Glomerular Filtration Rate In Group Research Articles

Randomized Trial of Mycophenolate Mofetil Versus Enteric-Coated Mycophenolate Sodium in Primary Renal Transplant Recipients Given Tacrolimus and Daclizumab/Thymoglobulin: One Year Follow-Up

It was of interest to compare enteric-coated mycophenolate sodium (EC-MPS) versus mycophenolate mofetil (MMF) among renal transplant recipients receiving a tacrolimus-based immunosuppressive regimen. Between December 2004 and February 2006, a single-center, open-label randomized trial of MMF (group A, n=75) versus EC-MPS (group B, n=75) was performed in primary renal transplant recipients receiving combined thymoglobulin/daclizumab induction along with reduced tacrolimus dosing and elimination of corticosteroids 1 week postoperatively. The primary endpoint was the incidence rate of acute rejection (AR) during the first 12 months posttransplant; secondary aims were to compare graft and patient survival, renal function, drug dosing and monitoring, gastrointestinal side effects, and other adverse events at 12 months of follow-up. Patient/graft survival in groups A and B were 100%/96% versus 99%/96%, respectively (N.S.). At 12 months, a total of nine patients (6%) experienced biopsy-proven AR, 3% (2/75) vs. 9% (7/75) in the MMF and EC-MPS arms, respectively (N.S.). At 12 months, the geometric mean*/SE serum creatinine concentration and arithmetic mean+/-SE calculated glomerular filtration rate in groups A and B, respectively, were 1.30*/1.03 and 61.4+/-2.0 vs. 1.26*/1.03 and 66.0+/-2.1 (N.S.). Incidence of new onset diabetes mellitus (11% vs. 11%), infections requiring hospitalization (13% vs. 15%), and gastrointestinal side effects (36% vs. 32%) appeared equivalent (N.S.). Early efficacy and toxicity were equivalent between the two study arms. Optimizing either MMF or EC-MPS along with a combined thymoglobulin/daclizumab induction, low tacrolimus dosing and steroid avoidance resulted in a low AR rate and an acceptably high renal function at 12 months.

Prevalence, Predictors, and Prognostic Value of Renal Dysfunction in Adults With Congenital Heart Disease

Renal insufficiency in patients with ischemic heart disease and acquired heart failure is associated with higher mortality and morbidity. We studied the prevalence of renal dysfunction in adult patients with congenital heart disease (ACHD) and its relation to outcome. A total of 1102 adult patients with congenital heart disease (age 36.0+/-14.2 years) attending our institution between 1999 and 2006 had creatinine concentration measured. Glomerular filtration rate (GFR) was calculated with the Modification of Diet in Renal Disease equation. Patients were divided into groups of normal GFR (> or =90 mL . min(-1) . 1.73 m(-2)), mildly impaired GFR (60 to 89 mL . min(-1) . 1.73 m(-2)), and moderately/severely impaired GFR (<60 mL . min(-1) . 1.73 m(-2)). Survival was compared between GFR groups by Cox regression. Median follow-up was 4.1 years, during which 103 patients died. Renal dysfunction was mild in 41% of patients and moderate or severe in 9%. A decrease in GFR was more common among patients with Eisenmenger physiology, of whom 72% had reduced GFR (<90 mL . min(-1) . 1.73 m(-2), P<0.0001 compared with the remainder), and in 18%, this was moderate or severe (P=0.007). Renal dysfunction had a substantial impact on mortality (propensity score-weighted hazard ratio 3.25, 95% CI 1.54 to 6.86, P=0.002 for moderately or severely impaired versus normal GFR). Deranged physiology in adult patients with congenital heart disease is not limited to the heart but also affects the kidney. Mortality is 3-fold higher than normal in the 1 in 11 patients who have moderate or severe GFR reduction.

ENDOTHELIN B RECEPTORS PRESERVE RENAL BLOOD FLOW IN A NORMOTENSIVE MODEL OF ENDOTOXIN-INDUCED ACUTE KIDNEY DYSFUNCTION

The aim was to investigate the role of endothelin 1 receptor subtypes in the early renal response to lipopolysaccharide (LPS) during normotensive endotoxemia with acute kidney dysfunction. Endotoxemia was induced in thiobutabarbital-anesthetized rats (n = 9 per group) by infusion of LPS (dosage, 1 mg/kg per hour i.v.). The study groups (1) sham-saline, (2) LPS-saline, (3) LPS-BQ123, (4) LPS-BQ788 and (5) LPS-BQ123 + BQ788 received isotonic saline, the ETA receptor antagonist BQ-123 (dosage, 30 nmol/kg per minute i.v.), and/or the ETB receptor antagonist BQ-788 (dosage, 30 nmol/kg per minute i.v.) before and during 2 h of LPS infusion. Renal clearance measurements, renal blood flow (RBF), and cortical and outer medullary perfusion (laser-Doppler flowmetry) and oxygen tension (Clark-type microelectrodes) were analyzed throughout. Before LPS administration, there were no significant differences between groups in glomerular filtration rate (GFR), RBF, or in cortical (CLDF) and outer medullary perfusion. However, mean arterial pressure (MAP) was elevated in LPS-BQ788 group compared with LPS-BQ123 + BQ788 group (P < 0.05). In saline-treated rats, endotoxin induced an approximate 35% reduction in GFR (P < 0.05), without significant effects on MAP, RBF, or on CLDF and cortical PO2. In addition, LPS increased outer medullary perfusion and PO2 (P < 0.05). The fractional urinary excretion rates of sodium, potassium, and water were not significantly different in LPS-saline group compared with sham-saline group. Neither selective nor combined ETA and ETB receptor blockade improved GFR. In BQ-788-infused rats, endotoxin produced marked reductions in RBF (-18% +/- 4% [P < 0.05]) and CLDF (-18% +/- 2% [P < 0.05]). Similarly, endotoxin decreased RBF (-14% +/- 3% [P < 0.05]) and CLDF (-10% +/- 2% [P < 0.05]) in LPS-BQ123 + BQ788 group. Endotoxin reduced MAP (-22% +/- 4% [P < 0.05]) in BQ-123-treated rats but did not significantly influence MAP in other groups. We conclude that in early normotensive endotoxemia, ETB receptors exert a renal vasodilator influence and contribute to maintain normal RBF.

Albuminuria and Estimated GFR 5 Years After Escherichia coli O157 Hemolytic Uremic Syndrome: An Update

Knowledge of the long-term prognosis of patients with diarrhea-associated hemolytic uremic syndrome (HUS) is important for patient counseling and follow-up. Estimates in the literature are highly variable, and previous studies did not use a healthy control group to establish outcomes attributable to HUS. Prospective cohort study. 19 children who recovered from HUS after contamination of their municipal water supply by Escherichia coli O157:H7. Outcomes of children who recovered from HUS were compared with a control group of 64 children who were healthy at the time of the outbreak. Both groups were similar in their demographics and follow-up testing. Proteinuria, blood pressure, glomerular filtration rate (GFR) estimated by using serum creatinine or cystatin C level, and biochemical measures 5 years after the outbreak. More children who recovered from HUS showed microalbuminuria than controls (20% versus 3%; relative risk, 6.0; 95% confidence interval, 1.1 to 32.8). There were no differences between groups in blood pressure or GFR when estimated by using serum creatinine level. GFR estimated by using cystatin C level was lower after HUS compared with controls (100 versus 110 mL/min/1.73 m(2); P = 0.02), but no child had a GFR less than 80 mL/min/1.73 m(2). Other results, including fasting glucose, albumin, and C-reactive protein levels, did not differ between groups. Although the homogenous nature of this outbreak is a strength, long-term results may generalize less well to patients with other strains of toxigenic E coli or in other settings. The prognosis of patients with HUS in this cohort was better than in other studies. Ongoing follow-up will clarify the clinical relevance of microalbuminuria and mild decreases in GFR 5 years after HUS recovery.

Outcome of Renal Insufficiency Patients Undergoing Coronary Artery Bypass Graft Surgery

Renal insufficiency (RI) is a prognostic marker in patients with cardiovascular disease. In this study, the latest standard of glomerular filtration rate (GFR) calculation, that is the modification of diet in renal disease (MDRD) study equation, is used to measure the difference in the outcome of coronary artery bypass graft (CABG) surgery in various GFR groups. Between 2000 and 2005, 1,055 patients underwent CABG surgery and were categorized into 5 groups according to the National Kidney Foundation guidelines: stage 1 = normal renal function; stage 2 = mild RI; stage 3 = moderate RI; stage 4 = severe RI; stage 5 = end-stage renal failure (excluded). Precautions were taken in RI patients to avoid perioperative hypotension, fluid overload and limited cardioplegia; cardiopulmonary bypass time was kept at a minimum by performing an essential number of grafts only. Thirty-day mortality occurred in 5 of 1,052 patients (0.48%) with no statistical difference in stages 1–4. There was increase in bleed requiring reoperation and total complications from stages 1 to 4, but it was not statistically significant. Preoperative renal dysfunction in CABG surgery patients is an important predictor of outcome. Patients undergoing CABG surgery can have acceptable results without significant increase in complications and mortality provided that risk factors are minimized perioperatively.

Association of Glomerular Filtration Rate With Unsuccessful Primary Percutaneous Coronary Intervention and Subsequent Mortality in Patients With Acute Myocardial Infarction From the HIJAMI Registry

Outcomes after percutaneous coronary intervention (PCI) for patients with acute myocardial infarction (AMI) complicated by renal insufficiency have not been well described. The aims of this study were to evaluate the association of estimated glomerular filtration rate (GFR) and risk of unsuccessful PCI for AMI, and to evaluate the prognostic importance of PCI success in patients with renal insufficiency. From the Heart Institute of Japan Acute Myocardial Infarction (HIJAMI) registry, 1,706 patients undergoing primary PCI were analyzed. The adjusted odds ratios for unsuccessful PCI of GFR 30-60 and <30 ml . min(-1) . 1.73 m(-2) were 1.97 (95% confidence interval (CI): 1.22-3.18) and 2.56 (95%CI: 1.13-5.78), respectively. During the mean follow-up period of 29 months, the adjusted hazard ratios for death of successful compared with unsuccessful PCI were 1.0 (reference) compared with 2.04 (95%CI: 0.87-4.81) in the highest GFR group, 1.51 (95%CI: 1.11-2.06) compared with 2.07 (95%CI: 1.19-3.62) in the intermediate GFR group, and 2.69 (95%CI: 1.72-4.22) compared with 10.07 (95%CI: 4.91-20.5) in the lowest GFR group. Decreased GFR was associated with the risk of unsuccessful primary PCI. Moreover, unsuccessful PCI was associated with strikingly poor long-term survival in patients with GFR <30 ml .min(-1) . 1.73 m(-2). Steady success is essential when using PCI for such a high-risk population.

Performance and comparison of the Cockcroft–Gault and simplified Modification of Diet in Renal Disease formulae in estimating glomerular filtration rate in a Chinese Type 2 diabetic population

Our aim was to assess performances of the Cockcroft-Gault and simplified Modification of Diet in Renal Disease (MDRD) formulae in estimating glomerular filtration rate (GFR) in Chinese diabetic populations and their association with vascular risks. A total of 1009 patients with Type 2 diabetes were categorized into low estimated GFR groups (GFR < 60 ml/min/1.73 m(2)) and control groups by the two equations. The performances of these formulae were assessed at different stages of kidney function. Carotid artery intima-media thickness (IMT) and the prevalence of diabetic retinopathy or albuminuria were compared among the groups. The ability of these formulae to identify established vascular risk markers using sensitivity, specificity, positive and negative predictive values were also compared. The prevalence of low estimated GFR was 32.7% with the Cockcroft-Gault formula and 5.2% with the MDRD formula, respectively. In low estimated GFR subjects by the MDRD formula, IMT was significantly thicker than those by the Cockcroft-Gault formula (1.2 mm vs. 1.0 mm; P < 0.05), with a higher prevalence of albuminuria (78.4 vs. 52.8%, P < 0.05) and diabetic retinopathy (46.5 vs. 30.5%; P < 0.05). The Cockcroft-Gault formula gave a specificity of 71.7% and a sensitivity of 37.0%, and the MDRD formula gave a specificity of 96.6% and a sensitivity of 7.9% in estimating low GFR relevant for established vascular risks. These formulae performed differently in Chinese diabetic populations. The simplified MDRD formula is minimally superior to the Cockcroft-Gault formula for its high specificity and positive predictive values in estimating low GFR relevant for vascular risks.

Impact of renal dysfunction and glucometabolic status on one month mortality after acute myocardial infarction

Patients with impaired glucometabolic status or renal function have a higher mortality after acute myocardial infarction. It is unclear whether this higher risk is independent or related to the quality of care. In a prospective registry, stress hyperglycaemia (SH) was defined as glucose level>140 mg/dl. Renal function was assessed by the glomerular filtration rate (GFR): normal (>/=60), mild (30-60) and severe dysfunction (<30 ml/min/1.72 m(2)). The level of risk was assessed by the TIMI risk index and the quality of care by the rate of use of five guidelines-recommended treatments. Among the 1388 patients included, 23% had diabetes, 16% had SH, renal function was normal in 55%, mildly impaired in 35% and severely impaired in 9.5%. At one month, the mortality rate was higher in patients with SH (18%) as compared with diabetics (9%) or those with normal glucometabolic status (5%). Similarly, the mortality rate was higher in those with impaired renal function. Multivariable analysis identified SH, GFR group, TIMI risk index, ST segment elevation MI and quality of care as independent predictors of one-month mortality. In patients with acute MI, SH and GFR<30 ml/min/m(2) are independent predictors of mortality after adjustment for the level of risk and acute care.

Renal Outcomes in High-Risk Hypertensive Patients Treated With an Angiotensin-Converting Enzyme Inhibitor or a Calcium Channel Blocker vs. a Diuretic. A Report From the Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Background: This study was performed to determine whether, in high-risk hypertensive patients with a reduced glomerular filtration rate (GFR), treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of renal disease outcomes compared with treatment with a diuretic. Methods: We conducted post hoc analyses of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertensive participants 55 years or older with at least 1 other coronary heart disease risk factor were randomized to receive chlorthalidone, amlodipine, or lisinopril for a mean of 4.9 years. Renal outcomes were incidence of end-stage renal disease (ESRD) and/or a decrement in GFR of 50% or more from baseline. Baseline GFR, estimated by the simplified Modification of Diet in Renal Disease equation, was stratified into normal or increased (90 mL /min per 1.73 m 2 , n=8126), mild reduction (60-89 mL/min per 1.73 m 2 , n=18 109), or moderate-severe reduction (60 mL/min per 1.73 m 2 , n=5662) in GFR. Each stratum was analyzed for effects of the treatments on outcomes. Results: In 448 participants, ESRD developed. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking amlodipine in the mild (relative risk [RR], 1.47; 95% confidence interval [CI], 0.97-2.23) or moderate-severe (RR,0.92; 95% CI, 0.68-1.24) reduction in GFR groups. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking lisinopril in the mild (RR, 1.34; 95% CI, 0.87-2.06) or moderate-severe (RR,0.98; 95% CI, 0.73-1.31) reduction in GFR groups. In patients with mild and moderate-severe reduction in GFR, the incidence of ESRD or 50% or greater decrement in GFR was not significantly different in patients treated with chlorthalidone compared with those treated with amlodipine (odds ratios, 0.96 [P = .74] and 0.85 [P=.23], respectively) and lisinopril (odds ratios, 1.13 [P=.31] and 1.00 [P=.98], respectively). No difference in treatment effects occurred for either end point for patients taking amlodipine or lisinopril compared with those taking chlorthalidone across the 3 GFR subgroups, either for the total group or for participants with diabetes at baseline. At 4 years of follow-up, estimated GFR was 3 to 6 mL/min per 1.73 m 2 higher in patients assigned to receive amlodipine compared with chlorthalidone, depending on baseline GFR stratum. Conclusions: In hypertensive patients with reduced GFR, neither amlodipine nor lisinopril was superior to chlorthalidone in reducing the rate of development of ESRD or a 50% or greater decrement in GFR. Participants assigned to receive amlodipine had a higher GFR than those assigned to receive chlorthalidone, but rates of development of ESRD were not different between the groups. Arch Intern Med. 2005;165:936-946

Renal Outcomes in High-Risk Hypertensive Patients Treated With an Angiotensin-Converting Enzyme Inhibitor or a Calcium Channel Blocker vs a Diuretic

This study was performed to determine whether, in high-risk hypertensive patients with a reduced glomerular filtration rate (GFR), treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of renal disease outcomes compared with treatment with a diuretic. We conducted post hoc analyses of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertensive participants 55 years or older with at least 1 other coronary heart disease risk factor were randomized to receive chlorthalidone, amlodipine, or lisinopril for a mean of 4.9 years. Renal outcomes were incidence of end-stage renal disease (ESRD) and/or a decrement in GFR of 50% or more from baseline. Baseline GFR, estimated by the simplified Modification of Diet in Renal Disease equation, was stratified into normal or increased (> or =90 mL /min per 1.73 m(2), n = 8126), mild reduction (60-89 mL /min per 1.73 m(2), n = 18 109), or moderate-severe reduction (<60 mL /min per 1.73 m(2), n = 5662) in GFR. Each stratum was analyzed for effects of the treatments on outcomes. In 448 participants, ESRD developed. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking amlodipine in the mild (relative risk [RR], 1.47; 95% confidence interval [CI], 0.97-2.23) or moderate-severe (RR, 0.92; 95% CI, 0.68-1.24) reduction in GFR groups. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking lisinopril in the mild (RR, 1.34; 95% CI, 0.87-2.06) or moderate-severe (RR, 0.98; 95% CI, 0.73-1.31) reduction in GFR groups. In patients with mild and moderate-severe reduction in GFR, the incidence of ESRD or 50% or greater decrement in GFR was not significantly different in patients treated with chlorthalidone compared with those treated with amlodipine (odds ratios, 0.96 [P = .74] and 0.85 [P = .23], respectively) and lisinopril (odds ratios, 1.13 [P = .31] and 1.00 [P = .98], respectively). No difference in treatment effects occurred for either end point for patients taking amlodipine or lisinopril compared with those taking chlorthalidone across the 3 GFR subgroups, either for the total group or for participants with diabetes at baseline. At 4 years of follow-up, estimated GFR was 3 to 6 mL /min per 1.73 m(2) higher in patients assigned to receive amlodipine compared with chlorthalidone, depending on baseline GFR stratum. In hypertensive patients with reduced GFR, neither amlodipine nor lisinopril was superior to chlorthalidone in reducing the rate of development of ESRD or a 50% or greater decrement in GFR. Participants assigned to receive amlodipine had a higher GFR than those assigned to receive chlorthalidone, but rates of development of ESRD were not different between the groups.

Reduced glomerular filtration rate in asymptomatic diabetic patients: Predictor of increased risk for cardiac events independent of albuminuria

This study aimed to investigate the prevalence of a reduced glomerular filtration rate (GFR) with and without albuminuria and its ability to predict cardiac events in asymptomatic diabetic patients undergoing stress-rest thallium-201 myocardial perfusion single-photon emission computed tomography. Diabetic patients have a higher prevalence of asymptomatic coronary heart disease. Therefore, identifying predictors of cardiac events in asymptomatic diabetic patients is needed. In 269 asymptomatic patients, baseline evaluation included diabetes-related complications, including creatinine clearance (CrCl) and albuminuria. During follow-up (mean 2.3 +/- 1.0 years), all cardiac events were recorded. Seventy-seven patients (29%) had a reduced GFR defined by CrCl <60 ml/min/1.73 m(2). Compared with the 177 patients with CrCl >/=60 ml/min/1.73 m(2), the reduced GFR group was older (p < 0.0001), had a longer duration of diabetes (p = 0.002), and had a higher prevalence of albuminuria (p = 0.04). Nevertheless, 35% of the reduced GFR group had normoalbuminuria. Patients with reduced GFR had a significant two-fold increase in total cardiac events (unstable angina, nonfatal myocardial infarction, and cardiac procedures) (25% vs. 13%, p = 0.019), and multivariate analysis found that reduced GFR was an independent predictor of cardiac events (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.1 to 4.46). Other independent predictors of cardiac events included stress-induced abnormal myocardial perfusion imaging (OR 3.1, 95% CI 1.3 to 7.5), an electrocardiographic ischemic response (OR 2.7, 95% CI 1.01 to 7.14), and peripheral artery disease (OR 2.1, 95% CI 1.05 to 4.23); however, albuminuria was not. A reduced GFR was common in our group of asymptomatic diabetic patients and was associated with a two-fold increase in cardiac events. Multivariate analysis found that reduced GFR independent of albuminuria was a significant predictor of cardiac events.

Urinary endothelin-1 excretion according to morpho-functional damage lateralization in reflux nephropathy.

Reflux nephropathy (RN) is a pathophysiological human model of reduced nephron reserve, due to loss of renal mass, but little information exists about the role of urinary endothelin-1 (uET-1) in this disease. The aim of this study was to assess the presence of uET-1-like-immunoreactivity (uET-1L) in RN patients, particularly if lateralized renal damage existed. Thirty patients with vescico-ureteral reflux (VUR) and consequent RN, were studied. The presence of VUR was established by voiding cysto-urethrography. RN was assessed and graded by 99mTc-dimercapto-succinic acid scan (DMSA). Renal plasma flow (ERPF) was evaluated by (123)I-Hippuran renal sequential scintigraphy, and glomerular filtration rate (GFR) by creatinine clearance. Forty-five healthy subjects were selected as a control group. uET-1L excretion, in both affected and control groups, was assayed. Mann-Whitney U test showed a significant difference between control and patient groups in both GFR and uET-1L. A good correlation between DMSA grading, single kidney clearance and VUR grade was shown. A significant relationship was also shown between uET-1L and both ERPF and GFR. Patients with RN were divided into two subgroups according to functional damage lateralization. Between the two groups, a significant difference was found only for uET-1L when GFR was applied as a covariate in ANCOVA analysis. Our preliminary results confirmed the increase of urinary ET-1L excretion in RN, especially when renal functional injury was lateralized.

Cystatin C is not more sensitive than creatinine for detecting early renal impairment in patients with diabetes

This study evaluated serum cystatin C as a potential new marker of glomerular filtration rate (GFR) in 49 patients who had steady-state diabetes with early renal impairment. We determined the correlation between GFR measured by chromium 51-labeled EDTA and levels of serum cystatin C, serum creatinine, serum [beta ]2-microglobulin, endogenous creatinine clearance, and Cockcroft formula. Sensitivity and specificity for the diagnosis of renal failure, defined as a GFR less than either 80 or 60 mL/min/1.73 m2, were calculated by receiver operating characteristic (ROC) curves for creatinine, cystatin C, and [beta ]2-microglobulin. Finally, we compared mean values of these three serum parameters in patients grouped according to GFR using the two definitions of renal failure. Correlation coefficients with GFR were [minus ]0.77 for serum creatinine level, [minus ]0.65 for serum cystatin C level, [minus ]0.71 for serum [beta ]2-microglobulin level, +0.56 for endogenous creatinine clearance, and +0.69 for Cockcroft formula (all P [lt ] 0.001). With a cutoff value of 60 mL/min/1.73 m2, areas under the ROC curve were 0.972 for [beta ]2-microglobulin, 0.925 for cystatin C, and 0.916 for creatinine levels. With a cutoff value of 80 mL/min/1.73 m2, these were 0.838 for [beta ]2-microglobulin, 0.780 for cystatin C, and 0.905 for creatinine levels (P [equals] not significant between parameters). These results were not altered after the exclusion of patients (n [equals] 8) with a serum creatinine level greater than 1.41 mg/dL. When patients were classified into three groups according to GFR (group 1, [gt ]80 mL/min/1.73 m2; group 2, 60 to 80 mL/min/1.73 m2; group 3, [lt ]60 mL/min/1.73 m2), mean values of serum parameters in the three groups were statistically different (P [lt ] 0.0001) except between groups 1 and 2 for cystatin C and [beta ]2-microglobulin. With patients classified into two groups (GFR [gt ] or [lt ] 80 mL/min/1.73 m2), mean values for each parameter were statistically different (P [lt ] 0.001). Sensitivity, specificity, and positive and negative predictive values for serum creatinine and serum cystatin C levels were very close for both definitions of renal failure. Serum cystatin C is not better than serum creatinine or serum [beta ]2-microglobulin levels for estimating GFR in patients with steady-state diabetes using ROC curves or other validation tests. [copy ] 2001 by the National Kidney Foundation, Inc.

ACE inhibition or angiotensin receptor blockade: Impact on potassium in renal failure

ACE inhibition or angiotensin receptor blockade: Impact on potassium in renal failure.BackgroundInhibition of the renin-angiotensin system is known to raise serum potassium [K+] levels in patients with renal insufficiency or diabetes. No study has evaluated the comparative effects of an angiotensin-converting enzyme (ACE) inhibitor versus an angiotensin receptor blocker (ARB) on the changes in serum [K+] in people with renal insufficiency.MethodsThe study was a multicenter, randomized, double crossover design, with each period lasting one month. A total of 35 people (21 males and 14 females, 19 African Americans and 16 Caucasian) participated, with the mean age being 56 ± 2 years. Mean baseline serum [K+] was 4.4 ± 0.1 mEq/L. The glomerular filtration rate (GFR) was 65 ± 5 mL/min/1.73 m2, and blood pressure was 150 ± 2/88 ± 1 mm Hg. The main outcome measure was the difference from baseline in the level of serum [K+], plasma aldosterone, and GFR following the initial and crossover periods.ResultsFor the total group, serum [K+] changes were not significantly different between the lisinopril or valsartan treatments. The subgroup with GFR values of ≤60 mL/min/1.73 m2 who received lisinopril demonstrated significant increases in serum [K+] of 0.28 mEq/L above the mean baseline of 4.6 mEq/L (P = 0.04). This increase in serum [K+] was also accompanied by a decrease in plasma aldosterone (P = 0.003). Relative to the total group, the change in serum [K+] from baseline to post-treatment in the lisinopril group was higher among those with GFR values of ≤60 mL/min/1.73 m2. The lower GFR group taking valsartan, however, demonstrated a smaller rise in serum [K+], 0.12 mEq/L above baseline (P = 0.1), a 43% lower value when compared with the change in those who received lisinopril. This blunted rise in [K+] in people taking valsartan was not associated with a significant decrease in plasma aldosterone (P = 0.14).ConclusionsIn the presence of renal insufficiency, the ARB valsartan did not raise serum [K+] to the same degree as the ACE inhibitor lisinopril. This differential effect on serum [K+] is related to a relatively smaller reduction in plasma aldosterone by the ARB and is not related to changes in GFR. This study provides evidence that increases in serum [K+] are less likely with ARB therapy compared with ACE inhibitor therapy in people with renal insufficiency. ACE inhibition or angiotensin receptor blockade: Impact on potassium in renal failure. Inhibition of the renin-angiotensin system is known to raise serum potassium [K+] levels in patients with renal insufficiency or diabetes. No study has evaluated the comparative effects of an angiotensin-converting enzyme (ACE) inhibitor versus an angiotensin receptor blocker (ARB) on the changes in serum [K+] in people with renal insufficiency. The study was a multicenter, randomized, double crossover design, with each period lasting one month. A total of 35 people (21 males and 14 females, 19 African Americans and 16 Caucasian) participated, with the mean age being 56 ± 2 years. Mean baseline serum [K+] was 4.4 ± 0.1 mEq/L. The glomerular filtration rate (GFR) was 65 ± 5 mL/min/1.73 m2, and blood pressure was 150 ± 2/88 ± 1 mm Hg. The main outcome measure was the difference from baseline in the level of serum [K+], plasma aldosterone, and GFR following the initial and crossover periods. For the total group, serum [K+] changes were not significantly different between the lisinopril or valsartan treatments. The subgroup with GFR values of ≤60 mL/min/1.73 m2 who received lisinopril demonstrated significant increases in serum [K+] of 0.28 mEq/L above the mean baseline of 4.6 mEq/L (P = 0.04). This increase in serum [K+] was also accompanied by a decrease in plasma aldosterone (P = 0.003). Relative to the total group, the change in serum [K+] from baseline to post-treatment in the lisinopril group was higher among those with GFR values of ≤60 mL/min/1.73 m2. The lower GFR group taking valsartan, however, demonstrated a smaller rise in serum [K+], 0.12 mEq/L above baseline (P = 0.1), a 43% lower value when compared with the change in those who received lisinopril. This blunted rise in [K+] in people taking valsartan was not associated with a significant decrease in plasma aldosterone (P = 0.14). In the presence of renal insufficiency, the ARB valsartan did not raise serum [K+] to the same degree as the ACE inhibitor lisinopril. This differential effect on serum [K+] is related to a relatively smaller reduction in plasma aldosterone by the ARB and is not related to changes in GFR. This study provides evidence that increases in serum [K+] are less likely with ARB therapy compared with ACE inhibitor therapy in people with renal insufficiency.

ACE inhibition or angiotensin receptor blockade: Impact on potassium in renal failure

Inhibition of the renin-angiotensin system is known to raise serum potassium [K(+)] levels in patients with renal insufficiency or diabetes. No study has evaluated the comparative effects of an angiotensin-converting enzyme (ACE) inhibitor versus an angiotensin receptor blocker (ARB) on the changes in serum [K(+)] in people with renal insufficiency. The study was a multicenter, randomized, double crossover design, with each period lasting one month. A total of 35 people (21 males and 14 females, 19 African Americans and 16 Caucasian) participated, with the mean age being 56 +/- 2 years. Mean baseline serum [K(+)] was 4.4 +/- 0.1 mEq/L. The glomerular filtration rate (GFR) was 65 +/- 5 mL/min/1.73 m(2), and blood pressure was 150 +/- 2/88 +/- 1 mm Hg. The main outcome measure was the difference from baseline in the level of serum [K+], plasma aldosterone, and GFR following the initial and crossover periods. For the total group, serum [K(+)] changes were not significantly different between the lisinopril or valsartan treatments. The subgroup with GFR values of < or = 60 mL/min/1.73 m(2) who received lisinopril demonstrated significant increases in serum [K(+)] of 0.28 mEq/L above the mean baseline of 4.6 mEq/L (P = 0.04). This increase in serum [K(+)] was also accompanied by a decrease in plasma aldosterone (P = 0.003). Relative to the total group, the change in serum [K(+)] from baseline to post-treatment in the lisinopril group was higher among those with GFR values of < or = 60 mL/min/1.73 m(2). The lower GFR group taking valsartan, however, demonstrated a smaller rise in serum [K(+)], 0.12 mEq/L above baseline (P = 0.1), a 43% lower value when compared with the change in those who received lisinopril. This blunted rise in [K(+)] in people taking valsartan was not associated with a significant decrease in plasma aldosterone (P = 0.14). In the presence of renal insufficiency, the ARB valsartan did not raise serum [K(+)] to the same degree as the ACE inhibitor lisinopril. This differential effect on serum [K(+)] is related to a relatively smaller reduction in plasma aldosterone by the ARB and is not related to changes in GFR. This study provides evidence that increases in serum [K(+)] are less likely with ARB therapy compared with ACE inhibitor therapy in people with renal insufficiency.

Glomerular filtration rate in primary Sjögren's syndrome with renal disease.

Renal disease in Primary Sjögren's syndrome (SS) is often overlooked, because of a paucity of symptoms. Distal renal tubular acidosis (dRTA) and tubulointerstitial nephritis (TIN) might be present. Only a few cases of SS with decreased glomerular filtration rate (GFR) have been reported. We have studied GFR in 27 female SS-patients, mean age 62 years (37-78). GFR was measured as the single injection 51Cr-EDTA plasma clearance. Eighteen women had normal GFR (group 1), and nine (33%) had values below the lower normal limit (group 2). In group 2, dRTA was present in 8/9 urolithiasis in 6/9, previous upper urinary tract infection (UTI) in 2/9 and TIN in 5/6 patients who were kidney biopsied. Among patients with dRTA 8/18 (44%) had decreased GFR. We conclude that decreased GFR is not unusual in SS-patients with dRTA, and decreased GFR is mostly associated with TIN. Urolithiasis and UTI may contribute to decreased GFR in some individuals.

Limitations of Serum Creatinine Level and Creatinine Clearance as Filtration Markers in Cirrhosis

Several studies carried out in a limited number of patients demonstrated a wide range of overestimation of glomerular filtration rate (GFR) by serum creatinine level and creatinine clearance (Ccr) in liver disease. We simultaneously evaluated Ccr, inulin clearance, and predicted GFR calculated from serum creatinine level in 56 cirrhotic patients. Inulin clearance was considered the gold standard for GFR evaluation. The sensitivity of serum creatinine level, predicted GFR, and Ccr in detecting renal failure was 18.5%, 51%, and 74%, respectively. On the basis of inulin clearance, patients were divided into two groups: those with normal GFR (mean, 106 +/- 34 mL/min per 1.73 m2) (group 1, 29 patients) and those with reduced GFR (mean, 56 +/- 19 mL/min per 1.73 m2) (group 2, 27 patients). Predicted GFR and Ccr were accurate markers of GFR in group 1 patients, while both overestimated GFR by about 50% in group 2 patients. An increased tubular secretion of creatinine accounted for the disparity between Ccr and inulin clearance in these patients. Our results indicate that renal failure is greatly underestimated on the basis of serum creatinine level and Ccr in cirrhotic patients. Clinical implications of this observation include excessive dosage of potentially nephrotoxic drugs and failure to recognize renal impairment induced by such medical treatments as diuretic therapy or paracentesis.

Reversal of Glomerular Hyperfiltration and Renal Hypertrophy by Blood Glucose Normalization in Diabetic Rats

Two groups of rats with streptozocin-induced diabetes and one group of nondiabetic control rats were studied. Group 1 diabetic rats received daily insulin to maintain blood glucose levels at 300-400 mg/dl for 44 wk. Group 2 diabetic rats received the same insulin regimen for 37 wk and then received an increased dose of insulin to return blood glucose levels close to normal for 7 wk. Group 3 nondiabetic rats were age-matched controls. Glomerular filtration rate (GFR) and kidney weight were elevated in moderately hyperglycemic group 1 rats compared with group 3 rats. Normalization of blood glucose returned both GFR (group 1, 1.83 +/- 0.04 ml/min; group 2, 1.36 +/- 0.05 ml/min; group 3, 1.45 +/- 0.07 ml/min) and kidney weight (group 1, 2.55 +/- 0.06 g; group 2, 1.82 +/- 0.05 g; group 3, 1.72 +/- 0.06 g) to normal in group 2 rats. Despite a sustained increase in GFR, group 1 rats did not exhibit any increase in glomerular volume (group 1, 2.77 +/- 0.09 x 10(6) microns3; group 2, 2.69 +/- 0.09 x 10(6) microns3; group 3, 2.81 +/- 0.7 x 10(6) microns3). Group 1 rats did, however, exhibit a significant increase in glomerular mesangial volume (group 1, 0.31 +/- 0.02 x 10(6) microns3; group 2, 0.28 +/- 0.02 x 10(6) microns3; group 3, 0.21 +/- 0.01 x 10(6) microns3), which was not reversed by normalization of blood glucose in group 2. These findings show that normalization of blood glucose can reverse established glomerular hyperfiltration and renal hypertrophy in moderately hyperglycemic diabetic rats. They further indicate that mesangial expansion is associated with sustained moderate hyperglycemia in this disease model.

Reduced Urinary Excretion of Epidermal Growth Factor in Incipient and Overt Diabetic Nephropathy

To study the relationship between glomerular and tubular function we investigated glomerular filtration rate (GFR), urinary albumin excretion, and urinary excretion of epidermal growth factor (EGF, a mitogenic peptide synthesized in the renal tubular cells) in normal subjects (group I, n = 7) and in Type 1 (insulin-dependent) diabetic patients with normoalbuminuria (group II, n = 11); with incipient nephropathy (microalbuminuria) (group III, n = 9); with nephropathy and normal GFR (group IV, n = 12); and with reduced GFR (group V, n = 8). EGF (nmol 24 h-1) decreased with progressive glomerular involvement, from 7.9 (4.1-10.5) (median and range) in group I, to 6.7 (1.3-9.2) in group II, 5.0 (3.6-7.4) in group III, 4.1 (2.5-9.5) in group IV, and 1.1 (0.1-2.5) in group V. The urinary excretion of EGF was significantly reduced in patients with elevated UAE (group III, IV, and V) compared with normal control subjects (p less than 0.05). A significant correlation between urinary excretion of EGF and GFR (r = 0.71, p less than 0.001) and an inverse correlation between the urinary excretion of EGF and albumin (r = -0.35, p less than 0.05) was demonstrated in the Type 1 diabetic patients with GFR greater than 90 ml min-1. Our study demonstrates that urinary excretion of epidermal growth factor diminishes with increasing nephron impairment, and that renal tubular function as judged by the excretion of EGF is reduced early in the development of diabetic kidney disease.

The One-Hour Clearance Rate Hour Creatinine in Healthy Men

In 20 normal young men, three consecutive, morning, 1-hour creatinine clearance studies, measured on both of two separate days after either modest or heavy hydration, were compared with each other and those of the 24-hour studies done the same day. Under either circumstance of hydration, differences between 1-hour and 24-hour clearance rates were not significant. Heavy hydration diminished the correlations between short-term and long-term clearance rates, but with one exception, the correlations remained significant. Measurements of clearance from the various one-hour collection periods were similar to one another. We conclude that values obtained from 1-hour creatinine clearance studies are reasonably reproducible and that carefully controlled 1-hour clearance studies can be used instead of 24-hour studies to determine glomerular filtration rate in groups or individuals.