Biomedical subjects

Philippe Lesavre

Publications and source records attributed to Philippe Lesavre.

23 records · Page 2Linked to original sources

PubMed2003

Molecular cytogenetic aberrations in autosomal dominant polycystic kidney disease tissue.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder characterized by focal cyst formation from any part of the nephron. The molecular bases include germinal mutation of either PKD1 or PKD2 genes, enhanced expression of several protooncogenes, alteration of the TGF-alpha/EGF/EGF receptor (EGFR) axis, and disturbed regulation of proliferative/apoptosis pathways. To identify new locations of ADPKD related oncogenes and/or tumor suppressor genes (TSG), comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) analyses were performed for a series of individual cysts (n = 24) from eight polycystic kidneys. By CGH, imbalances were detected predominantly on chromosomes 1p, 9q, 16p, 19, and 22q in all tissues. DNA copy number gain was seen on chromosomes 3q and 4q in five samples. The CGH data were supplemented by LOH analysis using 83 polymorphic microsatellite markers distributed along chromosomes 1, 9, 16, 19, and 22. The highest frequency of LOH was found on the 1p35-36 and 16p13.3 segments in cysts from seven samples. Allelic losses on 9q were detected in six, whereas deletions at 19p13 and 22q11 bands were observed in three polycystic kidneys. These results indicate that the deleted chromosomal regions may contain genes important in ADPKD initiation and progression.

Chromosome Aberrations↗

PubMed2002

Renal involvement in monoclonal (type I) cryoglobulinemia: two cases associated with IgG3 kappa cryoglobulin.

Renal involvement has been described rarely in monoclonal (type I) cryoglobulinemia, although this complication is frequent among patients with mixed (type II or III) cryoglobulin. We report two patients with glomerulonephritis and monoclonal IgGkappa cryoglobulin. Both patients presented with nephrotic syndrome, microscopic hematuria, and impaired renal function. Hepatitis C serology was negative, bone marrow aspiration was normal, and the renal biopsy specimen showed membranoproliferative glomerulonephritis with glomerular subendothelial deposits of monoclonal IgGkappa. In both cases, circulating cryoglobulin and monotypic tissue deposits were found to be IgG3kappa, suggesting that this isotype may have a particular propensity to cause this type of membranoproliferative glomerulonephritis. Although 18 cases of type I cryoglobulinemia with biopsy-proven glomerulonephritis have been reported to date, this is the first characterization of immunoglobulin heavy-chain isotype in this disease.

Aged↗

PubMed2002

SLE and idiopathic nephrotic syndrome: coincidence or not?

BACKGROUND: The association of systemic lupus erythematosus (SLE) with minimal change disease (MCD) and/or focal and segmental glomerulosclerosis (FSGS) has been described in isolated case reports. The relevance of this association is still debated. METHODS: We performed a retrospective and descriptive study of 11 patients with SLE who experienced idiopathic nephrotic syndrome (iNS) in an effort to determine the relevance of this unusual combination. RESULTS: All patients fulfilled at least four criteria (renal abnormalities excluded) of the American Rheumatologic Association for the diagnosis of SLE, and all had severe nephrotic syndrome (mean proteinuria, 9.23 +/- 6 g of protein/24 h; serum albumin concentration, 1.48 +/- 0.6 g/dL). None had a past medical history of lupus nephritis or a cause for secondary FSGS. Renal histological examination showed MCD (4 patients) or FSGS (7 patients) without mesangial proliferation. Immunofluorescence was negative in 8 patients. In 3 patients, immune deposits (immunoglobulin G, immunoglobulin M, C3, and C1q) were present, but confined to the mesangium without glomerular changes on light microscopy. The abrupt onset of nephrotic syndrome coincided with the appearance of SLE in 6 patients (group 1) and recurrence of SLE in 3 patients (group 2). Two patients in group 1 experienced SLE recurrence with concomitant relapse of nephrotic syndrome. In only 2 patients (group 3) were the two diseases independent. CONCLUSION: These results suggest that a relevant association exists between both diseases, and SLE could be a precipitating factor for iNS.

Adolescent↗

PubMed2002

Long-term renal injury in ANCA-associated vasculitis: an analysis of 31 patients with follow-up biopsies.

BACKGROUND: We reported previously that in renal disease in relation to antineutrophil cytoplasm auto-antibodies (ANCA)-associated vasculitis, renal outcome correlates better with the percentage of normal glomeruli than with separate active lesions. This may imply that glomeruli, once affected by necrotizing and crescentic lesions, are irreversibly damaged. We quantified and evaluated the course of renal lesions in the present study. METHODS: We retrospectively analysed 31 patients with renal disease in relation to ANCA-associated vasculitis, all treated with immunosuppressive drugs. In all patients, a renal biopsy was performed at diagnosis. A follow-up biopsy was performed in all patients on the indication of a suspected renal relapse, after a mean interval of 31 months. RESULTS: The mean percentage of normal glomeruli in the renal biopsy did not change over time (29% in the initial and 30% in the follow-up biopsy). The mean percentage of glomeruli with crescents, however, significantly decreased from 57 to 30% (P<0.001). The percentage of glomerulosclerosis significantly increased from 12 to 39% (P<0.001). The data were independent of diagnosis, gender, age, time interval between the biopsies, and treatment. CONCLUSIONS: This is the first study to quantify glomerular changes between two time points in patients with renal vasculitis. Our results suggest that, on average, no new glomeruli are recruited into the active disease process. The sum of the percentage of crescentic and sclerotic glomeruli in the initial biopsies is larger than the percentage of sclerotic glomeruli in the follow-up biopsies. Thus, therapy seems not only to prevent normal glomeruli from being recruited into the active disease process for a certain time, but seems also to allow part of the active lesions to revert into a normal phenotype, although another part of the active lesions will be transformed to a chronic phenotype.

Adult↗

PubMed2002

Mesangial IgG glomerulonephritis: a distinct type of primary glomerulonephritis.

Fourteen cases of mesangial IgG glomerulonephritis characterized by exclusive or predominant mesangial IgG deposits are reported. The median age at onset was 19 yr (range, 13 to 47 yr). No patient exhibited evidence of systemic lupus erythematous or other systemic diseases. Proteinuria was present in all cases (median, 2.4 g/d; range, 1 to 13 g/d), microscopic hematuria in 12 cases, and macroscopic hematuria in two cases. Five patients were hypertensive at the time of referral. In all cases, renal biopsies revealed mesangial IgG deposits and varying degrees of mesangial matrix expansion, in the absence of significant mesangial cell proliferation. Complement component (mainly C3) deposits were present in virtually all cases. Subepithelial deposits were also noted in nine cases. IgG deposits were polyclonal and consisted mainly of IgG1 and IgG3 subclasses. In electron-microscopic analyses, deposits were electron dense and granular. Treatment was purely supportive. After a mean follow-up period of 11 yr, seven patients had experienced progression to chronic renal failure, including four who had reached end-stage renal failure. Three patients exhibited persistently normal renal function. For one patient, a symptomatic recurrence of mesangial IgG deposits in the renal graft was diagnosed 4 yr after renal transplantation. Such a recurrence highlights the specificity of this type of glomerulonephritis. Mesangial IgG glomerulonephritis is a distinct, albeit rare, type of glomerulonephritis that exhibits far from benign outcome and may recur in renal transplants.

Adolescent↗