Diagnostic value of urinary N-acetyl-beta-D-glucosaminidase, its isoenzymes and the fractional excretion of sodium following renal transplantation

Daily total urine N-acetyl-beta-D-glucosaminidase activity, isoenzyme profile and fractional excretion of sodium were measured in 13 consecutive renal transplant patients. Rejection episodes were clinically diagnosed in 12 patients, 11 of whom (92%) showed an increased enzymuria either before or during the onset of clinical signs. The ratio of the two major isoenzymes (A/B) fell during 10 episodes (83%) and in six of these (50%) increased levels of the minor isoenzyme forms were observed. Increased fractional excretion of sodium was associated with nine (75%) of the episodes. Increased fractional excretion of sodium with a raised total enzymuria accompanied by a reduced A/B ratio and an increased proportion of the minor isoenzyme forms occurred in eight (67%) of the rejection episodes. The use of these measurements in the diagnosis of episodes of acute rejection in renal transplantation is discussed.     

Excretion of urinary N-acetyl-beta-D-glucosaminidase isoenzymes after renal transplantation in the rat

The urinary excretion of N-acetyl-beta-D-glucosaminidase isoenzymes A and B following kidney transplantation was studied in rats. High enzymuria with permanent marked isoenzyme B excretion occurred from the immediate post-operative period to the irreversible rejection episode. Isoenzyme B could represent as much as 10-40% of total N-acetyl-beta-D-glucosaminidase activity and it reflected the intensity of tubular lesions as observed by histological examination of allograft specimens. Thus, N-acetyl-beta-D-glucosaminidase B isoenzyme determination may reinforce the diagnostic value of total (A + B) urinary N-acetyl-beta-D-glucosaminidase activity determination during the various complications which can occur after transplantation.     

Early monitoring of human renal transplantations by N-acetyl-beta-D-glucosaminidase isoenzyme activities in urines

Monitoring of variations in N-acetyl-beta-D-glucosaminidase (NAG) urinary activity, following renal transplantation, has been proposed for the early diagnosis of rejection episodes. In this study, the measurement of urinary NAG-B activity was conducted as a complement to total NAG (A + B) measurement, which is normally used alone. Selective measurement of NAG-B activity is carried out after fixation of NAG-A on ion exchanger in test tubes. Results of NAG (A + B) activity confirm that the assay of urinary NAG is a useful indicator of rejection, but a positive correlation between NAG-B and NAG (A + B) activities was observed during the various complications which can occur after transplantation. The specific measurement of this isoenzyme does not, therefore, seem to provide additional information in the early monitoring of human renal transplantations. Apart from rejection episodes, other factors are likely to produce marked NAG-B excretion, e.g. gentamicin therapy.     

Renal and hormonal actions of atrial natriuretic peptide during angiotensin II or noradrenaline infusion in man

In order to study the renal and hormonal actions of atrial natriuretic peptide (ANP) during background infusions with angiotensin II (ANG II) or noradrenaline (NA), 69 healthy subjects were examined in three main groups receiving a 90-min infusion with either placebo, ANG II (1.5 ng kg^?1 min^?1), or NA (25 ng kg^?1 min^?1). Each of these three main groups were subdivided into two groups receiving an infusion with either placebo or ANP (10 ng kg^?1 min^?1) for the last 60 min of the background infusion. Lithium clearance was used to evaluate segmental tubular reabsorption. ANG II alone caused a decrease in glomerular filtration rate (GFR), renal plasma flow, urinary absolute and fractional excretion of sodium, both proximal and distal fractional tubular sodium reabsorption, and urinary flow. NA alone caused a decrease in renal plasma flow. ANP alone caused a decrease in renal plasma flow. Urinary absolute and fractional excretion of sodium were increased and the distal fractional tubular reabsorption of sodium decreased, whereas the proximal fractional tubular reabsorption was unchanged by ANP. ANG II + ANP: during a background ANG II infusion, ANP still increased fractional excretion of sodium. Proximal fractional reabsorption was decreased, whereas distal fractional reabsorption of sodium was unchanged by ANP during ANG II infusion. The ANP-induced decreases in proximal absolute (?147 vs. +714 μmol min^?1 1.73 m^?2P = 0.05) and fractional (?1.7% vs. +0.6%, P<0.01) tubular sodium reabsorption were more pronounced, and the decrease in distal fractional tubular reabsorption of sodium (?0.1% vs. ?1.4%, P<0.05) less pronounced compared with when ANP was given alone. NA + ANP: during a background NA infusion, ANP still increased urinary sodium excretion and decreased distal fractional reabsorption. None of the ANP-induced absolute changes seen during background infusion with NA were significantly different from the ANP-induced changes seen during placebo background infusion. It is concluded that the natriuretic action of low-dose ANP seems to be preserved during background infusions with ANG II and NA in man. Net sodium excretion during the combined infusion with ANG II and ANP seems to reflect the sum of the opposing influences of each peptide. Low-dose ANP had a very modest but significant inhibitory effect on proximal tubular sodium reabsorption prestimulated by ANG II infusion.     

A systematic review of urinary findings in experimental septic acute renal failure

OBJECTIVE: In experimental septic acute renal failure, urinary analysis is used to help diagnose and classify renal injury. However, the scientific basis for such use has not been systematically evaluated. Thus, we appraised the value of common urinary findings for the diagnosis and classification of experimental septic acute renal failure. DESIGN: Systematic review. SETTING: Academic medical center and university-based research laboratory. SUBJECTS: Experimental studies describing urinary biochemistry, derived indexes, and microscopy in septic acute renal failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty-seven articles fulfilled all inclusion criteria. Due to heterogeneity, no formal quantitative analysis was possible. The methods for induction of sepsis and models were variable. The urinary sodium, fractional excretion of sodium, and urine osmolality were reported in only four (15%), 21 (78%), and seven (26%) studies, respectively. The fractional excretion of sodium exhibited a decrease, no change, or an increase from baseline in 11 (52%), five (24%), and five (24%) studies, respectively. The urine osmolality decreased from baseline in all endotoxin-induced models but showed an early transient increase in six (22%) studies of cecal-ligation perforation. Proteinuria or urinary enzymuria was reported in only seven (26%) studies. Urinary microscopy was described in one study. Only ten studies (37%) simultaneously reported on histopathology. In all these studies, histology either was normal or showed minor ultrastructural changes on electron microscopy. CONCLUSIONS: No conclusions are possible on how several urinary tests perform in diagnosing or classifying acute renal failure or in predicting the presence of acute tubular necrosis in experimental sepsis. Additional research is necessary to define the diagnostic and prognostic value of urinalysis in experimental sepsis.     

Detection of rejection in renal allografts. Evaluation with duplex sonography and DTPA renal scintigraphy with kidney/aorta perfusion ratios

Duplex sonography and technetium-99m DTPA renal scintigraphy have been used to distinguish acute rejection from other forms of renal allograft dysfunction. In this study, duplex sonography and renal scintigraphy were compared as methods to detect rejection. Eighty-four episodes of renal allograft dysfunction that had concurrent duplex sonography and renal scintigraphy over a 17-month period were reviewed. During the duplex sonography examinations the resistive index (RI) was measured from the renal cortex. Scintigrams were evaluated for allograft perfusion and function. The kidney to aorta (K/A) ratio was calculated from the upstroke of the perfusion curve. All diagnoses were established by clinical criteria. Histologic proof was available in 49 cases. There were two episodes of hyperacute rejection, 30 episodes of acute rejection, 14 episodes of chronic rejection, and 38 episodes of dysfunction without rejection. Using an RI greater than or equal to 0.70, the sensitivity and specificity for detecting acute rejection were 90% and 76%, respectively, compared with 37% and 76% for renal scintigraphy. The K/A ratio was not helpful in the diagnosis of rejection.     

Further studies on the mechanism of the natriuretic response to low-dose dopamine in man: effect on lithium clearance and nephrogenic cAMP formation

The effect of intravenous infusion of low-dose dopamine on electrolyte excretion, lithium clearance, nephrogenous cAMP formation and renal haemodynamics was investigated in healthy volunteers. Dopamine significantly increased the urine flow rate by 70.6% and urinary sodium excretion by 72%, but did not change creatinine clearance, PRA or plasma levels of AVP, ANP and cAMP. Renal plasma flow significantly increased by 48.6%; the glomerular filtration rate was not changed. Lithium per se increased basal PRA, but had no effect on the increments of urine flow rate, sodium excretion and renal blood flow induced by dopamine. Dopamine significantly increased the fractional excretion of lithium (representing fractional excretion of sodium at the proximal level). The increase in urinary sodium excretion during dopamine infusion, significantly correlated with the increase in fractional excretion of lithium (r = 0.94; P less than 0.01) and the increase in nephrogenous cAMP formation (r = 0.96; P less than 0.01). No correlation was found between the increase in urinary sodium excretion and the increase in renal blood flow. In conclusion, this study confirms that low-dose dopamine increases renal blood flow and urinary sodium excretion in healthy volunteers. This natriuretic response appears to be due to interaction with proximal tubular dopamine receptors, which are positively coupled to adenylate cyclase.     

Differential effects of human atrial natriuretic peptide and furosemide on glomerular filtration rate and renal oxygen consumption in humans

Objective Imbalance in the renal medullary oxygen supply/demand relationship can cause hypoxic medullary damage and ischemic acute renal failure. Human atrial natriuretic peptide (h-ANP) increases glomerular filtration rate in clinical acute renal failure. This would increase renal oxygen consumption due to increased tubular load of sodium. Loop diuretics are commonly used in acute renal failure. Data on the effects of loop diuretics on glomerular filtration rate and renal oxygen consumption in humans are, however, controversial. We evaluated the effects of h-ANP and furosemide on renal oxygen consumption, glomerular filtration rate, and renal hemodynamics in humans.Design and setting Prospective two-agent interventional study in a university hospital cardiothoracic ICUPatients Nineteen uncomplicated, mechanically ventilated postcardiac surgery patients with normal renal function.Interventions h-ANP (25 and 50 ng/kg per minute, n=10) or furosemide (0.5 mg/kg per hour, n=9)Measurements and results Renal plasma flow and glomerular filtration rate were measured using the infusion clearance technique for ⁵¹Cr-labeled EDTA and paraaminohippurate, corrected for by renal extraction of PAH. h-ANP increased glomerular filtration rate, renal filtration fraction, fractional excretion of sodium, and urine flow. This was accompanied by an increase in tubular sodium reabsorption (9%) and renal oxygen consumption (26%). Furosemide infusion caused a 10- and 15-fold increase in urine flow and fractional excretion of sodium, respectively, accompanied by a decrease in tubular sodium reabsorption (–28%), renal oxygen consumption (–23%), glomerular filtration rate and filtration fraction (–12% and –7%, respectively).Conclusions The filtered load of sodium is an important determinant of renal oxygen consumption. h-ANP improves glomerular filtration rate but does not have energy-conserving tubular effects. In contrast, furosemide decreases tubular sodium reabsorption and renal oxygen consumption and thus has the potential to improve the oxygen supply/demand relationship in clinical ischemic acute renal failure.This research was supported by grants from the Swedish Medical Research Council (no. 13156), Medical Faculty of Gothenburg (LUA), and Gothenburg Medical Society.     

Effect of inhibition of converting enzyme on renal hemodynamics and sodium management in polycystic kidney disease

We compared the tubular transport of sodium and the erythrocyte sodium-lithium countertransport activity in hypertensive patients with autosomal dominant polycystic kidney disease (ADPKD) and in normotensive control subjects. In addition, we assessed the effects of inhibition of converting enzyme on renal hemodynamics and sodium excretion in hypertensive patients with ADPKD to provide information on mechanisms responsible for the increased renal vascular resistance and filtration fraction and the adjustment of the pressure-natriuresis relationship during saline expansion, observed in patients with ADPKD, hypertension, and preserved renal function. In comparison with normotensive control subjects, the hypertensive patients with ADPKD had lower renal plasma flows, higher renal vascular resistances and filtration fractions, and similar proximal and distal fractional reabsorptions of sodium. The administration of enalapril resulted in significant increases in the renal plasma flow and significant reductions in mean arterial pressure, renal vascular resistance, and filtration fraction, but the glomerular filtration rate remained unchanged. Despite the significant reduction in mean arterial pressure during inhibition of converting enzyme, the distal fractional reabsorption of sodium decreased while the total fractional excretion of sodium remained unchanged or increased slightly. No significant differences were detected between the normotensive control subjects and the hypertensive patients with ADPKD in erythrocyte sodium-lithium countertransport activity, plasma renin activity, plasma aldosterone concentration, or atrial natriuretic factor. These results suggest that the renal renin-angiotensin system plays a central role in the alterations in renal hemodynamics and sodium management associated with the development of hypertension in ADPKD.     

Urinary excretion of N-acetyl-beta-D-glucosaminidase in normal and complicated pregnancy

The urinary excretion of N-acetyl-beta-D-glucosaminidase activity, a sensitive indicator of renal tubular injury, was monitored during and after pregnancy. During normal pregnancy, enzymuria increased progressively to levels 3-4 times above normal in the third trimester. In diabetic mothers, enzyme excretion followed a similar pattern, but was generally higher than in uncomplicated pregnancies. Also in preeclampsia, enzymuria tended to be higher than in normal pregnancy. Enzyme excretion normalized about a year after normal pregnancies, but remained elevated in diabetic subjects and in patients who had developed preeclampsia. This latter finding indicates that marginal persistent renal damage may occur during preeclampsia.     

Atrial natriuretic factor and changes in dietary sodium intake in patients with chronic renal failure

1. In order to examine the potential role of atrial natriuretic factor in modulating the increased sodium excretion per nephron in chronic renal failure, we studied 12 uraemic patients on the last day of two successive 7 day periods during which their sodium intake was 100 and 20 mmol of sodium/day, respectively. 2. There was a parallel decrease from 6.31 +/- 0.75 to 2.17 +/- 0.32% in the fractional excretion of filtered sodium and from 234.4 +/- 74.9 to 80.6 +/- 20.3 pg/ml (supine position) or 140.1 +/- 43.6 to 60.7 +/- 14.6 pg/ml (upright position) in plasma atrial natriuretic factor. Both parameters were significantly correlated during the two periods of different sodium intake (P less than 0.05). The ratio of plasma guanosine 3':5'-cyclic monophosphate to plasma creatinine changed proportionally to plasma atrial natriuretic factor. Plasma aldosterone and plasma renin activity increased during the sodium-depleted period but only plasma renin activity was significantly correlated with fractional excretion of filtered sodium. 3. The predominant role of atrial natriuretic factor compared with that of aldosterone in the renal response to varying sodium intake is suggested both by regression analysis and by the effect of 5 day's treatment with a converting enzyme inhibitor (enalapril) in six other uraemic patients on a normal (100 mmol/day) sodium intake. Such treatment, although resulting in a significant increase in plasma renin activity and a significant decrease in plasma aldosterone, at least in the supine position, did not modify the fractional excretion of sodium and plasma atrial natriuretic factor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Volume Expansion on Sodium Excretion in the Presence and Absence of Increased Delivery from Superficial Proximal Tubules

The role of the proximal tubule in the natriuresis after volume expansion was investigated by evaluating sodium excretion both in the presence and absence of increased delivery from the proximal tubule. Proximal delivery was calculated from fractional reabsorption in superficial proximal tubules determined by micropuncture and glomerular filtration rate of the micropunctured kidney. Infusion of Ringer's solution in six dogs increased delivery from the proximal tubule 4.7±1 ml/min (P < 0.01) and increased fractional sodium excretion 3.6±1.1% (P < 0.025). Infusion of hyperoncotic albumin into the renal artery during sustained volume expansion decreased delivery from the proximal tubule 6.5±0.9 ml/min (P < 0.01). Although proximal delivery was restored to below control levels, fractional sodium excretion was significantly increased 2.5±0.5% (P < 0.01) as compared with the hydropenic control period. Fractional phosphate excretion was increased 15.5±3.7% (P < 0.01) after Ringer's infusion and was decreased 10.5±1.6% (P < 0.005) after intrarenal albumin infusion, suggesting that changes in superficial nephron reabsorption were paralleled by changes in reabsorption in deeper nephrons. Similar results were found in six additional dogs in which other factors known to affect phosphate reabsorption were controlled; however, these studies cannot completely eliminate a role for deep nephrons in the natriuresis after intrarenal albumin infusion. Since 70% of the natriuresis after volume expansion was present without increased delivery from superficial proximal tubules, it is likely that increased delivery from the proximal tubule contributes a relatively minor fraction to the natriuresis of volume expansion.     

Effects of insulin on renal haemodynamics and sodium handling in normal subjects

Diabetic patients treated with insulin injected subcutaneously are characterized by peripheral hyperinsulinaemia and an increased mass of total body exchangeable sodium. We hypothesized that this may cause, at least in part, the glomerular hyperfiltration seen in the diabetic state. Six normal subjects were studied on 2 days in random order. Day A: Basal state for 40 min, hyperinsulinaemic euglycaemic clamp for 1 h (insulin infusion rate 2 mU kg-1 min-1 and 50% glucose infusion) and hyperinsulinaemic euglycaemic clamp combined with volume expansion (2 1 isotonic sodium chloride) for 2 h. Day B: as day A, but without insulin and glucose infusion. During combined volume expansion and hyperinsulinaemia an increase in glomerular filtration rate (GFR) (128 +/- 6 vs 117 +/- 8 ml min-1 1.73 m-2, p less than 0.01) and lithium clearance (CLi) (50 +/- 4 vs 33 +/- 5 ml min-1 1.73 m-2, p less than 0.01) was observed compared with basal conditions. GFR and CLi were unchanged during day B. Insulin infusion reduced renal sodium excretion. Absolute proximal tubular reabsorption was unchanged on both days. Insulin infusion without volume expansion caused a decrease of 24% in the fractional distal sodium excretion. Superimposed volume expansion and the concomitant increase in GFR and CLi was accompanied by a subsequent enhanced fractional distal sodium excretion of 27%. The changes in plasma concentrations of aldosterone, renin, angiotensin II, atrial natriuretic peptide and catecholamines did not explain the differences in GFR. An increase in GFR of 10%, comparable with that observed in diabetic patients, was induced by combined hyperinsulinaemia and volume expansion in euglycaemic normal subjects. The enhanced GFR is probably a compensatory response to the sodium retention induced by the action of insulin on the distal tubules.     

Effects of prenalterol on renal function in patients after major vascular surgery

Hemodynamic and renal effects of prenalterol were studied in 13 mechanically ventilated patients on the first day after major vascular surgery. Prenalterol (1-[4-hydroxyphenoxy]-3-isopropylamino-2 propanol hydro-chloride), a partial beta-agonist with a predominant beta-1 and a weak beta-2-adrenoceptor activity, was infused into seven patients at rates of 0.5 and 1.0 microgram/kg.min (group A), and at a dose of 2.0 micrograms/kg.min in six patients (group B). Although no hemodynamic changes were observed in group A, systolic BP, mean BP, heart rate, and cardiac output increased significantly in group B. Catecholamine levels and plasma renin activity were unaltered in both groups, as was glomerular filtration rate. Renal blood flow did not change in group A but it increased by 25% in group B. Urine flow, fractional free water clearance, fractional sodium excretion, and fractional chloride excretion were unaltered in both groups. Fractional potassium excretion decreased by 20%, 22%, and 26% at the three infusion rates of prenalterol, respectively. We conclude that prenalterol does not directly influence renal function in the postoperative setting.     

A(1) receptor blockade induces natriuresis with a favorable renal hemodynamic profile in SHHF/Mcc-fa(cp) rats chronically treated with salt and furosemide.

Our goal was to test the hypothesis that A(1) receptor blockade induces diuresis/natriuresis with a favorable renal hemodynamic/cardiac profile in aged, lean SHHF/Mcc-fa(cp) rats, a rodent model of hypertensive dilated cardiomyopathy. Thirteen-month-old SHHF/Mcc-fa(cp) rats were pretreated for 72 h before experiments with furosemide (100 mg/kg by gavage 72, 48, and 24 h before experiments) to mimic the clinical setting of chronic diuretic therapy and were given 1% NaCl as drinking water to reduce dehydration/sodium depletion. Animals were instrumented for measurement of systemic and renal hemodynamics, renal excretory function, and cardiac performance, and baseline values were obtained during a 30-min clearance period. Animals then received either vehicle (n = 9), BG9719 [the S-enantiomer of 1,3-dipropyl-8-[2-(5,6-epoxynorbornyl)] xanthine (also called CVT-124)] (highly selective A(1) receptor antagonist; 0.1 mg/kg bolus + 10 microg/kg/min; n = 9) or furosemide (loop diuretic; 30 mg/kg; n = 8) and measurements were repeated during four subsequent clearance periods. Both BG9719 and furosemide increased urine volume and absolute and fractional sodium excretion. BG9719 increased renal blood flow and glomerular filtration rate, but did not affect fractional potassium excretion. Furosemide decreased renal blood flow and glomerular filtration rate and increased fractional potassium excretion. Neither drug altered afterload; however, furosemide, but not BG9719, decreased preload (central venous pressure and ventricular end diastolic pressure). Neither drug altered systolic function (+dP/dt(max)); however, furosemide, but not BG9719, attenuated diastolic function (decreased -dP/dt(max), increased tau). In the setting of left ventricular dysfunction, chronic salt loading and prior loop diuretic treatment, selective A(1) receptor antagonists are effective diuretic/natriuretic agents with a favorable renal hemodynamic/cardiac performance profile.     

Effect of meclofenamate on lithium excretion in response to changes in renal perfusion pressure

Previous studies in dogs have demonstrated that inhibition of prostaglandin synthesis markedly impairs the ability of the kidney to alter sodium excretion in response to changes in renal perfusion pressure (RPP). The objectives of the present study were to determine whether renal prostaglandins play a role in the urinary sodium excretory response to alterations in RPP in the rat and to determine the role of the proximal tubule in this response. RPP was changed from 127 to 109 mm Hg and then to 91 mm Hg with a servo-controlled cuff on the abdominal aorta. Fractional lithium excretion (FELi) was used as an index of ractional sodium reabsorption by the proximal tubule. As a function of increases in RPP, FELi increased, suggesting that fractional sodium reabsorption by the proximal tubule was decreased in response to increases in RPP in control animals. In meclofenamate-treated rats, increases in fractional sodium excretion and FELi in response to increases in RPP were attenuated compared with levels in control animals. The blunted response of FELi in meclofenamate-treated rats suggests that the attenuated increase in urinary sodium excretion observed during increases in RPP reflects an increase in proximal sodium reabsorption mediated by blockade of renal prostaglandins.     

Studies on the characteristics of the control system governing sodium excretion in uremic man

Sodium excretion was studied in a group of patients with chronic renal disease, (a) on constant salt intakes of varying amounts with and without mineralocorticoid hormone administration and, (b) after acute extracellular fluid volume expansion. The lower the steady-state glomerular filtration rate (GFR), the greater was the fraction of filtered sodium excreted on both a 3.5 and 7.0 g salt diet; and the lower the GFR, the greater was the change in fractional excretion in the transition from the 3.5 to the 7.0 g salt diet. This regulatory capacity did not appear to be influenced by mineralocorticoid hormone administration. After acute expansion of extracellular fluid (ECF) volume, the increment in sodium excretion exceeded the concomitant increment in filtered sodium in six of nine studies and in the remaining three studies, the increment in excretion averaged 59% of the Delta filtered load (i.e., only 41% of the increase in filtered sodium was reabsorbed). During saline loading, the decrease in fractional reabsorption of sodium tended to vary inversely with the steady-state GFR, although all patients received approximately the same loading volume. When an edema-forming stimulus was applied during saline infusion, the natriuretic response was aborted and the lag time was relatively short. When GFR and the filtered load of sodium were increased without volume expansion, the Delta sodium excretion averaged only 19% of the Delta filtered load; moreover, changes in fractional sodium reabsorption were considerably smaller than those observed during saline loading. The data implicate the presence of a factor other than GFR and mineralocorticoid changes in the modulation of sodium excretion in uremic man.     

Urinary N-acetyl-beta-D-glucosaminidase and aminopeptidase N in the diagnosis of graft rejection after live donor renal transplantation

An evaluation of the usefulness of urinary N-acetyl-beta-D-glucosaminidase (NAG) and aminopeptidase N (AAP) measurements in the diagnosis and prediction of acute and chronic renal allograft rejection was made. Enzyme activities were measured in 2,745 morning spot urine samples from 53 consecutive live donor renal allograft recipients up to 180 days after transplantation. Reference ranges of urinary enzyme activities in 14 recipients with normal graft function were higher than those established in a carefully selected group of healthy controls. 89 and 91% of 76 clinically diagnosed acute rejection episodes (ARE) in the remaining 39 graft recipients were accompanied by sharp increase over baseline of NAG and AAP respectively. All rejection episodes occurring in the early period after transplantation were characterised by high enzymuria. AAP was more sensitive than NAG as the magnitude of its increase over baseline was more, while NAG was more specific with less number of false positive elevations. Both enzymes were found to be equally good prognostic indices of graft loss and chronic graft deterioration. Regular monitoring of urinary NAG and AAP activities throughout the post transplant period would thus be valuable in (a) diagnosis and prediction of ARE in the early as well as late post operative period and (b) prediction of eventual graft outcome.     

Increased urinary zinc excretion after thermal injury.

Urinary zinc excretion normally plays a minor role in zinc homeostasis; however, urinary zinc excretion is markedly elevated after trauma or surgery, and mechanism(s) for this zinc loss are poorly defined. In this study we evaluated multiple potential mechanisms for increased urinary zinc excretion in patients with thermal injury. We documented that patients with severe thermal injury had markedly elevated urinary zinc excretion. Above 20% total body surface area burn, however, the severity of thermal injury did not correlate with urinary zinc excretion. Serum zinc concentrations were depressed on initial evaluation and gradually increased during the hospital course, whereas peak urinary zinc excretion occurred 2 to 5 weeks after injury. Thus the depression in serum zinc concentration did not temporally relate to the observed pattern of hyperzincuria. Increased urinary zinc excretion also did not temporally relate to urinary excretion of the amino acids cysteine and histidine (both of which tightly bind zinc) nor to urinary 3-methylhistidine excretion, a marker of muscle breakdown. Urinary amylase excretion, a marker of renal tubular dysfunction, did follow the pattern of urinary zinc loss to some extent, although this correlation was not perfect. Increased oral intake of zinc via zinc supplements resulted in significantly increased urinary zinc excretion. Patients receiving total parenteral nutrition (TPN) did not have significantly increased urinary zinc excretion when compared with people receiving their total nutrient intake by mouth.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the renal effects of low to high doses of dopamine and dobutamine in critically ill patients: a single-blind randomized study

OBJECTIVE: The renal effects of dopamine in critically ill patients remain controversial. Low-dose dobutamine has been reported to improve renal function. We compared the effects of various doses of dopamine and dobutamine on renal function in critically ill patients. DESIGN: Prospective, single-blind, randomized study. SETTING: University hospital, 19-bed multidisciplinary intensive care unit. PATIENTS: Twelve hemodynamically stable patients with mild nonoliguric renal impairment. INTERVENTIONS: Each patient randomly received four different doses of dopamine and dobutamine (placebo, 3, 7, and 12 microg/kg/min). Each infusion lasted for 4 hrs. Cardiac output and systemic hemodynamic variables were measured using a pulmonary arterial catheter at the beginning (HO) and the end (H4) of each infusion. The bladder was emptied at HO and H4 to determine urine volume and to collect samples. MEASUREMENTS AND MAIN RESULTS: The cardiac index increased significantly with both dopamine and dobutamine (p < .001). Mean arterial pressure (MAP) increased, with the maximum effect of 20% seen with 12-microg/kg/min dopamine infusion (p < .01). No change in MAP was seen with dobutamine. Dobutamine infusions did not change any renal variables. Conversely, all dopamine infusions significantly increased diuresis, creatinine clearance, and the fractional excretion of sodium (p < .01). Creatinine clearance increased from 61+/-16.9 (SD) mL/min to a maximum of 85.7+/-30 mL/min at the 7-microg/kg/min dose; fractional excretion of sodium increased from 0.26%+/-0.28% to a maximum of 0.62%+/-0.51% at the 12-microg/kg/min dose (p < .01). During dopamine infusions, there was a significant relationship between MAP and creatinine clearance (p = .018). CONCLUSIONS: At all doses studied, 4-hr infusions of dopamine significantly increased creatinine clearance, diuresis, and the fractional excretion of sodium in stable critically ill patients. Conversely, dobutamine did not modify these variables. Although the level of MAP might partially contribute to the improvement in renal variables, it is more likely that the activation of renal dopamine receptors played a prominent role.