. The main outcome measure was the occurrence of CIAKI, defined as a ≥25% increase in SCr within 2-3 days of CM. RESULTS: The three groups were similar with regard to age, gender distribution, weight, baseline serum levels of creatinine, sodium, potassium, urate and estimated creatinine clearance. A larger proportion of individuals received ACEIs/ARAs in the BN group (p < 0.05), but in the SN group, more patients declared a past history of acute myocardial infarction or had high blood pressure, and few displayed mild-moderate left ventricular dysfunction (p < 0.05). CIAKI occurred in 24/123 (19.5%) assessable patients (15/42 in the B0 group, 3/43 in the BN group and 6/38 in the SN group; p < 0.01). Thus, 15/42 patients who did not receive NAC developed CIAKI in contrast to 9/81 who did (p < 0.01). Multivariate logistic regression models showed that the use of NAC was the unique factor associated with a statistically significant influence for the occurrence of CIAKI (OR: 0.18; 95% CI: 0.04-0.72; p = 0.016). CONCLUSIONS: The results from this study show that: (1) the occurrence of CIAKI after low-osmolar CM administration is similar to that reported worldwide. (2) NAC-based renoprotective measures are superior for the prevention of CIAKI in patients with previous renal dysfunction. (3) They also demonstrate that bicarbonate expansion alone has limited value in preventing CIAKI. For those individuals at risk, combination prophylaxis including volume expansion plus NAC should be recommended to reduce the chance of overt kidney injury following CM administration.

Renal response to an acute protein challenge in pregnant women with borderline hypertension.

BACKGROUND: The renal reserve (RR), assessed after an oral protein challenge or the intravenous administration of amino acids, is still present in healthy pregnant women (NP), although resting glomerular filtration rate (GFR) and renal plasma flow (RPF) increase progressively throughout normal gestation. No studies have addressed this issue in hypertensive gravidas; the aim of this trial was to evaluate renal response to an acute protein load (PL) in NP and pregnant women with borderline hypertension (HP). METHODS: Five NP, eight HP and eight healthy non-pregnant women (CG) were evaluated. After fasting overnight, all subjects received an oral water load (20 mL/kg of body weight), the urinary output was then replaced orally with equal volumes of water. After two 30 min periods, an 80 g PL was provided. Creatinine clearance (CCr) was measured every 30 min from 1 h before and for 4 h following PL. Participants remained recumbent during the study, bladder emptiness was assessed by ultrasound immediately after each micturition. Baseline CCr was taken as the average of two 30 min periods before PL and peak Ccr as the maximal CCr recorded thereafter. RESULTS: The groups were similar with regard to age, weight or gestation age. Baseline CCr (NP: 118.5+/-6.0, HP: 127.4+/-6.7 and CG: 99.8+/-2.9 mL/min, P=0.004 (CG vs NP and HP), increased after PL to NP: 223.5+/-9.8 to HP: 178.5+/-13 and to CG: 149.1+/-4.0 mL/min, P<0.0004 (CG vs HP, CG vs NP and NP vs HP)). Peak minus baseline CCr was 97.3+/-10.1; 46.3+/-12.7 and 48.3+/-4.8 for NP, HP and CG, respectively (P<0.006 HP vs CG and NP). The peak CCr was obtained significantly earlier in both pregnant groups (Period 3) compared with the healthy non-pregnant women (Period 5) (P=0.02). The fractional proximal reabsorption of sodium (FPRNa+) at peak CCr was similar in the groups (NP: 0.74+/-0.01 HP: 0.78+/-0.02 and CG: 0.74+/-0.03, P=not significant (NS)) as was the distal delivery of sodium (DDNa+) (NP: 5.8+/-0.5; HP: 4.1+/-0.5 and CG: 4.3+/-0.4 meq/min, P=NS). Fractional excretion of urea (%) increased from 91.4+/-5.5 to 105.5+/-9.8%; 80.7+/-8.0 to 97.3+/-9.8; and 44.4+/-7.8 to 86.0+/-7.1 in NP, HP and CG, respectively (P=NS). There was a trend towards a poorer maternal and fetal outcome in the HP group. CONCLUSION: Mid-term borderline HP failed to increase CCr as much as NP did after a protein challenge, suggesting altered functional response of the nephron or lessened sensitivity of renal vasculature to additional vasodilator stimuli. These results support the interest of additional prospective studies with a larger number of patients to confirm these findings and evaluate the value of RR tests as predictors of outcome of pregnancies at risk.

Folic acid 5 or 15 mg/d similarly reduces plasma homocysteine in patients with moderate-advanced chronic renal failure.

BACKGROUND: Hyperhomocysteinaemia is an independent risk factor for cardiovascular disease with a remarkable prevalence in patients with chronic renal failure (CRF). Low doses of folic acid (FA) with or without vitamin B6 and B12 has been shown to effectively reduce plasma homocysteine (Hcy). The aim of this study was to compare the short-term effects of two different oral doses of FA (5 vs 15 mg/d) on plasma Hcy levels in subjects suffering from moderate-severe CRF. METHODS: A double-blind, double-dummy, comparative, two-stage randomised study was performed. Seventeen patients aged 45-71 years, with glomerular filtration rates between 15.4-50 mL/min 1.73/m2 were randomly assigned to receive FA 5 mg/d (FA-5, n: 8) or FA 15 mg/d (FA-15, n: 9) for 30 days. At the end of this 30-day double-blind period, all the participants were placed on FA 5 mg/d (open period), for 5 additional months. Both groups were also supplemented with vitamins B1, B6 and B12 throughout the trial. Blood samples were drawn at 0, 15, 30, 90 and 180 days to assess Hcy, complete blood count (CBC) and sequential multichannel analysis (SMA). Chest X-ray and a 12-lead electrocardiogram (ECG) were also performed. RESULTS: Plasma Hcy (mean +/- SEM) decreased from 27.9 +/- 1.4 (baseline) to 15.1 +/- 0.6, 13.3 +/- 0.9, 14.1 +/- 0.5 and 13.8 +/- 0.5 micromol/L (FA-5) and from 28.8 +/- 2.7 to 15.6 +/- 1.2, 14.4 +/- 1.3, 13.0 +/- 0.7 and 13.1 +/- 0.6 micromol/L (FA-15) at days 15, 30, 90 and 180, respectively. (P < 0.01 from day 15 to 180 vs baseline for both groups with no differences between them). Renal function remained stable throughout the entire period of the study in all but one patient in whom it deteriorated to pre-end stage disease. No adverse cardiovascular events developed during the trial. CONCLUSION: Both folic acid doses induced a significant and similar decrease in plasma Hcy in subjects with moderate-severe chronic renal failure. The possible dose-related effect of this approach in reducing the risk of accelerated sclerotic vascular disease and cardiovascular events in this especially vulnerable population should be a matter of further investigation.

The faster potassium-lowering effect of high dialysate bicarbonate concentrations in chronic haemodialysis patients.

BACKGROUND: Hyperkalaemia is common in patients with advanced renal disease. In this double-blind, randomized, three-sequence, crossover study, we compared the effect of three dialysate bicarbonate concentrations ([HCO3-]) on the kinetics of serum potassium (K+) reduction during a conventional haemodialysis (HD) session in chronic HD patients. METHODS: We studied eight stable HD patients. The choice of dialysate [HCO3-] followed a previously assigned treatment protocol and the [HCO3-] used were low bicarbonate (LB; 27 mmol/l), standard bicarbonate (SB; 35 mmol/l) and high bicarbonate (HB; 39 mmol/l). Polysulphone dialysers and automated machines provided blood flow rates of 300 ml/min and dialysis flow rates of 500 ml/min for each HD session. Blood samples were drawn at 0 (baseline), 15, 30, 60 and 240 min from the arterial extracorporeal line to assess blood gases and serum electrolytes. In three of the eight patients, we measured serum K+ 1 h post-dialysis as well as K+ removal by the dialysis. The same procedures were followed until the completion of the three arms of the study, with a 1 week interval between each experimental arm. RESULTS: Serum K+ decreased from 5.4+/-0.26 (baseline) to 4.96+/-0.20, 4.90+/-0.19, 4.68+/-0.13 and 4.24+/-0.15 mmol/l at 15, 30, 60 and 240 min, respectively, with LB; from 5.38+/-0.21 to 5.01+/-0.23, 4.70+/-0.25, 4.3+/-0.15 and 3.8+/-0.19 mmol/l, respectively, with SB; and from 5.45+/-0.25 to 4.79+/-0.17, 4.48+/-0.17, 3.86+/-0.16 and 3.34+/-0.11 mmol/l, respectively, with HB (P<0.05 for high vs standard and low [HCO3-] at 60 and 240 min). The decrease in serum K+ correlated with the rise in serum [HCO3-] in all but LB (P<0.05). Potassium rebound was 3.9+/-10.2%, 5.2+/-6.6% and 8.9+/-4.9% for LB, SB and HB dialysates, respectively (P=NS), while total K+ removal (mmol/dialysis) was 116.4+/-21.6 for LB, 73.2+/-12.8 for SB and 80.9+/-15.4 for HB (P=NS). CONCLUSIONS: High dialysate [HCO3-] was associated with a faster decrease in serum K+. Our results strongly suggest that this reduction was due to the enhanced shifting of K+ from the extracellular to the intracellular fluid compartment rather than its removal by dialysis. This finding could have an impact for those patients with life-threatening pre-HD hyperkalaemia.