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The purpose of the study is to assess the impact of cinacalcet on calcium and bone remodeling, in post-renal transplanted patients with persistent hypercalcaemia secondary to hyperparathyroidism. Thirteen renal-transplanted adult recipients with a glomerular filtration rate over 30 ml/min/1.73 m(2), a total serum calcium>2.60 mmol/l with ionized calcium>1.31 mmol/l and a parathyroid hormone serum level over 70 pg/ml, were treated with cinacalcet for 4 months followed by a 15-day wash out. The results show that cinacalcet lowers significantly total and ionized calcium respectively from 2,73 (2,67-2,86) to 2,31 (2,26-2,37) mmol/l (P<0.05) and from 1,39 (1,37-1,47) to 1,21 (1,15-1,22) mmol/l (P<0.05) with no alteration of the 24-hour urine calcium/creatinine ratio and no significant expected PTH serum level suppression (153 [115-214,9] and 166 [122-174] pg/ml). On the other hand, fasting urine calcium was significantly decreased from 0,61 (0,27-1,02) to 0,22 (0,15-0,37) (P<0.05) and bone-specific alkaline phosphatases increased from 20,5 (13-46,6) to 33,8 (12-58,9) ng/ml, upon cinacalcet treatment. After its discontinuation, all these effects were reversible. In conclusion, cinacalcet normalizes total and ionized calcium in renal-transplanted recipients with hypercalcemia secondary to hyperparathyroidism through a mechanism that could be independent of PTH serum level suppression. The increase in bone-specific alkaline phosphatases, biochemical markers of bone accretion and the significant decrease in fasting urine calcium suggest the possibility of a beneficial impact of cinacalcet on bone remodeling., (Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

Repair of inflammatory and/or ischemic renal injury involves endothelial, mesangial and epithelial regeneration. These structures may be rebuilt by resident progenitor cells and bone marrow-derived stem cells. Resident progenitor cells in adult kidney have not yet been conclusively identified. They are likely to be slowly cycling cells located mainly in the outer medulla and renal papilla. In glomerulonephritis with mesangiolysis, mesangial regenera- tion involves progenitor cells migrating from the juxtaglomerular apparatus and also bone marrow-derived cells. In acute ischemic renal failure, epithelial regeneration of proximal tubules results from the migration, proliferation and differentiation of resident progenitor cells; bone marrow-derived cells may play an accessory role. Molecular mechanisms underlying these repair processes could be targets for new therapeutic approaches.

Calpains are cysteine proteases first identified 50 years ago. Because they are present in the cytosol of mammalian cells and because they are activated in response to Ca2+ mobilization, they are thought to be involved mainly in cell signalling pathways. They could participate in cellular responses such as apoptosis, proliferation, extracellular matrix adhesion and motility, that have relevance to pathophysiological issues in ischemia, inflammation, repair and tumor progression. Here we consider calpain functions in inflammatory reaction. We report the recent observation that calpain inhibitors reduce the development of acute and chronic inflammation. This has opened the door for understanding how these enzymes are effective in inflammation. We present data suggesting that calpains are primarily responsible for the activation of nuclear factor-kappa B, a transcription factor with a pivotal role in inflammation. They are involved in inflammatory cell adhesion and migration, pro-inflammatory mediator release and anti-inflammatory hormone resistance as well. In addition, we emphasize the intriguing possibility that calpains are externalized during inflammatory process and that they play a role in the microenvironment of inflammatory cells. Thus, both intracellular and extracellular calpains would offer novel therapeutic targets in inflammation.

NF-kappa B comprises a family of transcription factors. These are thought to have a central role in the expression of genes involved in cell mobilization, cell proliferation and cell differentiation, and, hence, in inflammation, repair and fibrosis processes. In particular, NF-kappa B activation appears to drive a number of inflammatory diseases of the kidney and their progression to end-stage renal failure. Thus, targeting NF-kappa B activation would lead to the development of new pharmaceutical compounds that would provide novel treatment for these diseases.

Both pro- and anti-inflammatory mediators regulate the anti-inflammatory actions of glucocorticoids, in part by modifying the binding of glucocorticoids to specific receptors. For instance, somatostatin has been shown to increase glucocorticoid binding and signaling in macrophages. The mechanism of this regulation does not require an increased expression of glucocorticoid receptors but, rather, a stabilization of glucocorticoid receptor-associated heat shock protein 90. This is related to a decrease in calpain activity. Thus calpain inhibition may offer a new and exciting possibility for enhancing the anti-inflammatory efficiency of glucocorticoids.

Studies of glomerulonephritis models have shown that inflammatory reaction is responsible for the development of glomerulosclerosis and tubulo-interstitial sclerosis and, hence, for the progression to end stage renal failure. That macrophage accumulation and fibrosis extension are frequently not closely related events suggests that macrophages are not involved in progression process. Glomerular sclerosis is rather associated with the release of mediators from resident cells-mainly growth factors such as platelet-derived growth factor and transforming growth factor-beta--the synthesis and bioactivity of which are enhanced by inflammatory mediators. Tubulo-interstitial sclerosis is induced by inflammatory lesions of the glomerulus that lead to proteinuria. Indeed, reabsorption of proteins in proximal tubule triggers epithelial cells to release proinflammatory and prosclerotic mediators into the interstitium. New therapeutic approaches including gene transfer strategies are directed at suppressing the efficiency of such mediators.

Prognosis: Intracellular dehydration is the major risk in case of a polyuropolydipsic syndrome. Excepting osmotic polyuria, prognosis depends on a possibly progressive functional anomaly of the hypothalamopituitary axis., Pathophysiology: Polyuropolydipsia occurs when antidiuretic hormone (ADH) secretion is absent (central diabetes insipidis), the kidney does not respond to ADH (nephrogenic diabetes insipidus) or in case of physiological inhibition of ADH secretion (primary polydipsia)., Exploration: Dynamic explorations are associated with radioimmunoassay of ADH. They are particularly useful in case of atypical diabetes insipidus and include the water restriction test and a study of the sensitivity to exogenous ADH (dDAVP). The results orient the etiologic diagnosis and allow an evaluation of the fluid intake required as a function of the maximal concentrating capacity of the kidneys., Treatment of Central Diabetes Insipidus: Treatment is based on ADH analogs (dDAVP). The aim is to obtain a constant antidiuretic effect without hyponatremia or escape. In case of partial central diabetes insipidus, a non-hormone treatment using compounds which increase vasopressin release or its effect on the kidney can be proposed.

Stimulation of macrophages with endotoxin and/or cytokines is responsible for the expression of the inducible isoform of nitric oxide synthase (iNOS). Because macrophages are exposed to low pH within the microenvironment of inflammatory lesions, the potential role of low pH as an additional regulator of iNOS was investigated. Substitution of the culture medium of rat peritoneal macrophages at pH 7.4 with medium at pH 7.0 upregulated iNOS activity, as reflected by a 2.5-fold increase in nitrite accumulation. The increase in iNOS activity was associated with a similar increase in iNOS mRNA expression. Low environmental pH-induced iNOS gene expression involved the activation of nuclear factor-kappa B (NF-kappa B) transcription factor since [1] exposure of macrophages to low environmental pH increased NF-kappa B binding activity in the nucleus, and [2] treatment of macrophages with pyrrolidine dithiocarbamate or n-acetyl-leucinyl-norleucinal, two drugs preventing NF-kappa B translocation to the nucleus, canceled low pH-induced nitrite accumulation. The overall mechanism required the synthesis of tumor necrosis factor-alpha (TNF-alpha). Indeed, [1] elevated TNF-alpha bioactivity was observed in the medium of macrophages exposed to pH 7.0, and [2] incubation of macrophages with a neutralizing anti-TNF-alpha antibody impaired both NF-kappa B activation and nitrite accumulation in response to acid challenge. In summary, exposure of macrophages to acidic microenvironment in inflammatory lesions leads to the upregulation of iNOS activity through the activation of NF-kappa B.

Objectives and Methods: In France, the positive rate for unit-HCV antibodies in the sera of pregnant women is usually found to be between 0.7 and 3.9%. The aim of our prospective study was to determine the interactions between pregnancy and chronic viral hepatitis C in 12 pregnant women., Results: In our study, chronic viral hepatitis C did not influence maternal or neonatal outcome. The mean gestational age was 38.4 +/- 3 weeks. During follow-up, mean serum ALT levels were significantly lower (36 +/- 17 mU/mL) during the last three months of pregnancy compared to before pregnancy (237 +/- 144 mU/mL, P < 0.002) and after pregnancy (141 +/- 62 mU/mL, P < 0.0005). During the third trimester, serum ALT levels were normal in 90% of the women. However, the persistence of viremia during pregnancy and a rebound in serum ALT during the post-partum period have been noticed., Conclusion: The normalization of serum ALT levels during pregnancy, the persistence of viremia, and a rebound in serum ALT during post-partum could be related to pregnancy-induced changes in the immune system.

In this review the authors describe the physiopathological mechanisms responsible for inflammatory lesions in primary glomerulonephritis. Primary glomerular nephropathies can be reproduced experimentally: models have been set up for non-proliferative kidney diseases such as minimal change disease or membranous glomerulopathies, and for proliferative kidney diseases such as Berger's disease. Studies performed with these models have resulted in the identification of inflammatory mechanisms creating glomerular lesions which may be acute (proteinuria) or progressive (glomerular sclerosis). These mechanisms include activation of resident cells, notably mesangial cells, and recruitment of circulating cells such as neutrophils, monocytes/macrophages and platelets. These cells participate in the local inflammatory reaction by releasing soluble mediators including biologically active lipids, such as eicosanoids, reactive oxygen and nitrogen derivatives, proteases, cytokines and vasoactive polypeptides. The importance of these mediators has been deduced from the fact that they are produced locally in excess, their introduction produces lesions and, above all, their suppression by inhibitory or antagonistic pharmacological agents reduces the severity of the lesions. Several observations have shown that the development of all the lesions can be prevented simply by blocking the activity of only one of these mediators. It is therefore possible to consider replacing the conventional glucocorticoid treatment, which has multiple pharmacological actions, by a more specific treatment directed against a single mediator.

TNF alpha is generated in inflammatory lesions of the glomerulus. Both resident mesangial cells and infiltrating macrophages contribute to this generation, when exposed to bacterial lipopolysaccharide and immune complexes, respectively. TNF alpha has multiple actions on glomerular cells and on distant target cells that appear to promote in turn either amplification or limitation of TNF alpha release and TNF alpha binding. For instance, there is in vitro evidence that locally generated reactive oxygen metabolites: 1) cause increased release of TNF alpha into the extracellular space by accelerating the cleavage of its cell-associated precursor, and 2) reduce the expression of both cell-associated and soluble TNF alpha receptors. Thus it might be expected that reactive oxygen metabolites released at the site of glomerular inflammation limit autocrine, juxtacrine and paracrine effects of TNF alpha and simultaneously increase its widespread release into the circulation.

Emphysematous pyelonephritis is a rare condition which in most cases occurs as a result of Escherichia coli infection of the urinary tract in patients known as being diabetic. The gas-filled abscesses carry a high mortality rate, especially when the antibiotic treatment is not combined with early surgery. We report a case where the failure of medical treatment led to curative nephrectomy. Unusually, diabetes was revealed by the pyelonephritis. Another particularity of this case was that the emphysematous pyelonephritis was associated with genitourinary tuberculosis. This association, of which no other example could be found in the literature, is discussed.

The clinical classification of malignant hypercalcaemias according to the presence or absence of bone lesions no longer corresponds to the physiopathology of these hypercalcaemias as it is known today. Both focal osteolysis and humoral hypercalcaemia involve a number of substances, such as prostaglandins, cytokines, growth factors, PTH-rp and calcitriol, the action of which is neither specific nor single. A knowledge of their role in the pathogenesis of hypercalcaemia should lead to the development of antagonists for therapeutic purpose and to a better understanding of their individual physiological effects, since some of these mediators are present in non-tumoral tissues. In humoral hypercalcaemia, PTH-rp seems to play a major role on kidneys and bones.

Unlabelled: The aim of this study was to test the self-blood pressure (Self-BP) measurement device Copal UA-251 (Philips). This device uses auscultatory method for BP measurement. It was compared to reference methods: intraarterial and Hawksley Random Zero in 38 patients, selected in two groups: group RO (n = 18), compared Copal to Random Zero. 20 simultaneous measurements were recorded, with devices inversion at eleventh BP measurement, in 18 treated or untreated hypertensive patients. Group IA (n = 20) included 20 patients and compared Copal to intra-aortic measurement. Three simultaneous measurements were recorded, before a coronarography was performed, in 20 normo or hypertensive patients., Results: (Table: see text). 1) A significant difference was recorded for SBP evaluated by Copal versus RO and for DBP measured by Copal versus IA. 2) A significant correlation was assessed between the different methods of measurement. 3) Differences between couples of RO-Copal values are not correlated to BP level, neither for SBP (r = 0.07), nor DBP (r = 0.05). Same results occur for IA-Copal values (SBP: r = 0.36, DBP: r = 0.30). 4) No order effect was found; no discrepancy between arms occurred in BP measurement., Conclusion: comparing intraaortic measure, Copal is efficient for SBP measurement, but overestimate DBP. Compared to R0, Copal overestimates SBP, but is efficient for DBP measurement. Regarding these results, a self-BP measurement is possible with this device.

Arm girth and circumference often leads to difficulties in Blood Pressure (BP) measurement in obese patients. In order to assess the best method of BP measurement, we have compared in a triplicate study, Intra-arterial Pressure (INTRA) to indirect measurements: Mercury Sphygmomanometer (SPH) and oscillometric device Bard Sentron (SEN). SPH and SEN were successively connected to the same cuff (inflatable bladder 14 x 31 cm). Cuff was positioned on contralateral arm to arterial puncture. 19 subjects were studied (18 female); mean age was 51.3 +/- 9 years (extremes: 37-69), mean weight 104 +/- 19 kg (84-147), weight index 40 +/- 4.7 kg/m2 (34-49), and brachial circumference 39 +/- 4 cm (33-47). First out-patient mean blood pressure measurement was 182/104 mmHg (148-264/80-132). Mean SPH BP were 158 +/- 34/91 +/- 3 (98-230, 72-112) and mean INTRA: 171 +/- 37/85 +/- 5 (122-256/56-118). Mean systolic and diastolic differences (S, D, mmHg) were: (Table: see text). 1) SPH systolic BP underestimates HUM systolic BP. 2) Mean SEN measurements are very closed to HUM values. 3) A great intra-individual variability occurs since more than 50 per cent systolic SPH values show discrepancy of more than 10 mmHg for systolic and diastolic HUM BP; the same discrepancies occur for SEN vs HUM. 4) Differences between couples of values (HUM-SEN, HUM-SPH) are not correlated to BP level, neither for systolic nor for diastolic BP. 5) No significant correlation occurs when BP deltas are compared to weight index or arm circumference.(ABSTRACT TRUNCATED AT 250 WORDS)