Renal Function Variables Research Articles

Renal Function Variability is Associated with Adverse Clinical Outcomes in Hospitalized Acute Decompensated Heart Failure with Renal Dysfunction

Worsening renal function was known to be a prognostic factor in hospitalized acute decompensated heart failure (ADHF). We performed validation of the renal function variability (RFV), defined as coefficient of variance of serum creatinine levels at admission, discharge and 1-moth after discharge to predict clinical outcomes in these patients (pts). We analyzed 318 hospitalized ADHF pts (169 males, 63 ± 14 years old, 32.4% ischemic) from Yonsei ACute HearT failure (YACHT) Registry. Primary endpoint was a composite of all-cause mortality and HF rehospitalization. During follow-up period (median 660 days), primary endpoint occurred in 166 pts (52.2%) including 58 (18.3%) all-cause mortality. The pts with higher RFV (≥0.12) had higher serum blood urea nitrogen, creatinine and N-terminal pro B-type natriuretic peptide compared to those with lower RFV (<0.12). The higher RFV was related with lower event free survival in pts with renal dysfunction (estimated glomerular filtration rate < 60 mL/min/1.73m2 at admission) (49.2% vs 29.6% for higher RFV, log-rank p=0.021) but not in those without renal dysfunction (57.3% vs 61.5% for higher RFV, log-rank p=0.722). Our study demonstrated that higher RFV was related to adverse clinical outcomes in hospitalized ADHF pts with renal dysfunction, not in those without renal dysfunction. However, the external validation of this RFV should be needed in the large cohort.

Change in physiological variables in the last 2 weeks of life: An observational study of hospital in-patients with cancer

Background: Recognising dying remains a difficult clinical skill which has gained increasing importance in the United Kingdom since the Neuberger review. Clinical and research methods exist to aid recognition of dying but do not exhibit the level of accuracy required for such an important decision. Aim: To explore change in key clinical parameters as cancer patients near the end of life. Design: This is a retrospective cohort study of terminally ill patients. Data were collected from hospital case-notes. Case-note data were analysed using multilevel modelling to explore absolute values and rates of change of given variables. Setting/participants: Hospital in-patients who died from solid-tumour malignancies within a 3-month period in 2009 formed the cohort. The setting was an acute hospital trust in the North of England. Results: A total of 15,337 data points from the case-notes of 102 patients were analysed. There was a clinically and statistically significant deterioration in respiratory function and renal function over the last 2 weeks of life. Heart rate and serum sodium also changed but did not vary greatly from normal limits. White cell parameters, haemoglobin and albumin showed evidence for change over longer periods. Conclusion: Results demonstrate statistically and clinically significant change in routinely measured respiratory and renal function variables during the final 2 weeks of life in people dying with cancer. Although useful in acute early warning scores, in a terminally ill patient, relative haemodynamic stability should not be interpreted as reassuring. Further work is needed to understand how these findings apply to the individual or inform other prognostic work.

Genetic variants in nicotinic acetylcholine receptor genes jointly contribute to kidney function in American Indians

Cigarette smoking negatively affects kidney function. Genetic variants in the nicotinic acetylcholine receptor (nAChR) genes have been associated with nicotine dependence, and are likely to influence renal function and related traits. Whereas each single variant may only exert a small effect, the joint contribution of multiple variants to the risk of disease could be substantial. Using a gene-family approach, we investigated the joint association of 61 tagging SNPs in seven genes encoding the nAChRs with kidney function in 3620 American Indians participating in the Strong Heart Family Study, independent of known risk factors. Kidney function was evaluated by estimated glomerular filtration rate, urinary albumin/creatinine ratio, albuminuria and chronic kidney disease. The joint impact of smoking-related variants was assessed using the weighted truncated product method. Multiple SNPs showed marginal individual effect on renal function variability, and only a few survive multiple comparison correction. In contrast, a gene-family analysis considering the joint impact of all 61 SNPs reveals significant associations of the nAChR gene family with kidney function variables including estimated glomerular filtration rate, urinary albumin/creatinine ratio, and albuminuria (all Ps ≤ 0.0001) after adjusting for established risk factors including cigarette smoking. Genetic variants in nAChR genes jointly contribute to renal function or kidney damage in American Indians. The effects of these genetic variants on kidney function or damage are independent of traditional risk factors including cigarette smoking per se.

Variability in estimated glomerular filtration rate by area under the curve predicts renal outcomes in chronic kidney disease.

Greater variability in renal function is associated with mortality in patients with chronic kidney disease (CKD). However, few studies have demonstrated the predictive value of renal function variability in relation to renal outcomes. This study investigates the predictive ability of different methods of determining estimated glomerular filtration rate (eGFR) variability for progression to renal replacement therapy (RRT) in CKD patients. This was a prospective observational study, which enrolled 1,862 CKD patients. The renal end point was defined as commencement of RRT. The variability in eGFR was measured by the area under the eGFR curve (AUC)%. A significant improvement in model prediction was based on the −2 log likelihood ratio statistic. During a median 28.7-month follow-up, there were 564 (30.3%) patients receiving RRT. In an adjusted Cox model, a smaller initial eGFR AUC%_12M (P < 0.001), a smaller peak eGFR AUC%_12M (P < 0.001), and a larger negative eGFR slope_12M (P < 0.001) were associated with a higher risk of renal end point. Two calculated formulas: initial eGFR AUC%_12M and eGFR slope_12M were the best predictors. Our results demonstrate that the greater eGFR variability by AUC% is associated with the higher risk of progression to RRT.

Effects of pneumoperitoneum with carbon dioxide and helium on renal function and morphology in rats

To evaluate the effects of pneumoperitoneum with carbon dioxide and helium on renal function and morphology in a rat model. Twenty four rats were randomized into three groups (n=8): gasless insufflation ('open', Pressure=0 mmHg), carbon dioxide pneumoperitoneum at 12 mmHg, and helium pneumoperitoneum at 12 mmHg; all lasting 90 minutes.. A cystostomy was performed and the bladder was emptied. At the end of the experiment, the urine produced, a blood sample and the left kidney of each animal were collected. The following variables were obtained: serum sodium, potassium, urea and creatinine, urine volume and creatinine. The creatinine clearance was estimated for each animal. The kidneys were stained with hematoxylin and eosin (HE) and evaluated by a pathologist blinded to the groups. The CO2 and Helium groups did not differ in the variables evaluated. Both developed oliguria (p<0.001 vs. gasless). The CO2 group presented hyperkalemia compared to gasless (p=0.05), which did not attain significance in the helium group. Histopathological analysis revealed mild hydropic degeneration and congestion in the three groups, with no significant difference among them. The type of gas resulted in no difference in the variables of renal function and morphology assessed. The increase in serum potassium was only observed with CO2 insufflation suggests a combined effect of elevated intra-abdominal pressure and metabolic effects of pneumoperitoneum.

Usefulness of Stroke Volume Index Obtained with the FloTrac/Vigileo System for the Prediction of Acute Kidney Injury After Radical Esophagectomy

To assess the impact of stroke volume index (SVI) at the end of esophagectomy upon postoperative renal function. We reviewed medical records of 128 patients undergoing esophagectomy. Intraoperative hemodynamics were monitored with the FloTrac sensor/Vigileo monitor system in addition to standard monitors. Patients were divided into two groups according to SVI at the end of surgery: the normal SVI group (n = 76), with SVI ≥ 35 ml/m2, and the low SVI group (n = 52), with SVI<35 ml/m2. We compared postoperative renal function, indicated by serum creatinine and estimated glomerular filtration rate, on post-operative days 0 through 3. We also compared numbers of patients who developed postoperative acute kidney injury (AKI). Although there were no intergroup differences in preoperative renal function or other intraoperative hemodynamic variables, including arterial pressure, central venous pressure, stroke volume variation, a volume of infusion, urine output, and the total intraoperative in-out balance, estimated glomerular filtration rate was significantly lower and serum creatinine was significantly higher in the low SVI group than in the normal SVI group on postoperative days 1 and 2 (P<0.05). In addition, more patients developed postoperative AKI in the low SVI group than in the normal SVI group (12 of 52 vs. 5 of 76, P = 0.015). Low SVI at the end of esophagectomy may represent a risk factor for AKI in the early postoperative period. Further studies are required to examine whether maintaining SVI above 35 ml/m2 reduces the incidence of AKI after esophagectomy.

A fixed protocol for outpatient clinic routines in the care of patients with severe renal failure

Background: The primary aim of this study was to assess whether a fixed protocol, using a specially trained team, for intermediate follow-up to fulfillment of guideline targets is non-inferior to conventional follow-up in the care of uraemic patients. A secondary aim was to investigate possible impact on patient outcome. Methods: The cohort comprised 424 patients from seven centers. Inclusion criteria were either serum creatinine exceeding 200 µmol/l or calculated clearance below 30 ml/min, representing CKD 4 or 5a. Six centers followed a standardized protocol (group 1). One center provided controls (group 2). The study design was prospective and interventional. The variables measured were blood hemoglobin, bicarbonate, calcium, phosphate, intact parathyroid hormone, albumin, renal function variables, blood pressure and RAAS blockade. The number of patients achieving the set goals was analyzed as a time trend to determine if the intervention resulted in an improvement. Results: At baseline, group 1 had significantly lower GFR and higher serum creatinine, calcium, phosphate, calcium × phosphate product and bicarbonate, lower mean arterial pressure (MAP), systolic blood pressures and less use of RAAS. During the intervention, group 1 improved in the direction of guidelines for blood hemoglobin, albumin, bicarbonate and MAP. Outcome of secondary endpoints gave a risk of death of 30% in both groups, while the risk of renal replacement therapy was higher in group 1. Conclusions: However, the time to renal replacement therapy was significantly shorter in the intervention group, indicating that other variables than guideline achievements are important for the patient.

Impact of renal function on eligibility for chemotherapy and survival in patients who have undergone radical nephro‐ureterectomy

What's known on the subject? and what does the study add?: Radical nephroureterectomy (RNU), the standard of care treatment for high-risk urothelial carcinoma of the upper tract (UTUC), results in loss of a renal unit. Loss of renal function decreases eligibility for systemic chemotherapies and results in decreased overall survival in various malignancies. The study shows that only a small proportion of patients had a preoperative renal function that would allow cisplatin-based chemotherapy. Moreover, eGFR significantly decreased after RNU, thereby lowering the rate of cisplatin eligibility to only 16 and 52% of patients based on the thresholds of 60 and 45 mL/min/1.73 m(2) , respectively. Taken together with the rest of the literature, the findings of the study support the use of cisplatin-based chemotherapy, when indicated, in the neoadjuvant rather than adjuvant setting. To report (i) the estimated glomerular filtration rate (eGFR) changes in patients undergoing radical nephro-ureterectomy (RNU) for upper tract urothelial carcinoma (UTUC); (ii) the rate of change in eGFR in patients eligible for cisplatin-based chemotherapy; and (iii) the association of preoperative, postoperative and rate of change of renal function variables with survival outcomes. We performed a retrospective analysis of 666 patients treated with RNU for UTUC at seven international institutions from 1994 to 2007. The eGFR was calculated at baseline and at 3-6 months (Modification of Diet in Renal Disease formula (MDRD) and Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EP) equations). The median (interquartile range) eGFR decreased by 18.2 (8-12)% after RNU. A total of 37% of patients had a preoperative eGFR ≥ 60 mL/min/1.73 m(2) , which decreased to 16% after RNU (P < 0.001); 72% of patients had a preoperative eGFR ≥ 45 mL/min/1.73 m(2) , which decreased to 52% after RNU (P < 0.001). The distributions were similar when analyses were restricted to patients with locally advanced disease (pT3-pT4) and/or lymph node metastasis. Patients older than the median age of 70 years were more likely to have a decrease in eGFR after RNU (P < 0.001). None of the renal function variables was associated with clinical outcomes such as disease recurrence, cancer-specific and overall mortality; however, when analyses were restricted to patients who had no adjuvant chemotherapy and did not experience disease recurrence (n = 431), a preoperative eGFR ≥ 60 mL/min/1.73 m(2) (P = 0.03) and a postoperative eGFR ≥ 45 mL/min/1.73 m(2) (P = 0.04) were associated with better overall survival in univariable analyses. In patients who had UTUC, eGFR was low and furthermore, it significantly decreased after RNU. Renal function did not affect cancer-specific outcomes after RNU.

Effect of lipo-prostaglandin E1 on cystatin C, β2-microglobulin, and estimated glomerular filtration rate in patients with decompensated heart failure and renal dysfunction: a single-center, nonrandomized controlled study

A nonrandomized controlled study was conducted to evaluate the effect of lipo-prostaglandin E1 (lipo-PGE1) on cystatin C (CysC), β2-microglobulin (B2MG), and estimated glomerular filtration rate (eGFR) in patients with decompensated heart failure (DHF) and renal dysfunction. A total of 286 enrolled patients with DHF and renal dysfunction were nonrandomly assigned a 7-day standard treatment without (n = 146) or with (n = 140) lipo-PGE1 intervention. According to the baseline eGFR, patients were further classified into mild, moderate, and severe renal dysfunction subgroups. By the end of study period, there was no evidence of an immense improvement in B2MG, CysC, and eGFR in response to standard treatment (all P > 0.05). On the contrary, a noticeable decrease of B2MG and CysC was observed in patients receiving lipo-PGE1 intervention, as well as an increase in eGFR (all P < 0.05). Moreover, lipo-PGE1 intervention led to greater changes in renal function variables from baseline than with standard management (all P < 0.05). Most important, the favorable renal protective effects of lipo-PGE1 were maintained in three subgroups. Lipo-PGE1 intervention brought a substantial renoprotective benefit to hospitalized DHF patients as compared with standard therapy, suggesting it might offer a promising therapeutic option for the management of renal dysfunction associated with DHF.

Age-related change in kidney function, its influencing factors, and association with asymptomatic carotid atherosclerosis in healthy individuals—A 5-year follow-up study

ObjectivesTo better define the longitudinal changes in renal function, to examine the associated risk factors, and to investigate whether there is an independent association of decline in renal function with presence of carotid plaque in a middle-aged and elderly healthy population. Methods245 healthy individuals (98 males, 147 females) evaluated at baseline and 5 years later. ResultsOver five years, estimated glomerular filtration rate (eGFR) decreased from 98.1±15.6 to 90.4±17.3mL/min/1.73m2. There are three kinds of change in eGFR (elevated, stable and decreased) during follow-up, accounting for 14%, 29% and 57%, respectively. Multivariate analysis of cross-sectional data showed that gender, age, and serum uric acid (UA) were major factors which consistently affected eGFR at both baseline and follow-up, and that higher systolic blood pressure (SBP) and presence of plaque were involved in lower eGFR at the follow-up point. In longitudinal analysis, five baseline factors – age, SBP, low-density lipoprotein cholesterol (LDL-C), serum transferrin (TRF) and eGFR − independently predicted a greater variability in renal function. In addition, presence of plaque was an independent risk factor for a faster decline of eGFR. ConclusionsCross-sectional analysis demonstrates that renal function declines with increasing age. However, 43% of participants did not experience a decline in eGFR during follow-up. Besides older age and higher initial eGFR, presence of atherosclerotic carotid plaque, higher SBP, higher LDL-C and lower TRF are independent risk factors to predict a rapid decline of renal function in the healthy Chinese population.

Chronic kidney disease in the type 2 diabetic patients: prevalence and associated variables in a random sample of 2642 patients of a Mediterranean area

BackgroundKidney disease is associated with an increased total mortality and cardiovascular morbimortality in the general population and in patients with Type 2 diabetes. The aim of this study is to determine the prevalence of kidney disease and different types of renal disease in patients with type 2 diabetes (T2DM).MethodsCross-sectional study in a random sample of 2,642 T2DM patients cared for in primary care during 2007. Studied variables: demographic and clinical characteristics, pharmacological treatments and T2DM complications (diabetic foot, retinopathy, coronary heart disease and stroke). Variables of renal function were defined as follows: 1) Microalbuminuria: albumin excretion rate & 30 mg/g or 3.5 mg/mmol, 2) Macroalbuminuria: albumin excretion rate & 300 mg/g or 35 mg/mmol, 3) Kidney disease (KD): glomerular filtration rate according to Modification of Diet in Renal Disease < 60 ml/min/1.73 m2 and/or the presence of albuminuria, 4) Renal impairment (RI): glomerular filtration rate < 60 ml/min/1.73 m2, 5) Nonalbuminuric RI: glomerular filtration rate < 60 ml/min/1.73 m2 without albuminuria and, 5) Diabetic nephropathy (DN): macroalbuminuria or microalbuminuria plus diabetic retinopathy.ResultsThe prevalence of different types of renal disease in patients was: 34.1% KD, 22.9% RI, 19.5% albuminuria and 16.4% diabetic nephropathy (DN). The prevalence of albuminuria without RI (13.5%) and nonalbuminuric RI (14.7%) was similar. After adjusting per age, BMI, cholesterol, blood pressure and macrovascular disease, RI was significantly associated with the female gender (OR 2.20; CI 95% 1.86–2.59), microvascular disease (OR 2.14; CI 95% 1.8–2.54) and insulin treatment (OR 1.82; CI 95% 1.39–2.38), and inversely associated with HbA1c (OR 0.85 for every 1% increase; CI 95% 0.80–0.91). Albuminuria without RI was inversely associated with the female gender (OR 0.27; CI 95% 0.21–0.35), duration of diabetes (OR 0.94 per year; CI 95% 0.91–0.97) and directly associated with HbA1c (OR 1.19 for every 1% increase; CI 95% 1.09–1.3).ConclusionsOne-third of the sample population in this study has KD. The presence or absence of albuminuria identifies two subgroups with different characteristics related to gender, the duration of diabetes and metabolic status of the patient. It is important to determine both albuminuria and GFR estimation to diagnose KD.

Serum uric acid as an index of impaired renal function in congestive heart failure

BackgroundHyperuricemia is frequently present in patients with heart failure. Many pathological conditions, such as tissue ischemia, renal function impairment, cardiac function impairment, metabolic syndrome, and inflammatory status, may impact uric acid (UA) metabolism. This study was to assess their potential relations to UA metabolism in heart failure.MethodsWe retrospectively assessed clinical characteristics, echocardiological, renal, metabolic and inflammatory variables selected on the basis of previous evidence of their involvement in cardiovascular diseases and UA metabolism in a large cohort of randomly selected adults with congestive heart failure (n = 553). By clustering of indices, those variables were explored using factor analysis.ResultsIn factor analysis, serum uric acid (SUA) formed part of a principal cluster of renal functional variables which included serum creatinine (SCr) and blood urea nitrogen (BUN). Univariate correlation coefficients between variables of patients with congestive heart failure showed that the strongest correlations for SUA were with BUN (r = 0.48, P < 0.001) and SCr (r = 0.47, P < 0.001).ConclusionsThere was an inverse relationship between SUA levels and measures of renal function in patients with congestive heart failure. The strong correlation between SUA and SCr and BUN levels suggests that elevated SUA concentrations reflect an impairment of renal function in heart failure.

Response to Letters Regarding Article, “Using Dabigatran in Patients With Stroke: A Practical Guide for Clinicians”

Response: We appreciate the thoughtful comments and important issues raised by the letters published. As Casado-Nananjo et al highlight, there are anecdotal case reports of intravenous tissue-type plasminogen activator (tPA) for acute ischemic stroke being used without complications in patients treated with dabigatran as well as with catastrophic consequences in such settings. These reports often lack data about the timing of the last dose of dabigatran, renal function, and other important variables. One should remember that dabigatran is a potent anticoagulant, and tPA is a powerful lytic agent. There have been studies suggesting that a clot formed in patients taking dabigatran may be more susceptible to complete lysis when using tPA, but this might also be associated with higher rates of hemorrhage.1 Freeman and colleagues present a single case of successful endovascular therapy in a patient with a potentially large middle …

Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial

IntroductionTo evaluate whether alkaline phosphatase (AP) treatment improves renal function in sepsis-induced acute kidney injury (AKI), a prospective, double-blind, randomized, placebo-controlled study in critically ill patients with severe sepsis or septic shock with evidence of AKI was performed.MethodsThirty-six adult patients with severe sepsis or septic shock according to Systemic Inflammatory Response Syndrome criteria and renal injury defined according to the AKI Network criteria were included. Dialysis intervention was standardized according to Acute Dialysis Quality Initiative consensus. Intravenous infusion of alkaline phosphatase (bolus injection of 67.5 U/kg body weight followed by continuous infusion of 132.5 U/kg/24 h for 48 hours, or placebo) starting within 48 hours of AKI onset and followed up to 28 days post-treatment. The primary outcome variable was progress in renal function variables (endogenous creatinine clearance, requirement and duration of renal replacement therapy, RRT) after 28 days. The secondary outcome variables included changes in circulating inflammatory mediators, urinary excretion of biomarkers of tubular injury, and safety.ResultsThere was a significant (P = 0.02) difference in favor of AP treatment relative to controls for the primary outcome variable. Individual renal parameters showed that endogenous creatinine clearance (baseline to Day 28) was significantly higher in the treated group relative to placebo (from 50 ± 27 to 108 ± 73 mL/minute (mean ± SEM) for the AP group; and from 40 ± 37 to 65 ± 30 mL/minute for placebo; P = 0.01). Reductions in RRT requirement and duration did not reach significance. The results in renal parameters were supported by significantly more pronounced reductions in the systemic markers C-reactive protein, Interleukin-6, LPS-binding protein and in the urinary excretion of Kidney Injury Molecule-1 and Interleukin-18 in AP-treated patients relative to placebo. The Drug Safety Monitoring Board did not raise any issues throughout the trial.ConclusionsThe improvements in renal function suggest alkaline phosphatase is a promising new treatment for patients with severe sepsis or septic shock with AKI.Trial Registrationwww.clinicaltrials.gov: NCTNCT00511186

The effect of habitually large protein intake on renal function of strength athletes: an update

Background A quasi-experimental study was performed to evaluate the renal effects of large, chronic protein intakes among strength athletes. Population-specific data are still lacking regarding this cohort of athletes who commonly seek additional protein for performance and body composition purposes. Methods In a design involving self-report, estimated and direct measures, urinary variables of renal function (extrapolated morning fasted- and actual 12-hour creatinine clearance) were assessed via a DCA 2000 urinalysis analyzer (Bayer healthcare, LLC, Elkhart, IN) in Caucasian male strength trainers (N=17) who do (PROT) and do not (CTRL) seek ample protein intake via foods and supplements. Use of fasted urinary Cr values in some creatinine clearance (CrCl) expressions allowed for comparisons beyond spot measures, without interference of daytime meals and mild activities. CrCl was derived as follows: UCr xU vol /P Cr x min. where U = urinary and P = plasma. Direct plasma variables (i.e. a standard “renal panel”) were also measured via commercial techniques (LabCare Plus, Barberton, OH) and compared. Body mass and composition were also assessed via balance scale and dual x-ray absorptiometry (DEXA). All participants abstained from exercise for three days prior to testing. Results Over a reported 9.1+/-6.5 year period, chronic protein intakes (mean+/-SD: PROT 2.5 +/-0.83 g/kg, CTRL 1.27 +/-0.33 g/kg), were greater in the protein seeking group (p < 0.05) as verified by diet logs. Concomitant with significantly greater 12-hour urine output (PROT 1811 +/-896 ml vs. CTRL 1162 +/-447 ml), no statistically significant effects were detected in creatinine clearance extrapolated from fasting urinary Cr values (PROT 255.0 +/-147.9 ml/min*1.73m 2 vs. CTRL 196.5 +/-50.6 ml/min/1.73m 2 )or from actual 12-hour creatinine clearance (PROT 166.0 +/-59.1 ml/min*1.73m 2 vs. CTRL 160.2 +/-38.5 ml/min/m 2 ).Similarly, no differences were observed among serum variables including creatinine, BUN:Cr ratio, sodium, potassium, chloride, anion gap, calcium, albumin, or phosphorus. There was a trend toward higher BUN in PROT (8.8 +/-1.3 mg/dl vs. CTRL 8.4+/-1.8 mg/dl) but this disappeared when normalizing for serum creatinine. Groups did not differ in age but did differ in body mass (PROT 98.3 +/-16.8 kg vs. CTRL 83.3 +/-7.0 kg; p < 0.05) and fat free mass (PROT 79.0 +/-9.9 kg vs. CTRL 68.9 +/-6.7 kg; p < 0.05).

Abstract P250: How Much Decrement in Renal Function During Heart Failure Hospitalization is Due to Loop Diuretic Exposure?

Background: Worsening renal function (WRF) during heart failure (HF) hospitalization is an accepted correlate of poor prognosis. Loop diuretics are increasingly being considered as a potential cause of worsened HF outcomes, perhaps via WRF. However, the magnitude of worsening in renal function attributable to loop diuretics has not been quantified. Methods: This was a retrospective cohort study of patients who received care from a large health system and had a primary hospital discharge diagnosis of HF between Jan 1, 2000 and June 30, 2008. Patients with preexisting end-stage renal disease were excluded. Daily creatinine (Cr) measurements, furosemide dosing (only loop diuretic on hospital formulary), and radiocontrast dye studies were collected using administrative data. Day-to-day changes in Cr and MDRD estimated glomerular filtration (eGFR) calculated. The first Cr or eGFR value during hospitalization or in the emergency department was considered baseline. Generalized estimating equations were used to test the association furosemide exposure over previous 2 days to the daily change in Cr and eGFR. Covariates included undergoing radiocontrast study, age, race, gender, and baseline Cr or eGFR. Results: Among 6071 patients who met inclusion criteria there were a total of 20,645 observations. This cohort was 51% female, 68% African American, and baseline Cr was 1.36 mg/dl. Furosemide exposure was associated with an average daily increase in Cr of 0.021 mg/dL and decrease in eGFR of 0.72 ml/min/1.73m2 (per 100 mg furosemide daily, both p&lt;0.001). Over a typical length of stay of 5 days this would amount to a Cr increase of 0.11 mg/dL or decrease in eGFR of 3.6 ml/min/1.73m 2 . Furosemide exposure accounted for only 0.4% and 0.1% of the variation in Cr and eGFR changes, respectively. Undergoing radiocontrast study, African American race, and higher age were associated with day-to-day creatinine increases (all p&lt;0.01). Conclusions: While loop diuretic exposure is statistically associated with WRF among hospitalized HF patients, the associated magnitude of renal function change is very small, and loop diuretics explains little of the variability in renal function during hospitalization. More important predictive factors likely exist but remain unidentified.

Expression of CYP3A5 and P-glycoprotein in Renal Allografts With Histological Signs of Calcineurin Inhibitor Nephrotoxicity

Susceptibility to calcineurin inhibitor nephrotoxicity (CNIT) after solid organ transplantation could be related to an interindividual variability in renal expression and function of the metabolizing cytochrome P450 3A5 (CYP3A5) isoenzyme and of the multidrug efflux transporter P-glycoprotein (P-gp, ABCB1). We compared renal expression of CYP3A5 and P-gp, measured by immunohistochemistry, in 32 renal allograft biopsies with de novo arteriolar hyalinosis as a sign of CNIT with a control group, consisting of normal protocol allograft biopsies (n=50) and protocol biopsies demonstrating alloimmune injury (n=21). In addition, we studied the association between renal expression and donor and recipient single-nucleotide polymorphisms CYP3A5 A6986G (rs776746), ABCB1 C3435T (rs1045642), and G2677T (rs2032582). CYP3A5 positivity at the brushborder of the proximal tubules was present in 47% of CNIT and 14% of control biopsies (P<0.01). In contrast, brushborder staining for CYP3A5 in distal tubules was present in 10% of CNIT and 39% of control biopsies (P<0.01). No significant association between tubular cell P-gp expression and CNIT was detected. The presence of genetic polymorphisms CYP3A5 A6986G and ABCB1 C3435T and G2677T in donors and recipients was not predictive of the renal expression profile of these molecules. Based on retrospectively collected data of 103 renal transplant recipients receiving tacrolimus in combination with mycophenolate mofetil and corticosteroids, we found that renal expression and localization of CYP3A5 but not P-gp is associated with the occurrence of CNIT. Common genetic polymorphisms in these proteins did not influence their expression profile as measured by immunohistochemistry.

Evaluating the effects of 14‐day oral vedaprofen and tolfenamic acid treatment on renal function, hematological and biochemical profiles in healthy cats

The objective of this study was to evaluate the effects of the nonsteroidal anti-inflammatory drugs vedaprofen and tolfenamic acid on renal function after oral administration for 2 weeks in healthy cats. Experiments were performed using nineteen domestic short-haired cats randomly divided into one control (n=6) and two treatment groups. All cats in the first (n=6) and second treatment groups (n=7) received vedaprofen (0.5 mg/kg/day) and tolfenamic acid (4 mg/kg/day), respectively. During the experiment, renal function was evaluated using percent renal uptakes of (99m)Technetium-diethylenetriamine-pentaacetic acid ((99m)Tc-DTPA) collected from renal scintigraphy and blood samples used to determine complete blood count and biochemical profiles. Renal scintigraphy and blood collections were performed at days 0, 5, 11, 15, and 45. The percent of renal uptake after the administration of vedaprofen and tolfenamic acid were not significantly different compared to pretreatment (day 0) and control group levels. In addition, significant changes were not observed in hematological and biochemical profiles within or between groups, with the exception of slightly lower numbers in red blood cell counts compared to the normal value on day 45 in the tolfenamic acid-treated group. Taken together, we conclude 14-day administration of vedaprofen and tolfenamic acid might not cause any adverse effects on renal function, hematological and serum biochemical variables.

NT-proBNP and cardiac events in older diabetic patients

NT-proBNP is an excellent predictor of adverse events in patients with diabetes mellitus. Due to an aging population it is of interest to determine whether NT-proBNP can predict cardiac events with equal precision in subgroups with different ages. 1395 outpatients with diabetes mellitus were recruited for this prospective observational study. NT-proBNP, renal function, lipid status and other demographic variables were measured at baseline. The cohort was divided into three groups: Group I (609 patients under 60 years of age), group II (634 patients ranging from 60-75) and group III (152 patients older than 75). Patients were followed during a mean observation period of 11 months, 75 patients reached the defined endpoint, which was unplanned hospitalization due to a cardiac event. Mean age was 60 ± 30 years, mean HbA(1c) was 7.6% and mean NT-proBNP was 242 ± 437 pg/ml. In a multiple Cox regression model, age (hazard ratio (HR) 11.18, p < 0.01) and the absence of a cardiac disease (HR 0.49, p < 0.01) were important variables for short-term prognosis. The addition of the logarithm of NT-proBNP provided independent prognostic information (HR 1.81 p < 0.01) and significantly increased the explained variance of the model (χ(2 )= 22.93; d.f. = 1; p < 0.01). More importantly, the predictive power of this model was similar in different age-groups. The prognostic information of NT-proBNP was not influenced by age and this biomarker remained a reliable predictor of short-term cardiac events in patients with diabetes mellitus aged 75 years or older.

Relationship of Loop Diuretic Dosing and Acute Changes in Renal Function during Hospitalization for Heart Failure

Worsening renal function (WRF) during heart failure (HF) hospitalization is an accepted correlate of poor prognosis. Loop diuretics are increasingly being considered as a potential cause of worsened HF outcomes, perhaps via WRF. However, the magnitude of worsening in renal function attributable to loop diuretics has not been quantified. This was a retrospective cohort study of patients who received care from a large health system and had a primary hospital discharge diagnosis of HF between Jan 1, 2000 and June 30, 2008. Patients with preexisting end-stage renal disease were excluded. Daily creatinine (Cr) measurements, furosemide dosing (only loop diuretic on hospital formulary), and radiocontrast dye studies were collected using administrative data. Day-to-day changes in Cr and MDRD estimated glomerular filtration (eGFR) were calculated. The first Cr or eGFR value during hospitalization or in the emergency department was considered baseline. Generalized estimating equations were used to test the association furosemide exposure over previous 2 days to the daily change in Cr and eGFR. Covariates included undergoing radiocontrast study, age, race, gender, and baseline Cr or eGFR. Among 6071 patients who met inclusion criteria there were a total of 20,645 observations. This cohort was 51% female, 68% African American, and baseline Cr was 1.36 mg/dl. Furosemide exposure was associated with an average daily increase in Cr of 0.021 mg/dL and decrease in eGFR of 0.72 ml/min/1.73m2 (per 100 mg furosemide daily, both p<0.001). Over a typical length of stay of 5 days this would amount to a Cr increase of 0.11 mg/dL or decrease in eGFR of 3.6 ml/min/1.73m2. Furosemide exposure accounted for only 0.4% and 0.1% of the variation in Cr and eGFR changes, respectively. Undergoing radiocontrast study, African American race, and higher age were associated with day-to-day creatinine increases (all p<0.01). Reanaysis after classifying furosemide exposure into low (<40mg/day), medium (40-100mg/day), and high (>100mg/day) and censoring patients-days after radiocontrast exposure did not significantly affect the magnitude of the worsening renal function. While loop diuretic exposure is statistically associated with WRF among hospitalized HF patients, the associated magnitude of renal function change is very small, and loop diuretics explain little of the variability in renal function during hospitalization. More important explanatory factors likely exist but remain unidentified.