Urinary endothelin-1-like immunoreactivity excretion in Wilms' tumor survivors.

BACKGROUND: We evaluated urinary endothelin (ET)-1-like Immunoreactivity (uET-1 L) excretion in Wilms tumor (WT) survivors and investigated its relationships with glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Glomerular hemodynamics were also assessed by Gomez formulae. METHODS: Seventeen WT survivors underwent renal sequential scintigraphy for residual kidney function determination including ERPF and GFR. Forty-five healthy individuals were selected as the control group. uET-1 L was measured by radioimmunoassay from the 24-h urine collection. RESULTS: In WT survivors, uET-1 L excretion was significantly higher than in controls. Significant correlations were found between uET-1 L and ERPF and GFR. Cluster analysis, applied on uET-1 L, identified two different patient groups. Between them, GFR and ERPF were significantly different. No significant difference existed between the two clusters for age and sex, elapsed time from nephrectomy, treatment, or nephrectomy side. Applying Gomez formulae, significant difference was found for afferent and total renal resistance. CONCLUSIONS: According to our results, uET-1 L seems to be a marker of glomerular injury in patients with renal mass loss revealing renal overload condition. The uET-1 L role in renal damage progression and hemodynamic glomerular worsening in nephrectomized patients should be proven by prospective long-term follow-up studies, even for potential ET-1 receptor antagonist therapeutic use.

Evaluation of (123)I-orthoiodohippurate single kidney clearance rate by renal sequential scintigraphy in a large cohort of likely normal subjects aged between 0 and 18 years.

PURPOSE: Age-related values of (123)I-orthoiodohippurate (OIH) single kidney clearance rate (Cl) were estimated in a large cohort of likely normal children aged between 0 and 18 years. METHODS: Among 4,111 children examined in the past 10 years, 917 were selected with the following inclusion criteria: (a) mild ultrasonographic hydronephrosis with right differential renal function (DRF) <53% and >47% (498 pts), (b) known or suspected urinary tract infection with normal ultrasound, serum creatinine and DMSA and DRF <53% and >47% (419 pts). (123)I-OIH-Cl was assessed using a validated gamma camera method. Children were divided into 21 age classes: from 0 to 2 years, eight 3-month classes; from 2 to 14 years, twelve 1-year classes; from 14 to 18 years, one 4-year class. RESULTS: Cl, plotted against age, was fitted using an increasing function (y=a-be-cx). Mean (123)I-OIH-Cl of 1,834 kidneys was 306+/-22 ml/min/1.73 m(2) BSA. Mean (123)I-OIH-Cl of the right and left kidneys was 307+/-23 and 305+/-22 ml/min/1.73 m(2) BSA, respectively (p<0.002). The best-fitting (123)I-OIH-Cl growing function was: Cl=311-230e-0.69xAge (months). (123)I-OIH-Cl improved progressively starting from birth, reaching 96% and 98% of the mature value at 1 and 1.5 years, respectively. (123)I-OIH-Cl at birth (age=0) was 81 ml/min/1.73 m(2) BSA. After 18.6 days of life, the renal function had doubled its starting value, and it reached a plateau of 311 ml/min/1.73 m(2) BSA at 2 years. CONCLUSION: This work represents a systematic evaluation of ERPF by a gamma camera method in a large cohort of selected likely normal paediatric subjects.

Thromboxane inhibition improves renal perfusion and excretory function in severe congestive heart failure.

OBJECTIVES: The aim of this study was to evaluate whether thromboxane inhibition can favorably affect renal perfusion and clinical conditions in patients affected by severe heart failure. BACKGROUND: The renal formation of the vasoconstrictor thromboxane A(2) (TxA(2)) is increased during cardiac failure. METHODS: By oral administration of picotamide (a renal TxA(2) synthase and TxA(2)/prostaglandin H(2) receptor inhibitor), we blocked renal TxA(2). Fourteen patients in New York Heart Association functional class IV were studied according to a randomized, double-blinded, cross-over design. Each of the two eight-day periods of testing was preceded by a three-day period during which certain vasoactive medications were stopped. RESULTS: Daily 24-h total urinary thromboxane B(2) (TxB(2)), the stable metabolite of TxA(2), dropped at the end of picotamide treatment (p < 0.01 vs. baseline). Compared with placebo, effective renal plasma flow and the glomerular filtration rate increased (p < 0.01 and p < 0.05, respectively), thus leading to a significant decrease in the filtration fraction (p < 0.01). Renal vascular resistance decreased consistently (p < 0.01). In all patients, picotamide treatment was associated with an increase in diuresis and natriuresis (p < 0.001 vs. baseline). Plasma creatinine decreased (p < 0.05 vs. baseline). Patients also showed improvement in several clinical parameters, including a significant decrease in both pulmonary and venous pressure (p < 0.01 vs. baseline). CONCLUSIONS: These results indicate that renal thromboxane formation plays an important role in renal vascular resistance in patients with severe heart failure, such as those described in the present study. Inhibition of TxA(2) improves renal hemodynamics and kidney function and favorably affects indexes of cardiac performance.

SPECT semiquantitative analysis of adrenocortical (131)I-6 beta iodomethyl-norcholesterol uptake to discriminate subclinical and preclinical functioning adrenal incidentaloma.

UNLABELLED: The goal of this study was to evaluate the clinical reliability of the (131)I-6 beta-iodomethyl-norcholesterol ((131)I-NP-59) uptake semiquantitative evaluation method we propose for the characterization of adrenocortical masses in a selected population of patients with disease clinically classified as subclinical (SC) and preclinical (PC) Cushing's syndrome (CS) according to Reincke's definition. METHODS: Forty-seven consecutive patients with incidentally discovered unilateral adrenal masses were examined by a triple-head SPECT system after intravenous injection of (131)I-NP-59. Abdominal SPECT was performed at 24, 48, 72, and, in selected cases, 96 h after tracer injection. Connected with adrenals and liver, a standard elliptic region of interest (ROI) was manually drawn, taking care to avoid the gallbladder region. The adrenal ROI integral count, obtained by summing the 24-, 48-, and 72-h counting values, was normalized by the hepatic integral count. Subsequently, the adrenal percentage of relative uptake (UPT%) was computed. RESULTS: Discriminant analysis was performed on the variables UPT%, adrenocorticotropic hormone (ACTH) serum concentration, and CT mass dimension (CTMD) to determine the variable, or combination thereof, best discriminating between the SC-CS and PC-CS groups. Compared with both ACTH and CTMD variables, univariate analysis confirmed the UPT% variable as the most significant to discriminate between these 2 clinical groups. In fact, UPT% alone correctly classified 8 of 9 patients in the SC-CS group and 20 of 22 patients in the PC-CS group with 95% positive and 80% negative predictive values and with overall accuracy, sensitivity, and specificity equal to 90%, 91%, and 89%, respectively. When all 3 variables were submitted to stepwise discriminant analysis, the derived classification matrix, after cross-validation, correctly classified 9 of 9 patients in the SC-CS group and 18 of 22 patients in the PC-CS group with 100% positive and 69% negative predictive values and with overall accuracy, sensitivity, and specificity equal to 87%, 82%, and 100%, respectively. CONCLUSION: According to these initial results, use of the proposed semiquantitative approach associated with both laboratory screening for cortisol production and CTMD measure seems to be able to increase the clinical diagnostic accuracy of PC-CS. This approach could be used in the follow-up of adrenal mass function every time hormonal or clinical features are suggestive of adrenocortical hyperfunction.

123I-hippuran renal scintigraphy with evaluation of single-kidney clearance for predicting renal scarring after acute urinary tract infection: comparison with (99m)Tc-DMSA scanning.

UNLABELLED: The value of (123)I-hippuran (OIH) renal sequential scintigraphy (RSS) in predicting the evolution of defects detected by (99m)Tc-dimercaptosuccinic acid (DMSA) scanning during a first episode of acute pyelonephritis (APN) was assessed. METHODS: Fifty-eight children with APN underwent (99m)Tc-DMSA planar scanning and (123)I-OIH RSS during acute infection and at least 5 mo later. Renal lesions found by (99m)Tc-DMSA scanning were classified according to the following (99m)Tc-DMSA grading system: 0 = normal, 1 = 1 lesion, 2 = 2 lesions, and 3 = diffuse damage with renal parenchymal subversion. Renal scarring was diagnosed whenever a renal cortical defect detected at the first (99m)Tc-DMSA examination persisted on the follow-up (99m)Tc-DMSA examination. Single-kidney clearance rate (Cl) was evaluated by a method that was previously validated at our institution and is based on time-activity curves measured on the heart and kidney areas by the region-of-interest technique. RESULTS: (99m)Tc-DMSA scanning showed renal damage in 76 kidneys and had negative findings for the remaining 40 kidneys (2 patients had bilaterally negative findings). (99m)Tc-DMSA scanning determined 40 kidneys to be grade 0, 49 to be grade 1, 21 to be grade 2, and 6 to be grade 3. For (99m)Tc-DMSA grades of 0-3, the corresponding Cl mean values (in mL/min/1.73 m(2) of body surface area [BSA]) were 292 +/- 33, 237 +/- 39, 210 +/- 54, and 140 +/- 53, respectively. The Spearman regression coefficient (R) demonstrated a significant correlation between (99m)Tc-DMSA grade and Cl (R = 0.69, P < 0.0001). Thirty-six of the lesions detected by staging (99m)Tc-DMSA were shown to have recovered on follow-up renal scans, whereas 40 developed scars. A significant difference in Cl was found between the 2 groups (P < 0.0002). The Cl cutoff value was determined by univariate discriminant analysis; a Cl value of 232 mL/min/1.73 m(2) of BSA discriminated best between scarred and nonscarred kidneys, with a specificity, sensitivity, positive predictive value, negative predictive value, and overall accuracy of 95%, 95%, 90%, 97%, and 95%, respectively. CONCLUSION: Cl evaluation, in the course of acute urinary tract infection, is highly valuable in predicting the fibrotic evolution of renal damage detected on acute (99m)Tc-DMSA scanning. Also, our data show close agreement between Cl and the grade determined by staging (99m)Tc-DMSA.

Kinetic parameter estimation from renal measurements with a three-headed SPECT system: a simulation study.

We present here a direct least-squares estimation (DLSE) method for the determination of renal kinetic parameters from sequences of very fast acquisitions performed with a three-headed single photon emission computed tomography (SPECT) system. A simple linear model for the behavior of the radiopharmaceutical, as well as a spatial model for its spatial distribution are defined. The model enables one to estimate the kinetic parameters directly from the projections, once the plasma concentration function is known. A new technique for the accurate reconstruction of time-radioactivity curves based on the direct reconstruction of the region-of-interest contents from a series of data from three-projections is presented. The technique is used to determine the plasma concentration function with a sub-second time resolution. The spatially-variant geometrical response is also included in the model to compensate for the spatial resolution of the SPECT system. Results obtained from simulations are presented. Basic spatial and time features of the simulations are derived from a patient study. Noise and segmentation errors are also simulated. The DLSE method is compared with the conventional one of deriving kinetic parameters from the time series of reconstructed images. The standard deviation of results given by DLSE is less than 2%, whereas with the conventional method it is between 5% and 6%. Within the limit of statistical fluctuations, DLSE results are unbiased whereas those of the conventional method are overestimated by 24%.

Efficacy and Safety of Ramipril in Hypertensive Single-Kidney Patients.

The effects of medium-term antihypertensive treatment with the ACE inhibitor ramipril were studied on 10 hypertensive single-kidney patients in a double-blind study versus placebo. Patients with renovascular hypertension were excluded. Compared to placebo, ramipril induces a significant reduction of arterial blood pressure (p < 0.02 for systolic, p < 0.01 for diastolic, and p < 0.05 for mean blood pressure), renal vascular resistance (p < 0.005), and microalbuminuria (p < 0.005), but a significant rise of effective renal plasma flow (p < 0.01) and no significant variation of the glomerular filtration rate. The reduction of microalbuminuria was not related to arterial blood pressure variation. Our study shows that ramipril, in appropriately selected-kidney patients, is effective and safe in reducing arterial blood pressure, bringing about an improvement of renal function and reducing microalbuminuria, which is frequently observed in this condition.

Renal resistive index early detects chronic tubulointerstitial nephropathy in normo- and hypertensive patients.

BACKGROUND: We studied whether the measurement of intrarenal vascular resistance by Doppler ultrasonography, capable of investigating renal interstitial compartment, allows the early detection of chronic tubulointerstitial nephropathy (TIN). METHODS: 30 normotensive and 28 hypertensive (I-II OMS) patients with a clinical history suggestive of chronic TIN and normal renal function were enrolled. 40 healthy volunteers served as controls. Patients were considered TIN-negative or TIN-positive after investigating tubular function by urine concentrating and acidification tests. Renal sonographic parameters and renal resistive index (RRI) were obtained by duplex scanner. Glomerular filtration rate/effective renal plasmatic flow ratio was investigated by sequential renal scintigraphy in TIN-negative and TIN-positive patients; (99m)Tc-DMSA scintigraphy was also performed in TIN-positive patients. RESULTS: RRI values of TIN-positive normotensive and hypertensive patients were significantly higher (p < 0.01 for both) than those of TIN-negative patients and of controls. RRI values resulted to be linearly related to uricemia (r = 0.88, p < 0.0001) only in normotensive patients. RRI values also resulted to be linearly related to filtration ratio values (r = 0.60, p < 0.0001). (99m)Tc-DMSA scintigraphy confirmed interstitial renal damage (grade 1 and 2). CONCLUSION: RRI measurement allows the early identification of both normotensive and hypertensive patients with chronic TIN and signs of tubular dysfunction, when renal function is still preserved.

Urinary endothelin-1 excretion according to morpho-functional damage lateralization in reflux nephropathy.

BACKGROUND: Reflux nephropathy (RN) is a pathophysiological human model of reduced nephron reserve, due to loss of renal mass, but little information exists about the role of urinary endothelin-1 (uET-1) in this disease. The aim of this study was to assess the presence of uET-1-like-immunoreactivity (uET-1L) in RN patients, particularly if lateralized renal damage existed. METHODS: Thirty patients with vescico-ureteral reflux (VUR) and consequent RN, were studied. The presence of VUR was established by voiding cysto-urethrography. RN was assessed and graded by 99mTc-dimercapto-succinic acid scan (DMSA). Renal plasma flow (ERPF) was evaluated by (123)I-Hippuran renal sequential scintigraphy, and glomerular filtration rate (GFR) by creatinine clearance. Forty-five healthy subjects were selected as a control group. uET-1L excretion, in both affected and control groups, was assayed. RESULTS: Mann-Whitney U test showed a significant difference between control and patient groups in both GFR and uET-1L. A good correlation between DMSA grading, single kidney clearance and VUR grade was shown. A significant relationship was also shown between uET-1L and both ERPF and GFR. Patients with RN were divided into two subgroups according to functional damage lateralization. Between the two groups, a significant difference was found only for uET-1L when GFR was applied as a covariate in ANCOVA analysis. CONCLUSION: Our preliminary results confirmed the increase of urinary ET-1L excretion in RN, especially when renal functional injury was lateralized.

Renal, but not systemic, hemodynamic effects of dopamine are influenced by the severity of congestive heart failure.

OBJECTIVE: To determine whether the short-term systemic and renal hemodynamic response to dopamine is influenced by clinical severity of congestive heart failure. DESIGN: Effects of increasing doses of dopamine were assessed in patients consecutively admitted for acutely decompensated congestive heart failure. SETTING: Intensive care unit. PATIENTS: We enrolled 16 congestive heart failure patients stratified by clinical severity (New York Heart Association [NYHA] class III, n = 8; NYHA class IV, n = 8) and two additional NYHA class III patients as controls. INTERVENTIONS: Measurements were carried out throughout five 20-min experimental periods: baseline, dopamine infusion at 2, 4, and 6 microg x kg(-1) x min(-1), and recovery. Controls received a similar amount of saline. MEASUREMENTS AND MAIN RESULTS: Systemic and renal hemodynamics were determined respectively by right cardiac catheterization and radioisotopes (iodine 131-labeled hippuran and iodine 125-labeled iothalamate clearance). The peak increase in heart rate and cardiac index occurred at a dopamine dose of 4-6 microg x kg(-1) x min(-1). The dose-response relation was similar in NYHA classes III and IV. Improvement in effective renal plasma flow and glomerular filtration rate, peaking at 4 microg x kg(-1) x min(-1), was more rapid and marked in NYHA class III than class IV patients, in whom the renal fraction of cardiac output failed to increase. The systemic and renal effects of dopamine were independent of age. No change occurred in controls. CONCLUSIONS: The dose of dopamine producing an optimal improvement of systemic and renal hemodynamics in congestive heart failure is higher than usually reported. A greater clinical severity of congestive heart failure impairs the renal effects of dopamine, probably through a selective loss in renal vasodilating capacity.