The effect of hydrochloride pioglitazone on urinary 8-hydroxy -deoxyguanosine excretion in type 2 diabetics

ObjectiveTo observe the effects of hydrochloride pioglitazone on urinary 8-hydroxy-deoxyguanosine (8OHdG) excretion in type 2 diabetics and explore its possible reno-protective mechanisms.MethodsNinety-eight uncontrolled type 2 diabetics were assigned randomly into group DP (pioglitazone add-on) and group DS (sulfonylureas add-on). At the basal and after 12 weeks treatment, FBG, HbA1c, urinary 8-OHdG, urinary albumin(ALB) and urinary creatinine (Cr) were determined, respectively.ResultsCompared with pre-treatment, FBG, HbA1c and urinary 8-OHdG /Cr ratio(U8CR) were all obviously decreased in both therapy groups; urinary albumin/urinary creatinine ratio(UACR) markedly decreased in group DP (P < 0.01), while slightly decreased in group DS (P > 0.05) after twelve weeks of observation. After 12-week treatment, UACR and U8CR in group DP were significantly lower than those in group DS (both P < 0.05) without no marked difference in FBG and HbA1c between group DP and group DS. Meanwhile, U8CR had positive correlation with UACR (r= 0.755, P < 0.01).ConclusionPioglitazone can decrease urinary 8-OHdG excretion and lighten oxidative stress in vivo in type 2 diabetics, which may play a protective role for the kidney damage.     

Does uric acid-lowering treatment slow the progression of chronic kidney disease? A meta-analysis of randomized controlled trials

IntroductionHyperuricemia has been proposed as an independent factor in the development and progression of chronic kidney disease (CKD). However, the effect of uric acid-lowering therapies on delaying CKD progression is still uncertain. Therefore, this systemic review aims to assess the effect of uric acid-lowering therapies on renal outcomes in pre-dialysis CKD patients.MethodsPubMed, Cochrane Library, and Lilacs databases were searched until April 24, 2021, for randomized clinical trials of CKD patients on uric acid-lowering treatment with xanthine-oxidase (XO) inhibitors. The weighted mean difference (WMD) or standard mean difference (SMD) with confidence interval (CI) were pooled using a random-effects model.ResultsAmong 567 studies found, eighteen met the inclusion criteria (n = 2463 participants). Compared to the patient's control group, the WMD for the glomerular filtration ratio (GFR) and serum creatinine changes of the treated group was 2.02 ml/min/1.73 m² (95%CI 0.41 to 3.63, P = 0.014) and −0.19 mg/dl (95%CI −0.34 to −0.04, I² = 86.2%, P = 0.011), respectively. Subgroup analyses showed that the difference in follow-up time and CKD population type in the studies may explain the controversy about the role of uric acid-lowering therapies in CKD progression. The GFR and creatinine outcomes analysis by types of XO inhibitors showed no difference between the control and treated groups. Uric acid-lowering therapies were strongly associated with decreased serum uric acid and urinary protein–creatinine ratio and urinary albumin–creatinine ratio.ConclusionsThese findings suggest that uric acid-lowering treatment may slow CKD progress and reduce protein and albumin excretion. However, larger and properly powered randomized clinical trials with specific CKD populations are needed to confirm these findings.     

Urinary Neutrophil Gelatinase-Associated Lipocalin: A Potential Biomarker for Predicting Rapid Progression of Drug-Induced Chronic Tubulointerstitial Nephritis

IntroductionThe role of urinary biomarkers of kidney injury in the prediction of adverse clinical outcomes in drug-induced chronic tubulointerstitial nephritis (D-CTIN) has not been well described.MethodsA total of 36 patients with D-CTIN were enrolled in the study. The baseline urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL), α1-microglobin (α1-MG), albumin (mAlb) and total protein were measured, and estimated glomerular filtration rate change rates within a period of 6 to 33 (mean: 24 months) follow-up months were recorded.ResultsAreas under the receiver-operator characteristic curve of urinary NGAL, α1-MG, mAlb and total protein for predicting deterioration of estimated glomerular filtration rate were 0.707, 0.631, 0.685 and 0.678, respectively. The cutoff points that maximized the combined sensitivity and specificity for NGAL, α1-MG, mAlb and total protein were 37.71 ng/mL, 33.20 μg/mL, 6.91 mg/L and 60.00 mg/L, respectively. At these thresholds, the sensitivity and specificity was 64.7% and 78.9% for NGAL, 66.7% and 50.0% for α1-MG, 80.0% and 50.0% for mAlb and 70.6% and 63.2% for total protein, respectively. The median renal survival time (years) of patients with urinary NGAL level exceeding 37.705 ng/mL was shorter than that of patients with urinary NGAL level below 37.705 ng/mL (1.59 ± 0.79 versus 2.09 ± 0.63, P = 0.040, χ² = 4.218).ConclusionsIncrease of baseline urinary NGAL was better than α1-MG, mAlb and total protein in predicting renal function deterioration in patients with D-CTIN. This noninvasive approach has potential to serve as a practical tool in D-CTIN prognosis.     

Comparative Effects of Benidipine and Amlodipine on Proteinuria,Urinary 8-OHdG,Urinary L-FABP,and Inflammatory and Atherosclerosis Markers in Early-Stage Chronic Kidney Disease

IntroductionWe examined the effects of 2 calcium channel blockers, benidipine (T-, L-, and N-type) and amlodipine (L- and N-type), on renal, inflammatory, oxidative, and atherosclerosis markers in hypertensive patients with mild chronic kidney disease (CKD).MethodsForty hypertensive patients with CKD were assigned randomly to either of the 2 treatments: 8 mg benidipine once daily (n = 20, group A) or 5 mg amlodipine once daily (n = 20, group B). Treatment was continued for 12 months. Blood pressure, serum creatinine, estimated glomerular filtration rate, urinary protein excretion, urinary liver-type fatty acid-binding protein, interleukin-6, high mobility group box-1 protein, urinary 8-hydroxy-2′- deoxyguanosine, pulse wave velocity, intima-media thickness, and blood asymmetric dimethylarginine were monitored.ResultsBlood pressure decreased equally in both groups (P < 0.001, at 6 and 12 months versus before treatment). Serum creatinine and estimated glomerular filtration rate changed little during the experimental period in each group. However, urinary protein excretion (P < 0.001), urinary liver-type fatty acid-binding protein (P < 0.001), urinary 8-hydroxy-2'-deoxyguanosine (P < 0.001), blood interleukin-6 (P < 0.001), blood high mobility group box-1 (P < 0.5), and pulse wave velocity (P < 0.01) decreased more in group A than in group B with 12 months of treatment. The percent reductions in intima-media thickness and blood asymmetric dimethylarginine were significantly greater in group A than in group B (P < 0.001).ConclusionsBenidipine is more effective than amlodipine for protecting renal function and potentially for ameliorating atherosclerosis in hypertensive patients with mild CKD. T-type calcium channel blockers may be effective in patients with CKD.     

The association of the 174G > C polymorphism of interleukin 6 gene with diabetic nephropathy in patients with type 2 diabetes mellitus

AimsTo evaluate the association of 174G > C polymorphism on interleukin-6 (IL-6) gene with diabetic nephropathy in patients with type 2 diabetes.MethodsA total of 393 Greek subjects with type 2 diabetes (mean age 66.5 ± 10.0 years, men n = 203, women n = 190) were examined. Diabetic nephropathy was defined as presence of microalbuminuria and/or proteinuria. The IL-6 174G > C polymorphism was detected by polymerase chain reaction and appropriate restriction enzyme digestion. High sensitivity C-reactive protein was assayed by particle-enhanced immunonephelometry.ResultsThe genotype distribution (%) was GG: 49.1, GC: 26.8 and CC: 24.1, with no gender difference. The CC homozygotes had lower albumin excretion (mg/24 h) in comparison with the GC genotype [CC: 8.9 (4.0–20.9) vs GC: 21.95 (9.1–53.35), P = 0.004]. Participants with the GC genotype tended to have more frequently nephropathy than those with the GG or the CC genotype [GC: 44.55% vs GG: 35.1% and CC: 28.3%, P = 0.07)]. The CC homozygotes in comparison with GC heterozygotes had lower odds to have nephropathy (odds ratio: 0.51, 95% confidence intervals = 0.28–0.91, P = 0.02), even after adjustment for sex, age, duration of diabetes, body mass index, smoking, hypertension, lipids and glycated hemoglobin, (P = 0.01).ConclusionIn type 2 diabetes states, CC homozygotes have lower albumin excretion and are protected from nephropathy in comparison with GC genotypes.     

Altering dietary lysine:arginine ratio has little effect on cardiovascular risk factors and vascular reactivity in moderately hypercholesterolemic adults

BackgroundInformation is scarce regarding the effect of dietary protein type, with specific focus on the lysine-to-arginine (Lys:Arg) ratio, on cardiovascular risk factors and vascular reactivity in humans.ObjectiveDetermine the effect of dietary Lys:Arg ratio on cardiovascular risk factors and vascular reactivity in moderately hypercholesterolemic adults.DesignRandomized cross-over design of two 35-day diet phases; thirty adults (21 females and 9 males, ≥50 years, LDL cholesterol ≥120 mg/dL). Diets had 20% energy (E) protein, 30% E fat, 50% E carbohydrate and were designed to have low (0.7) or high (1.4) Lys:Arg ratio. Measures included fasting and postprandial lipid, lipoprotein, apolipoprotein concentrations; fasting high sensitivity C-reactive protein (hsCRP), small dense LDL (sdLDL) cholesterol, remnant lipoprotein cholesterol (RemLC), glycated albumin, adiponectin and immunoreactive insulin concentrations, endogenous cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) activities; cholesterol fractional synthesis rate (FSR); and flow mediated dilation (FMD) and peripheral artery tonometry (PAT).ResultsNo differences were observed in fasting and/or postprandial total, LDL, HDL and sdLDL cholesterol, RemLC, Lp(a) or apo B concentrations, LCAT and CETP activities, FSR, glycated albumin, immunoreactive insulin, FMD or PAT. The low, relative to the high, Lys:Arg ratio diet resulted in lower postprandial VLDL cholesterol (?24%, P = 0.001) and triglycerides (?23%, P = 0.001), and small but significant differences in fasting (?3%, P = 0.003) and postprandial (?3%, P = 0.018) apo AI, and fasting adiponectin concentrations (+7%, P = 0.035). Fasting and postprandial hsCRP concentrations were 23% lower after the low Lys:Arg ratio diet (P = 0.020 for both).ConclusionsDiets differing in Lys:Arg ratios had no or small effects on cardiovascular risk factors and vascular reactivity.     

Increased Mean Platelet Volume and C-Reactive Protein Levels in Patients With Chronic Urticaria With a Positive Autologous Serum Skin Test

IntroductionActivation of the coagulation cascade resulting in thrombin production is a prominent feature of exacerbations in chronic spontaneous urticaria (CU). Autologous serum skin test (ASST) causes wheal-and-flare reactions in 30% to 50% of CU cases.ObjectiveThe aim of this study was to evaluate the clinical and laboratory data in patients with CU with positive and negative ASST. To understand the role of platelets in CU, we investigated the relation between CU clinical severity, platelet count and their mean platelet volume (MPV).MethodsClinical and laboratory data were prospectively collected from 373 patients with CU who attended our Allergy and Clinical immunology Clinic during the period 2003 to 2007. The laboratory data were compared with 46 healthy subjects.ResultsThere were no significant differences in platelet counts between the groups, nevertheless the platelets in ASST-positive CU patients were characterized by a higher MPV (9.12 ± 1.25 fl), than that in ASST-negative patients (7.95 ± 1.08 fl; P = 0.039) and control group (7.72 ± 1.04 fl; P = 0.007). There was a significant positive correlation between CU severity score and MPV in ASST-positive patients (r = 0.44; P < 0.001) but not in ASST-negative patients. Higher levels of C-reactive protein (5.31 ± 2.74 mg/L) were measured in the ASST-positive CU group compared with the ASST-negative CU group (2.53 ± 1.27; P = 0.029) and the control group (2.34 ± 1.38; P = 0.003).ConclusionCU with positive ASST is characterized with higher clinical severity, increased MPV and C-reactive protein.     

Different Substrates of Non-Sustained Ventricular Tachycardia in Post-infarction Patients With and Without Left Ventricular Dilatation

BackgroundWe investigated the relationship between nonsustained ventricular tachycardia (NSVT) and left ventricular (LV) dilatation, function, remodeling, and scar tissue extent in patients with previous myocardial infarction (MI).Methods and ResultsEighty-two patients (ages 64 ± 10 years) with first previous MI were referred for 24-hour electrocardiogram recording and cine and delayed enhancement (DE) cardiac magnetic resonance (CMR). LV volumes, ejection fraction, systolic wall thickening, sphericity index, and core and peri-infarctual areas of scar tissue by CMR were evaluated. LV dilatation was observed in 39 patients. Episodes of NSVT were recorded in 32 patients: 23 with LV dilatation and 9 without. In the entire population, NSVT was related to ejection fraction, LV volumes, LV mass, and sphericity index; end-systolic volume (P = .001) resulted in the only independent predictor at multivariate analysis. In patients without LV dilatation, the occurrence of NSVT was only positively related with percentage of contracting segments with DE (P = .008). Conversely, in patients with LV dilatation, increase in LV mass (P = .020) and end-systolic volume (P = .038) were independent predictors of NSVT.ConclusionsNecrotic and viable myocardium coexistence within the same wall segments predicted occurrence of NSVT in patients without LV dilatation, whereas LV mass and end-systolic volume were predictors of NSVT in those with LV dilatation.     

SGLT2 inhibition increases serum copeptin in young adults with type 1 diabetes

AimsCopeptin, a surrogate of vasopressin, is elevated in type 1 diabetes (T1D) and predicts kidney disease and cardiovascular mortality. Given the cardiorenal protective effects of SGLT2 inhibition (SGLT2i), our aim was to examine: 1) the relationship between serum copeptin, metabolic, renal and systemic hemodynamic parameters in adults with T1D; and 2) serum copeptin after SGLT2i with empagliflozin.Materials and methodsIn this post-hoc, exploratory analysis, serum copeptin, glomerular filtration rate (GFR_Inulin), effective renal plasma flow (ERPF_PAH), plasma renin angiotensin aldosterone system markers, HbA_1c, 24-hour urine volume and sodium excretion were measured in 40 participants with T1D (24.3 ± 5.1 years) during eu- and hyperglycaemia before and after 8 weeks of 25 mg of daily empagliflozin.ResultsHigher baseline copeptin correlated with higher HbA_1c, lower 24-hour urine volume and sodium excretion, after correcting for age, sex, systolic blood pressure, and HbA_1c. Copeptin concentrations increased in response to empagliflozin under euglycaemia (4.1 ± 2.1 to 5.1 ± 2.8 pmol/L, P = 0.0053) and hyperglycaemia (3.3 ± 1.4 to 5.6 ± 2.8 pmol/L, P < 0.0001). The rise in copeptin in response to empagliflozin correlated with change in 24-hour urine volume, but was independent of changes in fractional excretion of sodium and haematocrit.ConclusionsElevated serum copeptin was associated with worse glycaemic control and lower diuresis and natriuresis. SGLT2i increased serum copeptin in adults with T1D, and the rise correlated with change in diuresis, but not natriuresis and hemo-concentration. Further work is required to evaluate the clinical implications of elevated copeptin with SGLT2i, including whether it is simply a marker of diuresis or may contribute to cardiorenal disease long-term.     

Relationship between blood pressure,cognitive function and education level in elderly patients with diabetes: A preliminary study

AimsThis study aimed to assess the relationship between blood pressure and cognitive function in elderly patients with diabetes mellitus (DM).MethodsA total of 32 patients with DM aged ≥ 65 years (seven women and 25 men; mean ± SD age: 74.3 ± 6.4 years) were included in this cross-sectional study. Relationships between blood pressure and neuropsychological tests were determined using Spearman's rank correlations (ρ) and multivariable linear regression models.ResultsLower diastolic blood pressure was associated with lower scores on the Frontal Assessment Battery (ρ = 0.32, P = 0.02), longer times to complete the Trail Making Test Part B (ρ = 0.51, P = 0.003), lower scores for the Finger Tapping Test (ρ = 0.36, P = 0.046) and less verbal fluency (ρ = 0.36, P = 0.047). In multivariable models, these relationships were attenuated after adjusting for levels of education.ConclusionThere was an association between lower diastolic blood pressure and poorer executive function in this cohort of elderly DM patients. These results underline the importance of systematic cognitive evaluation in elderly patients with DM, and suggest that a too-low diastolic blood pressure may have deleterious effects on mental function. Larger studies in the future are required to confirm these preliminary results.     

Peripheral adiposity in relation to offspring birth size in women with and without gestational diabetes: Preliminary data

ObjectiveTo document the relationship between maternal body composition parameters and offspring anthropometric measurements.MethodsA prospective sample of 48 pregnant women with either gestational diabetes (GDM, n = 21) or normal glucose tolerance (NGT, n = 27) was studied. Maternal weight, hip circumference and skinfold thicknesses were obtained at 32 weeks of gestation. Offspring length and weight, as well as cranial and thoracic perimeters were obtained at birth.ResultsReported maternal pregravid BMI correlated with offspring thoracic perimeter (ρ = 0.52, P < 0.05) and tended to correlate with birth weight (ρ = 0.41, P = 0.07). There were significant correlations between hip circumference and pregravid BMI, and with biceps, triceps, subscapular, thigh and total sum of skinfold thicknesses (ρ = 0.53–0.75, all P < 0.01). Hip circumference also correlated with offspring length (ρ=0.61), weight (ρ = 0.75) and thoracic perimeter (ρ = 0.60, all P < 0.05). Maternal hip circumference was an independent and significant predictor of offspring weight, explaining 14.1% of the observed variance (P < 0.05).ConclusionIn a sample of women with and without GDM, maternal hip circumference was strongly related to other body composition estimates and was also predictive of offspring size measurements at birth.     

High triglyceride-to-HDL cholesterol ratio associated with albuminuria in type 2 diabetic subjects

ObjectiveEmerging evidence indicates that metabolic syndrome (MetS) predisposes diabetic subjects to nephropathy. Aside from hypertension and hyperglycemia, it is unclear which component of MetS also contributes to increased urinary albumin excretion (UAE). We compared the MetS profiles of subjects divided into two groups based on their UAE.MethodsThe Asia Pacific Real-Life Effectiveness and Care Patterns of Diabetes Management (AP RECAP-DM) study is a cross-sectional survey in which type 2 diabetic subjects using oral anti-hyperglycemic drugs were enrolled. We analyzed the data of 162 type 2 diabetic subjects with normotension or taking antihypertensive medications.ResultsThere were 123 subjects with normal UAE (< 30 mg/g) and 39 with abnormal UAE (≥ 30 mg/g). MetS was more prevalent in the abnormal UAE group (79.5%) than in the normal UAE group (58.5%) (P = 0.018). Hypertriglyceridemia (odds ratio = 8.65, P < 0.001) and reduced high-density lipoprotein (HDL) cholesterol (odds ratio = 3.27, P = 0.022) were both independently associated with abnormal UAE. Using 3.4 as a cut-off value, a high triglyceride-to-HDL cholesterol ratio was a useful marker (odds ratio = 15.05, P < 0.001) for abnormal UAE.ConclusionsA high triglyceride-to-HDL cholesterol ratio was found to be an important risk factor for nephropathy in type 2 diabetic subjects.     

Evaluación multiparamétrica de la función ventricular derecha en la hipertensión arterial pulmonar asociada a cardiopatías congénitas

Introduction and objectivesOutcome in patients with congenital heart diseases and pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Two-dimensional echocardiographic parameters, such as strain imaging or RV end-systolic remodeling index (RVESRI) have emerged to quantify RV function.MethodsWe prospectively studied 30 patients aged 48 ± 12 years with pretricuspid shunt and PAH and investigated the accuracy of multiple echocardiographic parameters of RV function (tricuspid annular plane systolic excursion, tricuspid annular peak systolic velocity, RV systolic-to-diastolic duration ratio, right atrial area, RV fractional area change, RV global longitudinal strain and RVESRI) to RV ejection fraction measured by cardiac magnetic resonance.ResultsRV ejection fraction < 45% was observed in 13 patients (43.3%). RV global longitudinal strain (ρ [Spearman's correlation coefficient] = −0.75; P = .001; R² = 0.58; P = .001), right atrium area (ρ = −0.74; P < .0001; R² = 0.56; P < .0001), RVESRI (ρ = −0.64; P < .0001; R² = 0.47; P < .0001), systolic-to-diastolic duration ratio (ρ = −0.62; P = .0004; R² = 0.47; P < .0001) and RV fractional area change (ρ = 0.48; P = .01; R² = 0.37; P < .0001) were correlated with RV ejection fraction. RV global longitudinal strain, RVESRI and right atrium area predicted RV ejection fraction < 45% with the greatest area under curve (0.88; 95%CI, 0.71-1.00; 0.88; 95%CI, 0.76-1.00, and 0.89; 95%CI, 0.77-1.00, respectively). RV global longitudinal strain > −16%, RVESRI ≥ 1.7 and right atrial area ≥ 22 cm² predicted RV ejection fraction < 45% with a sensitivity and specificity of 87.5% and 85.7%; 76.9% and 88.3%; 92.3% and 82.4%, respectively.ConclusionsRVESRI, right atrial area and RV global longitudinal strain are strong markers of RV dysfunction in patients with pretricuspid shunt and PAH.     

Performance of Simplified Modification of Diet in Renal Disease and Cockcroft-Gault Equations in Patients With Chronic Spinal Cord Injury and Chronic Kidney Disease

IntroductionThe purpose of the study was to compare the performance of the simplified Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (CG) equations with 24-hour urinary creatinine clearance (Ccr) in patients with spinal cord injury (SCI) and chronic kidney disease.MethodsA retrospective diagnostic accuracy study of 116 patients with chronic SCI followed at the Memphis Veterans Affairs Medical Center Spinal Cord Injury Unit with measured Ccr (mCcr) < 90 mL/min/1.73 m².ResultsLinear regression analysis relating estimated glomerular filtration rate (eGFR) to mCcr showed a highly significant correlation between mCcr and eGFR (n = 116; r = 0.81, r² = 0.65, P < 0.0001); however, the relationship was more variable in the quadriplegic subjects (n = 52; r = 0.74, r² = 0.54, P < 0.0001) than in the paraplegic subjects (n = 64; r = 0.86, r² = 0.73, P < 0.0001). Both eGFR equations overestimated glomerular filtration rate (GFR) at all ranges of GFR in both subgroups of paraplegic subjects and quadriplegic subjects, with an MDRD fractional prediction error of 49% and 62%, respectively. Addition of a correction factor of 0.7 for MDRD and 0.8 for CG equations resulted in clinically acceptable fractional prediction error (below 20%) in both subgroups, especially in paraplegics with 3.9% and 3.6%, respectively. There was marked improvement in the performances of both eGFR equations, with better accuracy and precision after application of the correction factors.ConclusionsBoth MDRD and CG equations overestimate GFR in patients with chronic SCI at all stages of chronic kidney disease, particularly in quadriplegic subjects. An empirically derived correction factor markedly improved the performance and accuracy of both prediction equations.     

L’hypo-albuminémie contribue-t-elle à l’aggravation de l’insuffisance cardiaque ?

BackgroundHypoalbuminemia has now emerged as a powerful prognosticator in heart failure regardless of age, clinical presentation, left ventricular ejection fraction and usual prognostic markers. Growing evidence is that this prognostic value persists after adjusting for causative factors for hypoalbuminemia such as malnutrition, inflammation and liver dysfunction.ObjectiveTo address the prognostic relevance of hypoalbuminemia in frail elderly patients with well-characterized cardiogenic pulmonary edema at high risk for adverse outcome, beyond causative factors for low serum albumin levels. Serum albumin was measured after clinical stabilization to avoid hypervolemia.ResultsIn all, 67 patients with a mean age of 86 years were included. Hospital mortality was 30%. Patients who died and who survived were similar in age, ejection fraction, BNP concentration, serum creatinine, serum hemoglobin, total bilirubin and prealbumin. Patients who died had lower serum albumin levels (P < 0.001), higher blood urea nitrogen (P = 0.03) and higher C-reactive protein (P = 0.02). In multivariate analysis, serum albumin was the sole independent predictor of hospital death (P < 0.01), after adjusting for malnutrition (prealbumin P = ns), inflammation (C-reactive protein P = ns) and liver dysfunction (total bilirubin P = ns).ConclusionSerum albumin is a powerful prognosticator in frail elderly patients with acute cardiogenic pulmonary edema even after adjusting for main causative factors. These results suggest that hypoalbuminemia may contribute to the worsening of heart failure given the physiological properties of serum albumin that includes antioxidant activity and plasma colloid osmotic pressure action. Further studies are critically needed to address the relevance of prevention and correction of hypoalbuminemia in heart failure.     

Hypoalbuminemia and Lymphocytopenia in Patients With Decompensated Biventricular Failure

BackgroundIn patients hospitalized with decompensated biventricular failure having hypoalbuminemia and lymphocytopenia without underlying hepatic or renal disease, we addressed the presence of a protein-losing enteropathy (PLE).MethodsWe studied 78 patients having a dilated cardiomyopathy, who were hospitalized with congestive heart failure (CHF) and hypoalbuminemia of uncertain origin. In the first 19 patients, we investigated the presence of PLE using Tc-Dex⁷⁰ scintigraphy together with serum albumin 2 to 4 weeks later when compensation had been restored. In the next 59 patients, presenting with reduced serum albumin and relative lymphocyte count at admission, these parameters were again monitored (2–4 weeks) later when symptoms and signs of CHF had resolved.ResultsPLE, documented by Tc-Dex⁷⁰ scintigraphy, was found in 10 of 19 patients and whose hypoalbuminemia (2.7 ± 0.1 g/dL, mean ± standard error of mean) were corrected (3.3 ± 0.1 g/dL; P < 0.05) with the resolution of CHF, whereas in the 9 patients without a PLE, reduced baseline serum albumin (2.6 ± 0.1 g/dL) failed to improve on follow-up (2.6 ± 0.2 g/dL) in keeping with malnutrition. Relative lymphocyte count was reduced (14.6 ± 1.5%) in patients with PLE but was normal (21.4 ± 3.3%; P < 0.05) in those without PLE. Serum albumin and relative lymphocyte count were each reduced at admission (2.8 ± 0.1 g/dL and 14.4 ± 1.0%, respectively) in 59 patients and increased (P < 0.05) to normal values (3.5 ± 0.1 g/dL and 24.9 ± 1.0%) 2 to 4 weeks after they were compensated.ConclusionsEnteral losses of albumin and lymphocytes account for the reversible hypoalbuminemia and lymphocytopenia found in patients hospitalized with CHF having splanchnic congestion.     

Efficacy and Safety of Oral Conivaptan,a Vasopressin-Receptor Antagonist,Evaluated in a Randomized,Controlled Trial in Patients With Euvolemic or Hypervolemic Hyponatremia

BackgroundIn most cases of hyponatremia, arginine vasopressin secretion is inappropriately high. This placebo-controlled, randomized, double-blind multicenter study evaluated the efficacy and safety of oral conivaptan, a V_1A/V₂-receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia.MethodsEighty-three patients with serum [Na⁺] less than 130 mEq/L were stratified by volume status and randomly assigned to placebo or conivaptan 40 or 80 mg/d for 5 days.ResultsConivaptan increased the baseline-adjusted area under the serum [Na⁺]-time curve significantly more than placebo (P = 0.0001). Patients given either dose of conivaptan demonstrated a serum [Na⁺] of 4 mEq/L or greater above baseline significantly faster than those given placebo (P < 0.001) and maintained that increase for a greater total time (P = 0.0001). The least squares mean change in serum [Na⁺] from baseline to end of treatment was also significantly greater with conivaptan 40 and 80 mg/d (6.8 and 8.8 mEq/L, respectively) (P = 0.0001) than that with placebo (1.2 mEq/L). The percentage of patients who obtained an increase from baseline in serum [Na⁺] of 6 mEq/L or greater or normal serum [Na⁺] was significantly higher among patients given conivaptan 40 and 80 mg/d (67% and 88%, respectively) than among those given placebo (20%; P < 0.001). Conivaptan was well tolerated; the most frequent adverse events were urinary tract infection, anemia, pyrexia, cardiac failure, hypotension, and hypokalemia.ConclusionOral conivaptan was effective in increasing serum [Na⁺] in patients with euvolemic or hypervolemic hyponatremia and had a favorable safety profile.     

Effect of coronary slow flow on dispersion of P-wave & QT-interval and its relationship with Thrombolysis in Myocardial Infarction frame count

BackgroundSlow coronary flow (SCF) is defined as late opacification at the epicardial coronary arteries without stenosis, in this study we search the effect of isolated CSF on P-wave and QT-interval dispersion.Patients and methodsThirty five patients with CSF (group 1), and 30 control subjects (group II) matched in sex and age. Both groups underwent a standard 12-lead surface electrocardiogram. Maximal (P max), minimal P-wave durations (P min), P dispersion (PD), and QT dispersion were measured. All patients underwent selective coronary angiography. Coronary flow rates were documented by Thrombolysis in Myocardial Infarction (TIMI) frame count.ResultsCSF patients had more P maximum, P dispersion, C QT duration, QT dispersion, and C QT dispersion. TIMl frame counts of CSF patients were significantly higher than those of the control group for all three coronary vessels (P 0.0001). PD was positively correlated with LAD TIMI frame count (r = 0.42; P: 0.01); LCx TIMI frame count (r = 0.40; P: 0.01); and mean TIMI frame count (r = 0.44; P: 0.007), while weak correlated with RCA TIMI frame count (r = 0.22; and not statistically significant P: 0.18), C QT dispersion was positively correlated with LAD TIMI frame count (r = 0.54; P: 0.001); LCx TIMI frame count (r = 0.70; P: 0.001); and mean TIMI frame count (r = 0.50; P: 0.002), while weak correlated with RCA TIMI frame count (r = 0.24; and not statistically significant P: 0.15).ConclusionCSF was found to be associated with prolonged dispersion of P-wave and QT-interval.     

Symmetrical ambulatory arterial stiffness index: Relationship with microalbuminuria and renal function

ObjectiveThe aim of this study was to investigate the arterial stiffness parameters derived from the proposed linear relationship between SBP and DBP obtained by ABPM, regarding its relationships with two markers of renal disease, microalbuminuria and renal function.Design and methodsOne hundred and sixty six patients were studied: 73 males and 93 females mean age 55.2 ± 15.5 years. 36.2% were receiving antihypertensive drug treatment. Microalbuminuria was measured in 24-h urine collection as well as albumin to creatinine ratio (ACR) in first morning urine. The ambulatory BP was measured non-invasively for 24 h by the Spacelab devices.ResultsCorrelation test showed a significant relationship of Sym-AASI with age (p < 0.001), serum creatinine (p = 0.038), creatinine clearance (? 0.423, p < 0.001) and GFR (? 0.263, p < 0.001). On the other hand AASI was also correlated with age (p < 0.001) and creatinine clearance (p = 0.012), but not with the other parameters studied. 24-h albumin excretion rate was not correlated with Sym-AASI or AASI. Contrariwise, the albumin to creatinine ratio was correlated with Sym-AASI (p = 0.013). As expected, AASI and Sym-AASI increase as severity of renal diseases grows. The patients in the highest quartile of Sym-AASI distribution showed an older age (p < 0.001) and worse parameters of renal function (GFR, p < 0.001; and creatinine clearance, p < 0.008).ConclusionsSym-AASI, an improved method for detecting arterial stiffness, seems to get an independent relationship with these parameters of renal disease which could not be detected with AASI.     

Prevalence and risk factors of microalbuminuria in type 2 diabetes mellitus outpatients at University Sains Malaysia Hospital

Background and objectiveMicroalbuminuria is early stage of diabetic nephropathy as well as a marker of cardiovascular disease. The objective of this study is to determine the prevalence of microalbuminuria and associated risk factors among type 2 diabetic outpatients, attending a diabetic clinic in University Sains Malaysia Hospital (HUSM).Patients and methodsProspective study design was used in the data collection process.The study sample consists of 1066 type 2 diabetes mellitus outpatients who fit the inclusion criteria. All the patients were recruited from the diabetic outpatient clinics from HUSM. The study period was from January till December 2008. Microalbuminuria was diagnosed if the urinary albumin excretion more than 30 mg/g of creatinine.ResultsA total of 1661 patients were included in this study. Microalbuminuria was diagnosed in 273 (25.4%) patients. Multivariate logistic regression analysis indicated that microalbuminuria was positively associated with duration of hypertension (P = 0.044), HbA1c (P = 0.004), systolic blood pressure (<0.001), creatinine clearance (P = 0.007) and the presence of neuropathy (P = 0.004).ConclusionHigh prevalence of microalbuminuria was in type 2 diabetic outpatients. Predictive factors for microalbuminuria were duration of hypertension, HbA1c, systolic blood pressure, creatinine clearance and the presence of neuropathy. The study suggests the need to screen for microalbuminuria early and the active management of modifiable risk factors in particular, hyperglycemia, hypertension and creatinine clearance, to reduce the burden of end-stage renal disease in the future.