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Role for intrarenal mechanisms in the impaired salt excretion of experimental nephrotic syndrome.

A unilateral model of puromycin aminonucleoside (PAN)-induced albuminuria was produced in Munich-Wistar rats to examine the mechanisms responsible for renal salt retention. 2 wk after selective perfusion of left kidneys with PAN (n = 8 rats) or isotonic saline (control, n = 7 rats), increases in albumin excretion and decreases in sodium excretion were demonstrated in PAN-perfused but not in nonperfused kidneys of PAN-treated rats although systemic plasma protein concentration remained at control level. Total kidney glomerular filtration rate (GFR) and superficial single nephron (SN) GFR were also reduced selectively in PAN-perfused kidneys, on average by approximately 30%, due primarily to a marked decline in the glomerular capillary ultrafiltration coefficient (Kf), which was also confined to PAN-perfused kidneys. Values for absolute proximal reabsorption (APR) were also selectively depressed in PAN-perfused kidneys, in keeping with a similarly selective decline in peritubular capillary oncotic pressure measured in these kidneys, the latter also a consequence of the fall in Kf. In a separate group of seven PAN-treated rats, however, no differences were detected between PAN-perfused and nonperfused kidneys in the absolute amount of sodium reaching the early (0.77 +/- 0.09 neq/min vs. 0.74 +/- 0.08, P greater than 0.40) and late portions of superficial distal tubules (0.31 +/- 0.02) neq/min vs. 0.32 +/- 0.05, P greater than 0.50), despite the lesser filtered load of sodium in PAN-perfused kidneys. Suppressed sodium reabsorption in both proximal convoluted tubules and short loops of Henle of PAN-perfused kidneys contributed to this equalization of sodium delivery rates to the late distal tubule, as did comparable reabsorption along distal convolutions. In two additional groups of PAN-treated rats, infusion of saralasin (0.3 mg/kg per h, i.v.) led to substantial increases in total kidney GFR and SNGFR in PAN-perfused but not in nonperfused kidneys. Despite these increases in total and SNGFR, urinary sodium excretion by PAN-perfused kidneys remained at a level far below that for nonperfused kidneys, again indicating that the antinatriuresis characterizing the PAN-perfused kidney is due to alterations in sodium handling by the tubules rather than changes in GFR. These results therefore indicate (a) that reductions in Kf and depressed sodium reabsorption by proximal tubules and Henle's loop segments in this model are brought about by intrarenal rather than circulating or systemic factors, and (b) assuming that superficial nephrons are representative of the entire nephron population, renal salt retention in this model is due primarily to intrarenal factor(s) acting beyond the distal convolution.

Animals↗

Unusual renal pathology associated with a Wilms tumor in a 15-month-old infant.

Beckwith-Wiedemann syndrome is an overgrowth dis-order that predisposes to the development of a variety of malignancies including Wilms tumor. Pathologists may suspect the presence of Beckwith-Wiedemann syndrome, which may be clinically subtle, on the basis of the histopathology of the renal parenchyma adjacent to a Wilms tumor. These kidneys typically harbor multiple nephrogenic rests (especially perilobar nephrogenic rests), and their medullas have blunted papillae resulting from excessive fibromyxoid stroma, decreased collecting ducts, and decreased Henle loops. This complex of findings constitutes the so-called Beckwith Medulla. Extensions of this stroma-rich medulla into the cortex results in characteristic dysplastic medullary-ray nodules. Identification of these histologic abnormalities by the pathologist should prompt the clinician to evaluate the child for Beckwith-Wiedemann syndrome. Proper screening of these children can allow for early detection of cancers and treatment while these cancers are curable.

Antineoplastic Combined Chemotherapy Protocols↗

Renal tubular reabsorption of calcium in familial hypocalciuric hypercalcaemia.

To investigate the nephron site of the enhanced tubular calcium reabsorption in familial hypocalciuric hypercalcaemia (FHH), the renal plasma clearance of lithium and calcium and the glomerular filtration rate were determined simultaneously after an overnight fast in nine FHH patients and ten healthy controls. As the renal plasma clearance of lithium equals the rate of the proximal tubular fluid delivered into the thin descending loop of Henle's loop, the reabsorption of calcium in the proximal and distal tubule, respectively, could be calculated. We found that the FHH patients had a significantly higher fractional calcium reabsorption in the proximal tubule (77.6 +/- 4.7 (%) vs 73.3 +/- 3.1, P less than 0.05). The same held true for the absolute proximal calcium reabsorption (1.49 +/- 0.12 (mmol/l) vs 1.07 +/- 0.05, P less than 0.001). There was a significant linear correlation between the increased tubular capacity for calcium reabsorption and the absolute proximal calcium reabsorption (r = 0.70, P less than 0.05). The distal tubular calcium reabsorption did not differ in the two groups. Our results therefore suggest that the enhanced tubular calcium reabsorption in FHH takes place exclusively in the proximal renal tubule.

Adolescent↗

Nodular thickening of peritubular basement membranes in diabetic kidneys.

A conspicious renal change associated with diabetes is the thickening of the basement membranes. This was generally considered diffuse and little attention was paid to its nodular character. In the present study of the nodules, their topo-optical reation, electron microscopic fine structure as well as their trypsin digestibility after periodic acid-sulphatation revealed their basement membrane character. The increased basophilia obtained by the aldehyde-bisulphite-toluidine blue reaction indicated an increased amount of sugar components, whereas the decreased double refraction and the red polarization colours a decrease of the micellary arrangement. The change is mostly observed in diabetics; the specific localization around the Henle loops may refer eventual hyperosmolar effects, whereas the nodular character points to the role of local factors.

Basement Membrane↗

[Possible mechanisms of polyuria in progressive chronic renal failure].

AIM: Elucidation of the role of saluresis and osmotic diuresis in renal function of patients with chronic renal failure. MATERIAL AND METHODS: The trial included 68 subjects, among them 25 patients with chronic renal failure (CRF) of the third and fourth degree aged 16 to 72 years. Enzyme immunoassay was used to measure osmolality, sodium, potassium, magnesium, calcium and creatinine concentrations in the serum and urine as well as urine prostaglandin E2. RESULTS: Renal function was studied in CRF patients with a 75-90% fall of glomerular filtration rate. Creatinine clearance was 19.9 +/- 0.96, it varied in different patients from 10.6 to 29.7 ml/min. It is shown that diuresis does not correlate with the total ion excretion (Na+ plus K+)(r = 0.946, p < 0.0001). A correlation was found between excretion of these ions and Mg2+ ions this indicating location of reabsorption reduction in the thick ascending limb of Henle loop. In CRF patients (Na+ plus K+) excretion correlated with PGE2 excretion (r = 0.65, p < 0.0001). CONCLUSION: It is suggested that at this stage of chronic renal failure the mechanism of a diuresis increase is not due to osmotic diuresis but rather to secretion of prostaglandin E2 which inhibits cation reabsorption and stimulates diuresis. Differences are considered between osmotic diuresis and different types of saluresis; their possible mechanisms are discussed.

Adolescent↗

[Effect of natural zeolites on renal functions and water-salt metabolism in rats].

In vivo experiments on adult Wistar rats, it has been found that intake of natural zeolites resulted in temporary decrease of renal water, sodium and potassium excretion. At the same time, reabsorption of water and electrolytes increased. This effect was due to the stimulation of Na+, K(+)-ATPase activity in thick ascending limb of Henle loop and hormonal changes: increase of insulin, thyroxin and aldosterone concentration in plasma. The water and ion content in most of the tissues under study was higher in the experimental group than in control. It has been suggested that renal response in rats with zeolites intake was compensatory lower as a result of gastrointestinal losses of ions and ion accumulation in tissues.

Animals↗

Actions of adrenergic and cholinergic drugs on renal tubular cells.

There is convincing evidence to suggest that there are direct effects of adrenergic agents on renal tubules. During the last several years, considerable progress has been made in determining the type of adrenoceptors present in renal tubular cells through the use of radioligand binding and signal transduction methods. The receptor data are summarized in table 6. Almost all major nephron segments seem to have alpha 1- and alpha 2-adrenoceptors. However, there are few data describing the subtypes of alpha 1- or alpha 2-adrenoceptors in these segments. beta-Adrenoceptors are present in the CNT and collecting ducts of almost all species and in the thick ascending limbs of rats and mice. Adrenergic mediated signal transduction has been examined in some nephron segments, but virtually nothing is known about the relationship between the generation of adrenoceptor-mediated second messengers and changes in phosphorylation/activity of transport proteins (ion channels, ion pumps) in different types of renal tubular cells. There is general agreement that gluconeogenesis in the PCT is mediated by alpha 1-adrenoceptors through the PI and Ca2+ messenger system. Evidence also indicates that the increase in Na+ transport associated with renal nerve stimulation or adrenergic agonists in the PCT or the loop of Henle is mediated by alpha 1-adrenoceptors. Adrenergic agents modulate the effect of other hormones, such as PTH and vasopressin, on renal tubule transport by a decrease in cAMP, and this effect is mediated by alpha 2-adrenoceptors. There may be some interaction between the two alpha subtype-mediated effects in some nephron segments. beta-Adrenergic agonists stimulate cAMP formation in the PST, thick ascending limb (rat and mouse), CNT, and collecting duct segments. The physiological role of the beta-adrenoceptors in the PST is not known. beta-Adrenergic agonists stimulate sodium reabsorption by activation of the basolateral Cl- channel in the thick ascending limbs of rat and mice. The activation of beta-adrenoceptors in the CNT and CCD increases Cl- reabsorption and HCO3- secretion by stimulation of Cl/HCO3 exchange in the apical membrane of type B intercalated cell. The antikaliuretic effect of beta-adrenergic agonists is probably due to the stimulation of K+ reabsorption in type A intercalated cells in the CCD and OMCD. In the case of cholinergic drugs, the data in the literature are consistent with a model in which cholinergic agents increase papillary blood flow, resulting in the washout of the hypertonic medullary interstitium. This leads to a decrease in water abstraction out of the descending limb of Henle's loop.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Role of V1- and V2-receptors in mechanism of physiological paradox--an increase of reabsorption of the solute free water and simultaneous rise of diuresis].

In experiments on non-anesthetized rats with administration into stomach of water (5 ml/100 g body mass) direct correlation has been found between an increase of diuresis and excretion of solute free water (r = 0.98, p < 0.01), while after injection to these animals of 5 x 10(-11) M arginine-vasotocin - between an increase of diuresis and simultaneous rise reabsorption of solute free water (r = 0.8, p < 0.01). The rise of diuresis after the vasotocin injection is due to inhibition of sodium re- absorption, with the solute excretion fraction increasing from 2.6 +/- 0.2 % to 11.9 +/- 1.2, p < 0.001. A similar physiological paradox - an increase of diuresis with the simultaneous increase of reabsorption of solute free water - has been revealed at night hours in children with tendency for nocturnal enuresis (r = 0.64, p < 0.01). Mechanism responsible for this phenomenon consists in a rise of diuresis due to a decrease of sodium ion reabsorption in the ascending Henle loop limb. A problem is discussed of the homeostatic significance of a decrease of sodium reabsorption combined with an increase of solute-free water reabsorption; it is suggested that this phenomenon is based on a redistribution of reabsorption inside the nephron - a decrease of ion and water reabsorption in the initial parts of the nephron distal segment and an increase of solute free water reabsorption with the antidiuretic hormone-stimulated high osmotic permeability of terminal parts of renal tubules. An intraperitoneal injection of V1-anatagonist (OPC-21268) decreased the natriuretic component of response to arginine-vasotocin, while injection of V2-antagonist (OPC-31260) eliminated the antidiuretic component.

Absorption↗

[Effect of catecholamines on sodium resorption and oxygen tension in rat kidneys].

Functional significance of alpha- and beta-adrenoreceptors for the mechanism of catecholamines effect on sodium reabsorption and oxygen tension in the rat kidney, was studied. Adrenaline inhibited sodium excretion decreasing its filtration in glomeruli and stimulating its reabsorption in tubules. The oxygen tension in these conditions did not change in the renal cortex while oxygenation of the external cortical layer was significantly increased. The blocking agent for alpha-adrenoreceptors phentolamin abolished the inhibiting effect of adrenaline on the glomerular filtration and somewhat decreased the degree of oxygen tension growth in the external cortical layer, leaving the tubular effect unaltered. The blocking agent for beta-adrenoreceptors inderal did not affect the inhibitory action of adrenaline on the glomerular filtration but completely prevented its activating effect on the tubular reabsorption of sodium and on oxygenation of the external cortical layer. A conclusion was drawn that catecholamines stimulation of sodium reabsorption in the rat kidney follows excitation of beta-adrenoreceptors. The increase in oxygen tension in the external cortical layer under effect of catecholamines is supposed to improve energetic supply of the sodium active transport in the ascending portion of the Henle loops.

Animals↗

Lack of anion effect on volume expansion natriuresis in the developing canine kidney.

The renal response to volume expansion with sodium chloride or sodium bicarbonate was studied in 15 newborn and 13 adult dogs. Proximal and distal nephron function were estimated using the technique of distal nephron blockade. Fractional sodium reabsorption was 99.0 +/- 0.3% in newborn and 96.6 +/- 0.06% in adult during the NaCl expansion (P less than 0.01) and 98.1 +/- 0.7% in the newborn and 93.2 +/- 0.7% in the adult during NaHCO3 expansion (P less than 0.001). With either anion the higher fractional sodium reabsorption in the newborn was due to reabsorption of a greater fraction of the load presented to the distal nephron segment. The percent of the distal sodium load that was reabsorbed was 98.0 +/- 0.6% in the newborn and 92.2 +/- 1.0% in the adult during NaCl expansion, and 96.1 +/- 1.3% in the newborn and 81.5 +/- 2.4% in the adult during NaHCO3 expansion. Differences in distal nephron chloride, potassium and bicarbonate reabsorption among the groups support the hypothesis that the enhanced distal sodium reabsorption in the newborn occurred largely in the ascending loop of Henle with NaCl expansion, while it occurred in the late distal and cortical collecting tubules with NaHCO3 expansion. There was no difference between the natriuretic responses to NaCl or NaHCO3 in the newborn (P greater than 0.20); however, the natriuretic response to NaCl was less than that to NaHCO3 in the adult (P less than 0.001). This suggests that the bulk of the sodium that escaped reabsorption in Henle's loop during NaHCO3 expansion was reabsorbed in the late distal tubule in the newborn, but not in the adult.

Animals↗

Clinical trial with muzolimine in healthy and hypertensive subjects: new vistas on the drug action.

The mechanism of muzolimine (3-amino-1-[3,4-dichloro-alpha-methyl-benzyl]-2 pyrazolin-5-one) action is still not completely defined. The identified site of action is the Henle loop, similarly to furosemide which acts also by mediating renal prostaglandin synthesis. The aim of the present study was to evaluate the early effects of muzolimine (30 mg per os) on renal function and prostaglandin urinary excretion in healthy controls and hypertensive subjects. Urinary flow reached the peak values by the third hour after the drug and a diuretic effect not directly dependent on glomerular filtration was observed, especially in hypertensive patients. In these cases the diuresis increased also due to a low glomerular filtration rate and tubular phenomena were more evident than in controls: an increasing Na+ tubular excretion and a parallel decreasing % Na+ reabsorption. Blood pressure was not significantly influenced by muzolimine in healthy subjects, while it returned to normal values in the hypertensive group. A cyclooxigenase inhibitor, lysine acetylsalicylate (1 g i.m.) administered 10 minutes after muzolimine, was not able to modify the parameters under consideration. Therefore a mediation by prostaglandins on the diuretic and antihypertensive effects of the drug under study may probably be excluded.

Aged↗

Kidney pathology in endemic nephropathy.

Histopathologic analysis was made of kidneys from seven cases of typical endemic nephropathy and five cases of probable endemic nephropathy or upper urinary tract carcinoma from Yugoslavia. Glomeruli usually had an increased mesangial matrix and abnormal lobulation, sometimes with vacuolar degeneration. Particularly the straight ascending, descending and Henle loop tubules showed increased epithelial degeneration and regeneration. A network of interstitial scars and a subcapsular stratum of notable cortical degeneration contributed to severe renal atrophy. Unusual intrarenal vein thickening with or without obliteration was notable. Reactive glomerular, Bowman's epithelial and convoluted tubular alterations were ascribed to a filtered toxic material with carcinogenic properties which was considered eventually responsible for renal atrophy, fibrosis and some attributes of an autoimmune reaction.

Adult↗

Nephrogenic diabetes insipidus in a dog with renal medullary lesions.

Antidiuretic hormone (ADH) administration to a polyuric Miniature Poodle did not alter diuresis. Plasma ADH concentrations were high, and urine osmolality remained low during water deprivation. From these findings, it was concluded that the polyuria was of renal origin. In addition, the glomerular filtration rate was found to be high. Electron microscopic examination of the renal medulla revealed vacuoles containing myelinic figures and fingerprint structures in the cells of the Henle loops, blood vessels, and interstitium, similar to those in lysosomal lipid storage disease. Their absence in collecting duct epithelium indicated that the defect in concentrating ability was due to a disturbance of the counter-current multiplier mechanism rather than to a defect in ADH receptors.

Animals↗

[Histopathological changes in the kidney of experimental animals caused by lethal doses of thallium].

The experiment was carried out on 65 white male Wistar rats and 65 white male Swiss mice poisoned with thallium sulfate in doses 30-40 mg/kg body weight. The animals were sacrificed in the 4, 8, 24, 48th hours of experiment and their kidneys were submitted to light and an electron microscopic examination. Protein level in urine and urea level in blood serum of the rats were determined. With the light microscope necrosis of epithelium of Henle loops, hydropic degeneration, swelling and focal necrosis of epithelium of proximal convoluted tubules, and stromal oedema were seen. An electron microscopic study pointed out swelling and degenerative changes in the mitochondria, loss of microvilli in many cells, dilatation of endoplasmic reticulum and decrease of electron density of basement membranes. Urea level in blood serum and protein level in urine increased.

Animals↗

Effect of acute heat stress on some renal functions in the sickle cell patient.

1. The effect of acute temperature change on some renal functions was studied in 19 young sickle cell patients and 10 normal young adults (AA). 2. Glomerular filtration rate, Renal plasma flow and urine flow rate were highest in the SS followed by the SC and least in the AA at 20 degrees C. At 40 degrees C there was reduction in all the paramenters; the least reduction occurred in the normal controls. At 20 degrees C solute excretion was higher in the patients but at 40 degrees, excretion decreased to value close to that of controls in the SC but in the SS it remained high. 3. At 40 degrees, renal function in the patients approached that in normal controls, particularly in the SC. 4. It is suggested that functional changes occur not only in Henles loops but also in other postglomerular tubules and that the functional defect is unmasked during osmotic plus water diuresis and exposure to cool temperature.

Adult↗

[Ultrastructure of the internal medullary substance of the kidney in rodents of an arid zone].

Peculiar ultrastructural features of the kidney internal medullary substance have been studied in some typical representatives of the Middle Asia desert and semi-desert fauna (Spermophilopsis leptodactylus and Meriones erythrourus). Papillary organization in the species studied has a specific high differentiation of the fine nephron loop (Henle's) parts; flattening (especially in Meriones erythrourus) of epithelium in the collecting tubes while its cytoplasm is rather poor in organelle; high contents of the interstitial cells and their tight junction with canaliculi, capillaries, floccular material of the interstitial tissue; thinning of the interstitial sheets, especially between the collecting tubes and vessels, presence of collagene fibres in the interstitium, that is especially, specific for all the species of the Spermophilopsis leptodactylus studied. It is possible to suppose that development of similar features in the structure of the kidney internal medullary substance, where the main water resorption takes place in the species investigated, is connected with their life in similar environmental conditions with low hydratation level and is aimed to increase efficiency of the concentrating apparatus work.

Animals↗

Experiences with the treatment of alkaline reflux gastritis.

Between 1973 and 1978, we have treated 34 patients with alkaline reflux gastritis. All but one had a history of prior gastric surgery. Ten patients had severe diarrhea due to dumping or vagotomy or both. Eleven of the patients had undergone 17 unsuccessful remedial operations. Except for one patient whose gastrojejunostomy was dismantled and two patients who had interposition of a Henle loop between the stomach and the duodenum, all the patients were managed by construction of a 40 cm Roux-en-Y limb. In 10 patients with diarrhea, a 7 to 8 cm antiperistaltic segment was positioned 80 cm distal to the stomach. Ancillary procedures such as vagotomy and Hill hiatal hernia repair were done in some of the patients. Bile gastritis was well controlled by the 40 cm Roux limb. The short reversed segment placed 80 cm from the stomach effectively controlled diarrhea whether it was due to dumping or vagotomy and did not cause any of the problems of gastric stasis that we and others have observed with reversed segments positioned next to the stomach.

Adult↗

Aspects of regulation in kidney at the enzymic level: aldolase isozymes, aminopeptidase and alkaline phosphatase.

Histochemical and immuno-histochemical studies on kidney sections of adult rats and rats at different stages of development were carried out to estimate enzyme concentrations in nephron segments. Aminopeptidase and alkaline phosphatase were found from 3 days before birth in proximal tubule cells, aldolase-B and aldolase-A in all the nephron and collecting duct. The concentration of the enzymes remained remarkably constant from the 3rd day after birth onwards, except for aldolase-A in the distal tubule cells. The concentration of aldolase-B was higher than of aldolase-A in the distal tubule cells. The concentration of aldolase-B was higher than of aldolase-A, in glomerula and proximal tubules, that of aldolase-A was higher than that of aldolase-B in the ascending thick part of the Henle loop and in the following parts of the nephron. This implies that the concentration of the enzymes is the limiting factor for the regulation of substrate hydrolysis and that the nephron when formed can function as efficiently as the nephron of the adult rat with respect to these enzymes.

Aging↗