eGFR Group Research Articles

Role of corticosteroid therapy in IgA nephropathy; where do we stand?

Background: Current KDIGO guidelines suggest corticosteroids (CS) administration in IgA nephropathy (IgAN) with persistent proteinuria >1 g/d despite 3-6 months of supportive care and estimated glomerular filtration rate (eGFR) >50 mL/min/1.73 m2 . The benefits of CS in patients with eGFR 50 mL/min/1.73 m2 . Patients and Methods: A cohort of biopsy proven primary IgAN diagnosed between March 2010 - February 2015 who received oral CS with minimum follow-up of 6 months were included. They were categorized into two groups according to their eGFR (group 1 - eGFR 50 mL/min/1.73 m2 ). The eGFR and urine protein creatinine ratio (UPCR) were followed up at entry, 6 months, 12 months and at the end of follow-up. Outcomes studied were change in eGFR, proteinuria and progression to end-stage renal disease (ESRD). Results: Out of 44 patients, 23 were in group1 and 21 patients in group 2. At the end of follow-up, similar reduction of proteinuria (UPCR) was observed in both groups (P=0.62). However, group 1 had a significant fall in eGFR compared to improvement in group 2 (P=0.004). One in each group has reached CKD stage 5 (P=0.73). Conclusions: Addition of CS to conservative treatment in IgAN patients with initial eGFR 50 mL/min/1.73 m2 ).

EGFR testing scenario across 111 centres in India: A questionnaire-based survey.

e13111 Background: Lung cancer diagnosis now involves routine use of biomarker testing to identify the driver mutations. We conducted a survey of 111 medical oncologists across India to understand the current pattern of EGFR mutation testing at their respective centres. Methods: Medical oncologists from 111 institutes across India were interviewed face to face using a structured questionnaire. They were divided into two groups - Group 1 with in-house EGFR testing and Group 2 who send samples to central/commercial labs. Answers of the two groups were analysed to see the prevailing patterns of EGFR mutation testing and differences between the groups if any. Results: In India, 95% of medical oncologists recommend testing for EGFR mutations in patients with adenocarcinoma histology. 40% would also recommend testing in squamous histology. 80% of medical oncologists request for biomarker testing at the time of primary biopsy. From the time of biopsy, the average time duration to get EGFR test results is 18 days. In centres with in-house testing (Group 1), results are available in 10 days. 96% of the medical oncologists from Group 1 centres request for factoring additional sample for biomarker testing compared to only 69% from Group 2. 69% of medical oncologists in Group 1 centres would prefer to wait for the test results before initiating treatment compared to 46% in Group 2. EGFR TKIs are used in 60% of patients with diagnosed EGFR mutation in the first line. For patients in whom chemotherapy is initiated while waiting for test results, 50% of medical oncologists prefer completing 4-6 cycles before switching to targeted therapy. At the time of progression, rebiopsy is possible in 25% of the patients. Rapid disease progression and poor PS were the two most common reasons given for the low rebiopsy rates. Conclusions: Application of molecular testing is ‎improving. Yield can be improved by training of multidisciplinary team involved in tumor biopsy. There is scope and need to reduce the turnaround time. This will reduce the current scenario of commencing chemotherapy while waiting for test results. Increasing application of liquid biopsy will help in initial diagnosis as well as at relapse, especially for patients with poor PS or difficult access to tumor site.

Elevated Serum Uric Acid Level Predicts Rapid Decline in Kidney Function

Background: While elevated serum uric acid level (SUA) is a recognized risk factor for chronic kidney disease, it remains unclear whether change in SUA is independently associated with change in estimated glomerular filtration rate (eGFR) over time. Accordingly, we examined the longitudinal associations between change in SUA and change in eGFR over 5 years in a general Japanese population. Methods: This was a large, single-center, retrospective 5-year cohort study at St. Luke's International Hospital, Tokyo, Japan, between 2004 and 2009. We included 13,070 subjects (30-85 years) in our analyses whose data were available between 2004 and 2009. Of those, we excluded 492 subjects with eGFR <60 mL/min/1.73 m² at baseline. In addition to examining the entire cohort (n = 12,578), we stratified our analyses by baseline eGFR groups: 60-90, 90-120, and ≥120 mL/min/1.73 m². Linear and logistic regressions models were applied to examine the relationships between baseline and change in SUA, change in eGFR, and rapid eGFR decline (defined as the highest quartile of change in eGFR), adjusted for age, gender, body mass index, abdominal circumference, hypertension, dyslipidemia, and diabetes mellitus. Results: After multivariable adjustments including baseline eGFR, 1 mg/dL increase in baseline SUA was associated with greater odds of developing rapid eGFR decline (OR 1.27, 95% CI 1.17-1.38), and 1 mg/dL increase in SUA over 5 years was associated with 3.77-fold greater odds of rapid eGFR decline (OR 3.77, 95% CI 3.35-4.26). Conclusions: Elevated baseline SUA and increasing SUA over time were independent risk factors for rapid eGFR decline over 5 years.

Renal Function and Scaled Troponin in Patients Presenting to the Emergency Department with Symptoms of Myocardial Infarction

Background: Cardiac troponins are often found to be elevated in patients with renal dysfunction, even in the absence of acute myocardial injury. The objective of this report was to characterize the scaled troponin values and proportion of adjudicated acute myocardial infarction (AMI) among patients with and without renal dysfunction. Methods: The data was from a multicenter prospective study including patients presenting to the emergency department with symptoms of AMI. Troponin measurements were standardized across various assays by calculating the observed results as multiples of the assay-specific 99th percentile upper limit of normal. Patients with an estimated glomerular filtration rate (eGFR; calculated by the Chronic Kidney Disease Epidemiology Collaboration formula) <60 mL/min/1.73 m² were considered to have renal dysfunction. Results: Of 430 included patients, 249 (58%) were male and 181 (42%) were female, with a mean age of 55.9 ± 12.3 and 57.3 ± 12.8 years, respectively. Eighty-seven (20.2%) had renal dysfunction. The proportions of patients with at least one scaled troponin value above the 99th percentile cut-off point among patients with and without renal dysfunction were 40 (45.9%) and 81 (23.6%) respectively (p < 0.001). The proportions of patients with an adjudicated diagnosis of AMI among those with and without renal dysfunction were 20.7 and 18.7%, respectively (p = 0.67). Using scaled troponins, by the second test there was >5X and by the third test >15X separation in the excursion of troponin among those with AMI compared to those without. Conclusions: One or more elevated troponin values are common in those with renal dysfunction. Scaled troponins for eGFR groups were similar, indicating that the use of this interpretative technique is applicable in discerning AMI for those with and without renal dysfunction.

Prediction of Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) after Thoracic Surgery- The Role of Estimated GFR

Little is known about the prognostic utility of preoperative estimated GFR (eGFR) on perioperative Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) in apparently lower risk patients undergoing moderate risk surgeries like thoracotomy. The current study sought to identify a clinically relevant cut-off value of eGFR for identifying thoracotomy patients at higher risk for MACCE. Between July 2012 and July 2016, 436 consecutive patients were retrospectively studied after elective thoracotomy in a single institution. Patients were classified into six groups according to the calculated Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI) eGFR (ml min -11.73 m -2): Stage 1, eGFR >90; Stage 2, eGFR=60-89.9; Stage 3a, eGFR=45-59.9; Stage 3b, eGFR=30-44.9; Stage 4, eGFR=15-29.9; Stage 5, eGFR <15. All the eGFR groups were analysed for perioperative MACCE, length of hospital stay, and mortality. The incidence of perioperative MACCE in our study was 4.24%. The mean eGFR in our study as calculated by the CKD-EPI equation was 83 ml min-11.73 m-2. With the exception of nonfatal cardiac arrest which was not seen in any patient, the incidence of all MACCE increased with progressively worsening preoperative eGFR.It was seen by logistic regression analysis that the occurrence of any perioperative MACCE increased significantly with worsening eGFR (p<0.001). The increase in MACCE was particularly marked from Stage 3b onwards to the later stages (OR 1.9 in 3a vs. 3.6 in 3b). The two mortalities observed in the study were in Stages 4 and 5 with no deaths seen in the better eGFR subgroups. There was also an increased length of hospital stay with declining eGFR. Preoperative eGFR is a predictor of perioperative MACCE in homogenous moderate risk elective surgical population like thoracic surgeries. There is an inverse relationship between eGFR and MACCE, particularly manifested at eGFR values <45 ml/min/1.73. Routine use of preoperative eGFR for cardiovascular and cerebrovascular risk assessment in patients undergoing moderate risk surgeries like thoracotomy would be beneficial.

Do Implantable Cardioverter Defibrillators Reduce Mortality in Patients With Chronic Kidney Disease at All Stages?

The benefits of implantable cardioverter defibrillator (ICD) implantation in chronic kidney disease (CKD) patients with high sudden cardiac death (SCD) risk are uncertain. To clarify the effects of receiving an ICD in CKD patients, we conducted this meta-analysis to identify the effects of ICDs on patients with CKD, including those on dialysis. We searched the Cochrane library, EMBASE, PubMed, and clinical trials for studies published before July 2016. Eleven studies including 20,196 CKD patients were considered for inclusion. The pooled analysis suggested that patients with an estimated glomerular filtration rate (eGFR) < 60 mL/minute/1.73 m2 would benefit from receiving treatments with ICDs compared with patients without an ICD device (aHR = 0.74; 95% confidence interval [CI], 0.63 to 0.86). [corrected]. This is the first report of a subgroup analysis on the survival rate of ICD implantation in CKD patients according to an eGFR group. The subgroup analysis indicated a similar protective association of ICDs in stage 3 (aHR = 0.71; 95% CI, 0.61 to 0.82) and 5 (aHR = 0.71; 95% CI, 0.54 to 0.92) CKD patients [corrected] compared with the control group. However, there was no significant improvement in all-cause mortality in stage 4 CKD patients (aHR = 1.02; 95%CI, 0.75 to 1.37) [corrected]. This is the first meta-analysis reporting that ICD implantation reduces all-cause mortality in stage 3 and 5 [corrected] CKD patients. However, the data do not indicate there is any benefit to ICD implantation in stage 4 [corrected] CKD patients.

Factors influencing renal graft survival: 7-Year experience of a single center

Background and objectiveThe demand for kidney transplants exceeds the existing supply. This leads to a recently growing interest of research in the area of factors that could prolong graft long-term outcomes and survival. In Lithuania, approximately 90% of kidney transplantations are from deceased donors. Donor organs are received and shared only inside the country territory in Lithuania; therefore, donor data is accurate and precise. This study was performed to present particularities of kidney transplantation data in Lithuania and to identify the effect of donor and recipient factors and histologic findings on renal graft outcomes. The aim of this study was to identify the effect of donor and recipient factors and histologic findings on renal graft outcomes. Materials and methodsWe analyzed the influence of deceased donor and recipient factors and histological findings on the graft function in 186 renal transplant patients. Graft survival was estimated within the first year after transplantation. ResultsThe donors and recipients were older in worse eGFR group 1 year after transplantation. Dissimilarity of degree of glomerulosclerosis (GS), interstitial fibrosis (IF) and arteriolar hyalinosis (AH) were significant in inferior and superior renal function groups (GS >20% 11.4 vs. 0%, P=0.017; IF 9.3 vs. 0%, P=0.034; AH 69 vs. 26.2%, P<0.001). Nine independent variables were significantly associated with a worse renal transplant function 1 year posttransplantation: AH (OR=6.287, P<0.001), an episode of urinary tract infection (OR=2.769, P=0.020), acute graft rejection (OR=3.605, P=0.037), expanded criteria (OR=4.987, P=0.001), female gender donors (OR=3.00, P=0.014), cerebrovascular disease caused donor brain death (OR=5.00, P=0.001), donor's age (OR=1.07, P<0.001), and recipient's age (OR=1.047, P=0.022). Worse renal graft survival 1 year posttransplantation was associated with a delayed graft function and a higher level of glomerulosclerosis in time-zero biopsy. ConclusionsDonor factors, such as age, female gender, brain death of cerebrovascular cause and expanded criteria donor status had a significant negative impact on the renal graft function 1 year after transplantation. Recipients’ age, urinary tract infection and acute graft rejection episodes after transplantation were associated with a worse kidney function 1 year after transplantation. Lower 1-year graft survival was related to a delayed graft function (DGF) and a higher degree of glomerulosclerosis.

MicroRNA expression profiles and clinicopathological implications in lung adenocarcinoma according to EGFR, KRAS, and ALK status.

Lung adenocarcinoma has distinctive clinicopathological features that are related to specific genetic alterations, including EGFR and KRAS mutations and ALK rearrangement. MicroRNAs are small non-coding RNAs that post-transcriptionally regulate many important biological processes and influence cancer phenotypes. This study retrospectively investigated microRNA expression profiles, and their clinicopathological implications, in lung adenocarcinoma according to genetic status (EGFR, KRAS, ALK, and triple negative). A total of 72 surgically resected lung adenocarcinoma specimens (19 EGFR-mutated, 17 KRAS-mutated, 16 ALK-rearranged, and 20 triple negative cancers) were screened for 23 microRNAs using quantitative real-time reverse transcriptase polymerase chain reaction. We then evaluated the associations between the microRNA expressions and the cancers’ genetic and clinicopathological features. Eight microRNAs were associated with clinicopathological features, such as male sex and ever-smoker status (high miR-373-3p, miR-1343-3p, miR-138-1-3p, and miR-764; low miR-27b-3p) and vascular invasion (high miR-27b-3p; low miR-1343-3p and miR-764). Clustering and discriminant analyses revealed that the microRNA expression patterns in the ALK group were different from those in the EGFR and KRAS groups. Five microRNAs (high miR-1343-3p; low miR-671-3p, miR-103a-3p, let-7e, and miR-342-3p) were especially distinctive in the ALK group, compared to the EGFR and KRAS groups. Moreover, a significant association was observed between ALK-rearrangement, decreased miR-342-3p expression, and immunohistochemical loss of E-cadherin. Therefore, microRNA expression profiles appear to have distinctive clinicopathological implications in ALK-rearranged lung adenocarcinoma. Furthermore, the association of ALK rearrangement, decreased miR-342-3p expression, and E-cadherin loss might indicate that miR-342-3p is involved in the ALK-associated phenotypes and epithelial-mesenchymal transition.

Prescription of Guideline-Recommended Implantable Cardioverter Defibrillator and Cardiac Resynchronization Therapy Among Patients Hospitalized With Heart Failure and Varying Degrees of Renal Function

Implantable cardioverter defibrillators (ICD) and cardiac resynchronization therapy (CRT) reduce mortality in many patients with heart failure (HF), but the current use and effectiveness of ICD/CRT in patients with chronic kidney disease (CKD) are uncertain. We examined associations between kidney function and guideline-recommended prescription of ICD/CRT in the Get With The Guidelines-Heart Failure registry, a performance improvement program for hospitalized patients with HF. We compared differences in ICD and CRT prescription between the following categories of estimated glomerular filtration rate (eGFR; mL/min/1.73m2): ≥60, 59 to 30, <30, and dialysis dependent. From 2008 through 2014, 26,286 patients were eligible for ICD or CRT, and 16,123(61%) had an eGFR <60. De novo ICD and CRT prescription in this group was low at 45% and 30.5%, respectively. Compared to patients with eGFR ≥60, patients with eGFR 30 to 59 were more likely to receive an ICD (adjusted odds ratio [aOR] 1.08, 95% confidence intervals [CI] 1.01 to 1.14), whereas dialysis patients were less likely (aOR 0.61, 95% CI 0.5 to 0.76). Worse kidney function was associated with a decreased likelihood of CRT prescription (aOR 0.97 per 10ml/min eGFR decrease, p= 0.03). During the study period, the likelihood of both ICD and CRT prescription increased over time among patients with CKD (ICD aOR 1.12, 95% CI 1.07 to 1.18; CRT aOR 1.14, 95% CI 1.06 to 1.23, per year). Prescription of an ICT/CRT was associated with greater 1-year survival in all eGFR groups. In conclusion, there are significant CKD-based differences in prescription of ICD and CRT in HF. However, given the current state of evidence, it is unclear whether improved prescription of ICD and CRT in the CKD population will result in improvement in outcomes.

Renal Function and the Risk of Stroke and Bleeding in Patients With Atrial Fibrillation: An Observational Cohort Study.

We sought to determine the risk of stroke/thromboembolism and bleeding associated with reduced renal function in patients with atrial fibrillation and the risk of stroke and bleeding associated with warfarin treatment in specific estimated glomerular filtration rate (eGFR) groups. We conducted a register-based cohort study and included patients discharged with nonvalvular atrial fibrillation from 1997 to 2011 with available eGFR. A total of 17 349 patients were identified with eGFR available at baseline. All levels of lower eGFR were associated with higher risk of stroke/thromboembolism and bleeding. Use of warfarin was associated with higher bleeding risk in all eGFR groups; hazard ratios 1.23 (95% confidence interval [CI], 0.97-1.56), 1.26 (95% CI, 1.14-1.40), 1.18 (95% CI, 1.07-1.31), 1.11 (95% CI, 0.87-1.42), 2.01 (95% CI, 1.14-3.54) in patients with eGFR ≥90, 60 to 89, 30 to 59, 15 to 29, and <15 mL/min per 1.73 m2, respectively. Use of warfarin was associated with lower risk of stroke/thromboembolism in patients with eGFR ≥15 mL/min per 1.73 m2; hazard ratios 0.57 (95% CI, 0.43-0.76), 0.57 (95% CI, 0.51-0.64), 0.48 (95% CI, 0.44-0.54), 0.60 (95% CI, 0.45-0.80) in patients with eGFR ≥90, 60 to 89, 30 to 59, and 15 to 29 mL/min per 1.73 m2, respectively. Use of warfarin was not associated with lower risk of stroke/thromboembolism in patients with eGFR<15 mL/min per 1.73 m2; hazard ratio 1.18 (95% CI, 0.58-2.40). In patients with atrial fibrillation, the risk of stroke and bleeding was associated with levels of renal function. Warfarin treatment was associated with higher risk of bleeding in all eGFR groups and lower risk of stroke in patients with eGFR≥15 mL/min per 1.73 m2.

Variation in estimated glomerular filtration rate at dialysis initiation in children.

Data guiding the timing of dialysis initiation in children are limited. We sought to determine current practice and secular trends in Canada with respect to the timing of dialysis initiation in children based on estimated glomerular filtration rate (eGFR). This observational study included incident chronic dialysis patients aged ≤21years identified from the Canadian Organ Replacement Register who started dialysis in Canada between January 2001 and December 2010 at any of the nine participating Canadian centers (n = 583). Youth were categorized utilizing CKiD Schwartz eGFR into ≥10.5 (higher) or <10.5ml/min/1.73m2 (lower) eGFR groups. Differences at dialysis initiation by facility and region were examined, and secular trends were determined. Median eGFR at dialysis initiation was 8.1 (interquartile range 5.4-11.0)ml/min/1.73m2. Overall, 29% of the patients started dialysis with an eGFR of ≥10.5ml/min/1.73m2. The proportion of children starting with higher eGFR increased from 27.3% in 2001 to 35.4% in 2010 (p = 0.04) and differed by treatment facility (12-70%; p = 0.0001). Factors associated with higher eGFR at dialysis initiation in the adjusted regression model were female sex [odds ratio (OR) 1.48; 95% confidence interval (CI) 1.02-2.14], genetic cause of end-stage kidney disease (OR 2.77; 95% CI 1.37-5.58) and living ≥50km from treatment facility (OR 1.47; 95% CI 1.01-2.14). One-third of the children were found to have initiated dialysis with an eGFR ≥10.5ml/min/1.73m2, however significant practice variation exists with respect to timing of dialysis initiation by treatment facility. More data is required to evaluate the clinical implications of this practice variation.

High Brain Natriuretic Peptide Level and Renal Dysfunction Were Poor Prognostic Predictors After Cardiac Resynchronization Therapy

This aim of this study was to clarify the prognostic factors of cardiac resynchronization therapy (CRT). (Methods) One hundred-eight patients were received CRT (mean years: 67 years). Left ventricular (LV) function was assessed by echocardiography at baseline and 6 months after CRT. CRT responder was defined as the reduction of LV end-systolic volume (LVESV) < 15% at 6 months after CRT. (Results) Seventy-two patients (67%) were identified as CRT responders. Among age, body mass index, baseline QRS width, CLBBB morphology, baseline LVEF, LVESV, serum brain natriuretic peptide (BNP) level, estimated glomerular filtration rate (eGFR), andischemic etiology, a multivariate logistic analysis revealed that serum BNP level (P = .018) and eGFR (P = .030) were independent predictors of CRT responders (R2 = 0.22, P < .001). During follow-up period (872 ± 557 days), 32 patients (30%) had any cause death or hospitalization for worsening heart failure. According to Kaplan-Meier curve, patients with high serum BNP (<405 pg/ml: log-rank P < .001) and low eGFR (<43 ml/kg/1.73 m2: log-rank P = .01) group showed significantly poor prognosis after CRT compared with another group, respectively. (Conclusion) Basal high serum BNP level and renal dysfunction were poor prognostic predictors on worse clinical outcomes after CRT.

Low glomerular filtration rate and risk of myocardial infarction: A systematic review and meta-analysis

BackgroundChronic kidney disease is increasing in prevalence. The association between low baseline estimated glomerular filtration rate (eGFR) and future myocardial infarction has not been comprehensively assessed. MethodsA systematic review and meta-analysis of observational studies evaluating the risk for future myocardial infarction associated with eGFR <60 and 60–90ml/min/1.73m2 was completed. Data sources included PubMed, EMBASE, and the Cochrane Library. Included studies were required to have prospectively collected data, followed subjects for at least 6months, and reported baseline eGFR levels and the multivariable-adjusted relative risk for future myocardial infarction. A random effects model was used and subgroup analyses were conducted. Results26 publications representing 41 observational cohorts were selected. In total, 1,986,850 participants with more than 35,752 documented myocardial infarctions (follow-up range: 9months to ~20years) were evaluated. eGFR <60ml/min/1.73m2 was associated with a relative risk of 1.52 (95% confidence interval 1.39–1.67; p<0.00001) while eGFR 60–90ml/min/1.73m2 was associated with a relative risk of 1.21 (1.09–1.34; p=0.0002) for myocardial infarction. Significant heterogeneity existed among both eGFR groups. Subgroup analysis found a further increase in risk for myocardial infarction as eGFR declined from 30 to 60 to <30ml/min/1.73m2 (1.40, 95% confidence interval, 1.21–1.61 vs.1.94, 95% confidence interval, 1.51–2.50; p=0.03). ConclusionsDecreased baseline eGFR is independently associated with increased future myocardial infarction, and the risk increases with advanced renal insufficiency. Clinicians should be wary of acute coronary syndromes in patients with CKD.

Irreversible deterioration of estimated glomerular filtration rate in patients with acute myocardial infarction after primary percutaneous coronary intervention.

Contrast-induced nephropathy is a possible complication after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (MI). Deterioration of renal function is reported to be generally reversible. However, renal insufficiency worsens the prognosis for some patients with primary PCI. We evaluated sequential changes in renal function before primary PCI and until the chronic phase. We retrospectively studied 302 patients who had undergone PCI for acute MI. Renal function was evaluated based on estimated glomerular filtration rates (eGFRs) measured at the following four points: before PCI, within 1week after PCI, at discharge from the hospital, and 180-365days after MI. Patients were classified into the preserved eGFR group and the reduced eGFR group according to the median eGFR change from the basal level after PCI. Changes in eGFR in the two groups had significantly different time courses. In the preserved eGFR group, eGFR values during the chronic phase did not differ from the values obtained before PCI. In contrast, eGFRs in the reduced eGFR group did not recover to pre-PCI basal levels, with the median decrease being 10.3mL/min/1.73m2. The eGFR change after PCI was the strongest predictor of eGFR change during the chronic phase. In the reduced eGFR group, incidence of major adverse cardiac events was significantly higher (logrank: p=0.048), and the hazard ratio was 2.28 (95% confidence interval 1.02-5.60). A decline in eGFR after primary PCI for acute MI is not uncommon, and it appears to remain irreversible, even during the chronic phase.

Correlation between serum vitamin D level and arterial stiffness in elderly patients with impaired renal function

Objective To investigate the relationship between serum level of 25-hydroxyvitamin D and arterial stiffness in elderly patients with impaired renal function. Methods A cross-sectional study was conducted. Serum creatinine and 25-hydroxyvitamin D levels in elderly patients aged 60 years and over were detected at admission. The estimated glomerular filtration rate (eGFR) was calculated. Patients were divided into 2 groups of the normal eGFR (≥60 ml/min) group and the impaired eGFR (<60 ml/min) group. Carotid-femoral pulse wave velocity (cfPWV) was used to assess the arterial stiffness. The differences in serum 25-hydroxyvitamin D levels and arterial stiffness were compared between the two groups. Results A total of 256 patients were enrolled in this study. The mean(SD) age at admission was (74.5±9.4) years, with a range of 60~92 years, 172 males and 84 females. There were 143 cases in the normal eGFR group (control) and 113 cases in the impaired eGFR group. No differences in baseline clinical data including age, gender, body mass index, blood lipids, etc. were found between the two groups. Compared with the control group, serum 25-hydroxyvitamin D level was decreased and cfPWV was increased in the impaired eGFR group 〔(12.31 ±9.56)μg/L vs. (20.76 ± 12.97)μg/L, (15.1 ± 3.8) m/s vs. (12.9 ± 2.9) m/s, both P<0.05〕. Multiple liner regression analysis showed that serum 25-hydroxyvitamin D level was negatively associated with cfPWV (r=-0.59, P<0.05) after adjusting for age, gender and other confounders. Conclusions Serum vitamin D level is decreased and the arterial stiffness is increased in elderly patients with impaired renal function. Key words: Kidney function tests; Vitamin D; Arteriosclerosis

Security analysis of implanting drug-eluting stents for unprotected left main coronary artery disease patients with chronic kidney disease

To study the clinical characteristics and prognosis of unprotected left main (ULM) coronary artery disease patients with chronic kidney disease after drug-eluting stents (DES) implantation. 267 ULM coronary artery disease patients who has implanted DES were included in the study from January 2005 to March 2010. Patients were divided into two groups according to their estimated glomerular filtration rate (eGFR): eGFR <60 ml·min(-1)·1.73 m(-2) (77 patients), and eGFR≥ 60 ml·min(-1)·1.73 m(-2) (190 patients) . The clinical parameters and prognosis of ULM patients treated with DES in different eGFR groups were retrospectively compared. In higher eGFR group, left ventricular ejection fraction (LVEF) and morbidity of coronary ostial lesions were higher than the other group. Cerebrovascular diseases (13.0% vs 5.3%), chronic total occlusion (CTO, 28.6% vs 12.1%), hypertension (70.1% vs 53.2%) were more common in lower eGFR patients(all P<0.05). Total mortality and cardiac mortality were higher in eGFR<60 ml·min(-1)·1.73 m(-2) group (P=0.016, 0.006, respectively). Low eGFR level was an independent risk factor after adjusting multiple factors. For the ULM disease patients with reduction in kidney function (eGFR<60 ml·min(-1)·1.73 m(-2)), DES should be selected with a careful study considering its increasing risk of death. Chronic renal insufficiency is a risk factor and may predict poor prognosis for patients with ULM after DES implantation.

Impact of moderate to severe renal impairment on long-term clinical outcomes in patients with atrial fibrillation

BackgroundThe deleterious effect of renal impairment in non-valvular atrial fibrillation (AF) patients has recently been reported. We investigated the impact of moderate to severe renal impairment on long-term clinical outcomes in AF patients. MethodsA total of 2126 AF patients were enrolled and divided into two groups according to ≥ or <60mL/min estimated glomerular filtration rate (eGFR). Clinical outcomes including all-cause death, cardiac death, ischemic stroke (IS), bleeding, and admission for heart failure (HF) were analyzed. ResultsCompared to the ≥60mL/min eGFR group, <60mL/min eGFR patients were older; had a higher proportion of females; were more likely to have diabetes, hypertension, and history of stroke; and had higher CHADS2, CHA2DS2-VASc, and HAS-BLED scores. During the follow-up period (median 6.23 years), all-cause death, bleeding, admission for HF, and progression to persistent or permanent AF were significantly increased in the <60mL/min eGFR group compared to the ≥60mL/min eGFR group. After multivariate Cox regression analyses, <60mL/min eGFR increased the risk of all-cause death [hazard ratio (HR): 1.84; 95% confidence interval (CI): 1.03–3.28, p=0.04] and bleeding (HR: 1.28; 95% CI: 1.04–1.57, p=0.02). IS was only significantly increased in the <60mL/min eGFR group not receiving antithrombotic treatment. ConclusionModerate to severe renal impairment is a poor prognostic factor of long-term clinical outcomes in AF patients.

Safety and efficacy of sofosbuvir-containing regimens in hepatitis C-infected patients with impaired renal function.

Renal clearance is the major elimination pathway for sofosbuvir (SOF). We assessed the safety and efficacy of SOF-containing regimens in patients with varying baseline estimated glomerular filtration rate (eGFR). HCV-TARGET database is a multicentre, longitudinal 'real-world' treatment cohort. A total of 1789 patients [genotypes 1 (72%), 2 (17%) 3 (9%), 4-6 (2%)] had baseline eGFR determination: 73 with eGFR≤45 (18 with eGFR≤30, 5 on dialysis) were compared to 1716 with eGFR>45 ml/min/1.73 m(2) . Patients with baseline eGFR≤45 vs. >45 differed in being female (55% vs. 36%), age ≥65 years (24% vs. 16%), Black race (22% vs. 12%), having cirrhosis with decompensation (73% vs. 24%) and being post-transplant (49% vs. 10%), all P < 0.05. All patients with eGFR≤45 were treated with SOF 400 mg/day (including those on haemodialysis) and had median starting ribavirin (RBV) dose of 800 mg (IQR: 400-1200). Sustained virologic response (SVR) frequencies were similar across eGFR groups, ranging from 82-83%. Patients with eGFR ≤45 more frequently experienced anaemia, worsening renal function and serious AEs (all P < 0.05), and these associations persisted when limiting analysis to RBV-free regimens. Patients with baseline eGFR≤30 and eGFR 31-45 had similar frequencies of efficacy and safety outcomes. Sustained viral clearance was achieved in 83% of patients with renal impairment (eGFR ≤45 ml/min/1.73 m(2) ) treated with SOF-containing regimens. However, these patients had higher rates of anaemia, worsening renal dysfunction and serious adverse events regardless of use of RBV. Patient with renal impairment require close monitoring and should be treated by providers extensively experienced with SOF-containing regimens.

Soluble tumor necrosis factor receptor 1 is associated with diminished estimated glomerular filtration rate in colombian patients with type 2 diabetes

AimsThe tumor necrosis factor α (TNF-α) family of inflammatory molecules plays a crucial role in the pathogenesis of type 2 diabetes mellitus (DM2) complications. TNF-α soluble receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated with chronic kidney disease in DM2 patients. This cross-sectional study intended to determine serum concentrations of sTNFR1 and sTNFR2 in Colombian patients and correlated them with various clinical variables, especially kidney function. Methods92 Colombian patients with DM2 were recruited. Anthropometric variables, glycemic control parameters, lipid profile and renal function were assessed for each patient. Levels of sTNFR1 and sTNFR2 were determined using ELISA. Patients were stratified in two groups according to reduced estimated glomerular filtration rate (eGFR) (<60ml/min/1.73m2) and normal eGFR (≥60ml/min/1.73m2). ResultsSignificantly elevated levels of sTNFR1 and sTNFR2 were observed in the diminished versus normal eGFR group. Also, significant differences were noticed between both groups in haemoglobin A1c (HbA1c) values, percentage of hypertensive subjects treated with angiotensin receptor blocker (ARB) and subjects treated with metformin. No differences were observed regarding body mass index (BMI), albuminuria and lipid profile. Multivariable linear regression analysis revealed that sTNFR1 alone showed a significant association with low eGFR (p=0.009). However, after adjusting for age, the association weakens. Moreover, sTNFR1 and sTNFR2 showed a linear negative correlation with eGFR (r=–0.448, p<0.001 and r=–0.376, p<0.001, respectively). A positive correlation was also seen between sTNFR1 and HbA1c, whereas a negative correlation between both sTNFRs and high-density lipoprotein (HDL) cholesterol was found. ConclusionElevated levels of sTNFRs, especially sTNFR1, are associated with loss of kidney function in Hispanic patients with DM2. Future studies should focus on social and genetic determinants of inflammation and their association with CKD in this ethnicity.

Abstract P5-01-03: Stratifying triple-negative breast cancer prognosis using 18F-FDG-PET/CT imaging

Abstract Introduction: Triple-negative breast cancer (TNBC) is a highly diverse group of cancers, and may benefit from molecular-targeted therapies. This study aims to stratify prognosis of TNBC patients using pre-treatment 18F-FDG PET/CT, alone and with correlation to immunohistochemistry biomarkers. Method: 200 consecutive TNBC breast cancer patients treated between 2008 and 2012 who received lumpectomy or mastectomy as primary treatment were retrieved. Among the full cohort, 79 patients had pre-treatment 18F FDG PET/CT scans. Immunostaining status (percentage and intensity) of basal biomarkers (EGFR, CK5/6), Ki-67, P53, and other clinicopathological variables (age, tumor size, pathological T/N stage, nuclear grade, and lymph node metastasis) were obtained. Three PET image features were evaluated: maximum uptake values (SUVmax), mean uptake (SUVmean) and target volume (SUVvol) defined by SUV&amp;gt;2.5. The relationships among tumor metabolic activities and clinicopathological factors were evaluated. All variables were analyzed versus disease-free survival (DFS) using univariate and multivariate Cox analysis, Kaplan-Meier curves and log-rank tests. The optimal cutoff points of variables were estimated using time-dependent survival receiver operating characteristic (ROC) analysis. Results: All PET features significantly correlated with proliferation marker Ki-67 (all p&amp;lt;0.010). SUVmax stratified the prognosis of TNBC patients with optimal cutoff derived by ROC analysis (≤3.5 vs &amp;gt;3.5, AUC=0.654, p=0.006). Basal biomarkers EGFR and CK5/6 and image features SUVmax, SUVmean, SUVvol were significant associated with DFS in univariate Cox analysis, whereas SUVmax (p=0.001) and EGFR (p=0.001) were also significant in multivariate Cox analysis. To integrate prognosis of biological and imaging markers, patients were first stratified by EGFR into low (≤15%) and high (&amp;gt;15%) risk groups. Further, SUVmax was used as a variable to stratify the two EGFR groups. In the high EGFR group, patients with high FDG uptake (SUVmax&amp;gt;3.5) had worse survival outcome (median DFS=7.6 months) than those patients with low FDG uptake (SUVmax≤3.5, median DFS=11.6 months). In the low EGFR group, high SUVmax also indicated worse survival outcome (17.2 months) than low SUVmax (22.8 months). The risk stratification with integrative EGFR and PET was statistically significant with log-rank p&amp;lt;&amp;lt;0.001. Multivariate Cox analysis for disease-free survivalVariablesHR (95% CI)p-valuePathology, T stage, ≤ 3 vs &amp;gt;32.337(0.428-7.384)0.148EGFR, ≤15% vs &amp;gt; 15%9.109(1.997-41.55)0.004CK5/6, ≤ 50% vs &amp;gt; 50%1.471(0.598-3.614)0.401SUVmax, ≤3.5 vs &amp;gt; 3.53.883(1.13-13.32)0.031 TNBC patient risk groups stratified by EGFR and SUVmax (with the median values of variables)Risk groups (EGFR&amp;gt;15, SUVmax&amp;gt;3.5)patient#DFS monthsEGFR %SUVmaxSUVmeanSUVvolKi-67%1 (-, -)1222.852.00.60.2342 (-, +)1517.258.94.37.2673 (+, -)1311.6502.72.60.9354 (+, +)377.66011.35.210.960 Conclusions: Pre-treatment 18F-FDG PET/CT imaging has significant prognostic value for predicting survival outcome of TNBC patients. Integrated with basal-biomarker EGFR, PET imaging can further stratify patient risks in the pre-treatment stage, and help select appropriate treatment strategies for individual patients. Citation Format: Yue Y, Cui X, Bose S, Audeh W, Zhang X, Fraass B. Stratifying triple-negative breast cancer prognosis using 18F-FDG-PET/CT imaging. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-01-03.