Substance P decreases fluid absorption in the renal proximal tubule.

Substance P is a neuropeptide found principally in the central nervous system and peripheral afferent nerve fibers. It is widely distributed in the body, and its local release is thought to have important effects in the normal physiology and pathophysiology of several organ systems. Substance P releases histamine from mast cells and nitric oxide from endothelial cells. Systemic infusion of substance P causes a brisk natriuresis. Previously, proximal tubule transport in the kidney was measured in vivo during the infusion of substance P. Transport was inhibited. This could have been a direct action of substance P or secondary to the release of histamine or nitric oxide. Therefore, we have now studied the effect of substance P on isolated proximal tubules perfused in vitro. We found that 10(-10) M substance P caused a 50% reduction in the rate of fluid absorption in rabbit proximal straight tubule. This effect was reversible on removal of substance P from the bath. Inhibition of nitric oxide production with NG-monomethyl-L-arginine (10(-4) M) did not influence the action of substance P at 10(-10) M. The sensitivity of the proximal tubule to low concentrations of substance P, together with the recent findings of substance P-containing afferent fibers within the cortex of the kidney, suggest a role for substance P in the control of proximal tubule reabsorption, particularly in pathophysiological conditions associated with increased afferent nerve activity, such as ureteric occlusion.

Dopamine and protein phosphatase activity in renal proximal tubules.

In the brain, dopamine, via protein kinase A (PKA) activation of dopamine- and cAMP-regulated phosphoprotein (DARPP-32), inhibits protein phosphatase 1 (PP1) activity and keeps Na(+)-K(+)-adenosinetriphosphatase (ATPase) in its phosphorylated inactive state. In the present study, we examined the relationship among dopamine, PP1, and Na(+)-K(+)-ATPase activities in renal proximal tubules. PP1 activity in proximal tubules was not decreased by dopamine (5 x 10(-9)-10(-4) M), fenoldopam (5 x 10(-6) M), or norepinephrine (5 x 10(-7) M). In contrast, in the medullary thick ascending limb of Henle and in the brain striatum, PP1 activity was decreased by fenoldopam (5 x 10(-6) M). We also showed that the ability of dopamine (10(-6) M) to inhibit Na(+)-K(+)-ATPase activity in proximal tubules (assessed by ouabain-sensitive 86Rb uptake) occurred in the absence or presence of a sodium clamp with 5 microM monensin. Thus the inhibitory effect of dopamine on Na(+)-K(+)-ATPase activity in proximal tubules is not regulated by PP1 activity. Tautomycin and okadaic acid by themselves, at concentrations that inhibited PP1 activity, had no effect on Na(+)-K(+)-ATPase activity in proximal tubules. The ability of a dopamine D1 agonist, fenoldopam, to inhibit PP1 activity in brain striatum and in medullary thick ascending limb, but not in proximal tubules, suggests differential organ and nephron segment regulation of PP activity.

Neonatal renal function and physiology.

Birth rapidly changes the demands placed on the kidneys with respect to infant homeostasis. Conceptional age (gestational plus postnatal), general health, and medical management may independently, or, in concert, give rise to important metabolic abnormalities marked by apparent renal functional inadequacies. The chronology of the renal functional changes occurring with maturation in infants born before or at term is now well described. The confounding effects of treatment on the development of renal function in very low birth weight infants are also becoming more apparent. However, the mechanisms responsible for these changes are just becoming to be understood with the use of molecular biologic techniques.

The diagnosis of acute pyelonephritis in the piglet using single photon emission computerized tomography dimercaptosuccinic acid scintigraphy: a pathological correlation.

Single photon emission computerized tomography (SPECT) scintigraphy has proved to be an extremely sensitive renal imaging modality in children with genitourinary pathology, including pyelonephritis, particularly when compared to 2-dimensional planar imaging. This study was undertaken to corroborate SPECT dimercaptosuccinic acid (DMSA) scintigraphic findings with specific histopathology in acute pyelonephritis. Unilateral vesicoureteral reflux was produced in 19 Yorkshire piglets 3 to 4 weeks old. The bladders of 12 animals were inoculated with Escherichia coli 2 weeks later, after baseline SPECT DMSA scans had been obtained. The animals were then re-imaged at 3 (4), 7 (4) or 14 (4) days after infection and sacrificed for histological evaluation. Seven purposefully uninfected piglets with unilateral reflux served as controls and were followed for up to 6 weeks before imaging and sacrifice. SPECT proved to be 97% sensitive and 93% specific in providing the diagnosis of acute pyelonephritis. The SPECT findings were manifest by a spectrum of abnormal findings (mottling, striations, inner cortical scalloping and focal cortical defects), which correlated precisely with the extent and severity of cortical involvement in the acute pyelonephritic process. We propose a new classification scheme for SPECT DMSA renal scintigraphic imaging, and believe that this modality is exquisitely sensitive in providing the diagnosis as well as in evaluating the extent of renal parenchymal involvement when acute pyelonephritis is induced in the animal model.

Evaluation of renal function.

Renal function can now be evaluated in utero and after birth. Most of the methods used to investigate suspected renal dysfunction or disease are not presently applicable to the fetus; however, prenatal and postnatal evaluation of renal function has assumed a greater importance as the consequences of birth before term become more apparent.

Diuretic and natriuretic effects of sorbinil, an aldose reductase inhibitor.

The renal effects of sorbinil, an aldose reductase inhibitor that interferes with the conversion of glucose to sorbitol, were studied in rats and rabbits before and after fluid deprivation. The intracellular osmolar solute, sorbitol, is found in increasing concentrations from cortex to medulla in the kidney and may be involved in the urinary concentrating mechanism. Oral administration of sorbinil in the rabbit resulted in significant increases in urine flow rate and sodium excretion with a tendency toward decreased urine osmolality and increased potassium excretion both before and after water deprivation. When fluid intake was controlled in the rat study, significant increases in urine flow rate and sodium and potassium excretion and a significant decrease in urine osmolality occurred only in response to fluid deprivation. Thus, sorbinil has diuretic and natriuretic properties and may prevent the normal concentration of urine in the antidiuretic animal.

High resolution single photon emission computerized tomography (SPECT) 99mtechnetium-dimercapto-succinic acid renal imaging: a state of the art technique.

The 99mtechnetium-dimercapto-succinic acid renal scan has become the gold standard for evaluating renal parenchymal pathology. The traditional pinhole technique provides 2-dimensional imaging. Recent application of high resolution single photon emission computerized tomography (SPECT) has provided the means to obtain even greater cortical detail. With 360-degree imaging and computer reconstruction, SPECT provides coronal, sagittal and transaxial imaging. We prospectively compared the SPECT and pinhole techniques in 33 patients (65 renal units) ranging in age from 2.5 months to 18 years. Both scans were obtained in all patients. All scans were reviewed by an independent interpreter. Using SPECT imaging, diagnostic information was enhanced in 46 of the 65 kidneys (71%). Of the 24 kidneys that appeared "normal" by pinhole imaging 15 (63%) had defects on SPECT imaging. High resolution SPECT imaging improves the ability to identify cortical defects and visualize asymmetry of cortical thickness compared to standard pinhole imaging.

Colonic intussusception secondary to a calcium phosphate bezoar in a child receiving calcium carbonate for hyperphosphatemia.

We report a case of a calcium phosphate bezoar resulting in colonic intussusception in a boy with chronic renal failure who received calcium carbonate to control hyperphosphatemia. Because of concerns about aluminum-related disease in patients receiving aluminum hydroxide phosphate binders, calcium carbonate is being used more frequently to manage phosphate retention in renal failure. The development of bezoars may complicate this new form of therapy.

Postnatal development of renal function.

Renal function in the newborn is both qualitatively and quantitatively different from older infants, children and adults. Moreover, gestational age is of great importance in the interpretation of renal functional differences. These differences in renal function should not be viewed as solely immaturity per se but rather as functional adaptations to the needs of growth and development in many instances. Although the neonatal kidney is operating at a level appropriate for a given age, the decreased functional reserve makes it more vulnerable to stressful conditions. However, the low GFR and some of the decreased transport properties may actually be of benefit to the neonate. With respect to medications, one benefit of these neonatal differences appears to be less nephrotoxicity for certain drugs in the newborn compared with the adult.

Renal effects of atrial natriuretic factor in domestic fowl.

The renal hemodynamic and tubular effects of ANF were investigated using the Sperber technique in chickens. This technique takes advantage of the unique portal circulation of the avian kidney and permits direct access to the renal peritubular space independent of renal arterial blood flow and glomerular filtration. Infusion of ANF into the avian renal portal system increased urine flow rate and sodium excretion by as much as 300% and 100%, respectively. These changes occurred in the absence of significant alterations in glomerular filtration rate or renal plasma flow. There was no significant difference in urine flow, sodium excretion or glomerular filtration rate between the ANF-infused kidney and the contralateral, non-infused kidney. We conclude that the diuretic and natriuretic effects of ANF do not depend on changes in glomerular filtration rate and that the site of action of ANF is the renal medulla.

Acute renal failure. II. Management of suspected and established disease.

Because the pathogenesis of acute renal failure is multifactorial, clinical evaluation and ancillary studies must be performed systematically to reliably differentiate the various disorders. This assessment includes measurement of the serum creatinine and urea concentrations, urine composition and flow rate, and fractional excretion of sodium. Radiodiagnostic techniques such as ultrasound, radionuclide renal scans, and nuclear magnetic resonance may provide useful anatomic and functional information. With this data base, the physician can prescribe an individualized management plan that addresses the fluid, metabolic, and nutritional necessities of the child.

Renal alpha-adrenoceptors and sodium excretion in the dog.

The purpose of this study was to characterize the age-dependent role of alpha-adrenergic activity on renal vascular resistance (RVR) and renal blood flow (RBF) and the role of alpha 2-receptors in sodium transport. Intrarenal infusion of phentolamine in hydropenic anesthetized pups and adult dogs increased RBF and glomerular filtration rate (GFR) only in pups. The effect was most marked in the youngest pups (15.67 +/- 0.67 days). At 1.0 micrograms X kg-1 X min-1, phentolamine increased RBF from 1.38 +/- 0.04 to 1.64 +/- 0.04 ml X min-1 X g kidney wt-1 and GFR from 0.19 +/- 0.01 to 0.23 +/- 0.01 ml X min-1 X g kidney wt-1. Absolute (UNaV) and fractional (FENa) sodium excretions increased in all animals, but mean percent increases were greatest in adult dogs. Intrarenal yohimbine infusion in adult dogs (10-100 micrograms X kg-1 X min-1) produced a dose-related increase in UNaV and FENa without affecting RBF and GFR. UNaV increased from 0.22 +/- 0.05 to 0.54 +/- 0.12 mueq X min-1 X g kidney wt-1 and FENa increased from 0.32 +/- 0.05 to 0.63 +/- 0.06% at the dose of 100 micrograms X kg-1 X min-1. These studies confirm a modest role for alpha-adrenoreceptors in the high RVR characteristic of newborn pups and provide evidence for a role of alpha 2-adrenoceptors in the renal transport of sodium; the extent of the contribution of renal alpha-adrenergic system could not be tested in this experiment.

Age-dependent renal effects of intrarenal dopamine infusion.

Three groups of anesthetized puppies 16.4 +/- 1.2 (group I), 29.6 +/- 1.6 (group II), and 49.8 +/- 2.5 (group III) days of age were used to assess the renal response to graded doses of dopamine infusion into the renal artery. Dopamine infusion at 1 microgram X kg-1 X min-1 increased renal blood flow (RBF) from 3.61 +/- 0.31 to 4.22 +/- 0.43 ml X min-1 X g kidney wet wt-1 (P less than 0.05) only in the older puppies (group III). Glomerular filtration rate (GFR) increased in groups II and III from control values of 0.69 +/- 0.14 and 0.61 +/- 0.08 to 1.08 +/- 0.19 and 0.83 +/- 0.05 ml X min-1 X g kidney wet wt-1, respectively (P less than 0.05). However, urinary flow rate and sodium excretion were variably affected. Because dopamine is known to stimulate both alpha- and beta-adrenoceptors in addition to dopamine receptors, two additional groups of puppies 11.2 +/- 1.2 (group IV) and 72.8 +/- 2.4 (group V) days of age were studied to evaluate the renal effects of dopamine during the continuous intrarenal infusion of phentolamine and nadolol (an alpha- and a beta-adrenergic blocker, respectively). Dopamine elicited increases in RBF only in the older puppies (P less than 0.05). GFR, urinary flow rate, and sodium excretion increased in both groups; however, the magnitude of the change was greater for each parameter in the older group (P less than 0.05). These experiments suggest a maturational process for specific dopamine receptors and/or effector response, which may affect the observed age-dependent increases in RBF, GFR, and renal sodium handling.

Effects of dopamine blockade on renal sodium excretion.

The renal responses to a specific dopamine antagonist (cis-flupentixol) and its stereoisomer (trans-flupentixol), a weak dopamine antagonist, were examined during hydropenia and Ringer loading in anesthetized rats. During hydropenia glomerular filtration (GFR), absolute (UNaV), and fractional (FENa) sodium excretion rates were similar as were single-nephron filtration (SNGFR) and proximal tubular flow rate (VTF). After Ringer loading GFR, UNaV, and FENa increased in all groups, but the increments were less in the cis-flupentixol than in the control or trans-flupentixol group. SNGFR and VTF increased similarly in all groups. In another series of experiments Ringer loading was performed prior to drug administration. Perfusion pressure (PP) was decreased in trans-flupentixol rats by aortic constriction to control for cis-flupentixol-induced reduction in PP. UNAV and FENa were lower in the cis-flupentixol- than trans-flupentixol-treated rats at comparable PP and GFR. In conclusion, dopamine blockade attenuated the natriuresis of Ringer loading; the mechanism is uncertain but may be related to a tubular effect at a site beyond the proximal convoluted tubule and/or in deeper nephrons.