Lower Baseline Creatinine Clearance Research Articles

Real-world evidence of cisplatin versus carboplatin in patients with locally advanced nasopharyngeal carcinoma receiving concurrent chemoradiotherapy: A multicenter analysis.

Though concurrent chemoradiotherapy (CCRT) with cisplatin remains a standard of care for patients with locally advanced nasopharyngeal carcinoma (LA-NPC), carboplatin has alternatively been used without sufficient supportive evidences. Thus, we evaluated an efficacy and tolerability of carboplatin CCRT compared with cisplatin in LA-NPC patients. Patients with LA-NPC treated with CCRT were identified through the Thai multicenter head and neck cancer database. Patient tolerability and survival were analyzed and compared between regimens. Survivals were calculated by using the Kaplan-Meier method, and compared by the log-rank test. A p-value of<0.05 was considered statistically significant. A total of 135 of 980 patients (13.8%) were treated with carboplatin. Patients treated with carboplatin were significantly associated with older age (p<0.001), smoking (p=0.003), more comorbidity (p=0.014), kidney disease (p=0.016), and lower baseline creatinine clearance (p<0.001). Intensity-modulated radiation therapy was used significantly more in the cisplatin group than carboplatin group (p<0.001). Patients who received carboplatin were associated with delay (p=0.049) and hospitalization (p=0.006), whereas cisplatin CCRT had more dose reduction (p=0.001). Patients treated with cisplatin had CCRT interruption from grade 3-4 mucositis (p=0.019) more than carboplatin, whereas carboplatin had more grade 3-4 thrombocytopenia (p<0.001). The 5-year overall survival (OS) of patients treated with cisplatin and carboplatin was 59% and 49%, respectively (p=0.128). Cisplatin or carboplatin CCRT was not a significant predictor for OS and locoregional recurrence-free survival in multivariate analysis. Carboplatin CCRT provided acceptable efficacy and tolerability profiles in real-world practice. Carboplatin should be considered as an alternative regimen, particularly in cisplatin-ineligible patients with LA-NPC treated with CCRT.

Risk Factors for Major Bleeding and Clinically Relevant Non-major Bleeding in Japanese Patients Treated with Edoxaban.

Edoxaban is used to prevent and treat stroke or systemic embolism such as venous thromboembolism. Although bleeding is the most common complication of anticoagulants, only a few studies have addressed the safety of direct oral anticoagulants in East Asian patients. In this study, we investigated the risk factors for bleeding in Japanese patients receiving edoxaban. A retrospective review of the records of 198 patients who received 30 mg/d edoxaban in our hospital between April 2015 and March 2017 was performed. Subsequently, these patients were followed up to 1 year. Seven (3.5%) and 22 (11.1%) patients developed major bleeding and clinically relevant bleeding, respectively. In the univariate Cox regression analyses, low baseline hemoglobin levels (p = 0.002) and low baseline creatinine clearance (p = 0.020) were significantly associated with major bleeding. Multivariate Cox regression analysis revealed that a low baseline hemoglobin level was a significant risk factor for major bleeding and clinically relevant bleeding [hazard ratio 1.67 per 1 g/dL decrease (95% confidence interval 1.14-2.56, p = 0.008) and hazard ratio 1.31 per 1 g/dL decrease (95% confidence interval 1.06-1.62, p = 0.013), respectively]. Baseline hemoglobin level in quartiles also showed a quartile-dependent decrease in major bleeding and clinically relevant bleeding event. These results suggest that low baseline hemoglobin level is a significant risk factor for both major bleeding and clinically relevant bleeding in Japanese patients receiving edoxaban. Thus, these patients should be carefully monitored.

Rates and risk factors for nephrotoxicity and ototoxicity among tuberculosis patients in Tbilisi, Georgia.

SETTING: Treatment of multidrug-resistant tuberculosis (MDR-TB) is lengthy and utilizes second-line anti-TB drugs associated with frequent adverse drug reactions (ADRs).OBJECTIVE: To evaluate the prevalence of and risk factors for ADRs among patients with MDR- and extensively drug-resistant TB (XDR-TB).DESIGN: A retrospective chart review of patients initiating treatment for M/XDR-TB in 2010-2012 in Tbilisi, Georgia.RESULTS: Eighty (54%) and 38 (26%) of 147 patients developed nephrotoxicity per RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) classification and ototoxicity, respectively. Twenty-five (17%) patients required permanent interruption of injectables due to an ADR. Median hospital stay, total treatment duration and number of regimen changes were higher among those with nephrotoxicity and/or ototoxicity, compared to those without (P < 0.01). Multinomial logistic regression analysis identified increasing age (per year) as a risk factor for nephrotoxicity (aOR 1.08, 95%CI 1.03-1.12) and for both, nephro- and ototoxicity (aOR 1.11, 95%CI 1.05-1.17). Low baseline creatinine clearance (CrCl) was a significant risk factor for developing nephrotoxicity (aOR 1.05, 95%CI 1.02-1.07).CONCLUSION: Second-line injectable drug-related ADRs are common among M/XDR-TB patients. Patients with increasing age and low baseline CrCl should be monitored closely for injectable-related ADRs. Notably, our findings support WHO's latest recommendations on introduction of injectable free anti-TB treatment regimens.

BHIVA/BASHH guidelines on the use of HIV pre-exposure prophylaxis (PrEP) 2018.

We aim to provide evidence-based guidance on best clinical practice in the provision, monitoring and support of pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition. The guidelines include: (i) Guidance on risk assessment prior to PrEP; (ii) Baseline assessment; (iii) Dosing schedules; (iv) Monitoring; (v) Supporting adherence; (vi) Buying generic PrEP; and (vii) Cost-effectiveness. The guidelines are aimed at clinical professionals directly involved in, and responsible for, HIV prevention, and at community advocates and organisations responsible for supporting HIV prevention strategies in those at risk of HIV acquisition. A detailed review of the evidence base is included in Section 4. Sections 5 to 7 are intended to offer practical guidance in risk assessment, starting PrEP, ongoing management while on PrEP and stopping PrEP.

139 - Amlodipine and Calcineurin Inhibitor Induced Nephrotoxicity Following Allogeneic Hematopoietic Stem Cell Transplant

Background: Previous studies, primarily in the renal transplant population, have suggested that calcium channel blockers (CCBs) may protect against calcineurin inhibitor (CNI)-induced nephrotoxicity. However, this has not been evaluated in the hematopoietic stem cell transplant population. Methods: We reviewed data from 350 consecutive patients who underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) between 2006 and 2016 at a single institution to determine whether patients receiving amlodipine for hypertension had improved renal outcomes compared to patients who did not receive amlodipine. Subject data included up to one year from the initiation of a CNI. Results: Patients in the amlodipine group (n = 130) received 76 median days treatment with amlodipine and experienced a lesser median decline in creatinine clearance (CrCl) at predefined time points through day 180, as determined by a 2-tailed Mann-Whitney U-test. This trend remained through day 360 but did not reach statistical significance. At day 30, change in CrCl was -17.4 mL/min in the amlodipine cohort and -33.8 mL/min in the control group (P < .001). At day 180, median change in CrCl was -40.9 and -50.6 mL/min respectively (P = .005). A mixed-effects logistic regression model was used for multivariate analysis and found supra-therapeutic CNI levels (P < .0001), older age (P = .0006), past medical history of hypertension (P = .0171), and the use of antihypertensive medications other than amlodipine (P < .0001) correlated to a greater CrCl decline. For our secondary endpoint, we found that patients receiving amlodipine had a significantly lower risk of being hospitalized with acute kidney injury (AKI) (Figure 1). Probabilities of hospitalization were estimated utilizing the Kaplan-Meier method. Curves were compared and hazard-ratios calculated using log-rank tests. Hospitalization with AKI kidney injury occurred in 7.7% (10/130) of patients in the amlodipine cohort and 16.4% (36/220) of patients in the control group (P = .0218). Multivariate analysis found supratherapeutic CNI levels to also be an independent risk factor for hospitalization with AKI (P = .004). Patients receiving amlodipine were older (P = .005) and more likely to have a greater BMI (P = .0021), a greater baseline systolic and diastolic blood pressure (P < .0001), a lower baseline creatinine clearance (P = .016), and a past history of diabetes mellitus (P = .013) and hypertension (P < .0001) . Also, a higher rate of supratherapeutic CNI levels was found in the amlodipine cohort. Conclusion: Overall, we found more favorable renal outcomes in the amlodipine group despite holding greater baseline risks for renal decline compared to the control group. Our data support the use of amlodipine for hypertension in the allo-HSCT population and provide evidence suggesting that CCBs protect against CNI-induced nephrotoxicity.

Long-term outcomes for women versus men with unstable angina/non–ST-segment elevation myocardial infarction managed medically without revascularization: Insights from the TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes trial

Women with acute coronary syndromes (ACS) are less likely to undergo invasive revascularization than men, but sex-specific differences in long-term outcomes and platelet reactivity among medically managed ACS patients remain uncertain. We examined sex-specific differences in long-term ischemic and bleeding outcomes and platelet reactivity for medically managed ACS patients randomized to prasugrel versus clopidogrel plus aspirin. Data from 9,326 patients enrolled in TRILOGY ACS were analyzed to determine differences in long-term ischemic and bleeding outcomes between women (n = 3,650 [39%]) and men (n = 5,676 [61%]) randomized to prasugrel 10 mg/d (5 mg/d for patients ≥75 years and/or <60 kg) versus clopidogrel 75 mg/d. Sex-specific differences in 30-day platelet reactivity were analyzed in 2,564 (27%) patients participating in a platelet function substudy. Compared with men, women were older, weighed less, were less likely to have prior myocardial infarction or revascularization, and had lower baseline creatinine clearance and hemoglobin level values. Rates of the composite of cardiovascular death/myocardial infarction/stroke (20.2% vs 19.1%; P = .56), all-cause mortality (12.2% vs 11.7%; P = .88), and Global Use of Strategies to Open Occluded Arteries severe/life-threatening/moderate bleeding (3.8% vs 2.8%; P = .74) through 30 months were similar in women versus men. After adjustment, women had significantly lower risk for ischemic outcomes and all-cause mortality. There were no sex-specific, treatment-related differences in 30-day platelet reactivity. Long-term ischemic and bleeding outcomes in medically managed ACS patients were similar for women versus men, as was treatment-related platelet reactivity. Women had a higher baseline risk profile and, after adjustment, significantly lower risk of the primary composite end point and all-cause death through 30 months.

Tenofovir‐induced acute kidney injury in HIV‐infected patients in western India: a resource limited setting perspective

Background and objectiveTenofovir use in HIV positive patients is associated with 0.5–2.5% risk of acute kidney injury (AKI). Data on AKI due to tenofovir use in resource limited settings like India is sparse. Objective of this study is to determine incidence, risk factors and outcome of tenofovir‐induced acute kidney injury (serum creatinine&gt;2 mg/dl or creatinine clearance decrease by 50% compared to baseline) in HIV infected patients attending tertiary level HIV clinic in Western India.MethodsAll patients enrolled at the clinic from 2009 to 2012 who were initiated on tenofovir‐based ART and had regular follow up creatinine clearance values available were included in this retrospective observational cohort analysis. Patients already on tenofovir‐based ART during enrollment were also included.Summary of results512 patients were enrolled in the study with 70% being males. Average age of the cohort was 41 years, average body weight 56 kilograms and median baseline CD4 count 164 cells/mm3. Mean baseline creatinine clearance was 90 ml/min. Median duration of follow up was 26 months. Tenofovir‐induced AKI developed in 25 patients (incidence 4.88 %). Median time to developing AKI was 6 months. On stopping tenofovir, 15 patients had complete recovery of renal function, 5 had partial recovery while 5 patients died. Hemodialysis as a treatment option was used in 3 patients. Age&gt;50 yrs (p=0.001), baseline creatinine clearance&lt;50 ml/min (p=0.0001), diabetes mellitus (p=0.0001), use of tenofovir with protease inhibitors (p=0.001), presence of renal calculus disease (p =0.0001) and use of concomitant nephrotoxic medications (p=0.001) were significantly associated with risk of tenofovir AKI on applying Pearson's Chi square test.ConclusionsIncidence of tenofovir‐induced AKI in our cohort is higher than previously reported and could be attributed to lower body weight, lower baseline creatinine clearance, higher incidence of advanced HIV disease and higher incidence of co‐morbidities in our patients.

Risk Factors of Amphotericin B Toxicty in the Nonneonatal Pediatric Population

Amphotericin B (AmB) traditionally has been the mainstay of therapy for children with candidemia but is associated with drug-related toxicities (DRT). Studies investigating the risk factors for AmB DRT in children are limited. A retrospective review of patients aged 6 months to ≤18 years with candidemia who received ≥1 dose of AmB from 2003 to 2009 was conducted at Texas Children's Hospital, Houston, TX. Patient demographics, risk factors, drug dosages, laboratory adverse effects and infusion-related side effects (INFRT) were recorded. A total of 223 episodes of candidemia occurred in 179 patients. AmB was administered in 172 (77%) episodes. Amphotericin B deoxycholate, Amphotericin B lipid complex and liposomal Amphotericin B were administered in 65 (38%), 96 (55%) and 11 (6.4%) episodes, respectively. When the first episode of AmB use was analyzed separately (n = 138), DRT occurred in 83% (n = 114); nephrotoxicity occurred in 45% (n = 62), hypokalemia in 47% (n = 62) and INFRT in 31 % (n = 41). The most common INFRT was chills and rigors (80%, n = 33) followed by fever (31.7%, n = 13) and hypotension (9.7%, n = 4). Patients with lower baseline creatinine clearance were at increased risk of having nephrotoxicity than those with higher baseline creatinine clearance (P = 0.004). Nephrotoxicity was less likely in patients who received immunosuppressants (P = 0.02). Neutropenia (P = 0.02) and prior hypokalemia (P = 0.001) were independently associated with hypokalemia. The receipt of premedication was independently associated with a lower likelihood of INFRT (P ≤ 0.0001). It is important to note that most AmB-related DRT was quickly reversible. AmB-associated DRT was common and reversible in our nonneonatal pediatric population. Prospective studies are required to further evaluate risk factors and determine whether they are modifiable.

The role for saxagliptin within the management of type 2 diabetes mellitus: an update from the 2010 European Association for the Study of Diabetes (EASD) 46th annual meeting and the American Diabetes Association (ADA) 70th scientific session.

Saxagliptin is a potent, selective DPP4 inhibitor. Highlights from abstracts presented at the 2010 meetings of the European Association for the Study of Diabetes and the American Diabetes Association include studies and analyses that shed light on the promising role for saxagliptin within the management of type 2 diabetes mellitus. Data show that saxagliptin combination therapy improves HbA1c levels compared with placebo, particularly in patients with high HbA1c at baseline, long duration of disease, low baseline creatinine clearance, and low homeostasis model assessment 2 β-cell function at baseline. These efficacy benefits are achieved without any increase in hypoglycemia or other adverse events. The study results also show that the saxagliptin plus metformin combination is a good candidate for initial therapy in drug-naïve patients treated for as long as 72 weeks. Survey data presented confirm that hypoglycemia (and fear of hypoglycemia) is a barrier to patients' acceptance of diabetes treatment, limiting its efficacy. Therefore, therapies such as saxagliptin that have a low risk of hypoglycemia may be more acceptable to patients in helping them to achieve glycemic control and to optimize their quality of life. In patients with renal impairment, for whom metformin is contraindicated, saxagliptin monotherapy is a promising option for antidiabetic management as, when given at a reduced dose, it is well-tolerated with a safety profile similar to that of placebo.

Suboptimal endogenous erythropoietin response in chronic hepatitis C patients during ribavirin and PEG interferon treatment

During the treatment of hepatitis C, anaemia may necessitate pegylated-interferon and ribavirin dose reductions with reduced sustained viral response rates. Although erythropoietic growth factors are frequently used to improve anaemia, it is controversial whether endogenous erythropoietic response is insufficient under these circumstances. We aimed to identify risk factors for more pronounced anaemia and to evaluate endogenous erythropoietic response during antiviral therapy. One hundred and forty-five naive chronic hepatitis C patients on pegylated-interferon-ribavirin treatment were evaluated for haemoglobin, haematocrit, serum ribavirin and erythropoietin levels. About 99% of patients developed anaemia, with maximal decrease in haemoglobin of 2.5 ± 1.0 mmol/l (range 0.3-5.5 mmol/l). Older age, lower baseline creatinine clearance, higher baseline haemoglobin, more pronounced haemoglobin decrease after 2 weeks and higher week 24 serum ribavirin concentrations were independent risk factors for more pronounced anaemia. Serum erythropoietin levels increased from median 12 IU/l (range 4-63 IU/l) at baseline to 41 IU/l (range 12-683 IU/l) after 12 weeks of therapy and to 43 IU/l (range 7-3238 IU/l) at week 24 (P<0.001). Erythropoietin levels at baseline, week 12 and week 24 negatively correlated with haematocrit. The erythropoietic response to anaemia in our study population was significantly different from the normal human response to anaemia. Older age, lower baseline creatinine clearance, higher baseline haemoglobin, more pronounced haemoglobin decrease after 2 weeks and higher week 24 serum ribavirin concentrations were independent risk factors for more pronounced anaemia during antiviral therapy. Endogenous erythropoietin production is suboptimal during antiviral therapy, supporting use of erythropoietic growth factors.

TRANSRADIAL VS. TRANSFEMORAL APPROACH FOR PRIMARY ANGIOPLASTY IN ACUTE MYOCARDIAL INFARCTION: ANALYSIS FROM THE HORIZONS-AMI TRIAL.

Methods: We assessed outcomes of pts who underwent PCI for STEMI using RA vs. FA in the HORIZONS-AMI trial. Of 3,334 pts randomized to bivalirudin vs. to UFH + a GPIIb/IIIa inhibitor (GPI), PCI by operator choice was performed by the FA and RA in 3134 (94.0%) and 200 (6.0%) pts, respectively. Results: Pts treated by FA vs. RA tended to be older, with higher rates of smoking, hyperlipidemia, prior CABG, and lower baseline creatinine clearance and platelet count. RA was associated with signiicant reduction in 30-day major and minor bleeding due to reductions in both major hemorrhagic events and large hematomas. By multivariable analysis, RA (vs. FA) was an independent predictor of freedom from non-CABG major bleeding at 30 days (HR 0.40; 95% CI [0.18, 0.90]; p=0.03). Conclusions: In the large-scale, international HORIZONS-AMI trial, performance of primary PCI by the RA rather than the FA was infrequent, and was selected in younger STEMI pts with fewer comorbidities. Primary PCI using the RA was associated with reduced hemorrhagic complications compared to the FA. A randomized trial is required to determine the generalizability and advantages of this approach. 30 day events, % Radial (N=200)

Changes in haemoglobin during interferon alpha‐2b plus ribavirin combination therapy for chronic hepatitis C virus infection

Interferon alpha and ribavirin (RBV) combination therapy is associated with decreases in haemoglobin (Hb) concentrations and anaemia. The aim of this analysis was to better characterize the magnitude and frequency of Hb changes and risk factors. This retrospective analysis evaluated treatment-related changes in Hb in 677 patients who participated in either of two interferon alpha-2b plus RBV studies for chronic hepatitis C virus (HCV) infection. Study 1 included 192 interferon alpha-naïve patients randomized to receive RBV 1000-1200 mg/day plus interferon alpha-2b 3 million IU daily or three times weekly for 48 weeks. Study 2 included 485 interferon alpha-experienced patients randomized to receive RBV 1000-1200 mg daily plus interferon alpha-2b 3 million IU daily or three times weekly for 4 weeks, followed by three times weekly dosing for 44 weeks. More than 50% of all patients experienced a decrease in Hb > or =30 g/L. Women were 4.4 times as likely as men to experience a Hb level of <100 g/L; however, men were at a 40% higher risk to experience a Hb decline of >30 g/L from baseline. Daily use of interferon alpha-2b did not impact the magnitude of Hb decrease. In this pooled analysis, RBV dose reduction resulted in increases in Hb concentration of approximately 10 g/L. Lower baseline creatinine clearance, higher baseline Hb levels and increased age were independently associated with increased risk of Hb decreases of >27.7%. Lower baseline weight was not associated with increased risk of Hb decrease. Substantial Hb decreases occur frequently with interferon alpha/RBV combination therapy. Sex, the magnitude of the Hb decline and renal function are potentially important factors to consider in patients receiving RBV. Further research is needed to determine the impact on virological response and to develop strategies to manage the medical consequences.

Aggravated renal dysfunction during intensive therapy for advanced chronic heart failure

Background Chronic heart failure is associated with impaired renal function, which may worsen during therapy. The incidence, predictors, and consequences of aggravated renal dysfunction (ARD) in patients undergoing intensive therapy for advanced chronic heart failure are unknown. Methods We reviewed the experience of 48 consecutive patients hospitalized for treatment of advanced chronic heart failure who underwent intravenous diuretic therapy with a weight loss of ≥2 kg. Evaluation included baseline renal function and echocardiography in all patients and hemodynamic measurements in 38 (79%) patients. Results ARD, defined as ≥25% increase in serum creatinine concentration to ≥2 mg/dL, developed in 10 (21%) patients. Patients with ARD developing were older (aged 58 ± 16 years vs 51 ± 13 years; P = .006) and had lower baseline creatinine clearance (49 ± 21 mL/min vs 74 ± 26 mL/min; P = .01) but had the same serum creatinine at baseline. They were more likely to have atrial fibrillation (70% vs 29%, P = .02) but did not have lower filling pressures, cardiac output, or estimated renal perfusion pressure. Length of stay was longer if ARD developed (median 17 vs 9 days, P = .02). Mortality rate after discharge was increased in the patients with ARD (relative risk 5.3, P = .002). Conclusions In patients undergoing intensive treatment for heart failure, ARD is common and clinically significant. The relation among baseline factors, ARD, and worsened outcome may reflect complex cardiorenal interactions. Better understanding of the causes and prevention of ARD during heart failure therapy may in the future lead to better outcomes. (Am Heart J 1999;138:285-90.)