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Glomerular Filtration Rate (glomerular + filtration_rate)
Kinds of Glomerular Filtration Rate Selected AbstractsESTIMATING GLOMERULAR FILTRATION RATE MIGHT HELP TO AVOID HYPOGLYCEMIAJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 9 2006Andrea Corsonello MD No abstract is available for this article. [source] Estimation of Glomerular Filtration Rate in Older Patients with Chronic Renal Insufficiency: Is the Modification of Diet in Renal Disease Formula an Improvement?JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2003Edmund J. Lamb PhD OBJECTIVES: To evaluate a new formula for glomerular filtration rate (GFR), derived from the Modification of Diet in Renal Disease (MDRD) study in older people. DESIGN: An observational study of the performance of the MDRD formula compared with other formulae and creatinine clearance (ClCr) as measures of the GFR. SETTING: Volunteers were recruited via outpatient clinics. PARTICIPANTS: Fifty-two patients (27 men, 25 women: mean age 80, range 69,92) with a variety of medical diagnoses. Mean GFR was 53.3 mL/min/1.73 m2 (range 15.9,100.2). Exclusion criteria included renal replacement therapy/renal transplantation and cognitive impairment. MEASUREMENTS:51Chromium ethylenediaminetetraacetic acid (51Cr EDTA) was used as the reference method against which the formulaic estimates of GFR were compared using bias plot and regression analyses. RESULTS: The MDRD and Cockcroft and Gault formulae (both coefficient of determination (R2) = 0.84) gave the best fit with GFR, followed by the Jelliffe formula (R2 = 0.81), ClCr (R2 = 0.73) and the Baracskay formula (R2 = 0.56). ClCr (,1.2%) demonstrated minimal bias compared with the MDRD (8.0%) and Cockcroft and Gault (,10.4%) formulae. However, imprecision compared with 51Cr EDTA was lowest for the Cockcroft and Gault formula, with 50% of estimates lying between ,9.5 and ,0.5 mL/min/1.73 m2 of measured 51Cr EDTA clearance. This compares with ,6.7 and 10.1 mL/min/1.73 m2 for ClCr and 0.0 and 12.7 mL/min/1.73 m2 for the MDRD formula. CONCLUSION: Calculated estimates of GFR are an improvement over ClCr estimation. On balance, the MDRD formula does not improve the estimate of GFR compared with the Cockcroft and Gault formula in older Caucasian patients with chronic renal insufficiency. [source] Comparison of Glomerular Filtration Rate between Greyhounds and Non-Greyhound DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2006Wm Tod Drost Greyhounds have significantly higher serum creatinine (SCr) concentration than do non-Greyhound dogs that may be attributable to differences in glomerular filtration rate (GFR). By means of plasma clearance of technetium Tc 99m diethylenetriaminepentaacetic acid, GFR was measured in 10 Greyhounds and 10 non-Greyhound dogs with normal findings of physical examination, CBC, serum biochemical analysis, and urinalysis. Dogs were fed the same diet for a minimum of 6 weeks before GFR data collection. Greyhounds had significantly higher mean ± SD GFR (3.0±0.1 vs 2.5±0.2 ml/min/kg; P= .01) and SCr concentration (1.8±0.1 vs 1.5±0.1 mg/dL; P= .03) than did non-Greyhound dogs, but the serum urea nitrogen (SUN) concentration was not significantly different (18±1 vs 18±2 mg/dL; P= .8). Therefore, the higher SCr concentration in Greyhounds is not attributable to decreased GFR, and may be associated with the high muscle mass in the breed. Healthy Greyhounds have higher GFR than do non-Greyhound dogs. [source] Mechanisms of the Rapid Decline in Glomerular Filtration Rate following Lung Transplantation in Patients with Cystic FibrosisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2010O. J. O'Connell No abstract is available for this article. [source] Assessment of Changes in Kidney Allograft Function Using Creatinine-Based Estimates of Glomerular Filtration RateAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2007M. Gera These analyses assessed whether creatinine based estimates of glomerular filtration rate (eGFR) accurately represent (1) graft function at different times post-transplant and (2) changes in function over time. These analyses compared iothalamate GFR to eGFR in 684 kidney allograft recipients. Changes in graft function over time (GFR slope) were measured in 360 of 459 recipients (78%) who were followed for at least 3 years. Ninety-five percent of the patients were Caucasians and 72% received kidneys from living donors. All eGFR calculations correlated significantly with GFR at all time points. However, eGFR were less precise and less accurate during the first-year post-transplant than thereafter. The average rate of GFR change (slope) was ,2.93 ± 11.3%/year (,1.06 ± 5.3 mL/min/1.73m2/year). Fifty-four percent of patients had stable or positive GFR slopes. The GFR and eGFR slopes were highly correlated. However, eGFR slope, particularly when calculated by MDRD, significantly underestimated the number of patients with declining graft function. For example, 165 out of 360 patients (46%) lost GFR faster than ,1 mL/min/1.73m2/year. eMDRD identified only 83 of these patients (50%) while the eMayo formula identified 134 (81%). In conclusion, eGFR correlate with GFR but they have relatively low precision and accuracy particularly early post-transplant. eGFR slopes underestimate graft functional loss although some formulas are significantly better than others for this calculation. [source] Effect of angiotensin II and endothelin-1 receptor blockade on the haemodynamic and hormonal changes after acute blood loss and after retransfusion in conscious dogsACTA PHYSIOLOGICA, Issue 4 2004R. C. E. Francis Abstract Aim:, This study investigates angiotensin II and endothelin-1 mediated mechanisms involved in the haemodynamic, hormonal, and renal response towards acute hypotensive haemorrhage. Methods:, Conscious dogs were pre-treated with angiotensin II type 1 (AT1) and/or endothelin-A (ETA) receptor blockers or not. Protocol 1: After a 60-min baseline period, 25% of the dog's blood was rapidly withdrawn. The blood was retransfused 60 min later and data recorded for another hour. Protocol 2: Likewise, but preceded by AT1 blockade with i.v. Losartan. Protocol 3: Likewise, but preceded by ETA blockade with i.v. ABT-627. Protocol 4: Likewise, but with combined AT1plus ETAblockade. Results:, In controls, haemorrhage decreased mean arterial pressure (MAP) by approximately 25%, cardiac output by approximately 40%, and urine volume by approximately 60%, increased angiotensin II (3.1-fold), endothelin-1 (1.13-fold), vasopressin (116-fold), and adrenaline concentrations (3.2-fold). Glomerular filtration rate and noradrenaline concentrations remained unchanged. During AT1 blockade, the MAP decrease was exaggerated (,40%) and glomerular filtration rate fell. During ETA blockade, noradrenaline increased after haemorrhage instead of adrenaline, and the MAP recovery after retransfusion was blunted. The decrease in cardiac output was similar in all protocols. Conclusions:, Angiotensin II is more important than endothelin-1 for the short-term regulation of MAP and glomerular filtration rate after haemorrhage, whereas endothelin-1 seems necessary for complete MAP recovery after retransfusion. After haemorrhage, endothelin-1 seems to facilitate adrenaline release and to blunt noradrenaline release. Haemorrhage-induced compensatory mechanisms maintain blood flow more effectively than blood pressure, as the decrease in cardiac output , but not MAP , was similar in all protocols. [source] Interactive effect of retinopathy and macroalbuminuria on all-cause mortality, cardiovascular and renal end points in Chinese patients with Type 2 diabetes mellitusDIABETIC MEDICINE, Issue 7 2007P. C. Y. Tong Abstract Aims To examine the effect of albuminuria and retinopathy on the risk of cardiovascular and renal events, and all-cause mortality in patients with Type 2 diabetes. Methods A post-hoc analysis of 4416 Chinese patients without macrovascular complications at baseline (age 57.6 ± 13.3 years). Glomerular filtration rate (eGFR) was estimated by the abbreviated Modification of Diet in Renal Disease Study Group Formula, further adjusted for Chinese ethnicity. Clinical end points were all-cause mortality, cardiovascular events (heart failure or angina, myocardial infarction, lower limb amputation, re-vascularization procedures and stroke) and renal end points (reduction in eGFR by more than 50% or eGFR < 15 ml/min/1.73 m2 or death as a result of renal causes or need for dialysis). Results Compared with individuals without complications, subjects with retinopathy and macroalbuminuria had higher rates of cardiovascular events (14.1 vs. 2.4%), renal events (40.0 vs. 0.8%) and death (9.3 vs. 1.7%, P < 0.001). For composite event of death, cardiovascular and renal events, the presence of retinopathy, microalbuminuria alone, macroalbuminuria alone, retinopathy with microalbuminuria or retinopathy with macroalbuminuria increased the risk [hazard ratio (95% CI)] by 1.61 (1.05 to 2.47; P = 0.04), 1.93 (1.38 to 2.69; P < 0.001), 4.34 (3.02 to 6.22; P < 0.001), 2.59 [1.76 to 3.81; P < 0.001) and 6.83 (4.89 to 9.55; P < 0.001) fold, respectively. The relative excess risk as a result of interaction between retinopathy and macroalbuminuria was 15.31, implying biological interaction in the development of renal events. Conclusions In Chinese patients with Type 2 diabetes, retinopathy interacts with macroalbuminuria to increase the risk of composite cardio-renal events. [source] Acute liver damage in anorexia nervosaINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 1 2004Lorenza Di Pascoli Abstract We report a case of a 26-year-old White woman with a history of anorexia nervosa who developed severe liver damage and multiorgan dysfunction. At admission to our medical unit, her body mass index (BMI) was 10.8. Biochemical evaluation showed a marked increase in serum levels of aspartate aminotransferases (AST = 9,980 IU/L), alanine aminotransferase (ALT = 3,930 IU/L), amylase (1,002 IU/L), lipase (1,437 IU/L), creatine phosphokinase (CPK; 783 IU/L), and lactate dehydrogenase (LDH = 6,830 IU/L). Glomerular filtration rate was reduced (35 ml/min), reflecting dehydration and prerenal azotemia. No other cause of acute liver damage except malnutrition was evidenced. Hydration and nutritional support were the unique medical treatment. A rapid recovery occurred in few days and all laboratory data were normal at discharge after a 37-day hospitalization. © 2004 by Wiley Periodicals, Inc. Int J Eat Disord 36: 114,117, 2004. [source] Plasma Clearance of Exogenous Creatinine, Exo-Iohexol, and Endo-Iohexol in Hyperthyroid Cats before and after Treatment with RadioiodineJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2008I. Van Hoek Background: Glomerular filtration rate (GFR) can be measured by clearance methods of different markers showing discrepancies and different reproducibility in healthy cats. Studies comparing different methods of GFR measurement in hyperthyroid cats have not yet been performed. Hypothesis: Plasma clearance of exogenous creatinine (PECCT), exo-iohexol (PexICT), and endo-iohexol (PenICT) could lead to differences in GFR measurement and the need to use the same clearance method when comparing GFR before and after radioiodine treatment in hyperthyroid cats. Animals: Fifteen client-owned hyperthyroid cats. Methods: GFR was measured 1 day before and 1, 4, 12, and 24 weeks after treatment. Intravenous injection of iohexol was followed immediately by IV injection of creatinine. Plasma creatinine was measured by an enzymatic method. Plasma endo- and exo-iohexol were measured by high-performance liquid chromatography coupled to ultraviolet detection. Results: Globally, the 3 GFR methods resulted in significantly different (P < .001) GFR results. GFR results among the different methods were the same (P= .999) at all time points. All 3 techniques indicated decreasing GFR after 131I treatment. For each GFR technique, a significant decrease in GFR was observed between time point 0 and all other time points. This decrease stabilized 4 weeks after treatment, with very little decline afterward. Conclusion and Clinical Importance: It is mandatory to use the same GFR technique in follow-up studies. GFR testing at 4 weeks posttreatment could allow assessment of the final renal functional loss after treatment in hyperthyroid cats. [source] Change of glomerular filtration rate in healthy adults with agingNEPHROLOGY, Issue 5 2009XUEFENG SUN SUMMARY Aim: In order to determine the relationship between glomerular filtration rate (GFR) and age, the associated factors, and the accurate method of GFR in healthy adults, we conducted a cross-sectional study in community-dwelling adults in Beijing. Methods: Renal function of 201 clinically healthy subjects was determined using technetium-99 m-labelled diethylene triamine pentacetic acid (99mTc-DTPA). Estimated GFR was calculated with the Cockcroft,Gault (CG) equation, abbreviated Modification of Diet in Renal Disease (MDRD) equation, and plasma clearance of creatinine (Ccr). Serum cystatin C, biomarkers of inflammatory and endothelial cells were analyzed as well. Protein intake, carotid artery intima-media thickness and plaque formation were assayed as well. Results: Glomerular filtration rate was negatively associated with age and the correlation coefficient for 99mTc-GFR, CG-GFR, MDRD-GFR, Ccr were ,0.643, ,0.736, ,0.55 and ,0.619, respectively (P < 0.001), while the correlation coefficient between cystatin C and age was 0.681 (P < 0.001). Estimated GFR were associated with measured GFR, and the correlation coefficient for Ccr, CG-GFR and MDRD-GFR were 0.813, 0.582 and 0.418, respectively (P < 0.001). The area under the receiver,operator curve of Ccr was larger, CG was smaller while MDRD was the smallest, and the difference was significant (P < 0.001). So a predicted equation was presented by cystatin C and C-reactive protein for the elderly. Conclusion: In the clinically healthy adults, GFR declined with age. MDRD and CG equation are not suitable to estimate GFR in healthy adults. The predicted equation established by cystatin C and C-reactive protein may be more accurate. [source] Angiotensin-converting enzyme polymorphism gene and evolution of nephropathy to end-stage renal diseaseNEPHROLOGY, Issue 4 2003M Angels ORTIZ SUMMARY: Genetic polymorphisms of the renin-angiotensin system (RAS) have been implicated in the pathogenesis of nephropathy and end-stage renal disease (ESRD). The association between angiotensin-converting enzyme (ACE) gene polymorphism and nephropathy evolution was studied. A random sample of 161 subjects from the Nephrology Department (of Hospital de Sant Pau) were divided into two groups: (i) 117 with end-stage renal disease; (ii) 44 with established nephropathy; and (iii) control groups of 129 subjects. The ACE gene polymorphism was performed by using polymerase chain reaction. High DD genotype presentation was observed in the two groups of subjects with nephropathy (46.12 and 61.37%, respectively vs 35.66% in controls; P < 0.0482), and also, a decrease was observed in the II genotype (6.4 and 4.54%, respectively vs 13.17% in controls, P < 0.0404). Glomerular filtration rate (GFR) was evaulated after 44 months of follow up. An important decrease of GFR was observed in patients with DD polymorphism versus other genotypes (initial, 32.3 ± 7.9 and at 44 months, 18.35 ± 3.3 mL/min vs 31.4 ± 11.9 and 11.7 ± 3.2 mL/min; P < 0.039). In a non-longitudinal study of patients in ESRD, patients with an ACE-DD genotype had a lower period of time between diagnosis of nephropathy and ESRD than patients with other genotypes (10.45 ± 9.32 vs 19.5 ± 8.4 years; P < 0.034). In conclusion, the ACE gene that controls RAS response may influence the development and progression of nephropathy to ESRD. Patients who develop several types of nephropathy have a higher risk of severe evolution if they have a profile of ACE-DD genotype. [source] Glomerular toxicity persists 10 years after ifosfamide treatment in childhood and is not predictable by age or dose,PEDIATRIC BLOOD & CANCER, Issue 7 2010FRCPCH, Roderick Skinner PhD Abstract Background This prospective longitudinal single institution cohort study evaluated the natural history of and risk factors for chronic nephrotoxicity 10 years after ifosfamide treatment in childhood. Procedure Twenty-five patients (16 males) treated with ifosfamide were investigated at end of treatment (End), 1 and 10 years later. Glomerular filtration rate (GFR), serum phosphate (PO4) and bicarbonate (HCO3) and renal tubular threshold for phosphate (Tmp/GFR) were measured, and total nephrotoxicity score (Ns) graded. Results More patients had a low GFR at 1 (72%) and 10 (50%) years than at End (26%) (P,=,0.006 for End vs. 1 year). Electrolyte supplementation requirements for tubular toxicity resolved by 10 years (0% vs. 32% at End and 24% at 1 year; both P,<,0.05). At 10 years, 17% of patients had moderate overall nephrotoxicity and 13% clinically significant reduction of GFR (<60,ml/min/1.73,m2). Neither dose nor age at treatment predicted any measure of toxicity at 10 years or reduced GFR at any timepoint. Higher cumulative ifosfamide dose correlated with greater tubular and overall nephrotoxicity at End and/or 1 year (P,<,0.05 for each of PO4, HCO3, Tmp/GFR, Ns), but age at treatment did not differ between patients with normal or abnormal results. Conclusions Although clinically significant tubular toxicity had resolved by 10 years, GFR was <60,ml/min/1.73,m2 in 13% of patients, raising concerns about very long-term glomerular function. Higher cumulative dose was associated with greater tubular and overall toxicity at End and 1 year, but not at 10 years. Age at treatment did not predict nephrotoxicity at any timepoint. Pediatr Blood Cancer 2010;54:983,989 © 2010 Wiley-Liss, Inc. [source] Long-term glomerular filtration rate following pediatric liver transplantionPEDIATRIC TRANSPLANTATION, Issue 5 2005Silke Wiesmayr Abstract:, In adult patients a significant proportion of chronic renal failure after liver transplantation (LTX) has been described. This was attributed mainly to nephrotoxicity caused by Calcineurin inhibitors (CNI). If these results are transferable to pediatric patients was the aim of this study. Forty-five pediatric patients with a LTX performed between 1988 and 2003 were evaluated. Glomerular filtration rate was calculated using the Schwartz formula (calculated GFR (cGFR) (mL/min/1.73 m2) = k× height (cm)/serum creatinine (mg/dL)). Median age at LTX was 4 yr (range 0.3,18.1). Pretransplant median cGFR was significantly elevated with 157.5 mL/min/1.73 m2. Within the first 3 months after LTX median cGFR normalized to a median value of 102.7 (p < 0.05 vs. pretransplant cGFR). During long-term follow-up median cGFR remained stable with calculated values of 108.0 two years and 112.6 five years after transplantation. Using a linear and an exponential one compartment mathematical modeling of renal function the calculated GFR was stable even for very long observation times (n > 10 yr). Liver insufficiency prior to transplantation was associated with glomerular hyperfiltration. After successful liver transplantation cGFR normalized within the first 3 month and, in contrast to the reported GFR impairment in adult liver transplant recipients, remained stable, even in long-term follow-up. [source] Estimating GFR in children with 99mTc-DTPA renography: a comparison with single-sample 51Cr-EDTA clearanceCLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 3 2010Henrik Gutte Summary Glomerular filtration rate (GFR) measurement by 51Cr-ethylenediaminetetraacetic acid (EDTA) and blood sampling in children is usually cumbersome for the patient, parents and laboratory technicians. We have previously developed a method accurately estimating GFR in adults. The aim of the present study was to evaluate the accuracy of this non-invasive method in children. We calculated GFR from 99mTc-diethylene triamine pentaacetic acid (DTPA) renography and compared with 51Cr-EDTA plasma clearance of 29 children between the age of 1 month and 12 years (mean 4·7 years). The correlation between 99mTc-DTPA renography and 51Cr-EDTA plasma clearance was for all children R = 0·96 (n = 29, P<0·0001), for children above 2 years of age R = 0·96 (n = 18, P<0·0001) and for children <2 years R = 0·84 (n = 11, P<0·001). We conclude that assessment of GFR from 99mTc-DTPA renography is reliable and comparable to GFR calculated from 51Cr-EDTA plasma clearance. Because our method is non-invasive and only takes 21 min, it may be preferable in many cases where an assessment of renal function is needed in children especially when renography is performed anyhow. [source] Tubular reabsorption and diabetes-induced glomerular hyperfiltrationACTA PHYSIOLOGICA, Issue 1 2010P. Persson Abstract Elevated glomerular filtration rate (GFR) is a common observation in early diabetes mellitus and closely correlates with the progression of diabetic nephropathy. Hyperfiltration has been explained to be the result of a reduced load of sodium and chloride passing macula densa, secondarily to an increased proximal reabsorption of glucose and sodium by the sodium-glucose co-transporters. This results in an inactivation of the tubuloglomerular feedback (TGF), leading to a reduced afferent arteriolar vasoconstriction and subsequently an increase in GFR. This hypothesis has recently been questioned due to the observation that adenosine A1 -receptor knockout mice, previously shown to lack a functional TGF mechanism, still display a pronounced hyperfiltration when diabetes is induced. Leyssac demonstrated in the 1960s (Acta Physiol Scand58, 1963:236) that GFR and proximal reabsorption can work independently of each other. Furthermore, by the use of micropuncture technique a reduced hydrostatic pressure in Bowman's space or in the proximal tubule of diabetic rats has been observed. A reduced pressure in Bowman's space will increase the pressure gradient over the filtration barrier and can contribute to the development of diabetic hyperfiltration. When inhibiting proximal reabsorption with a carbonic anhydrase inhibitor, GFR decreases and proximal tubular pressure increases. Measuring intratubular pressure allows a sufficient time resolution to reveal that net filtration pressure decreases before TGF is activated which highlights the importance of intratubular pressure as a regulator of GFR. Taken together, these results imply that the reduced intratubular pressure observed in diabetes might be crucial for the development of glomerular hyperfiltration. [source] Serum and 24-hour Urine Analysis in Adult Cyanotic and Noncyanotic Congenital Heart Disease PatientsCONGENITAL HEART DISEASE, Issue 3 2009Efrén Martínez-Quintana MD ABSTRACT Introduction., Glomerulopathy is a complication of congenital heart disease patients. The risk of developing renal impairment is particularly high in cyanotic patients. Objective., The aim of this study was to determine the prevalence of renal dysfunction and microalbumiuria in adult cyanotic and non cyanotic congenital heart disease patients. Methods., Fourteen cyanotic and 22 noncyanotic congenital heart disease patients were studied in the Adult Congenital Heart Disease Unit at the Complejo Hospitalario Universitario Insular-Materno Infantil. Demographic characteristics, complete blood count, and 24-hour urianalysis were obtained, including abdominal ultrasound in those with cyanosis. Results., No differences were seen between age (years) (27.4 ± 8.2; 26.4 ± 8.3; P = .71), sex, size, weight, or glomerular filtration rate (mL/min/1.73 m2) (81.1 ± 22.9 vs. 84.9 ± 9.2, P = .482) between cyanotic and noncyanotic patients. However, Eisenmenger patients had significantly impaired renal function when compared with noncyanotic patients (73.0 ± 17.3 vs. 84.9 ± 9.2 mL/min/1.73 m2, P = .023). Significant differences were obtained in oxygen saturation (%) (83.8 ± 5.8 vs. 97.8 ± 0.8; P = .000), hematocrit (%) (59.3 ± 8.1 vs. 40.9 ± 8.5; P = .000), platelets (103/µL) (161.5 ± 70.5 vs. 277.9 ± 57.6; P = .000), serum uric acid (mg/dL) (7.5 ± 2.3 vs. 5.6 ± 1.5; P = .008) and microalbuminuria (mg/24 hours) (12.8 [0, 700.2] vs. 2.4 [0, 18.9]; P = .000) between cyanotic and noncyanotic patients. Five cyanotic patients (35.7%) had microalbuminuria (>30 mg/24 hours) and three of them (21.4%) proteinuria (>1 g/24 hours). No significant differences were seen between serum and urine parameters between cyanotic patients who had microalbuminuria (>30 mg/24 hours) and those cyanotic patients who did not have it (<30 mg/24 hours). Conclusions., Renal impairment is frequently seen in congenital heart disease patients, being associated occasionally with proteinuria and microalbuminuria in cyanotic ones. [source] The Cardio-Renal-Anemia Syndrome in Elderly Subjects With Heart Failure and a Normal Ejection Fraction: A Comparison With Heart Failure and Low Ejection FractionCONGESTIVE HEART FAILURE, Issue 4 2006Rose S. Cohen MD The prevalence and severity of anemia and renal dysfunction in heart failure patients with a normal ejection fraction (HFNEF) is uncharacterized. Two hundred eighty-five consecutive patients admitted to a community hospital with heart failure were stratified by the presence or absence of anemia and a normal or reduced ejection fraction. Comparisons of clinical variables were performed. In this sample, 62% of subjects were anemic, with no difference between those with a normal and a reduced ejection fraction (63% vs. 61%). Anemic HFNEF subjects had a lower glomerular filtration rate (37±21 mL/min vs. 52±35 mL/min; p<0.05) and more severe self-reported symptom scores than nonanemic HFNEF subjects. Multivariate analysis confirmed the association of renal dysfunction and anemia. The authors conclude that the degree and magnitude of anemia in elderly inpatients with heart failure does not differ by ejection fraction. Worse symptoms and more severe renal dysfunction were seen in HFNEF subjects with anemia than in HFNEF subjects without anemia. [source] MR determination of glomerular filtration rate in subjects with solitary kidneys in comparison to clinical standards of renal function: feasibility and preliminary report,CONTRAST MEDIA & MOLECULAR IMAGING, Issue 2 2009Richard W. Katzberg Abstract This study was conducted to demonstrate the feasibility of quantifying single kidney glomerular filtration rate (skGFR) by magnetic resonance (MR) by comparison to the clinical estimates of GFR in volunteer subjects with a single kidney. Seven IRB-approved subjects with a solitary kidney, stable serum creatinine (SCr) and a 24,h creatinine clearance (CrCl) volunteered to undergo an MR examination that determined renal extraction fraction (EF) with a breathhold inversion recovery echo planar pulse sequence and renal blood flow with a velocity encoded phase imaging sequence. The product of EF and blood flow determines GFR. These values were compared with the 24,h CrCl, estimated GFR by the modification of diet in renal disease (MDRD) regression analysis and the Cockroft,Gault (CG) determination of CrCl. The mean and standard deviation of differences between the MR GFR, MDRD and CG vs the 24,h CrCl were 12.3,±,35.7, ,8.9,±,18.5 and 1.2,±,19.6, respectively. The Student t -test showed that none of the mean differences were statistically significant between techniques. This clinical investigation shows that MR can be used for skGFR determination in human subjects with comparable values to those derived from clinically used serum-based GFR estimation techniques. Copyright © 2009 John Wiley & Sons, Ltd. [source] Blood volume, blood pressure and total body sodium: internal signalling and output controlACTA PHYSIOLOGICA, Issue 1 2009P. Bie Abstract Total body sodium and arterial blood pressure (ABP) are mutually dependent variables regulated by complex control systems. This review addresses the role of ABP in the normal control of sodium excretion (NaEx), and the physiological control of renin secretion. NaEx is a pivotal determinant of ABP, and under experimental conditions, ABP is a powerful, independent controller of NaEx. Blood volume is a function of dietary salt intake; however, ABP is not, at least not in steady states. A transient increase in ABP after a step-up in sodium intake could provide a causal relationship between ABP and the regulation of NaEx via a hypothetical integrative control system. However, recent data show that subtle sodium loading (simulating salty meals) causes robust natriuresis without changes in ABP. Changes in ABP are not necessary for natriuresis. Normal sodium excretion is not regulated by pressure. Plasma renin is log-linearly related to salt intake, and normally, decreases in renin secretion are a precondition of natriuresis after increases in total body sodium. Renin secretion is controlled by renal ABP, renal nerve activity and the tubular chloride concentrations at the macula densa (MD). Renal nerve activity is related to blood volume, also at constant ABP, and elevates renin secretion by means of ,1 -adrenoceptors. Recent results indicate that renal denervation reduces ABP and renin activity, and that sodium loading may decrease renin without changes in ABP, glomerular filtration rate or ,1 -mediated nerve activity. The latter indicates an essential role of the MD mechanism and/or a fourth mediator of the physiological control of renin secretion. [source] Effect of angiotensin II and endothelin-1 receptor blockade on the haemodynamic and hormonal changes after acute blood loss and after retransfusion in conscious dogsACTA PHYSIOLOGICA, Issue 4 2004R. C. E. Francis Abstract Aim:, This study investigates angiotensin II and endothelin-1 mediated mechanisms involved in the haemodynamic, hormonal, and renal response towards acute hypotensive haemorrhage. Methods:, Conscious dogs were pre-treated with angiotensin II type 1 (AT1) and/or endothelin-A (ETA) receptor blockers or not. Protocol 1: After a 60-min baseline period, 25% of the dog's blood was rapidly withdrawn. The blood was retransfused 60 min later and data recorded for another hour. Protocol 2: Likewise, but preceded by AT1 blockade with i.v. Losartan. Protocol 3: Likewise, but preceded by ETA blockade with i.v. ABT-627. Protocol 4: Likewise, but with combined AT1plus ETAblockade. Results:, In controls, haemorrhage decreased mean arterial pressure (MAP) by approximately 25%, cardiac output by approximately 40%, and urine volume by approximately 60%, increased angiotensin II (3.1-fold), endothelin-1 (1.13-fold), vasopressin (116-fold), and adrenaline concentrations (3.2-fold). Glomerular filtration rate and noradrenaline concentrations remained unchanged. During AT1 blockade, the MAP decrease was exaggerated (,40%) and glomerular filtration rate fell. During ETA blockade, noradrenaline increased after haemorrhage instead of adrenaline, and the MAP recovery after retransfusion was blunted. The decrease in cardiac output was similar in all protocols. Conclusions:, Angiotensin II is more important than endothelin-1 for the short-term regulation of MAP and glomerular filtration rate after haemorrhage, whereas endothelin-1 seems necessary for complete MAP recovery after retransfusion. After haemorrhage, endothelin-1 seems to facilitate adrenaline release and to blunt noradrenaline release. Haemorrhage-induced compensatory mechanisms maintain blood flow more effectively than blood pressure, as the decrease in cardiac output , but not MAP , was similar in all protocols. [source] Intrauterine growth restriction reduces nephron number and renal excretory function in newborn piglets,ACTA PHYSIOLOGICA, Issue 2 2002R. Bauer ABSTRACT To examine the effects of intrauterine growth restriction on nephron number, renal circulation, and renal excretory functions in newborns, studies were conducted on 1-day-old anaesthetized piglets, divided into normal weight (n = 6) and intrauterine growth restricted (n = 6) piglets. Renal blood flow was measured by coloured microspheres, glomerular filtration rate was measured by inulin clearance, and osmotic clearance and fractional sodium excretion were calculated. In addition, an estimation of the nephron number was performed by counting representative glomerular numbers in microscopic sections. Newborn intrauterine growth restricted piglets exhibited a reduced glomerular filtration rate and osmotic clearance (P < 0.05), whereas renal blood flow and the filtration fraction as well as fractional sodium excretion were similar in normal weight and intrauterine growth restricted piglets. The nephron number was markedly reduced in intrauterine growth restricted piglets even if the nephron number was related to body weight (P < 0.01). There was a positive correlation between nephron number and glomerular filtration rate (r = 0.69, P < 0.05). Reduced glomerular filtration rate of newborn intrauterine growth restricted piglets is associated with a reduced nephron number. Thus, at birth, compensatory response of renal function due to nephron deficit does not exist in intrauterine growth restricted piglets. [source] Pharmacokinetics of dipeptidylpeptidase-4 inhibitorsDIABETES OBESITY & METABOLISM, Issue 8 2010A. J. Scheen Type 2 diabetes (T2DM) is a complex disease combining defects in insulin secretion and insulin action. New compounds have been developed for improving glucose-induced insulin secretion and glucose control, without inducing hypoglycaemia or weight gain. Dipeptidylpeptidase-4 (DPP-4) inhibitors are new oral glucose-lowering agents, so-called incretin enhancers, which may be used as monotherapy or in combination with other antidiabetic compounds. Sitagliptin, vildaglipin and saxagliptin are already on the market in many countries, either as single agents or in fixed-dose combined formulations with metformin. Other DPP-4 inhibitors, such as alogliptin and linagliptin, are currently in late phase of development. The present paper summarizes and compares the main pharmacokinetics (PK) properties, that is, absorption, distribution, metabolism and elimination, of these five DPP-4 inhibitors. Available data were obtained in clinical trials performed in healthy young male subjects, patients with T2DM, and patients with either renal insufficiency or hepatic impairment. PK characteristics were generally similar in young healthy subjects and in middle-aged overweight patients with diabetes. All together gliptins have a good oral bioavailability which is not significantly influenced by food intake. PK/pharmacodynamics characteristics, that is, sufficiently prolonged half-life and sustained DPP-4 enzyme inactivation, generally allow one single oral administration per day for the management of T2DM; the only exception is vildagliptin for which a twice-daily administration is recommended because of a shorter half-life. DPP-4 inhibitors are in general not substrates for cytochrome P450 (except saxagliptin that is metabolized via CYP 3A4/A5) and do not act as inducers or inhibitors of this system. Several metabolites have been documented but most of them are inactive; however, the main metabolite of saxagliptin also exerts a significant DPP-4 inhibition and is half as potent as the parent compound. Renal excretion is the most important elimination pathway, except for linagliptin whose metabolism in the liver appears to be predominant. PK properties of gliptins, combined with their good safety profile, explain why no dose adjustment is necessary in elderly patients or in patients with mild to moderate hepatic impairment. As far as patients with renal impairment are concerned, significant increases in drug exposure for sitagliptin and saxagliptin have been reported so that appropriate reductions in daily dosages are recommended according to estimated glomerular filtration rate. The PK characteristics of DPP-4 inhibitors suggest that these compounds are not exposed to a high risk of drug,drug interactions. However, the daily dose of saxagliptin should be reduced when coadministered with potent CYP 3A4 inhibitors. In conclusion, besides their pharmacodynamic properties leading to effective glucose-lowering effect without inducing hypoglycaemia or weight gain, DPP-4 inhibitors show favourable PK properties, which contribute to a good efficacy/safety ratio for the management of T2DM in clinical practice. [source] Losartan modifies glomerular hyperfiltration and insulin sensitivity in type 1 diabetesDIABETES OBESITY & METABOLISM, Issue 6 2001S. Nielsen Aim: The effect of the angiotensin II receptor antagonist losartan on renal haemodynamics and insulin-mediated glucose disposal was examined in normotensive, normoalbuminuric type 1 diabetic patients using a double-blind, placebo-controlled, cross-over design. Methods: Diurnal blood pressure, glomerular filtration rate (GFR, determined using [125I]-iothalamate), renal plasma flow (RPF, determined using [131I]-hippuran) and urinary albumin excretion rate (UAE) were measured, and a hyperinsulinaemic, euglycaemic clamp with indirect calorimetry was performed in nine patients (age 30 ± 7 years (mean ±,s.d.), HbA1c 8.1 ± 1.1%) following 6 weeks' administration of either losartan 50 mg/day or placebo. Results: Diurnal blood pressure was significantly reduced after losartan compared with placebo (122/70 ± 11/8 vs. 130/76 ± 12/6 mmHg, p <,0.05). A significant decline in GFR (133 ± 23 vs. 140 ± 22 ml/min, p < 0.05) and filtration fraction (FF; GFR/RPF) (24.6 ± 3.5 vs. 26.2 ± 3.6%, p <,0.05) was observed in the losartan vs. placebo groups. RPF and UAE did not change. Isotopically determined glucose disposal rates were similar after losartan and placebo in the basal (2.61 ± 0.53 vs. 2.98 ± 0.93 mg/kg/min) and insulin-stimulated states (6.84 ± 2.52 vs. 6.97 ± 3.11 mg/kg/min). However, the glucose oxidation rate increased significantly after losartan vs. placebo in the basal state (1.72 ± 0.34 vs. 1.33 ± 0.18, mg/kg/min, p <,0.01) and during insulin stimulation (2.89 ± 0.75 vs. 2.40 ± 0.62 mg/kg/min, p <,0.03). Basal and insulin-stimulated non-oxidative glucose disposal tended to decrease after losartan; however, this was not significant. Endogenous glucose production and lipid oxidation were unchanged after treatment and similarly suppressed during hyperinsulinaemia. Glycaemic control, total cholesterol, high-density lipoprotein (HDL)-cholesterol and triglycerides were stable in both losartan and placebo groups. Conclusions: Losartan reduces blood pressure, glomerular hyperfiltration and FF, and improves basal and insulin-stimulated glucose oxidation in normotensive, normoalbuminuric type 1 diabetic patients. [source] Independent predictive roles of eotaxin Ala23Thr, paraoxonase 2 Ser311Cys and ,3 -adrenergic receptor Trp64Arg polymorphisms on cardiac disease in Type 2 Diabetes,an 8-year prospective cohort analysis of 1297 patientsDIABETIC MEDICINE, Issue 4 2010Y. Wang Diabet. Med. 27, 376,383 (2010) Abstract Aims, To examine the independent and joint effects of multiple genetic variants on a cardiac end-point in an 8-year prospective study of a Chinese diabetic cohort. Methods, Seventy-seven single nucleotide polymorphisms (SNPs) of 53 candidate genes for inflammation, thrombosis, vascular tone regulation and lipid metabolism were genotyped in 1297 Chinese patients with no prior history of coronary heart disease (CHD) or heart failure at baseline. Cardiac end-point was defined by the occurrence of CHD and/or heart failure. Results, In Cox regression model, after adjustment for baseline confounding variables including age, sex, smoking status, duration of diabetes, glycaemic control, lipid levels, waist circumference, blood pressure, albuminuria and estimated glomerular filtration rate, genetic variants, including Ala/Ala of SCYA11 (eotaxin) Ala23Thr, Cys/Cys or Cys/Ser of PON2 (paraoxonase 2) Ser311Cys and Arg/Arg of ADRB3 (,3 -adrenergic receptor) Trp64Arg, were independently associated with incident cardiac end-point, with respective hazard ratios (95% confidence interval) of 1.70 (1.10,2.61, P = 0.037), 1.42 (1.08,1.88, P = 0.013) and 3.84 (1.18,12.50, P = 0.025). Analysis of the joint effect of the risk alleles showed significant increased risk of the cardiac end-point with increasing number of risk alleles (P < 0.001). The adjusted risk for the cardiac end-point was 4.11 (P = 0.002) for patients carrying four risk alleles compared with those carrying one or no risk allele. Conclusions, The independent risk conferred by genetic variants encoding pathways such as inflammation and lipid metabolism, not adequately reflected by conventional biomarkers, may identify high-risk individuals for intensified control of modifiable risk factors. [source] Establishing pragmatic estimated GFR thresholds to guide metformin prescribingDIABETIC MEDICINE, Issue 10 2007J. S. Shaw Abstract Aims, Renal impairment is a contraindication to metformin treatment because of the perceived increased risk of lactic acidosis. Current guidelines define renal impairment according to the serum creatinine of the individual, but this measure is being supplanted by the use of estimated glomerular filtration rate (eGFR) as it gives a closer estimate to true GFR. This study aimed to establish pragmatic eGFR limits for use in patients being considered for metformin treatment. Methods, Estimated GFR measurements corresponding to currently used metformin creatinine limits of 130 and 150 µmol/l were derived and then applied to 12 482 patients with diabetes in Hull and East Yorkshire. Results, Few patients with a serum creatinine of 130 or 150 µmol/l have an eGFR of < 30 ml/min/1.73 m2[chronic kidney disease (CKD) stage 4 or greater], while most are between 30 and 59 ml/min/1.73 m2 (CKD stage 3). When applied to the 12 482 patients (median age 67 years, interquartile range 56,75), males predominated when using creatinine cut-offs (13.6% of males and 8.3% of females had creatinine > 130 µmol/l; 8.2% males and 5.2% females > 150 µmol/l), but not using eGFR CKD thresholds (3.3% males and 4.7% females < 30 ml/min/1.73 m2; 20.8% males and 28.1% females eGFR 30,59 ml/min/1.73 m2). Similar proportions of patients as currently would have metformin withheld if using eGFR cut-offs between 30 and 49 ml/min/1.73 m2. Conclusions, We have proposed pragmatic eGFR limits to guide metformin prescribing in patients with renal impairment. CKD stage 4 or greater should be an absolute contraindication to metformin, while CKD stage 3 should alert clinicians to consider other risk factors before initiating or continuing treatment. [source] The accuracy of cystatin C and commonly used creatinine-based methods for detecting moderate and mild chronic kidney disease in diabetesDIABETIC MEDICINE, Issue 4 2007R. J. MacIsaac Abstract Background, The accuracy of measuring serum cystatin C levels for detecting various stages of chronic kidney disease (CKD) in diabetes is still unclear. Methods In a cross-sectional study of 251 subjects, a reference glomerular filtration rate (GFR) was measured using 99cTc-DTPA plasma clearance (iGFR). Multivariate analysis was used to identify independent clinical and biochemical associations with serum cystatin C and iGFR levels. The diagnostic accuracy of cystatin C and commonly used creatinine-based methods of measuring renal function (serum creatinine, the MDRD four-variable and Cockcroft,Gault formulae) for detecting mild and moderate CKD was also compared. Results, In the entire study population the same five variables, age, urinary albumin excretion rates, haemoglobin, history of macrovascular disease and triglyceride levels were independently associated with both cystatin C and iGFR levels. A serum cystatin C level cut-off > 82.1 nmol/l (1.10 mg/l) had the best test characteristics as a screening tool for detecting moderate CKD (< 60 ml/min per 1.73 m2) when compared with creatinine-based methods. At the upper threshold for mild CKD (< 90 ml/min per 1.73 m2), cystatin C also had greater diagnostic accuracy than creatinine, but had similar diagnostic accuracy when compared with creatinine-based formulae for predicting renal function. Conclusions, This study suggests that the clinical and biochemical parameters associated with serum cystatin C levels are closely linked to those associated with GFR and highlights the potential usefulness of screening for moderate or mild CKD in subjects with diabetes by simply measuring serum cystatin C levels. [source] Reduced plasma total homocysteine concentrations in Type 1 diabetes mellitus is determined by increased renal clearanceDIABETIC MEDICINE, Issue 3 2005B. A. J. Veldman Abstract Introduction Elevated plasma levels of total homocysteine are related to the development of vascular complications. Patients with diabetes mellitus are particularly at risk for the development of these complications. Several factors determine plasma total homocysteine including renal function. Aims As early Type 1 diabetes is characterized by a relative glomerular hyperfiltration, increased renal clearance could contribute to decreased levels of homocysteine as observed in Type 1 diabetes mellitus. Therefore we investigated the relationship between plasma total homocysteine and the glomerular filtration rate (GFR). Methods In 92 Type 1 diabetes patients and 44 control subjects, we measured GFR and effective renal plasma flow (ERPF) by means of continuous infusion of inulin and p-aminohippurate. Fasting plasma total homocysteine was measured using high performance liquid chromatography. Results GFR (121 ± 21 resp. 104 ± 14 ml/min; P < 0.001) and ERPF (563 ± 127 resp. 516 ± 121 ml/min; P = 0.05) were significantly higher in Type 1 diabetes patients as compared with control subjects. Plasma total homocysteine was reduced in Type 1 diabetes patients as compared with control subjects (11.0 ± 4.5 resp. 13.4 ± 7 µmol/l; P = 0.01). Plasma total homocysteine was strongly correlated with GFR (Type 1 diabetes patients: r = ,0.43, P < 0.001; control subjects: r = ,0.39, P = 0.01). Conclusion GFR is a major determinant of plasma total homocysteine levels in Type 1 diabetes patients as well as control subjects. The reduced plasma total homocysteine levels in diabetes patients can be explained by an increased GFR. [source] Fabry disease: overall effects of agalsidase alfa treatmentEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2004M. Beck Abstract Background, Fabry disease is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme ,-galactosidase A. Progressive accumulation of the substrate globotriaosylceramide in cells throughout the body leads to major organ failure and premature death. The Fabry Outcome Survey (FOS) is a European outcomes database which was established to collect data on the natural history of this little-known disease and to monitor the long-term efficacy and safety of enzyme replacement therapy (ERT) with agalsidase alfa. This paper presents the first analysis of the FOS database on the effects of ERT on renal function, heart size, pain and quality of life. Design, The effects of 1 and 2 years of ERT with agalsidase alfa on renal function (assessed by estimated glomerular filtration rate), heart size (assessed by echocardiography), pain (assessed by the Brief Pain Inventory) and quality of life (assessed by the European Quality of Life Questionnaire EQ-5D) were analyzed in a cohort of 545 patients, 314 of whom were receiving treatment (188 for at least 12 months and 92 for at least 24 months; mean duration of treatment, 17 months; maximum duration, 56 months). Results, Treatment with agalsidase alfa stabilized renal function in patients with a mild or moderate deterioration in renal function at baseline, reduced left ventricular size in patients who had an enlarged heart at baseline, and improved pain scores and quality of life. These improvements were similar in hemizygous men and heterozygous women with Fabry disease. Conclusions, Enzyme replacement therapy with agalsidase alfa leads to significant clinical benefits in patients with Fabry disease, and treatment is likely to alter the natural history of this disorder. [source] Interactions between maternal subtotal nephrectomy and salt: effects on renal function and the composition of plasma in the late gestation sheep fetusEXPERIMENTAL PHYSIOLOGY, Issue 2 2008Amanda C. Boyce Effects of altered maternal salt intake between 122 and 127 days gestation (term is 150 days) were studied in eight fetuses carried by ewes which had renal insufficiency caused by subtotal nephrectomy (STNxF) and seven fetuses carried by intact ewes (IntF). Plasma sodium and osmolality were increased in ewes with subtotal nephrectomy on a high-salt intake (0.17 m NaCl in place of drinking water for 5 days; P < 0.05). The STNxF had normal body weights. A high maternal salt intake did not affect fetal blood pressure or heart rate. Plasma osmolality was higher in STNxF (P < 0.001), and plasma sodium and osmolality were increased by high salt (P < 0.001 and P < 0.04, respectively). The STNxF had higher urinary osmolalities (P= 0.002), which were also increased by a high maternal salt intake (P= 0.03). Renal blood flow fell in STNxF in response to a high maternal salt intake, but increased in IntF (P= 0.003). In STNxF but not IntF, glomerular filtration rate and urinary protein excretion were positively related to fetal plasma renin levels (P, 0.01). It is concluded that the salt intake of pregnant ewes with renal insufficiency affects maternal and fetal osmolar balance, fetal plasma sodium and fetal renal function. Since STNxF also had altered renal haemodynamic responses to high maternal salt and evidence of renin-dependent glomerular filtration and protein excretion, we suggest that interactions between dietary salt and pre-existing maternal renal disease impair glomerular integrity and function in the fetus. [source] Time course of the renal functional response to partial nephrectomy: measurements in conscious ratsEXPERIMENTAL PHYSIOLOGY, Issue 1 2007R. M. Chamberlain Previous investigations into the functional responses of the surviving nephrons following reductions in renal mass have been performed largely in anaesthetized animals and have taken little account of how the compensatory changes develop with time. The present study has assessed a method for determining glomerular filtration rate (GFR) in unrestrained, uncatheterized, conscious rats (plasma disappearance of 99mTc-diethylenetriamene pentaacetic acid (DTPA)) and has used this method to document the time course of the changes in GFR over a 32 day period following uninephrectomy or 5/6 nephrectomy. Concurrent measurements of excretion rates and of the clearance of lithium (the latter being an index of end-proximal fluid delivery) provided information on changes in overall tubular function and segmental reabsorption. After uninephrectomy, the GFR of the remaining kidney (compared with that of a single kidney of sham-operated animals) increased maximally (by ,50%) within 8 days; after 5/6 nephrectomy, the increase in the GFR of the remnant kidney was maximal (at ,300%) within 16 days. Overall excretion rates of sodium and potassium were well maintained in partially nephrectomized animals throughout the period of study, while the excretion of water increased (by ,30% after uninephrectomy and by ,120% after 5/6 nephrectomy), partly as a result of the compensatory increases in GFR but mainly as a consequence of moderate (after uninephrectomy) or marked (after 5/6 nephrectomy) reductions in fractional reabsorption. During the early period after 5/6 nephrectomy, potassium excretion sometimes exceeded the filtered load, indicating net secretion. Lithium clearance data indicated that the changes in tubular function after 5/6 nephrectomy include a reduction in fractional reabsorption in the proximal tubule, whereas after uninephrectomy any such effect on the proximal tubule is minor and transient. [source] | ||||||||||||||||||||||||||||||||||||||||