Changes In Renal Biomarkers Research Articles

212-OR: Five-Year Follow-Up of Lipid, Inflammatory, Hepatic, and Renal Markers in People with T2 Diabetes on a Very-Low-Carbohydrate Intervention Including Nutritional Ketosis (VLCI) via Continuous Remote Care (CRC)

Objective: To address the long-term effectiveness of VLCI for T2D, we report changes in lipids, inflammatory, hepatic, and renal markers at 5y. Research Design and Methods: Of the 200 subjects with T2D reaching 2-years in a non-randomized, controlled trial of CRC emphasizing VLCI, 169 (84.5%) consented to 3-year extension and 122 (61%) completed 5y. Metabolic changes from baseline (BL) to 5y were assessed with linear mixed effect models as an intent-to-treat analysis (n=169) . Holm-Bonferroni adjusted p-values are <0.05 unless otherwise noted. Results: At 5y, there were significant changes in HDLc from 43.0 mg/dl to 50.6 mg/dl (+17.7%) , apoA-I from 146.9 mg/dl to 153.5 mg/dl (+4.5%) , and no changes in Total Cholesterol, LDLc, apoB. There were marginal improvements in non-HDLc from 139.2 mg/dl to 128.9 mg/dl (-7.4%, unadjusted p-value <0.01) , and triglycerides from 202.3 mg/dl to 165.1 mg/dl (-18.4%, unadjusted p-value <0.01) . Inflammatory markers significantly improved: hs-CRP from 7.8 nmol/L to 4.4 nmol/L (-43.6%) , white blood cell count from 7.2 k/mm3 to 6.4 k/mm3 (-11.1%) . At all time points, liver markers have been in the normal range. There were no changes in renal biomarkers. eGFR was stable at CKD2. Subcohort completers’ analysis of those with eGFR<60 ml/min/1.73m2 (n=10) showed an increase from 47.8 to 57.1 ml/min/1.73m2 (p=0.01). Six of the subjects (60%) with BL CKD3 who completed 5y rose to CKD2. Of the 107 subjects with BL CKD2, 7 (6.5%) progressed to CKD3. Conclusions: People with T2D following VLCI for 5y show improvements in diabetic dyslipidemia and inflammation. Notably, there is no change in LDLc. There is no significant deterioration in liver and renal labs, although regression from CKD3 to 2 is possible with a VLCI and warrants further investigation. Disclosure C.G.Roberts: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.Phinney: Employee; Virta Health Corp. S.Hallberg: Advisory Panel; Atkins Nutritionals Inc., Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.J.Athinarayanan: Employee; Virta Health Corp. M.Vantieghem: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. B.M.Volk: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.N.Adams: Employee; Virta Health Corp. B.Fell: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.E.Ratner: Employee; Virta Health Corp. J.Volek: Advisory Panel; Abbott Diagnostics, Simply Good Foods, Stock/Shareholder; Virta Health Corp.

985. Impact of Age and Medical Comorbidities on Renal Outcomes in the DISCOVER Trial

BackgroundIn DISCOVER, emtricitabine/tenofovir alafenamide (F/TAF) was noninferior to F/tenofovir disoproxil fumarate (TDF) for preexposure prophylaxis (PrEP) in men who have sex with men and transgender women, with a superior renal laboratory profile. The differential impact of F/TAF and F/TDF on renal parameters among older individuals and those with medical comorbidities is unknown.MethodsDISCOVER randomized participants 1:1 to daily blinded F/TAF or F/TDF. We examined renal outcomes at week 48 including estimated glomerular filtration rate (eGFR) by Cockcroft-Gault, β2 microglobulin (M):Creatinine (Cr) and retinol binding protein (RBP):Cr ratios (markers of proximal renal tubular function), and discontinuations due to investigator reported study drug-related renal adverse events (AEs).ResultsMedian age was 34 years (yrs)(range 18-76), with 12.5% vs 10.9% < 25yrs, 12.2% vs 14.4% ≥ 50yrs, and 1.1% vs 0.9% > 65yrs for F/TAF and F/TDF, respectively. The prevalence of medical comorbidities at baseline were; eGFR < 90mL/min= 9.1% vs 9.3%, diabetes= 2.9% vs 3.3%, and hypertension= 10.5 vs 11.1%, for F/TAF and F/TDF, respectively. eGFR changes by age category and medical comorbidity status are found in the Table. Forty participants had study drug-related renal AEs; 14 with F/TAF and 26 with F/TDF. Of these, 25% were > 50yrs, 20% had baseline eGFR < 90mL/min, 7.5% had history of diabetes, and 22.5% had history of hypertension. β2M:Cr and RBP:Cr changes were more favorable in participants receiving F/TAF, with greater magnitude of difference in older participants (data not shown).Table. ConclusionThe DISCOVER trial allows for a large single variable comparison of the two tenofovir prodrugs in the absence of underlying HIV infection and in the absence of third antiretroviral agents. F/TAF was associated with favorable changes in renal biomarkers regardless of age or medical comorbidity. Participants ≥50yrs or with comorbidities were proportionately more likely to develop study drug related renal AEs, but these were present in the minority of cases.Disclosures Eric Daar, MD, BMS (Consultant)Gilead Sciences Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator)Janssen (Consultant)Merck (Consultant, Grant/Research Support)Teva (Consultant)Theratechnology (Consultant)Viiv Healthcare (Consultant, Grant/Research Support) Jason Brunetta, MD, AbbVie (Consultant)Gilead Sciences Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau, Other Financial or Material Support, Conference attendance sponsorship)Janssen (Other Financial or Material Support, Conference attendance sponsorship)Merck (Consultant, Speaker’s Bureau, Other Financial or Material Support, Conference attendance sponsorship)Viiv Healthcare (Consultant, Speaker’s Bureau, Other Financial or Material Support, Conference attendance sponsorship) Eric Cua, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) David Asmuth, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Christoph C. Carter, MD, Gilead Sciences Inc. (Employee, Shareholder) Yongwu Shao, PhD, Gilead Sciences Inc. (Employee, Shareholder) Pamela Wong, MPH, Gilead Sciences Inc. (Employee, Shareholder) Ramin Ebrahimi, MSc, Gilead Sciences Inc. (Employee, Shareholder) Moupali Das, MD, Gilead Sciences Inc. (Employee, Shareholder) Diana M. Brainard, MD, Gilead Sciences (Employee) Amanda Clarke, MD, Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator, Other Financial or Material Support, Conference attendance sponsorship)Viiv Healthcare (Consultant, Other Financial or Material Support, Conference travel sponsorship)

Ulinastatin treatment and renal injury in patients undergoing aortic valve replacement with cardiopulmonary bypass. A note of aution

We appreciate the constructive comments by Dr. Guillermo Lema regarding our article. Undoubtedly, patients with pre-existing renal dysfunction would be more prone to aggravation of the renal dysfunction after cardiac surgery. Theoretically, these patients would benefit the most from therapeutic measures aimed at reducing the postoperative kidney injury, yet it would also require a harder clinical endpoint such as the requirement of renal replacement therapy for validation. As the incidence of renal replacement therapy after cardiac surgery is low, this would require a substantial number of patients. In our study, we used differences in renal biomarkers as the primary endpoint in a relatively homogenous group of patients undergoing aortic valve replacement. Compared to other valvular procedures, aortic valve surgery is associated with relatively higher incidence of acute kidney injury [1]. As with the assessment of postoperative myocardial infarction using cardiac enzymes, the correlation between renal dysfunction and changes in renal biomarkers, especially creatinine, has been well validated [2]. Even transient elevations in the postoperative serum creatinine concentrations have been shown to be associated with adverse outcome following cardiac surgery. As this was the first study to address the reno-protective effect of ulinastatin, we tried to avoid the introduction of confounding factors as much as possible. In patients with pre-existing renal dysfunction, however, the concentrations of renal biomarkers would be already increased and diverse, which could act as a major confounder. Thus, to efficiently assess the potential reno-protective effect of ulinastatin using a small sample size, we had excluded patients with pre-existing renal dysfunction. This in turn, however, invariably confronts generalization of the observed results as was commented by Dr. Guillermo Lema. Notwithstanding the complex relationship between preoperative patient's co-morbid diseases and postoperative renal dysfunction and clinical outcome, we do acknowledge that a further study with a large sample size involving a heterogeneous group of patients would be necessary to draw a more definite conclusion adding value to the literature. We hope that our study would draw many attentions in that regard.