Claudio Bianchi

REAPPRAISAL OF SERUM β2-MICROGLOBULIN AS MARKER OF GFR

Introduction. Beta 2 microglobulin(β2M) is filtered by the glomeruli and reabsorbed by the proximal tubularcells where it is metabolized. Its plasma concentration increases with decreasingrenal function. Aim. To compare serum creatinine(Cr) and serum β2M as markers of GFR. Patientsand Methods. In 160 adult patients, with various kidney diseasesand different GFR, serum Cr (autoanalyzer), serum β2M (RIA) and GFR (bladdercumulative method using 99mTc-DTPA as glomerulartracer) were measured in the same day. Results.A linear relationship was observed between ln GFR and both ln serum Cr (lnCr= 3.112–0.716lnGFR; r = 0.92) and ln serum β2M (lnβ2M = 4.274–0.814lnGFR; r = 0.90). With decreasing GFR the increase in serum β2M was higherthan that of serum Cr (see regression coefficients that are significantlydifferent). The normal upper limit of serum Cr corresponds to a GFR 48.1 mL/minwhile that of serum β2M to a GFR 65.0. With decreasing GFR the increaseof serum β2M occurs before than that of serum Cr. Conclusions.With declining renal function, serum β2M increases more and before thanserum Cr. Serum β2M is a good endogenous marker of GFR, better than serumCr.

Measurement of Glomerular Filtration Rate in Man Using DTP A-99mTc

The aim of this study was the evaluation of the mechanism of renal excretion of DTPA-99mTc in man. For this purpose the renal clearances of DTPA-99mTc and diatrizoate-131

RELATIONSHIP BETWEEN RENAL FUNCTION AND BLOOD LEVEL OF CHROMOGRANIN A

Chromogranin A (CGA) is a low MW (49,000) acidic hydrophilic protein. It is synthesized in the chromaffm granules of the neuroendocrine cells, and has been found circulating in the blood of healthy subjects. The aim of this study was to assess the relationship between serum levels of CGA and renal function. One hundred two renal patients (45 M and 57 F; age 14–76 years, mean 52) participated in the study. Glomerular filtration rate (GFR) was measured by the bladder cumulative method, using 99mTc-DTPA as a tracer. Blood CGA was determined by RIA. Plasma creatinine, β2microglobulin (β2m) and tumor associated trypsin inhibitor (TATI) were also determined. The reduction in renal function was associated with an increase in all of the above studied parameters. In patients with advanced renal failure (GFR < 20 mL/min) CGA levels increased by 22-fold as compared to the patients with normal renal function (GFR > 100 mL/min). The other studied parameters were also increased but to a lesser degree, e.g., TATI 14-, β2m 8- and creatinine 5-fold. The results of this study demonstrate that renal handling of the CGA is similar to other low MW proteins, and it accumulates in the blood in renal failure.

99mTc-aprotinin: A new tracer for kidney morphology and function

AbstractAprotinin (Ap), a low-molecular-weight polypeptide (6500 dalton), is a protease inhibitor which is electively and stably accumulated in the kidney. In 112 adult patients, with either uni- or bilateral renal disease with different degrees of renal impairment (from normal GFR to advanced renal failure), renal scans were performed by means of Ap labelled with99mTc. Highly satisfactory renal scans were obtained in all patients. In 20 patients with renal failure (serum creatinine 1.8–8.5 mg/dl, mean 4.7) a comparison was made of the renal scans obtained with99mTc-Ap and with99mTc-DMSA.99mTc-Ap was slightly better than99mTc-DMSA, especially in patients with far advanced renal failure.Some aspects of the pharmacokinetics of99mTc-Ap were studied in 72 cases. In 22 of these patients plasma clearance of99mTc-Ap was determined by the single injection method using a two-compartment model. In patients with GFR>90 ml/min plasma clearance of99mTc-Ap was 67.6±8.4 SD ml/min. A good correlation was observed between plasma clearance of99mTc-Ap and GFR (r=0.74). After IV injection99mTc-Ap was stably fixed by the kidney. Renal radioactivity remained stable between the second and eighth hour after the injection. Urinary excretion of radioactivity measured in 35 patients in the first and in the second 2-h interval after IV injection of99mTc-Ap was negligible in all patients (2.7±1.5 SD percent of the dose in the first 2 h; 2.8±1.4 SD between the second and fourth hour). 99mTc-Ap is an excellent agent for renal imaging. It also seems promising for renal function studies.

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.

Glomerular and tubular effects of contrast media diatrizoate and iopromide

The aim of this study is to evaluate the nephrotoxicity of two contrast media (CM), with different physicochemical characteristics: diatrizoate (ionic high-osmolar), iopromide (nonionic low-osmolar). Intravenous urography was performed in 34 patients: 17 were examined with diatrizoate and 17 with iopromide, randomly assigned. Different parameters of glomerular and tubular function were measured before and at 6, 24, and 48 h after urography. Both contrast media induced a reversible increase of urine enzymes, which was significantly higher after diatrizoate. In particular, diatrizoate determined a relevant increase of brush border enzymes gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) and of cytosolic enzyme lactate dehydrogenase (LDH), while, after iopromide increases of urinary enzymes were less evident and were significant only for GGT and ALP. In addition, diatrizoate affected other tubular functions (clearances of phosphorus and uric acid) and slightly decreased glomerular function in a few patients. In no case did these glomerular and tubular effects have a clinical relevance. In conclusion, the nonionic low-osmolar contrast medium iopromide appeared less nephrotoxic than diatrizoate. The cost-benefit ratio needs further examination.

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.

Creatinine Clearance Can Be Predicted from Plasma Creatinine and Body Composition Analysis by Means of Electrical Bioimpedance

The aim of this study was to evaluate the possibility of predicting creatinine clearance (CCr) from plasma creatinine (PCr) and body com-position analysis by means of electrical impedance, thereby avoiding urine collection. Fat-free mass (FFM) and body cell mass (BCM) were measured in 50 renal patients (M29, F21; aged 17-74 years; mean 52.6) with different degrees of renal function (PCr 0.8-9.0 mg/dL, mean 2.13) by using a tetrapolar impedance plethysmograph. The relationship between 24 h-urinary creatinine excretion (UCr) and FFM and BCM was evaluated in 20 of the above reported patients (MI I, F9; PCr 0.8-9.0 mg/dL, mean 2.27). The mean ratio of 24 h UCr/FFM was 25.6 mg/kg in males and 22.5 in females and that of 24 h UCr/BCM was 51.9 mg/kg in males and 48.1 in females. CCr was estimated in the remaining 30 patients (M18, F12; PCr 0.9-8.8 mg/dL, mean 2.04) from individual FFM and BCM values and PCr. In the same patients CCr was predicted also according to the Cockcroft and Gault formula and, for comparison, was measured with the conventional method by collecting 24 h urine, CCr predicted from the values of FFM and BCM gave a good estimate of 24 h CCr, more precise than that of Cockcroft and Gault CCR. Also, the repeatability of the predicted CCr was clearly better than that of 24 h CCr. In conclusion, creatinine clearance can be predicted, avoiding urine collection, from plasma creatinine and body composition analysis by means of electrical impedance.

Serum tumour-associated trypsin inhibitor (TATI ) and renal function

Tumour-associated trypsin inhibitor (TATI) is a low molecular weight (MW) protein employed as a tumour marker. The blood levels of some low MW proteins increase in renal insufficiency. The aim of this study is to evaluate the relationship between serum TATI and glomerular filtration rate (GFR). Serum beta 2-microglobulin (beta 2M) and plasma creatinine were also determined. The decrease of GFR was accompanied by an increase in the other parameters. The maximum increase of TATI was from a mean basal value of 8.51 +/- 5.58 micrograms l-1 in subjects with normal renal function to 107.27 +/- 63.34 micrograms l-1 in patients with renal failure; beta 2M increased from 1.45 +/- 0.38 to 11.16 +/- 5.73 mg l-1 and creatinine from 1.05 +/- 0.17 to 5.07 +/- 1.93 mg dl-1. The increase in TATI occurs sooner and is greater than that of beta 2M and of creatinine. These results suggest that TATI is handled by the kidney. It is sensitive marker of reduction in renal function. When TATI is used as a tumour marker, renal function must be taken into account in the evaluation of the results.