Impaired Glomerular Filtration Rate Research Articles

Intensive Diabetes Therapy Reduces Risk of Impaired GFR in DCCT/EDIC Studies

Intensive Diabetes Therapy Reduces Risk of Impaired GFR in DCCT/EDIC Studies

Annexin A1 protein attenuates cyclosporine-induced renal hemodynamics changes and macrophage infiltration in rats

Cyclosporine (CsA) remains an important immunosuppressant for transplantation and for treatment of autoimmune diseases. The most troublesome side effect of CsA is renal injury. Acute CsA-induced nephrotoxicity is characterized by reduced renal blood flow (RBF) and glomerular filtration rate (GFR) due to afferent arteriole vasoconstriction. Annexin A1 (ANXA1) is a potent anti-inflammatory protein with protective effect in renal ischemia/reperfusion injury. Here we study the effects of ANXA1 treatment in an experimental model of acute CsA nephrotoxicity. Salt-depleted rats were randomized to treatment with VH (vehicles 1mL/kg body weight/day), ANXA1 (Ac2-26 peptide 1mg/kg body weight/day intraperitoneally), CsA (20mg/kg body weight/day subcutaneously) and CsA+ANXA1 (combination) for seven days. We compared renal function and hemodynamics, renal histopathology, renal tissue macrophage infiltration and renal ANXA1 expression between the four groups. CsA significantly impaired GFR and RBF, caused tubular dilation and macrophage infiltration and increased ANXA1 renal tissue expression. Treatment with ANXA1 attenuated CSA-induced hemodynamic changes, tubular injury and macrophage infiltration. ANXA1 treatment attenuated renal hemodynamic injury and inflammation in an acute CsA nephrotoxicity model.

Intensive Diabetes Therapy and Glomerular Filtration Rate in Type 1 Diabetes

An impaired glomerular filtration rate (GFR) leads to end-stage renal disease and increases the risks of cardiovascular disease and death. Persons with type 1 diabetes are at high risk for kidney disease, but there are no interventions that have been proved to prevent impairment of the GFR in this population. In the Diabetes Control and Complications Trial (DCCT), 1441 persons with type 1 diabetes were randomly assigned to 6.5 years of intensive diabetes therapy aimed at achieving near-normal glucose concentrations or to conventional diabetes therapy aimed at preventing hyperglycemic symptoms. Subsequently, 1375 participants were followed in the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. Serum creatinine levels were measured annually throughout the course of the two studies. The GFR was estimated with the use of the Chronic Kidney Disease Epidemiology Collaboration formula. We analyzed data from the two studies to determine the long-term effects of intensive diabetes therapy on the risk of impairment of the GFR, which was defined as an incident estimated GFR of less than 60 ml per minute per 1.73 m(2) of body-surface area at two consecutive study visits. Over a median follow-up period of 22 years in the combined studies, impairment of the GFR developed in 24 participants assigned to intensive therapy and in 46 assigned to conventional therapy (risk reduction with intensive therapy, 50%; 95% confidence interval, 18 to 69; P=0.006). Among these participants, end-stage renal disease developed in 8 participants in the intensive-therapy group and in 16 in the conventional-therapy group. As compared with conventional therapy, intensive therapy was associated with a reduction in the mean estimated GFR of 1.7 ml per minute per 1.73 m(2) during the DCCT study but during the EDIC study was associated with a slower rate of reduction in the GFR and an increase in the mean estimated GFR of 2.5 ml per minute per 1.73 m(2) (P<0.001 for both comparisons). The beneficial effect of intensive therapy on the risk of an impaired GFR was fully attenuated after adjustment for glycated hemoglobin levels or albumin excretion rates. The long-term risk of an impaired GFR was significantly lower among persons treated early in the course of type 1 diabetes with intensive diabetes therapy than among those treated with conventional diabetes therapy. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; DCCT/EDIC ClinicalTrials.gov numbers, NCT00360815 and NCT00360893.).

The angiographic morphologic features of the patients with chronic kidney dysfunction and coronary artery disease

ObjectiveTo analyse the angiographic morphologic features of the patients with chronic kidney dysfunction and coronary artery disease.MethodsAccording to the glomerular filtration rate (GFR) 299 consecutive patients who had undergone coronary...

Clinical Characteristics and Outcomes of Patients With Improvement in Renal Function During the Treatment of Decompensated Heart Failure

Background In the setting of acute decompensated heart failure, worsening renal function (WRF) and improved renal function (IRF) have been associated with similar hemodynamic derangements and poor prognosis. Our aim was to further characterize IRF and its associated mortality risk. Methods and Results Consecutive patients with a discharge diagnosis of congestive heart failure at the Hospital of the University of Pennsylvania were reviewed. IRF was defined as a ≥20% improvement and WRF as a ≥20% deterioration in glomerular filtration rate. Overall, 903 patients met the eligibility criteria, with 31.4% experiencing IRF. Baseline venous congestion/right-side cardiac dysfunction was more common ( P ≤ .04) and volume of diuresis ( P = .003) was greater in patients with IRF. IRF was associated with a greater incidence of preadmission (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.6–6.7; P < .0001) and postdischarge (OR 1.8, 95% CI 1.2–2.7; P = .006) WRF. IRF was associated with increased mortality (adjusted hazard ratio 1.3, 95% CI, 1.1–1.7; P = .011), a finding largely restricted to patients with postdischarge recurrence of renal dysfunction ( P interaction = .038). Conclusions IRF is associated with significantly worsened survival and may represent the resolution of venous congestion–induced preadmission WRF. Unlike WRF, the renal dysfunction in IRF patients occurs independently from the confounding effects of acute decongestion and may provide incremental information for the study of cardiorenal interactions.

Prognostic Importance of Early Worsening Renal Function After Initiation of Angiotensin-Converting Enzyme Inhibitor Therapy in Patients With Cardiac Dysfunction

Worsening renal function (WRF) in the setting of heart failure has been associated with increased mortality. However, it is unclear if this decreased survival is a direct result of the reduction in glomerular filtration rate (GFR) or if the mechanism underlying the deterioration in GFR is driving prognosis. Given that WRF in the setting of angiotensin-converting enzyme inhibitor (ACE-I) initiation is likely mechanistically distinct from spontaneously occurring WRF, we investigated the relative early WRF-associated mortality rates in subjects randomized to ACE-I or placebo. Subjects in the Studies Of Left Ventricular Dysfunction (SOLVD) limited data set (n=6337) were studied. The interaction between early WRF (decrease in estimated GFR ≥20% at 14 days), randomization to enalapril, and mortality was the primary end point. In the overall population, early WRF was associated with increased mortality (adjusted hazard ratio [HR], 1.2; 95% CI, 1.0-1.4; P=0.037). When analysis was restricted to the placebo group, this association strengthened (adjusted HR, 1.4; 95% CI, 1.1-1.8; P=0.004). However, in the enalapril group, early WRF had no adverse prognostic significance (adjusted HR, 1.0; 95% CI, 0.8-1.3; P=1.0; P=0.09 for the interaction). In patients who continued to receive study drug despite early WRF, a survival advantage remained with enalapril therapy (adjusted HR, 0.66; 95% CI, 0.5-0.9; P=0.018). These data support the notion that the mechanism underlying WRF is important in determining its prognostic significance. Specifically, early WRF in the setting of ACE-I initiation appears to represent a benign event that is not associated with a loss of benefit from continued ACE-I therapy.

Urological Disorders in Chronic Kidney Disease in Children Cohort: Clinical Characteristics and Estimation of Glomerular Filtration Rate

Urological disorders are the most common cause of pediatric chronic kidney disease. We determined the characteristics of children with urological disorders and assessed the agreement between the newly developed bedside glomerular filtration rate estimating formula with measured glomerular filtration rate in 586 patients in the Chronic Kidney Disease in Children study. The Chronic Kidney Disease in Children study is a prospective, observational cohort of children recruited from 48 sites in the United States and Canada. Eligibility requirements include age 1 to 16 years and estimated glomerular filtration rate by original Schwartz formula 30 to 90 ml/min/1.73 m(2). Baseline demographics, clinical variables and glomerular filtration rate were assessed. Bland-Altman analysis was conducted to assess agreement between estimated and measured glomerular filtration rates. Of the 586 participants with at least 1 glomerular filtration rate measurement 348 (59%) had an underlying urological diagnosis (obstructive uropathy in 118, aplastic/hypoplastic/dysplastic kidneys in 104, reflux in 87 and other condition in 39). Among these patients median age was 9 years, duration of chronic kidney disease was 7 years and age at first visit with a urologist was less than 1 year. Of the patients 67% were male, 67% were white and 21% had a low birth weight. Median height was in the 24th percentile. Median glomerular filtration rate as measured by iohexol plasma disappearance was 44.8 ml/min/1.73 m(2). Median glomerular filtration rate as estimated by the Chronic Kidney Disease in Children bedside equation was 44.3 ml/min/1.73 m(2) (bias = -0.5, 95% CI -1.7 to 0.7, p = 0.44). Underlying urological causes of chronic kidney disease were present in 59% of study participants. These children were diagnosed early in life, and many had low birth weight and growth delay. There is good agreement between the newly developed Chronic Kidney Disease in Children estimating equations and measured glomerular filtration rate in this population.

Clinical Characteristics and Outcomes of Patients with Improvement in Renal Function during the Treatment of Decompensated Heart Failure

In the setting of acute decompensated heart failure, worsening renal function (WRF) and improved renal function (IRF) have been previously associated with similar hemodynamic derangements and poor prognosis. Our aim was to further characterize the characteristics and subsequent outcomes of patients experiencing IRF. Consecutive patients with a discharge diagnosis of congestive heart failure at the Hospital of the University of Pennsylvania were reviewed. IRF was defined as a ≥20% improvement and WRF as a ≥20% deterioration in glomerular filtration rate. Overall, 903 patients met eligibility criteria, 31.4% experiencing IRF. Baseline venous congestion/right sided cardiac dysfunction was more common (p≤0.04) and volume of diuresis (p=0.003) was greater in patients with IRF. IRF was associated with a greater incidence of pre-admission (OR=4.2, p<0.0001) and post-discharge (OR=1.8, p=0.006) WRF. IRF was associated with increased mortality (adjusted HR=1.4, 95% CI 1.1-1.7, p=0.008), a finding largely restricted to patients with post-discharge recurrence of renal dysfunction (p interaction=0.038). IRF is associated with significantly worsened survival and may represent the resolution of venous congestion induced pre-admission WRF. Notably, this increased mortality was largely restricted to patients in which the renal dysfunction recurred after discharge. Future study of IRF and possible targeted therapy is warranted.

Temporal Trends in the Prevalence of Diabetic Kidney Disease in the United States

Diabetes is the leading cause of kidney disease in the developed world. Over time, the prevalence of diabetic kidney disease (DKD) may increase due to the expanding size of the diabetes population or decrease due to the implementation of diabetes therapies. To define temporal changes in DKD prevalence in the United States. Cross-sectional analyses of the Third National Health and Nutrition Examination Survey (NHANES III) from 1988-1994 (N = 15,073), NHANES 1999-2004 (N = 13,045), and NHANES 2005-2008 (N = 9588). Participants with diabetes were defined by levels of hemoglobin A(1c) of 6.5% or greater, use of glucose-lowering medications, or both (n = 1431 in NHANES III; n = 1443 in NHANES 1999-2004; n = 1280 in NHANES 2005-2008). Diabetic kidney disease was defined as diabetes with albuminuria (ratio of urine albumin to creatinine ≥30 mg/g), impaired glomerular filtration rate (<60 mL/min/1.73 m(2) estimated using the Chronic Kidney Disease Epidemiology Collaboration formula), or both. Prevalence of albuminuria was adjusted to estimate persistent albuminuria. The prevalence of DKD in the US population was 2.2% (95% confidence interval [CI], 1.8%-2.6%) in NHANES III, 2.8% (95% CI, 2.4%-3.1%) in NHANES 1999-2004, and 3.3% (95% CI, 2.8%-3.7%) in NHANES 2005-2008 (P <.001 for trend). The prevalence of DKD increased in direct proportion to the prevalence of diabetes, without a change in the prevalence of DKD among those with diabetes. Among persons with diabetes, use of glucose-lowering medications increased from 56.2% (95% CI, 52.1%-60.4%) in NHANES III to 74.2% (95% CI, 70.4%-78.0%) in NHANES 2005-2008 (P <.001); use of renin-angiotensin-aldosterone system inhibitors increased from 11.2% (95% CI, 9.0%-13.4%) to 40.6% (95% CI, 37.2%-43.9%), respectively (P <.001); the prevalence of impaired glomerular filtration rate increased from 14.9% (95% CI, 12.1%-17.8%) to 17.7% (95% CI, 15.2%-20.2%), respectively (P = .03); and the prevalence of albuminuria decreased from 27.3% (95% CI, 22.0%-32.7%) to 23.7% (95% CI, 19.3%-28.0%), respectively, but this was not statistically significant (P = .07). Prevalence of DKD in the United States increased from 1988 to 2008 in proportion to the prevalence of diabetes. Among persons with diabetes, prevalence of DKD was stable despite increased use of glucose-lowering medications and renin-angiotensin-aldosterone system inhibitors.

Evaluation of a new immunoassay for cystatin C, based on a double monoclonal principle, in men with normal and impaired renal function

Background.Elevated cystatin C in blood reflects impaired glomerular filtration rate (GFR), but current cystatin C assays, based on polyclonal antibodies and immunoturbidimetric or nephelometric detection, have several limitations. We evaluated a new immunoassay based on monoclonal antibodies in samples from patients with and without chronic kidney disease (CKD).Methods.The study enrolled 170 men without known CKD (Group A) and 104 men with CKD (Group B). All patients were assessed with iohexol clearance, plasma creatinine and plasma cystatin C by a conventional particle-enhanced immunoturbidimetric assay (PETIA) and by the new double monoclonal assay. In Group A, three serial blood draws were performed at median intervals of 4 h and 12 days between samples, to also allow assessments of the variability in cystatin C values with the new assay. Concordance correlation coefficients and the 95% limits of agreement were used to estimate the agreement of reciprocal cystatin C and reciprocal creatinine with iohexol clearance.Results.Median iohexol clearance (mL/min/1.73 m2) was 81 [interquartile range (IQR) 70, 92] in Group A and 23 (IQR 16, 34) in Group B. The concordance correlation with GFR for the new cystatin C assay compared to the established assay was similar in Group A (0.441 versus 0.465) but higher in Group B (0.680 versus 0.593). Cystatin C measured by both assays exhibited closer agreement with GFR than creatinine. The agreement between the two cystatin C assays was high, with concordance correlations of 0.815 in Group A and 0.935 in Group B. Compared to the conventional assay, the new assay tended to yield lower values of cystatin C at the low end of the range in Group A. The new cystatin C assay exhibited small intraindividual variability across serial samples (coefficient of variation ≤6%).Conclusions.In this first clinical evaluation, the new cystatin C assay performed similarly to the established PETIA in patients with normal GFR and better in patients with CKD. The new assay may offer an alternative to current commercial assays to detect and monitor impaired kidney function.

Efectos de la circulación extracorpórea sobre el filtrado glomerular en la cirugía cardiovascular pediátrica

Objective: know how extracorporeal circulation affects renal function taking as marker the impairment of the glomerular filtration rate. Material and Method: we performed a prospective analytical observational study in 63 pediatric patients that underwent elective cardiac surgery with extracorporeal circulation in the Pediatric Cardiac Center ¨William Soler¨ between october 2009 and april 2010. Variations of glomerular filtration rate during extracorporeal circulation were calculated by the Schwartz method and blood samples were taken to determine plasma creatinine values before and after extracorporeal circulation. Data were processed with the SPSS statistical package version 11.5.1. Results were expressed as mean, standard deviation and percentage. We considered that difference or significant association existed if the probability associated to the applied test was less than 0,05 (p<0,05). Analysis was performed by non-parametric testing given n < 30 and through related samples. Results: the decline in glomerular filtration rate post extracorporeal circulation was not associated to the type of cardiopathy (p<0,056) but it was associated to its previous state (p<0,000). The duration of extracorporeal circulation contributes significantly to the deterioration of the glomerular filtration rate (p<0,021); this did not happen with the aortic clamping time (p<0,06). The volume of urine obtained during the duration of extracorporeal circulation (p<0,051) and during the trans-operative period (p<0,056) was not an index of appropriate renal function measured by glomerular filtration rate. Conclusions: extracorporeal circulation affects significantly the renal function taking as a marker the impairment of glomerular filtration rate.

2054 EFFECT OF GLOMERULAR FILTRATION RATE ON 24-HOUR URINE ANALYSIS

You have accessJournal of UrologyStone Disease: Basic Research1 Apr 20112054 EFFECT OF GLOMERULAR FILTRATION RATE ON 24-HOUR URINE ANALYSIS Adam Kadlec, Kristin Greco, Zach Fridirici, Daniel Gerber, and Thomas Turk Adam KadlecAdam Kadlec Maywood, IL More articles by this author , Kristin GrecoKristin Greco Maywood, IL More articles by this author , Zach FridiriciZach Fridirici Maywood, IL More articles by this author , Daniel GerberDaniel Gerber Hamilton, NY More articles by this author , and Thomas TurkThomas Turk Maywood, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2285AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We tested the hypothesis that 24-hour urine analyses collected from patients with low glomerular filtration rates (GFR <60) would differ from normal counterparts. METHODS We used the Modification of Diet in Renal Disease (MDRD) equation to calculate GFR in 146 patients who gave a 24-hour urine analysis after undergoing urologic surgery for kidney stones. Patients were grouped by GFR with a cutpoint of 60 ml/hr. A two-sample t-test was used to calculate p-values. RESULTS Patients with GFR <60 had less urinary calcium excretion and a lower urinary pH. They also excreted more oxalate and sodium. Other commonly measured parameters did not significantly differ between groups. Supersaturation indices (SSI) did not differ between groups. CONCLUSIONS The levels of clinically relevant urinary minerals vary depending on GFR. Patients with impaired GFR have lower urine pH than normal counterparts. Table 1. Urinary excretion of certain lithogenic minerals is dependent on GFR status GFR <60 GFR ≥60 p-value Calcium (mg/day) 149±108 213±167 0.033 Oxalate (mg/day) 40±20 33±15 0.022 Uric Acid (mg/day) 485±237 558±216 0.089 Citrate (mg/day) 433±352 511±343 0.242 Urine pH 5.79±0.63 6.13±0.59 0.005 Volume (L/day) 1.94±0.69 1.86±0.74 0.559 Sodium (meq/day) 194±86 157±75 0.013 Sulfate (mmol/day) 17±10 16±8 0.675 Phosphorus (mg/day) 960±405 889±331 0.298 Magnesium (mg/day) 84±42 100±115 0.430 Table 2. Supersaturation Indices (SSI) Did Not Differ Between Groups SSI GFR <60 GFR >60 p-value Calcium Oxalate 1.40±1.13 1.79±1.12 0.073 Brushite 1.86±5.44 1.73±1.36 0.825 Monosodium Urate 2.05±1.95 2.60±2.26 0.194 Struvite 0.30±0.56 2.93±5.95 0.142 Uric Acid 1.68±1.26 2.21±7.70 0.684 © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e822 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Adam Kadlec Maywood, IL More articles by this author Kristin Greco Maywood, IL More articles by this author Zach Fridirici Maywood, IL More articles by this author Daniel Gerber Hamilton, NY More articles by this author Thomas Turk Maywood, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Long-term Renal Outcomes of Patients With Type 1 Diabetes Mellitus and Microalbuminuria&lt;subtitle&gt;An Analysis of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Cohort&lt;/subtitle&gt;&lt;alt-title&gt;Microalbuminuria Outcomes in Type 1 Diabetes&lt;/alt-title&gt;

Microalbuminuria is a common diagnosis in the clinical care of patients with type 1 diabetes mellitus. Long-term outcomes after the development of microalbuminuria are variable.We quantified the incidence of and risk factors for long-term renal outcomes after the development of microalbuminuria in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. The DCCT randomly assigned 1441 persons with type 1 diabetes to intensive or conventional diabetes therapy, and participants were subsequently followed up during the observational EDIC study. During the DCCT/EDIC study, 325 participants developed incident persistent microalbuminuria (albumin excretion rate, ≥30 mg/24 h at 2 consecutive study visits). We assessed their subsequent renal outcomes, including progression to macroalbuminuria (albumin excretion rate, ≥300 mg/24 h at 2 consecutive visits), impaired glomerular filtration rate (estimated glomerular filtration rate, <60 mL/min/1.73 m(2) at 2 consecutive study visits), end-stage renal disease, and regression to normoalbuminuria (albumin excretion rate, <30 mg/24 h at 2 consecutive visits).The median follow-up period after persistent microalbuminuria diagnosis was 13 years (maximum, 23 years). Ten-year cumulative incidences of progression to macroalbuminuria, impaired glomerular filtration rate, end-stage renal disease, and regression to normoalbuminuria were 28%, 15%, 4%, and 40%, respectively. Albuminuria outcomes were more favorable with intensive diabetes therapy, lower glycated hemoglobin level, absence of retinopathy, female sex, lower blood pressure, and lower concentrations of low-density lipoprotein cholesterol and triglycerides. Lower glycated hemoglobin level, absence of retinopathy, and lower blood pressure were also associated with decreased risk of impaired glomerular filtration rate.After the development of persistent microalbuminuria, progression and regression of kidney disease each commonly occur. Intensive glycemic control, lower blood pressure, and a more favorable lipid profile are associated with improved outcomes.

Papel protector del tratamiento antirretroviral en el deterioro de la función renal en una cohorte de pacientes infectados por el virus de la inmunodeficiencia humana

Background and objective To assess changes in renal function in a cohort of patients infected with the human immunodeficiency virus (HIV) and describe which factors are associated with deterioration. Patients and methods This was a prospective transversal study. The follow-up period was 12 months. Data were collected at baseline and one year including the glomerular filtration rate (GFR). We analyzed epidemiological data, comorbidities, CD4 lymphocytes, viral load, and AIDS status. Results A total of 365 patients. Three hundred and thirteen (85%) were under highly active antiretroviral therapy (HAART); the median CD4 was 606 ± 314 and the CV was undetectable in 85%. At 1-year, we found a mean deterioration in the GFR of 9.7 ml/h. Eighty patients (21.8%) had a fall in GFR > 10 ml/h, while in 20 patients (5.8%) it was > 30 ml/h. An association was found regarding age, treatment with didanosine (DDI) and males (OR 1.89 95% CI 1.3 to 4.08, OR 2.3 95% CI 1.9 to 23 and OR 3.47 95% CI 1.6 to 14.20 respectively). We found a protective role of being under HAART (OR 0.54, 95% CI, 0.25 to 0.8). Conclusions There was a protective role of HAART in the deterioration of GFR of patients with HIV infection. Male gender, age and use of DDI were associated with worsening renal function. Tenofovir and protease inhibitors were not associated with further deterioration of renal function.

Impaired GFR is the most important determinant for FGF-23 increase in chronic kidney disease

Objectives It is unclear whether fibroblast growth factor-23 (FGF-23) increases in response to phosphate accumulation or to decrease clearance in chronic kidney disease (CKD) as is the case with other low molecular weight proteins such as cystatin C (CysC). Design and methods This cross-sectional study measured serum FGF-23, CysC, and other serum markers of bone metabolism in 69 patients, aged 18 months–24 years, with various stages of CKD (eGFR = 11–214 mL/min). Results FGF-23 levels were significantly correlated with CysC and parathyroid hormone levels (PTH) on univariate non-linear regression analysis. In multivariate linear regression analysis, log (CysC) ( β = 0.660, p < 0.0001), log (PTH) ( β = 0.038, p = 0.37), and phosphate ( β = 0.222, p = 0.028) explained 69.1% of the variance of FGF-23. Conclusions CysC had the largest unique contribution to FGF-23 variance in this model, supporting the hypothesis that renal clearance may be the most responsible factor for elevated FGF-23 levels in early stages of CKD.

Is Insulin Resistance a Risk Factor for the Progression of Chronic Kidney Disease?

Background: The aim of this research was to establish whether there is a link between insulin resistance (IR) and glomerular filtration rate (GFR), and assess whether insulin-resistant subjects experience a more rapid deterioration in GFR. Methods: We enrolled 73 non-diabetic chronic kidney disease (CKD) stage 2–4 patients. All blood samples were taken after 10 h of overnight fasting. Fasting blood glucose (FBG), creatinine, uric acid, albumin, cholesterol, triglyceride, insulin, HbA1c, high-sensitivity C-reactive protein (hs-CRP) and intact parathyroid hormone (iPTH) levels as well as proteinuria were analyzed. Patients were followed up for a mean of 30 (24–35) months and renal and metabolic parameters were compared in conjunction with a homeostasis model assessment of IR (HOMA-IR) between the entry and the end of the study period. CKD progression was assessed by recording renal endpoints, which included end-stage renal disease, requiring renal replacement therapy, or overall mortality. Results: The study patients were divided into group 1 (n = 36), without IR, and group 2 (n = 37), with IR. Group 2 patients had a higher FBG (p = 0.003) and insulin level (p = 0.001) compared to group 1. The baseline and end of study systolic (p = 0.007) and diastolic (p = 0.001) blood pressures were decreased in group 1. In group 2, FBG (p = 0.008), HbA1c (p = 0.009), systolic (p = 0.024) and diastolic (p = 0.001) blood pressures and CRP (p = 0.047) were decreased. In group 2, 8 patients reached renal endpoints while in group 1, 9 patients reached study endpoints. HOMA-IR was not significantly higher among 17 patients who reached the renal endpoint than among the 56 who did not. At baseline, those patients who reached the renal endpoint showed lower GFR (p = 0.001), higher iPTH (p = 0.004) and hs-CRP (p = 0.002) levels. Conclusion: There was no significant difference in GFR at the end of the study between patients who had or did not have IR. Furthermore, HOMA-IR was not significantly different in patients with or without renal endpoints.

Removal of aprotinin from low-dose aprotinin/tranexamic acid antifibrinolytic therapy increases transfusion requirements in cardiothoracic surgery

This retrospective study investigated whether withdrawal of aprotinin from combined low-dose aprotinin/tranexamic acid (TXA) antifibrinolytic therapy altered postoperative blood loss and transfusion requirements in patients undergoing cardiothoracic surgery employing cardiopulmonary bypass (CPB). The study included data from patients receiving a combination of low-dose aprotinin (2×10(6)KIU in CPB prime; n=615) and 2000mg TXA or patients receiving TXA only (n=587). In both groups, TXA was given after protamine administration. Study endpoints were blood loss, transfusion requirements and reoperation. There were no differences in EuroSCORE, CPB time, antiangial medication and baseline coagulation parameters between groups. There were more males in the TXA group (85%) as compared to the TXA+aprotinin group (77%; P=0.02). Postoperative blood loss (0.80±0.69 vs. 0.66±0.52l; P=0.001) and transfusion of fresh frozen plasma (0.6±0.7 vs. 0.4±0.6U; P<0.001), packed cells (3.9±5.5 vs. 2.7±3.3U; P<0.001) and platelets (0.7±0.6 vs. 0.5±0.6U; P<0.001) was higher in the TXA group than in patients receiving combined therapy, respectively. There were more reoperations for bleeding in the TXA group (53 vs. 34, respectively; P=0.03) with similar mortality and deterioration in glomerular filtration rate. In conclusion, withdrawal of aprotinin from combined antifibrinolytic therapy is associated with increased blood loss, transfusion requirements and reoperations.

Chronic kidney disease stages 1-3 increase the risk of venous thrombosis.

End-stage renal disease has been associated with venous thrombosis (VT). However, the risk of VT in the early stages of chronic kidney disease (CKD) has not yet been investigated. The aim of this study was to investigate whether CKD patients with stage 1-3 disease are at increased risk of VT. Eight thousand four hundred and ninety-five subjects were included in a prospective cohort study, in which renal function and albuminuria were assessed, starting in 1997-1998, and were followed for the occurrence of VT until 1 June 2007. CKD patients were staged according to the Kidney Disease Outcomes Quality Initiative guidelines, on the basis of 24-h urine albumin excretion and estimated glomerular filtration rates. Objectively verified symptomatic VT was considered to be the endpoint. Of the 8495 subjects, 243 had CKD stage 1, 856 CKD stage 2, and 491 CKD stage 3. During a median follow-up period of 9.2 years, 128 individuals developed VT. The hazard ratios (HRs) for CKD stages 1, 2 and 3 were, respectively, 2.2 [95% confidence interval (CI) 0.9-5.1], 1.9 (95% CI 1.1-3.1) and 1.6 (95% CI 0.9-2.8) relative to those without CKD after adjustment for age, sex, body mass index, hypertension, diabetes, malignancy, and high-sensitivity C-reactive protein. Subjects with CKD stage 3 and albuminuria (≥ 30 mg d(-1)) had an adjusted HR of 3.0, and subjects with CKD stage 3 without albuminuria had an adjusted HR of 1.0. CKD stages 1 and 2, and CKD stage 3 in the presence of albuminuria, are risk factors for VT. The risk of VT is more related to albuminuria than to impaired glomerular filtration rate.

Occult renal dysfunction: a mortality and morbidity risk factor in coronary artery bypass grafting surgery

Elevated preoperative serum creatinine is considered an independent risk factor for postoperative mortality and morbidity in patients undergoing coronary artery bypass grafting. However, the impact of occult renal dysfunction, defined as an impairment of glomerular filtration rate with normal serum creatinine, is still unknown. The aim of this study was to analyze the effects of occult renal dysfunction on early outcomes after coronary artery bypass grafting. This was a retrospective, observational, cohort study of prospectively collected data on 9159 consecutive patients with normal serum creatinine levels undergoing coronary artery bypass grafting between April 1996 and February 2009. Patients were divided into two groups based on preoperative creatinine clearance estimated with the Cockcroft-Gault equation: 5484 patients with a creatinine clearance ≥ 60 mL/min and 3675 patients with a creatinine clearance < 60 mL/min (occult renal dysfunction group). Overall in-hospital mortality was 1%. Occult renal dysfunction was associated with a doubling in the risk of operative mortality (1.4% vs 0.7%; P = .001), postoperative renal dysfunction (5.1% vs 2.5%; P < .0001), and need for dialysis (0.8% vs 0.4%; P = .014). Moreover, occult renal dysfunction increased the risk of stroke (1% vs 0.3%; P < .0001), arrhythmia (28.5% vs 21.2%; P < .0001), and hospital stay > 7 days (36.45 vs 24.5%; P < .0001). In a multivariable analysis adjusting for preoperative risk factors, occult renal dysfunction was confirmed to be an independent predictor of mortality (odds ratio, 1.72), postoperative renal dysfunction (odds ratio, 1.9), dialysis (odds ratio, 1.82), stroke (odds ratio, 2.6) arrhythmia (odds ratio, 1.42), and hospital stay > 7 days (odds ratio, 1.65). Occult renal dysfunction is an independent risk factor for early mortality and morbidity in patients undergoing coronary artery bypass grafting.

Improvement in Renal Function After Late Conversion to Sirolimus-Based Immunosuppression in Composite Tissue Allotransplantation

Improvement in Renal Function After Late Conversion to Sirolimus-Based Immunosuppression in Composite Tissue Allotransplantation