Annalisa Lucchesi

Cystatin C, β2-microglobulin, and retinol-binding protein as indicators of glomerular filtration rate: comparison with plasma creatinine

BACKGROUND The aim of this study was to assess the diagnostic accuracy of plasma levels of three low-molecular weight proteins cystatin C, beta 2-microglobulin, and retinol-binding protein, as indicators of impairment of glomerular filtration rate in comparison with plasma creatinine. METHODS Glomerular filtration rate (GFR) was measured in 110 patients (51 M and 59 F, aged 18--79 years); creatinine (Creat), cystatin C (Cys), beta 2-microglobulin (beta 2M), and retinol-binding protein (RBP) were determined on the same day. The correlation coefficients between the different markers and GFR were determined. Receiver-operating characteristics (ROC) analysis was performed to assess their diagnostic accuracy. Furthermore, the relationship between plasma levels of the examined markers of GFR and body weight, height, fat-free mass (FFM) and body cell mass (BCM) was determined. FFM and BCM were calculated by means of total body electrical impedance measurement. RESULTS Serum concentrations of Cys, beta 2M and RBP increase progressively with the reduction of GFR. The magnitude of the increase in blood levels of Creat and beta 2M was higher than the increase of Cys, and much more than that of RBP, in particular in patients with GFR<20 ml/min/1.73 m(2). The correlation coefficients between GFR and 1/plasma concentrations were 0.647 for Creat, 0.651 for Cys, 0.731 for beta 2M, and 0.406 for RBP. ROC analysis indicated that the accuracy of beta 2M and Cys, as indicators of different degrees of GFR impairment (<80, <60, and <40 ml/min per 1.73 m(2)), was similar to that of Creat, while the diagnostic accuracy of RBP resulted significantly lower than that of Creat for any level of GFR. In patients without renal failure (GFR>40 ml/min per 1.73 m(2)), plasma concentrations of Creat were positively correlated with body weight (P<0.01), height (P<0.01), FFM (P<0.001) and BCM (P<0.001). Serum concentrations of RBP resulted correlated with FFM (P<0.05) and BCM (P<0.05), while no correlation was found between anthropometric data and Cys and beta 2M. CONCLUSION Cystatin C and beta 2-microglobulin have a diagnostic accuracy very similar to that of creatinine, while retinol-binding protein is not an adequate marker of glomerular filtration.

Serum levels of beta-trace protein and glomerular filtration rate--preliminary results.

The aim of this study was to evaluate the relationship between serum levels of beta-trace protein (BTP), a low molecular weight (MW) protein, and glomerular filtration rate (GFR). GFR and serum levels of BTP, and for comparison creatinine (Creat), cystatin C (Cys) and beta 2-microglobulin (beta 2M), were measured in 60 patients, with renal function ranging from normality to advanced renal failure. Serum levels of BTP progressively increased with the reduction of GFR. A good correlation was found between GFR and serum levels of BTP (r=0.918), Creat (r=0.932), Cys (r=0.937), and beta 2M (r=0.924). Furthermore, no statistically significant difference was found between BTP and Creat, Cys, beta 2M, as indicators of a moderate GFR impairment. These preliminary data indicate that BTP might be suitable as an indicator of GFR.

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.

Urinary excretion of proteins and tubular enzymes in renal transplant patients

The aim of this study was to evaluate, in renal transplant recipients with different function of the graft, the urinary excretion of some low molecular weight proteins and tubular enzymes frequently employed as indicators of tubular dysfunction. Urinary excretion of proteins and enzymes was measured in 51 renal transplant patients and, for comparison, in 73 patients affected by different kidney diseases with various degrees of renal function. Values of urinary beta 2-microglobulin and retinol-binding protein higher than normal were found in most transplanted patients, even in those with good renal function. On the other hand, in renal patients the urinary excretion of low molecular weight proteins was high only when creatinine clearance was lower than 30 mL/min/1.73 m2. Furthermore, an increased urinary excretion of tubular enzymes was found in a higher number of transplanted patients than of renal patients. This behavior was particularly evident for lysosomal enzyme N-acetyl-beta-D-glucosaminidase. In conclusion, a tubular dysfunction occurs in the transplanted kidneys, even in those with well preserved glomerular function.

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.

Prediction of Glomerular Filtration Rate From Body Cell Mass and Plasma Creatinine

The gold standards for the measurement of glomerular filtration rate (GFR) are inulin clearance and radioisotopic methods. However, creatinine clearance is the most used test to evaluate GFR in clinical practice. Its adequacy is questionable, since its repeatability is quite poor, mainly due to errors in the collection of urine. The aim of this study was to evaluate a new method to predict GFR from the body cell mass (BCM) and plasma creatinine (Pcr), avoiding urine collection. The values of BCM were obtained in 275 adult renal patients with different renal function, ranging from normality to advanced renal failure. The relationship of GFR (clearance of (99m)Tc-DTPA) with BCM and Pcr was calculated in the first 85 patients. A highly significant linear correlation was found between GFR and the ratio BCM/Pcr. Thereafter, GFR was predicted from BCM and Pcr (BCM GFR) with formulas derived from the relationships found between GFR and the ratio BCM/Pcr. For comparison, GFR was predicted also according to other prediction formulas: Cockcroft and Gault (CG GFR), and the simplified MDRD formula (MDRD GFR). BCM GFR gave a more precise estimate of GFR than CG GFR and MDRD GFR. In fact, BCM GFR had the best correlation and agreement with true GFR ((99m)Tc-DTPA). Furthermore, CG GFR and MDRD GFR markedly overestimated true GFR. Finally, the error of prediction of BCM GFR was definitely lower than that of the two other estimates of GFR. GFR can be predicted from BCM and plasma creatinine. This method, which is very simple and accurate, seems suitable to establish the adequate dosage of drugs cleared by the kidneys.

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.

Parathyroid hormone and large related C-terminal fragments increase at different rates with worsening of renal function in chronic kidney disease patients. A possible indicator of bone turnover status?

BACKGROUND The intact parathyroid hormone (PTH) serum value has been the non-invasive biomarker of choice for the early diagnosis of renal bone disease in the chronic kidney disease (CKD) patient population. It has now been known that the intact PTH assay value is the sum of 1-84 PTH (true hypercalcemic PTH) and large C-terminal PTH fragments, mainly 7-84 PTH, a fragment with hypocalcemic hormone actions. AIM The aim of this study was to investigate the differences among the different functional stages of CKD in the following PTH parameters: intact PTH, 1-84 PTH, 7-84 PTH, and the ratio 1-84 PTH/7-84 PTH. GFR (clearance of 99mTc-DTPA) was measured in 164 (85 males and 79 females) adult CKD patients with different degrees of renal function impairment (serum creatinine 0.50 12.1 mg/dl, mean 2.00). PATIENTS AND METHODS Plasma concentrations of calcium, phosphate, 1-84 PTH and intact PTH were also measured. The value of 7-84 PTH was calculated as the difference between intact PTH and 1-84 PTH. The reduction of, GFR was accompanied by an increase of intact PTH, with a prevalent increase of 7-84 PTH over 1-84 PTH, resulting in a decrease of the ratio 1-84 PTH/7-84 PTH. RESULTS The values of 7-84 PTH showed a discrimination between Stages 1 and 2 (GFR > 60 ml/min ) and Stage 3 (GFR 30 60 ml/ min) CKD patient populations. In fact, 7-84 PTH was already significantly increased in patients at CKD Stage 3. The analysis of individual patients indicated that a low value (< 1.4) of the ratio 1-84 PTH/7-84 PTH, suggestive for low bone turnover, was already found in more than 20% of CKD Stage 3 patients. CONCLUSION The results of the present study demonstrate that the reduction in GFR is accompanied by a higher increase in 7-84 PTH with respect to 1-84 PTH, which suggests the possibility that bone metabolism and calcemic status are already reduced in patients with moderate renal failure (CKD Stage 3).

Renal effects of cardiac angiography with different low-osmolar contrast media.

The aim of this study was to evaluate the renal effects of cardiac angiography performed with three low-osmolar contrast media (CM): iopromide (IPR), ioversol (IVR) and ioxaglate (IOX). IPR and IVR are non-ionic CM, IOX is an ionic CM. Different parameters of renal function were determined before and 6, 24, 48, 72 hrs after angiography in 45 patients: 15 patients were examined with IPR, 15 with IVR and 15 with IOX. Glomerular effects – Plasma creatinine increased slightly at the 24th hour after IVR and IOX and at 48 hours after IOP. A significant increase in plasma β2-microglobulin was observed, at the same time, only after IOX. A significant decrease in creatinine clearance was found at 6 hours after IOX. No significant variations in glomerular filtration rate (GFR) and in effective renal plasma flow were found at 48 hours after cardiac angiography; while filtration fraction was significantly reduced after IOP and IOX. Tubular effects – A marked decrease in sodium clearance and a relevant increase of urinary activities of different tubular enzymes were found after cardiac angiography with all CM, but were more evident after the ionic CM IOX, than after the two non-ionic agents. These tubular effects reached the maximum between 6 and 24 hours and returned to baseline within 72 hrs after cardiac angiography. In conclusion, slight glomerular effects were observed mainly after IOX. A reversible tubular malfunction was found with the three low-osmolar CM and was more evident after ionic CM IOX, thus suggesting that other mechanisms, besides osmolarity, play a role in tubular toxicity due to CM. In no patient did the glomerular and tubular effects of CM have a clinical relevance.