Evaluación de la función renal para la detección y seguimiento de la enfermedad renal crónica. Documento multidisciplinario de consenso 2021. Especial atención sobre situaciones clínicas específicas / Evaluation of renal function for the detection and follow-up of chronic kidney disease. Multidisciplinaryconsensus document 2021. Special attention to specific clinical situations

Resumen El filtrado glomerular (FG) se considera el mejor índice para evaluar la función renal en la práctica clínica. Recientemente, ha ganado popularidad la utilización de ecuaciones que estiman el FG, en distintas poblaciones, a partir de los niveles séricos de algunos biomarcadores. Sin embargo, no todas las fórmulas han sido validadas en los diversos escenarios clínicos probables. Las sociedades participantes: Sociedad Argentina de Nefrología, Asociación Bioquímica Argentina, Fundación Bioquímica Argentina y Confederación Unificada Bioquímica de la República Argentina, integradas por nefrólogos y bioquímicos, realizaron un consenso actualizado sobre la utilización del FG como herramienta de detección de la enfermedad renal crónica (ERC) en la Argentina. Se analizó la bibliografía existente y, teniendo en cuenta aspectos de nuestra realidad sanitaria, se establecieron sugerencias para su utilización. Se actualizaron las indicaciones del uso del FG medido. En sucesivos capítulos se puso foco en distintos estados del FG en diversas poblaciones y situaciones. En los estados de reducción del FG, se mencionaron tanto los fisiológicos propios del envejecimiento, como los determinados por situaciones patológicas, por ejemplo, el observado en la ERC avanzada o el determinado en aquellos pacientes que recibieron un trasplante renal. Se revisaron, por otro lado, las situaciones de incremento del FG, como las observadas en el embarazo o en la obesidad. Se refirieron, asimismo, las limitaciones de la estimación del FG, se reconoció su valor en situaciones de la práctica clínica habitual, o en contextos epidemiológicos definidos y se sugirieron las ecuaciones más adecuadas para su utilización en cada caso.

Abstract The glomerular filtration rate (GFR) is considered the best index to assess the renal function in clinical practice. Recently, the use of equations to estimate GFR in different populations, based on the serum levels of some biomarkers, has gained popularity. However, not all the equations have been validated in the various likely clinical scenarios. Thus, the participating societies, i.e. the Argentine Society of Nephrology, the Argentine Association of Biochemistry, the Argentine Foundation of Biochemistry, and the Unified Confederation of Biochemistry of Argentina, composed of nephrologists and biochemists, have established an updated consensus on the use of the GFR as a tool for the detection of chronic kidney disease (CKD) in Argentina. The consensus was established on the basis of the analysis of the existing literature and taking into account aspects of the health situation in Argentina. Suggestions for the use of the GFR were made, and the indications for its use were updated. The successive chapters of the consensus consider different values of the GFR in different populations and situations. The different situations considered and reviewed include cases of a decrease in the GFR, such as the physiological one related to aging and that related to pathological situations, as observed in advanced CKD or in patients who have received a kidney transplant, as well as cases of an increase in the GRF, such as that observed in pregnancy or obesity. The consensus also mentions the advantages and limitations of the estimation of the GFR in situations of usual clinical practice or in specific epidemiological contexts, and the most appropriate equations for its use in each case is suggested.

Resumo A filtração glomerular (FG) é considerada o melhor índice para avaliar a função renal na prática clínica. Recentemente, a utilização de equações que calculam a FG, em diferentes populações, ganhou popularidade a partir dos níveis séricos de alguns biomarcadores. Entretanto, nem todas as fórmulas têm sido validadas nos diversos cenários clínicos prováveis. As sociedades participantes: Sociedade Argentina de Nefrologia, Associação Bioquímica Argentina, Fundação Bioquímica Argentina e Confederação Unificada Bioquímica da República Argentina, integradas por nefrologistas e bioquímicos, realizaram um consenso atualizado sobre a utilização da FG, como ferramenta de detecção da doença renal crônica (DRC) na Argentina. Foi analisada a bibliografia existente e, considerando aspectos da nossa realidade sanitária, foram estabelecidas sugestões para sua utilização. Foram atualizadas as indicações do uso da FG medida. Em sucessivos capítulos se colocou o foco em diferentes estados da FG em populações e situações diversas. Nos estados de redução da FG, foram mencionados tanto os fisiológicos próprios do envelhecimento, quanto os determinados por situações patológicas, por exemplo, aquele observado na DRC avançada ou o determinado naqueles pacientes que receberam um transplante renal. Por outra parte, foram revistas as situações de aumento da FG como as observadas na gravidez ou na obesidade. Foram referidas, também, as limitações da estimativa da FG, foi reconhecido o seu valor em situações da prática clínica habitual, ou em contextos epidemiológicos definidos e se sugeriram equações mais adequadas para sua utilização em cada caso.

POD-1/Tcf21 overexpression reduces endogenous SF-1 and StAR expression in rat adrenal cells

During gonad and adrenal development, the POD-1/capsulin/TCF21transcription factor negatively regulates SF-1/NR5A1expression, with higher SF-1 levels being associated with increased adrenal cell proliferation and tumorigenesis. In adrenocortical tumor cells, POD-1 binds to the SF-1 E-box promoter region, decreasing SF-1 expression. However, the modulation of SF-1 expression by POD-1 has not previously been described in normal adrenal cells. Here, we analyzed the basal expression of Pod-1 and Sf-1 in primary cultures of glomerulosa (G) and fasciculata/reticularis (F/R) cells isolated from male Sprague-Dawley rats, and investigated whether POD-1 overexpression modulates the expression of endogenous Sf-1 and its target genes in these cells. POD-1 overexpression, following the transfection of pCMVMycPod-1, significantly decreased the endogenous levels of Sf-1 mRNA and protein in F/R cells, but not in G cells, and also decreased the expression of the SF-1 target StAR in F/R cells. In G cells overexpressing POD-1, no modulation of the expression of SF-1 targets, StAR and CYP11B2, was observed. Our data showing that G and F/R cells respond differently to ectopic POD-1 expression emphasize the functional differences between the outer and inner zones of the adrenal cortex, and support the hypothesis that SF-1 is regulated by POD-1/Tcf21 in normal adrenocortical cells lacking the alterations in cellular physiology found in tumor cells.

Enfoque diagnóstico de la hematuria en pediatría / Diagnostic approach to a child with hematuria

La hematuria es un hallazgo clínico observado por el paciente o un familiar cuando es macroscópica o bien incidental en un parcial de orina rutinario. La prevalencia es baja pero el enfoque diagnóstico al cual está enfrentado el clínico es amplio. La hematuria indica enfermedad, lesión o malformación del tracto urinario, por ello el médico general y el pediatra deben estar en capacidad de determinar a tiempo algunas de las causas con pronóstico grave o diagnóstico complejo que requieren la remisión al nefrólogo pediatra. Se hace énfasis en diferenciar si es o no de origen glomerular, adoptando un algoritmo de enfoque diagnóstico que orienta al clínico. Se realizó una búsqueda limitada de 2001-2014 en las principales bases de datos en inglés y español encontrando revisiones de la literatura, consensos de expertos y guías de práctica clínica basadas en la opinión de pediatras, nefrólogos y urólogos pediatras, así como de radiólogos que ofrecen una aproximación real a la imagenología. Está dirigida a personal de la salud, médicos generales y pediatras quienes enfrentan a diario esta condición clínica.

Hematuria is a clinical finding observed by the patient or a relative if it is macroscopic, or is an incidental finding in a routine urinalysis. Prevalence rate is low but the range of differential diagnoses faced by the physician is broad. Hematuria indicates disease, lesion or malformation of the urinary tract, thus the general practitioner and the pediatrician must be capable to determine the etiologies that have a poor prognosis or are difficult to diagnose which require prompt referral to a pediatric nephrologist. We emphasize on the development of a diagnostic algorithm to help the physician distinguish glomerular from non-glomerular hematuria. A limited search from 2001-2014 was conducted in the major data bases in English and Spanish finding literature reviews, expert consensus and clinical practice guidelines based on the opinion of pediatricians, and pediatric nephrologists and urologists, as well as radiologists who offer a real approach to imaging. It is oriented toward health care providers, general practitioners and pediatricians who face this clinical condition in their daily practice...

Aldosterone secretion in patients with septic shock: a prospective study / Secreção de aldosterona em pacientes com choque séptico: estudo prospectivo

OBJECTIVE: To assess serum levels of the main factors that regulate the activation of the zona glomerulosa and aldosterone production in patients with septic shock, as well as their response to a high-dose (250 µg) adrenocorticotropic hormone (ACTH) stimulation test. SUBJECTS AND METHODS: In 27 patients with septic shock, baseline levels of aldosterone, cortisol, ACTH, renin, sodium, potassium, and lactate were measured, followed by a cortrosyn test. RESULTS: Renin correlated with baseline aldosterone and its variation after cortrosyn stimulation. Baseline cortisol and its variation did not correlate with ACTH. Only three patients had concomitant dysfunction of aldosterone and cortisol secretion. CONCLUSIONS: Activation of the zona glomerulosa and zona fasciculata are independent. Aldosterone secretion is dependent on the integrity of the renin-angiotensin-aldosterone system, whereas cortisol secretion does not appear to depend predominantly on the hypothalamic-pituitary-adrenal axis. These results suggest that activation of the adrenal gland in critically ill patients occurs by multiple mechanisms.

OBJETIVO: Avaliar os níveis séricos dos principais fatores que regulam a ativação da zona glomerulosa e a produção de aldosterona em pacientes com choque séptico, assim como sua resposta ao teste de cortrosina em alta dose (250 µg). SUJEITOS E MÉTODOS: Em 27 portadores de choque séptico, foram aferidos níveis basais de aldosterona, cortisol, ACTH, renina, sódio, potássio e lactato, bem como realizado teste de cortrosina. RESULTADOS: Renina se correlacionou com níveis basais de aldosterona e sua variação após teste de cortrosina. Cortisol basal e sua variação não se correlacionaram com ACTH. Apenas três pacientes apresentaram disfunção concomitante da secreção de aldosterona e cortisol. CONCLUSÕES: Ativação das zonas fasciculada e glomerulosa são independentes. Secreção de aldosterona é dependente da integridade do sistema renina-angiotensina-aldosterona, enquanto secreção de cortisol não parece predominantemente dependente do eixo hipotálamo-hipófise-adrenal. Esses resultados sugerem que a ativação da adrenal em pacientes críticos ocorre por múltiplos mecanismos.

Effects of intrauterine malnutrition on the renal morphology of Wistar rats: a systematic review

Introduction: Many epidemiological studies suggest that the intrauterine environment is extremely importantto the determination of the individual’s future health. Alterations in the maternal nutritional state, reflectedon the weight on birth, may program the litter for the development of diseases on the adult age. Studies withanimals exposed to intrauterine malnutrition have suggested a reduction in the number of glomeruli, as wellas arterial pressure increase. To review in the literature the alterations of the renal physiology of adult Wistarrats exposed to malnourishment during intrauterine life. Material and methods: A search was performedin the following databases: SciELO, MEDLINE, PUBMED, SCIENCE DIRECT and LILACS. The mainsearch terms were “malnutrition” and “renal function” both in Portuguese and in English. Were includedoriginal articles involving albino rats. Were excluded the review articles as well as those involving humanbeings. Results: According to Franco et al. (2009) the renal function and the number of glomeruli werereduced by the intrauterine malnutrition, predisposing the adult animals to renal diseases. For Chen and Chou(2009) the glomerular ultrastructure is not affected by maternal undernutrition, suggesting that this factordoes not contribute to the hypertension pathogenesis after maternal malnutrition. Conclusion: Intrauterinemalnourishment seems to interfere in the renal functions programming with alterations to the glomerulimorphology, but its mechanisms are yet uncertain. More randomized studies and clinical essays are suggestedin order to comprehend the factors that cause such process.

Estereología renal en el cobayo (Cavia porcellus) / Renal stereology in the guinea pig (Cavia porcellus)

El cobayo (Cavia porcellus) es un roedor perteneciente al Orden Rodentia y a la Familia Caviidae, utilizado como animal de laboratorio y de consumo humano. Los parámetros cuantitativos del riñón entregan importante información de su morfofunción dada su labor en la homeostasis del organismo. El objetivo de este estudio fue describir el riñón de cobayo (Cavia porcellus), analizando las características estereológicas para futuros estudios experimentales. Se utilizaron 5 cobayos machos, obtenidos del Bioterio de la Universidad de La Frontera, Temuco, Chile. El riñón de cobayo pesó 3,2 g, aproximadamente. El riñón posee 140.298 glomérulos en total, Nv de 458 mm³, Vv de 7,89% y Sv de 3,58 mm²/ mm³. El volumen glomerular del riñón fue de 1,73 x 10(4)mm³ y el diámetro glomerular de 90 jm. Factores como especie, edad, peso corporal, peso y volumen renal, son importantes a considerar, ya que diferencian los resultados en investigaciones morfofuncionales.

The guinea pig, (Cavia porcellus) is a rodent pertaining to the Rodentia group and the Caviidae family, used as a laboratory animal and for human consumption. Quantitative parameters of the kidney provides important information of its morphofunction, given its labor in the organism's homeostasis. The aim or this study was to describe the kidney of the guinea pig (Cavia porcellus), analyzing the stereological characteristics for future experimental studies. Five male guinea pigs (Cavia porcellus) obtained from the Biotery of the Universidad de la Frontera, Temuco, Chile, were used. The kidney of the guinea pig weighed approximately 3.2g. The kidney has 140,298 total glomerulus, Nv of 458 mm³, Vv of 7.89% and Svof 3.58mm²/mm³. The glomerular volume of the kidney was of 1.73 x 10(4)mm³ and a glomerular diameter of 90 urn. Factors such as species, age, body weight and renal volume, are important to consider, as they differentiate the results in the morphofunctional investigations.

To observe and compare the histological features of fat induced adrenal cortex in albino rats

To observe and compare the histological features of fat induced adrenal cortex in albino rats. Prospective experimental study. Department of anatomy, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi from August 2008 to October 2008. Twenty, young, male albino rats were selected for this study and were divided into 2 groups. Group A served as control and received normal diet. Group B received high-fat diet with 20 gms of saturated fat in the form of unsalted dairy butter per 100 gms of diet. Both groups were further divided into two Al and A2, B1 and B2 according to period of study i.e. 4 and 6 weeks respectively. On completion of experimental period, animals were weighed then sacrificed. Adrenal glands were removed, weighed and processed for paraffin sectioning. Haematoxylin and eosin staining was done for histological study. Cortical zones examined for apparent zonal hypertrophy, and cellular and nuclear changes. Increase in body weight and weight of Adrenal glands were highly significant [P<0.001]. Apparent increase in zona fasciculata observed was consistent with increased activity of gland. Cells in this zone appeared vacuolated due to presence of fat. In some areas of zona glomerulosa pyknosis and distortion of cell out line seen. High-fat diet induces increase in body weight and weight of adrenal gland which were due to hypertrophied zona fasciculata mainly, suggesting that these findings lead to increased activity and secretion of glucocorticoids

Expression and Localization of General Transcription Factor IIA Gene in Hypokalemic Rat / 대한해부학회지

Potassium balance in chronic hypokalemia is regulated by ion channels, ion transporters, and various related genes. We isolated general transcription factor IIA (GTF IIA) gene using a DNA chip microassay, a useful method in cloning genes. Northern analysis and in situ hybridization (ISH) were carried out to analyze the expression and localization of GTF IIA mRNA in rat in relation to the amount of potassium in the diet. Isoform-specific 32P-labeled cDNA (Northern analysis) or digoxigenin-labeled cRNA (ISH) probes were used. Northern analysis demonstrated that GTF IIA mRNA was expressed abundantly in testis; modestly in heart, kidney, lung, adrenal gland, liver, and spleen; and weakly in brain, distal colon, duodenum, salivary gland, and stomach. In potassium-restricted animals, GTF IIA expression was decreased in the kidney, adrenal gland, and spleen, but expression was restored to normal levels in L3w. The expression level in the lung was decreased in L3d and L2w, and increased in L1w and L3w. ISH showed that mRNA for the GTF IIA gene was detected in the distal convoluted tubule, S3 segment of the proximal tubule, and cortical collecting duct in the normal group. In potassium-restricted groups, the hybridization signal was detected in the distal convoluted tubule, S3 segment of the proximal tubule, and entire collecting tubule. The signal intensity of the outer and inner medullary collecting ducts was higher in the potassium-restricted group than in the normal group but was decreased in the distal convoluted tubule and S3 segment of the proximal tubule. In the normal group, mRNA of the GTF IIA gene was detected in the zona glomerulosa cells of the adrenal gland, lymphocytes of the marginal zone, germinal center of the spleen, and bronchial epithelium and lymphocytes of the lung. mRNA for the GTF IIA gene was also detected in the cells of the basal portion of the intestinal glands of the distal colon and stomach, and in spermatogonia and spermatocytes of the seminiferous tubule. These results suggest that expression of GTF IIA differs between various tissues and that increased expression of the GTF IIA gene in the outer and inner medullary collecting ducts of the hypokalemic kidney might regulate the ion transporter genes in these segments.

Determinación de parámetros estereológicos en el riñón de conejo (Oryctolagus cuniculus) / Determination of the stereological parameters in the kidney of the rabbit (Oryctolagus cuniculus)

El número y volumen glomerular contiene información importante sobre la morfofunción del riñón. El objetivo de este trabajo fue determinar algunos parámetros estereológicos, compararlos con los de otros estudios y determinar patrones de normalidad, para futuros estudios experimentales. Se utilizaron 5 riñones de conejo (Oryctolagus cuniculus), obtenidos del Bioterio de la Universidad de La Frontera, Temuco, Chile. Los riñones fueron disecados y fijados en formalina tamponada al 10 por ciento, realizando una breve descripción morfológica de ellos y determinando su volumen por el método de Scherle. Las muestras fueron obtenidas por Orientator e incluidas en Paraplast®. Se utilizó un fragmento de cada riñón y de cada uno de ellos se obtuvieron 5 cortes de 5 µm, los cuales fueron teñidos con H-E y Tricrómico de Masson. El volumen promedio obtenido del riñón de conejo, fue 11,4 mm3 + - 1,146mm3. El número promedio de glomérulos en el riñón fue 195,09 + - 84,78 x 103 glomérulos; un Nv de 17,1 + - 7,43 glomérulos por mm3 y un volumen glomerular de 4,2 x 10-4 x mm3 + - 0,8 x 10-4 x mm3. El número total de glomérulos del conejo Oryctolagus cuniculus, es menor al obtenido en ovejas por Eleanor et al. (2004) de 559.000 + - 198.000 y en perros por Horster et al. (1971) de 589.000; y mayor que en ratas por Bertram et al. (1992) de 31.764 + - 3.667. El volumen glomerular fue menor que en ratas (6,6 x10-4), que en ovejas 4,39x10-4 y mayor que en perros 1,2x10-4. Estas diferencias nos incentivaron a determinar otros parámetros estereológicos que permitirán iniciar una línea de investigación experimental en este animal.

The glomerular number and volume contain important information regarding the morphofunction of the kidney.The objective of this investigation was to determine some stereological parameters, compare them to those of other investigations and determine the normalcy patterns for future experimental investigations. Five rabbit (Oryctolagus cuniculus) kidneys from the Biotery of the Universidad de La Frontera, Temuco, Chile were used.The kidneys were dissected and set in buffered formalin at 10%, doing a brief morphological description of them and determining their volume via the Scherle method. The samples were obtained by Orientator and included in the Paraplast. One fragment of each kidney was used and serialized cuts of each one of these 5 µm were obtained, which were dyed with H-E and Masson´s Trichrome. The average volume obtained from the rabbit kidney was 11.4 mm3 ± 1.146mm3. The average number of glomerules in the kidney was 195.09 ± 84.78 x 103 gomerules; a Nv of 17,1 ± 7.43 glomerules per mm3 and a glomerular volume of 4.2 x 10-4 x mm3 ±0.8 x 10-4 x mm3. The total number of rabbit Oryctolagus cuniculus glomerules, is less than that obtained in sheep by Eleanor et al.(2004) of 559.000 ± 198.000 and in dogs by Horster et al. (1971) of 589.000and higher than in rats by Bertram et al. (1992) of 31.764 ± 3.667. The glomerular volume was less than in rats (6.6 x 10-4), than in sheep 4.39x10-4 and higher than in dogs 1.2x10-4. These differences are encouraging, in order to determine other stereological parameters which would allow for the initiation of an experimental line of investigation in this animal.

Características ultraestructurales del músculo esquelético en pacientes con proteinuria glomerular / Ultrastructure of skeletal muscle in patients with glomerular proteinuria

La proteinuria produce un desbalance importante del metabolismo proteico y lipídico, que favorece la desproteinización del organismo, con grandes repercusiones sistémicas que llegan a afectar hasta el músculo esquelético. En los pacientes con falla renal, usualmente disminuye su masa muscular y se observa debilidad. Los pacientes urémicos terminales, manifiestan atrofia de las fibras musculares tipo II, además de daño miopático primario, causado probablemente por un déficit de la microcirculación. En un afán de dilucidar las posibles alteraciones ultraestructurales precoces presentes en el músculo esquelético de pacientes con glomerulopatías primarias que cursan con proteinuria, se estudiaron 4 pacientes (2 hombres y 2 mujeres) con edades entre 42 y 66 años, pertenecientes al servicio de nefrología del hospital militar ®Dr. Calos Arvelo¼ de Caracas-Venezuela. En todos ellos se realizaron mediciones de enzimas musculares (CK, LDH, AST y ALT), electromiografía de los miembros inferiores y biopsia del músculo cuadriceps femoral. En ninguno de los pacientes se observaron modificaciones en los niveles séricos de las enzimas y a excepción de uno de ellos (caso 4), los registros eletromiográficos fueron normales. A nivel ultraestructural se observó: hinchamiento de los componentes del sistema sarcotubular con presencia de tríadas prominentes, signos de atrofia muscular, núcleos hipercromáticos, glucógeno abundante y glucogenosomas. Algunos capilares intramusculares con la luz parcial o totalmente ocluida, citoplasma endotelial electrón denso, presencia de prolongaciones del citoplasma endotelial hacia la luz del capilar, vesículas pinocíticas y cavéolas. Dichos cambios nos permiten concluir el compromiso estructural del músculo esquelético en pacientes con proteinuria, el cual se hace más evidente a medida que avanza hacia la falla renal y que dicho compromiso tiene una base microvascular que condiciona cambios del metabolismo muscular.

The proteinuria produces an important unbalance of the protein and lipid metabolism that it favors thedesproteinitation of the organism, with big systemic repercussions that end up affecting the skeletal muscle. In the patients with renal failure it usually diminishes their muscular mass and weakness is observed. The terminal uremic patient, manifests atrophy of the fibers muscular type II, besides miopatic primary damage, caused probably for a deficit of the microcirculación. In a desire of elucidating the early ultraestructural alterations present in the skeletal muscle of patient with primary glomerulopaties that curse with proteinuria, four patients were studied (2 men and 2 women) with ages between 42 and 66 years, belonging to the service of nephrology of the military hospital ®Dr. Calos Arvelo¼ of Caracas-Venezuela. In all they were carried out mensurations of muscular enzymes (CK, LDH, AST and ALT), electromiografie of the inferior members and biopsy of the muscle femoral cuadriceps. In none of the patients modifications were observed in the seric levels of the enzymes and to exception of one of them (case 4); the eletromiografic registrations are normal. At ultraestructural level it was observed: swelling of the components of the system sarcotubular with presence of prominent triads, signs of muscular atrophy, hyperchromatic nuclei, abundant glucogen and glucogenosome. Some capillary ones intramuscular with the partial or completely occluded light, electron dense cytoplasm, presence of continuations of the endothelial cytoplasm toward the light of the capillary one, pinocitic vesicles and caveole. This changes allow us to conclude the structural commitment of the skeletal muscle in patient with proteinuria, which becomes more evident as it advances toward the renal failure and that said commitment has a microvascular origin that conditions changes of the muscular metabolism.

Expression of Preadipocyte Factor-1 (Pref-1) and Vitamin D3 Up-regulated Protein 1 (VDUP1) Genes in Rat Adrenal Gland following Chronic Immobilization Stress / 대한해부학회지

Preadipocyte factor-1 (Pref-1) is expressed in the neuroendocrine organs such as the pituitary gland, the adrenal gland, the pancreas, the testis, etc. Vitamin D3 up-regulated protein 1(VDUP1) gene is known to be a novel member of early response genes as an oxidative stress mediator. The aim of the present study was to investigate whether Pref-1 and VDUP1 is involved in stress response in the adrenal gland following chronic immobilization stress. In situ hybridization for Pref-1 and VDUP1 genes (Pref-1 and VDUP1) was performed in the rat adrenal glands following immobilization stress, 2 hr once daily for 7 days. In situ hybridization analysis revealed that Pref-1 expression was up-regulated in rat adrenal medulla following chronic immobilization stress. However, Pref-1 was down-regulated in the zona glomerulosa of the adrenal cortex following chronic immobilization stress. VDUP1 expression was up-regulated in the zona glomerulosa and the adrenal medulla following chronic immobilization stress. These results show that Pref-1 and VDUP1 may be novel genes responding to chronic immobilization stress in adrenal gland.

Mechanism of Angiotensin 2-Stimulated Aldosterone Secretion in Adrenal Glomerulosa Cells of Diabetic Rats ; Normal Phospholipase Activity and Intracellular Calcium Mobilization / 대한내분비학회지

BACKGROUND: Diabetic patients develop hypoaldosteronism which frequently caused hyperkalemia and metabolic acidosis and diabetic hypoaldosteronism is associated with selective unresponsiveness of aldosterone to angiotensin A-II, but mechanism of defect in A-II stimulated aldosterone response still remain unclear. METHODS: To elucidate the mechanism of defect in A-II stimulated aldosterone response, author evaluated the responses of aldosterone production to A-II, K+, and ACTH in adrenal glomerulosa cells prepared from streptozotocin induced diabetic rats, Inositol triphosphate (IP3) generated by activation of phospholipase C (PLC) and arachidonic acid and lysophospholipids generated by activation of phospholipase A2 (PLA2) were measured in A-II stimulated glomerulosa cells. Radiocalcium efflux and aldosterone response to second messenger of A-II such as PLC, IP3, PLA, AA and protein kinase C activator, 12-o-tetradecanoylphorbol 13 acetate (TPA). RESULTS: 1. Plasma renin activity and aldosterone levels were not different among control rats, untreated and insulin treated diabetic rats. 2. Basal, ACTH and K+ -stimulated aldosterone production were similar in cells from the three groups (p0.05). 4. Aldosterone responses to PLC, IP3, AA and TPA were significantly decreased in glomerulosa cells from diabetic rats compared with control and insulin treated diabetic rats (p0.05). 45Ca efflux to PLC, IP3 PLA2 and AA were similar among the three groups (p>0.05). CONCLUSION: These results suggested that decreased A-II-stimulated aldosterone response was present in glomerulosa cells from streptozotocin induced diabetic rats and reversed by insulin treatments. The main defect of altered A-II response of zona glomerulosa might be located in the step after activation of phospholipase and increase of intracellular calcium, and activation of PKC, or distal to that could be one of the causative mechanism.

Mechanisms of hyperkalemia associated with hyporeninemic hypoaldosteronism in streptozotocin-induced diabetic rats

This study was aimed at investigating the mechanisms of clinically important overt hyperkalemia in diabetes mellitus with underlying hyporeninemic hypoaldosteronism known as a classic model of the syndrome of hyporeninemic hypoaldosteronism (SHH). Rats (Sprague-Dawley, male) were streptozotocin-treated (60 mg/kg, ip) and used after 60 days. Rats with plasma glucose levels higher than 300 mg/dL (mean +/- SEM, 423 +/- 20 mg/dL, n = 8) were selected as the diabetic group. Age-matched normal rats served as control (mean plasma glucose, 88 +/- 2, mg/dL, n = 8). Serum potassium concentrations and osmolalities as well as serum creatinine levels were significantly higher in the diabetic than in the control group (5.07 +/- 0.09 vs. 4.68 +/- 0.11 mEq/L; 330 +/- 14 vs 290 +/- 3 mOsm/L; 0.40 +/- 0.03 vs 0.31 +/- 0.02 mg/dL, p < 0.05). Plasma renin activity (PRA) in the diabetic group was significantly lower than that in the control group (6.0 +/- 1.0 vs 12.1 +/- 1.1 ng Al/ml/h, p < 0.001). Plasma aldosterone concentration (PAC) was also significantly lower in the former than in the latter (368 +/- 30 vs 761 +/- 57 pg/ml, p < 0.001). Renomegaly, abnormal distal tubular cells with few organelles, and increased lipid droplets with pyknotic nucleus in zona glomerulosa of the adrenal glands were noted in the diabetic group. In conclusion, multifactorial causes including insulinopenia, hyperosmolality, elevated serum creatinine level and hypoaldosteronism with possible contribution of altered distal tubular response to aldosterone may have interacted to develop hyperkalemia in these diabetic rats.