Glomerular Filtration Rate Estimation Using ß2-Microglobulin and ß-Trace Protein in Adults With Solid Tumors: A Prospective Cross-Sectional Study.

RATIONALE & OBJECTIVE: ß2-Microglobulin (B2M) and ß-trace protein (BTP) are novel endogenous filtration markers that may improve the accuracy of estimated glomerular filtration rate (eGFR) beyond creatinine and cystatin C (eGFRcr-cys), but they have not been assessed in patients with cancer. STUDY DESIGN: Cross-sectional analysis. SETTING & PARTICIPANTS: Prospective cohort of 1,200 patients with active solid tumors recruited between April 2015 and September 2017. EXPOSURE: CKD-EPI equations without race combining B2M and/or BTP with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR). OUTCOME: Performance of equations compared with eGFRcr-cys and non-GFR determinants of serum B2M and BTP (SB2M, and SBTP, respectively). Measured GFR (mGFR) was determined using the plasma clearance of chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA). ANALYTICAL APPROACH: Bias was defined as the median of the differences between mGFR and eGFR, and 1-P30 was defined as the percentage of estimates that differed by more than 30% from the mGFR (1-P30). Linear regression was used to assess association of clinical and laboratory variables with SB2M, and SBTP after adjustment for mGFR. RESULTS: Mean age and mGFR were 58.8±13.2 SD years and 78.4±21.7 SD mL/min/1.73m2, respectively. Performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys (lesser bias and 1-P30). Performance of 2-marker panel equations was as good as eGFRcr-cys (lesser bias and similar 1-P30). SB2M and SBTP were not strongly influenced by cancer site. LIMITATIONS: Participants may have had better clinical performance status than the general population of patients with solid tumors. CONCLUSIONS: B2M and BTP can improve the accuracy of eGFR and may be useful as confirmatory tests in patients with solid tumors, either by inclusion in a multimarker panel equation with creatinine and cystatin C, or by substituting for cystatin C in combination with creatinine. PLAIN-LANGUAGE SUMMARY: The most accurate method to assess estimate kidney function is estimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFRcr-cys). We studied whether using ß2-microglobulin (B2M) and/or ß-trace protein (BTP) with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR) might be useful in patients with active solid tumors. The performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys. Performance of 2-marker panel equations was as good as eGFRcr-cys. We conclude that B2M and BTP can improve the accuracy of eGFR and may be useful as a confirmatory test in patients with solid tumors either by inclusion in multimarker panel equation with creatinine and cystatin C or by substituting for cystatin C in combination with creatinine.

A prospective cross-sectional study estimated glomerular filtration rate from creatinine and cystatin C in adults with solid tumors.

Current guidelines recommend estimating glomerular filtration rate (eGFR) using creatinine (eGFRcr) with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation as the first test for GFR evaluation, but the Cockcroft-Gault (CG) equation is still commonly used in oncology practice and clinical trials despite increasing evidence of its inaccuracy compared to measured GFR (mGFR). Guidelines recommend eGFR using cystatin C (eGFRcys) or both markers (eGFRcr-cys) as a confirmatory test, but neither was carefully evaluated in cancer patients. Therefore, we compared performance of the CKD-EPI equations and others to the CG equation in adults with a variety of solid tumors. The mGFR was determined by plasma clearance of 51Cr-EDTA. Bias was defined as the median of the differences between mGFR and eGFR while accuracy was defined as the percentage of estimates that differed by more than 30% from the measured GFR (1-P30). We prospectively recruited 1,200 patients between April 2015 and September 2017 with a mean age and mGFR of 58.8 years and 78.4 ml/min/1.73m2, respectively. Bias among eGFRcr equations varied from -8.1 to +6.1 ml/min/1.73 m2. CG was the least accurate, 1-P30 (95% confidence interval) was 24.9 (22.4- 27.3)%; CKD-EPI had 1-P30 of 19.1 (16.8-21.2)% while eGFRcr-cys had the best performance: bias -2.0 (-2.6 to -1.1) ml/min/1.73m2 and 1-P30 7.8 (6.3-9.4)%. Thus, the CG equation should not be preferred over CKD-EPI equation, and eGFRcr-cys can be used as a confirmatory test in adults with solid tumors. Hence, a major policy implication would be to adopt general practice guideline-recommended methods for GFR evaluation in oncology practice and clinical trials.

Comparison of plasma clearance of [51Cr]CrEDTA based on three, two and single samples to measure the glomerular filtration rate in patients with solid tumors: a prospective cross-sectional analysis.

OBJECTIVES: [51Cr]CrEDTA is used to measure the Glomerular Filtration Rate (GFR) in different clinical conditions. However, there is no consensus on the ideal number of blood samples to be taken and at what time points to measure its clearance. This study aimed to compare Slope Intercept (SI) and Single-Sample (SS) methods for measuring GFR in patients with solid tumors, stratified by age, GFR, and Body Mass Index (BMI). METHODS: 1,174 patients with cancer were enrolled in this prospective study. GFR was calculated by the SI method using blood samples drawn 2-, 4-, and 6-hours after [51Cr]CrEDTA injection (246-GFR). GFR was also measured using the SI method with samples at 2 and 4 hours (24-GFR) and at 4 and 6 hours (46-GFR), and SS methods according to Groth (4Gr-GFR) and Fleming (4Fl-GFR). Statistical analysis was performed to assess the accuracy, precision, and bias of the methods. RESULTS: Mean 246-GFR was 79.2 ± 21.9 mL/min/1.73 m2. ANOVA indicated a significant difference between 4Gr-GFR and the reference 246-GFR. Bias was lower than 5 mL/min/1.73 m2 for all methods, except for SS methods in subgroups BMI > 40 kg/m2; GFR > 105 or < 45. Precision was adequate and accuracy of 30 % was above 98% for all methods, except for SS methods in subgroup GFR < 45. CONCLUSION: 46-GFR and 246-GFR have high agreement and may be used to evaluate kidney function in patients with solid tumors. Single-sample methods can be adopted in specific situations, for non-obese patients with expected normal GFR.

Clinical features and outcomes of tuberculosis in kidney transplant recipients in Brazil: a report of the last decade.

BACKGROUND: Among kidney transplant recipients (KTRs), tuberculosis is one of the most common opportunistic infections and is associated with high morbidity and mortality. The aim of this study was to describe the incidence, clinical features, and prognosis of tuberculosis in KTRs. METHODS: Retrospective single-center observational study involving all cases of tuberculosis in KTRs between 2000 and 2010. RESULTS: Of the 1549 KTRs evaluated, 43 (2.8%) developed tuberculosis, translating to an annual incidence of 803 cases/100 000 patients, considerably higher than that reported for the general population of Brazil. The median time to tuberculosis (TB) onset after transplantation was 196 d (range, 19-3626 d). Of the KTRs with tuberculosis, 67% became infected within the first year post-transplant, 74% had pulmonary tuberculosis, and 7% had a previous history of active tuberculosis. No tuberculosis prophylaxis was employed before or after transplantation. The most common symptoms were fever (in 79%), cough (in 35%), and dyspnea (in 16%). The median time from the onset of symptoms to the start of treatment was 28 d. The median duration of antituberculosis therapy was 196 d. In 15 patients (35%), the immunosuppressive therapy was reduced, and the incidence of acute rejection was higher in patients with tuberculosis than in those without (44% vs. 28%). Mortality during tuberculosis treatment was 12% (5 cases), and all five deaths were attributed to tuberculosis. Ten-yr death-censored graft survival and patient survival were similar between patients with tuberculosis and those without. CONCLUSION: Among KTRs, symptoms of tuberculosis are often attenuated, which leads to delayed diagnosis, and tuberculosis-related mortality remains high.

Assessment of Kidney Function in Patients With Cancer.

Cancer patients are living longer. The sequelae of cancer treatment and the role of comorbid conditions present before the diagnosis, such as CKD, have been increasingly recognized. The interface between CKD and cancer is multifaceted. CKD is frequently observed in patients with cancer, and cancer treatment contributes to CKD development and progression. In addition, CKD has been recognized as an important risk factor for cancer development and reduced specific cancer survival. In this context, an accurate evaluation of the glomerular filtration rate (GFR) during oncologic treatment is pivotal and is used to define surgery strategies, program prophylactic management of contrasted examinations, make decisions on cisplatin eligibility, and adjust drug prescriptions, particularly chemotherapy agents. Although the most commonly used equations to estimate GFR based on serum creatinine levels in clinical practice (Cockcroft-Gault, Modification of Diet in Renal Disease Study, and CKD Epidemiology Collaboration equations) have not been validated in patients with cancer in large prospective studies, there is increasingly evidence supporting the use of CKD Epidemiology Collaboration equation to assess the GFR in patients with cancer, including for the use of chemotherapy prescriptions. Many patients with cancer may have changes in nutrition status and clearance measurements such as exogenous filtration markers might be extremely useful when clinical decisions differ depending on the GFR level. Future perspectives include the advent of new serum GFR biomarkers such as cystatin C, beta-trace protein, and beta-2 microglobulin as well as the GFR assessment by measuring total kidney parenchymal volume through image examinations.

[Attitude and opinion of medical students about organ donation and transplantation]. / Conhecimento e opinião de estudantes de medicina sobre doação e transplante de órgãos.

UNLABELLED: We analyzed the opinion and understanding of medical students about organ donation and transplantation. METHODS: 347 students voluntarily completed a questionnaire with 17 queries concerning organ donation and transplantation. They were analyzed to identify general tendencies and divided into five groups, according to their year of study (first through sixth year), to assess differences among the years. Students of the fifth and sixth years were placed in the same group. Results were analyzed by the Chi-square test. RESULTS: The intention to become a post mortem or living donor was of 89% and 90% respectively; however, only 62% were aware of living donation risks. 70% of the 347 students admitted regular or little knowledge of the subject, 90.2% considered organ transplantation an important issue for a medical graduation program, 76.9% considered informed/expressed consent the best organ donation criterion and 64.3% of them chose severity of patient disease as the best allocation condition. As students progressed in their studies their understanding about transplantation improved. Students of the fourth, fifth and sixth year manifested a negative attitude about organ donation to alcohol addicts, non donors, drug users, law offenders and foreigners. CONCLUSION: This data show the great interest and positive attitude of medical students toward organ donation and transplantation, despite the fact that most of them admitted having insufficient knowledge on the subject. A negative attitude by students of the fourth, fifth and sixth year on organ donation to alcohol addicts, non donors, drug users, law offenders and foreigners was also observed.

Sustained low-efficiency extended dialysis (SLED) with single-pass batch system in critically-ill patients with acute kidney injury (AKI).

BACKGROUND: Single-pass batch dialysis (SBD) is a well-established system for treatment of end-stage renal disease. However, little evidence is available on sustained low-efficiency extended dialysis (SLED) performed with SBD in patients with acute kidney injury (AKI) in the intensive care unit (ICU). METHODS: All SLED-SBD sessions conducted on AKI patients in nine ICUs between March and June 2010 were retrospectively analyzed regarding the achieved metabolic and fluid control. Logistic regression was performed to identify the risk factors associated with hypotension and clotting during the sessions. RESULTS: Data from 106 patients and 421 sessions were analyzed. Patients were 54.2 ± 17.0 years old, 51 % males, and the main AKI cause was sepsis (68 %); 80 % of patients needed mechanical ventilation and 55 % vasoactive drugs. Hospital mortality was 62 %. The median session time was 360 min [interquartile range (IQR) 300-360] and prescribed ultrafiltration was 1500 ml (IQR 800-2000). In 272 sessions (65 %) no complications were recorded. No heparin was used in 269/421 procedures (64 %) and system clotting occurred in 63 sessions (15 %). Risk factors for clotting were sepsis [odds ratio (OR) 2.32 (1.31-4.11), p = 0.004], no anticoagulation [OR 2.94 (1.47-5.91), p = 0.002] and the prescribed time (hours) [OR 1.14 (1.05-1.24), p = 0.001]. Hypotension occurred in 25 % of procedures and no independent risk factors were identified by logistic regression. Adequate metabolic and fluid balance was achieved during SLED sessions. Median blood urea decreased from 107 to 63 mg/dl (p < 0.001), potassium from 4.1 to 3.9 mEq/l (p < 0.001), and increased bicarbonate (from 21.4 to 23.5 mEq/l, p < 0.001). Median fluid balance during session days ranged from +1300 to -20 ml/24 h (p < 0.001). CONCLUSIONS: SLED-SBD was associated with a low incidence of clotting despite frequent use of saline flush, and achieved a satisfactory hemodynamic stability and reasonable metabolic and fluid control in critically-ill AKI patients.

Conhecimento e opinião de estudantes de medicina sobre doação e transplante de órgãos / Attitude and opinion of medical students about organ donation and transplantation

OBJETIVOS: Analisar o conhecimento e a opinião de estudantes de medicina sobre doação e transplante de órgãos. MÉTODOS: Trezentos e quarenta e sete estudantes responderam, voluntariamente, questionário com 17 perguntas sobre doação e transplante de órgãos. Eles foram avaliados globalmente, para verificar tendências gerais, e agrupados de acordo com o seu ano no curso médico (primeiro ao sexto), para avaliar diferenças entre os períodos. Alunos do quinto e sexto ano foram reunidos em um só grupo. Os resultados foram analisados pelo teste Qui quadrado. RESULTADOS: A intenção de ser doador post mortem foi de 89 por cento e intervivo de 90 por cento, contudo, apenas 62 por cento sabiam dos riscos da doação intervivo. Entre os 347 estudantes, 70 por cento admitiram conhecimento regular, ruim ou péssimo do assunto, 90,2 por cento consideraram importante o tema transplante para a graduação médica, 76,9 por cento consideraram o consentimento informado/expresso como o melhor critério de doação e 64,3 por cento optaram pela gravidade da doença do paciente como melhor forma de alocação. O entendimento sobre transplante aumentou conforme o avanço no curso de graduação. Estudantes do quarto, quinto e sexto ano adotaram atitude negativa, em comparação aos dos anos iniciais, quanto à doação de órgãos para pacientes alcoólatras, não doadores, usuários de drogas ilícitas, estrangeiros e criminosos. CONCLUSÃO: Este trabalho demonstrou grande interesse e atitude positiva dos estudantes de medicina sobre doação e transplante de órgãos, embora a maioria tenha declarado conhecimento deficiente sobre o tema. Observamos também atitude negativa dos estudantes do quarto, quinto e sexto ano médico em relação à doação para alcoólatras, não doadores, usuários de drogas ilícitas, estrangeiros e criminosos.

We analyzed the opinion and understanding of medical students about organ donation and transplantation. METHODS: 347 students voluntarily completed a questionnaire with 17 queries concerning organ donation and transplantation. They were analyzed to identify general tendencies and divided into five groups, according to their year of study (first through sixth year), to assess differences among the years. Students of the fifth and sixth years were placed in the same group. RESULTS:were analyzed by the Chi-square test. RESULTS: The intention to become a post mortem or living donor was of 89 percent and 90 percent respectively; however, only 62 percent were aware of living donation risks. 70 percent of the 347 students admitted regular or little knowledge of the subject, 90.2 percent considered organ transplantation an important issue for a medical graduation program, 76.9 percent considered informed/expressed consent the best organ donation criterion and 64.3 percent of them chose severity of patient disease as the best allocation condition. As students progressed in their studies their understanding about transplantation improved. Students of the fourth, fifth and sixth year manifested a negative attitude about organ donation to alcohol addicts, non donors, drug users, law offenders and foreigners. CONCLUSION: This data show the great interest and positive attitude of medical students toward organ donation and transplantation, despite the fact that most of them admitted having insufficient knowledge on the subject. A negative attitude by students of the fourth, fifth and sixth year on organ donation to alcohol addicts, non donors, drug users, law offenders and foreigners was also observed.