Tubulointerstitial injury and the progression of chronic kidney disease

In chronic kidney disease (CKD), once injury from any number of disease processes reaches a threshold, there follows an apparently irreversible course toward decline in kidney function. The tubulointerstitium may play a key role in this common progression pathway. Direct injury, high metabolic demands, or stimuli from various other forms of renal dysfunction activate tubular cells. These, in turn, interact with interstitial tissue elements and inflammatory cells, causing further pathologic changes in the renal parenchyma. The tissue response to these changes thus generates a feed-forward loop of kidney injury and progressive loss of function. This article reviews the mechanisms of this negative cycle mediating CKD

Influence of dietary NaCl intake on renin gene expression in the kidneys and adrenal glands of rats

The aim of this study was to examine the influence of dietary NaCl intake on renin gene expression in the kidneys and adrenal glands of adult rats. Rats were kept on low (0.02%, w/w), normal (0.6%) or high (4%) NaCl diets and plasma renin activity (PRA) and the relative abundance of renin messenger ribonucleic acid (mRNA) in renal and adrenal tissue were followed for 20 days. In animals on a normal-salt diet PRA and renal renin mRNA levels did not change with time. PRA values in animals on the low-salt diet increased transiently (about threefold) and then declined again during the third week of treatment. Renal renin mRNA levels in these animals paralleled the changes of PRA. Conversely, in the animals kept on a high-salt diet PRA values decreased transiently and renal renin mRNA decreased continuously to about 50% of control values. Arterial blood pressure measured in conscious animals was not significantly influenced by the different salt diets. To establish whether the changes in renin mRNA levels are mediated by renal nerve input, animals on the different diets were also studied after unilateral renal denervation. Renal nerve section led to a 50% decrease of renin mRNA levels in the denervated kidneys in animals kept on the normal-salt diet. In the animals on the low-salt diet renin mRNA rose to similar levels in the denervated to those in the innervated kidney, while in animals receiving a high-salt diet renin mRNA was further decreased in the denervated kidneys.(ABSTRACT TRUNCATED AT 250 WORDS

Modelling the carbon cycle in the turbidity maximum of the Seine estuary

Estuaries are characterised by long residence time (CIFFROY et al. 2003, ), accumulation of high amounts of suspended matter (SM) in the turbidity maximum zone. They receives the waters of the whole drainage basin before transfer to the coastal and oceanic domains. Thus the question of the role of the estuaries for transformation, production and exportation of nutrients and organic matter was regularly renewed (DAY et al. 1989, ) and, given the complexity of estuaries and contexts, remains largely discussed (ABRIL et al. 2002, ). Given the difference between dissolved and particulate species transport, particulate organic matter fate is essentially under concern (KNOX 1986, ). This question was studied in the framework of SEINE AVAL, research program dedicated to the Seine estuary. In order to determine the relative importance of the sources of POC in the estuary and to interpret the high organic carbon (POC) content of the suspended matter (SM) in the turbidity maximum (up to 5 %) (ABRIL et al. 2002, ), a modelling of the carbon cycle was undertaken, based on in situ and laboratory measurements.info:eu-repo/semantics/publishe

Modelling the carbon cycle in the turbidity maximum of the Seine estuary

info:eu-repo/semantics/nonPublishe

The renal Na+/phosphate cotransporter NaPi-IIa is internalized via the receptor-mediated endocytic route in response to parathyroid hormone.

The major renal Na(+)/phosphate cotransporter, NaPi-IIa, is regulated by a number of factors including parathyroid hormone (PTH), dopamine, and dietary phosphate intake. PTH induces the acute internalization of NaPi-IIa from the brush border membrane (BBM) and its routing to and subsequent degradation in lysosomes. Previous work indicated that megalin, part of the apical receptor-mediated endocytic apparatus, may play a role in the PTH-induced removal of NaPi-IIa. Here we examined in rats the time-dependent internalization route of NaPi-IIa after acute PTH application using immunohistochemistry and markers of several endocytic compartments. NaPi-IIa removal from the BBM was detectable as early as 5 min after PTH injection. After 10-15 min, NaPi-IIa was localized in subapical compartments positive for clathrin. Shortly thereafter, NaPi-IIa appeared in endosomes stained for EEA1 (early endosomal antigen 1). After 45-60 min, NaPi-IIa was found in late endosomes/lysosomes marked with lgp120. In contrast, no change in the subcellular localization of megalin and the Na(+)/H(+) exchanger NHE3 was detected up to 60 min after PTH injection. To further characterize the internalization route, insulin, as a marker for receptor-mediated endocytosis, and horseradish peroxidase (HRP) and fluorescein isothiocyanate (FITC)-dextran (10 kDa), as markers for fluid-phase mediated endocytosis, were used. NaPi-IIa colocalized with insulin 5-30 min after PTH injection but did not overlap with HRP or FITC-dextran. These results demonstrate a distinct internalization route of NaPi-IIa in response to acute PTH application that may involve the receptor-mediated endocytic pathway including clathrin-coated vesicles and EEA1-positive early endosomes, and routes NaPi-IIa to lysosomes for degradation

Which factor mediates reno-renal control of renin gene expression?

The results suggest that the suppression of renin gene expression in the contralateral kidneys of stenosed kidneys is not due to compensatory renal growth nor mediated by systemic blood pressure, angiotensin II AT1 receptors or renal nerves. We therefore hypothesize that kidneys with reduced perfusion release a humoral factor that acts as a potent inhibitor of renin gene expression

Role of Interferon-Gamma in Interleukin 12-Induced Pathology in Mice

Interleukin 12 (IL-12) activates natural killer (NK) and T cells with the secondary synthesis and release of interferon-gamma (IFN-gamma) and other cytokines. IL-12-induced organ alterations are reported for mice and the pathogenetic role of IFN-gamma is investigated by the use of mice deficient in the IFN-gamma receptor (IFN-gamma R(-/-)). IL-12 caused a rapid infiltration of liver and splenic red pulp with activated macrophages; this and increased NK cells resulted in a fivefold increase of splenic weight in wild-type mice. Splenomegaly was associated with myelosuppression and decreasing peripheral leukocyte counts. IL-12-induced changes in wild-type mice were associated with markedly increased IFN-gamma serum levels and up-regulation of major histocompatibility complex (MHC) class I and II expression in various epithelia. IL-12 induced a qualitatively similar macrophage infiltration in IFN-gamma R(-/-) mice, less marked splenomegaly (to 2 x normal), and no MHC upregulation. Strikingly increased vascular endothelial intercellular adhesion molecule-1 expression was apparent in both IFN-gamma R(-/-) and IFN-gamma R(+/+) mice. Restricted to mutant mice was a severe, invariably lethal, interstitial, and perivascular pulmonary macrophage infiltration with diffuse pulmonary edema. Extensive quantitative reverse transcriptase polymerase chain reaction analysis revealed an increase of only IL-6 and IL-10 pulmonary gene transcripts in IFN-gamma R(-/-) mice compared with wild-type mice. IL-12-induced myelosuppression is due to IFN-gamma-release from NK cells and T cells, and is associated with macrophage activation and distinct MHC class I and II antigen upregulation. The pulmonary pathology in IFN-gamma R(-/-) mice, however, reveals a toxic potential for IL-12 and suggests that endogenous IFN-gamma plays a protective role in preventing fatal pulmonary disease in these mice