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Objective: Impact of prenatal diagnosis (PD) of major abnormalities on neonatal outcome is matter of debate. Unfortunately cases with and without PD may sometimes not be comparable. This is generally related to a lower maturity (GA) and weight (BW) secondary to a high rate of preterm cesarean sections (CSs) for clinical convenience. Present study tried to find out if in utero transfer to a Center with co-located surgical facilities reduces these potential risk factors., Methods: 152 cases with prenatally detectable conditions were studied and divided according to PD; the following data were compared: GA, BW, obstetrical complications, associated malformations, mode and site of delivery, outcome. Cases with PD delivered in our Center (Inborn, IB) or transferred after birth (Outborn, OB) were compared., Results: 61 cases had a PD (IB/OB ratio 34/27); GA and BW were lower respect to no-PD cases and a higher CS rate was found among OB cases, not justified by complicated pregnancies. No differences in outcome were observed., Conclusions: Elective preterm CS is still largely practiced for fetuses with PD of a major congenital anomaly in Centers without co-located surgical facilities either in the presumption of safer delivery or to facilitate postnatal transfer. This leads to a lower GA and BW and may spoil potential impact of PD on outcome. This may be avoided promoting prenatal transfer to a Center with co-located surgical facilities.

Objective: To analyze risk factors for type 2 diabetes among women attending menopause clinics in Italy for counselling about the menopause., Subjects: Women attending a network of first-level outpatient menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms., Methods: Cross-sectional study with no exclusion criteria. Type 2 diabetes was defined according to National Diabetes Data Groups Indications and the fasting blood glucose at an oral glucose tolerance test within the previous year., Results: Out of the 44 694 considered in this analysis, 808 had a diagnosis of diabetes type 2 (1.8%). In comparison with women aged < 50 years, the multivariate odds ratios (OR) of type 2 diabetes were 1.31 (95% confidence interval (CI), 0.99-1.74) for women aged 50-52 years, 1.66 (95% CI, 1.27-2.17) at 53-56 years and 2.84 (95% CI, 2.20-3.67) in women aged > or = 57 years. Type 2 diabetes was less frequently reported in more educated women (OR high school/university vs. primary school = 0.44 (95% CI, 0.36-0.55)). Being overweight was associated with an increased risk of type 2 diabetes. In comparison with women reporting a low level of physical activity, the multivariate OR of type 2 diabetes was 0.67 (95% CI, 0.54-0.84) for women reporting regular physical activity. In comparison with premenopausal women, the multivariate OR of type 2 diabetes was 1.38 (95% CI, 1.03-1.84) in women with natural menopause. This finding was present also after allowing for the potential confounding effect of age. The multivariate OR of diabetes for users of hormonal replacement therapy was 0.58 (95% CI, 0.46-0.73)., Conclusions: This large cross-sectional study suggests that postmenopausal women are at higher risk of type 2 diabetes after allowance for the effect of age. Other main determinants of risk of type 2 diabetes in women around menopause were low socioeconomic status and being overweight. Diabetes was found less frequently in those taking hormone replacement therapy.

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 beta2-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.

Beta2-microglobulin (beta2M) is highly accumulated by the kidneys of normal rats. The aim of this study was to verify if uninephrectomy can modify the renal uptake of labeled beta2M. For this purpose the radioactivity of plasma and those of the remaining kidney, liver and urine have been measured in uninephrectomized rats (NX) and in controls (C) at different times after the injection as i.v. bolus of 131I-beta2M. The experiments were performed in 114 Sprague-Dawley male rats. Fifty seven animals underwent right nephrectomy, the other animals being the C. NX and their C were divided in 3 groups, studied 2, 4 and 6 weeks after nephrectomy, respectively. Part of the animals were sacrificed 12 min after the injection of labeled beta2M (peak-time, i.e. time of highest kidney accumulation of 131I-beta2M in the normal rat) and part 10 min later. The results demonstrate that: - uninephrectomy increases plasma retention of 131I-beta2M - kidney uptake (total and per gram) is always higher in NX - liver uptake (much lower than that of kidney) is not influenced by uninephrectomy - urine excretion of radioactivity is minimal in both NX and C. The behavior of beta2M is similar to that we previously observed with alpha1-microglobulin and lysozyme. The higher kidney content of some low mw proteins after uninephrectomy could play a role in the progressive reduction of renal function determined by the reduction of renal mass.

Introduction: Beta 2 microglobulin (beta2M) is filtered by the glomeruli and reabsorbed by the proximal tubular cells where it is metabolized. Its plasma concentration increases with decreasing renal function., Aim: To compare serum creatinine (Cr) and serum beta2M as markers of GFR., Patients and Methods: In 160 adult patients, with various kidney diseases and different GFR, serum Cr (autoanalyzer), serum beta2M (RIA) and GFR (bladder cumulative method using 99mTc-DTPA as glomerular tracer) were measured in the same day., Results: A linear relationship was observed between In GFR and both In serum Cr (lnCr=3.112-0.716 lnGFR; r=0.92) and ln serum beta2M (lnbeta2M= 4.274-0.814 lnGFR; r = 0.90). With decreasing GFR the increase in serum beta2M was higher than that of serum Cr (see regression coefficients that are significantly different). The normal upper limit of serum Cr corresponds to a GFR 48.1 mL/min while that of serum beta2M to a GFR 65.0. With decreasing GFR the increase of serum beta2M occurs before than that of serum Cr., Conclusions: With declining renal function, serum beta2M increases more and before than serum Cr. Serum beta2M is a good endogenous marker of GFR, better than serum Cr.

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, beta2microglobulin (beta2m) 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-, beta2m 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.

The aim of this study was to evaluate the early effects of high and low-osmolar contrast media on glomerular function in rats by using a new method based on the measurement of the urinary excretion of 99mTc-DTPA. Thirty-six Sprague-Dawley male rats were examined: nine rats were injected with diatrizoate (ionic high-osmolar contrast medium), nine rats with iohexol (nonionic low-osmolar contrast medium), and nine rats with saline as controls. The urinary excretion of 99mTc-DTPA in the first minutes after i.v. injection was assumed as an index of glomerular filtration rate. A lower urinary excretion of 99mTc-DTPA was found in rats treated with contrast media in comparison with control rats. This effect was more evident after diatrizoate but was statistically significant also after iohexol. In conclusion, a reduction in the glomerular filtration rate probably occurs in the first few minutes after contrast media administration. The measurement of urinary excretion of 99mTc-DTPA could be a simple method to detect acute glomerular effects due to contrast media or to other drugs.

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.

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.

TATI (tumor associated trypsin inhibitor) is a low molecular weight protein employed as a tumor marker. To evaluate the role of the kidney in the clearance of TATI, we studied the rat kidney uptake of 125I-TATI. Total body scan demonstrated a high radioactivity in the kidneys of the rats and none in other organs. The relationship between serum TATI and glomerular filtration rate (GFR) was studied in man. For comparison serum beta 2-microglobulin (beta 2M) arid plasma creatinine were also determined. The decrease in GFR was accompanied by an increase in the other parameters. Serum TATI increased in patients with renal failure (GFR < 20 mL/min) 12.4 times with respect to subjects with normal renal function (p < 0.001, non-parametric Mann-Whitney test), beta 2M increased 7.6 times (p < 0.001) and creatinine 4.7 times (p < 0.001). The increase in TATI is statistically significant already in patients with GFR 60-40 mL/min (p < 0.005). These results suggest that TATI is handled by the kidney. It is a sensitive marker of reduction in renal function.

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.

In order to quantify the decline in renal function, repeated measurements of GFR are necessary. The conventional procedure is cumbersome and time expending so that alternative clearance techniques are needed. We propose a simple isotopic technique for measuring GFR by 99mTc-DTPA and external counting of the bladder by gamma camera (bladder cumulative method). This consists in the measurement by external counting of the amount of labelled filtration marker accumulated in the bladder after intravenous bolus injection. In 36 adult patients with all degrees of renal impairment (serum creatinine 0.9-9.3 mg/dL) GFR was measured twice, once by the conventional method (continuous i.v. infusion of the filtration marker and urine collection by spontaneous voiding) and once by the bladder cumulative method. 99mTc DTPA was used in performing both methods. A satisfactory agreement was found between GFR measured by bladder cumulative method (BCM) and by conventional method (CM). The BCM averaged 60.0 +/- 36.7 mL/min and the CM +/- SD averaged 62.8 +/- 36.6 mL/mm. The ratio BCM/CM +/- SD was 0.95 +/- 0.14 (y = 0.94x + 1.14; r = 0.94). Considering the 17 patients with renal insufficiency (GFR < 60 mL/min) an even better agreement between the two methods was found. In these patients the BCM averaged 28.4 +/- 17.2 mL/min; the CM averaged 29.1 +/- 16.6 mL/min; and the ratio BCM/CM was 0.96 +/- 0.08 (y = 1.03x - 1.47; r = 0.99). The day-to-day variability of BCM, studied in another 11 patients, was lower than that of creatinine clearance (variation coefficient for duplicate measurements: 7.18 +/- 6.65 SD for BCM, 15.68 +/- 8.80 SD for CM, p < 0.01). The bladder cumulative method is a simple procedure for the accurate measurement of GFR, in particular in patients with renal insufficiency. It represents a reliable tool for estimating the decline in 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.

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.

A 64-year-old woman, affected by stage IIIc epithelial ovarian cancer, experienced acute renal failure after the first cycle of chemotherapy with cyclophosphamide and cis-platinum, despite standard prophylactic measures of hydration-diuresis. In this paper we report data obtained during 5 additional cycles of chemotherapy. The schedule of treatment was modified by dividing standard dose of cis-platinum by three and administering this divided dose for 3 days. The following five cycles of treatment did not cause a clinically relevant impairment of glomerular function or evident tubular toxicity. A high-risk patient was treated safely combining hydration-diuresis measures with lengthening of cis-platinum administration over 3 days.

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.

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.