Renal Creatinine Clearance Research Articles

Positive association of residual kidney function with hemoglobin level in patients on peritoneal dialysis independent of endogenous erythropoietin concentration

BackgroundHow residual kidney function (RKF) functions in the prevention of anemia in peritoneal dialysis (PD) patients is unclear. In this study, we investigated the association between RKF and hemoglobin (Hb) level.MethodsWe performed a cross-sectional analysis of the association between RKF, defined as the mean renal creatinine and urea clearance (rCUC), and the Hb level in 50 PD patients registered retrospectively. The independent variable was mean rCUC as continuous or categorical variable by tertile, and the dependent variable was Hb level as continuous or dichotomous variable using Hb cutoff of 10 g/dL. We conducted a multivariable regression analysis and calculated the c-statistic for Hb level < 10 g/dL using a receiver operating characteristic curve.ResultsIn multivariable regression analysis, mean rCUC was significantly associated with Hb level independent of dose of erythropoiesis-stimulating agent (ESA) and endogenous erythropoietin (eEPO) concentration. Multivariable adjusted least square means of the Hb level were higher with increase in the mean rCUC tertile. The c-statistic (95% confidential interval) for a Hb level < 10 g/dL was significantly greater in the model with mean rCUC than without [0.931 (0.789–0.980) vs. 0.856 (0.697–0.939), P = 0.044].ConclusionA decline in RKF is associated with anemia in PD patients independent of ESA dose and eEPO concentration.Trial registrationUMIN000018902

Herbal teas heavy metal evaluation with renal function assessment in regular consumers in Benin

Herbal teas are openly sold in markets and main streets of big cities like Cotonou in Benin. Most people treat themselves at low cost with wide variety of herbal plants with proven therapeutic properties. The purpose of this research was to evaluate the content of heavy metals in herbal teas sold daily in Cotonou. In addition, we would evaluate if this heavy metal content of herbal teas could affect the renal function of regular consumers. Therefore, herbal teas samples were collected from selected sellers at well-known places. Samples’ analyses were done by reverse anodic stripping voltammetry with the Metalyser HM 3000 coupled to PC 101 NT pump. Biological markers of kidney failure in blood and urine of regular consumers were also assessed. Renal creatinine clearance and albuminuria were measured, the ratio of micro-albuminuria/creatininuria was calculated, and then red and white blood cells were counted. The results indicate that 7.69 and 30.77% of the herbal teas samples displayed an abnormal high concentration in cadmium (Cd) and lead (Pb) concentration, respectively. Statistical significant difference was found between the analyzed herbal tea samples in regard to Cd and Pb content (P E‚ 0.01). No obvious biological sign of severe kidney damage has been noted among regular consumers using their blood and urine samples. Only 8.60% of them had clearances between 60 and 89 ml/min/1.73 m2 with mild kidney failure. This study indicates that some herbal teas contain toxic chemicals such as Cd and Pb over recommended limits of 3 and 10 µg/L, respectively. The regular consumption of these herbal teas could be health threatening for the population. Key words: Herbal teas, heavy metals, environmental pollution, human renal function, anodic stripping voltammetry.

Active Brown Fat During 18F-FDG PET/CT Imaging Defines a Patient Group with Characteristic Traits and an Increased Probability of Brown Fat Redetection

Brown adipose tissue (BAT) provides a means of nonshivering thermogenesis. In humans, active BAT can be visualized by 18F-FDG uptake as detected by PET combined with CT. The retrospective analysis of clinical scans is a valuable source to identify anthropometric parameters that influence BAT mass and activity and thus the potential efficacy of envisioned drugs targeting this tissue to treat metabolic disease. Methods: We analyzed 2,854 18F-FDG PET/CT scans from 1,644 patients and identified 98 scans from 81 patients with active BAT. We quantified the volume of active BAT depots (mean values in mL ± SD: total BAT, 162 ± 183 [n = 98]; cervical, 40 ± 37 [n = 53]; supraclavicular, 66 ± 68 [n = 71]; paravertebral, 51 ± 53 [n = 69]; mediastinal, 43 ± 40 [n = 51]; subphrenic, 21 ± 21 [n = 29]). Because only active BAT is detectable by 18F-FDG uptake, these numbers underestimate the total amount of BAT. Considering only 32 scans of the highest activity as categorized by a visual scoring strategy, we determined a mean total BAT volume of 308 ± 208 mL. In 30 BAT-positive patients with 3 or more repeated scans, we calculated a much higher mean probability to redetect active BAT (52% ± 25%) as compared with the overall prevalence of 4.9%. We calculated a BAT activity index (BFI) based on volume and intensity of individual BAT depots. Results: We detected higher total BFI in younger patients (P = 0.009), whereas sex, body mass index, height, mass, outdoor temperature, and blood parameters did not affect total or depot-specific BAT activity. Surprisingly, renal creatinine clearance as estimated from mass, age, and plasma creatinine was a significant predictor of BFI on the total (P = 0.005) as well as on the level of several individual depots. In summary, we detected a high amount of more than 300 mL of BAT tissue. Conclusion: BAT-positive patients represent a group with a higher than usual probability to activate BAT during a scan. Estimated renal creatinine clearance correlated with the extent of activated BAT in a given scan. These data imply an efficacy of drugs targeting BAT to treat metabolic disease that is at the same time higher and subject to a larger individual variation than previously assumed.

Transporters affecting biochemical test results: Creatinine-drug interactions.

Creatinine is eliminated by the kidneys through a combination of glomerular filtration and active transport. Drug-induced increases in serum creatinine (SCr) and/or reduced creatinine renal clearance are used as a marker for acute kidney injury. However, inhibition of active transport of creatinine can result in reversible and, therefore, benign increases in SCr levels. Herein, the transporters involved in creatinine clearance are discussed, in addition to limitations of using creatinine as a biomarker for kidney damage.

Circadian Rhythms in Water and Solute Handling in Adults with a Spinal Cord Injury

We evaluated nocturnal urine production and circadian rhythms of renal function (glomerular filtration, and water and solute diuresis) in adults with spinal cord injury compared to controls. This prospective observational study was done at Ghent University Hospital, Belgium. Participants were asked to perform a 24-hour urine collection. A blood sample was taken to calculate the diuresis rate and the renal clearance of creatinine, free water, solutes, sodium and urea. A total of 119 patients were divided into 32 with spinal cord injury, and 68 controls with and 19 without nocturnal polyuria. Spinal cord injured patients showed no circadian rhythms in the diuresis rate or in the renal clearance of creatinine, free water, solutes, sodium or urea. Controls without nocturnal polyuria reported a lower nighttime diuresis rate and lower nighttime clearance of creatinine, solutes, sodium and urea compared to daytime levels. Controls with nocturnal polyuria had no circadian rhythms in the diuresis rate or creatinine clearance and a significant increase in nocturnal free water clearance compared to daytime levels. Comparing the mechanisms underlying nocturnal urine production between patients with spinal cord injury and controls revealed important differences. Spinal cord injured patients showed absent circadian rhythms in the renal clearance of creatinine (glomerular filtration), free water (water diuresis) and solutes such as sodium and urea (solute diuresis). Future research must be done to evaluate the role of patient stratification to find the most effective and safe treatment or combination of treatments for spinal cord injured patients with complaints or complications related to nocturnal polyuria.

CONIFER - Non-Interventional Study to Evaluate Therapy Monitoring During Deferasirox Treatment of Iron Toxicity in Myelodysplastic Syndrome Patients with Transfusional Iron Overload

Background: The non-interventional study CONIFER was designed to assess the safety and clinical practicability of deferasirox for the treatment of transfusional iron overload in myelodysplastic syndrome (MDS) patients. Methods: Patients included in the study were diagnosed with MDS and received at least 1 treatment with deferasirox. The observation period covered the time from the initial visit until the last follow-up. Results: The data of 99 patients with MDS scored mainly as International Prognostic Scoring System (IPSS) low and intermediate 1 were evaluated. The mean age of the participants was 75 years and 58% of the patients were male. Iron overload was assessed by serum ferritin level (mean baseline serum ferritin 2,080 ± 1,244 µg/l). Patients were treated for a mean duration of 16 months (mean daily dose at baseline 11.8 ± 7.0 mg/kg). Stratification of serum ferritin levels by deferasirox dose showed a reduction at the higher but no reduction at the lower dose (< 15 mg/kg vs. ≥ 15 mg/kg and < 20 mg/kg vs. ≥ 20 mg/kg). The majority of patients (81%) were affected by at least 1 adverse event, with decreased renal creatinine clearance being the most frequent. Conclusion: Higher doses (≥ 15 mg/kg) of deferasirox effectively and safely reduced serum ferritin levels in MDS patients with transfusional iron overload.

Adrenal, metabolic and cardio-renal dysfunction develops after pregnancy in rats born small or stressed by physiological measurements during pregnancy.

Women born small are at an increased risk of developing pregnancy complications. Stress may further increase a woman's likelihood for an adverse pregnancy. Adverse pregnancy adaptations can lead to long-term diseases even after her pregnancy. The current study investigated the effects of stress during pregnancy on the long-term adrenal, metabolic and cardio-renal health of female rats that were born small. Stress programmed increased adrenal Mc2r gene expression, a higher insulin secretory response to glucose during intraperitoneal glucose tolerance test (+36%) and elevated renal creatinine clearance after pregnancy. Females that were born small had increased homeostatic model assessment-insulin resistance and elevated systolic blood pressure after pregnancy, regardless of stress exposure. These findings suggest that being born small or being stressed during pregnancy programs long-term adverse health outcomes after pregnancy. However, stress in pregnancy does not exacerbate the long-term adverse health outcomes for females that were born small. Females born small are more likely to experience complications during their pregnancy, including pregnancy-induced hypertension, pre-eclampsia and gestational diabetes. The risk of developing complications is increased by stress exposure during pregnancy. In addition, pregnancy complications may predispose the mother to diseases after pregnancy. We determined whether stress during pregnancy would exacerbate the adrenal, metabolic and cardio-renal dysfunction of growth-restricted females in later life. Late gestation bilateral uterine vessel ligation was performed in Wistar Kyoto rats to induce growth restriction. At 4months, growth-restricted and control female offspring were mated with normal males. Those allocated to the stressed group had physiological measurements [metabolic cage, tail cuff blood pressure, intraperitoneal glucose tolerance test (IPGTT)] conducted during pregnancy whilst the unstressed groups were unhandled. After the completion of pregnancy, dams were aged to 12months and blood pressure, and metabolic and renal function were assessed. At 13months, adrenal glands, pancreases and plasma were collected at post-mortem. Females stressed during pregnancy had increased adrenal Mc2r gene expression (+22%), higher insulin secretory response to glucose during IPGTT (+36%) and higher creatinine clearance (+29%, indicating increased estimated glomerular filtration rate). In contrast, females that were born small had increased homeostatic model assessment-insulin resistance (+54%), increased water intake (+23%), urine output (+44%) and elevated systolic blood pressure (+7%) regardless of exposure to stress. Our findings suggest that low maternal birth weight and maternal stress exposure during pregnancy are both independently detrimental for long-term adrenal, metabolic and cardio-renal health of the mother, although their effects were not exacerbated.

To Save or not to Save the Kidney: Relieving Unilateral Obstruction May Significantly Improve an Initially Low Split Renal Creatinine Clearance

To Save or not to Save the Kidney: Relieving Unilateral Obstruction May Significantly Improve an Initially Low Split Renal Creatinine Clearance

Quantitative arterial spin labelling perfusion measurements in rat models of renal transplantation and acute kidney injury at 3 T

ObjectivesTo employ ASL for the measurement of renal cortical perfusion in particular renal disorders typically associated with graft loss and to investigate its potential to detect and differentiate the related functional deterioration i.e., in a setting of acute kidney injury (AKI) as well as in renal grafts showing acute and chronic transplant rejection. Materials and Methods14 Lewis rats with unilateral ischaemic AKI and 43 Lewis rats with renal grafts showing acute or chronic rejections were used. All ASL measurements in this study were performed on a 3T MR scanner using a FAIR True-FISP approach to assess renal blood flow (RBF). Perfusion maps were calculated and the cortical blood flow was determined using a region-of-interest based analysis. RBF of healthy and AKI kidneys as well as of both rejection models, were compared. In a subsample of 20 rats, creatinine clearance was measured and correlated with cortical perfusion. ResultsRBF differs significantly between healthy and AKI kidneys (P<0.001) with a mean difference of 213±80ml/100g/min. Renal grafts with chronic rejections show a significantly higher (P<0.001) mean cortical perfusion (346±112ml/100g/min) than grafts with acute rejection (240±66ml/100g/min). Both transplantation models have a significantly (P<0.001) lower perfusion than healthy kidneys. Renal creatinine clearance is significantly correlated (R=0.85, P<0.001) with cortical blood flow. ConclusionPerfusion measurements with ASL have the potential to become a valuable diagnostic tool, regarding the detection of renal impairment and the differentiation of disorders that lead to a loss of renal function and that are typically associated with graft loss.

The Complexities of Interpreting Reversible Elevated Serum Creatinine Levels in Drug Development: Does a Correlation with Inhibition of Renal Transporters Exist?

In humans, creatinine is formed by a multistep process in liver and muscle and eliminated via the kidney by a combination of glomerular filtration and active transport. Based on current evidence, creatinine can be taken up into renal proximal tubule cells by the basolaterally localized organic cation transporter 2 (OCT2) and the organic anion transporter 2, and effluxed into the urine by the apically localized multidrug and toxin extrusion protein 1 (MATE1) and MATE2K. Drug-induced elevation of serum creatinine (SCr) and/or reduced creatinine renal clearance is routinely used as a marker for acute kidney injury. Interpretation of elevated SCr can be complex, because such increases can be reversible and explained by inhibition of renal transporters involved in active secretion of creatinine or other secondary factors, such as diet and disease state. Distinction between these possibilities is important from a drug development perspective, as increases in SCr can result in the termination of otherwise efficacious drug candidates. In this review, we discuss the challenges associated with using creatinine as a marker for kidney damage. Furthermore, to evaluate whether reversible changes in SCr can be predicted prospectively based on in vitro transporter inhibition data, an in-depth in vitro-in vivo correlation (IVIVC) analysis was conducted for 16 drugs with in-house and literature in vitro transporter inhibition data for OCT2, MATE1, and MATE2K, as well as total and unbound maximum plasma concentration (Cmax and Cmax,u) data measured in the clinic.

Population pharmacokinetics of meropenem during continuous infusion in surgical ICU patients.

Continuous infusion of meropenem is a candidate strategy for optimization of its pharmacokinetic/pharmacodynamic profile. However, plasma concentrations are difficult to predict in critically ill patients. Steady-state concentrations of meropenem were determined prospectively during continuous infusion in 32 surgical ICU patients (aged 21-85 years, body weight 55-125 kg, APACHE II 5-29, measured creatinine clearance 22.7-297 mL/min). Urine was collected for the quantification of renal clearance of meropenem and creatinine. Cystatin C was measured as an additional marker of renal function. Population pharmacokinetic models were developed using NONMEM(®) , which described total meropenem clearance and its relationship with several estimates of renal function (measured creatinine clearance CLCR , Cockcroft-Gault formula CLCG , Hoek formula, 1/plasma creatinine, 1/plasma cystatin C) and other patient characteristics. Any estimate of renal function improved the model performance. The strongest association of clearance was found with CLCR (typical clearance = 11.3 L/h × [1 + 0.00932 × (CLCR - 80 mL/min)]), followed by 1/plasma cystatin C; CLCG was the least predictive covariate. Neither age, weight, nor sex was found to be significant. These models can be used to predict dosing requirements or meropenem concentrations during continuous infusion. The covariate CLCR offers the best predictive performance; if not available, cystatin C may provide a promising alternative to plasma creatinine.

A Pilot Study Examining the Effects of Tolvaptan on Residual Renal Function in Peritoneal Dialysis for Diabetics.

For patients with end-stage renal disease (ESRD), peritoneal dialysis (PD) serves as a possible renal replacement therapy. However, most PD patients, particularly those with ESRD and diabetes mellitus, reportedly discontinue PD early, resulting in shorter survival periods and poorer prognosis because of overhydration. Recently, the vasopressin-2 receptor antagonist tolvaptan was approved for volume control in patients with heart failure. The present study aimed to identify the effects of tolvaptan in diabetic PD patients. In this pilot study, the tolvaptan group (n = 12) were treated with 15 mg/day of tolvaptan 2 weeks after PD initiation and were prospectively analyzed for 1 year, and patients in the control group (n = 12) did not receive tolvaptan and were retrospectively analyzed for 1 year. In addition to the biochemical tests, echocardiograms, serum atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels, peritoneal Kt/V, and creatinine clearance (CCr) were examined at baseline and at 6 and 12 months after PD initiation. In the control group, the urine volume, renal Kt/V, and renal CCr levels consistently decreased; however, these parameters were stably maintained during the study period in the tolvaptan group. Atrial natriuretic peptide, CRP levels and the left ventricular mass index of the tolvaptan-treated group were significantly lower than those in the control group, whereas total protein and albumin levels were significantly higher at 6 and 12 months in the tolvaptan group. There were no obvious adverse effects. These data suggest that tolvaptan may preserve residual renal function and improve volume control in PD patients with diabetes mellitus.

Controlled Rewarming after Hypothermia: Adding a New Principle to Renal Preservation.

Early graft dysfunction due to preservation/reperfusion injury still represents a notable issue after kidney transplantation, affecting long term prognosis of graft viability. One trigger of postischemic cell dysfunction could be recognized in the abrupt temperature shift from hypo‐ to normothermia, leading to mitochondrial dysfunction and proapoptotic signal transduction.Here we propose a technique to cope with this “rewarming injury” by interposing a period of gentle warming up by hypo‐ to subnormothermic machine perfusion of the isolated graft prior to warm reperfusion. Porcine kidneys were subjected either to 18 hours of hypothermic machine preservation (HMP) or 18 hours static cold storage + 3 hours of gentle, machine controlled oxygenated rewarming (COR). Functional integrity was evaluated in both groups by subsequent normothermic reperfusion in vitro.The functional benefit of COR was documented by an approximately twofold increase in renal clearances of creatinine as well as urea upon warm reperfusion, compared to controls. This was accompanied with a notable mitigation of postischemic mitochondrial dys‐homeostasis. COR significantly improved renal oxygen consumption and maintained total NAD tissue content upon reperfusion. Mitochondrial initiation of cellular apoptosis, as evidenced by activation of caspase 9 was also largely prevented after COR but not in controls.The concept of gentle regenerative graft rewarming could become a valuable adjunct in renal transplantation.

PATTERNS AND PREDICTORS OF USE OF ANTICOAGULANTS FOR ACUTE VENOUS THROMBOEMBOLISM

Few studies have identified patterns and predictors of use of novel oral anticoagulants compared to warfarin for acute venous thromboembolism (VTE) in clinical practice. To describe the use of anticoagulants (AC) and to identify patient’s characteristics associated with the choice of rivaroxaban over warfarin for the treatment of VTE. A retrospective cohort was built from outpatient visits and inpatients records of hospitalisation between February 18, 2013, and September 18, 2013 (ie. starting 2 months following the availability of rivaroxaban for the treatment of VTE at our institution). This cohort includes new AC’s users treated in a tertiary care center for VTE. General characteristics and the type of AC prescribed was described using means and proportions and predictors of use of novel AC were analysed using two-tailed Student’s t-test for continuous variables and chi-square test for categorical variables. In an 8-months period, 261 patients were included; 67 (26%) had a diagnosis of cancer, 52 (20%) had at least one previous episode of VTE and 17 (7%) had confirm inherited thrombophilia. The median age was 65 years and 52% of the patients were women. The median body mass index was 28 (data were available for 199 patients) and the median length of stay was 8 days for hospitalisation (118 patients). Overall, 146 (56%) received warfarin, 43 (16%) received rivaroxaban and 72 (28%) received a prescription for long-term low molecular weight heparin at discharge. When compared to patients on warfarin, those who received rivaroxaban at discharge were younger (53 versus 63 years, p=0,001), had a higher mean creatinine clearance (93 versus 79 mL/min, p=0,002), were more likely to have an ambulatory visit rather than a hospitalisation (31% versus 60%, p<0,001) and were more likely to have a deep venous thrombosis than a pulmonary embolism (36% versus 58%, p=0,011). In new users of oral anticoagulants for the management of VTE, more subjects were on warfarin. Patients on rivaroxaban were younger and had a higher renal creatinine clearance. Rivaroxaban was more frequently prescribed in subjects who were not hosiptalized.

THROMBOXANE A2 IS INVOLVED IN PLATELET SIGNALING VIA GPIBα/PKCδ AXIS IN RESPONSE TO THROMBIN

p1⁄40,002), were more likely to have an ambulatory visit rather than a hospitalisation (31% versus 60%, p<0,001) and were more likely to have a deep venous thrombosis than a pulmonary embolism (36% versus 58%, p1⁄40,011). CONCLUSION: In new users of oral anticoagulants for the management of VTE, more subjects were on warfarin. Patients on rivaroxaban were younger and had a higher renal creatinine clearance. Rivaroxaban was more frequently prescribed in subjects who were not hosiptalized.

Mechanisms of renal control of potassium homeostasis in complete aldosterone deficiency.

Aldosterone-independent mechanisms may contribute to K(+) homeostasis. We studied aldosterone synthase knockout (AS(-/-)) mice to define renal control mechanisms of K(+) homeostasis in complete aldosterone deficiency. AS(-/-) mice were normokalemic and tolerated a physiologic dietary K(+) load (2% K(+), 2 days) without signs of illness, except some degree of polyuria. With supraphysiologic K(+) intake (5% K(+)), AS(-/-) mice decompensated and became hyperkalemic. High-K(+) diets induced upregulation of the renal outer medullary K(+) channel in AS(-/-) mice, whereas upregulation of the epithelial sodium channel (ENaC) sufficient to increase the electrochemical driving force for K(+) excretion was detected only with a 2% K(+) diet. Phosphorylation of the thiazide-sensitive NaCl cotransporter was consistently lower in AS(-/-) mice than in AS(+/+) mice and was downregulated in mice of both genotypes in response to increased K(+) intake. Inhibition of the angiotensin II type 1 receptor reduced renal creatinine clearance and apical ENaC localization, and caused severe hyperkalemia in AS(-/-) mice. In contrast with the kidney, the distal colon of AS(-/-) mice did not respond to dietary K(+) loading, as indicated by Ussing-type chamber experiments. Thus, renal adaptation to a physiologic, but not supraphysiologic, K(+) load can be achieved in aldosterone deficiency by aldosterone-independent activation of the renal outer medullary K(+) channel and ENaC, to which angiotensin II may contribute. Enhanced urinary flow and reduced activity of the thiazide-sensitive NaCl cotransporter may support renal adaptation by activation of flow-dependent K(+) secretion and increased intratubular availability of Na(+) that can be reabsorbed in exchange for K(+) secreted.

Relationship Between Residual Renal Function and Serum Fibroblast Growth Factor 23 in Patients on Peritoneal Dialysis

Fibroblast growth factor 23 (FGF23) levels in dialysis patients are influenced by various factors, including phosphorus load. However, the clinical parameters that determine serum FGF23 levels in patients on peritoneal dialysis (PD) remain unclear. The aim of the present study was to examine the effects of clinical factors, on serum FGF23 levels, with an emphasis on residual renal function (RRF). This cross-sectional study included 56 outpatients undergoing PD therapy. Urine volume ≥ 100 mL/day or renal creatinine (Cr) clearance was used as a surrogate marker for RRF. Clinical characteristics were compared between patients with and without RRF. Linear regression analysis was conducted with serum FGF23 level as the dependent variable and renal Cr clearance as the main independent variable. The median and interquartile range of serum FGF23 levels were 5970 (1451-11,688) pg/mL. Patients with RRF showed higher urinary and total phosphate eliminations, and lower serum FGF23 and phosphate levels than patients without RRF. Multivariate linear regression analysis showed that the renal Cr clearance and serum phosphate and dialysis history were negatively associated with serum FGF23 levels, even after adjusting for potential confounders including peritoneal Cr clearance. Further, the predictabilities of serum FGF23 were comparable among renal Cr clearance, Kt/V for urea, and renal phosphate clearance. RRF determined by renal Cr clearance or residual urine volume is an independent negative determinant of serum FGF23 levels in PD patients.

Accuracy of the estimation of glomerular filtration rate within a population of critically ill patients

Accuracy of glomerular filtration rate (GFR) estimates has been questioned and several authors recommend routine use of measured renal creatinine clearance (CLCR) as a surrogate of GFR in the intensive care unit (ICU). Our purpose was to compare estimates of GFR using Cockroft-Gault (CG), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease Study (MDRD) equations with 8h-CLCR, within a population of critically ill patients with a wide range of measured CLCR. Through a prospective, observational study of 54 patients with normal serum creatinine (sCr) admitted to ICU, daily 8h-CLCR (reference method) and GFR estimates (644 paired samples) were matched and compared. Augmented renal clearance (ARC) was defined as 8h-CLCR >130 ml/min/1.73 m(2). No significant difference was found between mean 8h-CLCR (135.5 ml/min/1.73 m(2)) and CG equation (135.7 ml/min/1.73 m(2)), but significant differences (p < 0.01) were found for the MDRD (124.4 ml/min/1.73 m(2)) and CKD-EPI (107.6 ml/min/1.73 m(2)) equations. Correlation between 8h-CLCR and all estimates was weak (R = 0.2, 0.19 and 0.34, respectively). We observed poor agreement in terms of precision (40.9, 39.8 and 33.4%, respectively). Analysing subgroups, we observed that all equations significantly underestimated 8h-CLCR >120 ml/min/1.73 m(2) and overestimated 8h-CLCR <120 ml/min/1.73 m(2) (p < 0.05). The incidence of ARC patients was 55.6%. Estimates of GFR using CG, CKD-EPI and MDRD formulae are flawed in the critically ill with normal sCr, significantly underestimating renal function in those with ARC and overestimating it in those with normal or decreased 8h-CLCR. Globally, the population exhibited ARC on more than half of the ICU admission days.

Activated protein C ameliorates impaired renal microvascular oxygenation and sodium reabsorption in endotoxemic rats.

IntroductionWe aimed to test whether continuous recombinant human activated protein C (APC) administration would be able to protect renal oxygenation and function during endotoxemia in order to provide more insight into the role of coagulation and inflammation in the development of septic acute kidney injury.MethodsIn anesthetized, mechanically ventilated Wistar rats, endotoxemia was induced by lipopolysaccharide administration (10 mg/kg i.v. over 30 min). One hour later, the rats received fluid resuscitation with 0 (LPS + FR group; n = 8), 10 (APC10 group; n = 8), or 100 (APC100 group; n = 8) μg/kg/h APC for 2 h. Renal microvascular oxygenation in the cortex and medulla were measured using phosphorimetry, and renal creatinine clearance rate and sodium reabsorption were measured as indicators of renal function. Statistical significance of differences between groups was tested using two-way ANOVA with Bonferroni post hoc tests.ResultsAPC did not have notable effects on systemic and renal hemodynamic and oxygenation variables or creatinine clearance. The changes in renal microvascular oxygenation in both the cortex (r = 0.66; p < 0.001) and medulla (r = 0.80; p < 0.001) were correlated to renal sodium reabsorption.ConclusionRenal sodium reabsorption is closely correlated to renal microvascular oxygenation during endotoxemia. In this study, fluid resuscitation and APC supplementation were not significantly effective in protecting renal microvascular oxygenation and renal function. The specific mechanisms responsible for these effects of APC warrant further study.Electronic supplementary materialThe online version of this article (doi:10.1186/2197-425X-1-5) contains supplementary material, which is available to authorized users.

Cost-Effectiveness of Apixaban, Dabigatran, Rivaroxaban, and Warfarin for Stroke Prevention in Atrial Fibrillation

To estimate the cost-effectiveness of stroke prevention in patients with nonvalvular atrial fibrillation by using novel oral anticoagulants apixaban 5 mg, dabigatran 150 mg, and rivaroxaban 20 mg compared with warfarin. A Markov decision-analysis model was constructed using data from clinical trials to evaluate lifetime costs and quality-adjusted life-years of novel oral anticoagulants compared with warfarin. The modeled population was a hypothetical cohort of 70-year-old patients with nonvalvular atrial fibrillation, increased risk for stroke (CHADS2 ≥ 1), renal creatinine clearance ≥ 50 mL/min, and no previous contraindications to anticoagulation. The willingness-to-pay threshold was $50 000/quality-adjusted life-years gained. In the base case, warfarin had the lowest cost of $77 813 (SD, $2223), followed by rivaroxaban 20 mg ($78 738 ± $1852), dabigatran 150 mg ($82 719 ± $1959), and apixaban 5 mg ($85 326 ± $1512). Apixaban 5 mg had the highest quality-adjusted life-years estimate at 8.47 (SD, 0.06), followed by dabigatran 150 mg (8.41 ± 0.07), rivaroxaban 20 mg (8.26 ± 0.06), and warfarin (7.97 ± 0.04). In a Monte Carlo probabilistic sensitivity analysis, apixaban 5 mg, dabigatran 150 mg, rivaroxaban 20 mg, and warfarin were cost-effective in 45.1%, 40%, 14.9%, 0% of the simulations, respectively. In patients with nonvalvular atrial fibrillation and an increased risk of stroke prophylaxis, apixaban 5 mg, dabigatran 150 mg, and rivaroxaban 20 mg were all cost-effective alternatives to warfarin. The cost-effectiveness of novel oral anticoagulantss was dependent on therapy pricing in the United States and neurological events associated with rivaroxaban 20 mg.