Albumin Creatinine Research Articles

Therapeutic Role of Tangshenkang Granule () in Rat Model with Diabetic Nephropathy.

To evaluate the renal protective effect of Tangshenkang Granule () in a rat model of diabetic nephropathy (DN). Forty male Sprague-Dawley rats were randomly divided into control, DN, Tangshenkang and benazepril groups. DN model was established in the rats of DN, Tangshenkang and benazepril groups. Tangshenkang Granule solution and benazepril hydrochloride solution were intragastrically administered daily to the rats in the Tangshenkang and benazepril groups for 8 weeks, respectively. Urinary albumin and creatinine were detected. The albumin/creatinine (ACR) was calculated in addition to 24 h urinary protein (24-h UPr), serum creatinine (Scr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and creatinine clearance rate (Ccr). Right kidneys were harvested for pathological observation using periodic acid-silver methenamine-Masson staining. The average glomerular diameter (DG), average glomerular (AG) and mesangial areas (AM) were measured. The thickness of glomerular basement membrane (TGBM) was detected using transmission electron microscope. Compared with rats in the control group, rats in the DN group showed significantly decreased body weight, increased hypertrophy index, 24-h urinary volume, 24-h UPr, ACR, Scr, BUN, Ccr, blood lipids as well as renal pathological indices including DG, AG, AM, AM/AG and TGBM (P <0.05). Compared with the DN group, the weights of rats in the Tangshenkang and benazepril groups were significantly increased, and the renal hypertrophy indices were significantly decreased (P <0.05). The 24-h urinary volumes, ACR, 24-h UPr, Scr, BUN, Ccr, LDL, DG, AG, AM and TGBM were obviously decreased (P <0.05). Compared with the benazepril group, the Tangshenkang group showed significantly decreased levels of ACR, 24-h UPr, AG and AM (P <0.05). Tangshenkang Granule decreased the urinary protein, attenuated the high glomerular filtration rate and improved lipid metabolism in DN rats, and prevented further injury induced by diabetic nephropathy.

Insulin Pump Therapy Is Associated with Lower Rates of Retinopathy and Peripheral Nerve Abnormality.

ObjectiveTo compare rates of microvascular complications in adolescents with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI).Research Design and MethodsProspective cohort of 989 patients (aged 12–20 years; diabetes duration >5 years) treated with CSII or MDI for >12 months. Microvascular complications were assessed from 2000–14: early retinopathy (seven-field fundal photography), peripheral nerve function (thermal and vibration threshold testing), autonomic nerve abnormality (heart rate variability analysis of electrocardiogram recordings) and albuminuria (albumin creatinine ratio/timed overnight albumin excretion). Generalized estimating equations (GEE) were used to examine the relationship between treatment and complications rates, adjusting for socio-economic status (SES) and known risk factors including HbA1c and diabetes duration.ResultsComparing CSII with MDI: HbA1C was 8.6% [70mmol/mol] vs. 8.7% [72 mmol/mol]) (p = 0.7), retinopathy 17% vs. 22% (p = 0.06); microalbuminuria 1% vs. 4% (p = 0.07), peripheral nerve abnormality 27% vs. 33% (p = 0.108) and autonomic nerve abnormality 24% vs. 28% (p = 0.401). In multivariable GEE, CSII use was associated with lower rates of retinopathy (OR 0.66, 95% CI 0.45–0.95, p = 0.029) and peripheral nerve abnormality (OR 0.63, 95% CI 0.42–0.95, p = 0.026), but not albuminuria (OR 0.46, 95% CI 0.10–2.17, p = 0.33). SES was not associated with any of the complication outcomes.ConclusionsIn adolescents, CSII use is associated with lower rates of retinopathy and peripheral nerve abnormality, suggesting an apparent benefit of CSII over MDI independent of glycemic control or SES.

Clinical effect of compound danshen dripping pills on diabetic nephropathy in the elderly

Objective To observe the clinical effect of compound danshen dropping pills on the early diabetic kidney disease. Methods A total of 850 type 2 diabetes mellitus (T2DM) patients with diabetic nephropathy (DN) at stage Ⅲ who met the criteria for DN from January 2012 to July 2012, aged 60 to 75 years 〔mean age (66.6±4.8) years〕, were retrospectively analyzed and randomized into the treatment group (n=601) and the control group (n=249). All patients received rational hypoglycemic, antihypertensive, lipids-adjusting treatment and the treatment group received compound danshen drop pill (15 pills, tid), additionally. Laboratory indexes such as urine albumin (UA) and urine creatinine (UCR) were examined 24 weeks after treatment. Results The levels of UA and UCR, and the UA/UCR ratio (ACR) in the treatment group were decreased after versus before treatment . The decreases of UA and UCR had significant differences between the treatment and control group 〔(39.1±78.7) mg/L vs. (14.7±77.1) mg/L, (1.1±4.5) mmol/L vs. (-0.3±3.6) mmol/L, t=4.15 and 4.86, both P<0.01〕. Conclusions The comprehensive treatment combined with compound danshen dropping pills for 24 weeks can more effectively reduce UA and ACR, thereby it has effects in treating DN and delaying the progression of DN. Key words: Diabetes mellitus, type 2; Diabetic kidney disease; Albuminuria

Biochemical and Hormones Study on Diabetic Nephrotic Patients

Background: Diabetes mellitus is a growing epidemic and is the most common cause of chronic kidney disease (CKD) and kidney failure. Diabetic nephropathy affects approximately 20–40% of individuals who have diabetes. Diabetic nephropathy can be detected by the measurement of urine albumin or serum creatinine. Visceral adipose tissue-derived serine proteinase inhibitor (vaspin) was identified in the visceral adipose tissue of OLETF (Otsuka Long-Evans Tokushim a Fatty) rats, an animal model of obesity and type 2 diabetes mellitus (T2DM). Material and methods: In this study conducted on 70 individuals in the age group of 35-70 years, from Kirkuk General Hospital. study group consists 40 individuals with diabetic nephropathy and 30 ages and sex matched healthy individuals (control). Reasults: Serum vaspin of diabetic nephropathy patients showed a high significant relationship (p<0.0001). as compared with the controls. There is high significant decrease (p<0.001) in the serum levels of T4 and T3. There is high significant increase (p<0.001) in the serum levels of TSH as compared with the controls. There is high significant increase (p<0.001) in the serum concentration of K+ and uric acid and glucose as compared with the controls. There is high significant decrease (p<0.001) in the serum levels of Ca++ and Na+ as compared with the controls. There is high significant increase (p<0.001) in the serum levels of Cholesterol, TG, LDL and VLDL as compared with the controls. There is significant decrease (p<0.05) in the serum levels of HDL as compared with the controls. Conclusion: The hormones (vaspin, TSH, T4, T3) have higher diagnostic validity values in the current study, which may be useful as a diagnostic tool to identify recurrence of the diabetic nephropathy syndromes.

The Expression of Tristetraprolin and Its Relationship with Urinary Proteins in Patients with Diabetic Nephropathy.

ObjectiveTristetraprolin (TTP), also known as zinc finger protein 36, is an RNA binding protein that has a significant role in regulating the expression of mRNAs containing AU-rich elements. We postulated that TTP might regulate interleukin (IL)-6 and IL-18 expression in diabetes. This study aimed to test the hypothesis that the levels of TTP are correlated with nephropathy in patients with type 2 diabetes.MethodsEighty-seven patients (61.3±9.6 years old) who had been diagnosed with type 2 diabetes mellitus and 41 age and sex matched healthy control subjects were enrolled. The diabetes patients were classified into those without proteinuria, with microalbuminuria, and with clinical proteinuria groups according to the ratio of urinary excretion of albumin/creatinine (ACR).ResultsSerum and urinary levels of IL-6 and IL-18 were significantly elevated, but those of TTP were significantly decreased in patients with diabetes as compared with control subjects. In addition, serum and urinary levels of IL-6 and IL-18 were significantly higher, but those of TTP were significantly lower in patients with proteinuria than in patients without proteinuria or with microalbuminuria. There was a significant correlation between serum TTP and IL-6/IL-18 (correlation coefficients of -0.572 and -0.685, P < 0.05).ConclusionThese results show that diabetes with clinical proteinuria is accompanied by decreased urinary and serum level of TTP and increased levels of IL-6 and IL-18. Decreased TTP expression might occur prior to the increase in IL-6 and IL-18, and decrease of TTP might provide an earlier marker for glomerular dysfunction than IL-6 and IL-18.

Abstract MP16: ReninAAV Uninephrectomized db/db Mice as a Novel Diabetic Kidney Diesease Model for Testing New Therapeutics on Top of RAS Inhibition

ReninAAV comprises a novel approach to induce persistent hypertension in diverse murine models. ReninAAV induced hypertension is persistent and facilitates the development of animal models of diseases accelerated or driven by hypertension such as diabetic kidney disease (DKD). A single injection of ReninAAV (5x10 9 GC) in uninephrectomized (uNx) db/db mice results in progressive DKD. Impaired renal function was detected as early as one week post injection with an 8.9±3.1-fold increase in ACR (albumin:creatinine) as compared to baseline values, and at 11 weeks post injection significantly (p&lt;0.01) increased serum creatinine (0.20±0.03mg/dL) and ACR were detected (68,890±7,209μg/mg) versus LacZAAV uNx db/db controls (0.08±0.01mg/dL and 1,364±83μg/mg, respectively). To determine if treatment with the ACEi Linsinopril halted progression of renal disease uNx db/db were given ReninAAV and followed for 4 weeks until ACR reached approximately 15,000μg/mg. Mice were randomized into 4 treatment groups: untreated, Lisinopril low (30mg/L), Lisinopril medium (100mg/L) and Lisinopril high (300mg/L) and followed for an additional 8 weeks. Untreated mice showed progressive increase in ACR developing a final ACR of 35,318±4,177μg/mg. Lisinopril dose dependently reduced ACR significantly compared to baseline (p&lt;0.001, final ACR of 7,869±1632, 2,730±582 and 2,014±44μg/mg for the 30, 100 and 300 mg/L groups respectively), albeit still elevated compared to control LacZAAV uNx db/db mice (1,364±831μg/mg) that did not receive ReninAAV. Lisinopril treatment at 100 and 300mg/L also resulted in improvement in final serum creatinine values (p&lt;0.05, 0.18±0.01 and 0.14±0.01mg/dL respectively vs untreated ReninAAV group 0.26±0.03mg/dL), yet residual increased serum creatinine were apparent compared to control LacZAAV uNx db/db mice (0.08±0.012mg/dL). This study establishes ReninAAV treated uNx db/db mice as a novel model of progressive DKD and demonstrates that suppression of RAS with Lisinopril improved, but only partially prevented progression of renal disease, thus enabling testing of new potential therapeutics on top of RAS inhibition.

A study examining the bias of albumin and albumin/creatinine ratio measurements in urine.

The objective of the study was to examine the bias of albumin and albumin/creatinine (ACR) measurements in urine. Pools of normal human urine were augmented with purified human serum albumin to generate a series of 12 samples covering the clinical range of interest for the measurement of ACR. Albumin and creatinine concentrations in these samples were analyzed three times on each of 3 days by 24 accredited laboratories in Canada and the USA. Reference values (RV) for albumin measurements were assigned by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) comparative method and gravimetrically. Ten random urine samples (check samples) were analyzed as singlets and albumin and ACR values reported according to the routine practices of each laboratory. Augmented urine pools were shown to be commutable. Gravimetrically assigned target values were corrected for the presence of endogenous albumin using the LC-MS/MS comparative method. There was excellent agreement between the RVs as assigned by these two methods. All laboratory medians demonstrated a negative bias for the measurement of albumin in urine over the concentration range examined. The magnitude of this bias tended to decrease with increasing albumin concentrations. At baseline, only 10% of the patient ACR values met a performance limit of RV ± 15%. This increased to 84% and 86% following post-analytical correction for albumin and creatinine calibration bias, respectively. International organizations should take a leading role in the standardization of albumin measurements in urine. In the interim, accuracy based urine quality control samples may be used by clinical laboratories for monitoring the accuracy of their urinary albumin measurements.

Large-Volume Paracentesis in Patients with Cirrhotic Ascites: Does It Increase the Risk of Serious Bleeding and the Need for Transfusion?

Background: Liver cirrhosis is the most common cause of ascites. For cirrhotic ascites that does not respond to diuretics and salt restriction, large-volume paracentesis is an alternative option. Methods: A retrospective cohort study of patients admitted to the Day care unit at King Abdulaziz University Hospital for therapeutic paracentesis of cirrhotic ascites was performed from March 2013-April 2014. The demographic data and results, including the platelet count, hemoglobin level, prothrombin time (PT), international normalized ratio (INR), serum creatinine, serum albumin, and bilirubin levels, were recorded. We recorded all of the bleeding episodes. Results: We recorded 118 admissions for 13 patients. Nine of them were male (69.2%), and the mean age was 58.6 ± 15.8 years. All patients had a Child-Pugh score of C. The platelet count was lower than normal for 78 admissions (66.1%), and the PT was prolonged for 99 admissions (84%). Three episodes of bleeding occurred in our cohort, all of which were mild and controlled by the local application of pressure. One patient required a platelet transfusion for severe thrombocytopenia, low platelets count was associated with elevated creatinine and low albumin levels (P = 0.014 and 0.003, respectively). Similarly, a prolonged PT was associated with low albumin, high bilirubin, low platelet, and high creatinine levels (P = 0.013, < 0.001, = 0.006, and < 0.001, respectively). Conclusions: Large-volume paracentesis is associated with only a small risk of bleeding in patients with cirrhotic ascites, and a transfusion of fresh frozen plasma (FFP) and platelets is not needed for the majority of patients.

The significance of persistent fever in the treatment of suspected bacterial infections among inpatients: a prospective cohort study.

Antibiotic escalations are frequently guided by fever persistence. Unnecessary antibiotic escalation is associated with resistance induction. We examined whether fever persistence is associated with adverse outcomes among medical inpatients with sepsis. In a single-center prospective cohort study, we included consecutive medical inpatients with suspected or documented bacterial infections. Data were collected on days 0, 2, 4, and 30 days from episode onset. We examined the association between fever persistence at 4 days and 30-day mortality on univariate and multivariate analysis. Inappropriate empirical antibiotic treatment (IAET) was defined for patients with microbiologically documented infections (MDIs). Odds ratios (ORs) are presented with 95% confidence intervals (CIs). A total of 1,621 patients were included. Among patients with MDIs, 38/206 (18.4%) given appropriate empiric therapy had continued fever on day 4, compared to 64/231 (27.7%) of patients receiving IAET, OR 0.59, 95% CI 0.37-0.93. Fever persistence was not associated with mortality after adjustment for other risk factors. Among patients with presumed sepsis who did not have MDIs, persistent fever was significantly associated with 30-day mortality on a multivariate analysis, adjusted OR 2.77 (95% CI 1.78-4.31). Other risk factors for mortality included older age, nosocomial infections, malignancy, dyspnea, shock, decreased albumin, and elevated creatinine. For patients with MDIs, fever persistence for up to 4 days is a marker of IAET, but is not associated with mortality, and should not, in itself, trigger antibiotic escalation. For patients without MDIs, fever persistence should trigger careful re-evaluation, as it is associated with mortality.

Impact of pregnancy on the concentrations of selected phthalates

Developing fetus can be exposed to toxicants during pregnancy. Impact of human pregnancy on the concentrations of phthalate metabolites mono(carboxynonyl) (MCNP), mono(carboxyoctyl) (MCOP), mono-2-ethyl-5-carboxypentyl, mono-n-butyl, mono-(3-carboxy propyl), monoethyl, mono-2-ethyl-5-hydroxyhexyl, mono-2-ethylhexyl, monoisobutyl, mono-2-ethyl-5-oxohexyl phthalate, mono-benzyl, sum of low molecular weight phthalates (∑LMW), sum of high molecular weight phthalates (∑HMW), and sum of diethylhexyl phthalates was assessed. Data from the National Health and Nutrition Examination Survey for the years 2005–2010 were used for this purpose. Regression models with logs of these metabolites as dependent variables and age, race/ethnicity, education, pregnancy, smoking and iron storage status, study year, family poverty income ratio (PIR), body mass index, urine albumin, and urine creatinine as independent variables were fitted. Pregnant females were found to have significantly lower concentrations of ∑HMW and MCNP than non-pregnant females. Concentrations of ∑LMW during the third trimester of pregnancy were significantly lower than during the second trimester of pregnancy.

Renal lymph circulation blockage alters the epithelial cell phenotype and tubular integrity: role of distinct regulation of BMP7 and TGF-β/Smads signaling pathway

To investigate the effect of lymph circulation blockage on the alteration of renal epithelial cell phenotype and the tubular integrity, as well as the underlying mechanisms. Wistar rats received left renal lymph ligation and right renal nephrectomy (KL group) or right renal nephrectomy without lymph ligation (KN group) and then were killed on day 14, day 28 and day 56. The urine, blood and kidney tissue were collected for the analysis of protein and gene expressions and morphological changes. The urine albumin and serum creatinine (Cr) in KL group were significantly increased compared with KN group. Masson and PAS staining indicated the epithelial cell degeneration, necrosis, sublethal loss and atrophy in KL rats, but not in KN group. Interestingly, from the atrophic tubules, some epithelial cells exhibited polarity changes with hypertrophy contrasting to the normal epithelial morphology of KN group throughout the experiment. By EM, ligated kidneys showed irregularly wrinkled basement membranes and epithelial cell swelling. Some intertubular areas of the KL kidney were expanded with fibrotic matrix and fibroblast-like cells. In line with these morphological changes, the fibroblast cell markers of FSP1 and α-SMA were markedly increased in contrast to the remarkable reduction in epithelial cell marker E-cadherin and tight junction protein ZO-1. Moreover, the TGF-β1/Smad2/3 signaling pathway was significantly activated in KL rats in contrast to a robust downregulation of BMP7/Smad5 signaling. Disturbance of renal lymphatic circulation resulted in the epithelial cell phenotypic alteration and impaired tubular integrity possibly via distinct regulation of TGFβ1/Smads and BMP7/Smad5 signaling pathway.

Evaluation of the URiSCAN Super Cassette ACR Semiquantitative Urine Dipstick for Microalbuminuria Screening

Microalbuminuria tests are used as screening tools for diseases, such as diabetic nephropathy, cardiovascular disease, and hypertension. The purpose of this study was to evaluate the utility of a newly introduced semiquantitative urine dipstick, URiSCAN Super cassette ACR (URiSuper-ACR [where ACR is albumin/creatinine ratio]; YD Diagnostics Corp., Korea), as a screening tool for microalbuminuria. Albumin and creatinine levels in randomly selected spot urine samples of 1,040 patients were semiquantitatively measured using URiSuper-ACR. Results using URiSuper-ACR system were compared to measurements obtained by quantitative analyzer. We also calculated diagnostic sensitivity, specificity, precision, linearity, and categorical concordance rates for the diagnosis of microalbumiuria using this system. Furthermore, we performed interference tests using standard controls to evaluate possible influence of various factors. URiSuper-ACR test showed 88.8% and 86.3% sensitivity and 90.1% and 93.8% specificity for albumin concentration and ACR, respectively. It also showed 91.1% and 92.6% positive predictive values and 87.6% and 88.5% negative predictive values, respectively. The concordance rate between URiSuper-ACR and quantitative method for albumin and creatinine concentration within the same category were 78.4% and 67.1%, respectively, and for the ±1 category were 98.8% and 99.5%, respectively. For ACR, an 80.0% concordance rate was seen within the same category. The within-run coefficients of variation (CVs) were 3.0∼15.4% and 5.2∼23.5% for albumin and creatinine, respectively, showing good linearity. In interference tests, no interference was observed except for cases with high specific gravity. URiSuper-ACR showed good diagnostic performance for the detection of microalbuminuria and may be a useful screening test in clinical laboratories.

Usefulness of HPLC Assay for Early Detection of Microalbuminuria in Chronic Kidney Disease

Since the degree and increase of albuminuria predict cardiovascular and renal diseases even within the range of normoalbuminuria. The high-performance liquid chromatography (HPLC) assay has been reported as a useful tool for earlier detection of microalbuminuria than turbidimetric immunoassay (TIA) in diabetes but has not been evaluated for other common diseases that caused chronic kidney disease (CKD). We measured albumin in spot urine by TIA and HPLC assay in 119 patients with diabetes, hypertension, IgA nephropathy in complete remission, or autosomal-dominant polycystic kidney disease whose dipstick screening tests were negative. There were significant correlations (r = 0.946) between TIA and HPLC assay, and the ratios of urine albumin/creatinine (ACR) measured by HPLC assay were always higher than those measured by TIA. The value of microalbuminuria was highest in IgA nephropathy patients, and higher in diabetic patients with hypertension than in those without hypertension. Fifty-one patients were classified as having normoalbuminuria and 42 as having microalbuminuria by both TIA and HPLC assay. However, 26 patients (21.8%) were classified having as normoalbuminuria by TIA but microalbumnuria by HPLC assay. Three of these patients were reclassified as microalbuminuria by both assays within 1 year. These results suggest that ACR measurements by HPLC assay are better than TIA for early detection and monitoring of microalbuminuria in patients with diabetes and hypertension.

Nutritional Assessment of Renal Transplant Recipients Using DEXA and Biochemical Parameters

Introduction and Aims: Malnutrition is frequently encountered in patients with CKD. Despite successful renal transplantation, malnutrition ensues. We evaluated the relationship between serum albumin levels, and various indicators of nutritional status. Methods: We did a retrospective study of 249 post-transplant patients who successfully underwent renal transplantation (between1995-2012) at a tertiary care center. Serum parameters such as albumin (bromocresol green Method) hemoglobin, electrolytes, creatinine, prednisolone dose and presence of diabetes mellitus were analyzed. Lifestyle factors such as smoking, alcohol and diet, BMI were also looked at. We classified Serum Albumin as <3-3. 4 g/dL, 3. 5-3.9 g/dL, and more than 4 g/dL. We classified BMI as per WHO guidelines. Dual Energy X-Ray Absorptiometry was used to evaluate body composition, including lean body mass, fat body mass and fat percentage. Descriptive statistics, co-relational statistics and Pearson’s Chi-Square test was used. Results: Among the 150 Males and 99 females, the mean age was 46 ± 13 years. The mean serum albumin value was 3. 6 ± 0.6 g/dL. 10% had a normal BMI, 62% Pre Obese, 21% Class 1 Obese, 5% Class 2 Obese, and 2% Class 3 Obese. A meat-based diet was ingested by 76% of our study group, and 24% were pure vegetarians. The mean dose of prednisolone taken was 20 ± 10 mg/day. 5% of the transplant patients were deceased and 1% had a failed graft. On follow up we found a significant positive correlation between serum albumin and hemoglobin (p=0. 002), LDL (p=0.046), Fat% (p=0.032) and a meat-based diet (p=0.032). A serum albumin value of>4g/dL was observed in 46% of those ingesting a meat-based diet, in contrast to 25% pure vegetarians. 66% of the vegetarians had a serum albumin value ranging from <3-3. 4 g/dL. There were negative correlations between prednisolone dose and serum albumin (p=0.005), FM (p=0. 006), Fat% (p=0. 002) and serum Creatinine (p=0.013). A positive correlation between hemoglobin levels and LDL (p=0.005), FM (p= 0.004), HCO3- (p=0. 015) and Cl-(p=0.012), and hemoglobin levels and potassium levels (p=0.015) were observed. No significant co-relation was observed between serum albumin and patient survivals. Conclusions: Serum albumin varies with diet, and is significantly higher among those eating a meat-based diet following transplant. Post-transplant mild obesity was prevalent in 62% of our study group. A higher fat content was associated with higher serum albumin levels, which may reflect a better nutritional status. Lower maintenance doses of prednisolone may improve the Albumin Levels. A further randomized controlled trial looking at the role of protein supplementation in vegetarians following renal transplantation as well as evaluating the effect of lowered prednisolone dose is warranted.

The predictive value of albuminuria for renal and nonrenal natural deaths over 14 years follow-up in a remote aboriginal community.

BackgroundAustralian aboriginal people living in remote regions have extraordinary higher rates of mortality compared with other Australian ethnicities. Albuminuria marks the underlying renal disease. This study assessed the predictive value of albuminuria for nonrenal and renal deaths in a remote Australian aboriginal community over a follow-up period of >14 years.MethodsFrom 1992 to 1997, 85% of community members participated in a health screen, which included measurement of urine albumin/creatinine (ACR) levels. Deaths and dialysis initiations were recorded until 30 November 2010. The rates of natural nonrenal and renal deaths were assessed over a mean of 14 years in the 956 participants aged 18 years and over at baseline, and mortality associated with baseline levels of albuminuria (ACR ≥ 2.7 mg/mmol) was estimated.ResultsThere were 203 natural deaths; 70 were renal deaths and 133 were nonrenal deaths, including 60 cardiovascular disease (CVD) deaths. Higher baseline ACR predicted all categories of natural death, with no apparent lower threshold for effect. Baseline ACR ≥ 2.7 mg/mmol predicted a 3.3-fold increase in all natural deaths, a 2-fold increase in nonrenal deaths and a 1.7-fold increase in CVD deaths, after adjustment for other factors. Eighty-nine percent (62 out of 70) of renal deaths occurred in those with ACR ≥ 34 at baseline, with a 24-fold increase in risk. Albuminuria (ACR ≥ 2.7 mg/mmol) contributed to 66% of risk for all natural deaths over the interval.ConclusionsAlbuminuria was still a remarkable predictor for all-cause natural death over an average of 14 years follow-up interval in this aboriginal community.

Risk factors for oral mucositis (OM) in multiple myeloma (MM) patients receiving high-dose melphalan (Mel) prior to autologous stem cell transplantation (SCT).

e19565 Background: OM is a common complication of high-dose melphalan in MM patients (pts). Proposed risk factors for OM in SCT include: low albumin and high serum creatinine (Cr) levels, both were evaluated in MM patients undergoing Mel/ASCT. (Grazziutti, ML, Bone Marrow Transplant 2006). Methods: This is a single center retrospective chart review of 214 sequentially treated MM pts who received Mel 200mg/m2 conditioning prior to SCT between January 2005-September 2011. Data collected included: demographics, Hgb, Cr, C-reactive protein and albumin on the day of SCT, length of hospital stay. OM assessment was graded as follows: Grade 1, no OM; Grade 2, mild OM; the pts maintained adequate oral intake; Grade 3, decreased oral intake and/or use of oral narcotics; Grade 4, severe OM needing intravenous narcotics. Results: The table below describes pt characteristics grouped by OM grade. Overall, 56 pts (27%) had grade 3/4 OM. Multivariate analysis of variance revealed no statistically significant correlation between OM grade and Hgb, Cr, albumin, CRP; the overall test’s p value = 0.55. There were no racial or gender differences with regard to grade of mucositis, the p-values range are 0.75 and 0.31, respectively (likelihood ratio chi-square test). Most interestingly, OM did not impact length of hospital stay. Conclusions: We did not establish any predictive risk factors for OM as previously described. Analysis of the impact of OM on MM response and event and overall survival will be presented. Studies of Mel pharmacogenetics may provide insight to patients' predisposition to OM. [Table: see text]

Association between urinary albumin-to-creatinine ratio and prehypertension

This study was operated to investigate the association between urinary albumin-to-creatinine ratio (UACR) and physical situations as hypertension and prehypertension among women. Blood pressure, height, weight and waist circumference were measured and factors such as cigarette smoking, alcohol intake, family history of hypertension, were investigated. Blood glucose and lipid, serum uric acid, urinary albumin and urinary creatinine were tested on 1796 women aged ≥ 30 years living in the Jinchang district of Suzhou. Associations between UACR and hypertension as well as prehypertension were analyzed, by using ordinal multinomial logistic regression models. The mean levels of UACR were 15.54 (7.67, 32.53), 9.01 (5.45, 18.06), 7.13 (4.60, 12.50) mg/g and the rates of higher UACR were 27.57%, 13.42%, 9.61% in hypertensive, pre-hypertensive and normotensive subjects, respectively, with significant differences noticed among the three groups (P < 0.05). The average systolic blood pressure/diastolic blood pressure appeared to be 125.3/80.9, 128.8/82.7, 130.8/84.0 and 135.1/85.9 mm Hg for participants with UACR in the first, second, third and fourth quartile, respectively. The risks of prehypertension or hypertension increased with increasing UACR levels. Dose-response relationship was seen between UACR and risks of prehypertension or hypertension. Multivariable adjusted odds ratios (95%CI) of prehypertension or hypertension in the upper quartiles of UACR were 1.32 (1.02, 1.70), 1.72 (1.32, 2.24), and 2.37 (1.80, 3.11), respectively, when compared with the lowest quartile. Elevated UACR was associated with both hypertension and prehypertension among women.

Does the antiviral therapy of patients with chronic hepatitis exert nephrotoxic effects?

Introduction: HBV and HCV chronic hepatitis can be accompanied by secondary renal disease. In addition, these patients receive antiviral drugs with potential nephrotoxicity. It is known that interferon (IFN) therapy in HCV-infected kidney transplant recipients is followed by rejection of the transplant in 50% of the cases. Ribavirin is contraindicated in hemodialyzed patients and in patients with a GFR <50 ml/min/1.73 m2. IFN therapy requires dosage reduction and close monitoring in patients with a GFR <50 ml/min/1.73 m2 and in patients with end stage renal disease. The aim of our study was to assess the nephrotoxicity of antiviral drugs in patients with chronic hepatitis by measuring three renal biomarkers: urinary albumin, N-acetyl-β-d-glucosaminidase (NAG) and α 1-microglobulin, as well as glomerular filtration rate (GFR-MDRD4) before and at 6 months of therapy.Methods: Fifty-five patients (28 male and 27 female, with a mean age of 47.85 ± 12.03 years) with chronic hepatitis (40 patients with HCV, 13 patients with HBV, 1 patient with HBV+HCV, and 1 patient with HBV+HDV) were enrolled into the study. Different antiviral drug associations were used on a case-by-case basis. The 40 patients with HCV chronic hepatitis received either Peg-IFN-α 2a+Ribavirin (37 patients) or Peg-IFN-α 2b+Ribavirin (3 patients). The 13 patients with HBV chronic hepatitis received Peg-IFN-α 2a (9 patients), Lamivudine (2 patients), Entecavir (1 patient), or Adefovir (1 patient). The patient with HBV+HCV chronic hepatitis received Peg-IFN-α 2a+Ribavirin. The patient with HBV+HDV chronic hepatitis received IFN-α 2a. Urinary albumin (ELISA), NAG (colorimetrical method), α 1-microglobulin (ELISA), and serum creatinine were measured before and at 6 months of antiviral therapy. Urinary markers were expressed as either mg/gCr (for albumin and α 1-microglobulin) or U/gCr (for NAG). Statistical analysis (Pearson’s correlation coefficient, paired t-test and χ2-test) was performed.Results: At 6 months of therapy urinary albumin/gCr did not increase significantly: 16.58 ± 23.39 vs. 15.85 ± 24.96 mg/gCr before therapy, p = 0.87. Urinary NAG/gCr did not increase significantly: 4.21 ± 3.37 vs. 3.83 ± 3.2 U/gCr before therapy, p = 0.53. Urinary α 1-microglobulin/gCr was almost unchanged: 4.38 ± 4.47 vs. 4.38 ± 3.57 mg/gCr before therapy, p = 0.99. The GFR did not decline significantly: 92.41 ± 22.21 vs. 94.59 ± 36.1 ml/min/1.73 m2 before therapy, p = 0.7. Ten patients (18.18%) were albuminuric before therapy, and 14 patients (25.45%) were albuminuric at 6 months of therapy, a non-significant increase (p = 0.35). We found a correlation between urinary albumin/gCr and NAG/gCr and between urinary albumin/gCr and α 1-microglobulin/gCr both at baseline and at 6 months of therapy: r = 0.54, p = 0.0005; r = 0.29, p = 0.03; r = 0.51, p = 0.0005; and r = 0.4, p = 0.002, respectively. In the patient receiving Adefovir, a known nephrotoxic drug, two of the three biomarkers (urinary albumin/gCr and NAG/gCr) increased, most notably NAG/gCr. Both HCV and HBV chronic hepatitis therapy were associated with non-significant changes in renal biomarker excretion and GFR.Conclusions: With the exception of Adefovir, all of the drug associations used in this study were safe.

Occult Hepatitis B Flare-up after Chemotherapy Treatment in HBsAg Negative Patient

Reactivation of Hepatitis B virus causing liver damage is a concern in patients with chronic HBV infections who receive immunosuppressive or cytotoxic treatments. HBV screening should be considered for all patients going to receive immunosuppressive regimens which have the potential to induce reactivation of HBV infection. We discuss here a case of occult Hepatitis B flare after chemotherapy in a patient who had negative acute hepatitis profile including HBsAg prior to therapy and baseline serum AST, ALT, INR, albumin, bilirubin and serum creatinine were within normal limits.

New trends in the laboratory diagnostics of proteinuria and albuminuria

According to current clinical trials, albumin excretion is an early indicator of cardiovascular damage. While proteinuria is considered as a marker of kidney function, albuminuria indicates cardiovascular risk first of all. Sensitivity of the previous laboratory tests does not meet the clinical requirements, and the error of urine collection makes the results misleading. For that reason recent guidelines suggest to calculate albumin/creatinine (ACR) and protein/creatinine (PCR) measured from the first morning urine. For the clinical diagnosis of albuminuria the sensitive immunoturbidimetric assays are suggested. Albumin dipsticks are not recommended for the measurement of albuminuria. Wide-range urinary protein reagents are also available with high sensitivity, while serum reagents are not applicable (Biuret). The traceability of calibrator to a reference material is a critical requirement. Proteinuria and albuminuria of a patient should be monitored in the same laboratory, using a fixed method and cut-off value. Albumin/creatinine value should be reported together with gender-dependent reference range.