Spectrum Of Renal Function Research Articles

Advanced Interatrial Block across the Spectrum of Renal Function

Background and Objective: Interatrial block (IAB) is defined as a conduction delay between the right and left atria. No data are available about the prevalence of both partial IAB and advanced IAB among the different stages of chronic kidney disease. The aim of this study was to describe the prevalence and type of advanced IAB across the spectrum of renal function, including patients on dialysis and the clinical characteristics associated with advanced IAB. Materials and Methods: Retrospective, single-center study of 151 patients consecutively admitted to the Nephrology and Ophthalmology Unit for 3 months. The study population was divided into three groups according to stages of chronic kidney disease. We evaluated the prevalence and pattern of IAB among the groups and the clinical characteristics associated with advanced IAB. Results: The prevalence of partial IAB was significantly lower in end-stage kidney disease (ESKD) group compared to control group (36.7% vs. 59.6%; p = 0.02); in contrast the prevalence of advanced IAB was significantly higher in both chronic kidney disease (CKD) (17.8% vs. 5.3%, p = 0.04) and ESKD group (24.5% vs. 5.3%, p = 0.005) compared to control group. The atypical pattern of advanced IAB was more frequent in both the ESKD and CKD group than in the control group (100% and 75% vs. 33.3%; p = 0.02). Overall, among patients that showed advanced IAB, 17 (73.9%) showed an atypical pattern by morphology and 2 (8.7%) showed an atypical pattern by duration of advanced IAB. The ESKD group was younger than the control group (65.7 ± 12.3 years vs. 71.3 ± 9.9 years; p = 0.01) and showed a higher prevalence of beta blockers (42.9% vs. 19.3%; p = 0.009), as in the CKD group (37.8% vs. 19.3%; p= 0.04). Conclusions: The progressive worsening of renal function was associated with an increasing prevalence of advanced IAB. Advanced IAB may be a sign of uremic cardiomyopathy and may suggest further evaluation with long-term follow-up to investigate its prognostic significance in chronic kidney disease.

2551. Assessing Meropenem Concentrations in Children with Septic Shock: Population-Based Pharmacokinetic (PK) Modeling of Meropenem Demonstrates Variability from Acute Kidney (AKI) to Augmented Renal Clearance (ARC)

Abstract Background The primary objective of this study was to characterize meropenem (MERO) pharmacokinetics (PK) in critically ill infants and children with septic shock to develop dosing recommendations to achieve therapeutic drug exposure in this complex population with a spectrum of renal function from augmented renal clearance (ARC) to acute kidney injury (AKI). Methods Children ≥4 weeks old hospitalized with septic shock requiring fluid resuscitation and pressors, receiving MERO 20 mg/kg IV every 8 hr as standard-of-care, were enrolled and studied prospectively from 2019 to 2023. Population PK modeling was used to derive Bayesian post-hoc PK parameters (NONMEM 7.3). Renal biomarkers (serum creatinine [SCr], cystatin C [CYS], serum neutrophil gelatinase-associated lipocalin [NGAL]) were evaluated as covariates. Estimated glomerular filtration rate (e-GFR) was calculated by the modified Schwartz equation. Results A total of 304 MERO serum concentrations were included from 26 participants. Median age was 12.6 yr (range 1.2-19.6); weight 38.4 kg (10-98); SCr 0.36 mg/dL (0.09-2.57); CYS 448.9 mg/d (178.3-1824.1), and NGAL 176.05 ng/mL (29.3-1000). Median MERO serum concentration was 11 mcg/mL (range 0.033-217, interquartile range [IQR] 1.873-37.85). A two-compartment model with allometrically scaled weight on clearance (0.75) best described the data. Significant covariates (final model) were e-GFR, CYS, NGAL, age, diagnosis of appendicitis and albumin. Using the final model, the median CL was 0.15 (range 0.05-0.51, interquartile range [IQR] 0.06-0.25) L/hr/kg and V1 0.20 (0.07-0.57, IQR 0.12-0.31) L/kg, with GFR 139 (23-364, IQR 93-204) mL/min/1.73 m2 (Figure). The distribution of MERO concentrations, CL and GFR across quartiles documents wide variations in renal function observed in septic shock, from AKI to ARC (Figure). Meropenem Serum Concentration, Meropenem Renal Clearance, and Glomerular Filtration Rate, by Quartiles Conclusion Wide variation in MERO plasma exposure was documented in children with septic shock across the spectrum of renal function. GFR-based dosing recommendations may optimize MERO dosing and improve outcomes in this population. This work was supported by NICHD grant 1 R01 HD095547-01 Disclosures Edmund Capparelli, PharmD, Melinta: Advisor/Consultant

Steroidal MRA Across the Spectrum of Renal Function: A Pooled Analysis of RCTs

BackgroundMineralocorticoid receptor antagonists (MRAs) are underused in patients with kidney dysfunction, and their efficacy among patients with chronic kidney disease (CKD) is uncertain. ObjectivesThe goal of this study was to analyze the efficacy and safety of steroidal MRAs across the spectrum of estimated glomerular filtration rates (eGFRs) in randomized controlled trials. The study included patients with heart failure (HF) or myocardial infarction and advanced CKD who participated in the RALES (Randomized Aldactone Evaluation Study), EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure), TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) in the Americas, and EPHESUS (Eplerenone Post-AMI Heart Failure Efficacy and Survival Study) trials. MethodsThis study used individual patient data meta-analysis using Cox models stratified by trial with treatment-by-eGFR interaction terms. eGFR was recalculated by using the Chronic Kidney Disease Epidemiology Collaboration creatinine formula. ResultsA total of 12,700 patients were included, of whom 331 (2.6%) had an eGFR ≤30 mL/min/1.73 m2 (mean eGFR: 26.8 ± 3.2 mL/min/1.73 m2). Patients with advanced CKD had higher annualized event rates for all studied outcomes: placebo event rate for the composite of cardiovascular death or HF hospitalization was ∼3-fold higher in patients with eGFR ≤30 compared with those with eGFR >90 mL/min/1.73 m2: 41.6 vs 14.6 events per 100 person-years. MRAs (vs placebo) reduced the composite of cardiovascular death or HF hospitalization, but the effect was attenuated as eGFR decreased: the corresponding HRs by eGFR categories were: HR for >90 mL/min/1.73 m2: 0.62 (95% CI: 0.49-0.78); HR for 61-90 mL/min/1.73 m2: 0.69 (95% CI: 0.61-0.77); HR for 46-60 mL/min/1.73 m2: 0.84 (95% CI: 0.74-0.95); HR for 31-45 mL/min/1.73 m2: 0.79 (95% CI: 0.68-0.91); and HR for ≤30 mL/min/1.73 m2: 0.96 (95% CI: 0.70-1.32) (treatment-by-eGFR interaction P for trend = 0.033). Investigator-reported hyperkalemia and worsening renal function were more frequent (2- to 3-fold) among MRA users, and hyperkalemia was more frequent as eGFR decreased (treatment-by-eGFR interaction P for trend = 0.002). ConclusionsSteroidal MRAs reduced HF hospitalizations and mortality across a wide range of eGFR. However, declining benefit and worsening safety may limit their use in patients with lower eGFR, particularly those with levels ≤30 mL/min/1.73 m2.

Population pharmacokinetics and pharmacodynamics of a novel vascular adhesion protein-1 inhibitor using a multiple-target mediated drug disposition model

ASP8232 is a novel inhibitor of vascular adhesion protein-1 that was under evaluation for reducing residual albuminuria in patients with diabetic kidney disease. To characterize the pharmacokinetics (PK) of ASP8232 and its effect on vascular adhesion protein 1 (VAP-1) plasma activity and VAP-1 concentrations (pharmacodynamics, PD) in an integrated and quantitative manner, a target mediated drug disposition model was developed based on pooled data from four completed clinical trials with ASP8232 in healthy volunteers, and in patients with diabetic kidney disease and diabetic macular edema, respectively. In this model, the binding of ASP8232 to its soluble and membrane-bound target in the central and peripheral compartments were included. The model was able to adequately describe the non-linear PK and PD of ASP8232. The observed difference in PK between healthy volunteers and renally impaired patients could be explained by an effect of baseline estimated glomerular filtration rate on ASP8232 clearance and relative bioavailability. The relationship between ASP8232 concentration and VAP-1 inhibition was successfully established and can be applied to simulate drug exposure and degree of VAP-1 inhibition for any given dose of ASP8232 across the spectrum of renal function.

Estimated Glomerular Filtration Rate as a Risk Stratification Tool for Early Complications in Revision Total Hip and Knee Arthroplasty

BackgroundEstablishing an association between postoperative outcomes and the spectrum of renal function would allow for more informed decisions to manage surgical risks and improved patient-specific care. Estimated glomerular filtration rate (eGFR) can be calculated from standard prescreening measurements to gauge renal function. This work investigates the effect of eGFR, as a continuous and categorical variable, on mortality and major and minor complications in patients undergoing revision total knee and hip arthroplasty. Methods25,056 patients having undergone revision total hip and knee arthroplasty from 2013 to 2016 were identified using the National Quality Improvement Program database. The investigated outcomes included 30-day mortality, major complications, and minor complications. Multivariate regression models were created to evaluate the effect of eGFR on the outcomes of interest. Multivariate spline regressions were generated to assess for nonlinear relationships between eGFR as a continuous variable and the outcomes. ResultsOur study revealed that as eGFR decreased <60 mL/min/1.73 m2, mortality (P = .0001), any major complication (P < .001), and any minor complication (P < .001) increased. Patients with eGFR 15-30 mL/min/1.73 m2 had increased risk for mortality (P = .033). There was an increased risk for any major complication at an eGFR 30-60 and <15 mL/min/1.73 m2, (P < .05). There was an increased risk of minor complications for those with hyperfiltration and <60 mL/min/1.73 m2. ConclusionPatients with lower preoperative eGFR generally display an increased risk for complications after revision total hip and knee arthroplasty. Proper consideration should be given to this patient population before surgical intervention to allow for preventative measures to be taken to improve patient outcomes.

4877Renal function and intensive blood pressure lowering in high-risk adults without diabetes: insights from the Systolic Blood Pressure Intervention Trial (SPRINT)

Abstract Background The Systolic Blood Pressure Intervention Trial (SPRINT) found that intensive blood pressure (BP) lowering reduced the rates of cardiovascular events and mortality but increased the risk of certain adverse events, in patients with and without chronic kidney disease at baseline. However, it is unclear whether intensive BP management is well-tolerated and modifies risk uniformly across the entire spectrum of renal function. Purpose To assess the relationship between renal function, treatment response to intensive BP lowering, and cardiovascular (CV) outcomes. Methods SPRINT was a randomized, controlled trial in which 9,361 individuals ≥50 years of age, at high CV risk but without diabetes who had a systolic BP (SBP) 130–180 mmHg, were randomized to intensive (target SBP &lt;120mmHg) or standard antihypertensive treatment (target SBP &lt;140mmHg). The primary efficacy endpoint was the composite of acute coronary syndromes, stroke, acute decompensated heart failure, or death from CV causes. The primary safety endpoint was the composite of serious adverse events (SAE). Renal function was assessed using the estimated glomerular filtration rate (GFR), calculated with the Modification of Diet in Renal Disease equation. We first assessed whether a linear association was present between eGFR and clinical endpoints using restricted cubic splines. We then examined the prognostic implications of eGFR, unadjusted and adjusted for demographic, clinical, and laboratory variables. We further explored the effects of intensive BP lowering across the eGFR spectrum. Results Baseline eGFR was available for 9,324 (&gt;99%) individuals. Mean eGFR was similar between the two groups (intensive group 71.8 ml/min/1.73m2 vs. standard group 71.7 ml/min/1.73m2; P=0.92). Median follow-up was 3.3 years (range 0–4.8), with 561 primary efficacy events (6%) and 3,522 SAE (38%) recorded during the study period. Baseline eGFR was non-linearly associated with the risk of the primary efficacy endpoint, death from CV causes, death from any cause, acute decompensated heart failure, SAE, electrolyte abnormality, and acute kidney injury (test for non-linearity, P&lt;0.05; test for overall trend, P&lt;0.001) and remained significantly associated with all tested endpoints upon multivariable adjustment (P&lt;0.05). Baseline eGFR significantly modified the effects of intensive BP lowering on the primary efficacy endpoint (P=0.02), acute decompensated heart failure (P=0.01), SAE (P=0.01), and acute kidney injury (P=0.04). The Figure shows treatment effects (hazard ratios) across the spectrum of eGFR for these four endpoints. P-values are for the interaction between eGFR and treatment effect. Significant interactions were not detected for other endpoints. Figure 1 Conclusions In SPRINT, lower eGFR was associated with a greater risk of both CV events and SAE. Patients with higher eGFR appeared to derive more benefit from intensive BP lowering while the relationship with safety events was complex.

Copeptin Associates with Cause-Specific Mortality in Patients with Impaired Renal Function: Results from the LURIC and the 4D Study.

In chronic kidney disease (CKD) arginine vasopressin (AVP) cannot efficiently act via renal V2-receptors. AVP is upregulated leading to augmented activation of V1a- and V1b-receptors, which might contribute to the increase in cardiovascular and infectious complications in CKD. Here, we evaluate copeptin, a surrogate of AVP, and its association with cause specific mortality among patients within the whole spectrum of renal function. Copeptin was measured in baseline samples from the LURIC (n = 3131 patients with coronary angiograms) and the 4D-Study (n = 1241 type 2 diabetic hemodialysis patients). Patients were stratified into 4 groups: estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2, 60-89 mL/min/1.73 m2, <60 mL/min/1.73 m2, and hemodialysis. The association of copeptin with mortality was assessed by Cox proportional hazards regression during 9.9 years of median follow-up in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study and 4 years of median follow-up in the German Diabetes Dialysis Study (4D-Study). Median copeptin increased with decreasing eGFR: 5.6 [interquartile range (IQR), 3.1-8.1] pmol/L (eGFR ≥90 mL/min/1.73 m2), 6.7 (2.9-10.5) pmol/L (eGFR 60-89 mL/min/1.73 m2), 15.3 (6.7-23.9) pmol/L (eGFR <60 mL/min/1.73 m2), and 80.8 (51.2-122) pmol/L (hemodialysis), respectively. Per SD increase in copeptin, the risk of coronary, infectious, and all-cause mortality increased by 25, 30, and 15% [hazard ratios (HR), 1.25; 95% CI, 1.13-1.39; HR, 1.30; 95% CI, 0.98-1.71; and HR, 1.15; 95% CI, 1.05-1.25], respectively, in patients with eGFR 60-89 mL/min/1.73 m2. Except for coronary death, results were similar among patients with more advanced renal disease. No significant association was found in patients with normal renal function. Copeptin concentrations were independently associated with coronary, infectious, and all-cause mortality in patients with renal impairment. In patients with normal renal function no significant association was found.

Efficacy of Folic Acid Therapy on the Progression of Chronic Kidney Disease: The Renal Substudy of the China Stroke Primary Prevention Trial.

The efficacy of folic acid therapy on renal outcomes has not been previously investigated in populations without folic acid fortification. To test whether treatment with enalapril and folic acid is more effective in slowing renal function decline than enalapril alone across a spectrum of renal function at baseline from normal to moderate chronic kidney disease (CKD) among Chinese adults with hypertension. In this substudy of eligible China Stroke Primary Prevention Trial (CSPPT), 15 104 participants with an estimated glomerular filtration rate (eGFR) 30 mL/min/1.73 m2 or greater, including 1671 patients with CKD, were recruited from 20 communities in Jiangsu province in China. Participants were randomized to receive a single tablet daily containing 10 mg enalapril and 0.8 mg folic acid (n = 7545) or 10 mg enalapril alone (n = 7559). The primary outcome was the progression of CKD, defined as a decrease in eGFR of 30% or more and to a level of less than 60 mL/min/1.73 m2 if the baseline eGFR was 60 mL/min/1.73 m2 or more, or a decrease in eGFR of 50% or more if the baseline eGFR was less than 60 mL/min/1.73 m2; or end-stage renal disease. Secondary outcomes included a composite of the primary outcome and all-cause death, rapid decline in renal function, and rate of eGFR decline. Overall, 15 104 Chinese adults with a mean (range) age of 60 (45-75) years were recruited; median follow-up was 4.4 years. There were 164 and 132 primary events in the enalapril group and the enalapril-folic acid group, respectively. Compared with the enalapril group, the enalapril-folic acid group had a 21% reduction in the odds of the primary event (odds ratio [OR], 0.79; 95% CI, 0.62-1.00) and a slower rate of eGFR decline (1.28% vs 1.42% per year; P = .02). Among the participants with CKD at baseline, folic acid therapy resulted in a significant reduction in the risks for the primary event (OR, 0.44; 95% CI, 0.26-0.75), rapid decline in renal function (OR, 0.67; 95% CI, 0.47-0.96) and the composite event (OR, 0.62; 95% CI, 0.43-0.90), and a 44% slower decline in renal function (0.96% vs 1.72% per year, P < .001). Among those without CKD at baseline, there was no between-group difference in the primary end point. Enalapril-folic acid therapy, compared with enalapril alone, can significantly delay the progression of CKD among patients with mild-to-moderate CKD. clinicaltrials.gov Identifier: NCT00794885.

What is the relationship between renal function and visit-to-visit blood pressure variability in primary care? Retrospective cohort study from routinely collected healthcare data

ObjectiveTo determine the relationship between renal function and visit-to-visit blood pressure (BP) variability in a cohort of primary care patients.DesignRetrospective cohort study from routinely collected healthcare data.SettingPrimary care in Nijmegen,...

Abstract 10944: The Optimal Definition of Contrast-Induced Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Interventions

Background: Multiple definitions exist for contrast induced acute kidney injury (CI-AKI) in the setting of percutaneous coronary interventions (PCI). It is unknown which definition is best associated with adverse events and whether this association is stable across patients with various degrees of baseline renal function. Hypothesis: We hypothesized that commonly used CI-AKI definitions would not be stable in risk prediction for mortality across the spectrum of renal function. Further, we sought to identify the optimal CI-AKI definition which would be both highly predictive of mortality and stable in its association regardless of baseline renal function. Methods: We applied logistic regression models to multiple current CI-AKI definitions to examine the impact of baseline renal function on a candidate CI-AKI definition’s correlation with the adverse outcome of mortality. We then utilized Likelihood ratios to examine candidate definitions and identify those where association with mortality remained constant regardless of baseline serum creatinine (SCr). These definitions were then assessed for specificity, sensitivity and positive and negative predictive values to identify an optimal definition. Results: Our study cohort comprised of 119,554 patients who underwent PCI in the state of Michigan between 2010-2014. Most commonly used definitions were not associated with mortality in a constant fashion across baseline renal function. Of the 266 candidate definitions examined, 16 definition’s association with mortality was not significantly altered by baseline SCr. CI-AKI defined as an absolute increase of SCr ≥ 0.3 mg/dl and a relative SCr increase ≥ 50% was selected as the optimal candidate using Perkins and Shisterman decision theoretic optimality criteria and was highly predictive of and specific for mortality. Conclusions: We identified the optimal definition for CI-AKI to be an absolute increase in SCr ≥ 0.3 mg/dl and a relative SCr increase ≥ 50%. Further work is needed to validate this definition in independent studies, in other clinical settings, and to establish its utility for clinical trials and quality improvement efforts.

Dominance of traditional cardiovascular risk factors over renal function in predicting arterial stiffness in subjects with chronic kidney disease

The predictors of arterial stiffness across the spectrum of renal function are unclear. These predictors were investigated across a wide range of estimated glomerular filtration rates (eGFR). Carotid-femoral pulse wave velocity (PWV; an index of arterial stiffness) was measured in 264 subjects with chronic kidney disease (CKD) stages 3-5 from three nephrology clinics ('lower GFR group'). PWV was also measured in 149 subjects without previously recognized CKD ('higher GFR group') including n = 26 with eGFR between 30 and 60 ml/min/1.73 m(2) and n = 123 with eGFR between 60 and 100 ml/min/1.73 m(2). The association between PWV and eGFR was investigated using linear regression. The 413 subjects had a mean age of 61.9 years, were 51% male, 28% diabetic and 79% hypertensive. In age-adjusted analyses within the 'lower GFR group', 'higher GFR group' and combined group, PWV correlated with higher systolic blood pressure (SBP), pulse pressure (PP), diabetes mellitus, body mass index (BMI) and resting heart rate (all P < 0.0008). In addition, PWV correlated inversely with eGFR in the 'higher GFR group' (P = 0.03) and combined group (P < 0.0001). In multivariable regression analyses of the combined group (n = 413), PWV was independently predicted by eGFR (P < 0.05). However, eGFR explained at most 4% of the variability in PWV in age-adjusted analyses (compared with 13-15% explained by SBP, PP or diabetes) and <1% of PWV variability in models adjusting for age, SBP, diabetes, heart rate and BMI (P < 0.0001). Although eGFR may independently predict PWV, the contribution of GFR per se does not appear to be clinically meaningful when compared with traditional cardiovascular risk factors.

Clinical Outcomes and Therapeutic Strategy in Patients With Acute Myocardial Infarction According to Renal Function Data From the Korean Acute Myocardial Infarction Registry

The aim of the present study was to evaluate the relationship between clinical outcomes after acute myocardial infarction (MI) and renal function by glomerular filtration rate (GFR) in patients with normal or mildly elevated serum creatinine concentrations. As part of the Korean Acute Myocardial Infarction Registry (KAMIR), 6,834 acute MI patients with a serum creatinine concentration of <or=2.0 mg/dl were enrolled from November 2005 to December 2006. The renal function was stratified arbitrary to 5 groups: (1) normal function, >90.0; (2) preserved function, 75.0-89.9; (3) mild dysfunction, 60.0-74.9; (4) moderate dysfunction, 45.0-59.9; (5) severe dysfunction, <45 ml.min(-1). 1.73 m(-2). Clinical characteristics, mortality and adverse events were analyzed among each group. Although reperfusion and medical therapies were underused, the rates of mortality and adverse events were increased with declining renal function. After adjustment with confounders, severe and moderate renal dysfunctions were important risk predictors of in-hospital mortality, long-term mortality and adverse events. The spectrum of renal function, when it was presented by GFR, is broad and is an important risk predictor for adverse outcomes after acute MI, even in patients with normal or mildly elevated serum creatinine concentrations. Furthermore, standard treatments were underused in any degree of renal dysfunction.

Impact of Renal Disease on Natriuretic Peptide Testing for Diagnosing Decompensated Heart Failure and Predicting Mortality

Concomitant occurrence of kidney disease (KD) and heart failure (HF) is common and associated with poor outcomes. Natriuretic peptide studies have typically excluded many individuals with KD. We compared the accuracy of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) for diagnosing decompensated HF and predicting mortality across the spectrum of renal function. BNP and NT-proBNP were prospectively measured in a cohort of 831 dyspnea patients. KD was defined as an estimated glomerular filtration rate <60 mL . min(-1) . (1.73 m(2))(-1). The accuracy and predictive value of each test for diagnosing decompensated HF and predicting all-cause 1-year mortality were assessed by ROC area under the curve (AUC) and multivariate regression analysis. Among the 831 dyspnea patients, 393 (47%) had KD. The diagnostic accuracies of BNP and NT-proBNP in detecting decompensated HF were similar to each other in patients without KD (AUC 0.75 vs 0.74, respectively; P = 0.60) and in patients with KD (AUC 0.68 vs 0.66; P = 0.10). One-year mortality rates were 36.3% and 19.0% in those with and without KD, respectively (P <0.001). Progressively higher BNP and NT-proBNP concentrations remained predictive of increased mortality in KD patients. Compared with the lowest quartile, quartile 4 of BNP had an adjusted hazards ratio (HR) of 2.6 (95% CI 1.4-4.8; P = 0.004 for trend) and NT-proBNP quartile 4 had an HR of 4.5 (95% CI 2.0-10.2; P <0.001 for trend). Only NT-proBNP remained a predictor of death after adjustment for clinical confounders and the other natriuretic peptide marker. NT-proBNP and BNP are equivalent predictors of decompensated HF across a spectrum of renal function, but NT-proBNP is a superior predictor of mortality.

Effect of Renal Function on the Pharmacokinetics of Valsartan

The effect of renal function on the pharmacokinetics of valsartan was investigated in this trial. In order to cover the full spectrum of renal function, a total of 19 subjects with normal renal function and various degrees of renal dysfunction, as determined by creatinine clearance (CLCR), were assigned to four groups: normal renal function (CLCR > 90 ml/min), and mild (CLCR 61 to 90 ml/min), moderate (CLCR 30 to 60 ml/min) and severe (CLCR < 30 ml/min) renal dysfunction. Creatinine clearance was determined following a 24-hour urine collection just prior to drug administration. Each subject received a single oral dose of 80mg of valsartan (capsule) after an overnight fast. Blood samples were collected at frequent intervals up to 48 hours postdose and plasma valsartan concentrations were determined. Pharmacokinetic parameters [area under the plasma concentration-time curve (AUC), maximum plasma valsartan concentration (Cmax), time to reach Cmax (tmax), and the terminal elimination half-life (t½)] were calculated. Statistical analysis using a cubic polynomial regression function was performed to examine a relationship between renal function and the pharmacokinetic parameters of valsartan.

Estimation of quantitative proteinuria by using the protein-creatinine ratio in random urine samples.

The protein-creatinine ratio was measured in urine samples obtained at three different times of the day and compared to the 24-hour protein excretion in 51 patients with a wide spectrum of renal function and proteinuria. A linear correlation, which was highly significant, was found between the two variables. The higher correlation was found in urine samples obtained at 08.00 and at 12.00 h and the lowest in samples obtained at 16.00 h. This correlation did not depend on the degree of proteinuria or on the sex of the patients, but was slightly dependent on the glomerular filtration rate. The protein-creatinine ratio was essentially identical with the 24-hour protein excretion. Thus, the normal range of proteinuria was represented by a ratio of less than 0.2, while nephrotic patients had a ratio above 3.5. We suggest that the protein-creatinine ratio in random urine samples could replace the timed collection methods at least for follow-up and screening.