The Mycophenolate-based Immunosuppressive Regimen Is Associated With Increased Mortality in Kidney Transplant Patients With COVID-19.

BACKGROUND: The chronic use of immunosuppressive drugs is a key risk factor of death because of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTRs), although no evident association between the class of immunosuppressive and outcomes has been observed. Thus, we aimed to compare COVID-19-associated outcomes among KTRs receiving 3 different immunosuppressive maintenance regimes. METHODS: This study included data from 1833 KTRs with COVID-19 diagnosed between March 20 and April 21 extracted from the national registry before immunization. All patients were taking calcineurin inhibitor associated with mycophenolate acid (MPA, n = 1258), azathioprine (AZA, n = 389), or mammalian targets of rapamycin inhibitors (mTORi, n = 186). Outcomes within 30 and 90 d were assessed. RESULTS: Compared with patients receiving MPA, the 30-d (79.9% versus 87.9% versus 89.2%; P < 0.0001) and 90-d (75% versus 83.5% versus 88.2%; P < 0.0001) unadjusted patient survivals were higher in those receiving AZA or mTORi, respectively. Using adjusted multivariable Cox regression, compared with patients receiving AZA, the use of MPA was associated with a higher risk of death within 30 d (adjusted hazard ratio [aHR], 1.70; 95% confidence interval [CI], 1.21-2.40; P = 0.003), which was not observed in patients using mTORi (aHR, 0.78; 95% CI, 0.45-1.35; P = 0.365). At 90 d, although higher risk of death was confirmed in patients receiving MPA (aHR, 1.46; 95% CI, 1.09-1.98; P = 0.013), a reduced risk was observed in patients receiving mTORi (aHR, 0.59; 95% CI, 0.35-0.97; P = 0.04) compared with AZA. CONCLUSIONS: This national cohort data suggest that, in KTRs receiving calcineurin inhibitor and diagnosed with COVID-19, the use of MPA was associated with higher risk of death, whereas mTORi use was associated with lower risk of death.

Temporal Reduction in COVID-19-Associated Fatality Among Kidney Transplant Recipients: The Brazilian COVID-19 Registry Cohort Study.

Data from the general population suggest that fatality rates declined during the course of the pandemic. This analysis, using data extracted from the Brazilian Kidney Transplant COVID-19 Registry, seeks to determine fatality rates over time since the index case on March 3rd, 2020. Data from hospitalized patients with RT-PCR positive SARS-CoV-2 infection from March to August 2020 (35 sites, 878 patients) were compared using trend tests according to quartiles (Q1: <72 days; Q2: 72-104 days; Q3: 105-140 days; Q4: >140 days after the index case). The 28-day fatality decreased from 29.5% (Q1) to 18.8% (Q4) (pfor-trend = 0.004). In multivariable analysis, patients diagnosed in Q4 showed a 35% reduced risk of death. The trend of reducing fatality was associated with a lower number of comorbidities (20.7-10.6%, p for-trend = 0.002), younger age (55-53 years, pfor-trend = 0.062), and better baseline renal function (43.6-47.7 ml/min/1.73 m2, pfor-trend = 0.060), and were confirmed by multivariable analysis. The proportion of patients presenting dyspnea (pfor-trend = 0.001) and hypoxemia (pfor-trend < 0.001) at diagnosis, and requiring intensive care was also found reduced (pfor-trend = 0.038). Despite possible confounding variables and time-dependent sampling differences, we conclude that COVID-19-associated fatality decreased over time. Differences in demographics, clinical presentation, and treatment options might be involved.

The effect of nonsurgical periodontal therapy on hepcidin and on inflammatory and iron marker levels.

Serum hepcidin levels may increase in response to infection and inflammation. The present study investigated the effect of nonsurgical periodontal therapy (NSPT) on levels of serum hepcidin, inflammatory markers, and iron markers. An interventional study was conducted on 67 patients (age 30-65 years) without other diseases, except for chronic periodontitis (CP). Patients were allocated to either CP or control groups. The CP group received supragingival and subgingival scaling and root planing procedures, whereas the control group received supragingival scaling. Probing depth (PD), bleeding on probing, clinical attachment level (CAL), visible plaque index (VPI), serum hepcidin and interleukin-6 (IL-6) levels, high-sensitivity C-reactive protein (hs-CRP), hematological markers, and iron markers were measured at baseline and at 90 days after NSPT. The CP group had statistically significant lower mean values for mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) (p ≤ 0.05). The control group had statistically significant reductions in hemoglobin, hematocrit, MCV, and MCH (p ≤ 0.05). Serum hepcidin, IL-6, and erythrocyte sedimentation rate (ESR) levels were significantly decreased in both groups after NSPT. Periodontal markers were more markedly reduced in the CP group compared with the control group (p ≤ 0.05). These findings suggest that NSPT may reduce the serum levels of IL-6, hepcidin, and periodontal parameters.

The effect of nonsurgical periodontal therapy on hepcidin and on inflammatory and iron marker levels

Abstract Serum hepcidin levels may increase in response to infection and inflammation. The present study investigated the effect of nonsurgical periodontal therapy (NSPT) on levels of serum hepcidin, inflammatory markers, and iron markers. An interventional study was conducted on 67 patients (age 30-65 years) without other diseases, except for chronic periodontitis (CP). Patients were allocated to either CP or control groups. The CP group received supragingival and subgingival scaling and root planing procedures, whereas the control group received supragingival scaling. Probing depth (PD), bleeding on probing, clinical attachment level (CAL), visible plaque index (VPI), serum hepcidin and interleukin-6 (IL-6) levels, high-sensitivity C-reactive protein (hs-CRP), hematological markers, and iron markers were measured at baseline and at 90 days after NSPT. The CP group had statistically significant lower mean values for mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) (p ≤ 0.05). The control group had statistically significant reductions in hemoglobin, hematocrit, MCV, and MCH (p ≤ 0.05). Serum hepcidin, IL-6, and erythrocyte sedimentation rate (ESR) levels were significantly decreased in both groups after NSPT. Periodontal markers were more markedly reduced in the CP group compared with the control group (p ≤ 0.05). These findings suggest that NSPT may reduce the serum levels of IL-6, hepcidin, and periodontal parameters.

Increased urinary cystatin C level is associated with interstitial fibrosis and tubular atrophy in kidney allograft recipients.

AIM: The objective of this study was to investigate the correlation between the urinary excretion of cystatin C (CysC) and the presence of interstitial fibrosis/tubular atrophy (IF/TA) in renal transplant (RT) recipients. METHODS: This prospective study included 21 adult patients who had undergone renal biopsy and RT ≥6 months prior. According to the renal biopsy reports, the patients were divided into groups with (n=12) or without (n=9) IF/TA. Analytical parameters included the following: serum and urinary levels of CysC, creatinine (Cr) and sodium (Na), total urinary protein, urinary CysC/creatinine ratio [u(CysC/Cr)], fractional excretion of sodium (FENa) and estimated glomerular filtration rate (eGFR) based on the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: The values of uCysC, u(CysC/Cr), proteinuria, and FENa were significantly higher in patients with IF/TA than in patients without IF/TA. The values of eGFR were statistically lower in patients with IF/TA (p=0.001). Values of uCysC significantly correlated with those of serum Cr, FENa, and eGFR (p<0.001). Among the patients with IF/TA, 67% presented with glomerulosclerosis (segmental/global). CONCLUSION: Elevated levels of urinary CysC are associated with interstitial fibrosis and tubular atrophy in RT recipients and may become a useful tool for monitoring kidney allografts.

Estudo das alterações ecocardiográficas nos primeiros seis meses após o transplante renal / Study of echocardiographic alterations in the first six months after kidney transplantation

FUNDAMENTO: Alterações cardíacas são muito frequentes nos indivíduos portadores de doença renal crônica terminal e estão associadas com a morbimortalidade. OBJETIVOS: Avaliar as alterações evolutivas cardíacas após o transplante renal. MÉTODOS: Foram avaliados prospectivamente 40 pacientes com doença renal crônica terminal, imediatamente antes e com um mês, três meses e seis meses após o transplante renal, por meio de estudo ecocardiográfico com Doppler tecidual. Os parâmetros de massa ventricular, função sistólica e diastólica foram analisados. RESULTADOS: A média da idade foi 31,6 anos e 40% eram do sexo feminino. Observamos redução do diâmetro diastólico do VE (52,23 para 49,95 mm, p = 0,021) e do índice de massa do VE (131,48 para 113,039 g/m², p = 0,002) após o transplante renal. A razão E/e' média reduziu no terceiro e no sexto meses após o transplante renal em relação ao exame basal (8,13 e 7,85 vs 9,79, p < 0,05). A fração de ejeção aumentou a partir do primeiro mês do transplante renal em relação a exame basal (69,72% vs 65,68%, p < 0,05). A prevalência de disfunção diastólica reduziu 43% no período avaliado. A fração de ejeção e a razão E/e' média basais estiveram associadas com redução do índice de massa do VE após o transplante renal. O índice de massa do VE basal, o sexo feminino e a redução do fósforo sérico apresentaram associação com a redução da razão E/e' média após o transplante renal. CONCLUSÃO: O transplante renal promoveu alterações significativas nos parâmetros ecodopplercardiográficos de massa do VE, função sistólica e função diastólica nos pacientes com doença renal crônica terminal.

BACKGROUND: Cardiac disorders are very common in individuals with chronic kidney disease and are associated with morbimortality. OBJECTIVE: To evaluate cardiac alterations after kidney transplantation. METHODS: We prospectively evaluated 40 patients with chronic kidney disease, immediately before and one month, three months and six months after kidney transplantation, using tissue Doppler echocardiographic study. The left ventricular mass, systolic and diastolic function parameters were analyzed. RESULTS: The mean age was 31.6 years and 40% of patients were female. We observed a reduction in left ventricular diastolic diameter (52.23 to 49.95 mm, p = 0.021) and LV mass index (131.48 to 113.039 g/m2, p = 0.002) after kidney transplantation. The mean E/e' decreased in the third and sixth months after kidney transplantation, when compared to basal values (8.13 and 7.85 vs. 9.79, p <0.05). The ejection fraction increased from the first month after kidney transplantation compared to basal assessment (69.72% vs. 65.68%, p <0.05). The prevalence of diastolic dysfunction decreased 43% during the evaluated period. The basal ejection fraction and mean E/e' were associated with reduced LV mass index after kidney transplantation. The LV mass index at baseline, female sex and decrease in serum phosphorus were associated with a reduction in the mean E/e ' ratio after kidney transplantation. CONCLUSION: Kidney transplantation resulted in significant alterations in Doppler echocardiographic parameters of LV mass, systolic and diastolic function in patients with chronic kidney disease.

Study of echocardiographic alterations in the first six months after kidney transplantation.

BACKGROUND: Cardiac disorders are very common in individuals with chronic kidney disease and are associated with morbimortality. OBJECTIVE: To evaluate cardiac alterations after kidney transplantation. METHODS: We prospectively evaluated 40 patients with chronic kidney disease, immediately before and one month, three months and six months after kidney transplantation, using tissue Doppler echocardiographic study. The left ventricular mass, systolic and diastolic function parameters were analyzed. RESULTS: The mean age was 31.6 years and 40% of patients were female. We observed a reduction in left ventricular diastolic diameter (52.23 to 49.95 mm, p = 0.021) and LV mass index (131.48 to 113.039 g/m2, p = 0.002) after kidney transplantation. The mean E/e' decreased in the third and sixth months after kidney transplantation, when compared to basal values (8.13 and 7.85 vs. 9.79, p <0.05). The ejection fraction increased from the first month after kidney transplantation compared to basal assessment (69.72% vs. 65.68%, p <0.05). The prevalence of diastolic dysfunction decreased 43% during the evaluated period. The basal ejection fraction and mean E/e' were associated with reduced LV mass index after kidney transplantation. The LV mass index at baseline, female sex and decrease in serum phosphorus were associated with a reduction in the mean E/e ' ratio after kidney transplantation. CONCLUSION: Kidney transplantation resulted in significant alterations in Doppler echocardiographic parameters of LV mass, systolic and diastolic function in patients with chronic kidney disease.

Cystatin C: a marker of renal function in transplant patients: [review] / Cistatina C: um marcador de função renal em pacientes transplantados: [revisão]

Assessment of renal function in patients submitted to kidney transplantation is of great importance in clinical practice, and the glomerular filtration rate is used as an indicator for this purpose. Measurement of serum creatinine is the most widely used method for the estimation of gromerular filtration rate. However, the disadvantages of this method are physiological and analytical influences (e.g., muscle mass, gender, certain antibiotics, bilirrubin, ketones) with the assay and inadequate sensitivity for the early detection of small declines in gromerular filtration rate. Cystatin C is a nonglycosylated low molecular weight (13 kDa) protein of the superfamily of cysteine proteinase inhibitors, which isconstantly produced by all nucleated cells. Due to its low molecular weight, cystatin C is freely filtered by the renal glomeruli and then almost completely reabsorbed and metabolized in the proximal tubules without interference from other low molecular weight proteins, thus permitting its use as a good marker of glomerular filtration. We present here a review of studies published so far regarding the use of cystatin C as a promising marker for the assessment of glomerular filtration in renal transplant patients.

A avaliação da função renal em pacientes submetidos a transplante renal é de grande importância na prática clínica, sendo utilizada para esse fim como indicador a medida da taxa de filtração glomerular. A determinação da creatinina sérica é o procedimento mais utilizado para essa avaliação, porém as desvantagens desse método são as influências fisiológicas e analíticas, por exemplo, massa muscular, sexo, certos antibióticos, bilirrubinas, cetonas, com o ensaio e inadequada sensibilidade para detecção precoce de pequenos declínios na taxa de filtração glomerular. A cistatina C é uma proteína não glicosilada de baixo peso molecular (13KDa), produzida constantemente em todas as células nucleadas, pertencente à superfamília das proteínas inibidoras da cisteína proteinase. É livremente filtrada pelos glomérulos renais devido ao seu baixo peso molecular, sendo a seguir quase totalmente reabsorvida e metabolizada nos túbulos proximais, não sofrendo influência de outras proteínas de baixo peso molecular, o que permite sua utilização como um bom marcador da filtração glomerular. Esta revisão aborda o uso da cistatina C como marcador promissor de avaliação da filtração glomerular em pacientes transplantados renais, com base em estudos até o momento realizados nesta população.

Avaliação do desempenho das equações de Cockcroft-Gault e do estudo "Modification of Diet in Renal Disease" em transplantados renais / Assessing the performance of Cockcroft-Gault equations and study "Modification of Diet in Renal Disease" in kidney transplant patients

Objetivo: Verificar a validade clínica das equações de Cockroft-Gault e MDRD para a estimativa do clearance de creatinina em transplantados renais e avaliar a influência de diferentes níveis de clearance no desempenho dessas equações. Métodos: O grupo estudado compôs-se de 140 pacientes transplantados renais em acompanhamento ambulatorial, sendo 81 homens (58%) e 59 mulheres (42%), com idade média de 37,5 anos. Foi calculada a estimativa da TFG pelas equações e comparada ao clearence de creatinina medido pela urina de 24h. Para análise estatística, foram utilizadas as medidas de acurácia, bias e precisão. A acurácia recomendada pelas diretrizes do K/DOQI (2002) foi considerada como referência para a validação clínica das equações. Resultados: Nenhuma equação atingiu acurácia mínima para sua validação quando analisadas no conjunto dos pacientes, sendo a melhor acurácia (73,5%) e o melhor bias (-0,4) alcançados pela equação de Cockcroft-Gault corrigida. Nos pacientes com Clearance de creatinina menor que 60 mL/min/1,73m², novamente nenhuma equação alcançou o desempenho mínimo, sendo a melhor acurácia (68,6%) e o melhor bias (0,8) observados na equação MDRD com cinco variáveis. Nos pacientes com clearance de creatinina maior ou igual a 60mL/min/1,73m², a equação de Cockroft-Gault corrigida foi a única a ultrapassar a referência mínima necessária para sua validação, alcançando a melhor acurácia (87,6%) e o melhor bias (-9,4). Conclusões: Em geral, nenhuma das equações se mostrou clinicamente satisfatória nos transplantados renais. Apenas a equação de Cockcroft-Gault corrgida pela superfície corporal se mostrou aceitável para o grupo com melhor função renal.