Renal resistive index in experimental partial and complete ureteral obstruction

RATIONALE AND OBJECTIVES: Recent clinical work suggests that the Doppler resistive index (RI) may be useful in distinguishing obstructive from nonobstructive hydronephrosis. We evaluated the usefulness of the RI in a rabbit model of hydronephrosis. METHODS: Unilateral partial ureteral obstruction was produced in nine rabbits and complete obstruction in another nine. Three sham operations were performed, and these animals served as control subjects. The RI was measured in all kidneys before and 6 hr after surgery and on days 1, 4, and 7 postoperatively. The RI and the difference in RI (delta RI) between the obstructed and normal kidney were evaluated over time using a two-way analysis of variance. The intravenous urography and Whitaker tests served as gold standards. RESULTS: Hydronephrosis was observed on sonograms in all obstructed kidneys. Comparing groups, there was no significant difference in mean RI or delta RI between the three groups at any time point. Looking at individual groups over time, there was no significant change in mean delta RI, whereas the change in mean RI was significantly elevated above baseline only in the complete obstruction group at 6 hr (p = .002) and on days 4 (p = .008) and 7 (p = .006). In evaluating varying thresholds of RI and delta RI, we could not consistently discriminate between normal and obstructed kidneys. CONCLUSION: Although complete obstruction caused a significant increase in RI, partial obstruction failed to do so. RI and delta RI values proved to be insensitive predictors of obstruction in this rabbit model.     

Clinical value of renovascular resistive index measurement in the diagnosis of acute obstructive uropathy

PURPOSE: We evaluated the clinical use of the renal resistive index in identifying patients with acute urinary tract obstruction. MATERIALS AND METHODS: Of 54 patients with suspected acute urinary tract obstruction who underwent measurements of renal resistive index 19 had unilateral obstruction documented with excretory urography and comprise our study sample. The contralateral nonobstructed kidneys served as controls. Criteria for obstruction were a resistive index of 0.70 or greater or a side to side difference of 0.10 or greater. We calculated sensitivity, specificity, and positive and negative predictive values. RESULTS: Sensitivity for obstruction was 42% with 11 false-positive cases, specificity was 79%, and positive and negative predictive values were 67 and 57%, respectively. CONCLUSIONS: Renal resistive index measurements are not valuable in detecting acute urinary tract obstruction.     

Diagnosis of obstructive hydronephrosis in infants: comparison sonograms performed 6 days and 6 weeks after birth

OBJECTIVE: The purpose of this study was to compare the usefulness of renal sonograms obtained 6 days and 6 weeks after birth in differentiating obstruction from nonobstruction in patients with antenatal pyelocaliceal dilatation shown by sonography and to establish sonographic criteria to determine the degree of postnatal pyelocaliceal dilatation that warrants further investigation. MATERIALS AND METHODS: Criteria for an infant to enter the study were fetal pyelectasis of 4 mm or greater, two postnatal sonograms with the second showing persisting pyelectasis extending at least into the infundibula, and a voiding cystourethrogram showing normal findings. One hundred thirty kidneys in 100 infants met the study criteria. The first postnatal sonogram was obtained at a mean age of 6 days (range, 1-14 days) and the second at a mean age of 6.6 weeks (range, 3-16 weeks). The degree of pyelectasis was measured in the anteroposterior direction on the transverse postnatal sonograms. The diagnosis of obstruction was made by excretory urography in 99 infants and nephrostography in one infant. Kidneys were categorized as definitely obstructed, possibly obstructed (anatomic features of obstruction on excretory urogram but functionally not obstructed), or not obstructed. Receiver-operating-characteristic (ROC) curves based on renal pelvic diameters were plotted for both sonograms; the ability to detect definite obstruction or possible obstruction was compared for the two time periods; and optimal cutoff points were determined. RESULTS: The mean diameter of the renal pelvis was not significantly different between the sonogram obtained at 6 days and the sonogram obtained at 6 weeks for the 86 nonobstructed kidneys. For the 27 kidneys that were obstructed, the mean pelvic diameter increased from 18 mm (range, 5-54 mm) on the sonogram obtained at 6 days to 22 mm (range, 11-60 mm) on the sonogram obtained at 6 weeks. The mean pelvic diameter of 17 kidneys categorized as possibly obstructed increased from 6 mm (range, 0-11 mm) to 10 mm (range, 6-20 mm) between the first and second sonograms. The ROC curves for all sonograms obtained at 6 weeks provided cutoff points with greater sensitivity and specificity than did the curves for the sonograms obtained at 6 days. The optimal cutoff points were 6 mm for possible obstruction (sensitivity, 100%; specificity, 57%) and 11 mm for definite obstruction (sensitivity, 100%; specificity, 57%) and 11 mm for definite obstruction (sensitivity, 100%; specificity, 96%). CONCLUSION: Renal obstruction may be underestimated or missed on a renal sonogram obtained 6 days after birth. A sonogram obtained 6 weeks after birth is more specific for detecting obstruction.     

Detection of obstructive uropathy in the fetus: predictive value of sonographic measurements of renal pelvic diameter at various gestational ages

OBJECTIVE: The goal of our study was to analyze the fetal renal pelvic diameters measured sonographically at several gestational intervals in live-born neonates subsequently found to have either obstructive uropathy or normal kidneys. This information will improve the efficacy of sonography in the diagnosis of obstructive uropathy. SUBJECTS AND METHODS: From an ongoing prospective study assessing the significance of fetal renal pelvic diameters of 4 mm or more at obstetric sonography, the findings in 29 obstructed kidneys in 24 babies were compared with the findings in 380 kidneys from 233 infants who had no obstruction. Twenty-three infants had unilateral obstruction of the ureteropelvic junction, two had unilateral renal obstruction at the ureterovesical junction, one had posterior urethral valves and in addition had both kidneys obstructed because of obstruction at the ureterovesical junction, one kidney was obstructed because of megaloureter, and one kidney was obstructed because of obstruction in a duplex collecting system. Obstruction was identified on nephrostograms, excretory urograms, or radionuclide renograms. The sonographic findings were compared at three gestational age ranges: 16-23 weeks' gestation, 24-30 weeks' gestation, and 31-40 weeks' gestation. The progression of pelvic dilatation in both groups (12 obstructed and 86 unobstructed) was analyzed for the subset of kidneys examined in all three time periods. RESULTS: At 16-23 weeks' gestation, the difference in mean pelvic diameter between obstructed and unobstructed kidneys was not statistically significant, but the difference between obstructed and unobstructed groups at 24-30 weeks' and 31-40 weeks' gestation was significant (p < .001). Renal pelvic diameter showed a much greater rise in diameter through pregnancy in the obstructed group than in the unobstructed group (p < .0003). The sensitivity of the cutoff point of 4-mm renal pelvic diameter for detecting obstruction was 76% before 23 weeks' gestation, including kidneys with a marked decrease in function postnatally; the sensitivity of a 10-mm cutoff point at 16-23 weeks' gestation was 12%. The likelihood that a fetus had renal obstruction increased with increasing diameter of the fetal renal pelvis in all three time periods. CONCLUSION: Kidneys with significant obstruction postnatally may have no dilatation of the renal pelvis before 23 weeks' gestation. Most obstructed kidneys had pelvic diameters of less than 10 mm before 23 weeks' gestation. During pregnancy, renal pelvic diameter increases at a greater rate in kidneys that later are shown to be obstructed than in those that are not obstructed.     

Perinatal transport casebook. Maternal transport: a protocol for ambulance transfer from rural to regional facility

BACKGROUND: Renal functional reserve is the normal increase in renal blood flow after a protein load, and reduced or absent renal functional reserve is an early index of renal impairment. Renal blood flow is frequently reduced during acute oedematous exacerbations of chronic obstructive pulmonary disease (COPD). It is possible that patients with severe COPD in the stable state may have a reduced or absent renal functional reserve which could be a factor in oedema formation. METHODS: Sixteen stable patients with severe COPD and five normal controls were studied. The mean (SD) arterial oxygen and carbon dioxide tensions (PaO2, PaCO2) and forced expiratory volume in one second (FEV1) of patients with COPD were 8.1 (1.04) kPa, 6.3 (0.69) kPa, and 0.74 (0.27) 1, respectively. The pulsatility index (PI), an index of renovascular resistance, was measured non-invasively by Doppler ultrasonography at baseline and at intervals after a protein load of 250 g steak. RESULTS: The PI fell after the protein load in the normal subjects from 1.04 (0.19) to 0.84 (0.17), mean difference 0.20, 95% confidence interval of difference (CI) 0.14 to 0.27, p < 0.001. In the COPD group there was no change; baseline PI = 1.04 (0.16), PI after protein load = 1.08 (0.19), mean difference = -0.04, 95% CI-0.11 to 0.04, p = NS. Six of the patients with COPD were normocapnic and 10 were hypercapnic (PaCO2 > or = 6.0 kPa). The normocapnic patients had no significant change in PI (baseline PI = 1.07 (0.15), PI after protein load = 1.01 (0.16), mean difference = 0.06, 95% CI -0.03 to 0.15) while in the hypercapnic patients the PI tended to rise (baseline PI = 1.03 (0.17), PI after protein load = 1.12 (0.21), mean difference = -0.09, 95% CI 0.18 to 0.007, p = 0.06). CONCLUSIONS: Renal haemodynamics were unchanged after a protein load in patients with severe COPD, suggesting that they had no renal functional reserve. This may be a factor in the development of oedema frequently seen in patients with severe COPD, particularly in hypercapnic patients.     

Intrarenal arterial Doppler sonography in the detection of renal vein thrombosis of the native kidney

OBJECTIVE: Previous studies of transplant kidneys and recent reports on native kidneys have suggested intrarenal arterial Doppler findings can be helpful in the noninvasive workup of renal vein thrombosis. We used arterial Doppler sonography to evaluate cases of possible acute renal vein thrombosis in native kidneys that had equivocal results on standard Doppler analysis of the renal vein. MATERIALS AND METHODS: Twenty native kidneys in 12 patients with clinical findings suggestive of acute renal vein thrombosis had Doppler studies of the main renal vein that failed to show normal flow. In all 20 kidneys, duplex Doppler study of arcuate/interlobar intrarenal arteries was done and the resistive index was determined. The Doppler findings were compared with subsequent findings on either renal venograms (n = 11) or MR images (n = 9), which served as the reference "gold" standards. RESULTS: The prevalence of renal vein thrombosis was 25% (5/20). Ten kidneys had very abnormal findings on arterial Doppler studies (absent or reversed end-diastolic flow), but only two of these were proved to have renal vein thrombosis. In six other kidneys, end-diastolic flow was identified but the resistive index was still elevated (> or = 0.70), and only one of these kidneys was proved to have renal vein thrombosis. Four kidneys had normal arterial Doppler studies, and 50% (two) of these were proved to have renal vein thrombosis. When absent or reversed end-diastolic flow was used as a sign of renal vein thrombosis, intrarenal arterial Doppler analysis had a sensitivity of 40% (2/5) and a specificity of 47% (7/15). CONCLUSION: Unlike the reported experience in transplanted kidneys, intrarenal arterial Doppler analysis is neither sensitive nor specific for renal vein thrombosis in native kidneys. An intrarenal arterial Doppler study with normal findings should not prevent further workup if Doppler findings in the renal vein are equivocal, nor should absent or reversed end-diastolic arterial signals be considered highly suggestive of renal vein thrombosis.     

Age-related and vasomotor stimuli-induced changes in renal vascular resistance detected by Doppler ultrasound

Indirect measurement of renal vascular resistance by duplex Doppler waveform analysis was evaluated in relation to aging and some pathophysiological conditions. Baseline renal resistive index (RRI) (peak systolic frequency shift - lowest diastolic frequency shift/peak systolic frequency shift) was measured in healthy controls aged 20 to 85 years by analyzing the blood flow velocity waveform of interlobar arteries. RRI changes induced by sympathetic activation (cold pressor test and handgrip test) or by fluid load were evaluated. Both repeatability and reproducibility were very good, as the intra and interoperator variations were all less than their reproducibility coefficients. RRI showed a significant increase with aging (ANOVA P < .001), particularly evident in subjects older than 50 years. Both the cold pressor test and handgrip test induced in all the subjects (n = 16) a significant increase in RRI (P < .001), from 0.59 +/- 0.04 to 0.69 +/- 0.04 (12 +/- 6%) for the cold pressor test and from 0.57 +/- 0.03 to 0.66 +/- 0.03 (15 +/- 2%) for the handgrip test. In eight subjects intravenous fluid load (0.25 mL/kg/min of 0.9% NaCl for 120 min) caused a significant decrease in RRI (P < .001), from 0.62 +/- 0.02 to 0.53 +/- 0.01 (17 +/- 2%), which was inversely related to mean blood pressure rise (r = 0.71, P < .001). These data show that pulsed wave Doppler analysis is an accurate method for an indirect evaluation of changes in renal vascular resistance induced by common vasomotor stimuli.     

Acute obstruction of the renal collecting system: the intrarenal resistive index is a useful yet time-dependent parameter for diagnosis

The aim of this study was to determine whether the intrarenal resistive index (RI) can be used for the diagnosis of acute obstruction in patients with renal colic and to determine whether the index is time-related. Seventy patients referred to the Emergency Department with acute renal colic and without known associated renal disease underwent duplex Doppler ultrasonography to determine the intrarenal RI at the symptomatic and asymptomatic side. The age range of the patients was 18-72 years. An RI greater than 0.68 and/or an interrenal difference in RI greater than 0.06 and/or an increase in RI of more than 11% compared with the normal side proved reliable cut-off values to diagnose acute renal obstruction. In addition, time dependency of the increase in RI was noted. No significant differences were observed within the first 6 h after the onset of symptoms. From 6 to 48 h, however, the mean RI in the affected kidney (0.70 +/- 0.06; mean +/- SD) was significantly different from that in the normal kidney (0.59 +/- 0.04) (P < 0.001). In the same period the mean difference in RI was 0.08-0.13 (P < 0.001). After 48 h the sensitivity of RI dropped substantially. It is concluded that renal duplex Doppler ultrasonography is useful for diagnosing acute renal obstruction between 6 and 48 h after the onset of symptoms.     

Role of the kidneys in the metabolism of furosemide: its inhibition by probenecid

The site where furosemide is metabolized and the location where probenecid reduces furosemide metabolism remain poorly defined. The liver appears to play a minor role, and there is indirect evidence suggesting that the kidneys could be responsible for the metabolism of furosemide. To assess the role of the kidneys in the metabolism of furosemide, its intravenous kinetics have been studied in control and anephric rabbits, after the ligation of the renal pedicles. Two additional groups of rabbits, control and anephric, have received probenecid before the administration of furosemide. In the control group, the total clearance of furosemide was 18.65 +/- 1.01 mL/ min per kg; urinary and metabolic clearances of furosemide were 7.95 +/- 0.65 and 10.70 +/- 1.11 mL/min per kg, respectively. In anephric rabbits, total clearance was reduced by 85% to 2.69 +/- 0.26 mL/min per kg (P < 0.001), secondary to the abolition of furosemide renal excretion and to the reduction in metabolic clearance from 10.70 +/- 1.11 to 2.69 +/- 0.26 mL/min per kg (P < 0.001). The pretreatment with probenecid reduced the total clearance of furosemide by 80%, to 3.62 +/- 0.24 mL/min per kg (P < 0.001), because of a reduction of 90 and 75% in urinary and metabolic clearances, respectively. The administration of probenecid to anephric rabbits did not reduce further the metabolic clearance. It is concluded that the kidneys are responsible for 85% of furosemide total clearance, either via excretion (43%) or biotransformation (42%), and that probenecid inhibits both processes.     

Age-dependent differences in the effect of ischaemia on the rat kidney: prevention of the postischaemic damage by different drugs

The acute and subchronic effects of temporary renal ischaemia (45 min) were investigated in one- and two-month old rats. During bilaterial occlusion of renal arteries, the systemic blood pressure (BP) decreased from 90 to 55 and from 100 to 75 mmHg in one- and two-month old rats, respectively. Immediately after reperfusion, BP returned to the baseline level. This temporary drop in BP was prevented by continuous infusion of normal saline, dopamine, or mannitol. However, postischaemic lethality was very similar in all groups (45% in young and 28% in adult rats). An increase in blood urea concentration was observed only 24 hours after the ligation procedure. However, the rats died within 4 postischaemic days often without an elevation in blood urea. Different treatment schedules (infusion of normal saline, dopamine, and mannitol, bolus injection of dimethyl sulfoxide /DMSO/, mannitol, or furosemide, 7-day treatment with thiamazole) were compared. Lethality was reduced only by thiamazole in young rats (45% vs 11%, p < or = 0.01). No ammelioration was seen in adult rats; the lethality was increased in these rats after furosemide (28% vs 73%, p < or = 0.01). The increase in blood urea concentration regularly observed in all rats 24 hours after ischaemia, was lower in all treated groups of young rats except dopamine. In adults, only saline infusion ammeliorated this increase; on the other hand furosemide led to a higher increase than in untreated controls. Saline infusion, DMSO, mannitol, furosemide, and thiamazole treatment are all partially protective in young rats.     

Renal Doppler ultrasonography in the diagnosis of acute obstructions of the upper urinary tract

A comparative study of the resistivity indices (RI) obtained in both kidneys has been carried out in 30 controls and 60 patients with suspected unilateral acute obstruction of the upper urinary tract. Doppler findings (difference in the mean RI of both kidneys, delta RI) in the pathologic population have been systematically correlated to the data yielded by intravenous pyelography (IVP). In the control population delta RI was always < or = 0.03 (mean delta RI = 0.01, SD = 0.01). Considering that an increase in delta RI > or = 0.05 (> mean RI + 3 SD) is significant, 93% sensitivity and 100% specificity are obtained for the diagnosis of unilateral acute obstruction. Comparison of the resistivity indices of both kidneys is more specific and more sensitive than the assessment of the index on the obstructed side only; it improves the performance of ultrasonography in the initial diagnosis of acute urinary tract obstruction.     

Effects of furosemide on glomerular filtration rate and clearance of practolol, digoxin, cephaloridine, and gentamicin

Furosemide was shown to decrease inulin clearance in 20 of 27 normal subjects. The depression in inulin clearance occurred in both water-loaded and non-water-loaded subjects. The renal clearance of practolol, but not digoxin, was reduced when furosemide was given. The average total plasma clearances of gentamicin and of cephaloridine over a 6-hr period were decreased after furosemide. The reduced clearances of the antibiotics were associated with higher plasma levels, the increase in antibiotic concentration being as much as 100% at 1 hr after an intravenous bolus injection.     

Effect of intravenous furosemide on the renal excretion of digoxin

The effect of an 80-mg intravenous dose of furosemide on the urinary excretion of digoxin was determined in three adult men with normal renal function, each of whom was taking 0.25 mg digoxin daily on a chronic basis. On two separate days, serum samples were taken and urine was collected every 2 hours over an 8-hour period for determination of digoxin, creatinine, calcium, and sodium concentrations. On the first day of study, a saline bolus was given intravenously, and on the second day, furosemide was given. In all subjects, urinary digoxin excretion increased after furosemide in direct proportion to the increase in urine volume. No consistent correlation was seen between digoxin excretion and creatinine, calcium, or sodium output. No significant changes in serum digoxin were found in this active study. These results are consistent with the hypothesis that increasing glomerular filtration rate or total urine volume increases the renal excretion of digoxin and may result in increased total urinary output of this glycoside.     

Dietary v intravenous salt loading for the assessment of salt sensitivity in normotensive men

The purpose of this study was to compare the blood pressure response to two commonly used protocols for the assessment of salt sensitivity in normotensive men, involving either the rapid intravenous administration of a saline load followed by diuretic-induced salt depletion, or the more physiologic but time-consuming approach involving dietary salt depletion and repletion. Twenty-two healthy male volunteers (22-35 years old) were given a saline load (2 L of 0.9% NaCl over 4 h, i.v.), and on the following day, a low-salt diet (20 mmol NaCl) and furosemide (3 x 40 mg, po). Resting mean arterial blood pressure (MABP) was assessed after the saline load and on the morning following salt depletion. After a 2-week wash-out period, subjects were given a low-salt diet (20 mmol/day NaCl) for 2 weeks, supplemented by either 220 mmol/day NaCl or placebo for 1 week each. At the end of each week, resting MABP was assessed in the supine subjects. Although MABP changes were quite variable (iv, mean -2.1 mm Hg; range, -9.1 to +5.6; diet, mean -2.0 mm Hg; range, -14.3 to +7.2), there was a significant correlation between the salt-induced changes in MABP (r = 0.56, P < .01) and diastolic blood pressure (r = 0.56, P < .01) between the two protocols. However, in individual subjects, blood pressure response to the intravenous protocol did not uniformly predict the blood pressure response to the dietary protocol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Furosemide disposition in patients on CAPD

Single doses of oral and intravenous furosemide were given to 8 healthy male volunteers (40 mg) and 11 patients with renal failure maintained on continuous ambulatory peritoneal dialysis (CAPD) (80 mg). In the volunteers, absorption was variable. Only one half of the intravenous dose and one third of the oral dose was available for renal pharmacological action as judged by the urinary recovery. In the patients, absorption was also variable and was markedly delayed (tmax 128 vs 90 min) but more complete (bioavailability 70.1 vs 53.6%). The differences between the two groups were not significant, however (95% C.I.: -90 to 30 and -40.4 to 7.5 respectively). The mean elimination half-life was significantly longer in the patients following both the oral (228 vs 65.1 min) and intravenous dose (195 vs 60.3 min). The total body clearance of furosemide in the volunteers was 138 ml x min(-1) and this was much lower in the CAPD patients (61.9 ml x min(-1)) in whom the renal clearance was negligible. Although there were trends indicating differences in absorption between the two groups, the significant differences in furosemide disposition observed in CAPD patients were due to renal failure.     

Description of costs and effectiveness of a hypertension control program in primary care]

Our purposes were to determine whether sonography can distinguish between obstructed and nonobstructed rats and to compare the diagnostic accuracy of sonography and radiography in the diagnosis of small bowel obstruction. Nonstrangulating small bowel obstruction was created in 19 rats; sham laparotomies were performed in 18 controls. Serial radiographs and sonograms, including duplex Doppler sonography, were obtained. Bowel diameter and bowel wall thickness were evaluated retrospectively. Bowel diameter, bowel wall thickness, and resistive indices increased in the animals with obstruction; controls remained unchanged (P = 0.002). Sonography demonstrated a significantly higher diagnostic accuracy than radiography at 24 hours and beyond (P = 0.023). Ultrasonography is sensitive and more accurate than radiography in diagnosing small bowel obstruction using objective criteria in the animal model.     

Prenatal diagnosis by FISH of a 22q11 deletion in two families

OBJECTIVE: To investigate the predictive value of an intravenous fluid bolus during tilt table testing on clinical outcome and to evaluate of oral therapy is an effective treatment for patients with vasodepressor syncope. DESIGN: Retrospective cohort. SETTING: Regional pediatric cardiology outpatient clinic. PATIENTS: Patients (N = 58) with a positive baseline tilt table testing result who were treated with oral fluid therapy between February 1991 and March 1996. INTERVENTIONS AND MAIN OUTCOME MEASURES: Patients with a positive tilt table test result were given an intravenous bolus of isotonic saline solution. Responders were identified as having a negative tilt table test result after the bolus. Patients were prescribed a protocol of oral fluid therapy. Data were obtained from the medical record and a mailed survey. RESULTS: Of the 58 subjects, 90% had no recurrent syncope while receiving oral fluid therapy. During tilt table testing, the mean decrease in mean arterial pressure seen with symptomatic events was lower after the intravenous fluid. The heart rate, which dropped during the initial test, increased during the rests after the intravenous bolus. In the nonresponders, symptomatic episodes occurred significantly later in the tilt table test when given fluids. The response to intravenous fluid bolus had positive predictive value of 92% and negative predictive value of 11% of clinical outcome. CONCLUSIONS: Our data suggest that oral fluid therapy is an effective treatment for vasodepressor syncope in our population. Fluid bolus response during tilt table testing has a high positive but a low negative predictive value of response to oral fluid therapy. We now recommend oral fluid therapy as a primary intervention and reserve tilt table testing for oral fluid therapy failures.     

Breakdown of blood pressure and body fluid homeostasis in heart transplant recipients

OBJECTIVES: This study was designed to investigate disturbances in arterial blood pressure and body fluid homeostasis in stable heart transplant recipients. BACKGROUND: Hypertension and fluid retention frequently complicate heart transplantation. METHODS: Blood pressure, renal and endocrine responses to acute volume expansion were compared in 10 heart transplant recipients (57 +/- 9 years old [mean +/- SD]) 20 +/- 5 months after transplantation, 6 liver transplant recipients receiving similar doses of cyclosporine (cyclosporine control group) and 7 normal volunteers (normal control subjects). After 3 days of a constant diet containing 87 mEq/24 h of sodium, 0.154 mol/liter saline was infused at 8 ml/kg per h for 4 h. Blood pressure and plasma vasopressin, angiotensin II, aldosterone, atrial natiuretic peptide and renin activity levels were determined before and at 30, 60, 120 and 240 min during the infusion. Urine was collected at 2 and 4 h. Blood pressure, fluid balance hormones and renal function were monitored for 48 h after the infusion. RESULTS: Blood pressure did not change in the two control groups but increased in the heart transplant recipients (+15 +/- 8/8 +/- 5 mm Hg) and remained elevated for 48 h (p < or = 0.05). Urine flow and urinary sodium excretion increased abruptly in the control groups sufficient to account for elimination of 86 +/- 9% of the sodium load by 48 h; the increases were blunted (p < or = 0.05) and delayed in the heart transplant recipients, resulting in elimination of only 51 +/- 13% of the sodium load. Saline infusion suppressed vasopressin, renin activity, angiotensin II and aldosterone in the two control groups (p < or = 0.05) but not in the heart transplant recipients. Heart transplant recipients had elevated atrial natriuretic peptide levels at baseline (p < or = 0.05), but relative increases during the infusion were similar to those in both control groups. CONCLUSIONS: Blood pressure in heart transplant recipients is salt sensitive. These patients have a blunted diuretic and natriuretic response to volume expansion that may be mediated by a failure to reflexly suppress fluid regulatory hormones. These defects in blood pressure and fluid homeostasis were not seen in liver transplant recipients receiving cyclosporine and therefore cannot be attributed to cyclosporine alone. Abnormal cardiorenal neuroendocrine reflexes, secondary to cardiac denervation, may contribute to salt-sensitive hypertension and fluid retention in heart transplant recipients.     

The renal factor in the post-traumatic "fluid overload" syndrome

Hypervolemia with hypertension often occurs 36-72 hours following massive blood and fluid replacement for hypovolemic shock. This syndrome of "fluid overload" has been attributed to the rapid intravascular flux of previously sequestered fluid in patients with impaired diuresis. This hypothesis was tested in 35 injured patients who received a mean of 9.3 L of blood and 17.4 L of salt during resucitation. The renal parameters measured soon after resuscitation included: 1) renal clearance of inulin (GFR), para-amino hippurate (ERPF), milliosmoles, sodium, and free water; 2) inulin space, renal vascular resistance (RVR), O2 consumption, renin, renal blood flow (RBF), and response to furosemide. Eighteen patients developed hypertension, hypervolemia, and respiratory insufficiency. When compared to the 17 normovolemic, non-hypertensive patients, the 18 hypervolemic patients had significantly increased RVR, with a significant decrease in RBF despite an increase in plasma volume and cardiac output. Furosemide produced less diuresis and natriuresis in the hypertensive patients. The balance between hypovolemia and "fluid overload" seemed percarious in the hypertensive patients. Peripheral renin and catecholamine levels were normal in both groups. Patients with post-traumatic "fluid overload" appear to have a combination of hypervolemia, respiratory insufficiency, hypertension, increased cardiac output, decreased extracellular fluid space, and decreased renal perfusion. These findings suggest that decreased interstitial fluid space compliance rather than "fluid overload" is the underlying factor leading to respiratory insufficiency. The therapeutic aspects of these findings are discussed.     

A constitutive law for mitral valve tissue

BACKGROUND: Obstructive nephropathy is a primary cause of renal failure in infancy. Chronic unilateral ureteral obstruction (UUO) in the neonatal rat results in reduced renal expression of epidermal growth factor (EGF), renal tubular epithelial (RTE) cell apoptosis and interstitial fibrosis. We wished to determine whether these changes could be prevented by exogenous administration of EGF. METHODS: Thirty-three Sprague-Dawley rats underwent UUO within the first 48 hours of life, and received daily injections of either EGF (0.1 mg/kg/day) or saline (control) for the following seven days, after which obstructed and intact opposite kidneys were removed for study. These were compared to 11 sham-operated rats that received either no injections, EGF injections, or saline injections. Renal cell proliferation was determined by proliferating cell nuclear antigen, apoptosis was measured by the TUNEL technique, and the distribution of vimentin, clusterin, transforming growth factor-beta 1 (TGF-beta 1), and alpha-smooth muscle actin were determined by immunohistochemistry. Tubular dilation, tubular atrophy, and interstitial collagen deposition were quantitated by histomorphometry. RESULTS: Compared to controls, EGF treatment increased RTE cell proliferation in the obstructed kidney by 76%, decreased apoptosis by 80%, and reduced vimentin, clusterin and TGF-beta 1 immunostaining (all P < 0.05). EGF treatment reduced tubular dilation by 50%, atrophic tubules by 30%, and interstitial fibrosis by 50% (all P < 0.05). There was no significant effect of EGF on renal alpha smooth muscle actin distribution. There was no effect of saline or EGF injections on kidneys from sham-operated rats for any of the parameters studied. CONCLUSIONS: We conclude that EGF stimulates RTE cell proliferation and maturation and reduces apoptosis in the neonatal rat kidney subjected to chronic UUO. These effects may contribute to the reduction in tubular dilation, tubular atrophy, and interstitial fibrosis. By preserving renal development, administration of EGF attenuates the renal injury resulting from chronic UUO.