Early Markers Of Renal Dysfunction Research Articles

Early markers of renal dysfunction in patients with beta-thalassemia major

Studies of renal involvement in thalassemia syndromes have been varied and few. The most important cause of mortality and morbidity in these patients is organ failure due to iron deposition. We report here a cross-sectional study carried out between February 2005 and February 2006 on all beta-thalassemia major patients being treated in Mofid Children's hospital, Tehran. The aim of the study was to detect renal dysfunction in these patients. The patient cohort consisted of 103 patients with various disease severities. Fresh first morning urine samples were collected and analyzed for sodium (Na), potassium (K), calcium (Ca), creatinine (Cr), phosphate, uric acid (UA), N-acetyl beta-D-glucosaminidase (NAG) and amino acids. We also carried out a complete blood count evaluation and assayed fasting blood sugar and serum ferritin, sodium, potassium, creatinine, uric acid and amino acids in all patients. The mean age of our patient cohort was 12.5+/-5.53 years and 53.4% were female. Abnormal levels of urinary NAG were detected in 35.9% of patients (confidence interval 26-45%). Abnormal levels of fractional excretion (FE)-Na, FE-K and FE-UA and abnormal urine protein Pr/Cr and urine Ca/Cr ratios were present in 29.1, 7.8, 52.4, 0.3 and 22.3% of the patients, respectively. There was a significant relationship between urinary NAG and the age of the patient (R=0.35), duration of deferoxamine therapy (R= 0.31), duration of receiving blood transfusions (R=0.34) and level of fasting blood sugar (R=0.2). We concluded that renal disorders are not rare in patients with beta-thalassemia major and that they may increase in terms of frequency with age, increased duration of transfusion and deferoxamine usage and high levels of blood sugar.

TIME-COURSE REDUCTION OF RENAL FUNCTION IN RATS ON HIGH SODIUM INTAKE: ACUTE REVERSAL BY POTASSIUM CANRENOATE

1. Time course of renal alterations associated with long-term (since weaning) administration of a high sodium (HS, 8% NaCl) diet was assessed in Sprague-Dawley rats. Reversal by acute administration of the mineralocorticoid receptor antagonist, potassium canrenoate (40 mg/kg, i.p.) or the type 1 angiotensin II receptor antagonist, losartan (10 mg/kg, i.v.), was evaluated at the age of 5 months (i.e. after 21 weeks of HS feeding). 2. High sodium intake had no detectable effect on blood pressure; however, albuminuria was always higher in the HS than control group. Glomerular filtration rate, renal plasma flow and filtration fraction decreased significantly after 12 weeks of HS diet by approximately 50, 30 and 20%, respectively. Canrenoate was effective and markedly reversed the renal hypofiltration associated with HS feeding without change in systemic blood pressure. In contrast, losartan reduced blood pressure and it was devoid of a beneficial effect on renal function. 3. The present observations indicate that hypofiltration and hypoperfusion of the kidney occurred progressively and require a long period of exposure to a high sodium intake. Albuminuria, which increased before detectable changes in renal function, may represent an early marker of renal dysfunction. The beneficial effect of acute administration of potassium canrenoate favours the participation of aldosterone, at least partially, in the sustained deterioration of renal function after 21 weeks of high sodium feeding.

Early markers of renal dysfunction in patients with sickle cell/β-thalassemia

Progressive renal failure is one of the main complications in HbS/beta-thalassemia (HbS/beta-thal). Early identification of patients at high risk of developing renal failure is of great importance as it may allow specific measures to delay the progression of renal damage and thus reduce the incidence of end-stage renal failure and mortality. Early predictors of renal impairment in HbS/beta-thal remain to explore. Within this context, we studied 87 compound HbS/beta-thal patients (36 males/51 females; median age 39 years) and 30 healthy controls. In addition to conventional renal biochemistries we measured serum cystatin-C (Cys-C), urine N-acetyl-beta-D-glucosaminidase (NAG) excretion and serum and urinary beta(2)-microglobulin (beta(2)-M). Cystatin-C, NAG and serum beta(2)-M levels were higher in patients than controls. The incidence of patients with high levels of Cys-C, NAG, and beta(2)-M was 32.1, 74.7, and 70.1% respectively, while only 6.8% of patients had increased serum creatinine levels. Cystatin-C and serum beta(2)-M showed a strong correlation with creatinine clearance and age, while NAG positively correlated with proteinuria. An inverse correlation was also shown between hemoglobin and beta(2)-M, NAG, and Cys-C levels. Seven patients with proteinuria received therapy with angiotensin-converting enzyme (ACE) inhibitors. Changes of poteinuria positively correlated with NAG levels. These results indicate that Cys-C is an accurate marker of renal dysfunction, and urinary NAG excretion can be considered as a reliable index of the tubular toxicity, and possible predictor of proteinuria and eventual renal impairment in HbS/beta-thal patients. Furthermore, NAG measurement may be used for monitoring ACE-inhibitors therapy in HbS/beta-thal patients with proteinuria.

Biomarkers in chronic kidney disease: utility and issues towards better understanding

Biomarkers are substances that reflect the presence of a given disease, its pathophysiology or organ damage. These indicators are increasingly proposed to assess prognosis or the response to treatment. This review examines the value of a series of biomarkers which have been recently tested in prospective studies in chronic kidney disease and end-stage renal disease patients. C reactive protein has coherently emerged as an early marker of renal dysfunction. The usefulness of this measurement for predicting the evolution of chronic kidney disease or for monitoring the response to renoprotective treatment, however, still remains unproven. On the other hand the measurement of C reactive protein can be recommended for monitoring the risk of atherosclerotic complications in patients with chronic kidney disease and end-stage renal disease, particularly in those with evidence of coronary heart disease or other cardiovascular complications (i.e. in the vast majority of patients followed up in nephrology clinics). There is growing interest in homocysteine and asymmetric dimethyl arginine as biomarkers of cardiovascular and renal risk but the usefulness of these biomarkers in clinical practice remains to be proven. Brain natriuretic peptide and troponin T are strongly related to cardiovascular outcomes in end-stage renal disease patients but their value in this population still requires to be proper tested in specifically designed intervention studies. Among emerging biomarkers C reactive protein is the only one which is very near to fulfilling the methodological requirements for being recommended in clinical practice.

α1-MICROGLOBULIN - A POTENTIAL MARKER FOR EARLY RENAL DYSFUNCTION IN CHILDREN WITH ELEVATED BLOOD LEAD CONCENTRATIONS. † 2175

Background: Studies of the long term effects of childhood plumbism disagree on the significance of renal abnormalities. One early study found no evidence of renal dysfunction in patients who had experienced lead poisoning 9-17 years, but in a more recent report survivors of childhood lead poisoning had increased risk of hypertension developing in the setting of supranormal creatinine clearance. In adult males chronically exposed to lead N-acetyl-β-D-glucosaminidase (NAG) and α1-microglobulin(α1M) were the most sensitive indicators of lead-induced changes in the nephron. Aim: To determine whether NAG, α1M, andβ2-microblobulin (β2M) are useful markers of early renal dysfunction in children with elevated blood lead concentrations(CPB). Methods: Twenty patients (mean age 47.2 mos, range 13-94 mos) with elevated CPB (>8.0 μg/dL), no history of renal disease, and who were followed in the Lead Clinic of The Children's Hospital of The King's Daughters (CHKD) were studied. Twenty children with normal renal function (serum creatinine 0.40 mg/dL). The meanβ2M Index of those 5 patients was significantly higher than their matched controls (0.17 vs. 0.12, p = 0.043), and the other 15 clinic patients (0.17 vs. 0.11, p = 0.04). The maximum CPB of the 5 patients was also higher than the other clinic patients (33.7 μg/dL vs. 22.8 μg/dL, p = 0.091), although statistical significance was not achieved due to limited sample size. Conclusion: Urinaryα1M and β2M Index may be useful markers of early renal dysfunction in children exposed chronically to elevated CPB.

Assessment of a screening protocol for occupational renal disease.

Using 10 guidelines for medical screening programs, this review assesses a screening protocol that seeks to identify presymptomatic occupational renal disease among workers with nephrotoxin exposure. The protocol uses urinary markers of early renal dysfunction for the screening test. The review reveals that arguments for screening are the clinical significance of renal disease, worker acceptance of urine collection, the availability of exposure reduction as an intervention, and the availability of diagnostic and treatment facilities. Obstacles to screening are the lack of an effective intervention, the lack of strong evidence to indicate that an elevation in the urinary markers represents a preclinical stage of occupational renal disease, and the absence of firm numbers to demarcate normal from elevated concentrations of urinary markers. Given these obstacles, screening for occupational renal disease is not recommended.

Does occupational cobalt exposure determine early renal changes?

A cohort of workers occupationally exposed to cobalt (Co) dusts was examined to assess possible subclinical renal effects attributable to Co. Cross-sectional investigations involved 26 workers with a mean age of 34.2 (S.D., 8.3), chronically-exposed (median, 3.5 years; range, 0.9–11) to Co dusts in hard-metal manufacturing factories. Thirty-five healthy control workers, with a mean age of 32.5 (S.D., 4.6) were also examined. Individual interviews were used to exclude subjects with renal or systemic diseases, intake of nephrotoxic drugs, and exposure to known nephrotoxins. Exposure levels, assessed by ambient and biological monitoring, showed an estimated exposure approaching the ACGIH-recommended TLV of 50 μg/m 3. Immunochemical methods were used to measure urinary albumin, retinol-binding protein (RBP), β 2-microglobulin (β 2m), and tubular brush-border antigens. The prevalence of abnormal values for early markers of renal dysfunction was similar in Co-exposed workers and in controls. However, within the reference interval, the cumulated frequency distribution for β 2m was shifted towards higher values in the exposed group. No relationship was detected between renal markers and either intensity or duration of exposure. In spite of a limited number of observations, these findings suggest that the kidney is not a target organ during occupational exposure to Co.

The Beta 2 Microglobulin Urine to Serum Ratio: An Early Marker of Renal Dysfunction in Primary Hyperparathyroidism

The Beta 2 Microglobulin Urine to Serum Ratio: An Early Marker of Renal Dysfunction in Primary Hyperparathyroidism

Early biological indicators of S-(1,2-dichlorovinyl)-L-cysteine nephrotoxicity in the rabbit.

The progression of changes in rabbit kidney function following dosing with the nephrotoxin S-(1,2-dichlorovinyl)-L-cysteine (DCVC, 20-50 mg/kg) was determined. Proteinuria was observed 0.5-1 hr after administration of DCVC at doses of 20-50 mg/kg. Blood urea nitrogen levels, glomerular filtration rates, urinary glucose excretion, and urine volume were also altered following DCVC dosing; however, these parameters were less sensitive than proteinuria as markers of early renal dysfunction. None of these latter four indicators were affected by low DCVC doses, nor were they altered by high DCVC doses until 1.5-2.5 hr after dosing. Dose-dependent morphological changes to kidney structure were also observed 5 hr after DCVC administration. Low doses caused damage restricted to brush border membranes in the pars recta, while higher doses produced a necrotic lesion encompassing all regions of the proximal tubule. This study indicates that DCVC can cause rapid renal dysfunctional changes which are first detected by elevated urinary protein excretion.