Calculated Creatinine Clearance Research Articles

OP.7D.07] 24-HOUR CENTRAL BLOOD PRESSURE IS BETTER ASSOCIATED WITH TARGET ORGAN DAMAGE OF HYPERTENSION THAN BRACHIAL BLOOD PRESSURE

Objective: The VASOTENS international, multicenter, observational, non-randomized, prospective study aims at evaluating the impact of 24-hour pulse wave analysis of ambulatory blood pressure (BP) recordings on target organ damage and cardiovascular prognosis of hypertensive patients. In the present analysis of study baseline data we checked whether organ damage of hypertension i) is better associated with 24-hour central than peripheral BP and ii) is related to ambulatory arterial stiffness, estimated by pulse wave velocity (PWV) and augmentation index (AIx). Design and method: In 334 hypertensive patients (mean age 53+/−15, 52% males, 45% treated) we obtained 24-hour ABPMs, echocardiograms, carotid ultrasonograms and serum creatinine. Hypertensive organ damage was estimated by calculation of left ventricular mass index (LVMI, cardiac damage), intima-media thickness (IMT, vascular damage) and creatinine clearance (CC, renal damage). 24-hour hemodynamics and stiffness were estimated through the validated VASOTENS technology, based on transfer function analysis of brachial oscillograms. 24-hour brachial (bSBP) and aortic systolic BP (aSBP), standard deviation of bSBP, PWV and AIx were obtained. Relation of vascular indices with LVMI, IMT and CC was evaluated by bivariate and multivariate analysis (stepwise linear regression analysis). Results: In the bivariate analysis a statistically significant relation was found for age, bSBP and aSBP vs. LVMI and IMT (see table, correlation coefficients or r). IMT was also significantly related to SBP variability and arterial stiffness, whereas increasing age, SBP variability and AIx were significantly associated with a decline of renal function.In the multivariate analysis, including all variables entered in the bivariate model, adjusted by sex, statistically significant (p < 0.001) association was observed for aSBP and age with LVMI (standardized regression coefficient 0.25 and 0.18, respectively), and for age with IMT (0.56) and CC (−0.53). Conclusions: In hypertensive patients age appears to be the major determinant of organ damage, with central SBP, and marginally peripheral SBP, PWV and AIx, also playing a significant role. Our results suggest that estimation of 24-hour central hemodynamics and arterial stiffness in ambulatory conditions may help improve the individualized assessment of the BP-associated organ damage of hypertension

Can we reliably predict the level of anticoagulation after enoxaparin injection in elderly patients with renal failure?

The aim of this study was to evaluate the activity of anti-activated factor X (anti-Xa) in patients with different degrees of chronic renal failure (CRF), treated with therapeutic doses of low molecular weight heparin. This prospective study evaluated the effect of age, renal function, BMI, gender, in determining the efficacy and safety of treatment with enoxaparin, evaluated by assessing the anti-Xa. The therapeutic anticoagulant range was set between 0.20 and 0.70U/mL. Two hospital geriatric units. 98 patients (64 men, 34 women, mean age 82years) with CRF, treated with enoxaparin at therapeutic dosage, for deep vein thrombosis or acute coronary syndrome. Anti-Xa was assessed 4h after the third administration of LMWH using Chromogenix test. Renal function was assessed by calculating creatinine clearance according to Cockcroft formula. The dose of enoxaparin ranged between 53 and 200U/kg; total 4000-16000U/day. The mean anti-Xa was 0.41U/mL (95% CI 0.36-0.45). Multiple regression analysis selected only the dose of enoxaparin, but not age, creatinine clearance, BMI, gender, as a predictor of anti-Xa serum levels. In seven patients anti-Xa was above the range but none of them received more than 150U/Kg enoxaparin (100U/kg if creatinine clearance <30mL/min). Ten patients (eight men, two women) showed suboptimal levels of anti-Xa, regardless enoxaparin dose or creatinine clearance. Enoxaparin dose reduction according to renal function decreases the risk of overdosing and potentially the risk of bleeding. The risk of under dosing seems less predictable; therefore, anti-Xa assay may be useful in severe clinical situations that require higher anticoagulant activity.

Refining the Policy for Timing of Kidney Transplant Waitlist Qualification.

Earlier qualification for the kidney transplant waitlist expedites transplant and is therefore associated with improved outcomes. U.S. Organ Procurement and Transplantation Network policies state that "measured or calculated creatinine clearance or glomerular filtration rate less than or equal to 20 mL/min" triggers waitlist time accrual. The choice of qualification method is somewhat arbitrary, and the policy implies that decline in renal function is monotonic. (1) We used survival analysis to quantify temporal differences in waitlist qualification by applying 3 kidney-function-estimating equations (Cockcroft-Gault, Modification of Diet in Renal Disease study, Chronic Kidney Disease Epidemiology Collaboration) to serial creatinine measurements from 3 patient cohorts: 1 of waitlisted patients at a major U.S. academic center and 2 national, multicenter cohorts of chronic kidney disease patients (African American Study of Kidney Disease and Hypertension, Modification of Diet in Renal Disease). (2) Survival analysis assessed whether requiring patients to demonstrate persistently reduced renal function on 2 occasions at least 90 days apart would meaningfully change qualification order. On average, time to waitlist qualification would be delayed on the order of 1 to 2 years by using calculated creatinine clearance (per the Cockcroft-Gault equation). Compared with current policy, requiring demonstration of persistently reduced renal function delayed qualification by 0.6 to 2.1 years and caused 40% to 50% of patients to switch the order in which they qualify by 6 months or more. The kidney transplantation policies should be revised, such that timing of waitlist qualification is more standardized. We suggest that mention of using calculated creatinine clearance be dropped from the Organ Procurement and Transplantation Network policy wording and the units to quantify kidney function be changed to mL/min per 1.73 m2. Some consideration should be given to whether requiring persistently reduced renal function would better identify patients most likely to benefit from earlier waitlist qualification.

Contrast-induced nephropathy in patients undergoing endovascular peripheral vascular intervention: Incidence, risk factors, and outcomes as observed in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium.

The incidence, risk factors, and outcomes associated with Contrast-induced nephropathy (CIN) after Percutaneous Vascular Intervention (PVI) in contemporary medical practice are largely unknown. A total of 13 126 patients undergoing PVI were included in the analysis. CIN was defined as an increase in serum creatinine from pre-PVI baseline to post-PVI peak Cr of ≥0.5 mg/dL. CIN occurred in 3% (400 patients) of the cohort, and 26 patients (6.5%) required dialysis. Independent predictors of CIN were high and low body weight, diabetes, heart failure, anemia, baseline renal dysfunction, critical limb ischemia, and a higher acuity of the PVI procedure and a contrast dose that was greater than three times the calculated creatinine clearance (CCC) (adjusted OR 1.4, 95% CI: 1.1-1.8, P = 0.003). CIN was strongly associated with adverse outcome including in-hospital death (adjusted OR 18.1, CI 10.7-30.6, P < 0.001), myocardial infarction (adjusted OR 16.2, CI 8.9-29.5, P < 0.001), transient ischemic attack/stroke (adjusted OR 5.5, CI 3.2-14.9, P = 0.001), vascular access complications (adjusted OR 3.4, CI 2.3-5, P < 0.001), and transfusion (adjusted OR 7, CI 5.4-9, P < 0.001). Hospital stay was longer in patients who developed CIN versus those who did not. CIN is not an uncommon complication associated with PVI, can be reliably predicted from pre-procedural variables, including a contrast dose of greater than three times the CCC and is strongly associated with the risk of in-hospital death, MI, stroke, transfusion, and increased hospital length of stay.

Do We Need to Personalize Renal Function Assessment in the Stratification of Patients Undergoing Cardiac Surgery?

BackgroundRenal dysfunction is an independent predictor of morbidity and mortality in cardiac surgery. For a better assessment of renal function, calculation of creatinine clearance (CC) may be necessary.ObjectiveTo objectively evaluate whether CC is a better risk predictor than serum creatinine (SC) in patients undergoing cardiac surgery.MethodsAnalysis of 3,285 patients registered in a prospective, consecutive and mandatory manner in the Sao Paulo Registry of Cardiovascular Surgery (REPLICCAR) between November 2013 and January 2015. Values of SC, CC (Cockcroft-Gault) and EuroSCORE II were obtained. Association analysis of SC and CC with morbidity and mortality was performed by calibration and discrimination tests. Independent multivariate models with SC and CC were generated by multiple logistic regression to predict morbidity and mortality following cardiac surgery.ResultsDespite the association between SC and mortality, it did not calibrate properly the risk groups. There was an association between CC and mortality with good calibration of risk groups. In mortality risk prediction, SC was uncalibrated with values > 1.35 mg /dL (p < 0.001). The ROC curve showed that CC is better than SC in predicting both morbidity and mortality risk. In the multivariate model without CC, SC was the only predictor of morbidity, whereas in the model without SC, CC was not only a mortality predictor, but also the only morbidity predictor.ConclusionCompared with SC, CC is a better parameter of renal function in risk stratification of patients undergoing cardiac surgery.

Acute kidney injury in Ureteric Stones:Single centre short term analysis.

Objective:To analyze acute kidney injury (AKI) frequency, risk factors and outcome in ureteric stone patients.Methods:This is an observational retrospective study performed in a single tertiary care centre in Abu Dhabi from October 2014 till August 2015. Convenient sampling was done on 152 consecutive patients who underwent decompression surgery (Ureterorenoscopy LASER Lithotripsy and DJ Stenting) for ureteric stones. Serum Creatinine was used to calculate creatinine clearance by cock croft Gault formula in all patients before and after procedure. Analysis was done on SPSS version 17.Results:Out of 152 patients who under went decompression surgical procedure for ureteric stones AKI was seen in 49(32.2%). Patients with AKI were found to be more higher age, increasedweight, bilateral stones, lower ureteric stones and with co morbidities in comparison to those who were without acute kidney injury. Patients developing AKI, 89.7% recovered either partially(20.4 %) or completely (69.3%).Conclusion:AKI is seen more in ureteric stone patients with older age, increased weight, bilateral stones, lower ureteric stones and with co morbidities. Recovery is good when obstruction is relieved.

Role of calculated glomerular filtration rate using percutaneous nephrostomy creatinine clearance in the era of radionuclide scintigraphy.

Context:Gates method tends to over-estimate glomerular filtration rate (GFR) in borderline functioning kidneys. We study the role of calculated GFR in these cases in decision-making regarding performing kidney-sparing surgery or nephrectomy.Aims:The aim of this study is to find the correlation between GFR calculated by percutaneous nephrostomy (PCN) urine creatinine clearance in obstructed kidneys and GFR by radionuclide scintigraphy. It also studies the role of this calculated GFR in borderline functioning kidneys.Settings and Design:Single tertiary care center; retrospective.Materials and Methods:A total of 46 patients in whom PCN was inserted as an emergency measure in an obstructed kidney and for whom diethylene-triamine-penta-acetic acid/ethylene-di-cysteine (DTPA/EC) scan was also done (Gates method) were analyzed retrospectively. PCN creatinine clearance was calculated for 3 consecutive days, and the mean value was used.Statistical Analysis Used:Pearson's correlational analysis; Chi-square test.Results:Overall strong correlation was found between the two GFR values (Pearson's r = 0.540692, P < 0.001). Totally 26 patients (56.52%) had comparable GFR values (P > 0.05). Among the 36 patients with borderline functioning kidneys, DTPA/EC scan significantly over-estimated GFR in one-third of the patients. The management plan was changed in 7 out of those patients (46.67%), with nephrectomy performed in all instead of kidney-sparing procedure. When the highest value of calculated GFR was compared, 28 patients had comparable GFRs (60.87%).Conclusions:GFR based on radionuclide scintigraphy may be insufficient for evaluation of residual renal function to determine the management of obstructed kidney with borderline function. For adequate decision-making, other factors including creatinine clearance via PCN should also be considered. Gates method tends to overestimate GFR as compared to calculated creatinine clearance at low GFR levels.

The Safety and Efficacy of Full Versus Reduced Dose Betrixaban in the Acute Medically Ill VTE (Venous Thromboembolism) Prevention with Extended Duration Betrixaban (APEX) Trial

Background: The exposure of all the currently licenced DOACs is increased in renal impairment and by certain drug interactions. The Acute Medically Ill VTE (Venous Thromboembolism) Prevention with Extended Duration Betrixaban (APEX) trial assessed the safety and efficacy of extended-duration thromboprophylaxis using betrixaban versus standard dosing of enoxaparin among acutely ill medical patients. The full 80 mg dose of betrixaban was halved to 40 mg among subjects with severe renal insufficiency (calculated creatinine clearance <30ml/min), or receiving a concomitant strong P-glycoprotein (P-gp) inhibitor.Objectives and Methods: The goal of this analysis is to assess the efficacy and safety of full (80 mg) and reduced dose (40 mg) betrixaban relative to enoxaparin in the APEX trial. Subjects were stratified into the two dose groups prior to randomization according to the pre-specified dosing criteria. The primary efficacy outcome was the composite of asymptomatic proximal and symptomatic venous thromboembolism (proximal or distal deep-vein thrombosis, symptomatic nonfatal pulmonary embolism, or death from venous thromboembolism). The principal safety outcome was major bleeding.Results: The median concentration of betrixaban among subjects administered the 80 mg dose was higher than that of the 40 mg dose (19 ng/ml vs 11 ng/ml, p<0.0001). In the primary analysis Cohort 1 (the elevated D-dimer +ve patients), the primary efficacy outcome was significantly reduced among subjects treated with 80 mg of extended dose betrixaban vs enoxaparin [6.3% (95/1516) vs 8.4% (130/1549), RRR = 0.26 (0.04-0.42), p=0.023]. A similar reduction was observed in the entire modified Intention to Treat (mITT) population [4.87% (122/2506) vs 7.06% (181/2562), RRR = 0.30 (0.13 - 0.44), p=0.001]. In contrast, among subjects receiving 40 mg of betrixaban there was no significant difference in the primary outcomes compared with enoxaparin across Cohorts 1, 2, and 3. There was no excess of major bleeding associated with administration of either the full 80 mg dose or the reduced 40 mg dose of betrixaban as compared with enoxaparin.Conclusion: For extended duration prophylaxis against VTE in hospitalized medically ill patients, the full 80 mg dose of extended duration betrixaban achieves higher serum concentrations than the 40 mg dose and is associated with improved efficacy across all cohorts relative to standard dose enoxaparin, without an excess risk of major bleeding. Based upon the approximate halving of plasma concentrations in this analysis and the lack of improvement in clinical outcomes, the reduced 40 mg dose may have been excessively downwardly adjusted. Conversely, the 80 mg dose was efficacious in all cohorts, including cohort 1. The inclusion of the 40 mg dose in the primary analysis may explain at least in part the marginal statistical result in the original report. DisclosuresCohen:Takeda: Consultancy; Medscape: Speakers Bureau; XO1: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Speakers Bureau; Portola: Consultancy, Honoraria, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Speakers Bureau; NHS: Membership on an entity’s Board of Directors or advisory committees; Lifeblood: Membership on an entity’s Board of Directors or advisory committees; Department of Health: Membership on an entity’s Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria; Janssen: Consultancy; Aspen: Consultancy, Speakers Bureau; Boehringer Ingelheim: Consultancy, Speakers Bureau; Colation to Prevent Venous Thromboembolism: Other: Founder; Leo Pharma: Consultancy; UK Government Health Select Committee: Membership on an entity’s Board of Directors or advisory committees; Johnson & Johnson: Consultancy, Honoraria, Speakers Bureau; ONO: Consultancy, Honoraria. Goldhaber:Portola: Consultancy. Hull:Portola: Consultancy. Hernandez:Portola: Consultancy. Gold:Portola Pharmaceuticals: Employment. Wiens:Portola: Employment, Equity Ownership. Harrington:Portola: Consultancy. Gibson:Portola: Consultancy.

First in Human Study with GSK2857916, an Antibody Drug Conjugated to Microtubule-Disrupting Agent Directed Against B-Cell Maturation Antigen (BCMA) in Patients with Relapsed/Refractory Multiple Myeloma (MM): Results from Study BMA117159 Part 1 Dose Escalation

BackgroundExpression of BCMA, a cell surface receptor in the TNF superfamily, is restricted to B cells at later stages of differentiation and is requisite for the survival of long lived plasma cells. BCMA is expressed on MM cells at variable levels.GSK2857916 is a humanized IgG1 anti-BCMA antibody conjugated to the microtubule disrupting agent monomethyl auristatin-F via a stable, protease-resistant maleimidocaproyl linker. Upon binding to BCMA, GSK2857916 is rapidly internalized and active drug is released within the cell. GSK2857916 also exhibits enhanced antibody-dependent cell-mediated cytotoxicity resulting from afucosylation of the FC domain which increases affinity to FCγRIIIa expressed on immune effector cells. The rationale for investigating GSK2857916 in MM is supported by the restricted pattern of BCMA expression and by evidence from preclinical studies.MethodsBMA117159 (NCT02064387) is a Phase I open-label study investigating safety, pharmacokinetics (PK), pharmacodynamics (PD), antidrug antibodies (ADA) and clinical activity of GSK2857916 in relapsed/refractory MM and other hematologic malignancies expressing BCMA. Dose escalation (Part 1) is conducted exclusively in MM patients; primary objective is safety, determination of maximum tolerated dose (MTD) and recommended phase 2 dose. GSK2857916 is administered every 3 weeks as a1 hr intravenous infusion with no mandatory prophylaxis for infusion related reactions (IRR). Bayesian Logistic Regression Model is applied for dose recommendations. Eligible MM patients must have prior treatments with alkylators, proteasome inhibitors, immunomodulators and stem cell transplantation, if transplant eligible, and have documented disease progression on or within 60 days of last therapy. Additional key inclusion criteria include: ANC >1x109/L; hemoglobin >8 g/dL; PLT >50x109/L; INR <1.5; PTT <1.5xULN; total bilirubin ≤1.25xULN; AST and ALT <1.5xULN; serum creatinine <1.2xULN or calculated creatinine clearance >60 mL/min; albuminuria <500mg/24hr; LVEF >50% and troponin <1xULN. Patients remain on treatment until progression, unacceptable toxicity, consent withdrawal or completing 16 treatment cycles. Blood is collected for PK and ADA analyses; blood and bone marrow aspirates are collected for PD analyses.ResultsTo date 24 MM patients have enrolled and completed the 21 day DLT observation period. Patients were enrolled at the following 8 dose levels: 0.03 (n=1); 0.06 (n=1); 0.12 (n=4); 0.24 (n=4); 0.48 (n=4); 0.96 (n=3); 1.92 (n=4), and 3.4 mg/kg (n=3). The median age is 60 years (range 39-71); 50% are male. Eighty-three percent received ≥4 prior lines. Sixty-three percent had IgG and 29% had IgA types. Seven patients (29%) had adverse cytogenetics defined as del17p13, or t(4;14) . Overall, 23 patients (96%) experienced adverse events (AE); the most frequent (≥20%) regardless of cause were nausea (42%), fatigue (38%), anemia (29%), chills (29%), pyrexia (29%), thrombocytopenia (29%), dry eye (21%), and hypercalcemia (21%). Grade 3/4 AEs reported in ≥10% of patients were thrombocytopenia, anemia, and neutropenia. Eight serious AEs were reported in 6 patients with 1 event of limbal stem cell dysfunction considered drug related; this event has not resolved. There were no AEs leading to treatment discontinuation. Four patients required dose reduction due to AEs: ocular toxicity (n=1), corneal disorder/ocular toxicity (n=1), dry eyes (n=1), and keratitis (n=1). IRRs (all Grade 1 or 2) were reported in 7 patients (29%) across dose levels and occurred with the first dose administration. The most frequent symptoms were chills. No DLTs were reported. Sixteen patients discontinued treatment due to disease progression (n=14), patient decision (n=1), completing 16 cycles of scheduled treatment (n=1); 8 patients are ongoing. There was1 MR at 0.24 mg/kg, and 1 VGPR, 3 PR, and1 MR at doses ≥0.96 mg/kg; resulting in a clinical benefit rate of 25% (unconfirmed responses).ConclusionGSK2857916 was well tolerated with no DLTs up to 3.4mg/kg q3w; MTD was not reached. AEs were manageable with ocular toxicity emerging as the most frequent reason for dose modifications. Clinical activity has been seen at higher doses. Complete safety, ADA, PD, and clinical activity data from all dose levels evaluated in Part 1 for q3w schedule will be presented.Study is funded by GlaxoSmithKline; drug linker technology is licensed from Seattle Genetics DisclosuresCohen:Janssen: Consultancy; Bristol-Meyers Squibb: Consultancy, Research Funding. Trudel:Glaxo Smith Kline: Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Equity Ownership, Honoraria; Oncoethix: Research Funding; BMS: Honoraria; Amgen: Honoraria. Richardson:Celgene: Membership on an entity's Board of Directors or advisory committees. Anderson:Takeda: Speakers Bureau; AMGEN/Onyx: Speakers Bureau; Celegene: Speakers Bureau. DeWall:GlaxoSmithKline: Employment, Equity Ownership. Ellis:GlaxoSmithKline: Employment, Equity Ownership. He:GlaxoSmithKline: Employment, Equity Ownership. Mazumdar:GlaxoSmithKline: Employment, Equity Ownership. Wang:GlaxoSmithKline: Employment, Equity Ownership. Opalinska:GlaxoSmithKline: Employment, Equity Ownership. Voorhees:GlaxoSmithKline: Research Funding; Celgene, BMS: Honoraria; Takeda: Consultancy, Honoraria; Novartis: Consultancy.

IS RENAL IMPAIRMENT CONCEALED IN ELDERLY DIABETICS????

&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To compare and evaluate the renal profile of elderly and younger diabetics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This cross sectional study was conducted in a tertiary care teaching hospital. Patients with type-2-diabetes were grouped into elderly (age≥60years) and younger diabetics. Patients’ demographics, duration of diabetes and serum creatinine were recorded. Cockcroft-Gault formula was used to calculate creatinine clearance (Clcr). Statistical analysis was done using Students’‘t’ test and Pearson’s correlation. Regression analysis to adjust for covariables was done wherever required.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 477 diabetics were included (elderly &lt;em&gt;n&lt;/em&gt;=320, young &lt;em&gt;n&lt;/em&gt;=157). Body mass index (BMI) was significantly lower (p=0.003) and duration of diabetes was significantly longer (p=0.001) among elderly. Significant difference was noted in serum creatinine (1.06±0.32 vs 0.95±0.29 mg/dl; p=0.0002) and Clcr (57.82±17.41 vs 88.07±24.60 ml/min; p=0.001) between elderly and younger diabetics. Only 4.7% of elderly, whereas 47.8% of young had normal Clcr. Clcr showed a negative correlation with age in elderly (r=-0.389, p&amp;lt;0.001) and young (r=-0.396, p&amp;lt;0.001) and positive correlation with BMI in elderly (r=0.401, p&amp;lt;0.001) and young(r=0.337, p&amp;lt;0.001). Regression analysis of Clcr in elderly and young showed a positive correlation for BMI and inverse relationship for age and duration of diabetes mellitus.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Almost 95% of the elderly and 50% of younger diabetics had impaired creatinine clearance. Renal impairment was concealed in most of them since mean serum creatinine was 1 mg/dl. Indian elderly diabetics should be considered renally impaired and drugs for all conditions need adjustment for creatinine clearance.&lt;/p&gt;

Effect of changing from first- to second-line antiretroviral therapy on renal function: a retrospective study based on data from a single health facility in Namibia

ABSTRACTBackground: Tenofovir disoproxil fumarate (TDF) and lopinavir/ritonavir (LPV/r) can cause renal impairment with this combination co-administered during second-line combination antiretroviral therapy (cART) potentially associated with greater risk of nephrotoxicity. As a result, the aim of this study is to assess effects of second-line cART on renal function.Methods: Retrospective longitudinal study in patients receiving cART.Results: 71 patients received TDF, zidovudine or stavudine, each combined with 3TC/NVP or 3TC/EFV. Before second-line cART, 46.5% had abnormal kidney function. First-line cART had no relationship with calculated creatinine clearance (CrCl). During second-line cART, more males than females had abnormal renal function and more females experienced increases in CrCl. Calculated CrCl during second-line cART related strongly with CrCl during first-line cART. Time spent on cART weak had a week relationship with CrCl.Conclusion: Patients on first-line cART for several years without renal impairment may experience new onset impairment during second line cART. Patients with pre-existing renal impairment just before switching to second-line cART may experience a further decline.

Relationship between ultrasonographically determined kidney volume and progression of chronic kidney disease.

Aim To investigate a correlation between calculated creatinine clearance as a measure of kidney's functional abilities and ultrasonographically determined kidney volume, which represents actual size of the kidney, in fact residual renal mass in chronic kidney disease, in order to determine possibilities of ultrasound as a diagnostic method in diagnosing and follow up of chronic renal disease. Methods Prospective study included 150 patients with registered demographic and anthropometric data, and also with relevant laboratory tests of renal function. Longitudinal diameter, thickness and width of the kidney and renal volume calculated according to the Dinkel's formula were measured by ultrasound. A correlation between the measured volume of the kidneys and calculated creatinine clearance was done by the Spearman method, with statistical significance of p<0.05. Results Statistically significant correlation between the estimated creatinine clearance values and the average of the calculated values of kidney volume was found (p<0.01). Average value of the kidneys' volume showed a linear decrease with the progression of chronic kidney disease: the kidney volume in the control healthy group was 171.7 ± 32.6 mL (95.22- 229.59 mL), and in the subjects classified in stage IV it was 74.7 ± 24.6 mL (43.22-165.65 mL). Conclusion Calculated volume of kidney well correlated with creatinine clearance as a measure of functional ability of the kidneys and with the stage of chronic renal disease. It can be used in clinical practice for monitoring of chronic kidney disease in conjunction with other clinical and laboratory parameters.

Can S-1 replace fluorouracil for advanced gastric cancer? A PRISMA-compliant systematic review and meta-analysis.

It remains to be seen whether S-1 can be a replacement for infusional fluorouracil (5-FU) for advanced gastric cancer (AGC). The aim of this study was to compare the efficacy and safety of S-1 with 5-FU in AGC.PubMed and Cochrane Library were searched. Randomized controlled trials and meta-analyses comparing S-1 with 5-FU for AGC were eligible. Meta-analysis was performed using RevMan 5.2.Seven trials involving 2443 patients were included. Compared with 5-FU, S-1 showed no significant prolongation of overall survival (OS) (hazard ratio [HR] = 0.91, 95% confidence interval [CI] [0.83–1.01], P = 0.07) and progression-free survival (HR = 0.89, 95% CI [0.70–1.13], P = 0.35), but longer time to treatment failure (HR = 0.74, 95% CI [0.56–0.97], P = 0.03). The objective response rates were comparable (risk ratio [RR] = 1.36, 95% CI [0.95, 1.96], P = 0.10). Regarding treatment-related deaths and hematological toxicities, there was significant heterogeneity between Asian and non-Asian trials, and subgroup analysis was applied. In Asian patients, there was a significant increase in hematological toxicities such as leukopenia (grade 1–4: RR = 1.22, 95% CI [1.08, 1.37], P = 0.001; grade 3–4: RR = 2.21, 95% CI [1.52, 3.21], P < 0.0001), neutropenia (grade 1–4: RR = 1.29, 95% CI [1.11, 1.48], P = 0.0005; grade 3–4: RR = 1.87, 95% CI [1.11, 3.17], P = 0.02), and thrombocytopenia (grade 1–4: RR = 1.71, 95% CI [1.22, 2.41], P = 0.002) in S-1-containing regimens compared with 5-FU-containing regimens, but without significant difference in treatment-related mortality rate (risk difference [RD] = 0.00, 95% CI [−0.01, 0.01], P = 0.68). In non-Asian patients, S-1-containing regimens were, however, associated with significantly fewer treatment-related deaths (RD = −0.02, 95% CI [−0.05, −0.00], P = 0.04), as well as less all grade 1–4 and grade 3–4 hematological toxicities except anemia. There was no significant heterogeneity in nonhematologic toxicities between Asian and non-Asian trials. Lower incidence of grade 1–4 nausea, diarrhea, mucositis, grade 3–4 mucositis, increased creatinine, and decreased calculated creatinine clearance was observed in S-1-containing regimens.S-1 could not improve OS, but increase some hematological toxicities in Asian patients. Therefore, special attention on hematological toxicities should be paid to Asian patients because S-1 is administered on an outpatient basis.

Use with caution in renal impairment – implications for drug dosing in the general practice setting

Abstract of a poster presentation at the 2016 National Medicines Symposium, 19-20 May, Canberra, Australia. Disciplines Medicine and Health Sciences | Social and Behavioral Sciences Publication Details Jordan, M., Stewart, A., Blaze, J., Hall, J., Frew, H. & Mullan, J. (2016). Use with caution in renal implications for drug dosing in the general practice setting. National Medicines Symposium 2016: Poster Abstracts (pp. 167-167). Australia: NPS. Authors Margaret L. Jordan, Adele F. Stewart, Julie M. Blaze, Jeffrey G. Hall, Haley Frew, and Judy Mullan This conference paper is available at Research Online: http://ro.uow.edu.au/smhpapers/3763 167 P o ster ab stacts 379 “Use with caution in renal impairment” – implications for drug dosing in the general practice setting Jordan M1, Stewart A1, Blaze J2, Hall J2, Frew H1, Mullan J3 1Woonona Medical Pratice, 2Bulli Medical Practice, 3School or Medicine, University of Wollongong Introduction: The number of medicines requiring attention in declining kidney function, and prescribed by GPs, is growing. A clinical pharmacist was integrated within a general practice, to investigate the management of anticoagulants. The results highlighted the implications of using readily available estimates (uncorrected Glomerular Filtration Rate, “eGFR”) for dosing of the non-vitamin K antagonist oral anticoagulants (NOACs) and informed a second project in a separate practice. Aims: To describe how kidney function is assessed in two general practices, the implications on use of renally-excreted medicines and the impact of a pharmacist. Methods: Two general practice research projects were undertaken. Study 1 investigated the impact of the pharmacist on the management of warfarin and NOACs, compared to the results from a retrospective review. Study 2 assessed appropriateness of medicine management in patients over 65 with impaired kidney function, before and after pharmacist input. Medicines most commonly prescribed were targeted. Estimates of kidney function were compared (eGFR and calculated creatinine clearance [eCrCl]) in both studies. Results: Study 1: Prior to pharmacist input, eGFR was used to guide drug-dosing of NOACS: usage was appropriate for 50% patients compared to 100% at the study close (P = 0.0245). Study 2: The appropriateness of management of the target medicines (pregabalin, NOACS, antidiabetic agents, statins, digoxin) improved from 42% to 88% (P<0.0001) despite similarities in measures of kidney function (P=0.4872). The means of kidney function metrics (eGFR vs eCrCl) differed significantly from each other in both stages: 63mL/min/1.73m2 vs 47mL/min; (P <0.001.) Implications for practice change: Significant differences in the estimates of kidney function lead to discrepancies in drug dosing, particularly for the NOACs. GPs have an ever-increasing range of medicines to manage, with competing sources for guidance. The input of a clinical pharmacist can improve the management of medicines in kidney impairment in general practices.

Calculated creatinine clearance using the CKD-EPI-formula shows a reliable prediction and high correlation to 24-h-urine in patients with diabetes mellitus but underrates systematically potentially leading to withdrawal or no prescription of oral antidiabetics

Calculated creatinine clearance using the CKD-EPI-formula shows a reliable prediction and high correlation to 24-h-urine in patients with diabetes mellitus but underrates systematically potentially leading to withdrawal or no prescription of oral antidiabetics

COMPARISON OF THE PROGNOSTIC UTILITIES OF CREATININE-BASED AND CALCULATED CREATININE CLEARANCE-BASED MID-TERM RENAL INSUFFICIENCY UNDERGOING PERCUTANEOUS CORONARY INTERVENTION

Contrast-induced acute kidney injury derived from creatinine value for 3-days, as well as persistent renal damage derived from calculated creatinine clearance (CCC) at 3-months has impact on worse clinical outcomes after percutaneous coronary intervention (PCI). While, there is little data regarding

Dual kidney transplants from adult marginal donors successfully expand the limited deceased donor organ pool.

The need to expand the organ donor pool remains a formidable challenge in kidney transplantation (KT). The use of expanded criteria donors (ECDs) represents one approach, but kidney discard rates are high because of concerns regarding overall quality. Dual KT (DKT) may reduce organ discard and optimize the use of kidneys from marginal donors. We conducted a single-center retrospective review of outcomes in adult recipients of DKTs from adult marginal deceased donors (DD) defined by limited renal functional capacity. If the calculated creatinine clearance in an adult DD was <65 mL/min, then the kidneys were transplanted as a DKT. Over 11.5 yr, 72 DKTS were performed including 45 from ECDs, 17 from donation after cardiac death (DCD) donors, and 10 from standard criteria donors (SCD). Mean adult DD and recipient ages were both 60 yr, including 29 DDs and 26 recipients ≥65 yr of age. Mean pre-DKT waiting and dialysis vintage times were 12 months and 25 months, respectively. Actual patient and graft survival rates were 84.7% and 70.8%, respectively, with a mean follow-up of 58 months. One yr and death-censored graft survival rates were 90% and 80%, respectively. Outcomes did not differ by DD category, recipient age, or presence of delayed graft function (DGF). Eleven patients died at a mean of 32 months post-DKT (eight with functioning grafts) and 13 other patients experienced graft losses at a mean of 33 months. The incidence of DGF was 25%; there were two cases (2.8%) of primary non-function. Mean length of initial hospital stay was 7.2 d. Mean serum creatinine and glomerular filtration rate levels at 12 and 24 months were 1.5 and 53 and 1.5 mg/dL and 51 mL/min/1.73 m(2) , respectively. DKT graft survival and function were superior to concurrent single ECD and similar to concurrent SCD KTs. Two patients underwent successful kidney retransplantation, so the dialysis-free rate in surviving patients was 87%. The proportion of total renal function transplanted from adult DD to DKT recipients was 77% compared to 56% for patients receiving single KTs. Dual kidney transplantation using kidneys from adult marginal DDs that otherwise might be discarded offer a viable option to counteract the growing shortage of acceptable single kidneys. Excellent medium-term outcomes can be achieved and waiting times can be reduced in a predominantly older recipient population.

Chemotherapy for Muscle-Invasive Bladder Cancer: Better Late Than Never?

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A 64-year-old man with a history of cigarette smoking but no significant comorbidities presented with hematuria and dysuria. Computed tomography scans demonstrated a mass and thickening of the bladder wall and no evidence of metastasis. His laboratory evaluation showed normal blood cell counts and comprehensive metabolic panel with a calculated creatinine clearance of more than 60 mL per minute. A transurethral resection of the bladder tumor and biopsy identified transitional cell carcinoma or urothelial carcinoma invading the muscularis propria of the bladder. On the basis of the bladder-confined mass on computed tomography scan, the tumor was assigned a clinical stage of cT2N0. The patient was advised to undergo neoadjuvant chemotherapy followed by radical cystectomy (RC). The patient had multiple concerns regarding neoadjuvant chemotherapy, particularly toxicities, especially the possibility of chronic neurologic and renal toxicities, and the potential harm from delay of RC, especially if the bladder cancer was resistant to chemotherapy. After a discussion of approximately 1 hour, he elected to proceed with upfront RC and extended lymph node dissection in conjunction with construction of a neobladder. Pathology revealed pathologic extravesical urothelial carcinoma, with disease in one of 25 lymph nodes removed (ypT3N1). Four weeks after RC, he returned to discuss further management with the medical oncologist. He exhibited an Eastern Cooperative Oncology Group performance status of 0, normal blood cell counts, and a calculated creatinine clearance of more than 60 mL per minute.

Cisplatin Induced Nephrotoxicity- An Assessment Based on Calculated Creatinine Clearance

Cisplatin Induced Nephrotoxicity- An Assessment Based on Calculated Creatinine Clearance

Preoperative Renal Function Predicts Hospital Costs and Length of Stay in Coronary Artery Bypass Grafting

Renal failure remains a major source of morbidity after cardiac surgery. Whereas the relationship between poor renal function and worse cardiac surgical outcomes is well established, the ability to predict the impact of preoperative renal insufficiency on hospital costs and health care resource utilization remains unknown. Patient records from a statewide The Society for Thoracic Surgeons (STS) database linked with estimated cost data were evaluated for isolated coronary artery bypass graft (CABG) operations (2000 to 2012). Patients with documented preoperative renal failure/dialysis were excluded. Preoperative renal function was determined using calculated creatinine clearance (CrCl). Multivariable regression analyses utilizing restricted cubic splines evaluated the continuous relationship between CrCl and risk-adjusted outcomes. A total of 46,577 isolated CABG operations were evaluated with a median STS predicted risk of mortality score of 1.2% (interquartile range, 0.7% to 2.4%), including 9% off-pump CABG. Median CrCl was 85 mL/min (range, 2 to 120 mL/min), and median total cost was $25,011. After adjustment for preoperative risk factors, worsening CrCl (declining renal function) was highly associated with greater total costs of hospitalization (coefficient=-122, p < 0.001) and postoperative length of stay (coefficient=-0.03, p < 0.001). Furthermore, predicted total costs were incrementally increased by 10%, 20%, and 30% with worsening of CrCl from 80 mL/min to 60, 40, and 20 mL/min. As expected, decreasing CrCl was also associated with an increased risk-adjusted likelihood for hemodialysis and mortality (both p < 0.001). Preoperative renal function is highly associated with the cost of CABG. Assessment of renal function may be used to preoperatively predict cost and resource utilization. Optimizing renal function preoperatively has the potential to improve patient quality and costs by approximately 6% ($1,250) for every 10 mL/min improvement in creatinine clearance.