Changes In sCr Research Articles

Long-term exposure to pemetrexed induces chronic renal dysfunction in patients with advanced and recurrent non-squamous cell lung cancer: a retrospective study

BackgroundPemetrexed (PEM) is administered over a long term to patients with non-squamous cell lung cancer as a maintenance therapy after platinum combination induction chemotherapy. Although decreased renal function owing to long-term PEM exposure has been reported, changes in the renal function of individual patients have not been reported. This study aimed to evaluate serum creatinine (Scr) in individual patients over time and determine whether long-term PEM exposure contributed to increased Scr.MethodsA retrospective study was performed using 90 non-squamous cell lung cancer patients, who had received maintenance therapy with PEM ± bevacizumab (BEV) after carboplatin + PEM ± BEV therapy at the Sapporo Minami-Sanjo Hospital from February 2012 to February 2019. Using Scr at the start of induction chemotherapy as the baseline, we calculated the correlation coefficient (r) of the rate of Scr change in an individual patient and the number of treatment courses to divide patients into two groups for comparison: patients with + 0.4 < r ≦ + 1.0 and an observed positive correlation (the r+0.4< group), and patients with − 1.0 ≦ r ≦ + 0.4 and no observed positive correlation (the r+0.4≧ group).ResultsStatistically significant differences between the r+0.4< group and the r+0.4≧ group were observed for the following parameters: the median cumulative dose of PEM (interquartile range) [9100 (6365, 12,260) mg/body vs. 5600 (4140, 7440) mg/body, P < 0.01]; the number of patients taking nonsteroidal anti-inflammatory drugs at the start of treatment [15 patients (31%) vs. 3 patients (7%), P < 0.01]; and the median number of treatment courses starting from induction chemotherapy [11 (8, 14) courses vs. 8 (6, 11) courses, P < 0.01]. Next, the results of univariate and multivariate analyses demonstrated that the cumulative dose of PEM (≧ 7000 mg/body vs < 7000 mg/body, OR 2.40; 95% CI, 1.22–4.75, P = 0.01) was an independent explanatory variable of the r+0.4< group.ConclusionsLong-term PEM exposure may induce chronic renal dysfunction. Hence, maintaining kidney function during PEM treatment by reducing the use of combination drugs and the risk of other renal dysfunctions, such as dehydration, may help patients continue therapy and contribute to their long-term survival.

Effect of losartan on the recoverability of renal function in anuric and oliguric patients with a solitary obstructed kidney: a double-blind randomized placebo-controlled trial.

To assess the role of the angiotensin receptor blocker losartan on the recoverability of renal function after de-obstruction in patients with anuria and oliguria. This was a double-blind randomized placebo-controlled trial in anuric or oliguric patients with calcular obstruction of solitary kidney. Patients with an anomalous kidney or those with an American Society of Anesthesiology score of >3 were excluded. After relief of obstruction, patients were allocated to receive either losartan potassium 25mg or placebo for 3months. Serum creatinine (sCr) and renographic glomerular filtration rate (GFR) were measured at nadir and after 3months. Changes in sCr and renographic GFR were calculated by subtracting the values at nadir from those at 3months. Improvement, stabilization or deterioration of sCr and renographic GFR were defined as percentage increase or decrease from nadir ≥10%, while changes <10% were considered as stabilization. A total of 76 patients completed 3months of follow-up. Demographics and peri-operative data were comparable in the two groups. The median (range) sCr change was -1.05 (-1.8, 0.4) and -0.5 (-1.3, 0.1) mg/dL in the losartan and placebo, groups, respectively (P = 0.07). In the losartan group, renographic GFR had improved in 26 (59.1%) and deteriorated in six (13.6%) patients, while, in the placebo group, it had improved in eight (25%) and deteriorated in 10 patients (31.3%; P = 0.01). Losartan also enhanced renographic GFR improvement vs placebo by a median (range) of 6.9 (-9, 44) vs 1.4 (-10, 32) mL/min (P = 0.004). In patients with anuria and oliguria, losartan treatment contributes to renal function recoverability after relief of calcular obstruction of the solitary kidney.

Characterizing dynamics of serum creatinine and creatinine clearance in extremely low birth weight neonates during the first 6 weeks of life

BackgroundCharacterizing the dynamics of serum creatinine concentrations (Scr) and associated creatinine clearance (CLcr) as a measure of kidney function in extremely low birth weight (≤ 1000 g; ELBW) neonates remains challenging.MethodsWe performed a retrospective study that included longitudinal Scr (enzymatic assay) data from 148 ELBW neonates up to 6 weeks after birth. Change of Scr and inter-individual variability was characterized with nonlinear mixed-effect modeling. Key covariates such as gestational age (GA), mode of delivery (MOD), and treatment with ibuprofen or inotropic agents were investigated.ResultsA total of 2814 Scr concentrations were analyzed. GA was associated with Scr at birth (higher with advancing GA), and GA and MOD showed an association with postnatal maturation of CLcr (faster clearance increase with advancing GA and after C-section). Small CLcr decrease (≤ 5%) was quantified during ibuprofen treatment. For a GA of 27 weeks, mean Scr (estimated CLcr) at birth was 0.61 mg/dl (0.23 ml/min), increasing to 0.87 mg/dl (0.27 ml/min) at day three, and decreasing to 0.36 mg/dl (0.67 ml/min) at day 42 after birth.ConclusionsWe report the first mathematical model able to characterize Scr and CLcr in ELBW neonates during the first 6 weeks of life in a quantitative manner as a function of GA, MOD, and ibuprofen treatment. This model allows the derivation of GA-adjusted reference ranges for ELBW neonates and provides a rationale for normative Scr concentrations, and as such will help clinicians to further optimize monitoring and treatment decisions in this vulnerable patient population.

Kidney Transporters and Drug-Induced Injury in Drug Development.

Influx and efflux kidney tubular transporters are major determinants of the disposition of xenobiotics, including pharmaceutical drugs. On the basolateral membrane of proximal tubular cells, there are influx transporters, such as organic cation transporters. On the apical membrane of proximal tubular cells, there are efflux transporters, such as multidrug and toxin extrusion proteins. The secretion process across the apical membrane into the lumen occurs via efflux transporters which plays an important role in serum creatinine (sCr) elimination in urine. The interference of a pharmaceutical drug with transporters can lead to changes in sCr with no alterations in biomarkers or light microscopic evidence indicative of renal injury. Identification of transporters that influence drug disposition, toxicity, and overall nonclinical safety assessment is important in drug discovery and development programs. This mini review describes some key aspects of kidney tubular transporters and drug-induced renal toxicities in safety risk assessment and drug development.

Laparoscopic based renal denervation in a canine neurogenic hypertension model

BackgroundPrevious renal denervation (RDN) studies showed controversial results in reducing blood pressure. The aim of this study was to provide evidence supporting the effectiveness of laparoscopic-based renal denervation (L-RDN) in treating hypertension.MethodsSixteen Beagle dogs were randomly divided into RDN group (n = 12) and sham group (n = 4). Neurogenic hypertension was generated in all dogs via carotid artery route. L-RDN was performed in the RDN group, with sham operation performed as a control. Blood pressure (BP) changes were recorded at 2, 4, 6, and 8 weeks after the procedure. Changes in serum creatinine (sCr), blood urea nitrogen (BUN) and level of norepinephrine (NE) were analyzed. Histological changes of kidney and renal arteries were also evaluated.ResultsBP and NE levels were significantly elevated after hypertension induction (p < 0.01). Systolic and diastolic BP of RDN group were decreased by 15.5 mmHg and 7.3 mmHg (p < 0.0001 and p = 0.0021, respectively) at the eighth week after L-RDN. Invasive systolic and diastolic BP of RDN group were significantly decreased by 14.5 mmHg and 15.3 mmHg (p < 0.0001). In contrast, there was no significant decrease in blood pressure in the sham group. In addition, RDN group but not the sham group showed a significant decrease in NE levels (p < 0.001), while no significant changes in sCr and BUN were observed in both groups. Pathological examinations showed no discernible damage, tear, or dissection to the renal arteries in RND group.ConclusionsL-RDN lowered BP and NE levels in hypertensive dogs without affecting renal artery morphology and kidney function.

Risk prediction for severe acute kidney injury by integration of urine output, glomerular filtration, and urinary cell cycle arrest biomarkers

Frequent assessment of urine output (UO), serum creatinine (sCr) and urinary cell cycle arrest biomarkers (CCAB) may improve acute kidney injury (AKI) prediction. To study the performance of UO, short term sCr changes and urinary CCAB to predict severe AKI. We measured 6 hours of UO, 6-hourly sCr changes, and urinary CCABs in all critically ill patients with cardiovascular or respiratory failure or early signs of renal stress between February and October 2018. We studied the association of such measurements, and their combination, with the development of AKI Stage 2 or 3 of the Kidney Disease: Improving Global Outcomes (KDIGO) definition at 12 hours. We evaluated predictive performance with logistic regression, area under the receiver operating characteristic (AUROC) curve, and net reclassification indices. We computed an optimal cut-off value for each biomarker. We assessed 622 patients and, as per the exclusion criteria, we enrolled 105 critically ill patients. After 12 hours of enrolment, AKI occurred in 32 patients (30%). UO, sCr change over 6 hours and CCABs were significantly associated with severe AKI at 12 hours, with all variables achieving an AUROC > 0.7 after adjustment. Combination of any of the two or three variables achieved an AUROC > 0.7 for subsequent severe AKI at 12 hours. The optimal predictive high specificity cut-off values were ≤ 0.4 mL/kg/h for UO, variation of +15 μmol/L over 6 hours in sCr, and ≥ 1.5 (ng/mL)2/1000 for CCABs. In this prospective study, an integrative approach using UO, short term sCr change and/or urinary CCABs showed a satisfactory performance for the prediction of severe AKI development at 12 hours.

3:54 PM Abstract No. 270 Percutaneous cryoablation for stage 1 renal cell carcinoma: 10-year prospective oncologic outcomes and comparison with matched surgical cohorts from the National Cancer Database

Ablation is increasingly recognized as a curative therapy for select patients with stage 1 renal cell carcinoma (RCC). Current literature on ablation outcomes is largely retrospective in nature and limited by lack of long-term follow-up and biopsy confirmation of disease in many cases. The objective of this study was to address those limitations and rigorously assess long-term oncologic outcomes in a prospective cohort after cryoablation for Stage 1 RCC. This was an IRB-approved prospective 10-year study of 134 consecutive patients treated with CT-guided cryoablation for biopsy-proven RCC. Overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS) were estimated using interval censored data and Turnbull’s nonparametric survival analysis methods. Survival was compared to available postnephrectomy outcomes in matched subgroups from the National Cancer Database. Long-term renal function was also estimated using serum creatinine (sCr), glomerular filtration rate (GFR), and new hemodialysis requirement during follow-up. Of 134 patients, 19 (14%) were Stage 1B. Median tumor size was 2.8 ± 1.4 cm. At 5 and 10 years, respectively, OS was 86.5 ± 3.2% and 72.1 ± 5.4%; RFS was 85.0 ± 2.9% and 69.1 ± 5.1%; DSS was 94.3 ± 2.1% at both time points. Cryoablation outperformed both partial and radical nephrectomy in terms of OS based on matched subgroup data from the NCDB. In subgroup analysis, the Kaplan-Meier OS and RFS curves dipped significantly with advanced age above 80 years, and both 5- and 10-year DSS rose to 100% with age above 85. No significant changes in sCr or GFR were observed at 10 years. The 10-year unadjusted hemodialysis risk for patients with normal baseline creatinine was 2.3%. This 10-year prospective study in patients with Stage 1 RCC shows that image-guided, percutaneous cryoablation provides long-term survival and renal outcomes at least equivalent to that of nephrectomy, with an improved peri-operative risk profile. Subgroup analysis suggests that cryoablation does not confer survival benefit to patients diagnosed with Stage 1 RCC above the age of 80.

Pemetrexed (Pem) with pembrolizumab (Pembro) maintenance: A post hoc subgroup safety analysis of KEYNOTE-189.

51 Background: KEYNOTE-189 showed that Pembro+Pem and platinum (Plat) followed by Pembro+Pem improved survival vs Placebo(Plac)+Pem+Plat followed by Plac+Pem in nonsquamous metastatic non-small cell lung cancer. Real-world data suggest Pem is being discontinued after the first 4 cycles with Plat (data on file), perhaps due to toxicity concerns. This study evaluated changes in toxicities and renal impairment in patients (pts) receiving Pem maintenance. Methods: Using KEYNOTE-189 patient data, pts receiving ≥5 cycles of Pem (including the first 4 cycles with Plat) were selected, and a subgroup with renal adverse events were identified by system organ class and preferred term (MedDRA 20.1). Pts with treatment-emergent adverse events (TEAEs) and changes in serum creatinine (sCR) were summarized every 4 cycles. Results: 310 pts in the Pembro+Pem+Plat arm and 135 in the Plac+Pem+Plat arm received ≥5 cycles of Pem. 30 and 5 pts experienced renal events in each arm, respectively. Table shows pts with Gr. 3-5 TEAEs in each period of 4 cycles. Gr. 3-5 TEAEs generally decreased after cycle 4. Pts with renal events had increasing maximum sCR changes from baseline with every 4 cycles. Conclusions: The percentage of pts with renal and Gr. 3-5 TEAEs did not increase with prolonged treatment with Pembro+Pem. Toxicity increased moderately with Pembro+Pem vs Plac+Pem in later cycles. The incidence of Gr. 3-5 renal toxicity was consistently low across the cycles. These data support the safety of prolonged Pem and Pembro in pts after 4 cycles of Pembro, Pem, and Plat along with careful monitoring of renal function. Clinical trial information: NCT02578680 . [Table: see text]

Feasibility of Using eGFR to Diagnose Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography

Background: Contrast-induced nephropathy (CIN) is one of the common complications of coronary angiography (CAG). The changes of serum creatinine (Scr) before and after angiography were used to diagnose CIN in the world. But Scr is not a sensitive index to reflect early renal dysfunction. Estimated glomerular filtration rate (eGFR) is a comprehensive indicator to evaluate renal function but does not have accepted standard to diagnose CIN till now. This study aimed to investigate the feasibility of using eGFR to diagnose CIN in patients undergoing CAG. Methods: We included 300 coronary heart disease (CHD) patients who underwent CAG. Their demographics and basal renal function were recorded. Changes of Scr and eGFR before and after CAG were compared at the same time. Logistic regression was used to find independent influence factors of CIN. Receptor operating characteristic (ROC) curve was used to find the optimum cut-off value of eGFR for diagnosing CIN. Results: Among 300 patients with CHD, 64 (41 males and 23 females) of them were affected by CIN after CAG, with a total incidence of 21.3%. Among 271 patients whose Scr were normal (&lt; 133 μmol/L) before CAG, 109 (40.2%) of them with impaired eGFR (&lt; 90 ml/min/1.73m²). Patients had normal eGFR before CAG were less likely to develop CIN than those with normal Scr (15.4% vs 20.7%, P &lt; 0.05). Logistic regression analysis showed that men, diabetes, multivessel lesion and eGFR were independent factors of CIN. ROC curve showed that the optimum cut-off value for diagnosing CIN was eGFR decrease by 22.5% after CAG (sensitivity = 98.4%, specificity = 98.3%, AUC = 0.973, 95%CI: 0.942-1.000, P = 0.000). Conclusions: eGFR is an independent factor of CIN, which is more sensitive than Scr in reflecting early renal dysfunction. Using eGFR to diagnose CIN is feasible in the clinic, but the cut-off value still needs to be confirmed by large scale clinical trials.

Target Identification of Active Constituents of Shen Qi Wan to Treat Kidney Yang Deficiency Using Computational Target Fishing and Network Pharmacology.

Background: Kidney yang deficiency syndrome (KYDS) is one of the most common syndromes treated with traditional Chinese medicine (TCM) among elderly patients. Shen Qi Wan (SQW) has been effectively used in treating various diseases associated with KYDS for hundreds of years. However, due to the complex composition of SQW, the mechanism of action remains unknown. Purpose: To identify the mechanism of the SQW in the treatment of KYDS and determine the molecular targets of SQW. Methods: The potential targets of active ingredients in SQW were predicted using PharmMapper. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out using the Molecule Annotation System (MAS3.0). The protein–protein interaction (PPI) network of these potential targets and “components-targets-pathways” interaction networks were constructed using Cytoscape. We also established a KYDS rat model induced by adenine to investigate the therapeutic effects of SQW. Body weight, rectal temperature, holding power, water intake, urinary output, blood urea nitrogen (BUN), serum creatinine (Scr), adrenocorticotrophic hormone (ACTH), cortisol (CORT), urine total protein (U-TP), and 17-hydroxy-corticosteroid (17-OHCS) were measured. Additionally, the mRNA expression levels of candidates were detected by qPCR. Results: KYDS-caused changes in body weight, rectal temperature, holding power, water intake, urinary output, BUN, Scr, ACTH, CORT, U-TP, and 17-OHCS were corrected to the baseline values after SQW treatment. We selected the top 10 targets of each component and obtained 79 potential targets, which were mainly enriched in the proteolysis, protein binding, transferase activity, T cell receptor signaling pathway, and focal adhesion. SRC, MAPK14, HRAS, HSP90AA1, F2, LCK, CDK2, and MMP9 were identified as targets of SQW in the treatment of KYDS. The administration of SQW significantly suppressed the expression of SRC, HSP90AA1, LCK, and CDK2 and markedly increased the expression of MAPK14, MMP9, and F2. However, HRAS levels remained unchanged. Conclusion: These findings demonstrated that SQW corrected hypothalamic–pituitary–target gland axis disorder in rats caused by KYDS. SRC, MAPK14, HRAS, HSP90AA1, F2, LCK, CDK2, and MMP9 were determined to the therapeutic target for the further investigation of SQW to ameliorate KYDS.

Preventive Effects of Nicorandil Against Contrast-Induced Nephropathy in Patients With Moderate Renal Insufficiency Undergoing Percutaneous Coronary Intervention.

We investigated the preventive effect of nicorandil on contrast-induced nephropathy (CIN) in patients with moderate renal insufficiency undergoing percutaneous coronary intervention (PCI). A total of 250 patients with a creatinine clearance (crCl) ≤60 mL/min undergoing PCI were randomly assigned to either a nicorandil group (nicorandil 10 mg 3 times/d and hydration; n = 125) or a control group (hydration only; n = 125). The first end point was the incidence of CIN defined as an increase in serum creatinine (Scr) levels by ≥0.5 mg/dL or ≥25% within 72 hours after exposure to the contrast medium. The secondary end points were (1) changes in Scr, blood urea nitrogen, and crCl and (2) the incidence of major adverse events during hospitalization. The incidence of CIN was 1.6% (2/125) in the nicorandil group and 9.6% (12/125) in the control group (P = .011). There was no obvious difference in the incidence of major adverse events during hospitalization between the nicorandil and the control group (4.0% vs 4.8%, P = 1.000). Multivariate logistic regression analysis showed that nicorandil was a protective factor for CIN (odds ratios = 0.126, 95% confidence interval: -19.996 to -0.932, P = .012). Prophylactic administration of nicorandil may prevent against CIN in patients with moderate renal insufficiency undergoing PCI.

Long- and Short-Term Changes in Serum Creatinine Prior to LVAD Surgery are Associated with Postoperative Outcomes

Purpose Declining renal function portends poor prognosis in advanced HF. Hemodynamic optimization with diuretics, inotropes, and temporary mechanical circulatory support is frequently performed for optimization of end-organ function before LVAD surgery. We aimed to study the relationship between long- and short-term changes in serum creatinine (sCr) that occur prior to implant and postoperative outcome in LVAD pts. Methods We retrospectively identified 146 LVAD pts with sCr at 3 time points: 1-year (1y), day of index admission, and 1-day (1d) prior to LVAD. Pts were classified based on the changes in sCr that occurred between 1y and 1d prior to LVAD as: Improved = sCr reduction >10% (n=42); Stable = sCr change ≤10% (n=50); Worsened = sCr increase >10% (n=54). Pts were also classified as Optimized using the following exploratory cutoffs: sCr reduction of ≥10, 15, and 20% during the index admission. The primary endpoint was survival free from renal replacement therapy (RRT) after LVAD. Multivariable Cox models were developed to adjust for age, sex, race and sCr 1d pre-LVAD. Results On average, sCr increased from 1 y to the time of index admission, while subsequently declined prior to LVAD (Fig A). Among 147 pts, 47 (31%) met the primary endpoint. In univariable model, Stable 1y-1d sCr was associated with a reduced risk for the primary endpoint (Fig B). After adjustment, there was only a trend towards significance in Stable vs. Improved (p=0.06). Optimization of sCr during index admission was not associated with improved outcomes. Furthermore, in an adjusted model, a decrease in sCr≥15% was significantly associated with increased risk for the primary endpoint (Fig B). Conclusion In the year preceding LVAD implant, a stable renal function is associated with a trend towards improved post-LVAD survival free from RRT. Moreover, a decrease in sCr≥15% during index admission was associated with worse outcome. The effect of sarcopenia on sCr levels in advanced HF may explain these paradoxical findings.

Effect of Shenfukang II on kidney function and TGF-β1/Smads expression with 5/6 nephrectomy in rats

Objective To study the effect of Shenfukang Ⅱ on kidney function and TGF-β1/Smads signal pathway with 5/6 nephrectomy model in rats. Methods Thirty SD rats were randomly divided into the sham operation group, model group and Shenfukang group according to a random number table. We used 5/6 nephrectomy to prepare animal models. The rats were given Shenfukang Ⅱ particles 450 mg/(kg•d) gavage, the others group were given equal volume of saline gavage, once a day, continuous 21 days. The rats were given gavage at the 9 th week after operation. The changes of renal function index BUN, SCR and UA of rats in each group were detected 21 days after administration. The expression of TGF-β1, TGFβR1, Smad7, pSmad2, pSmad3 in renal tissues were detected by immunohistochemistry. The Smad7, pSmad2 and pSmad3 detected the expression of in renal tissues by Western Blot. Results Compared with the model group, the content of BUN (15.03 ± 2.19 mmol/L vs. 24.30 ± 2.82 mmol/L), SCR (74.22 ± 7.36 μmol/L vs. 93.61 ± 14.73 μmol/L) in Shenfukang group significantly decreased (P<0.05). The expression of TGF-β1, TGFβR1, pSmad2 and pSmad3 significantly decreased in kidney tissue, while the expression of Smad7 significantly increased in kidney tissue. The expression of p-smad2 (0.47 ± 0.03 vs. 0.64 ± 0.04) and p-smad3 (0.43 ± 0.04 vs. 0.55 ± 0.02) significantly decreased (P<0.05), and the expression of Smad7 (0.54 ± 0.03 vs. 0.39 ± 0.02) significantly increased (P<0.05). Conclusions Shenfukang Ⅱ have improved on kidney function with 5/6 nephrectomy model rats. The study revealed that Shenfukang II may play an anti-fibrotic effect on regulating TGF-β1/Smads signaling pathway with 5/6 nephrectomies model. Key words: Transforming growth factor beta1; 5/6 Nephrectomy model; Kidney function; Rats

2259. Effect of Discontinuation of Tenofovir Disoproxil Fumarate (TDF) on Renal Function in Elderly Veterans

BackgroundA new formulation of tenofovir with alafenamide (TAF) has been introduced that promises to reduce the risk of renal disease. However, the clinical impact of TAF in elderly persons with HIV/AIDS and comorbid renal disease has not been fully investigated. Using patient data from Louis Stokes Cleveland VA Medical Center, this study examines the effect of TDF discontinuation on renal function.MethodsWith IRB approval, clinical data from 272 veterans with HIV/AIDS were gathered to estimate glomerular filtration rate (eGFR) using CKD-EPI (CE) and Cockcroft-Gault (CG) formulae.Results122 patients were excluded because they did not meet the criteria for the study or for insufficient data. The remaining 150 patients had a mean age of 57.7 years, 96.7% were male, 51% African American, 50% were smokers, 28% had diabetes and 63% had vascular disease risk factors. Baseline mean sCR value was 1.1 ± 0.3. Mean CD4 was 672 ± 372 on TDF containing regimens (703 ± 344 after switch) and 66% (69%) had viral loads <20 cp/mL. Serum creatinine (sCr) values before and after the discontinuation of TDF were collected, and eGFR and rate of change for eGFR and sCr were calculated. In a univariate manner, variables were also examined within 3 subgroups: smokers, diabetics and patients with vascular disease risk factors. Changes in boosting medication were rare (5 patients started cobicistat and 7 patients discontinued ritonavir) and thus had little effect on average changes in sCr and eGFR in this cohort. Overall, discontinuation of TDF stabilized sCR (Figure 1). Mean sCr increased by 0.13 and eGFR declined by 5.755 (CE) or 11.822 (CG) during the mean 181 days of observation prior to TDF discontinuation. After the switch, mean sCr increased by 0.002 during a mean of 396 days of observation; eGFR increased by 1.198 (CE) or 1.300 (CG). Similar trends were observed in the 3 subgroups. In all groups, discontinuation of TDF led to improvement in eGFR.ConclusionDiscontinuation of TDF and initiation of TAF or other non TDF containing regimen stabilizes eGFR in elderly men with HIV and underlying risk for renal disease. Disclosures All authors: No reported disclosures.

Effects of Niaoduqing Particles () on Delaying Progression of Renal Dysfunction: A Post-trial, Open-Label, Follow-up Study.

To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min-1•1.73 m-2, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) μmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min-1•1.73 m-2, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min-1•1.73 m-2 per year. Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).

Cardiac and Vascular Surgery-Associated Acute Kidney Injury: The 20th International Consensus Conference of the ADQI (Acute Disease Quality Initiative) Group.

Acute kidney injury (AKI) occurs in 7% to 18% of hospitalized patients and complicates the course of 50% to 60% of those admitted to the intensive care unit, carrying both significant mortality and morbidity.[1][1] Even though many cases of AKI are reversible within days to weeks of occurrence, data

Application of iodixanol in gemstone spectral imaging with low CT dosage

Objective To study the application value of iodixanol in gemstone spectral imaging with low CT dosage. Methods Forty hundred and twenty-six cancer patients with normal kidney function were selected.All of them underwent enhanced gemstone spectral CT scan with low dosage.They were individed into two groups with random number table, including observation group(n=213) and control group(n=213). The observation group was injected isotonic iodixanol(270mgI/mL) intravenously, while the control group was injected hypertronic iohexol (350mgI/mL) intravenously.With the same injection speed, the acute adverse reaction within 1h and delayed adverse reaction between 1h~7d were recorded.Meanwhile, the changes of Scr and Ccr, the occurrence rate of contrast-induced nephropathy(CIN) and short-term prognosis were also recorded. Results Fifty-three patients occurred acute adverse reaction, among them 18 cases(8.45%) were in the observation group, 35 cases(16.43%) were in the control group, there was statistically significant difference between the two groups(χ2=10.791, P 0.05). Conclusion The intravenous injection of iodixanol can reduce the occurrence of acute adverse reaction, will not increase the incidence of CIN.It can be used safely. Key words: Tomography, X-ray computed; Iodixanol; Contrast media

Renoprotection by Direct Renin Inhibition: A Systematic Review and Meta- Analysis

Even mild abnormalities of the renal structure or function can increase the risk of mortality and complications in other organs. Therefore, safe and effective treatments are necessary in order to influence the progression of renal disease. We used 2 methods to assess the renoprotective effects of aliskiren: 1) a statistical analysis of clinical trials that investigated aliskiren-induced renoprotection, in terms of changes in serum creatinine concentration (sCr) or estimated glomerular filtration rate (eGFR), and, 2) clinical trials that investigated the renoprotective effects of aliskiren with respect to changes in albuminuria or proteinuria. In the forest plot, the overall risk ratio (%) for renal impairment with respect to changes in sCr or eGFR was 0.97 (0.88-1.06; overall p=0.48). The tabulation of data from clinical trials included 10 entries for monotherapy with aliskiren and 6 entries for add-on aliskiren. All of the clinical trials, except one, showed a decrease in proteinuria or albuminuria following aliskiren treatment. In conclusion, inhibiting renin and prorenin with aliskiren is a more promising renoprotective treatment compared with blocking the renin/prorenin receptors (RPR). One of the main mechanisms by which aliskiren may confer renoprotection is by decreasing albuminuria and proteinuria. However, it does not seem to change sCr and eGFR in patients at risk of developing renal disease. Furthermore, co-administration of an angiotensinconverting- enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) and aliskiren was shown to decrease albuminuria and proteinuria to a greater extent compared with monotherapy with these agents.

Stroke volume variation and serum creatinine changes during abdominal aortic aneurysm surgery: a time-integrated analysis.

Patients undergoing abdominal aortic aneurysm (AAA) surgery with suprarenal clamping are at high risk for acute kidney injury (AKI) and major cardiac and cerebrovascular events (MACCE). We aimed to assess whether the stroke volume variation (SVV), a measure of hemodynamic instability, is associated with AKI in hypertensive patients undergoing elective AAA surgery with suprarenal clamping. In a cohort of 51 hypertensive patients, we performed serial measurements of SVV (n = 459) and serum creatinine (sCr) (n = 255). AKI was defined according to the KDIGO clinical practice guidelines. Data were analyzed by repeated-measures ANOVA and regression analysis of time-integrated changes of both SVV and sCr. AKI developed in 45% of patients (stage 1: 31%; stage 2: 10%; stage 3: 2%). The diuresis during surgery (beta - 0.29 Z-score 95% [CI -0.54, -0.05]; p = 0.02), clamp time (beta 0.29 Z-score [0.05-0.52]; p = 0.02), and time-integrated changes in SVV from baseline to 12h after surgery (beta 0.31 Z-score [0.03-0.60]; p = 0.03) were independent predictors of the time-integrated changes in sCr from baseline to 48h after the end of surgery. In a model adjusted for age and sex, patients with AKI had an increased risk for MACCE during a mean follow-up of 3.5 ± 1.1years (HR 5.53 [1.52-20.06]; p = 0.004). SVV increases progressively during and after AAA surgery in subjects who will develop AKI. The increase of SVV precedes and predicts the rise in sCr and is a good discriminator of the development of AKI. AKI is associated with an increased long-term risk for MACCE.

Incidence, Predictors, and Impact on Six-Month Mortality of Three Different Definitions of Contrast-Induced Acute Kidney Injury After Coronary Angiography

We assessed incidence, predictors, and impact on 6-month mortality of contrast-induced acute kidney injury (CI-AKI) after coronary angiography with or without percutaneous coronary intervention in patients with acute coronary syndrome (ACS), according to 3 different CI-AKI definitions. Serum creatinine (sCr) was assessed at baseline and 48 to 72 hours after procedure to classify patients into 3 CI-AKI groups: Group 1: increase in sCR ≥25% over baseline but absolute increase <0.5 mg/dl; Group 2: absolute increase ≥0.5 mg/dl; Group 3: absolute increase ≥0.3 mg/dl or ≥50% over baseline. The association between CI-AKI and all-cause 6-month mortality was assessed using multivariate Cox regression. Among 1,002 patients included, median age was 68 [57 to 79] years. The sample had the following characteristics: 70% men, 25% diabetics, 22% had a history of myocardial infarction, 21% had baseline estimated glomerular filtration rate (as calculated by the Modification of Diet in Renal Disease) <60 ml/min/1.72 m2, 34% had ST-segment elevation myocardial infarction, 61% underwent percutaneous coronary intervention, and 43% had multivessel disease. Based on changes in sCr, 89 patients (8.9%) were classified in Group 1; 69 (6.9%) in Group 2; and 157 (15.7%) in Group 3, whereas sCr did not increase >25% in the remaining 844 (84.2%). CI-AKI was significantly associated with 6-month all-cause mortality using the definitions for Group 2 (hazard ratio 3.1, 95% confidence interval [CI] 1.5 to 6.6, p = 0.002) and Group 3 (hazard ratio 2.03, 95% CI 1.03 to 4.0, p = 0.04), but not Group 1. In conclusion, based on the definition used for CI-AKI, CI-AKI is observed in 6% to 15.7% of patients. An increase of 25% over baseline sCr does not identify high-risk patients. CI-AKI defined as an increase in sCr >0.3 mg/dl identifies 15.7% of the population at 2-fold higher risk of mortality.