The influence of cytomegalovirus infections on patient and renal graft outcome: a 3-year, multicenter, observational study (Post-ECTAZ Study).

Cytomegalovirus (CMV) infections posttransplant may increase the risk of acute rejection, graft failure, patient death, opportunistic infections, malignancy, diabetes, and cardiovascular complications. ECTAZ, a multicenter, randomized trial compared safety and efficacy at 12 months (M12) of two doses daclizumab (54 patients, group D) with thymoglobulin (55 patients, group T), plus cyclosporine (CsA), mycophenolate mofetil and steroids in first cadaveric kidney transplant patients. D+/R- patients received oral ganciclovir prophylaxis for 90 days. Post-ECTAZ is a 36-month, multicenter, observational study including recipients who participated in ECTAZ trial. We studied the indirect effects of CMV infections, whether recipients experienced (CMVi+) or not (CMVi-) a CMV infection/syndrome/disease. We compared 49 patients in the group CMVi+ with 54 patients in the group CMVi-. At month 36 (M36), patient survival, graft survival and renal function were comparable. The incidence of biopsy-proven acute rejection was 16.3% in the CMVi+ group versus 24.1% in the CMVi- group (not significant). The incidence of infections was increased in the CMVi+ group (P = .004), but not diabetes, malignancies, and cardiovascular complications. Our study shows at M36 that CMV infection/syndrome/disease episodes were associated with a higher incidence of infections but no difference for other long-term complications. Our data suggest that anti-CMV prophylaxis could decrease the risk for long-term related CMV complications.

Renal transplantation in patients with AA amyloidosis nephropathy: results from a French multicenter study.

Although end-stage renal disease related to AA amyloidosis nephropathy is well characterized, there are limited data concerning patient and graft outcome after renal transplantation. We performed a multicentric retrospective survey to assess the graft and patient survival in 59 renal recipients with AA amyloidosis. The recurrence rate of AA amyloidosis nephropathy was estimated at 14%. The overall, 5- and 10-year patient survival was significantly lower for the AA amyloidosis patients than for a control group of 177 renal transplant recipients (p = 0.0001, 0.028 and 0.013, respectively). In contrast, we did not observe any statistical differences in the 5- and 10- year graft survival censored for death between two groups. AA amyloidosis-transplanted patients exhibited a high proportion of infectious complications after transplantation (73.2%). Causes of death included both acute cardiovascular events and fatal septic complications. Multivariate analysis demonstrated that the recurrence of AA amyloidosis on the graft (adjusted OR = 14.4, p = 0.01) and older recipient age (adjusted OR for a 1-year increase = 1.06, p = 0.03) were significantly associated with risk of death. Finally, patients with AA amyloidosis nephropathy are eligible for renal transplantation but require careful management of both cardiovascular and infectious complications to reduce the high risk of mortality.

Angiotensin-2 receptors (AT1-R and AT2-R), new prognostic factors for renal clear-cell carcinoma?

BACKGROUND: The growth factor Angiotensin-2 signals through Angiotensin receptor type 1 (AT1-R) in a broad range of cell types and tumours and through the type-2 receptor (AT2-R) in a more restricted group of cell types. Although numerous forms of cancer have been shown to overexpress AT1-R, expression of AT1-R and AT2-R by human renal clear-cell carcinoma (RCCC) is not well understood. In this study, the expression of both angiotensin receptors was quantified in a retrospective series of RCCC and correlated with prognostic factors. METHODS: Angiotensin receptor type 1 and AT2-R expressions were quantified on tumour tissues by immunohistochemistry (IHC), western blot and quantitative reverse transcriptase PCR (qRT-PCR). IHC results were correlated to Fuhrman's grade and patient progression-free survival (PFS). RESULTS: A total of 84 RCCC were analysed. By IHC, AT1-R and AT2-R were expressed to a greater level in high-grade tumours (AT1-R: P<0.001, AT2-R: P<0.001). Univariate analysis showed a correlation between PFS and AT1-R or AT2-R expression (P=0.001). By multivariate analysis, only AT2-R expression correlated with PFS (HR 1.021, P=0.006) and cancer stage (P<0.001). By western blot, AT1-R and AT1-R were also found to be overexpressed in higher Fuhrman's grade (P<0.01 and P=0.001 respectively). By qRT-PCR, AT1-R but not AT2-R mRNA were downregulated (P=0.001 and P=0.118, respectively). CONCLUSION: Our results show that AT1-R and AT2-R proteins are overexpressed in the most aggressive forms of RCCC and that AT2-R expression correlates with PFS. AT1-R or AT2-R blockage could, therefore, offer novel directions for anti-RCCC therapy.

Interstitial fibrosis quantification in renal transplant recipients randomized to continue cyclosporine or convert to sirolimus.

Conversion from cyclosporine (CsA) to sirolimus at week 12 after kidney transplantation is associated with a significant improvement in renal function. The aim of this analysis was to investigate the effect of this conversion on interstitial fibrosis (IF), a hallmark of chronic allograft injury, in patients taking part in the CONCEPT trial. This multicenter, prospective, trial included 193 renal recipients randomized at week 12 to switch from CsA to sirolimus or to continue CsA, with mycophenolate mofetil. Routine biopsy with automated, quantified assessment of IF by a program of color segmentation was performed at 1 year in 121 patients. At 1 year, renal function was significantly improved in the conversion group as assessed by estimated GFR (MDRD) and measured GFR. Biopsy results, however, showed no between-group difference in percentage of IF. Calculated GFR at 1 year was significantly associated with the percentage of IF (p = 0.004, R(2)= 0.07). By multivariate analysis diabetic patients had more fibrosis than non-diabetic patients. In conclusion, although kidney transplant patients converted from CsA to sirolimus showed significant improvement in renal function, we found no difference of IF on 1-year biopsies.

[Epidemiologic description of amyloidosis diagnosed at the University Hospital of Rennes from 1995 to 1999]. / Epidémiologie descriptive des amyloses diagnostiquées au CHU de Rennes de 1995 à 1999.

INTRODUCTION: The frequency of amyloidosis is not well known in France. We compiled a register of amyloidosis diagnosed from 1995 to 1999 in the University Hospital of Rennes. PATIENTS AND METHODS: This retrospective study was performed between 01 January 1995 and 31 december 1999. Diagnosis was assessed on positivity of red Congo by anatomopathology. Immunohistochemistry allowed the definition the type of amyloidosis. Clinical data, staging and outcome of patients were analysed. RESULTS: Forty-three amyloidosis were diagnosed (27 women, 16 men) with an incidence of 8,6 new cases per year. Mean age was 63.7 years. Five diagnosis were realised in 1995, six in 1996, six in 1997, 12 in 1998, 14 in 1999. Twenty amyloidosis were AL type (46.5%), seven AA (16.3%), 1 beta2 microglobulin type, 15 (35%) remained of undetermined type. Thirty-three amyloidosis (77%) were systemic, 10 were localized to one organ (23%). When diagnosis was made, biopsies concerned affected organs in 86% of the cases, accessory sites (labial salivary glands, bone marrow) in only 14% of the cases. Twenty-five patients died (58%). Two deaths were treatment-related, 16 to amyloidois, seven patients died of another complaint. CONCLUSION: Increased incidence of amyloidosis needs to be confirmed. We emphasize the importance of immunohistochemical typing on frozen samples, the value of accessory biopsies and the need for complete extension staging.

Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression.

BACKGROUND: The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. METHODS: This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day. RESULTS: At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P<0.001), fever (25.2% vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and thrombocytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction). CONCLUSION: Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.

["De novo" cancer after organ transplantation]. / Les cancers "de Novo" après transplantation d'organe.

From March 1972 to 1st of January 1996, 804 kidney, liver and pancreas transplants were performed in 690 patients. 39 post transplant cancers occurred in 27 patients. 21 skin tumors (15 squamous cell carcinoma, 4 basocellular carcinomas, 1 squamous carcinoma, 1 melanoma), 4 squamous cancers (anus, esophagus, tongue, and parotid), 4 post-transplant lymphoproliferative disorders, 1 non-Hodgkin's lymphoma T, 4 gynecological tumors (breast, ovarian peritoneal carcinomatosis, 2 uterine cervix cancers), 4 miscellaneous tumors (larynx, right colon, brain, prostate, own kidney). 14 patients died (14/27: 52%). Post transplant de novo cancers are a major risk in transplant patients These cancers are mainly represented by skin tumors and lymphomas. Skin cancers are mainly spinocellular and occur in the areas which are exposed to the sun. Post transplant lymphoproliferative disorders are very close to Burkitt's lymphoma, they produced B lymphocyte proliferation due to the reduction of the control of T lymphocytes and induced by Epstein-Barr virus. They can disappear with the diminution of immunosuppression.

[Calcified intertrigo, a rare cause of cutaneous calcinosis]. / Intertrigo calcifie une forme rare de calcinose cutanee.

INTRODUCTION: Calcinosis cutis is classically described in patients presenting chronic renal failure with secondary hyperparathyroidism. There are three clinical types described in the literature: cutaneous necrosis (secondary to vascular calcification), panniculitis with calcification of the adipose tissue and necrosis of the skin and dermo-hypodermic calcinosis without necrosis usually called metastatic calcinosis. The latter can affect all tissues but skin involvement is rare. CASE REPORT: A case of calcinosis cutis is presented in a 50 years old woman with moderate secondary hyperparathyroidism and chronic renal failure caused by renal amyloidosis. She was referred by the renal unit to our service for erythematous, woody-hard, infiltrated plaques with petechial purpura satellite lesions, involving the flexural areas, that appeared within a few weeks. DISCUSSION: This observation is original by the topography of the cutaneous lesions the involvement of the fexural areas is unusual and by the histologic aspect of pseudoxanthome elastic-like. We must notice that the hyperparathyroidism had always been very moderate (normal parathormonemia) compared to the rapid development of an important dermic calcinosis.

[Anti-basement-membrane antibody mediated, rapidly progressive, glomerulonephritis. Diagnostic and therapeutic strategy based on a retrospective study of 14 cases]. / Glomérulonéphrites rapidement progressives à anticorps anti-membrane basale glomérulaire. Stratégie diagnostique et thérapeutique à partir d'une étude rétrospective de 14 cas.

Fourteen cases of anti-GBM antibody-induced RPGN were evaluated retrospectively in terms of renal function improvement and therapeutic risks. Nine men and 5 women (mean age: 55.3 years) were observed over a 9 year period; in three patients, hemoptysis was associated with renal disease (Goodpasture's syndrome). Most of these patients had received combinations of steroid therapy (ST), immunosuppressive drugs (IS) and plasma exchanges (PE). Age, duration of symptoms prior to diagnosis, initial renal function, therapeutic modalities and complications were assessed according to renal outcome: 9 patients (group A, "non-responders") remained on dialysis irrespective of the treatment administered; 5 patients (group B, "responders") recovered renal function. Complications, especially infections, were twice as frequent in group A. Two of the 4 recorded deaths were related to the disease or the treatment. Analysis of clinical and pathological values at the time of entry into the study for both groups indicated that oliguria/anuria, serum creatinine greater than 500 mumol/l and greater than 50% crescents, when associated, were factors predictive of poor renal outcome; in these patients, dialysis may be required except in cases of pulmonary hemorrhage. In all other patients, treatment with ST, IS and PE is recommended. Active hemoptysis necessitates pulse steroids or PE; if absent, further tests (carbon monoxide uptake, bronchoalveolar lavage, lung biopsy) are indicated before use of aggressive therapy.

[Urologic complications after 333 kidney transplantations]. / Complications urologiques après 333 transplantations rénales.

26 urological complications were observed in 25 patients following 333 kidney transplantations. The low incidence of these complications (7.8%) is largely due to the systematic resort to the Leadbetter-Politano ureterovesical anastomosis, except in one case (uretero-ureterostomy due to the shortness of the graft). We recorded 9 urinary fistulae and 17 cases of ureteral obstruction. Urinary lithiasis was excluded from this work. Urinary fistulae occur almost only between the second week and the end of the first month. Ureteral obstructions occur relatively early (within 30 days in 14 cases and within the first 48 hours in 9 cases). Two grafts were lost (8% of complications, but 0.6% of the entire series), and one patient died following transplantectomy. In 10 of 26 cases (38.5%), the etiology of the urological complication was related to the harvesting technique (2 short ureters, 8 ischemic ureters).

[Glomerulonephritis in Henoch-Schoenlein purpura. Anatomo-clinical correlations and immunopathological study of twenty-five cases. (author's transl)]. / La néphropathie du purpura rhumatoïde. Corrélations anatomo-cliniques et étude immunopathologique de vingt-cinq observations.

Twenty-five observations (children and adults) of glomerulo-nephritis secondary to Schoenlein-Henoch purpura were studied retrospectively. Histological studies done early in the course of the disease-less than one year after the first attack-enabled us to made, in function of the evolution, clinical and pathological correlations using the method of Levy et al. The intensity of the clinical signs at the time of biopsy appeared proportional to the degree of cellular proliferation whether it was endo or extracapillary form; it is much more difficult to define when mesangial proliferation predominates or in the absence of proliferation. In addition to the usual immunopathological abnormalities, this study found that IgE plasma concentration was frequently elevated. Thus, IgE may play a role in the pathogenesis of this systemic disease.

Pulmonary uptake of Tc-99m-Labeled methylene diphosphonate in a patient with a parathyroid adenoma.

Intense diffuse uptake of Tc-99m-labeled methylene diphosphonate was seen in both lungs of a patient submitted to surgery for a primary parathyroid adenoma. Five scans performed over the 3 yr following the operation showed persistence of lung uptake despite restoration of normal blood calcium concentration. Mild chronic renal failure caused by the hypercalcemia also persisted postoperatively. The present case confirms that pulmonary uptake of bone tracer can occur asymptomatically when both hypercalcemia and renal failure are present. Lung uptake of a bone tracer probably reflects tissue deposition of hydroxyapatite rather than of amorphous structures. Correction of the hypercalcemia failed to resolve the abnormal scan pictures.

Hereditary lecithin cholesterol acyltransferase deficiency. Report of a new family with two afflicted sisters.

One case of lecithin cholesterol acyltransferase (LCAT) deficiency is discovered by renal biopsy. Through the study of a French family, native to Brittany, one sister is found to be carrier of the trait. This finding suggests that the gene defect hitherto reported from Scandinavia is not restricted to this region. The patient shows typical signs of the disease, corneal opacities, anemia with a hemolytic component and lack of plasma LCAT activity. She has proteinuria, HTA, hematuria, no renal insufficiency. Signs previously unreported were noted: sensorineural hearing loss and platelet environment disorder. Histological abnormalities of two types are found: foam cells and subendothelial deposits, of which the tinctorial characteristics indicate a lipid composition. The lack of glomerular fluorescent staining observed is not in favor of an immune complex nephropathy. The study of this case suggests the determining role of lipid abnormalities in the genesis of anemia and of the vascular depositions in the induction of renal failure encountered in several cases of LCAT deficiency.