Effect Of Renal Insufficiency Research Articles

Effect of renal insufficiency on the short- and long-term outcomes of endoscopic submucosal dissection for early gastric cancer: Propensity score-matched analysis.

It is unclear whether renal insufficiency (RI) itself is a risk factor for adverse outcomes after gastric endoscopic submucosal dissection (ESD). We aimed to evaluate the safety and efficacy of gastric ESD in patients with and without RI using propensity score-matching analysis. In all, 4775 patients with 4775 early gastric cancer lesions undergoing ESD were analyzed. 1:1 propensity score-matching was performed between patients with and without RI using 12 variables. After matching, logistic regression and survival analyses were performed for short- and long-term outcomes of ESD, respectively. The matching yielded 188 pairs of patients with and without RI. In both univariable and multivariable analyses, the presence of RI was not significantly associated with postprocedural bleeding (unadjusted odds ratio 1.81, 95% confidence interval 0.74-4.42; adjusted odds ratio 1.86, 95% confidence interval 0.74-4.65, respectively). When RI patients were subclassified into patients with estimated glomerular filtration rate (eGFR) 30-59 mL/min/1.73 m2 and eGFR <30 mL/min/1.73 m2 , no significant differences in bleeding rates were found compared to their matched controls in both groups. Perforation, en bloc resection, en bloc and R0 resection, and curative resection rates of RI patients were 2.1%, 98.4%, 91.0%, and 78.2%, respectively, which were comparable to those of non-RI patients. During a median follow-up of 119 months, there was no difference in gastric cancer-specific survival between patients with and without RI (P = 0.143). The outcomes of ESD were comparable in patients with and without RI. Decreased renal function itself may not be a reason to keep patients with RI from receiving gastric ESD.

The Effects of Renal Insufficiency and Age on Mortality in Geriatric Patients with Non-ST-Segment Elevation Myocardial Infarction

The Effects of Renal Insufficiency and Age on Mortality in Geriatric Patients with Non-ST-Segment Elevation Myocardial Infarction

Abstract P571: Effects of Renal Insufficiency on Congestive Heart Failure and Coronary Artery Disease Burden in Patients Undergoing Elective Percutaneous Coronary Intervention

Background: We investigated coronary artery disease (CAD) burden and rates of death and stroke in stable patients with renal insufficiency undergoing elective percutaneous coronary intervention (PCI). Methods: Data from 2015 NY state Angioplasty registry was utilized. There were 33,508 PCI recipients (65+/-11 years old; 32% females, 40% with diabetes, 6.4% with COPD, 6.9% with history of CHF, and 8.25% with peripheral artery disease) without history of recent myocardial infarction (MI in less than 24 hours), shock, or prior coronary artery bypass surgery. Patients were divided according to the glomerular filtration rate (GFR) status consistent with the National Kidney Foundation classification: 24% had a GFR more than 90 ml/min (group G1) , 49% GFR of 60-89 (G2), 15% GFR of 45-49 (G3a), 6.9% GFR 30-44 (G3b), 2% GFR of 15-29 (G4), and 4% with GFR of less than 15 ml/min (G5). Results: With decline in GFR, prevalence of CHF increased significantly. CHF was present in 3.6% of G1 patients undergoing elective PCI, 4.49% of G2, 10.20% of G3a, 17% of G3b, 22.26% of G4 and 22.20% of G5 patients (P&lt;0.0001). With decline in GFR, CAD burden was also significantly increased. Left main or three vessel CAD was present in 19.39% of G1 patients undergoing elective PCI, 19.13% of G2, 22.62% of G3a, 25.83% of G3b, 29% of G4 and 27.8% of G5 patients (p&lt;0.001). Furthermore, advanced kidney disease was associated with increased rates of post elective PCI stroke and death. Specifically, post PCI stroke occurred in 0.11% of G1 patients, 0.13% of G2, 0.33% of G3a, 0.27% of G3b, 0.7% of G4, and 0.6% of G5 patients (p&lt;0.001). Similarly, post elective PCI mortality occurred in 0.16% in G1 patients, 0.19% in G2, 0.41% in G3a, 1.04% in G3b, 1.22% in G4 and 1.49% in G5 patients (p&lt;0.0001). After adjustment for co-morbidities such as diabetes, CVD, and COPD, risk of post PCI stroke and death was significantly increased by 3.528 (95%CI 1.866-6.671, p&lt;0.0001) in patients with GFR less than 15 ml/min. Conclusion: In patients undergoing elective PCI, renal insufficiency is associated with increased rates of post-procedural death and stroke as well as increased prevalence of CHF. Additional research is needed to decrease risk of elective interventions in this vulnerable group of CAD patients.

Classical versus non-classical EGFR mutations: Erlotinib response and impact of renal insufficiency.

Erlotinib is an effective treatment option for EGFR-mutant non-small cell lung cancer. It is important to predict patients who will respond better to erlotinib. We designed this study to investigate the effect of renal insufficiency (RI) on erlotinib treatment outcomes. All patients receiving erlotinib were stratified into 3 groups. Group 1 consisted of non-RI subjects with classical epidermal growth factor receptor (EGFR) mutations, Group 2 consisted of those with RI (Estimated glomerular filtration rate <60 mL/min) and classical EGFR mutations, and Group 3 consisted of those with non-classical EGFR mutations. 82 patients were included in the study. Median progression-free survival (PFS) in patients with classical mutation was approximately 6 months shorter in those with RI, although not statistically significant. Median overall survival (OS) in Group 1, 2 and 3 was 34.1 months, 35.2 months, and 15 months, respectively and although not statistically significant, median OS was 20 months shorter in Group 3. Univariate and multivariate cox-regression analysis revealed shorter PFS and OS in males and those with ECOG ≥2 while PFS and OS were longer in those with recurrent lung tumors and generating rash during erlotinib treatment. There was no difference between RI and non-RI patients in terms of adverse events except for fatigue and appetite loss. This research showed OS in patients with and without RI was comparable. Although not statistically significant, PFS in patients with classical mutation was approximately 6 months shorter in those with RI patients.

A New Estimate of the Glomerular Sieving Coefficient for Retinol-Binding Protein 4 Suggests It Is Not Freely Filtered

A New Estimate of the Glomerular Sieving Coefficient for Retinol-Binding Protein 4 Suggests It Is Not Freely Filtered

Effect of renal insufficiency and diabetes mellitus on in-hospital mortality after acute coronary syndromes treated with primary PCI. Results from the ALKK PCI Registry

BackgroundIt is known that patients with acute coronary syndromes (ACS) and diabetes mellitus (DM) are at higher risk for in-hospital adverse events. However, we hypothesized that the higher event rate is due to the patients' subgroup with renal failure (RF), a common sequel of DM. Methods and resultsWe used data of the prospective ALKK-PCI registry including all consecutive percutaneous coronary interventions (PCI) for ACS of 48 hospitals between 2008 and 2013. We divided 69,651 patients in four groups according to their history of DM and RF (GFR < 60 ml/min). All-cause, in-hospital mortality of the following four groups: noDM/noRF, DM/noRF, DM/RF, RF/noDM, was: 3.5%, 6.6%, 21.9%, and 14.1% for STEMI and 1.5%, 2.1%, 7.2%, and 5.4% for NSTE-ACS. In a multivariate analysis we looked for independent mortality-predictors. Odds ratios with confidence intervals for the following variables: DM without RF, DM with RF, RF without DM were: 1.62 (1.37–1.90), 3.02 (2.43–3.76), and 2.13 (1.80–2.52) for STEMI and 1.20 (0.99–1.45), 2.72 (2.18–3.88), and 2.08 (1.69–2.56) for NSTE-ACS. We also calculated mortality in four groups (60–90, 45–60, 45–30, <30 ml/min) according to the estimated glomerular filtration rate (eGFR). Mortality rates were: 5.0%, 12.8%, 17.7%, and 31.5% for STEMI and 2.1%, 3.8%, 7.1%, and 12.0% for NSTE-ACS (p for trend <0.0001 for both). ConclusionsIn-hospital death after PCI in patients with ACS and DM is mainly observed in the subgroup with co-existing RF. In a multivariate analysis, DM without RF was a significant mortality-predictor in STEMI, but not in NSTE-ACS. RF, irrespective of co-existent DM, was a stronger predictor than DM alone for both ACS-types (OR > 3) and mortality increased with decreasing eGFR.

Effects of renal impairment on transporter-mediated renal reabsorption of drugs and renal drug-drug interactions: A simulation-based study.

Renal impairment (RI) significantly impacts the clearance of drugs through changes in the glomerular filtration rate, protein binding and alterations in the expression of renal drug transport proteins and hepatic metabolizing enzymes. The objectives of this study were to evaluate quantitatively the effects of renal impairment on the pharmacokinetics of drugs undergoing renal transporter-mediated reabsorption. A previously published semi-mechanistic kidney model incorporating physiologically relevant fluid reabsorption and transporter-mediated active renal reabsorption (PMID: 26341876) was utilized in this study. The probe drug/transporter pair utilized was γ-hydroxybutyric acid (GHB) and monocarboxylate transporter 1 (SCL16A1, MCT1). γ-Hydroxybutyric acid concentrations in the blood and amount excreted into urine were simulated using ADAPT 5 for the i.v. dose range of 200-1500mg/kg in rats and the impact of renal impairment on CLR and AUC was evaluated. A 90% decrease in GFR resulted in a>100-fold decrease in GHB CLR . When expression of reabsorptive transporters was decreased and fu was increased, CLR approached GFR. The effect of renal impairment on CLR was reduced when the expression of drug metabolizing enzymes (DME) was increased as a result of increased metabolic clearance; the converse held true when the DME expression was decreased. In conclusion, this study quantitatively demonstrated that the effects of renal insufficiency on the clearance of drugs is modulated by transporter expression, contribution of renal clearance to overall clearance, expression of drug metabolizing enzymes, fraction unbound and drug-drug interactions with inhibitors of renal transporters that may be increased in the presence of renal impairment.

The influence of body composition on renal function in patients with coronary artery disease and its prognostic significance: a retrospective cohort study.

ObjectiveWe try to analyse the effect of renal functions on death in CAD patients with different body compositions.MethodsA retrospective analysis was conducted in 2989 consecutive patients with CAD confirmed by coronary angiography were enrolled and were grouped into two categories: basically preserved renal function (PRF) (eGFR ≥60 ml/min) and obviously reduced renal function (RRF) (eGFR <60 ml/min). The influence of renal insufficiency on mortality of CAD was detected in every tertile of body composition, including body mass index (BMI), body fat (BF) and lean mass index (LMI). The end points were all-cause mortality.ResultsThe mean follow-up time was 29.1 ± 12.5 months and death events occurred in 271 cases. The percentage of patients with RRF was positively correlated with BF and inversely correlated with the LMI, but no relationship to BMI. The survival curves showed that the risk of death was significantly higher in the RRF patients in all subgroups stratified using BMI, BF, or LMI (log rank test, all p < 0.001). The COX multivariate regression analysis showed that the risk of death was significantly higher in the RRF patients with high BF (HR 1.95, CI 1.25–3.05) and low LMI (HR 1.82, CI 1.19–2.79). Meanwhile, risk of death was significantly higher in RRF patients with a high BMI (HR 2.08, CI 1.22–3.55) or low BMI (HR 1.98, CI 1.28–3.08) but this risk was not significant in patients with a medium BMI (HR 1.12, 0.65–1.94). The subgroup analysis of patients with acute coronary syndrome (ACS) showed similar results.ConclusionsFor patients with CAD, renal insufficiency was positively correlated with BF, inversely correlated with LMI, and unrelated to BMI. The effect of renal insufficiency on the risk of death of CAD was related to body composition.

Estimated GFR (eGFR) by prediction equation in staging of chronic kidney disease compared to gamma camera GFR

Background: Glomerular filtration rate is an effective tool for diagnosis and staging of chronic kidney disease. The effect ofrenal insufficiency by different method of this tool among patients with CKD is controversial.Objective: The objec­tive of this study was to evaluate the performance of eGFR in staging of CKD compared to gamma camera based GFR.Methods: This cross sectional analytical study was conducted in the Department of Biochemistry Bangabandhu Sheikh Mujib Medical University (BSMMU) with the collaboration with National Institute of Nuclear Medicine and Allied Sciences, BSMMU during the period of January 2011 to December 2012. Gama camera based GFR was estimated from DTP A reno gram and eGFR was estimated by three prediction equations. Comparison was done by Bland Altman agree­ment test to see the agreement on the measurement of GFR between three equation based eGFR method and gama camera based GFR method. Staging comparison was done by Kappa analysis to see the agreement between the stages identified by those different methods.Results: Bland-Altman agreement analysis between GFR measured by gamma camera, CG equation ,CG equation corrected by BSA and MDRD equation shows statistically significant. CKD stages determined by CG GFR, CG GFR corrected by BSA , MDRD GFR and gamma camera based GFR was compared by Kappa statistical analysis .The kappa value was 0.66, 0.77 and 0.79 respectively.Conclusions: This study findings suggest that GFR estimation by MDRD equation in CKD patients shows good agreement with gamma camera based GFR and for staging of CKD patients, eGFR by MDRD formula may be used as very effective tool in Bangladeshi population.

Prevalence and Effect of Renal Insufficiency in Newly Diagnosed Solid Cancer Patients: A Large Cohort Study with 9128 Patients from China

Prevalence and Effect of Renal Insufficiency in Newly Diagnosed Solid Cancer Patients: A Large Cohort Study with 9128 Patients from China

Constituintes químicos e estudos toxicológicos do óleo essencial extraído das folhas de Citrus limon Burn (Rutaceae)

A caracterização química do óleo essencial de folhas de Citrus limon (Rutaceae) resultou na identificação de mistura de monoterpenos (limoneno, linalol, cis-óxido de limoneno, trans-óxido de limoneno, citronelal, neral, geranial, nerol e acetato de geranil). As estruturas dos compostos do óleo essencial foram identificadas por GC/MS, por comparação com dados da literatura. Os efeitos da administração crônica oral do óleo essencial de folhas de Citrus limon foram investigados sobre parâmetros bioquímicos e hematológicos em camundongos Swiss machos. Os animais (n = 10/grupo) foram tratados por via oral diariamente durante 30 dias com óleo essencial de folhas de Citrus limon, nas doses de 50, 100 ou 150 mg kg-1 de massa corporal e os parâmetros bioquímicos e hematológicos avaliados. O tratamento não causou nenhuma morte ou toxicidade nos animais. A administração do óleo essencial não alterou os parâmetros bioquímicos e hematológicos e a massa dos órgãos, exceto por diminuição de 21 e 11% em uréia e ácido úrico, respectivamente, e 9%, nos níveis plasmáticos de aspartato transaminase (AST). Para os parâmetros hematológicos, houve pequenas mudanças nas contagens de neutrófilos, linfócitos, eosinófilos e monócitos, mas estes não foram diferentes dos valores de referência. Além disso, houve diminuição significativa nos triglicerídeos detectado nos animais tratados com dose de 150 mg kg-1 de óleo essencial. Em conclusão, a administração crônica de óleo essencial não induziu nenhum efeito de risco na maioria dos parâmetros bioquímicos e hematológicos estudados em camundongos Swiss machos. No entanto, a diminuição dos níveis de uréia e ácido úrico em doses elevadas, sugere um possível efeito de insuficiência renal e aumento no teor de AST, sugerindo possível sobrecarga hepática que deve ser investigada com mais detalhe.

The effect of naturally occurring renal insufficiency on serum pancreatic-specific lipase in cats

Feline pancreatitis is a common but likely an under-diagnosed condition. The recent development of pancreatic-specific lipase testing for this species has resulted in improved diagnostic testing. In cats, the effect of renal insufficiency has not been adequately evaluated. This paper reveals increased pancreatic-specific lipase in cats with renal insufficiency, but not pre-renal azotaemia, and suggests a significant effect of renal insufficiency on serum pancreatic-specific lipase concentrations.

Pharmacokinetics of Dexrazoxane in Subjects With Impaired Kidney Function

Dexrazoxane is approved as a cardioprotective agent for use in female patients with breast cancer who are receiving doxorubicin. The effect of renal insufficiency on elimination is not known. The pharmacokinetics of dexrazoxane 150 mg/m(2), given as a 15-minute constant-rate intravenous infusion, were assessed in 24 men and women with varying degrees of renal function in a single-dose, open-label, parallel-group study. Blood and urine samples were measured by a validated liquid chromatography/mass spectrometry assay. Dexrazoxane pharmacokinetic parameters were derived by standard noncompartmental methods. The effect of kidney function and effect of body surface area on the pharmacokinetics of dexrazoxane were analyzed using linear and nonlinear regression in the SPSS statistical program. Dexrazoxane clearance is decreased in subjects with kidney dysfunction. Compared with normal subjects (creatinine clearance [CL(CR)] >80 mL/min), mean area under the concentration curve from time 0 to infinity (AUC(0-inf)) was 2-fold greater in subjects with moderate (CL(CR) 30-50 mL/min) to severe (CL(CR) <30 mL/min) renal dysfunction. Modeling demonstrated that equivalent exposure (AUC(0-inf)) could be achieved if dosing were reduced by 50% in subjects with CL(CR) less than 40 mL/min compared with control subjects (CL(CR) >80 mL/min). Modeling study results suggested that equivalent exposure could be achieved if dosing was halved in subjects with CL(CR) less than 40 mL/min compared with controls.

Pharmacokinetics of Laropiprant and Glucuronide Metabolite in Patients with Severe Renal Insufficiency

Flushing symptoms limit the use of niacin as an effective treatment for dyslipidemia; laropiprant, a prostaglandin D2 receptor subtype 1 antagonist, reduces niacin-induced flushing and is being developed in combination with niacin. The aims of this study were to both determine the effect of renal insufficiency on plasma pharmacokinetics of laropiprant and to assess safety and tolerability in patients with severe renal insufficiency. This open-label study compared the pharmacokinetics of a single laropiprant 40-mg dose in 8 nondialyzed, severe renal insufficiency patients (RIs) with healthy matched subjects (HSs) (24-hour creatinine clearance <30 mL/min/1.73 m(2) and >80 mL/min/1.73 m(2) for RIs and HSs, respectively). In RIs, laropiprant was well tolerated and the area under the concentration time curve (AUC(0-infinity)) was modestly higher (ratio of geometric least-squares means [GMR] for RIs to HSs was 1.58; 90% confidence interval [CI], 1.06-2.35); neither the maximum laropiprant plasma concentration (C(max)) nor the time to C(max) (T(max)) was significantly affected. The apparent terminal half-life (t(1/2)) was 26.0 and 14.8 hours for RIs and HSs, respectively (P = 0.007). Similarly, for the inactive laropiprant glucuronide metabolite, the GMR for AUC(0-infinity) was 2.17 (90% CI, 1.44-3.27), and the apparent t(1/2) values were 25.3 to 14.5 hours (P = 0.037) in RIs and HSs, respectively. Renal insufficiency had no clinically significant effect on laropiprant pharmacokinetics. Because niacin and its metabolites are excreted through the kidneys, the combination of niacin with laropiprant should be used with caution in patients with renal impairment.

Should We Manage Patients With Non-ST Segment Elevation Myocardial Infarction With Renal Failure With an Invasive Strategy?

Szummer and colleagues raise an important question: Should we manage patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) with an early invasive strategy?1 It makes good sense to do this. We know that patients with renal dysfunction are at high risk,2 and the American College of Cardiology/American Heart Association and European Society of Cardiology guidelines both recommend an early invasive strategy for patients with unstable angina/NSTEMI who are high risk.3,4 Neither guideline, however, specifically notes that renal dysfunction should be a specific indication for an invasive strategy. Article see p 851 The investigators analyzed 23262 consecutive NSTEMI patients who had been included in a nationwide coronary care unit registry between 2003 and 2006 called the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART).1 Patients were divided into medically or invasively treated if revascularized within 14 days of admission. They found that for patients with worse renal function, the rate of performing revascularization was lower. This “risk paradox” has been seen in other registries, in which higher-risk patients are actually managed less intensively.5 They also found that 1-year mortality was substantially higher for those on dialysis or having an estimated glomerular filtration rate (GFR) <15 mL/min (≈55%) versus ≈40% for those with estimated GFR 15 to 29 mL/min and <5% for those with normal renal function. Thus, estimated GFR is clearly an important risk marker. They went on to compare mortality between medically managed patients and those who had revascularization and found overall a difference in mortality, with 36% lower adjusted mortality among those who had revascularization. They then split out the group by baseline renal function and found a lower mortality for those who had been revascularized versus not in most groups but not …

Abstract 5885: Impacts of Renal Insufficiency on the Prevalence of Heart Failure With Preserved Ejection Fraction in Hypertensive Patients

Renal insufficiency is a predictor of hospitalization for heart failure in hypertensive patients. However, the onset of heart failure in patients with kidney diseases is principally attributed to left ventricular systolic dysfunction induced by myocardial infarction or long-term hypertension, and the effects of renal insufficiency on the prevalence of symptomatic heart failure stage without systolic dysfunction remain unclear. This study aimed to assess the effects of renal insufficiency on the prevalence of heart failure with preserved ejection fraction. Out of 650 hypertensive outpatients with ejection fraction≥50%, 191 patients met the Framingham heart failure criteria. The multiple logistic regression analysis revealed that obese, female, estimated glomerular filtration rate (eGFR) &lt;60 ml/min/1.73m 2 and a ratio of transmitral E velocity to early diastolic mitral annular velocity (E/E′) &gt;15 were independent predictors of the prevalence of heart failure (Table ). To assess the effect of the renal insufficiency, the patients were divided into three groups as follow; CKD-A: eGFR≥75 (n=158), CKD-B: 60≤eGFR&lt;75 (n=207), CKD-C: eGFR&lt;60ml/min/1.73m 2 (n=285). The patients in CKD-B group represented higher E/E′ ratio and lower E′ velocity than those in CKD-A group. These indices were not different between the patients in CKD-B and CKD-C group. Hemoglobin concentration was significantly decreased and brachial-ankle pulse wave velocity was significantly elevated in the patients in CKD-C group compared to the other groups. Left ventricular diastolic dysfunction and renal insufficiency are independent risk factors for the prevalence of heart failure with preserved ejection fraction in hypertensive patients. Renal insufficiency exerts its effects through the modulation of extracardiac factors such as anemia and arterial stiffening rather than through the promotion of diastolic dysfunction. Table. Multivariate analysis of determinants of heart failure with EF≥50%

Difference of Clinical Characteristics between Hypertensive Patients with and without Diastolic Heart Failure: The Roles of Diastolic Dysfunction and Renal Insufficiency

Clinical characteristics were compared between hypertensive patients with and without heart failure in the absence of reduced ejection fraction (EF) to gain insights into the effects of renal insufficiency on the prevalence of diastolic heart failure. Study subjects consisted of 691 hypertensive patients with an EF>40%. Patients with serum creatinine >2.5 mg/dL were excluded from the study. The Framingham heart failure criteria were met by 198 patients, and competing risks of the prevalence of heart failure were analyzed. The multiple logistic regression analysis revealed that obesity, female gender, creatinine clearance (CCr), and a ratio of transmitral E velocity to early diastolic mitral annular velocity (E/ E')>15 were independently associated with the prevalence of heart failure with preserved EF. Patients with 60< or =CCr<90 mL/min represented higher E/E' ratio and lower E' velocity than the patients with CCr> or =90 mL/min, although there was no difference in the prevalence of heart failure between the two groups. These indices were not different between the patients with 60< or =CCr<90 mL/min and CCr<60 mL/min, although the prevalence of heart failure was higher in the patients with CCr<60 mL/min. The hemoglobin concentration was significantly decreased and the brachial-ankle pulse wave velocity was significantly elevated in patients with CCr<60 mL/min. Thus, progressive left ventricular diastolic dysfunction and renal insufficiency are competing risks of the prevalence of diastolic heart failure in hypertensive patients. Renal insufficiency may exert its effects through the modulation of extracardiac factors such as anemia and arterial stiffening rather than through the promotion of diastolic dysfunction.

Effect of Renal Insufficiency on the Pharmacokinetics of Sitagliptin, a Dipeptidyl Peptidase-4 Inhibitor

Sitagliptin is an oral, once-daily, potent, and highly selective dipeptidyl peptidase–4 inhibitor for the treatment of type 2 diabetes (1). In subjects with normal renal function (creatinine clearance >80 ml/min), 75–80% of an oral dose was excreted unchanged in urine. Renal clearance was ∼350 ml/min, indicating that active secretion of sitagliptin rather than only filtration is involved in renal excretion. Thus, renal excretion is the primary mechanism of elimination for sitagliptin (2). The purpose of this study was to evaluate the pharmacokinetics of single doses of sitagliptin in patients with various degrees of renal insufficiency (RI). This was an open-label, two-part study in 30 otherwise healthy male and female subjects (18–75 years of age) with BMI ≤40 kg/m2. Subjects were assigned to one of five groups ( n = 6/group), based on the following criterion for degree of RI: mild (creatinine clearance 50–80 ml/min), moderate (30–50 ml/min), severe ( 80 ml/min). Healthy subjects ( n = 145) from 11 other studies were included in a historical control group to supplement those studied here. Creatinine clearance values were based on measured 24-h urinary creatinine excretion (this study) or calculated using the Cockroft-Gault formula (historical controls). Because sitagliptin plasma concentrations were expected to increase with RI, a 50-mg dose was expected to be well …

Hyperglycemia in the Hospital Setting

To the Editor: I would like to draw attention to two special situations that were not specifically mentioned in the review of management of hyperglycemia in the hospital setting by Dr. Inzucchi (Nov. 2 issue).1 One is the effect of renal insufficiency on determination of the starting dose of insulin. Since insulin clearance is decreased in patients with renal insufficiency, reducing the starting dose of insulin is essential to avoid hypoglycemia. The second situation is the case of patients who are receiving glucocorticoids. Through increasing insulin resistance, glucocorticoids cause hyperglycemia mainly in the postprandial state. Therefore, these patients frequently require higher prandial doses of insulin than basal doses; the rule of a 1:1 ratio between basal and bolus insulin doses frequently does not apply.

Renal Function, Congestive Heart Failure, and Amino-Terminal Pro-Brain Natriuretic Peptide Measurement: Results From the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study

The relationship between renal insufficiency and amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels remains unclear. We examined this relationship in the context of patients who presented to the emergency department of an urban tertiary care medical center with dyspnea. Even in the presence of renal insufficiency, NT-proBNP remained a valuable tool for the diagnosis of acute congestive heart failure and it provides important prognostic information. We sought to examine the interaction between renal function and amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels. The effects of renal insufficiency on NT-proBNP among patients with and without acute congestive heart failure (CHF) are controversial. We examined the effects of kidney disease on NT-proBNP-based CHF diagnosis and prognosis. A total of 599 dyspneic patients with glomerular filtration rates (GFRs) as low as 14.8 ml/min were analyzed. We used multivariate logistic regression to examine covariates associated with NT-proBNP results and linear regression analysis to analyze associations between NT-proBNP and GFR. Receiver-operating characteristic analysis determined the sensitivity and specificity of NT-proBNP for CHF diagnosis. We also assessed 60-day mortality rates as a function of NT-proBNP concentration. Glomerular filtration rates ranged from 15 ml/min/1.73 m2 to 252 ml/min/1.73 m2. Renal insufficiency was associated with risk factors for CHF, and patients with renal insufficiency were more likely to have CHF (all p < 0.003). Worse renal function was accompanied by cardiac structural and functional abnormalities on echocardiography. We found that NT-proBNP and GFR were inversely and independently related (p < 0.001) and that NT-proBNP values of > 450 pg/ml for patients ages <50 years and >900 pg/ml for patients > or =50 years had a sensitivity of 85% and a specificity of 88% for diagnosing acute CHF among subjects with GFR > or =60 ml/min/1.73 m2. Using a cut point of 1,200 pg/ml for subjects with GFR <60 ml/min/1.73 m2, we found sensitivity and specificity to be 89% and 72%, respectively. We found that NT-proBNP was the strongest overall independent risk factor for 60-day mortality (hazard ratio 1.57; 95% confidence interval 1.2 to 2.0; p = 0.0004) and remained so even in those with GFR <60 ml/min/1.73 m2 (hazard ratio 1.61; 95% confidence interval 1.14 to 2.26; p = 0.006). The use of NT-proBNP testing is valuable for the evaluation of the dyspneic patient with suspected CHF, irrespective of renal function.