No abstract

e16536 Background: Tyrosine kinase inhibitors (TKI) are currently the recommended treatment option for advanced renal cell carcinoma (aRCC) patient. Previous studies have shown some hepatorenal toxicity of TKI regimens, but differences in toxicity and long-term toxicity of TKIs have rarely been reported. This study aims to compare short- and long-term hepatorenal toxicity differences between pazopanib and sunitinib, and to explore the factors predisposing to hepatorenal toxicity. Methods: COMPARZ study was a randomized phase III non-inferiority study comparing pazopanib and sunitinib in aRCC patients. Patients without liver metastasis and with available alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin results were enrolled to evaluate the effect of TKI on liver function. Patients with available serum creatinine (Cr), blood urea nitrogen (BUN), urine protein/creatinine ratio (UPC), and creatinine clearance (CrCl) were enrolled to evaluate factors associated with abnormal renal function. Lab indicators were compared between baseline and at months 12, 24, and 36 by paired t-test respectively. Linear mixed models were used to compare the difference in changes between treatment arms. Multivariate logistic regression was performed to examine the factors associated with recorded adverse events of hepatorenal toxicities. Results: Patients with abnormal liver function tests at baseline had higher elevated ALT, AST and total bilirubin levels at 12 months after TKIs treatment compared with patients who had normal baseline results. ALT levels were not significantly different between pazopanib arm and sunitinib arm at 12, 24 and 36 months. However, patients in the sunitinib arm had significantly higher AST levels than the pazopanib arm at 12 months (p = 0.049). There was no significant difference in total bilirubin level between pazopanib and sunitinib arm. Asian race and pazopanib were two factors that was significantly associated with increased risk of developing abnormal liver function. At 12 months, Cr levels were higher in the sunitinib arm compared with the pazopanib arm . BUN levels were lower in the pazopanib arm at 12 months but conversely was higher in the sunitinib arm at 24 months. UPC levels were significantly elevated in both treatment arms at 12 months (p < 0.001) and 24 months (p = 0.008). CrCl levels decreased in both treatment arms, and was more obvious in the sunitinib group at 12 months and 24 months. Notably, male patients, Asian race, high BMI, and sunitinib were risk factors that were significantly associated with abnormal renal function. Conclusions: Compared with sunitinib, pazopanib was associated with a higher risk of hepatoxicity but lower risk of nephrotoxicity. Overall, Asian patients have a higher risk of developing abnormal liver and renal functions after TKI treatment.

Objective: The primary aim of this study is to examine the hemodynamics of retrobulbar and intrarenal in the changes of early stage of type 2 diabetes mellitus (T2DM) patients from 2000 to 2015 and to assess incidence associated with diabetic kidney disease (DKD) and diabetic retinopathy (DR). Method: Our study contained 60 subjects newly diagnosed of T2DM were divided into 2 groups base on the mean resistive index (RI) (≤0.7 and >0.7) of hemodynamic and to compare between-group differences of the early changes in hemodynamics of retrobulbar and intrarenal and also to conclude the incidences of diabetic kidney disease (DKD) and diabetic retinopathy (DR)subsequently with a long follow-up duration(2000–2015). First, to compare the mean RI of central retinal artery (CRA) between 2 groups. Second, to compare the mean RI of intrarenal hemodynamics in the bilateral interlobular renal arteries, renal function parameters (blood urea nitrogen (BUN), creatinine (Cr), blood glucose parameters (glycosylated hemoglobinA1c (HbA1c), fasting plasma glucose (FBG), and 2-hour postprandial blood glucose (2hPBG)), glomerular filtration rate (GFR), albumin excretion rate (AER), and urine albumin-to-creatinine ratio (UACR) between 2 groups. Results: First part of our follow-up studies was to compare hemodynamic RI index of retrobulbar in years of 2000 and 2015, both renal function and blood glucose parameters were fund significantly enhanced in subject group RIs ≤0.7. Incidence of DKD and DR was notably lower in group RIs ≤0.7 than group RIs > 0.7, difference was statistically significant (P < .05). Incidence of HbA1c ≤7% was higher in group RIs ≤0.7 than group RIs >0.7, but difference was not statistically significant (P > .05). Incidence of proliferative diabetic retinopathy (PDR) was notably lower in group RIs ≤0.7 than group RIs >0.7, but the difference was not statistically significant (P > .05). Second part of our follow-up studies was to compare hemodynamic RI index of interlobular renal in years of 2000 and 2015, both renal function and blood glucose parameters were fund significantly enhanced in subject group RIs ≤0.7. Compared data of various incidences from first part of study were coherent with second part. (Incidence of DKD and DR was notably lower in group RIs ≤0.7 than group RIs >0.7, difference was statistically significant (P < .05). Incidence of HbA1c ≤7% was higher in group RIs ≤0.7 than group RIs >0.7, but difference was not statistically significant (P > .05). Incidence of PDR was notably lower in group RIs ≤0.7 than group RIs >0.7, but the difference was not statistically significant (P > .05). Conclusions: RIs of retrobulbar and interlobular renal which would serve as a good predictors for the hemodynamics changes in retrobulbar and intrarenal would assess incidence of DKD and DR during the preclinical stage in long-term range excluding renal function and HbA1c in T2DM patients.

PurposeThe main objectives of this study were to assess the early changes in pulmonary function and intrarenal haemodynamics and to determine the correlation between pulmonary function and intrarenal haemodynamics in patients with type 2 diabetes mellitus (T2DM).Methods96 patients with T2DM (diabetes group) without diabetes kidney disease (DKD) and 33 healthy subjects (control group) were enrolled in studies intended to assess the early changes in pulmonary function and intrarenal haemodynamics associated with diabetes, as well as to determine the correlation between pulmonary function and intrarenal haemodynamics.ResultsPulmonary functional parameters were negatively correlated with HbA1c levels and diabetes duration (P< 0.05). Moreover, renal functional parameters were positively correlated with HbA1c levels and diabetes duration (P<0.05). Additionally, pulmonary functional parameters were negatively correlated with renal functional parameters (P<0.05). Multiple linear regression analysis of the relationship between pulmonary functional parameters and the bilateral kidney arterial resistivity index (RI) showed that all the pulmonary functional parameters were significantly correlated with the arterial RI (P< 0.05).ConclusionsPatients displayed changes in pulmonary function and intrarenal haemodynamics during the preclinical stages of DKD. Regulating glycaemia may improve intrarenal haemodynamics in the bilateral interlobular renal arteries. Moreover, during the preclinical stages of DKD, the right kidney RI is a effective predictor of early changes in pulmonary function in adult T2DM patients.Trial registrationClinicalTrials.gov (NCT02798198); registered 8 June 2016.