Regulation of kidney on potassium balance and its clinical significance / 生理学报

Virtually all of the dietary potassium intake is absorbed in the intestine, over 90% of which is excreted by the kidneys regarded as the most important organ of potassium excretion in the body. The renal excretion of potassium results primarily from the secretion of potassium by the principal cells in the aldosterone-sensitive distal nephron (ASDN), which is coupled to the reabsorption of Na+ by the epithelial Na+ channel (ENaC) located at the apical membrane of principal cells. When Na+ is transferred from the lumen into the cell by ENaC, the negativity in the lumen is relatively increased. K+ efflux, H+ efflux, and Cl- influx are the 3 pathways that respond to Na+ influx, that is, all these 3 pathways are coupled to Na+ influx. In general, Na+ influx is equal to the sum of K+ efflux, H+ efflux, and Cl- influx. Therefore, any alteration in Na+ influx, H+ efflux, or Cl- influx can affect K+ efflux, thereby affecting the renal K+ excretion. Firstly, Na+ influx is affected by the expression level of ENaC, which is mainly regulated by the aldosterone-mineralocorticoid receptor (MR) pathway. ENaC gain-of-function mutations (Liddle syndrome, also known as pseudohyperaldosteronism), MR gain-of-function mutations (Geller syndrome), increased aldosterone levels (primary/secondary hyperaldosteronism), and increased cortisol (Cushing syndrome) or deoxycorticosterone (hypercortisolism) which also activate MR, can lead to up-regulation of ENaC expression, and increased Na+ reabsorption, K+ excretion, as well as H+ excretion, clinically manifested as hypertension, hypokalemia and alkalosis. Conversely, ENaC inactivating mutations (pseudohypoaldosteronism type 1b), MR inactivating mutations (pseudohypoaldosteronism type 1a), or decreased aldosterone levels (hypoaldosteronism) can cause decreased reabsorption of Na+ and decreased excretion of both K+ and H+, clinically manifested as hypotension, hyperkalemia, and acidosis. The ENaC inhibitors amiloride and Triamterene can cause manifestations resembling pseudohypoaldosteronism type 1b; MR antagonist spironolactone causes manifestations similar to pseudohypoaldosteronism type 1a. Secondly, Na+ influx is regulated by the distal delivery of water and sodium. Therefore, when loss-of-function mutations in Na+-K+-2Cl- cotransporter (NKCC) expressed in the thick ascending limb of the loop and in Na+-Cl- cotransporter (NCC) expressed in the distal convoluted tubule (Bartter syndrome and Gitelman syndrome, respectively) occur, the distal delivery of water and sodium increases, followed by an increase in the reabsorption of Na+ by ENaC at the collecting duct, as well as increased excretion of K+ and H+, clinically manifested as hypokalemia and alkalosis. Loop diuretics acting as NKCC inhibitors and thiazide diuretics acting as NCC inhibitors can cause manifestations resembling Bartter syndrome and Gitelman syndrome, respectively. Conversely, when the distal delivery of water and sodium is reduced (e.g., Gordon syndrome, also known as pseudohypoaldosteronism type 2), it is manifested as hypertension, hyperkalemia, and acidosis. Finally, when the distal delivery of non-chloride anions increases (e.g., proximal renal tubular acidosis and congenital chloride-losing diarrhea), the influx of Cl- in the collecting duct decreases; or when the excretion of hydrogen ions by collecting duct intercalated cells is impaired (e.g., distal renal tubular acidosis), the efflux of H+ decreases. Both above conditions can lead to increased K+ secretion and hypokalemia. In this review, we focus on the regulatory mechanisms of renal potassium excretion and the corresponding diseases arising from dysregulation.

Activation of renal outer medullary potassium channel in the renal distal convoluted tubule by high potassium diet / 生理学报

Renal outer medullary potassium (ROMK) channel is an important K+ excretion channel in the body, and K+ secreted by the ROMK channels is most or all source of urinary potassium. Previous studies focused on the ROMK channels of thick ascending limb (TAL) and collecting duct (CD), while there were few studies on the involvement of ROMK channels of the late distal convoluted tubule (DCT2) in K+ excretion. The purpose of the present study was mainly to record the ROMK channels current in renal DCT2 and observe the effect of high potassium diet on the ROMK channels by using single channel and whole-cell patch-clamp techniques. The results showed that a small conductance channel current with a conductance of 39 pS could be recorded in the apical membrane of renal DCT2, and it could be blocked by Tertiapin-Q (TPNQ), a ROMK channel inhibitor. The high potassium diet significantly increased the probability of ROMK channel current occurrence in the apical membrane of renal DCT2, and enhanced the activity of ROMK channel, compared to normal potassium diet (P < 0.01). Western blot results also demonstrated that the high potassium diet significantly up-regulated the protein expression levels of ROMK channels and epithelial sodium channel (ENaC), and down-regulated the protein expression level of Na+-Cl- cotransporter (NCC). Moreover, the high potassium diet significantly increased urinary potassium excretion. These results suggest that the high potassium diet may activate the ROMK channels in the apical membrane of renal DCT2 and increase the urinary potassium excretion by up-regulating the expression of renal ROMK channels.

The mechanism of blood pressure regulation by high potassium diet in the kidney / 生理学报

Hypertension is one of the strongest risk factors for cardiovascular diseases, cerebral stroke, and kidney failure. Lifestyle and nutrition are important factors that modulate blood pressure. Hypertension can be controlled by increasing physical activity, decreasing alcohol and sodium intake, and stopping tobacco smoking. Chronic kidney disease patients often have increased blood pressure, which indicates that kidney is one of the major organs responsible for blood pressure homeostasis. The decrease of renal sodium reabsorption and increase of diuresis induced by high potassium intake is critical for the blood pressure reduction. The beneficial effect of a high potassium diet on hypertension could be explained by decreased salt reabsorption by sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT). In DCT cells, NCC activity is controlled by with-no-lysine kinases (WNKs) and its down-stream target kinases, Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress-responsive 1 (OSR1). The kinase activity of WNKs is inhibited by intracellular chloride ([Cl-]i) and WNK4 is known to be the major WNK positively regulating NCC. Based on our previous studies, high potassium intake reduces the basolateral potassium conductance, decreases the negativity of DCT basolateral membrane (depolarization), and increases [Cl-]i. High [Cl-]i inhibits WNK4-SPAK/OSR1 pathway, and thereby decreases NCC phosphorylation. In this review, we discuss the role of DCT in the blood pressure regulation by dietary potassium intake, which is the mechanism that has been best dissected so far.

The function and regulation of basolateral Kir4.1 and Kir4.1/Kir5.1 in renal tubules / 生理学报

Basolateral inwardly-rectifying K channels (Kir) play an important role in the control of resting membrane potential and transepithelial voltage, thereby modulating water and electrolyte transport in the distal part of nephron. Kir4.1 and Kir4.1/Kir5.1 heterotetramer are abundantly expressed in the basolateral membrane of late thick ascending limb (TAL), distal convoluted tubule (DCT), connecting tubule (CNT) and cortical collecting duct (CCD). Loss-of-function mutations in KCNJ10 cause EAST/SeSAME syndrome in humans associated with epilepsy, ataxia, sensorineural deafness and water-electrolyte metabolism imbalance, which is characterized by salt wasting, hypomagnesaemia, hypokalaemia and metabolic alkalosis. In contrast, mice lacking Kir5.1 have severe renal phenotype apart from hypokalaemia such as high chlorine metabolic acidosis and hypercalcinuria. The genetic knockout or functional inhibition of Kir4.1 suppresses Na-Cl cotransporter (NCC) expression and activity in the DCT. However, the downregulation of Kir4.1 increases epithelial Na channel (ENaC) expression in the collecting duct. Recently, factors regulating expression and activity of Kir4.1 and Kir4.1/Kir5.1 were identified, such as cell acidification, dopamine, insulin and insulin-like growth factor-1. The involved mechanisms include PKC, PI3K, Src family protein tyrosine kinases and WNK-SPAK signal transduction pathways. Here we review the progress of renal tubule basolateral Kir, and mainly discuss the function and regulation of Kir4.1 and Kir4.1/Kir5.1.

Effects of diclofenac sodium on renal parenchyma and prevention by vitamin-E in adult albino rats

To determine the preventive role of Vitamin E on renal parenchyma after given of Diclofenac Sodium in albino rats. Experimental Study This study was conducted in the Department of Anatomy Baqai Medical University and Muhammad Medical College, Mirpurkhas from June 2011 to November 2011, For this experimental study, 30 albino rats were taken. They were divided into three groups ; A, B and C. The animals in group-A given normal saline 10 ml/kg per day. Group-B received diclofenac sodium 2 mg/kg per day and group-C receives diclofenac sodium 2mg/kg/day dissolved in distilled water with vitamin-E 2 mg/kg/day dissolved in olive oil administered half an hour before the diclofenac sodium by feeding tube per day for 2 weeks. On day 15 all animals were sacrificed with deep ether anesthesia. Their kidneys were removed, fixed in 10% formalin. Representative blocks were taken and embedded in liquid paraffin. For routine histological examination 5 micro m thick section cut by microtome and stained with H and E, PAS and silver methenamine. Renal histology was done under light microscope to see the proximal and distal tubular diameter and count. No significant [P>0.05] changes were observed in the histopathology of kidney tissues of the groups A and C rats. The group B significantly [P<0.001] affected the histopathology of kidney. It may be concluded that diclofenac sodium produces changes in kidney, which may be attributed to ischaemia induced by inhibition of prostaglandin synthesis resulting in tubular necrosis in albino rats simultaneous administration of vitamin-E partially protect the morphological and histological changes induced by diclofenac sodium

Refractory rickets caused by mild distal renal tubular acidosis

Type I (distal) renal tubular acidosis (RTA) is a disorder associated with the failure to excrete hydrogen ions from the distal renal tubule. It is characterized by hyperchloremic metabolic acidosis, an abnormal increase in urine pH, reduced urinary excretion of ammonium and bicarbonate ions, and mild deterioration in renal function. Hypercalciuria is common in distal RTA because of bone resorption, which increases as a buffer against metabolic acidosis. This can result in intractable rickets. We describe a case of distal RTA with nephrocalcinosis during follow-up of rickets in a patient who presented with clinical manifestations of short stature, failure to thrive, recurrent vomiting, dehydration, and irritability.

Avaliações clínico-patológicas e laboratoriais da intoxicação experimental por monofluoroacetato de sódio em ovinos / Clinic-pathological and laboratory aspects of experimental poisoning by sodium monofluoroacetate in sheep

O objetivo deste trabalho foi verificar se a administração de doses únicas e de frações diárias da dose letal de monofluoroacetato de sódio (MF) a ovinos induzem a clássica degeneração hidrópico-vacuolar (DHV) dos túbulos uriníferos contornados distais observada no rim de bovinos intoxicados por plantas brasileiras que causam "morte súbita" (PBCMS). MF foi administrado, por via oral, em doses únicas de 0,5 e 1,0mg/kg, cada dose para dois ovinos, e em doses subletais repetidas diariamente de 0,1mg/kg/dia, por quatro dias, e 0,2mg/kg/dia por seis dias, cada dose para um ovino. Todos os ovinos que receberam MF morreram, exceto um que recebeu 0,5mg/kg e não mostrou sintomas. A evolução da intoxicação variou de 3min a 33h5min. Clinicamente os animais apresentaram taquicardia, respiração abdominal, tremores musculares, ligeira perda de equilíbrio, por vezes cambaleavam, deitavam e apoiavam a cabeça no flanco. Na fase final, os ovinos caíam em decúbito lateral, esticavam os membros, faziam movimentos de pedalagem, apresentavam opistótono e morriam. O exame ecocardiográfico evidenciou dilatação cardíaca e redução da fração de encurtamento sistólico. A análise dos níveis séricos de uréia e creatinina revelou moderada a acentuada azotemia. MF provocou "morte súbita" em todos os ovinos que mostraram sintomas. À necropsia verificaram-se aurículas e veias jugulares, cavas, ázigos e pulmonares moderadamente ingurgitadas e, em alguns animais, edema pulmonar. O exame histopatológico revelou, em todos os ovinos, leve a acentuada DHV das células epiteliais dos túbulos contornados distais, associada à picnose nuclear. Adicionalmente, verificaram-se discreta vacuolização e, por vezes, necrose de coagulação de hepatócitos. Não encontramos referências a esse tipo peculiar de lesão, exceto das descrições sobre lesões renais associadas à ingestão de PBCMS e de recentes estudos em bovinos intoxicados com MF. Este trabalho demonstra, em ovinos, que tanto doses letais únicas quanto subdoses diárias de MF induzem a DHV dos túbulos uriníferos contornados distais associada à picnose nuclear.

The objective of this study was to verify if the ingestion of single doses of sodium monofluoroacetate (MF) and daily fractions of 1/2.5 and 1/5 of the lethal dose causes the same lesion as the one observed in the kidney of cattle poisoned by Brazilian sudden death causing plants (BSDCP). MF was administered orally in single doses of 0.5 and 1.0mg/kg to four sheep, and repeated daily doses of 0.1 and 0.2mg/kg to two others. Death occurred in five of six animals. The course of poisoning lasted from 3min to 33h5min. Clinically the animals presented palpitation, abdominal breathing, slight balance loss with sometimes swaying gait, they laid down and placed the head on their flank. In the "dramatic phase", all the sheep fell into lateral decubitus, stretched out the legs, made peddling movements, presented opistotonus, and died. The electrocardiographical examination showed heart dilatation and reduction of the systolic shortening fraction. Laboratory hematological exams revealed increased urea and creatinine. MF caused the clinical and pathological symptoms of "sudden death". At postmortem examination, heart auricles and jugular, cava, azygos and pulmonary veins of all animals were moderately engorged, and in some sheep, pulmonary edema was observed. Histopathology revealed hydropic-vacuolar degeneration (HVD) of the epithelial cells of the distal convoluted kidney tubules associated with nuclear picnosis in all the sheep. Vacuolation and less often necrosis of liver cells was seen in some cases. No references to that peculiar type of lesion could be found in the literature, except the description of kidney lesions in animals associated with the ingestion of BSDCP, and recent studies of MF poisoning in cattle. The present study demonstrated in sheep that single lethal doses or repeated doses of fractions of the lethal dose of MF causes HVD of the distal convoluted kidney tubules, associated with nuclear picnosis.

Noncrystalline uric acid inhibits proteoglycan and glycosaminoglycan synthesis in distal tubular epithelial cells (MDCK)

Hyperuricemia is associated with renal stones, not only consisting of uric acid (UrAc) but also of calcium oxalate (CaOx). Glycosaminoglycans (GAGs) are well-known inhibitors of growth and aggregation of CaOx crystals. We analyzed the effect of noncrystalline UrAc on GAG synthesis in tubular distal cells. MDCK (Madin-Darby canine kidney) cells were exposed to noncrystalline UrAc (80 µg/mL) for 24 h. GAGs were labeled metabolically and characterized by agarose gel electrophoresis. The expression of proteoglycans and cyclooxygenase 2 (COX-2) was assessed by real-time PCR. Necrosis, apoptosis and prostaglandin E2 (PGE2) were determined by acridine orange, HOESCHT 33346, and ELISA, respectively. CaOx crystal endocytosis was evaluated by flow cytometry. Noncrystalline UrAc significantly decreased the synthesis and secretion of heparan sulfate into the culture medium (UrAc: 2127 ± 377; control: 4447 ± 730 cpm) and decreased the expression of perlecan core protein (UrAc: 0.61 ± 0.13; control: 1.07 ± 0.16 arbitrary units), but not versican. Noncrystalline UrAc did not induce necrosis or apoptosis, but significantly increased COX-2 and PGE2 production. The effects of noncrystalline UrAc on GAG synthesis could not be attributed to inflammatory actions because lipopolysaccharide, as the positive control, did not have the same effect. CaOx was significantly endocytosed by MDCK cells, but this endocytosis was inhibited by exposure to noncrystalline UrAc (control: 674.6 ± 4.6, CaOx: 724.2 ± 4.2, and UrAc + CaOx: 688.6 ± 5.4 geometric mean), perhaps allowing interaction with CaOx crystals. Our results indicate that UrAc decreases GAG synthesis in MDCK cells and this effect could be related to the formation of UrAc and CaOx stones.

Time since death from degenerative changes in the Kidney.

Time since death is made out from gross postmortem changes like cooling of the body, postmortem staining, rigor mortis, decomposition etc. In the present study Histological changes in the Kidney tissue were studied at various postmortem intervals in the human body died due to road traffic accidents. This study is conducted in the Department of Forensic Medicine in collaboration with Department of Pathology, G.S.V.M. Medical College, Kanpur, U.P. A total of 45 cases are taken belonging to both sexes i.e. 36 males and 9 females were studied. These are of different age groups. All road traffic accidents are taken into account. In this study control can not be taken because the histological changes of tissue after death is influenced a great deal by atmospheric temperature and humidity besides other external and internal factors. Therefore these must be taken into account in all studies of postmortem interval whether histological, biochemical or physical.

Changes produced in cerebellum and kidney of rabbits after chronic exposure to mobile phone microwaves. a histopathological study

The use of mobile phones is currently one of the faster growing technological developments. The microwave emitted by these telephones are considered as one of the non-ionizing radiations which still having much uncertainties about the severity of effects of both acute and chronic exposure to their various types. The direct biological effects of exposure to this kind of ionizing radiation have not been studied extensively particularly from the histological point of view. The close proximity of the antenna of such a device to the head and the abdominal organs has raised concerns about the biological interactions between these Electromagnetic Radiation [EMR] and cerebellum and kidney. So these organs were chosen to be target organs for our present study. The present work was performed to assess and investigate the histopathological effects of the frequent and long term exposure to the microwaves emitted by the mobile phone on cerebellum and kidney of rabbits. Male and female rabbits have been used in this experiment for normal and exposed groups. Animals were sexually immature and classified into 3 groups: Normal control [non-exposed] rabbits [male, female], irradiated [exposed] female rabbits, irradiated [exposed] male rabbits. The radiation exposure was carried out on heads of animals for 30 min/ day for a period of 90 days at the frequency of 900 MHz [Specific Absorption Rate "SAR" was 0.62 W/ kg]. For kidney the duration of exposure was 90 min/ day for a period of 90 days at the same range of frequency but the device was operated but not activated. The exposure of the experimental animals of both sexes to this type of non-ionizing radiations resulted in many histopathological alterations in both cerebellum and kidney. In cerebellum herniation of some cerebellar folia, detaching of epithelia of the pial surface and generalized perineural, perivascular and periglial edema could be recorded. The Purkinje cells appeared degenerated, sometimes highly destructed, irregular in shape, dark in staining, small in size, ill-defined and surrounded by widened preicellular spaces. In some regions of cerebellar tissue an absence of Purkinje layer after the degeneration of their cells was detected. The granular cells appeared in darkly stained, clusters aggregated as gliosis, small in size with hyperchromatic pyknotic nuclei. The granular cell layer in some fields accepted a generalized spongiform appearance resulted in compression and degeneration throughout the cerebellar cortex. The molecular later contained few destructed nerve cells, vacuolated matrix and sometimes infiltrated with degenerated dark cells. In some examined fields it accepted a spongiform appearance after severe damage to its constituent fibers and cells. The renal tissue exhibited pronounced tubular necrosis, vacuolar degeneration in glomeruli, narrowing of the Bowman's space, partial necrosis in the medullary elements with some pyknotic nuclei in the interstitium, tubular collapse, atrophied renal epithelia of the renal tubules forming necrotic remnants, glomerular sclerosis, the renal tubules may be reduced to collapsed skeletons, desquamation and absence of the normal renal epithelia. The distal convoluted tubules were more sensitive and more affected than the proximal convoluted tubules. In both of the tested organs [cerebellum, kidney] the effects of EMR were more destructive and more adverse in irradiated males than irradiated females. The chronic exposure to the radiofrequency radiation of the mobile phone resulted in many histopathological alterations in cerebellum and kidney. The subject which leads us to suggest that these radiations may be neurotoxic and nephrotoxic at least under the conditions used in the present experiment [30 min/ day for cerebellum and 90 min/ day for kidney for a period of 90 days at SAR value of 0.62 W/ Kg]

Expression of PKD1 and PKD2 transcripts and proteins and its significance in different types of kidney tissues and kidney lines / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression and function of PKD1 and PKD2 in different kidney tissues and cell lines.</p><p><b>METHODS</b>Immunoprecipitation, Western blotting, In situ hybridization and immunohistochemical staining methods were used to observe the expression of PKD1 mRNA and PKD2 mRNA and their protein abundance in different kidney tissues and cell lines.</p><p><b>RESULTS</b>Coordinate expressions of PKD1 and PKD2 were found in all kidney tissues and cell lines. Distribution of PKD1 mRNA and PKD2 mRNA and their protein polycystin-1 and polycystin-2 in normal human adult kidney tissue were mainly expressed in the medullary collecting ducts and distal tubules. Positive staining was also found in the majority of cyst-lining epithelial cells of PKD1 cystic kidney tissue, PKD1 cyst-lining epithelia cell line and LLC-PK1. The expression level of them in cystic epithelia of ADPKD kidney tissue was much higher than that in adult renal tubules (P < 0.01).</p><p><b>CONCLUSIONS</b>Similar expression pattern of PKD1 and PKD2 and their different tissue distribution in different kidney tissues show that the molecular mutuality of PC-1 and PC-2 might be the base of their functional correlation. Polycystins might play an important role in the maintenance of tubular architecture.</p>

Structure of the kidney of Bufo arenarum: intermediate segment, distal tubule and collecting tubule

The ultrastructure of the intermediate segment (IS), distal tubule and collecting tubule (CT) of the south american toad Bufo arenarum, was studied by light and transmission electron microscopy. The IS is composed of cubical ciliated cells which propel the urine along the renal tubule. The distal tubule is divided into two portions: the early distal tubule (EDT) and the late distal tubule (LDT). The EDT is characterized by only one type of cells with well developed basolateral interdigitations and numerous elongated mitochondria, which are oriented normal to the basal surface. The "macula densa--like" is a specialized zone of the EDT in contact with the vascular pole, where cells are more tightly packed than in the rest of the tubule. The LDT shows two types of cells called dark and light cells according to the appearance of their cytoplasm. Dark cells have microplicae and few but long microvilli at their luminal surface, and abundant mitochondria in their cytoplasm. Light cells show basal and lateral infoldings and few mitochondria. The CT, which is composed of dark and light cells, exhibits an enlarged lumen with an undulated surface and dilated spaces between neighbouring cells. This work is a contribution to the knowledge of the kidney of B. arenarum; frequently used as an experimental model for physiological and biochemical studies.

Hipospadia distal / Distal hypospadias

Entre Enero de 1992 y marzo de 2000,67 pacientes con hipospadia distal subcoronal fueron operados por el mismo cirujano o alguno del equipo usando la técnica de Mathieu modificada.Las edades variaron entre 1 y 10 años(media 4,5 años)En 66 la técnica estandarizada se utilizó en forma primaria.Una técnica modificada de abordaje glandular se realizó en uno.Los resultados estéticos inmediatos y tardíos fueron buenos,A pesar que el número de pacientes fue reducido no hubo complicaciones mayores,La internación fue de hospital de día,disminuyendo la ansiedad de los niños que se retiraron sin catéter ni vendaje.El procedimiento en un tiempo,la cirugía precoz,los lentes de aumento y las suturas menos irritativas contribuyen al mejor resultado

side effects of the nonsteroidal anti-inflammatory drug [NSAID] ketoprofen on histological and ultrastructural aspects of the kidneys of albino rats

The present work deals with the effect of the therapeutic dose of the nonsteroidal anti-inflammatory drug, ketoprofen on the microscopic structure of the kidney of the albino rat. The present study also sheds light on the risk of using over-dosage either by mistake or in an unwise attempt at quick relieving the body pain. The intramuscular therapeutic dose of ketoprofen to albino rat was calculated and was found to equal 13.5 mg /kg body weight. Fifty adult male albino rats, Rattus norvegicus were used in the present study. The rats were equally allocated to five groups, each of 10 rats. Rats of the first group were kept as control. Rats of the second and third groups were injected daily with the therapeutic dose of ketoprofen for four and eight successive weeks respectively. Rats of the fourth and fifth groups were injected daily with double the therapeutic dose of ketoprofen for four and eight successive weeks respectively. In rats given the therapeutic dose of ketoprofen daily for four weeks and sacrificed 24 hours after the last dose, light microscope examination showed that Malpighian corpuscles and the kidney tubules revealed signs of degeneration. In rats given the therapeutic dose of ketoprofen daily for eight weeks the histological changes were in progression. A few numbers of glomeruli were increasingly congested and shrunken into dense masses of unrecognized structural details. The luminal borders of the cells lining the proximal convoluted tubules together with their microvilli were damaged. The electron micrographs of ultrathin sections of kidneys of rats given the therapeutic dose of ketoprofen daily for eight weeks showed that the glomerular capillaries were disorganized and occasionally their lining endothelium showed degeneration. The podocytes showed deteriorated and rarefied cytoplasm; and their primary processes were fragmented. Also, the foot processes appeared occasionally broad. In some cells of proximal convoluted tubules the microvilli completely disappeared. Occasionally, these cells gave broad blebs into the tubule lumen which became almost obliterated. The cytoplasm of few cells lining the distal convoluted tubules became moderately rarefied and vacuolated. In animals given double the therapeutic dose for four weeks many kidney glomeruli were fragmented and showed marked congestion and increased mesangium. The parietal walls of Bowman's capsules were damaged. The kidney tubules showed generalized hyalinization. A few numbers of t he tubule lining cells displayed pyknotic nuclei; some nuclei were karyolysed and even vanished. In animals given daily double the therapeutic dose of ketoprofen for eight successive weeks, the glomeruli were sclerotic and necrotic and the kidney tubules showed generalized hyalinization. In EM micrographs of kidney ultrathin sections, the configuration of the primary processes and the pedicels was greatly interrupted and disorganized. The capillary endothelium displayed signs of degeneration and disarray. The capillary basement membrane of the glomeruli exhibited regional attenuation or deformity. In some lining cells of the distal convoluted tubules, the cell organelles including mitochondria and lysosomes were noticeably electron dense, whereas the Golgi apparatus as well as the endoplasmic reticulum elements was degenerated

Estudio sobre el compromiso tubular en litiasis renal / Kidney tubules'damage in renal litiasis

Este trabajo recibió el Premio Víctor R. Miatello de la Sociedad Argentina de Nefrología, 1996. Por razones de la extensión del trabajo, se publica sólo un resumen del mismo, el cual no incluye tablas, figuras, gráficos y bibliografía. Una copia completa del mismo se encuentra a disposición en la biblioteca de la Sociedad Argentina de Nefrología

Renal actions of angiotensin-(1-7)

The heptapeptide angiotensin-(1-7) is considered to be a biologically active endproduct of the renin-angiotensin system. This angiotensin, which is devoid of the most known actions of angioatensin II such as induction of drinking behavior and vasoconstriction, has several selective effects in the brain and periphery. In the present article we briefly review recent evidence for a physiological role of angiotensin-(1-7) in the control of hydroelectrolyte balance.

Histogênese da doença renal policística autossômica dominante: estudo imuno-histoquímico / Histogenesis of the cysts in the autosomal dominant polycystic kidney disease. Immunohistochemistry study

A histogênese dos cistos na doença policística autossômica dominante (DRPAD) foi investigada em 33 pacientes por imuno-histoquímica. A idade média dos pacientes foi 46,4 anos e a relaçäo masculino:feminino foi 16:17. A maioria dos pacientes apresentou hipertensäo arterial (88 por cento), insuficiência renal crônica (92 por cento) e hematúria (70 por cento). Aneurismas cerebrais, diverticulose colônica e cistos hepáticos e pancreáticos foram encontrados em 56 por cento dos casos. O peso médio dos 53 rins estudados foi 1468 g e o diâmetro médio dos cistos foi 4,2 cm. Em 4 casos, material histológico de 1 dos rins näo esteve disponível. Os anticorpos e lectinas utilizados para identificar os diferentes segmentos dos néfrons foram: vimentina (Vim)-epitélio parietal da cápsula glomerular (G); Lotus tetragonolubus (LTA) e anti-antígeno CD 15 (Cd 15)-túbulo proximal (TP); anti-proteína de Tamm-Horsfall (PTH)-túbulo distal (TD), e anti-antígeno epitelial de membrana (EMA), anti-citoceratina (Ck) 19, Ulex europaeus (UEA-I), Arachis hypogaea (PNA), Dolichos biflorus (DBA) e Glycine maximum (SBA)-túbulo distal (TD) e ducto coletor (DC). Em estudo piloto, analisaram-se 3 rins normais obtidos de autópsias (rins controles-RC) e áreas preservadas de 2 rins com DRPAD (áreas de controle interno-CI), obtendos-e em todos os casos coloraçäo de: G por Vim, TP-LTA e CD15; TD-PTH; TD e DC-EMA, Ck 19, UEA-I, PNA e DBA. Näo houve coloraçäo com SBA. Os 49 rins com DRPAD produziram o seguinte perfil imuno-histoquímico: i) áreas preservadas: anti-Vim-G=82 por cento; LTA-TP=96 por cento; anti-CD 15-anti-Ck 19-TD e Dc=86 por cento e 89 por cento dos casos, respectivamente; ii) Áreas císticas: LTA, anti-CD 15, anti-PTH, anti EMA e anti-Ck 19=7 por cento, 6 por cento, 18 por cento, 97 por cento e 95 por cento dos casos, respectivamente. Näo houve coloraçäo com anti-Vim. Os resultados indicaram que os cistos em casos de DRPAD têm perfil imuno-histoquímico de túbulos distais e ductos coletores.

Efectos de la administración de dosis crecientes de kalikreína sobre la secreción de bicarbonato en nefrón distal / Effect of the administration of increasing doses of kallikrein on bicarbonate secretion on distal nephron

La localización de vesículas secretoras de kalikreína renal en contacto con la membrana apical en el túbulo conector permite asumir la presencia de la enzima activa en la membrana luminal de segmentos distales a su sitio de secreción. Los presentes experimentos fueron realizados a fin de demostrar la hipótesis de que la kalikreína renal está involucrada en el transporte de bicarbonato en el segmento correspondiente a túbulo colector cortical. La administración intraluminal de kalikreína glandular (1 y 3 µ/ml) por arteria renal hacia el sistema tubular de riñón, con interrupción simultánea del flujo sanguíneo renal (in vivo stop-flow anterógrado), incrementó la actividad de kalikreína renal en la primera fracción de 140 µl de la orina colectada luego de dos minutos de la oclusión de uréter (p<0,05 y p<0,01). Aumento en la secreción de bicarbonato fue detectado en las primeras fracciones de 140 µl de orina del grupo control, que recibió sólo el vehículo, comparadas con las del grupo experimental, en el cual fue administrada kalikreína glandular en dosis de 1 µg (p<0,05) y 3 µg (p<0,01). Luego de la inyección retrógrada de kalikreína a través del uréter hacia los túbulos colectores corticales (stop-flow retrógrado), la concentración de bicarbonato referida a polyfructosan en fracción de orina fue significativamente inferior que la correspondiente al riñón contralateral control (p<0,05). Se observó incremento en la actividad de kalikreína renal en la misma fracción respecto del control (p<0,05). La confirmación de la llegada de las soluciones al segmento correspondiente al túbulo colector cortical fue realizada mediante estudios histológicos de microscopía óptica y electrónica de trasmisión, administrando por vía ascendente peroxidasa y sulfuro de mercurio coloidal. La integridad de las células intercalares y principales correspondientes a túbulo colector cortical fue evidenciada mediante microscopía electrónica de barrido. Estos resultados confirman y extienden datos previos (J Physiol 1995, Renal Physiol Biochemistry 1994), mostrando que la kalikreína renal actúa en el transporte de bicarbonato en membrana luminal del túbulo colector cortical