Showing papers by "Philippe Lesavre published in 2003"

Molecular Cytogenetic Aberrations in Autosomal Dominant Polycystic Kidney Disease Tissue

Abstract: 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.

Complement inhibition in renal diseases

Abstract: The activation of complement and its deleterious consequences have been observed in many renal diseases. Complement contributes to injury in several forms of glomerulonephritis (GN), in acute and chronic humoral rejection after renal transplantation, and at the time of ischaemiaureperfusion injury. It is also thought to accelerate the progression of chronic renal damage. Most of the evidence for the role of complement in enhancing injury comes from experimental data obtained in murine models, in which the addition of complement inhibitors blocks or reduces damage. The first evidence that excessive complement activation can be reversed in humans has been recently reported by Remuzzi et al. [1]. These authors reported a combined liver and kidney transplantation in a young child with haemolytic uraemic syndrome (HUS) and a mutation of factor H by which they were able to restore the defective factor H activity with no recurrence of the disease. The biological markers of complement activation normalized after transplantation as well. In contrast to inhibitors of the coagulation cascade, the clinical application of complement inhibitors has not yet started; this might explain why so little attention has been given by clinicians to this field. With major progresses made in the last 10 years on the engineering of molecules, it is likely that complement inhibition will be introduced in clinical practice soon. Here we would like to emphasize some of the aspects of complement relevant to renal diseases, for which specific inhibitors of complement might produce beneficial effects, but also the possible caveats related to the inhibition of an enzymatic cascade central to the normal function of the innate immune system. Complement

Myeloma cast nephropathy: clinical presentation

Abstract: Renal failure develops in approximately 45% of patients with multiple myeloma (MM). In nephrology departments treating patients with the most severe renal involvement, myeloma cast nephropathy (MCN) represents 63–87% of cases assessed by renal biopsy1. In the autopsy series studied by Ivanyi, MCN was found in 32% (18 of 57), renal amyloidosis in 11 % (six) and kappa light chain deposits (LCD) in 5% (three)2. Thus, MCN is the most frequent lesion in myeloma patients and is the major cause of renal failure. However, cast nephropathy is not specifiic to myeloma since it can be observed, albeit very rarely, in non-myeloma patients (see ref. 1). In recent decades MM and renal failure are discovered simultaneously more and more frequently. Nephrologists should therefore be aware of the diagnosis of MM, and the management of these patients requires close collaboration between hematologists and nephrologists.