Prognostic value of plasminogen activator inhibitor type 1 mRNA in microdissected glomeruli from transplanted kidneys.

BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) exerts antifibrinolytic and profibrotic activities. Inside the glomerulus, PAI-1 is mainly synthesized by mesangial cells. We hypothesized that thrombin, via its receptor protease activated receptor type 1 (PAR-1), present on the membrane of glomerular cells, is an important mediator of PAI-1 synthesis. METHODS: Using the technique of Peten et al., we microdissected the glomeruli of 23 kidney transplanted patients admitted in our department from 1993 to 1997, and we followed-up these patients for up to 5 years, with sometimes iterative renal biopsies. With this technique, we also microdissected the glomeruli of three patients who have had a nephrectomy for cancer (control patients). We investigated mRNA expression of the PAI-1, the thrombin receptor PAR-1, the alpha2 chain of type IV (alpha2 IV) collagen, and of a housekeeping gene (cyclophilin) by reverse transcription-polymerase chain reaction. The results were correlated with the renal function and the histological findings classified into acute rejection (9 biopsies), chronic rejection (22 biopsies), or normal (8 biopsies). RESULTS: A significant up-regulation of PAI-1 and alpha2 IV collagen mRNA was observed in acute rejection (P<0.05) when compared to normal kidneys. A positive correlation exists between alpha2 IV collagen mRNA level and the degree of cellular infiltration. A negative correlation was found between the level of mRNA of PAR-1 and the degree of vascular thrombosis (P=0.005) and glomerulosclerosis (P=0.04). A positive correlation was found between the degradation of renal function and the mRNA level of PAI-1 at the time of the renal biopsy (P<0.05). CONCLUSIONS: These results suggest that glomerular PAI-1 mRNA may be predictive of the long-term renal graft function.

Association of a POEMS syndrome and light chain deposit disease: first case report.

Monoclonal immunoglobulin (Ig) deposition diseases are characterized by deposition in tissues of excessive amounts of the Ig, compromising organ functions. Light chain deposition disease (LCDD) and AL amyloidosis are the commonest [Buxbaum 1992]. LCDD is usually characterized by rapidly progressive renal failure with glomerular and tubular deposits of Ig fragments mostly composed by kappa light chain. Monoclonal Ig production can also be observed associated with various symptoms, that, taken together, have been described as the Crow-Fukase syndrome or POEMS syndrome. It associates polyneuropathy, organomegaly, endocrinopathy, monoclonal Ig, and skin changes. In POEMS syndrome, renal abnormalities are rare and are reported as a moderate renal insufficiency with mild proteinuria or acute functional renal insufficiency leading in some cases to end-stage renal failure [Fukatsu et al. 1991]. Although a monoclonal Ig is produced, no Ig deposit disease had been described in POEMS syndrome except a case of AL amyloidosis [Toyokuni et al. 1992]. Here, to our knowledge, we report the first case of an LCDD associated with a POEMS syndrome. Although an autologous bone marrow graft was realized, the monoclonal component reappeared and was responsible for end-stage renal disease, cachexia and death.

[Diffuse colitis associated with mycophenolate mofetil treatment: apropos of 1 case]. / Colite diffuse associée à un traitement par mycophénolate mofétil: a propos d'une observation.

Mycophénolate mofétil (MMF) or Cellcept is a potent immunosuppressor that inhibits purin synthesis used to prevent human allograft rejection. The most important secondary effects include haematological and intestinal disorders. Among them, diarrhea is the most common. It is dose-dependant and appears commonly during the first 2 months of treatment. Its physiopathology remains unclear. We reported a case of colitis, 6 months after a kidney transplantation. The patient was treated since day 2 with 2 grams per day of MMF. Morphological analysis showed a diffuse colitis from the coecum to the rectum. Histological samples confirmed a colitis with atrophic crypts but with mucosal secretions and some cryptic abscesses. No granuloma or CMV inclusion was founded. Histochemical immunostaining for CMV was negative. Finally, symptoms regressed within 5 days after tapering down MMF dose in association with metronidazole treatment. The role of MMF in inducing colitis is discussed.