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P Ronco

Publications and source records attributed to P Ronco.

At least 19 recordsLinked to original sources
PubMed2006

Renal cortical regulation of COX-1 and functionally related products in early renovascular hypertension (rat).

Renal volume regulation is modulated by the action of cyclooxygenases (COX) and the resulting generation of prostanoids. Epithelial expression of COX isoforms in the cortex directs COX-1 to the distal convolutions and cortical collecting duct, and COX-2 to the thick ascending limb. Partly colocalized are prostaglandin E synthase (PGES), the downstream enzyme for renal prostaglandin E(2) (PGE(2)) generation, and the EP receptors type 1 and 3. COX-1 and related components were studied in two kidney-one clip (2K1C) Goldblatt hypertensive rats with combined chronic ANG II or bradykinin B(2) receptor blockade using candesartan (cand) or the B(2) antagonist Hoechst 140 (Hoe). Rats (untreated sham, 2K1C, sham + cand, 2K1C + cand, sham + Hoe, 2K1C + Hoe) were treated to map expression of parameters controlling PGE(2) synthesis. In 2K1C, cortical COX isoforms did not change uniformly. COX-2 changed in parallel with NO synthase 1 (NOS1) expression with a raise in the clipped, but a decrease in the nonclipped side. By contrast, COX-1 and PGES were uniformly downregulated in both kidneys, along with reduced urinary PGE(2) levels, and showed no clear relations with the NO status. ANG II receptor blockade confirmed negative regulation of COX-2 by ANG II but blunted the decrease in COX-1 selectively in nonclipped kidneys. B(2) receptor blockade reduced COX-2 induction in 2K1C but had no clear effect on COX-1. We suggest that in 2K1C, COX-1 and PGES expression may fail to oppose the effects of renovascular hypertension through reduced prostaglandin signaling in late distal tubule and cortical collecting duct.

Adrenergic beta-Antagonists↗
PubMed2006

Minimal change nephrotic syndrome and classical Hodgkin's lymphoma: report of 21 cases and review of the literature.

Minimal change nephrotic syndrome (MCNS) is described as a paraneoplastic manifestation of classical Hodgkin's lymphoma (cHL). We reassessed the pathophysiological and clinical significance of this association. A retrospective study was performed to evaluate a cohort of adult patients who developed MCNS and cHL. Twenty-one patients recruited in 15 French centers were analyzed. cHL was associated with inflammatory and general symptoms in most cases. The morphological subtype was predominantly nodular sclerosis (71.4%). MCNS appeared before the diagnosis of lymphoma in eight patients (38.1%) and in this case, it was characterized by a nephrotic syndrome (NS) frequently resistant (50%) or dependent (12.5%) to steroid treatment. Interestingly, diagnosis (3-120 months after MCNS) and effective treatment of the hemopathy were associated with the disappearance of the MCNS. cHL was diagnosed before MCNS in nine patients (42.9%), and in this case, glomerulopathy was associated with cHL relapse in 55.5% of cases. In four patients (19%), the two diseases occurred simultaneously. Extensive immunohistochemical study of lymph nodes was performed in eight patients and did not reveal particular features. In conclusion, MCNS associated with cHL is frequently dependent or resistant to steroid regimen, but remission of NS is obtained with the cure of lymphoma.

Adolescent↗
PubMed2005

Dysregulation of IL-2/IL-2R system alters proliferation of early activated CD4+ T cell subset in patients with end-stage renal failure.

BACKGROUND/AIM: Although CD4+ T cells are preactivated in patients with end-stage renal failure (ESRF), these patients present an impairment of T cell immune response, which is partly responsible for the higher incidence of infection in this population. The aim of the present study was to analyze the mechanisms underlying the altered function of activated CD4+ T cells in patients with ESRF. METHODS: Thirty patients undergoing chronic hemodialysis (HD) and 20 patients with ESRF were compared with 15 sex- and age-matched controls. CD4+ T cell early activation (CD69, CD25), interleukin-2 (IL-2)/IL-2 receptor (IL-2R) system, and proliferation capacity of CD69+/CD4+ T cells were assessed ex vivo after blood draw sampling, in culture conditions and after phytohemagglutinin (PHA) stimulation. RESULTS: Although the CD4+ T cell count was lower in chronic HD patients than in predialysis patients and controls (p = 0.007), CD4+ T cells showed a pre-activation state as demonstrated by higher percentage of CD69+/CD4+ T cells and CD25+/CD4+ T cells in chronic HD patients compared with the other groups ex vivo. Furthermore, CD69+/CD4+ T cells from chronic HD patients spontaneously released more IL-2 (22 +/- 6 pg/ml) than those from pre-dialysis patients (12 +/- 4 pg/ml, p = 0.005) and controls (5 +/- 3 pg/ml, p = 0.001). However, after PHA stimulation, CD69+/CD4+ T cells from chronic HD patients expressed lower cell surface CD25 density, and were unable to show further activation. Indeed, these cells produced less IL-2 and released more soluble IL-2R, and correlatively with IL-2 production, they showed lower proliferation capacity compared with predialysis patients (p = 0.001) and controls (p < 0.001). They also displayed decreased responsiveness to exogenous human recombinant IL-2. The restoration of the PHA stimulation index of CD69+/CD4+ T cells from chronic HD patients in the presence of normal human serum as well as the decreased stimulation index of CD69+/CD4+ T cells from control subjects incubated with HD serum, strongly suggest that uremic toxins and mediators induced by HD affect the IL-2/IL-2R pathway. CONCLUSION: These findings demonstrate the presence, in chronic HD patients, and to lesser extent, in predialysis patients, of abnormally high proportion of spontaneously preactivated CD4+ T cells whose proliferation and further activation are blunted due to dysregulation of the IL-2/IL-2R system.

Antigens, CD↗
PubMed2001

delta Ef1 binds to a far upstream sequence of the mouse pro-alpha 1(I) collagen gene and represses its expression in osteoblasts.

The transcription of type I collagen genes is tightly regulated, but few cis-acting elements have been identified that can modulate the levels of expression of these genes. Generation of transgenic mice harboring various segments of the mouse pro-alpha1(I) collagen promoter led us to suspect that a repressor element was located between -10.5 and -17 kilobase pairs. Stable and transient transfection experiments in ROS17/2.8 osteoblastic cells confirmed the existence of such a repressor element at about -14 kilobase pairs and showed that it consisted in an almost perfect three-time repeat of a 41-base pair sequence. This element, which we named COIN-1, contains three E2-boxes, and a point mutation in at least two of them completely abolished its repressor effect. In gel shift assays, COIN-1 bound a DNA-binding protein named delta EF1/ZEB-1, and mutations that abolished the repressor effect of COIN-1 also suppressed the binding of delta EF1. We also showed that the repressor effect of COIN-1 was not mediated by chromatin compaction. Furthermore, overexpression of delta EF1 in ROS17/2.8 osteoblastic cells enhanced the inhibitory effect of COIN-1 in a dose-dependent manner and repressed the expression of the pro-alpha 1(I) collagen gene. Thus, delta EF1 appears to repress the expression of the mouse pro-alpha 1(I) collagen gene, through its binding to COIN-1.

Animals↗
PubMed2001

[How to slow the progression of chronic renal insufficiency].

In patients with chronic renal failure, three kinds of treatments can slow the progression of renal insufficiency: optimal control of blood pressure; use of converting enzyme inhibitors; low-protein diet. The MDRD study strongly suggests that blood pressure should not be higher than 130/85 mmHg in patients with chronic renal failure, and than 125/75 mmHg in patients with chronic renal failure and proteinuria above 1 g/d. Converting enzyme inhibitors have been shown to be beneficial to patients with IDDM and either microalbuminuria or overt diabetic nephropathy and to patients with chronic renal failure and proteinuria above 1 g/d. A diet containing less than 1 g/kg/d of proteins should be prescribed to patients with chronic renal failure, and this protein content should be lowered to 0.75 g/kg/d (or to 0.60 g/kg/j in some cases) when creatinine clearance falls below 25 mL/min.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Idiopathic membranous glomerulonephritis is associated with altered patterns of self-reactive IgM and IgG antibody repertoires.

Idiopathic membranous glomerulonephritis (MGN) is an immune complex nephropathy characterized by the subepithelial deposition of immunoglobulin (Ig)G. The pathogenesis of the disease remains largely unknown, but recent evidence suggests that human MGN may involve an autoimmune component. In the present study, we have analyzed the IgM and IgG antibody repertoires of patients with MGN towards self- and nonself-antigens using a technique of quantitative immunoblotting on a panel of whole human tissue or solubilized bacterial cell extracts as sources of antigens. Data were compared by means of multiparametric statistical analysis. We demonstrate that the antibody repertoires of self-reactive IgM and IgG in plasma of patients with MGN exhibit significantly altered patterns of reactivity, as compared with those of healthy controls. In contrast, multiparametric statistical analysis does not discriminate the reactivity patterns of IgM and IgG in plasma of patients and healthy controls towards nonself antigens. These observations indicate that a failure in the regulation of physiological self-reactivity is associated with immune complex nephropathy in MGN.

Adult↗
PubMed2001

No evidence for point mutations of the calcium-sensing receptor in familial idiopathic hypercalciuria.

BACKGROUND: Idiopathic hypercalciuria (IH) is frequently associated with nephrolithiasis. As 40% of patients have a positive familial history of IH, an autosomal dominant mode of inheritance has been suggested. Numerous genes have been studied in this regard but none have been found to be linked to IH. Mutation of the calcium-sensing receptor (CaR) has never been studied. Therefore, we conducted a study to detect such mutations. METHODS: Seven families with IH and nephrolithiasis were recruited in a prospective study. Forty-two family members underwent 24-h urine calcium measurement. Twenty-five of them with 24-h hypercalciuria also underwent extensive metabolic evaluation. Blood samples were collected in one or two affected family members in each family and exons 2-7 of the CaR gene were sequenced. RESULTS: In the seven families, at least one parent and more than half of the children had hypercalciuria (21/30), consistent with autosomal dominant inheritance. Among the nine affected family members whose CaR gene has been studied, all nine had absorptive hypercalciuria, three also had fasting hypercalciuria, and one had renal phosphorous leak. No mutation of the CaR gene was detected in these seven families. Two previously reported polymorphisms were detected, each of them in five families: A986S and C-to-T change at -60 in intron 5. CONCLUSION: In these seven families, IH is not related to the CaR gene mutation. Although we cannot exclude that point mutations can be found in other families, familial IH does not seem to be generally associated with CaR mutation.

Adult↗
PubMed2000

Abnormal expression of glomerular basement membrane laminins in membranous glomerulonephritis.

BACKGROUND: Proteinuria associated with glomerular diseases is secondary to alterations of the charge-selective and/or size-selective properties of the glomerular basement membrane (GBM), but molecular alterations that are responsible for these functional changes are still poorly understood. Analysis of mice harbouring a null mutation in the gene encoding the beta 2 chain of laminin has suggested that the presence of abnormal laminin chains within the GBM can be responsible for proteinuria. METHODS: We have investigated whether abnormal laminin ss chains could be detected by immunohistochemistry within the GBM of patients with proteinuria and minimal change disease (five patients), focal and segmental glomerulosclerosis (five patients), or primary membranous glomerulonephritis (10 patients). Three patients with mesangiocapillary glomerulonephritis and three patients with IgA nephropathy were also studied as controls. RESULTS: We showed that the GBM of all 10 patients with membranous glomerulonephritis, but not of patients with other glomerulopathies, contained laminin beta 1, which is normally expressed only during metanephros development. The re-expression of the beta 1 chain of laminin was not associated with that of the embryonic alpha 1 chain of type IV collagen, or with the loss of expression of vimentin and synaptopodin, two markers of differentiated podocytes. CONCLUSIONS: The presence of new laminin isoforms within the GBM of patients with membranous glomerulonephritis could play a role in the occurrence of proteinuria, by modifying either the sieving properties of the GBM or the interactions between podocytes and the GBM.

Adult↗
PubMed2000

Microscopic polyangiitis with alveolar hemorrhage. A study of 29 cases and review of the literature. Groupe d'Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P).

Microscopic polyangiitis (MPA) is a systemic small-vessel vasculitis primarily associated with necrotizing glomerulonephritis and pulmonary capillaritis. In this retrospective study of 29 patients with MPA and alveolar hemorrhage (AH), we characterized the pulmonary manifestations at presentation and assessed the short- and long-term outcome. AH was diagnosed when bronchoalveolar lavage was macroscopically bloody, or contained hemosiderin-laden macrophages, in the absence of lung infection or pulmonary edema. MPA was diagnosed when AH was associated with focal segmental necrotizing glomerulonephritis at kidney biopsy or pathologically proved small-vessel vasculitis. There were 17 women and 12 men, with a mean age of 55.8 +/- 16.7 years. The onset was rapidly progressive, but in 8 (28%) patients, symptoms preceded the diagnosis for more than 1 year. The most constant systemic findings associated with AH were glomerulonephritis in 28 (97%) patients; fever (62%); myalgia and arthralgia (52%); weight loss (45%); ear, nose, and throat symptoms (31%); and skin involvement (17%). Lung opacities were bilateral in 26 (90%) patients, most frequently involving the lower part of the lungs. Bronchoalveolar lavage, performed in 27 patients, was hemorrhagic in 25 (93%), and contained numerous siderophages in others. Most patients were severely anemic (mean hemoglobin, 8.1 +/- 1.8 g/dL). ANCA, present in 27 (93%) patients, gave a perinuclear (14), cytoplasmic (11), or mixed (1) pattern. Mean serum creatinine level was 407 +/- 415 mumol/L. Renal biopsy confirmed the presence of necrotizing glomerulonephritis in 27 patients. Patients were treated with corticosteroids (100%), cyclophosphamide (79%), plasmapheresis (24%), dialysis (28%), and mechanical ventilation (10%). The overall mortality rate was 31% (9 patients). Deaths were related to vasculitis (5 patients) or side effects of treatment (4). Deaths were more frequent in aged or mechanically ventilated patients. The 5-year survival rate was 68%. The recovery of respiratory function among survivors was clinically considered complete in 20 (69%) patients. However, 7 patients (24%) had persistent alterations on pulmonary function tests. Of the 11 patients who had relapses, 2 died from AH.

Adult↗
PubMed2000

Identification of a short cis-acting element in the human vasopressin type 2 receptor gene which confers high-level expression of a reporter gene specifically in collecting duct cells.

In the kidney, water reabsorption is mainly regulated by the binding of arginine vasopressin to vasopressin type 2 (V2) receptors. These receptors are expressed selectively in principal cells of the collecting ducts. To identify molecular mechanisms responsible for the cell-specific expression of the V2 receptor, we have analyzed the proximal promoter of the corresponding gene. We report the identification of a 33-bp enhancer [collecting duct tissue-specific element 1 (CSE1)] that induced high levels of expression of the luciferase reporter gene in three collecting duct cell lines, but not in other renal cell lines. In gel shift assays, CSE1 bound a DNA-binding protein expressed selectively in collecting duct cell lines, and a 7-bp mutation, which abolished the activity of CSE1 in transient transfection experiments, also abolished the binding of this protein. Furthermore, decoy experiments performed using CSE1 showed that this sequence was involved not only in the expression of a construct containing 4.2 kb of the V2 receptor proximal promoter, but also in the expression of the endogenous V2 receptor gene. CSE1 appears to act mostly by counteracting the inhibitory effects of a strong ubiquitous repressor element that we called CIE1. Collectively, these results identify the first functional collecting duct-specific cis-acting element.

3T3 Cells↗
PubMed2000

Nonnephrotoxic, dynamic, contrast enhanced magnetic resonance urography: use in nephrology and urology.

PURPOSE: We assessed the value of breath-hold, gadolinium (Gd) enhanced magnetic resonance urography for diagnosing urinary tract disease. MATERIALS AND METHODS: Dynamic magnetic resonance urography was performed in 38 consecutive patients presenting with urological disease in whom excretory urography was contraindicated. Renal function was impaired in 18 cases with a serum creatinine of 140 to 400 micromol./l. Fast spoiled, gradient echo sequences were acquired during breath-holding 5, 10 and 15 minutes after intravenous injection of 10 ml. of a Gd chelate. Opacification of the collecting system was evaluated using a scale of 0 to 3. Diagnostic value of the examinations was also analyzed. RESULTS: Dynamic magnetic resonance urography was sufficient for making the diagnosis in 95% of cases. We identified 71 pathological findings and the surgical anastomosis was always well visualized. Mean image quality score was 2.34 points for renal calices, 2.86 for renal pelves and 2.48 for ureters. Image quality significantly improved after injecting a diuretic. CONCLUSIONS: Gd enhanced magnetic resonance urography provides quality dynamic imaging of the urinary tract. It is a new approach for diagnosing urinary tract disorders in patients in whom excretory urography should be avoided.

Adult↗
PubMed1999

A solid-phase immobilized epitope immunoassay (SPIE-IA) permitting very sensitive and specific measurement of angiotensin II in plasma.

We have developed a new enzyme immunometric assay for angiotensin II (AII) based on SPIE-IA technology (solid-phase immobilized epitope-immunoassay). A monoclonal antibody with optimal properties (mAb3 131) was selected from a series of 19 anti-AII mAbs. The mAb had to be purified from ascitic fluid in a specific manner in order to remove endogenous AII from the antibody-binding sites. We established a sensitive (minimum detectable concentration 0.5 pg/ml) and precise (CV below 15% in the 2-100 pg/ml range) SPIE-IA. Using different AII-related peptides, we observed that this new assay has a specificity profile that compares favourably with the corresponding competitive immunoassay. We have used the assay to measure AII in 42 plasma samples, and demonstrated a good correlation with values obtained using a commercial radioimmunoassay. Assay specificity was supported by HPLC fractionation experiments, confirming the absence of interference induced by endogenous AII-related products.

Acetylcholinesterase↗
PubMed1999

[Factors of progression and chronic renal insufficiency and their prevention].

End-stage renal failure is a major cause of health-related expenditures in the Western countries. It can be prevented in many instances by therapeutic intervention first settled in animal models. Murine experimental models of nephron loss have led to the identification of several factors involved in renal disease progression. They include increased glomerular capillary hydrostatic pressure, glomerular hypertrophy, high blood glucose, high-level proteinuria, hypoxia, and genetic factors. The role of glomerular capillary hypertension and hypertrophy cannot, however, be established with certainty in man. Clinical studies have shown that male gender, increased systemic blood pressure, severe urinary albumin loss, type of initial nephropathy, diabetes, and genetic factors, all accelerate progression of renal disease to end-stage renal failure. It is now feasible to halt the progression of renal insufficiency. Clinical trials have demonstrated the beneficial effects of angiotensin converting enzyme inhibitors, particularly in those patients with high-level proteinuria, and of blood glucose control in diabetic patients. The place that restricted protein diet and lipid lowering intervention should take, remains debated. Further clinical trials aimed at testing the efficacy of new drugs including endothelin receptor antagonists are warranted in those patients with vascular or tubulo-interstitial renal diseases.

Combined Modality Therapy↗