Amalia Lucchetti

Which method for quantifying ?microalbuminuria? in diabetics?: Comparison of several immunological methods (immunoturbidimetric assay, immunonephelometric assay, radioimmunoassay and two semiquantitative tests) for measurement of albumin in urine

We have compared the chemical and clinical characteristics of an immunonephelometric assay (INA), two immunoturbidimetric assays (ITA) and two semiquantitative methods with those of a solid-phase radioimmunoassay (RIA) for measurement of urinary albumin (UA) concentration in 136 diabetic patients. INA and RIA had similar accuracy, and provided comparable results. However, RIA has slightly greater sensitivity than INA, which is easier and faster. Good agreement was also found between RIA and the two ITA methods, although one of these overestimated RIA values in the low-medium range (5–30 mg/l) of urinary albumin. ITA seems suitable for initial screening of albuminuria in diabetic patients but more sensitive procedures (such as RIA and INA) seem preferable for measurement of UA concentrations in the normal range. The two semi-quantitative methods showed high sensitivity but poor specificity, because of the large number of false positive results. About 50% of diabetic patients “positive” by these methods did not have microalbuminuria. The utility of these methods is questionable, because many samples from diabetic patients need to be reassayed by a more specific and sensitive assay such as the RIA, INA or ITA methods.

Gamma-glutamyltransferase is a reliable marker for tubular effects of contrast media.

The aim of this study was to evaluate the usefulness of the measurement of urinary excretion of the brush-border enzyme gamma glutamyl-transferase (GGT), in comparison with that of alanine aminopeptidase (AAP), as a marker for tubular toxicity due to contrast media (CM). Urinary activities of AAP and GGT were measured prior to the administration of CM and 1, 3 and 5 days after in forty-nine adult renal patients undergoing a radiological examination with intravascular administration of CM. The behavior of GGT was similar to that of AAP. In fact, urinary activities of both AAP and GGT increased greatly after CM. This effect was maximal on the 1st day and statistically significant for both enzymes. Furthermore, on the 1st day a relevant increase of enzyme activity (at least +50% over the basal value) was observed in the same number of patients (67%) for AAP and GGT. The concordance between GGT and AAP variations was high and statistically significant. Finally, different variables (osmolarity, dose of CM, and baseline renal function of the patients) had a similar effect on urinary excretion of AAP and GGT. The repeatability of duplicated determinations of GGT resulted better than that of AAP. In conclusion, the good concordance of the results of GGT with those of AAP justifies the use of GGT as a marker for tubular effects due to CM. Furthermore, the measurement of GGT has a better repeatability than that of AAP.

Tubular Toxicity Is the Main Renal Effect of Contrast Media

The aim of this study is to evaluate the effects of contrast media on both tubular and glomerular function. Different parameters of tubular and glomerular function were determined before and at 1, 3, and 5 days after the intravascular administration of contrast media in 100 adult renal patients (plasma creatinine 0.6-10.8 mg/dL, mean: 1.3). Urinary activities of five tubular enzymes (alanine aminopeptidase, gamma-glutamyltransferase, alkaline phosphatase, lactate dehydrogenase, N-acetyl-beta-D-glucosaminidase) increased significantly on the first day after the administration of contrast media, indicating a tubular damage. Glomerular filtration rate and the conventional tests of glomerular function (plasma creatinine, creatinine clearance, and urinary proteins) presented only slight variations after the administration of contrast media. In conclusion, contrast media principally affected the renal tubule (as demonstrated by enzymuria), while their effects on glomerular function were very mild.

EFFECTS ON RENAL HEMODYNAMICS AND TUBULAR FUNCTION OF THE CONTRAST MEDIUM IOHEXOL IN RENAL PATIENTS

Renal function was assessed in 20 (11 female and 9 male, age 21-76 years, mean 53) renal patients with a creatinine clearance 25-145 ml/min, mean 95, to evaluate the effects of iohexol, a non-ionic low-osmolar contrast medium. Intravenous urography was performed in 16 patients and computed body tomography in 4, using a dose of iohexol ranged between 0.6-3.3 (mean 1.17) g/kg b.w. Different parameters of renal function were determined in the week preceding and 1, 3 and 5 days after the administration of iohexol. The principal renal effect of iohexol was an increase of urinary alanine aminopeptidase, gamma-glutamyltransferase, lactate dehydrogenase, alkaline phosphatase and N-acetyl-beta-D-glucosaminidase. The maximum increase of enzymuria was observed on day 1 after the administration of iohexol. In most cases enzymes returned to base-line values within 3 days. No relevant variation of renal hemodynamics (glomerular filtration rate and effective renal plasma flow) was observed after iohexol. In conclusion, iohexol can increase of urinary enzymes, but the effect is rapidly reversible and is not accompanied by a clinically significant impairment of renal hemodynamics.

Effects of Contrast Media on Renal Hemodynamics and Tubular Function: Comparison between Diatrizoate and Iopamidol

The administration of iodinated radiologic contrast media (CM) is the third cause of acute renal failure: about 12% of the cases in hospitalized patients (1,2).

Renal Effects of Ionic and Nonionic Contrast Media: Comparison between Diatrizoate Meglumine and Iopamidol

Renal damage is a potential adverse side effect of the administration of iodinated contrast media (CM). Infact, CM represent one of the most frequent causes of renal failure (1,2). The renal damage determined by CM is sometimes irreversible (3). The mechanisms of this renal injury are not yet well understood. Hyperosmolality of the administered CM has been claimed to be an important factor of renal damage (4). No exhaustive data are available concerning the effects on renal function and nephrotoxicity of the different CM available. The aim of this study is the comparative evaluation of renal effects and nephrotoxicity of two different CM: diatrizoate meglumine (a high-osmolality ionic CM) and iopamidol (a new low-osmolality nonionic agent), after intravenous administration.

Increased urinary albumin excretion aggregates with atherosclerotic risk factors in type 2 (non-insulin-dependent) diabetes mellitus

Supranormal urinary albumin excretion (microalbuminuria) is an early indicator of microangiopathy, i.e. diabetic nephropathy, and is associated with higher cardiovascular mortality in both type 1 and type 2 diabetes. The relationship between the presence of microalbuminuria and some atherosclerotic risk factors has been evaluated in 318 (170 male, 148 female) type 2 (non-insulin-dependent) diabetic subjects [age 63±10 years; known duration of diabetes 10.9±8.8 years; age at diabetes diagnosis 52±11 years; systolic blood pressure (BP) 150±23 mmHg; diastolic BP 86±11 mmHg (mean±SD)]. In “early morning” urine samples, albumin (immunonephelometry) and creatinine were assayed. On the basis of the albumin/creatinine ratio (A/C, mg/mmol), patients were categorized as normoalbuminuric (Na; A/C<2.0;n=159, 50%), microalbuminuric (ma; A/C 2–20;n=135, 42.5%) or macroalbuminuric (Ma; A/C >20;n=24, 7.5%). The three groups were closely matched for age, age at diagnosis, duration of diabetes, and fasting plasma and urinary glucose levels. Systolic and diastolic BP rose progressively with increasing urinary A/C ratio levels. While high-density lipoprotein (HDL) cholesterol was unaffected by albuminuria, total cholesterol (218±45 vs 198±43 mg/dl,P<0.001) and low-density lipoprotein (LDL) cholesterol (145±42 vs 131±38 mg/dl,P<0.05) levels were higher in microalbuminuric than in normoalbuminuric patients. Further, a significant correlation (r=0.16,P<0.01) existed between albuminuria and triglyceride concentrations. Prevalence of arterial hypertension, defined as BP≥160/95 mmHg and/or drug treatment (Na, 51%; ma, 65%; Ma, 78%;P<0.001) and obesity, defined as body mass index (BMI)>30 (Na, 15%; ma, 26%; Ma, 32%;P<0.05) rose with increasing A/C ratios. Both coronary heart disease (30% vs 15%) and intermittent claudication (18% vs 7%) were more frequent in microalbuminuric than in normoalbuminuric subjects. Finally, multiple stepwise regression analysis showed that urinary albumin excretion is significantly and independently associated with coronary heart disease and intermittent claudication, also taking into account hypertension and other established cardiovascular risk factors. In type 2 diabetes microalbuminuria tends to aggregate with risk factors for atherosclerotic vascular disease, e.g. increased prevalence of hypertension and obesity, elevated total and LDL cholesterol, and raised triglycerides levels. These abnormalities may only explain the excess of cardiovascular morbidity and mortality in part. Microalbuminuria per se may be an important and independent cardiovascular risk factor.

Diltiazem: Its Antihypertensive Activity without Renal Effects in Man

Antihypertensive activity and renal effects of diltiazem have been evaluated in 13 adult patients. After a week of treatment with placebo diltiazem was administered per os at a daily dose of 240 mg for 6 weeks. Blood pressure decreased from a mean value of 152/99 mm Hg (±13/6) to 144/91 (±17/8). Pulse rate decreased from 74 (±9) to 69 (±8). Plasma urea, creatinine, uric acid and their clearances, GFR, ERPF and urine enzymes remained stable during therapy. Plasma potassium decreased from 4.0 (±0.4) mEq/1 to 3.7 (±0.3); plasma glucose increased from 81 (±15) mg/dl to 98 (±30). These results indicate that diltiazem is an effective antihypertensive agent which does not cause any adverse renal effect.

Serum and urinary enzyme activities in renal artery embolism

Renal artery embolism is not a rare occurrence, especially in patients with valvular heart disease, but the early diagnosis of this condition is infrequently accomplished. We report the clinical and laboratory data of 2 patients with valvular heart disease who presented with unilateral renal artery embolization. The usefulness of the determination of serum and urinary enzymes and renal function tests is discussed. We propose that these parameters support an earlier and more accurate diagnosis of renal artery embolism.

Chronic Intravascular Hemolysis Following Cardiac Replacement With the St. Jude Medical Prosthesis: Comparative Study With the Bjork — Shiley Prosthesis

This study compares 153 patients with SJM prosthetic valves and 37 patients with Björk-Shiley valves for evidence of intravascular hemolysis and analyzes the degree of hemolysis by position (mitral or aortic), diameter, number of pros theses and duration of implant. The hematological status of all the patients was assessed by the following laboratory tests: hemoglobin concentration, serum lactatedehydrogenase (LDH), red blood cells count (RBC) , reticulocytes, serum iron, serum haptoglo bin, hemosiderinuria and schistocytes count. The results of laboratory tests and the characteristics of implant were com pared by the Pearson X2 for qualitative variables and by the analysis of covari ance, using the regression approach, for continuous variables. This study indicates a significantly higher degree of hemolysis in the St. Jude Medical group as shown by LDH and haptoglobin values which are the most reliable sources revealing qualitative hemolysis. The relationship between hemolysis, duration of implant, diameter, number and position of the prostheses, inside the SJM group, shows significance only between hemolysis and number of prostheses. Furthermore, the data show a higher degree of hemolysis in the mitral posi tion for SJM prosthesis and in aortic position for Björk-Shiley (B-S) prosthesis. The explanation for this difference may be the turbulent flow of regurgitant leakage at the pivots recesses in the SJM valve which is higher in the mitral position where there is the maximal pressure gradient and the asynchronous closure of the two leaflets. The authors conclude that, in spite of the higher degree of hemolysis shown by the SJM prosthesis, there is no reason to revaluate its use because no case of clinically significant hemolytic anemia was observed in this study.