The liver-kidney axis: Is serum leptin a potential link in non-alcoholic fatty liver disease-associated chronic kidney disease?

BACKGROUND AND STUDY AIMS: Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for chronic kidney disease (CKD). Previous studies argued that leptin levels increase significantly with the progression of CKD. But the association between leptin and CKD has not been investigated in patients with NAFLD. Therefore, we conducted this study to establish whether increased leptin level is associated with CKD in NAFLD patients. PATIENTS AND METHODS: In our prospective study with a follow up period of six months thirty-five teetotaller biopsy-proven NAFLD patients were divided as groups with mild, versus advanced, fibrosis. Liver fibrosis was also assessed with Fibroscan. Serum leptin levels were measured by radioimmunoassay. For insulin resistance we used the homeostasis model assessment method (HOMA-IR). For the kidney function, we used the abbreviated formula Modification of Diet in Renal Disease (MDRD) formula, which estimates GFR. For statistical analysis, Student's-t test, Mann-Whitney test, linear regression-binary logistic regression analyses and the ROC curve analysis were used. RESULTS: Advanced fibrosis and increased HOMA-IR were risk factors for decreased eGFR. Leptin correlated inversely with advanced fibrosis (p: 0.03) and low leptin was a risk factor for CKD (p: 0.02). In ROC curve analysis, advanced fibrosis and low leptin were risk factors for decreased eGFR (p: 0.007 and 0.004, respectively). Low leptin level was dependently associated with decreased eGFR. CONCLUSION: Advanced fibrosis in NAFLD patients is a risk factor for CKD. Leptin correlated inversely with advanced fibrosis. Unlike the previous studies, which were not performed in NAFLD patients, we found decreased leptin in NAFLD patients with decreased eGFR. Low leptin level was found to be a dependent predictor for differentiating NAFLD patients with high risk for CKD.

Creatinine Clearance Measurement with Bioelectrical Impedance Analysis in Heart Failure Patients: Comparison with Estimated-Creatinine Clearance Formulas.

BACKGROUND: Kidney disease is common in patients with heart failure (HF). The Donadio equation combines plasma creatinine and bioimpedance vector analysis (BIVA) to estimate creatinine clearance. This study aimed to compare the Donadio formula to the Cockcroft-Gault (CG), Modification of Diet in Renal Disease Study (MDRD-4), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in patients with HF. METHODS: We analysed data from 900 patients (mean age: 76 ± 10 years) with HF. All of them underwent clinical, laboratory, BIVA, and echocardiographic evaluations. RESULTS: Donadio equation overestimated eGFR as compared to CG and CKD-EPI formulas (+6.8 and +12 mL/min/1.73 m2, respectively) while computing similar results to MDRD-4 (overestimation: +0.1 mL/min/1.73 m2). According to the different formulas, the prevalence of renal insufficiency (eGFR< 30 ml/min/1.73 m2) in relation to the different formulas was as follows: 24% with Donadio, 21% with CG, 13% with MDRD-4, and 23% with CKD-EPI formulas. All the equations demonstrated a high precision rate (r>0.8 for all). There was a "good" agreement between the Donadio and CG/MDRD-4 formulas and "fair" with the CDK-EPI formula. The Donadio equation showed a high accuracy in predicting severe renal dysfunction (eGFR< 30 mL/min/1.73 m2) in patients with HF (AUC > 0.9), showing comparable performances to CG. CONCLUSION: The Donadio formula provided an estimation of GFR comparable to MDRD-4 in HF patients, independently from acute or chronic HF conditions. The use of BIVA in HF patients may be adopted both for HF management and for evaluating kidney function.

Different Renal Function Equations and Dosing of Direct Oral Anticoagulants in Atrial Fibrillation.

Background: Randomized trials of direct oral anticoagulants (DOACs) adopted the Cockcroft-Gault (CG) formula to calculate estimated glomerular filtration rate (eGFR) to determine the dosages of DOACs. Objectives: The authors aimed to investigate the agreements/disagreements of eGFRs calculated using different equations (CG, Modified Diet in Renal Disease [MDRD], and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formulas), and their impacts on the dosages of DOACs and clinical outcomes. Methods: Medical data from a multicenter health care provider in Taiwan including 39,239 patients with atrial fibrillation were used. Among these patients, there were 11,185 and 2,323 patients treated with DOACs and warfarin, respectively. Results: At the cutoff values of eGFR of <15, 15-50, and >50 mL/min, the agreements were 78% between MDRD and CG and 81% between CKD-EPI and CG. The disagreements among the different equations were largely due to overestimations, especially for patients aged >75 years and with a body weight of <50 kg (58.8% for MDRD and 50.9% for CKD-EPI). Among patients receiving DOACs whose dosages were defined as "on label" based on MDRD or CKD-EPI, only those whose dosages were "truly on label" based on CG were associated with a lower risk of major bleeding (adjusted HR: 0.34; 95% CI: 0.26-0.45) compared to warfarin. Conclusions: The adoptions of MDRD or CKD-EPI rather than CG would result in inappropriate dosing of DOACs (mainly overdosing), which would attenuate the advantages of DOACs compared to warfarin. The CG equation should be used as the gold standard to calculate eGFRs and guide the DOAC dosages.

Long-term Care of the Adult Liver Transplant Recipient.

While outcomes after liver transplantation have increased over the last two decades, this is primarily as a consequence of a reduction in early deaths and survival of those who survive the first 6 months has not significantly changed. Causes of premature death and graft loss include cardiovascular disease, renal impairment, malignancy and some infections. As the number of transplant recipients increase, care is being given by primary and secondary care clinicians. Management of the well patient is crucially dependent on careful assessment and where appropriate intervention, especially of cardiovascular risk - such as advice about avoidance of weight gain; management of hypertension, hyperlipidaemia and diabetes; and provision of appropriate lifestyle advice. Other interventions include surveillance for de novo malignancies, active management of immunosuppressive regimen with the need to tailor immunosuppression to the individual. Prompt investigation of abnormalities of liver function is essential. Immune-mediated graft damage still occurs but is less common as a cause for graft loss. Adherence is sometimes an issue, especially in teenagers and young adults, and should be considered and support given where needed. Immunisations (avoiding live and attenuated vaccines) should be encouraged. Recurrence of disease remains an issue, and some interventions (such as appropriate use of antiviral therapy for those grafted with viral hepatitis, use of ursodeoxycholic acid for those grafted for primary biliary cholangitis or long-term steroids for those grafted for autoimmune disease) may improve and maintain graft function. Close collaboration between recipient and the attending clinicians in primary, secondary and tertiary care and close attention to modifiable conditions will lead to improved outcomes.

Carboplatin dose calculations for patients with lung cancer: significant dose differences found depending on dosing equation choice.

BACKGROUND: Carboplatin is the backbone cytotoxic agent for many chemotherapy regimens for lung cancer. Dosing of carboplatin is complicated due to its relationship to renal function and narrow therapeutic index. Overestimation of renal function may lead to supratherapeutic dosing and toxicity, while underestimation may lead to underdosing and therapeutic failure. Although the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations have higher accuracy in estimating glomerular filtration rate (eGFR), the Cockcroft Gault (CG) formula has been historically used for carboplatin dosing internationally. METHODS: We compared these formulae to identify patient profiles that were associated with significant carboplatin dose variation by retrospectively analysing the carboplatin dosing of 96 patients with lung cancer. Carboplatin doses were calculated using eGFR generated by MDRD, CKD-EPI 2009 and CKD-EPI 2021 equations. These three hypothetical doses were compared to actual CG-based doses prescribed. RESULTS: MDRD and CKD-EPI equations resulted in comparable carboplatin doses; however, CG doses diverged markedly with up to 17% of the patients receiving a carboplatin dose that was at least 20% higher than a non-CG formula would have predicted, and 20% received a dose that was at least 20% lower than a non-CG formula would have predicted. Our data suggest CG use overestimates kidney function in patients with a higher bodyweight and body surface area (BSA) while underestimating it in patients with a lower bodyweight and BSA. Importantly, we demonstrate potential real-world benefit as CKD-EPI predicted lower doses for patients whose (CG-derived) carboplatin dose was later reduced following clinical assessment prior to infusion. CONCLUSIONS: We have therefore confirmed significant differences in carboplatin dosing depending on the equation used in our modern patient population and suggest that use of CKD-EPI provides the most clinically appropriate carboplatin dosing and should be implemented as the new standard of care internationally.

The effect of race coefficients on preemptive listing for kidney transplantation.

Background: Race coefficients of estimated glomerular filtration rate (eGFR) formulas may be partially responsible for racial inequality in preemptive listing for kidney transplantation. Methods: We used the Scientific Registry of Transplant Recipients database to evaluate differences in racial distribution of preemptive listing before and after application of the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) race coefficients to all preemptively listed non-Black kidney transplant candidates (eGFR modulation). Odds of preemptive listing were calculated by race, with Black as the reference before and after eGFR modulation. Variables known to influence preemptive listing were included in the model. Results: Among 385 087 kidney-alone transplant candidates from 1 January 2010 to 2 December 2020, 118 329 (30.7%) candidates were identified as preemptively listed (71.7% White, 19% Black, 7.8% Asian, 0.6% multi-racial, 0.6% Native American and 0.3% Pacific Islander). After eGFR modulation, non-Black patients with an eGFR ≥20 mL/min/1.73 m2 were removed. Compared with Black candidates, the adjusted odds of preemptive listing for White candidates decreased from 2.01 [95% confidence interval (95% CI) 1.78-2.26] before eGFR modulation to 1.18 (95% CI 1.0-1.39; P = 0.046) with the MDRD and 1.37 (95% CI 1.18-1.58) with the CKD-EPI equations after adjusting for race coefficients. Conclusions: Removing race coefficients in GFR estimation formulas may result in a more equitable distribution of Black candidates listed earlier on a preemptive basis.

Functional tests in patients with ischemic heart disease.

Lately, easier and shorter tests have been used in the functional evaluation of cardiac patients. Among these, walking speed (WS) and Timed Up and Go (TUG) tests are associated with all-cause mortality, mainly cardiovascular and the rate of re-hospitalization, especially in the elderly population. We prospectively analyzed a group of 38 patients admitted to the Cardiology Clinic from Elias Hospital, Romania, with chronic coronary syndrome (CCS) (n=22) and STEMI (n=16). We assessed the patients immediately after admission and before discharge with G-WALK between the 1st and 30th of September 2019. Our study group had a mean age of 62.7±12.1 years. Patients with a low WS were older (69.90±12.84 vs. 59.90±10.32 years, p=0.02) and had a lower serum hemoglobin (12.38±1.20 vs. 13.72±2.07 g/dl, p=0.02). The WS significantly improved during hospitalization (p=0.03) after optimal treatment. The TUG test performed at the time of admission had a longer duration in patients with heart failure (14.05 vs. 10.80 sec, p=0.02) and was influenced by patients' age (r=0.567, p=0.02), serum creatinine (r=0.409, p=0.03) and dilation of right heart chambers (r=0.399, p=0.03). WS and TUG tests can be used in patients with CCS and STEMI, and are mainly influenced by age, thus having a greater value among the elderly.

Individualized prediction for the occurrence of acute kidney injury during the first postoperative week following cardiac surgery.

STUDY OBJECTIVE: To develop individualized dynamic predictions for the occurrence of acute kidney injury (AKI) during the first postoperative week after cardiac surgery. DESIGN: Observational retrospective cohort study. SETTING: Single university teaching hospital in Madrid, Spain. PATIENTS: 3960 cases of major cardiac surgery performed from January 2002 to December 2013. MEASUREMENTS: Baseline demographic and clinical characteristics, intraoperative risk factors, and repeated postoperative estimated glomerular filtration rates (eGFR). The primary outcome was AKI during the first postoperative week (stage 1 or higher of the Acute Kidney Injury Network). The dataset was split in two random samples (exploratory and validation). By combining time-to-event outcomes (AKI), and longitudinal data (repeated postoperative eGFR), we developed two different joint models for patients with normal and high baseline levels of serum creatinine (sCr). MAIN RESULTS: AKI occurred in 1105 patients (31%, 95% confidence interval [CI] 29.5-32.5) in the exploratory sample and 128 (32.2%, 95% CI 27.6-36.8) in the validation sample. For high baseline sCr patients, the risk of an AKI event was associated with the eGFR trajectory (hazard ratio [HR] 0.91, 95% CI 0.90-0.92), as well as with age, and cardiopulmonary bypass time. The normal baseline sCr model incorporated the same covariates and intraoperative transfusion. In this second model, the risk of an AKI event was associated with both the eGFR trajectory (HR 0.91, 95% CI 0.91-0.92, for the current value of eGFR), and with its slope at that point (HR 0.96, 95% CI 0.94-0.99). So AKI risk decreased when the eGFR values increased, in accordance with the speed of this rise. Internal validation showed good discrimination and calibration of both joint models. The AUCs were always higher than 0.7. CONCLUSIONS: The joint models obtained combining both patient risk factors and postoperative eGFR values, are useful to predict individualized risk of cardiac surgery-associated AKI. Predictions can be updated as new information is gathered.

The Glomerular Filtration Rate: From the Diagnosis of Kidney Function to a Public Health Tool.

The prevalence of chronic kidney disease (CKD) continues to increase worldwide, as well as the associated morbidity and mortality and the consequences on the patients' quality of life and countries' economies. CKD often evolves without being recognized by patients and physicians, although the diagnosis is based on two simple laboratory data: the estimated glomerular filtration rate (eGFR) and urine analysis. To measure GFR, the knowledge about the physiologic processes at the nephron level, the concept of clearance, and the identification of creatinine as a suitable endogenous marker for measuring the creatinine clearance (CrCl) had to be previously developed. On those bases, different equations to calculate CrCl (Cockcroft and Gault, 1976), or estimated GFR (four variables MDRD, 1999; CKD-Epi, 2009, among others) were generated. They all include creatinine and some demographic data, such as sex and age. However, to compare results throughout life or among laboratories, the creatinine determination must be standardized. In addition, the accuracy of these equations remains controversial in certain subgroups of patients. For these reasons, other mathematical models to improve CrCl estimation have been developed, such as when urine cannot be collected, in debilitated elderly patients and patients with trauma, diabetes, or obesity. Currently, eGFR in adults can be measured and reported immediately, using isotope dilution mass spectrometry traceable creatinine-based equations. In conclusion, based on knowledge obtained from renal physiology, eGFR can be used in the clinic for the diagnosis and early treatment of CKD, as well as a public instrument to estimate the prevalence.

Evaluating the Impact and Rationale of Race-Specific Estimations of Kidney Function: Estimations from U.S. NHANES, 2015-2018.

BACKGROUND: Standard equations for estimating glomerular filtration rate (eGFR) employ race multipliers, systematically inflating eGFR for Black patients. Such inflation is clinically significant because eGFR thresholds of 60, 30, and 20 ml/min/1.73m2 guide kidney disease management. Racialized adjustment of eGFR in Black Americans may thereby affect their clinical care. In this study, we analyze and extrapolate national data to assess potential impacts of the eGFR race adjustment on qualification for kidney disease diagnosis, nephrologist referral, and transplantation listing. METHODS: Using population-representative cross-sectional data from the United States National Health and Nutrition Examination Survey (NHANES) from 2015-2018, eGFR values for Black Americans were calculated using the Modification of Diet in Renal Disease (MDRD) equation with and without the 1.21 race-specific coefficient using cohort data on age, sex, race, and serum creatinine. FINDINGS: Without the MDRD eGFR race adjustment, 3.3 million (10.4%) more Black Americans would reach a diagnostic threshold for Stage 3 Chronic Kidney Disease, 300,000 (0.7%) more would qualify for beneficial nephrologist referral, and 31,000 (0.1%) more would become eligible for transplant evaluation and waitlist inclusion. INTERPRETATION: These findings suggest eGFR race coefficients may contribute to racial differences in the management of kidney. We provide recommendations for addressing this issue at institutional and individual levels. FUNDING: No external funding was received for this study.

Correlación entre las ecuaciones para la estimación del filtrado glomerular (MDRD, CKD-EPI,) y la depuración de creatinina en orina de 24 horas en pacientes oncológicos / Correlation between the equations for the estimation of the filtering glomerular (MDRD, CKD-EPI,) and creatinine clearance in 24-hour urine in cancer patients

Demostrar la correlación entre las ecuaciones MDRD, CKD-EPI con la depuración de creatinina de 24 horas en pacientes oncológicos. Estudio transversal realizado en el Instituto Oncológico Nacional Dr Juan Tanca Marengo durante el periodo de tiempo comprendido entre el mes de agosto 2019 a agosto de 2020. Al evaluar las distintas variable MDRD obtuvo un valor promedio de 44,81 ml/min/m2 con un intervalo de 41,07 ­ 48,55 ml/min/m2 , la variable CKD-EPI el valor promedio fue 43,59 + 18,09 ml/min/m2 con un intervalo de 40,01 ­ 47,18 ml/min/m2 , para el estándar de referencia depuración de creatinina de 24 horas el promedio fue de 54ml/min/m2 Al evaluar la relación entre los dos estimadores de TFG se encontró que ambos presentan una fiabilidad regular presentando una correlación intraclase de 0,43 (p<0,05) entre los estimadores CKD-EPI y MDRD en relación con la TFG de creatinina de 24horas. Cuando se evaluó pacientes con tumores sólidos y hematológicos, se encontró una mayor correlación intraclase con la escala MDRD-4 0,60 (0,25 ­ 0,82) < 0,05 en tumores hematológicos en comparación con CKD-EPI. En la población general, CKD-EPI es la fórmula recomendada, y se está recomendado con mayor frecuencia en pacientes oncológicos. Nuestro estudio demostró que la ecuación MDRD es la fórmula que mejor se correlaciona con la depuración de creatinina de 24 horas, siendo mejor en el grupo de tumores hematológicos, pero no existe diferencia estadísticamente significativa entre las dos ecuaciones.

To demonstrate the correlation between the MDRD, CKD-EPI equations with the 24-hour creatinine clearance in cancer patients. Cross-sectional study carried out at the National Oncological Institute Dr Juan Tanca Marengo during the period of time between the month of August 2019 to August 2020. When evaluating the different MDRD variables, an average value of 44.81 ml / min / m2 was obtained with an interval of 41.07 ­ 48.55 ml / min / m2, the CKD-EPI variable the average value was 43.59 + 18 , 09 ml / min / m2 with an interval of 40.01 ­ 47.18 ml / min / m2, for the reference standard creatinine clearance of 24 hours the average was 54 ml / min / m2 When evaluating the relationship between the two estimators of GFR, it was found that both present a regular reliability, presenting an intraclass correlation of 0.43 (p <0.05) between the CKD-EPI and MDRD estimators in relation to the 24-hour creatinine GFR. When patients with solid and hematological tumors were evaluated, a higher intraclass correlation was found with the MDRD-4 scale 0.60 (0.25 ­ 0.82) <0.05 in hematological tumors compared to CKD-EPI. In the general population, CKD-EPI is the recommended formulation, and it is more frequently recommended in cancer patients. Our study showed that the MDRD equation is the formula that best correlates with 24-hour creatinine clearance, being better in the group of hematological tumors, but there is no statistically significant difference between the two equations.

Prevalence of Renal Impairment in a US Commercially Insured Rheumatoid Arthritis Population: A Retrospective Analysis.

INTRODUCTION: Global prevalence estimates for chronic kidney disease (CKD) in rheumatoid arthritis (RA) vary. This study assessed real-world prevalence estimates of renal impairment, based on estimated glomerular filtration rate (eGFR), among commercially insured patients with RA in the United States (US). METHODS: In this retrospective cohort study, we used administrative claims data from the HealthCore Integrated Research Database (HIRD®) between January 2013 and December 2018. Adult patients with ≥ 2 claims for RA and ≥ 2 serum creatinine (SCr) measurements ≥ 90 days apart on or after the index date were included. eGFR was calculated per the Modification of Diet in Renal Disease equation. Prevalence of eGFR-based renal impairment was estimated for the overall RA population and for two subgroups: patients on advanced therapies (biologic disease-modifying antirheumatic drugs/tofacitinib) and patients stratified based on health plan types. RESULTS: Among 128,062 patients with ≥ 2 RA claims, 42,173 had qualifying SCr measurements, 16,197 were on advanced RA therapies, and 4911 had Medicare Advantage or Supplemental plus Part D coverage. For the overall population and the subgroup on advanced therapies, mild renal impairment was observed in 52% and 51%, moderate renal impairment in 9% and 7%, and severe renal impairment in 0.5% and 0.3% of patients, respectively. Moderate and severe renal impairment was more prevalent in the Medicare Advantage/Supplemental plus Part D population compared to the commercial coverage population. CONCLUSIONS: Approximately 7-10% of commercially insured adult patients in the US with RA had moderate or severe renal impairment. Assessment of renal function is an important consideration for safe treatment.

Calculating estimated glomerular filtration rate without the race correction factor: Observations at a large academic medical system.

BACKGROUND AND AIMS: Creatinine-based MDRD and CKD-EPI equations include a race correction factor, which results in higher eGFR in Black patients. We evaluated the impact on our patient population upon adoption of the CKD-EPI equation and the removal of the race correction factor from the equation. MATERIALS AND METHODS: Retrospective analysis of blood creatinine results and respective eGFR values calculated by the MDRD or CKD-EPI equation without the race correction factor (CKD-EPINoRace) in a large academic medical system over a 20.5-month period. RESULTS: In our population, when changing from MDRD to CKD-EPINoRace, we observed that 3.5% of all patients were reclassified to categorically have worse kidney function. However, we also observed fewer patients overall with eGFR below 60 mL/min/1.73 m2. Around 60 and 20 mL/min/1.73 m2, 2.96% and 0.16% of all patients > 65 years of age were reclassified, as were 4.29% and 0.03% of all Black patients, respectively. When calculated with CKD-EPINoRace, median eGFR was not meaningfully different between Black and non-Black patients (p = 0.02). CONCLUSIONS: Changing from MDRD to CKD-EPINoRace could lead to a lower referral rate to nephrology. The distributions of creatinine and eGFR calculated with CKD-EPINoRace were not meaningfully different in Black and non-Black patients.

Comparability of serum creatinine-Based glomerular filtration rate equations in West African adult communities.

BACKGROUND: The clinical diagnosis of chronic kidney disease (CKD) is based on estimated glomerular filtration rate (GFR) using serum creatinine-based equations. Many formulas are used in estimating GFR. OBJECTIVES: We set out to determine the degree of agreement between the Cockcroft-Gault (CG), 4-variable Modification of diet in renal disease (MDRD). Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in our indigenous population. PATIENTS AND METHODS: Adult participants were recruited across all sectors of life, education, and occupation. Blood pressure, fasting blood glucose, lipid profile, urinalysis, serum creatinine, and anthropometry were measured. Estimated GFR (eGFR) was computed using CG, MDRD, and CKD-EPI equations with and without the race factor. The Lin's concordance index (rho_c) and Bland-Altman analysis were used to determine the degree of agreement between various pairs of creatinine-based eGFR equations [MDRD with the race factor (MDRDw)]; MDRD without the race factor (MDRD); CKD-EPI with race factor (CKD-EPIw); CKD-EPI without the race factor (CKD-EPI), and the CG equation. RESULTS: Two hundred and sixty-one adults, mean age 47.5 ± 9.9 years, 45.2% females participated in the study. Hypertension prevalence in the study population was 41.4 (95% CI 35.3-47.6%) while diabetes mellitus was 8.1% (95% CI 5.0-12.0%). The proportion of individuals with eGFRCKD-EPI less than 60 ml/min/1.73 m2 was 17.6 (95% CI 13.2-22.8%). All pairs of rho_c were lower than the threshold of 0.9 except for eGFRCKD-EPI versus eGFRCKD-EPw. CONCLUSION: There is significant discordance in the eGFR obtained from the various serum creatinine-based GFR equations in our population suggesting the need to validate these equations and determine the best equation for our general population.

Performance of the various serum creatinine-based GFR estimating equations in pediatric kidney transplant recipients, stratified by age and CKD staging.

BACKGROUND: Numerous equations are used to estimate glomerular filtration rate (eGFR), based on serum creatinine (SCr), demographic and anthropometric data, none established in pediatric kidney transplant recipients. This study aimed to validate the available SCr-based eGFR equations in comparison with a measured (mGFR), stratified by chronic kidney disease (CKD) stage and age at the time of testing. METHODS: One hundred twenty-seven pediatric kidney transplant recipients with 411 mGFR values (plasma clearance of iothalamate) were enrolled in this retrospective study. The bias, precision, and accuracy (percentage of estimates within 10% and 30% of mGFR) of five SCr eGFR equations (original Schwartz, CKiDSCr equation, Pottel, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) were assessed. RESULTS: Height-independent Pottel equation performed well across all the categories of age and CKD staging. CKiDSCr equation performed well in CKD stages II-V. The CKiDSCr equation had a lower bias in children < 15 years of age, while MDRD and CKD-EPI equations had less bias in children > 15 years. Overall, both the Pottel and CKiDSCr equations had high accuracy (80%) and low bias (< 5 ml/min/1.73 m2). In contrast, the original Schwartz, MDRD, and CKD-EPI equations displayed high bias and low precision/accuracy. CONCLUSIONS: Given their low bias and high accuracy across ages and CKD stages, the Pottel or the CKiDSCr equation is better to assess eGFR in pediatric kidney transplant recipients. The Pottel equation outperformed other eGFR equations in adolescents.

Long-term Management of the Adult Liver Transplantation Recipients.

The survival of liver transplantation (LT) recipients has been improved remarkably in short-term. The major causes of mortality in long-term include nonimmunological causes such as cardiovascular, de novo malignancy, chronic kidney disease, and recurrence of primary disease. Rejection-related mortality is rare in the long-term after LT. We discuss nonrejection causes of long-term morbidity/mortality, risk factors, and management strategies in LT recipients. In addition, we discuss osteoporosis, contraception, and pregnancy in LT recipients.

Midazolam and hydroxymidazolam plasma concentrations can be monitored with selected biochemical and physiological parameters of palliative care patients.

RATIONALE & OBJECTIVE: Midazolam is one of top three drugs used in palliative care. Its use increases in the last days of hospice patients' lives while safe dosage can be challenging. Equations currently used to estimate glomerular filtration rate, e.g: the Cockroft-Gault (eGFRCR) and the Modification of Diet in Renal Disease (eGFRMDRD) ones, do not generate precise calculations, especially in palliative patients exhibiting variations in body parameters. Our aim was to seek new relationships between mean midazolam (Mavg) and alfahydroxymidazolam (OH-Mavg) concentrations in plasma, and selected biochemical and physiological parameters of palliative patients, to enable optimal midazolam pharmacotherapy. STUDY DESIGN, PARTICIPANTS AND INTERVENTIONS: The pilot study included 11 Caucasians, aged 42-95, with advanced cancer disease, receiving midazolam in a hospice in-patient unit. We tested correlations among Mavg, BMI, eGFRMDRD, midazolam clearance (CL), OH-Mavg, bilirubin (Bil) and blood creatinine concentration (Cr). F test and leave-one out (LOO) validation was applied to verify the correlations' significance and predictive ability. RESULTS: We found ten statistically significant (p < 0.05) correlations related to midazolam pharmacokinetics and physiological factors. We formulated two equations with high degree of predictive ability, based on the eGFRMDRD→CL and the (Bil + BMI × Ln(Cr))→Mavg-(OH-Mavg) correlations. The limitations of the study mainly revolve around its pilot nature and the need to continue testing the results on a bigger population. No funding to disclose. CONCLUSIONS: The significance of correlations corresponding to the arithmetic expressions confirms that Bil, BMI, Ln(Cr) analyzed simultaneously report a series of processes on which midazolam metabolism depends. Two of ten correlations proposed came close to meet all LOO validation criteria. Current findings can help optimize midazolam treatment in palliative therapy.

Proinflammatory cytokines predict the incidence of diabetic peripheral neuropathy over 5 years in Chinese type 2 diabetes patients: A prospective cohort study.

BACKGROUND: Inflammation has been implicated in the pathogenesis of diabetic peripheral neuropathy (DPN) as suggested in various cross-sectional studies. However, more convincing prospective studies in diabetes patients are scarce. Therefore, we aimed to evaluate whether proinflammatory cytokines could predict the incidence of DPN through a prospective study with a five-year follow-up. METHODS: We followed up 315 patients with diabetes who did not have DPN, recruited from five community health centers in Shanghai in 2014, for an average of 5.06 years. Based on the integrity of blood samples, 106 patients were selected to obtain the proinflammatory cytokines. Plasma markers of proinflammatory cytokines at baseline included interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and intercellular adhesion molecule 1 (ICAM-1). Neuropathy was assessed by MSNI at baseline and during follow-up. FINDINGS: Among the 106 chosen patients, 63 developed DPN after 5.06±1.14 years of follow-up. The baseline plasma levels of TNF-α, IL-6, and ICAM-1 were higher in the neuropathic group (p<0.05). In multivariate models, increased plasma levels of TNF-α (hazard ratio, HR: 8.74 [95% confidence interval, CI: 1.05-72.68]; p <0.05) and ICAM-1 (HR 23.74 [95% CI:1.47-383.81]; p<0.05) were both associated with incident DPN, after adjusting for known DPN risk factors. INTERPRETATION: Increased plasma levels of proinflammatory factors, especially TNF-α and ICAM-1, predicted the incidence of DPN over 5 years in Chinese diabetes patients, but larger longitudinal studies are required for confirmation. FUNDING: National Natural Science Foundation of China, Shanghai Talent Development Fund Program, Shanghai Shenkang Hospital Developing Center Clinical Scientific and Technological Innovation Program, Shanghai Science and Technology Committee Program, Shanghai General Hospital Program of Chinese traditional and Western medicine combination and Shanghai Municipal Commission of Health and Family Planning Clinical Research Project.

Comparison of Equations To Estimate Glomerular Filtration Rate and Their Impact on Frequency of Cisplatin-associated Acute Kidney Injury.

Background: Accurate estimation of kidney function is essential for patient selection and drug dosing in patients with cancer. eGFR equations are necessary for decision making and monitoring. Our aim was to identify which of these equations-estimated creatinine clearance (eCrCl) by Cockcroft-Gault (CG), eGFR by Modification of Diet in Renal Disease (eGFRMDRD), CKD Epidemiology Collaboration (eGFRCKD-EPI) or the recently proposed Janowitz-Williams equation (eGFRJ-W)-would be most suitable for GFR estimation among patients with cancer receiving cisplatin. Methods: We assembled a cohort of 5274 patients with cancer treated with cisplatin-based chemotherapy at two large cancer centers. We ascertained the frequency of cisplatin-associated AKI (C-AKI) defined as a ≥0.3 mg/dl rise in serum creatinine over baseline. We compared baseline eGFR and eCrCl using Bland-Altman (B-A) plots, coefficients of variation (CV), and concordance correlation coefficients. We calculated the positive predictive value (PPV), negative predictive value (PPV), accuracy, and area under the curve (AUC). Results: Patients were predominantly middle aged (median 58 years, IQR 49-66 years), overweight (median BMI 26.2, IQR 23.1-29.8 kg/m2), and White (88%), with a median baseline creatinine of 0.8 mg/dl and median cisplatin dose of 99 mg. C-AKI developed in 12% of the cohort. eGFRCKD-EPI had the highest PPV and AUC. eGFRCKD-EPI and eGFRMDRD, along with their BSA-modified counterparts, had the closest agreement with the lowest CV (7.2, 95% CI, 7.0 to 7.3) and the highest concordance. C-AKI was lowest when using eGFRCKD-EPI to define eGFR ≥60 ml/min per 1.73 m2. Conclusions: On the basis of its superior diagnostic performance, eGFRCKD-EPI should be used to estimate GFR in patients being considered for cisplatin-based chemotherapy.