Bellini duct carcinoma

The modern era has brought an appreciation that renal cell carcinoma (RCC) includes diverse subtypes derived from the various parts of the nephron, each with its distinctive genetic basis and tumor biology. Carcinoma of the collecting ducts of Bellini (CDC) is a rare subtype of RCC, with a predictably poor prognosis. This rare subtype represents less than 1% of all kidney carcinomas. It derives from presumably numerous chromosomal losses. It is of chief importance to differentiate CDC from other types of renal cell cancer. Typically, it is characterized by a firm, centrally located tumor with infiltrative borders. Regarding the histopathologic characteristics, we can find complex, highly infiltrative cords with inflamed (desmoplastic) stroma, with high-grade nuclei and mitoses. Most reported cases of CDC had been high grade, advanced stage, and unresponsive to conventional therapies. This rare form of disease highlights the importance of multidisciplinary teams in the management of cancer patients.

New insights into the transcriptional regulation of aquaporin-2 and the treatment of X-linked hereditary nephrogenic diabetes insipidus

The kidney collecting duct (CD) is a tubular segment of the kidney where the osmolality and final flow rate of urine are established, enabling urine concentration and body water homeostasis. Water reabsorption in the CD depends on the action of arginine vasopressin (AVP) and a transepithelial osmotic gradient between the luminal fluid and surrounding interstitium. AVP induces transcellular water reabsorption across CD principal cells through associated signaling pathways after binding to arginine vasopressin receptor 2 (AVPR2). This signaling cascade regulates the water channel protein aquaporin-2 (AQP2). AQP2 is exclusively localized in kidney connecting tubules and CDs. Specifically, AVP stimulates the intracellular translocation of AQP2-containing vesicles to the apical plasma membrane, increasing the osmotic water permeability of CD cells. Moreover, AVP induces transcription of the Aqp2 gene, increasing AQP2 protein abundance. This review provides new insights into the transcriptional regulation of the Aqp2 gene in the kidney CD with an overview of AVP and AQP2. It summarizes current therapeutic approaches for X-linked nephrogenic diabetes insipidus caused by AVPR2 gene mutations.

Notch signaling in the collecting duct regulates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction in mice

BACKGROUND/AIMS: Mind bomb-1 (Mib1) encodes an E3 ubiquitin ligase, which is required for the initiation of Notch signaling. Recently, it was demonstrated that the renal collecting duct plays an important role in renal fibrosis. Here, we investigated the role of Notch signaling in renal fibrosis using conditional knockout mice with the specific ablation of Mib1 in renal collecting duct principal cells. METHODS: Mib1-floxed mice (Mib1f/f ) were crossed with aquaporin 2 (AQP2)-Cre mice in order to generate principal cell-specific Mib1 knockout mice (Mib1f/f :AQP2-Cre+). Unilateral ureteral obstruction (UUO) was performed, and mice were sacrificed 7 days after UUO. RESULTS: After performing the UUO, renal tubulointerstitial fibrosis and the expression of transforming growth factor β were markedly enhanced in the obstructed kidneys of Mib1f/f mice compared with the sham-operated kidney of Mib1f/f mice. These changes were shown to be even more pronounced in the obstructed kidneys of Mib1f/f :AQP2-Cre+ mice than in those of the Mib1f/f mice . Furthermore, the number of TUNNEL-positive cells in renal collecting duct was higher in the obstructed kidneys of Mib1f/f :AQP2-Cre+ mice than in the kidneys of Mib1f/f mice. CONCLUSIONS: Notch signaling in the renal collecting duct plays an important role in the regulation of renal tubulointerstitial fibrosis and apoptosis after UUO.

A Minireview on Vasopressin-regulated Aquaporin-2 in Kidney Collecting Duct Cells

The kidney collecting duct is an important renal tubular segment for the regulation of body water and salt homeostasis. Water reabsorption in the collecting duct cells is regulated by arginine vasopressin (AVP) via the vasopressin V2-receptor (V2R). AVP increases the osmotic water permeability of the collecting duct cells through aquaporin-2 (AQP2) and aquaporin-3 (AQP3). AVP induces the apical targeting of AQP2 and transcription of AQP2 gene in the kidney collecting duct principal cells. The signaling transduction pathways resulting in the AQP2 trafficking to the apical plasma membrane of the collecting duct principal cells, include AQP2 phosphorylation, RhoA phosphorylation, actin depolymerization and calcium mobilization, and the changes of AQP2 protein abundance in water balance disorders have been extensively studied. These studies elucidate the underlying cellular and molecular mechanisms of body water homeostasis and provide the basis for the treatment of body water balance disorders.

Step-by-Step robotic heminephrectomy for duplicated renal collecting system

Introduction A duplicated renal collecting system is a relatively common congenital anomaly rarely presenting in adults. Aim In this video we demonstrate our step-by-step technique of Robotic heminephrectomy in a patient with non-functioning upper pole moiety. Materials and Methods Following cystoscopy and ureteral catheter insertion the patient was placed in 600 modified flank position with the ipsilateral arm positioned at the side of the patient. A straight-line, three arm robotic port configuration was employed. The robot was docked at a 90-degree angle, perpendicular to the patient. Following mobilization the colon and identifying both ureters of the duplicated system, the ureters were followed cephalically toward, hilar vessels where the hilar anatomy was identified. The nonfunctioning pole vasculature was ligated using hem-o-lok clips. The ureter was sharply divided and the proximal ureteral stump was passed posterior the renal hilum. Ureteral stump was used as for retraction and heminephrectomy is completed along the line demarcating the upper and lower pole moieties. Renorrhaphy was performed using 0-Vicryl suture with a CT-1 needle. The nonfunctioning pole ureter was then dissected caudally toward the bladder hiatus, ligated using clips, and transected. Results The operating time was 240 minutes and blood loss was 100 cc. There was no complication post-operatively. Conclusions Wrist articulation and degree of freedom offered by robotic platform facilitates successful performance of minimally invasive heminephrectomy in the setting of an atrophic and symptomatic renal segment. .

Actualidad de la enfermedad renalpoliquística / Polycystic Renal Disease: An Update

La enfermedad renal poliquística (PKD) es una enfermedad genética común queconsiste en la aparición progresiva de lesiones quísticas en los riñones, que remplazanel parénquima renal, lo que conduce a enfermedad renal crónica terminal. La PKDtiene dos patrones de herencia: autosómico dominante y autosómico recesivo. Laforma autosómica dominante es más común y menos grave que la autosómica recesiva.Se conoce que la PKD es causada por mutación en varios loci humanos. La formaautosómica dominante puede ser causada por mutaciones en dos genes diferentes(PKD1 y PKD2); en tanto que la forma autosómica recesiva solo tiene un gen causal(PKHD1). Existen numerosas publicaciones que buscan explicar la fisiopatología dela enfermedad. Esto refleja un esfuerzo internacional por comprender la naturalezade la enfermedad, para desarrollar terapias que eviten la aparición de los quistes o laprogresión de los que ya están instaurados. El objetivo de esta revisión es difundirel conocimiento que se tiene hasta el momento, acerca de la enfermedad renalpoliquística. Por lo tanto, realizamos un breve recuento de las características clínicasde la enfermedad y el tratamiento actual disponible...

Polycystic Kidney Disease (PKD) is a commongenetic condition, which is characterizedby gradual appearance of multiple cysts in thekidneys; this causes the destruction of renalparenchyma leading to chronic renal disease.PKD has two patterns of inheritance: autosomaldominant and autosomal recessive. Theautosomal dominant form is more commonand less severe than the autosomal recessive. Itis known that PKD is caused by mutation in severalhuman loci. The autosomal dominant formcan be caused by mutations in 2 different genes(PKD1 and PKD2). The autosomal recessiveform has only one causal gene (PKHD1). Thereare numerous publications worldwide that seekto explain the pathophysiology of the disease;this reflects an international effort to understandthe nature of the disease, to develop therapiesto prevent the appearance of cysts or the progressionof those already existent lesions. The objectiveof this review is to update the knowledge wehave so far, about polycystic kidney disease thereforewe decided to conduct a brief review ofthe clinical features of disease and the treatmentavailable today...

Tubulocystic carcinoma of kidney associated with papillary renal cell carcinoma.

Tubulocystic renal cell carcinoma (TCRCC) is a rare variant of renal cell carcinoma, which has distinct histology but there is some controversy about its association with papillary renal cell carcinoma (PRCC) and cell of origin in literature. We report an 18-year-old girl with the rare TCRCC of kidney associated with PRCC with metastases to the para-aortic nodes. The patient presented with hematuria and a right renal mass with enlarged regional nodes for which a radical nephrectomy with retroperitoneal lymph node dissection was done. On gross examination, a solid cystic lesion involving the lower pole and middle pole of the kidney measuring 12x9x9 cm was seen along with an additional cystic lesion in upper pole of kidney. Microscopically the main tumor showed the typical histology of a tubulocystic carcinoma with multiple cysts filled with secretions lined by variably flattened epithelium with hobnailing of cells. The mass in the upper pole was a high-grade PRCC and the nodal metastases had morphology similar to this component. To conclude, at least a small but definite subset of TCRCC is associated with PRCC, and cases associated with PRCC do seem to have a higher propensity for nodal metastasis as in the case we report.

Renal Expression of Ammonia Transporters in Rats with Amiloride-Induced Renal Tubular Acidosis / 대한내과학회지

BACKGROUND/AIMS: Renal tubular acidosis (RTA) decreases the net acid excretion, predominantly due to a decrease in urinary ammonia excretion. This study examined whether this decrement is associated with changes in the renal expression of the ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg), in rats with amiloride-induced RTA. METHODS: Male Sprague-Dawley rats were treated intraperitoneally with amiloride (3 mg/kg/day) for 6 days. Rhbg and Rhcg expression was evaluated by immunoblotting and immunohistochemistry. Cell height, total cellular expression, expression in the apical 25% of the cell, and apical expression as a percentage of total expression were quantified using immunohistochemistry with quantitative morphometric analysis. RESULTS: After amiloride treatment for 6 days, the serum bicarbonate level was decreased, and serum potassium was increased. The total urinary ammonia excretion and potassium excretion were decreased. The total Rhbg and Rhcg protein expression levels were not changed in the cortex or outer medulla of the kidney. Light microscopy and immunohistochemistry with quantitative morphometric analysis demonstrated that total Rhcg expression was decreased in the cortical collecting duct (CCD) and outer medullary collecting duct (OMCD) in amiloride-induced RTA, whereas Rhbg immunoreactivity was unchanged. CONCLUSIONS: Rats with amiloride-induced RTA have decreased urinary ammonia excretion associated with decreased Rhcg expression in the CCD and OMCD, suggesting that the ammonia transporter Rhcg plays an important role in the pathogenesis of amiloride-induced RTA.

Membrane Trafficking of Collecting Duct Water Channel Protein AQP2 Regulated by Akt/AS160

Akt (protein kinase B (PKB)) is a serine/threonine kinase that acts in the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. The PI3K/Akt signaling pathway, triggered by growth factors and hormones including vasopressin, is an important pathway that is widely involved in cellular mechanisms regulating transcription, translation, cell growth and death, cell proliferation, migration, and cell cycles. In particular, Akt and Akt substrate protein of 160 kDa (AS160) are likely to participate in the trafficking of aquaporin-2 (AQP2) in the kidney collecting duct. In this study, we demonstrated that 1) small interfering RNA (siRNA)-mediated gene silencing of Akt1 significantly decreased Akt1 and phospho-AS160 protein expression; and 2) confocal laser scanning microscopy of AQP2 in mouse cortical collecting duct cells (M-1 cells) revealed AS160 knockdown by siRNA increased AQP2 expression in the plasma membrane compared with controls, despite the absence of dDAVP stimulation. Thus, the results suggest that PI3K/Akt pathways could play a role in AQP2 trafficking via the AS160 protein.

Cicatrização renal após nefrectomia parcial laparoscópica sem fechamento do sistema coletor em porcos / Kidney healing after laparoscopic partial nephrectomy without collecting system closure in pigs

Introdução: Embora alguns estudos tenham descrito as semelhanças e diferenças anatômicas entre o rim humano e o rim suíno, pouco é conhecido sobre a cicatrização renal neste animal. O conhecimento da cicatrização do rim do porco é especialmente importante em procedimentos cirúrgicos que incisem o tecido renal e o sistema coletor, como é o caso da nefrectomia parcial. O objetivo do presente trabalho é estudar a cicatrização renal em porcos após nefrectomia parcial laparoscópica sem o fechamento do sistema coletor. Materiais e Métodos: Quatorze porcos machos com peso médio de 30 kg foram submetidos à nefrectomia parcial laparoscópica esquerda, removendo 25% do comprimento renal no pólo caudal (n=7) ou no pólo cranial (n=7). A técnica cirúrgica empregada envolveu acesso laparoscópico transperitoneal, clampeamento em bloco dos vasos renais, excisão do tecido renal com tesoura a frio e aplicação de energia monopolar para hemostasia do parênquima, deixando o sistema coletor aberto. Os animais foram avaliados clinicamente por 14 dias e então foram mortos. Níveis séricos de creatinina e uréia foram obtidos antes e em diferentes momentos após a cirurgia. São relatados ainda os achados de necropsia, pielografia retrógrada ex vivo e aspectos histológicos dos pólos renais operados. Resultados: Os níveis séricos de uréia e creatinina tiveram leve aumento inicial retornando aos valores pré-operatórios durante o período avaliado. Durante a necropsia verificou-se que não houve extravasamento de urina a partir do rim operado e que este se cobriu com tecido fibroso, aderindo-se aos tecidos adjacentes. Nas pielografias retrógradas não foi verificado nenhum extravasamento de contraste pelos pólos operados. Os achados histológicos mostraram grande deposição de colágeno tipo I sobre o pólo renal operado, vedando-o completamente. Conclusão: O rim suíno não é um bom modelo para pesquisas ou treinamento cirúrgico em que a cicatrização do sistema coletor seja um aspecto importante.

Introduction: Although some studies have described similarities and diferences between human and pig kidney anatomy, little is known regarding renal healing in this animal model. The knowledge of pig kidney healing is especially important in surgical procedures which incise the renal parenchyma and collecting system, such as partial nephrectomy. The aim of this study is to access kidney in pigs after laparoscopic partial nephrectomy without closuring of the collecting system. Materials and Methods: Fourteen male pigs with mean weight of 30 kg were submitted to left partial laparoscopic nephrectomy, removing 25% of the kidney length at caudal pole (n=7) or at cranial pole (n=7). Briefly, the surgical technique involved a transperitoneal laparoscopic access, en bloc vascular clamping of renal artery an vein, tissue excision with cold scissor and monopolar energy parenchyma hemostasis, leaving the collecting system opened. The animals were clinically evaluated during fourteen days, and afterwards were killed. Serum levels of creatinine and urea were assessed prior and at different moments after surgery. Necropsy findings, retrograde ex vivo pyelogram and histological aspects of operated renal poles are also described. Results: Serum creatinine and urea showed a slight initial increase with a gradual return to preoperative levels during the evaluated period. At necropsy, no signs of urine leakage were found and kidneys were covered by a fibrous tissue with adherences to adjacent organs. Also, in the retrograde pyelograms obtained, we did not find contrast medium leakage by operated poles. Histological findings showed great deposition of type I collagen over operated renal pole, sealing it completely. Conclusion: The pig kidney is not an adequate experimental model for research and training of surgery on which collecting system healing is an important aspect to be considered.

Ubiquitination of Aquaporin: in the kidney

Ubiquitination is known to be important for endocytosis and lysosomal degradation of aquaporin-2 (AQP2). Ubiquitin (Ub) is covalently attached to the lysine residue of the substrate proteins and activation and attachment of Ub to a target protein is mediated by the action of three enzymes (i.e., E1, E2, and E3). In particular, E3 Ub-protein ligases are known to have substrate specificity. This minireview will discuss the ubiquitination of AQP2 and identification of potential E3 Ub-protein ligases for 1-deamino-8-D-arginine vasopressin (dDAVP)-dependent AQP2 regulation.

Fluorescence Quenching to Measure dDAVP-induced Cell Volume Changes in Kidney Collecting Duct Cell / 대한신장학회지

PURPOSE: Cell volume regulation is critical in kidney collecting duct cells which are subjected to large transepithelial osmotic gradients and stimulation of vasopressin. The present study aimed at validating the usefulness of the fluorescence quenching method to measure rapid changes in the cell volume of the kidney collecting duct cells in response to changes of extracellular osmolality and/or dDAVP (V2 receptor agonist) stimulation. METHODS: M-1 cell (a mouse cortical collecting duct cell line) was used and the data presented traces of cellular fluorescence in M-1 cells loaded with calcein collected over time as extracellular osmolality was repeatedly changed or dDAVP was treated. And the "initial relative rate of cell volume changes" was calculated. RESULTS: M-1 cells loaded with calcein revealed that fluorescence was increased when exposed to low extracellular osmolality (250 mOsm/KgH2O), whereas it was decreased by high extracellular osmolality (350 mOsm/KgH2O). This could reflect volume-dependent changes in fluorescence intensity in the range of quenching concentrations. The calculated "initial relative rate of cell volume changes" in M-1 cells during 1 sec was increased-7-fold by dDAVP treatment (10(-8)M, 2 min), compared with vehicle treatment when extracellular osmolality was changed from 350 to 250 mOsm/KgH2O. CONCLUSION: This study suggests that a fluorescence quenching method could be exploited for investigating an effect of dDAVP or other drugs/chemicals on the relative rate of cell volume changes in the kidney collecting duct cells.

Renal Handling of Ammonium and Acid Base Regulation

Renal ammonium metabolism is the primary component of net acid excretion and thereby is critical for acid - base homeostasis. Briefly, ammonium is produced from glutamine in the proximal tubule in a series of biochemical reactions that result in equimolar bicarbonate. Ammonium is predominantly secreted into the luminal fluid via the apical Na++xchanger, NHE3. The thick ascending limb of the loop of Henle reabsorbs luminal ammonium, predominantly by transport of NH4+y the apical Na++Cl - cotransporter, BSC1/NKCC2. This process results in renal interstitial ammonium accumulation. Finally, the collecting duct secretes ammonium from the renal interstitium into the luminal fluid. Although in past ammonium was believed to move across epithelia entirely by passive diffusion, an increasing number of studies demonstrated that specific proteins contribute to renal ammonium transport. Recent studies have yielded important new insights into the mechanisms of renal ammonium transport. In this review, we will discuss renal handling of ammonium, with particular emphasis on the transporters involved in this process.

Expression of Rh Glycoproteins in the Mammalian Kidney

Ammonia metabolism is a fundamental process in the maintenance of life in all living organisms. Recent studies have identified ammonia transporter family proteins in yeast (Mep), plants (Amt), and mammals (Rh glycoproteins). In mammalian kidneys, where ammonia metabolism and transport are critically important for the regulation of systemic acid - base homeostasis, basolateral Rh B glycoprotein and apical/basolateral Rh C glycoprotein are expressed along the distal nephron segments. Data from experimental animal models and knockout mice suggest that the Rh glycoproteins appear to mediate important roles in urinary ammonia excretion.

Newer insights into renal regulation of water homeostasis.

The regulation of high osmolality is an important driving force for water reabsorption and urinary concentration--the key functions of the kidney for maintaining optimum body fluid volume. New evidence shows that transcription factor tonicity responsive enhancer binding protein (TonEBP) and calcineurin-nuclear factor of activated T cells through cross-talk enhance Aquaporin 2 (AQP2) expression. AQP2 is the predominant vasopressin regulated water channel of the kidney collecting duct and is essential for urinary concentration. The serine/threonine phosphatase calcineurin is an important signaling molecule involved in kidney development and function. One potential target of calcineurin action is the water channel AQP2. The nuclear factor of activated T cells (NFAT) family has recently been expanded by the discovery of a new member, NFAT 5, or Ton EBP. Ton EBP is the only known mammalian transcription factor that regulates gene expression in response to hypertonicity. This review examines the importance of AQP2, calcineurin, NFATc and TonEBP in the renal regulation of water homeostasis.

Estudo da toxicidade induzida por fosfolipase A2 isolada do veneno de Crotalus durissus terrificus em rim isolado de rato e em túbulos proximais isolados de coelho [manuscrito] / Study of the toxicity induced by phospholipase A2 isolated from Crotalus durissus terrificus venom in isolated rat kidney proximal tubules and in isolated rabbit [manuscript]

Apesar de muito se discutir sobre os efeitos citotóxicos dos venenos ofídicos, pouco ainda é conhecido sobre os mecanismos de ação sobre as diversas células, e em especial, sobre as células renais. No caso particular da citotoxicidade dos venenos crotálicos, tem-se postulado a participação de diversos metabólicos da hidrólise de lipídios de membrana, e, mais recentemente, da disfunção mitocondrial. O presente trabalho teve como objetivo estudar o efeito da fosfolipase A2 (FLA2) isolada do veneno da Crotalus durissus terrificus sobre rim isolado de rato assim como estudar a toxicidade e as alterações da função mitocondrial induzidas pelas FLA2s de pâncreas de porco (PFLA2) e de veneno da C. d. terrificus (VSFLA2) em suspensões de túbulos proximais (TP). No rim isolado foi observado aumento no fluxo urinário, no ritmo de filtração glomerular (RFG) e na pressão de perfusão (PP) enquanto ocorreram decréscimos nos percentuais de transporte total de sódio (%TNA+), de potássio (%TK+) e de cloreto (%TCl-)...

Manejo renal de la ß2 microglobulina: su significado en portadores de la nefronoptisis del adolescente / Renal handling of ß2 microglobulin: its significance in carries of adolescent nephrothisis (NPH3)

La nefronoptisis del adolescente (NPH3) constituye una variedad de la nefronoptisis. En Venezuela, la incidencia anual está alrededor de 1 a 3 casos por año todos los casos pertenecen a un árbol genealógico común. El presente estudio tuvo como objetivo evaluar la función tubular proximal en pacientes portadores del gen de la NPH3 con función renal conservada, para lo cual se utilizó como marcador biológico la ß2 microglobulina (ß2M). Se incluyeron en el estudio 8 pacientes: 7 portadores heterocigotos y un homocigoto del gen de la NPH3 y 10 controles sanos. Se determinaron las concentraciones plasmáticas y urinarias de ß2M y se calcularon los índices de ß2M urinaria/creatinina urinaria, así como la excreción fraccional de ß2M, la ß2M filtrada y el porcentaje de reabsorción de ß2M. Se evidenció un aumento de la concentración plasmática de ß2M no relacionada con disminución de la filtración glomerular. La excreción fraccionada urinaria de ß2M así como los índices urinarios relación U ß2M/Ucr y la excreción fraccionada de ß2M fueron normales. La carga filtrada estuvo elevada sin aumento en la excreción con un porcentaje de reabsorción normal. En el grupo estudiado no se demostró una alteración en la excreción urinaria de ß2M; se evidenció un aumento en la carga filtrada sin aumento en el porcentaje de reabsorción normal. En el grupo estudiado no se demostró una alteración en la excreción urinaria de ß2M; se evidenció un aumento en la carga filtrada sin aumento en el porcentaje de reabsorción ni en la excreción lo que plantea otro mecanismo de captación o de degradación de la sustancia a nivel del tubulo contorneado proximal, mecanismo aún no dilucidado.

Immunolocalization of anion exchanger 1 (Band 3) in the renal collecting duct of the common marmoset

The purpose of this study was to determine the expression and distribution of band 3 in the collecting duct and connecting tubules of the kidney of the marmoset monkey (Callithrix jacchus), and to establish whether band 3 is expressed in type A intercalated cells. The intracellular localization of band 3 in the different populations of intercalated cells was determined by double-labeling immunohistochemistry. Immunohistochemical microscopy demonstrated that band 3 is located in the basolateral plasma membranes of all type A intercalated cells in the connecting tubule (CNT), cortical collecting duct (CCD), and outer medullary collecting duct (OMCD) of the marmoset. However, type B intercalated cells and non-A/ non-B intercalated cells did not show band 3 labeling. Electron microscopy of the CNT, CCD and OMCD confirmed the light microscopic observation of the basolateral plasma membrane staining for band 3 in a subpopulation of interacted cells. Basolateral staining was seen on the plasma membrane and small coated vesicles in the perinuclear structure, some of which were located in the Golgi region. In addition, there was no labeling of band 3 in the mitochondria of the CNT, CCD and in OMCD cells. The intensity of the immunostaining of the basolateral membrane was less in the CNT than in the CCD and OMCD. In contrast, band 3 immunoreactivity was greater in the intracellular vesicles of the CNT. From these results, we suggest that the basolateral Cl-/HCO3- exchanger in the monkey kidney is in a more active state in the collecting duct than in the CNT.

H+_Atpasa Vacuolar Renal. Fisiología y Regulación / Vacuolar H (+)_ATPase renal. Physiologi and Regulation

Las H+ _ATPasas vacuolares son complejos proteicos ubicuos con múltiples subunidades que incluyen un dominio catalítico V1 compuesto por proteínas periféricas que hidrolizan adenosina trisfosfato (ATP) y proveen energía a la bomba de H+ a través de un segundo dominio transmembrana Vº en contra de importantes gradientes. Estas H+_ATPasas vacuolares, que intervienen en la translocación de protones, son responsables en células eucariotas de la acidificación de las organelas intracelulares y de la acidificación de los espacios luminales e intersticiales adyacentes a las membranas plasmáticas celulares. Mutaciones en los genes que codifican las subunidades de H+ATPasa vacuolar específicas de células intercalares de ríñón; Vºa4 y V1B1, causan el síndrome de acidosis tubular distal renal. Esta revisión se focalizará en función, regulación y en el rol de H+ATPasa vacuolar en fisiología renal. La localización de H+ _ATPasa en el rión y su rol en la regulación de pHintracelular, transporte de protones y la homostsis del ácido base, será discutida.