Recurent and de novo membranous glomerulopathy after kidney transplantation.

The aim of this study was to compare the clinical characteristics of recurrent and de novo membranous glomerulopathy (MG) among a cohort of 614 recipients transplanted between 1989 and 2006. Lupus nephritides were excluded. The diagnosis was established on protocol biopsies performed 1, 2, 4, or 8 years after transplantation or because of proteinuria/nephrotic syndrome and/or an increased serum creatinine level. HCV infection, cryoglobulinemia, monoclonal gammopathy, skin cancers, Kaposi sarcoma, diabetes mellitus, anti-HLA antibodies, and graft survival were not significantly different between the groups. Seventeen MG were diagnosed in 15 patients (2.45% of the whole group), including 6 recurrent MG (35%) and 11 de novo MG (75%). Recurrent MG occurred earlier than de novo MG (15.58 +/- 19.13 vs 49.27 +/- 32.71 months). Recipients with de novo MG were more frequently infected with HCV, which seemed to be the main etiologic factor for de novo MG, and may be linked to a Th2 polarization of the immune response.

Detection of Foxp3+ cells on biopsies of kidney transplants with early acute rejection.

This retrospective study was conducted to examine whether the presence of Foxp3+ cells in biopsies of kidney transplants displaying early acute rejection (AR) predicted the outcome of the episode. Seventeen biopsies showing AR included in this study were obtained at 42 +/- 30 days after transplantation. Lesions were graded according to the Banff classification. Foxp3 staining was performed on paraffin-embedded sections with a monoclonal antibody after antigen retrieval. We evaluated relationships between the number and the location of Foxp3+ cells, the type of rejection, and the serum creatinine value at 1 year. Foxp3+ cells were detected in 11 of 17 biopsies with AR (9.5 +/- 13.3 cells/mm(2)). These elements were mixed with other interstitial inflammatory cells. Intraepithelial tubular Foxp3+ cells were seen in 9 biopsies (1.5 +/- 2.5 cells/mm(2)). Foxp3+ cells were associated with borderline lesions (25.5 +/- 22.4/mm(2)); type 1 AR (7.18 +/- 9/mm(2)) and type 2 AR (1.99 +/- 3.46/mm(2)). The average number of cells per field was not different in C4d(+) and C4d(-) AR (6 +/- 8.35 vs 8.5 +/- 14.7/mm(2)). Graft loss within the first year was higher among the group of recipients without Foxp3+ cells (3/6) than those with Foxp3+ cells (0/11). All AR with intraepithelial tubular Foxp3 cells had favorable outcomes. Foxp3 has been proposed as a relevant marker of CD4(+)CD25(+) regulatory T cells. This study showed that Foxp3+ cells can be detected in kidney transplant biopsies with AR. The absence of Foxp3+ cells, especially in epithelial tubular cells, might indicate a poor prognosis following an AR episode.

Recurrence of IgA nephropathy with crescents in kidney transplants.

Crescentic IgA nephropathy is an uncommon finding in native kidneys (3%-5%) and in renal transplants. This study was performed to determine the frequency of relapsing crescentic IgA nephropathy after kidney transplantation. Over a 15-year period, 42 patients (25 men, 17 women) of age range 17 to 59 years with biopsy-proven IgA nephropathy in their native kidneys were entered into this retrospective study, because they had undergone kidney transplantation and had sequential allograft biopsies during their follow-up. Mean follow-up after transplantation was 8.9 years (range, 1-15 years). In their native kidneys, 5 patients (12%) had more than 20% crescents, and only 2 (5%) had more than 50% of glomeruli involved. As expected, 52.4% of recipients showed recurrent mesangial IgA deposits in their kidney grafts. The 2 patients with diffuse crescentic IgA nephropathy in their native kidneys experienced acute graft dysfunction at 15 and 47 months. Graft biopsy showed recurrent IgA deposits with cellular crescents in 30% and 20% of glomeruli, respectively. Despite corticosteroid pulse therapy, graft failures occurred 2 and 27 months later. No crescentic proliferation was observed during follow-up in any other case. Only 5 other grafts failed because of chronic allograft nephropathy, without any relationship to the relapse of IgA deposits. These data suggested for the first time that only diffuse crescentic IgA nephropathy in the native kidneys was associated with the occurrence of crescents in the kidney transplants, a finding that raises the possibility of a particular subgroup of IgA nephropathies.

Rheumatoid arthritis-induced pseudotumoral AA amyloidosis of the bladder with vesico-peritoneal fistula.

Rheumatoid arthritis-induced AA amyloidosis of the bladder is rare, with fewer than 25 cases reported so far. This localization may be life-threatening with a mortality rate of about 60%, most often due to massive hematuria or multiorgan failure as a result of systemic amyloidosis. We report the case of a 72-year-old woman with a long history of rheumatoid arthritis who developed gross hematuria that induced severe anemia. Ultrasonography and tomodensitometry revealed a large mass localized in the upper part of the bladder. Cystoscopy showed a congestive inflammatory area with a large vesicoperitoneal fistula. Biopsies revealed amyloidosis, and immunohistochemical staining of the specimens defined the process as AA amyloidosis. The amyloid deposits were also found in the rectum, duodenum, uterus and kidneys. This case of rheumatoid arthritis-induced AA amyloidosis of the bladder is characterized by its pseudotumoral aspect and the existence ofa vesico-peritoneal fistula: only 2 cases have been reported so far. Treatment was symptomatic, and the patient died from cachexia. The pseudotumoral forms of AA amyloidosis, including amyloidosis of the bladder, deserve an early correct diagnosis. Otherwise, an incorrect diagnosis, especially cancer, may prompt inappropriate treatments.

Expression of TGFbeta-1 and Type I TGFbeta-receptor on sequential biopsies of renal transplants with chronic allograft nephropathy.

The aim of this study was to determine the expression of transforming growth factor-beta (TGFbeta)-1 and type I TGFbeta-receptor on sequential biopsies from renal transplants with and without chronic allograft nephropathy. Twenty-four renal transplant recipients entered the study. They underwent sequential biopsies performed before (T1: 1.44 +/- 1.2 months) and 6 months after (T2: 15.96 +/- 7.2 months) transplantation. Lesions were graded according to the criteria of the Banff classification. C4d was detected by fluorescence microscopy. Immunohistochemistry was performed in order to identify cells expressing TGFbeta-1 and type I TGFbeta-receptor. In normal renal tissue (n = 4), TGFbeta-1 is expressed by tubular epithelial cells and endothelial cells lining glomerular and peritubular capillaries, whereas type 1 TGFbeta-receptor is expressed by tubular epithelial cells and smooth muscle cells in the media of arteries. In recipients with chronic allograft nephropathy (group 1, n = 14), diffuse epithelial expression of both molecules was found in more patients at T2 than at T1 (42.8% vs 21.4%). In contrast, this pattern of expression remained stable or decreased over time in recipients with long-term normal transplants (group 2, n = 10). Furthermore, type 1 TGFbeta-receptor was detected on the smooth muscle cells of arteries in 12/14 (85.7%) of recipients in group 1 and only in 4/9 (44.4%) of recipients in group 2. No relationship was noticed with regard to C4d deposits. These data suggest that the synthesis of TGFbeta-1 and type I TGFbeta-receptor increases over time in recipients developing chronic allograft nephropathy. Further studies are in progress in order to quantify mRNA of both molecules with real-time polymerase chain reaction.

Successful hepatorenal transplantation in hereditary amyloidosis caused by a frame-shift mutation in fibrinogen Aalpha-chain gene.

Hereditary systemic amyloidosis comprises several autosomal dominant diseases caused by mutations in a number of plasma proteins, including the fibrinogen Aalpha-chain. Four mutations in the fibrinogen Aalpha-chain that are able to induce amyloidosis have been identified so far, the most common being the Glu526Val mutation. We have observed a family in which the father and his son reached end-stage renal failure because of renal amyloidosis induced by a frame-shift mutation in the fibrinogen Aalpha-chain gene producing a novel amyloid protein. Two kidney transplantations in the father and one in the son resulted in fast graft loss caused by recurrence of amyloid deposition. We then performed hepatorenal transplantation in the son. Three years later, liver and kidney functions are normal without recurrence of amyloid deposition. This case, together with three others with the Glu526Val mutation in the extensive literature, suggests that liver transplantation can cure hereditary fibrinogen amyloidosis, whatever the mutation may be.

Induction of tissue factor expression on human umbilical vein endothelial cells by cell-specific HLA class I antibody: preliminary data.

Donor-specific antibodies may play an important role in the development of chronic allograft rejection process. However, the mechanisms leading to intimal vascular proliferation and fibrosis remain poorly understood. The aim of this study was to examine whether donor-specific HLA antibodies induce overexpression of tissue factor (TF) by endothelial cells. HLA typed human umbilical vein endothelial cells (HUVEC) were incubated for 1 to 12 hours with LPS (10 microg/mL), and increasing concentrations (1 to 500 microg/mL) of anti-HLA A1 antibody specific for an antigen expressed by HUVEC and of an anti-HLA A2 antibody for which A2 was not expressed by the HUVEC. Expression of TF mRNA transcripts was quantified using real time Q-RT PCR and TF activity was tested in cell lysates of cultured HUVEC using a chromogenic TF activity assay. HUVEC-specific anti-HLA A1 antibody at low concentrations (10 microg/mL) induced both a significant increase of TF mRNA transcripts after 1 hour of incubation and TF activity after 3 hours incubation compared to incubation with medium alone or with the nonspecific anti-HLA A2 antibody (n = 4 for all experiments, P < .05). These data show for the first time that specific anti-HLA antibody can induce overexpression of TF on endothelial cells. TF, a transmembrane glycoprotein involved not only in the onset of the coagulation cascade, but also in cell proliferation and anti-apoptotic processes, may play a role in the development of alloantibody-induced chronic rejection.

Chondroblastoma of the temporal bone associated with a persistent hypoglossal artery.

A case of a chondroblastoma of the skull-base associated with a persistent hypoglossal artery (PHA) is presented. Neuroradiological findings of the PHA and the tumour are reported. The existence of a carotico-basilar communication such as a PHA should be recognized prior to skull base surgery because of the potential risk of cerebral ischemia.

[Clinical and histological features of cutaneous drug reactions]. / Aspects anatomo-cliniques des atteintes cutanées médicamenteuses.

Over the last 20 years, our understanding of cutaneous adverse drug reactions has improved, especially with regard to the management of affected patients. The pathophysiological mechanisms have been studied to improve our understanding. We report different clinical and histological features of cutaneous drug reactions to distinguish a non drug-induced rash from a cutaneous adverse drug reaction.

Disparate effects of chronic and acute theophylline on cyclosporine A nephrotoxicity.

We previously developed a model of acute cyclosporine A (CsA)-induced vasomotor nephrotoxicity in rabbits. As exogenous adenosine infusion mimics the haemodynamic changes that characterize acute renal failure (ARF), we wanted to know whether adenosine was a mediator in this model and whether an adenosine receptor blocker could prevent the CsA-induced ARF. Group 1 were untreated controls. Group 2 received CsA (25 mg/kg per day) for 5 days. Renal function parameters were measured, showing ARF in all animals compared to controls. Theophylline (1 mg/kg i.v. bolus) was then administered and renal function was reassessed. Theophylline significantly reduced renal vascular resistance (-8%) and increased renal blood flow (RBF) (+20%), glomerular filtration rate (GFR) (+50%), filtration fraction (+24%) and diuresis (+73%), suggesting that adenosine was involved in the CsA-induced ARF. In group 3, theophylline (30 mg/kg per day) was given concomitantly with CsA for 5 days. GFR was normalized, but theophylline did not hinder the drop in RBF seen with CsA alone in group 2. Microscopy observation of the kidneys showed that chronic theophylline administration aggravated the morphological changes induced by CsA alone. We conclude that CsA administration for 5 days induced a vasomotor nephropathy with an adenosine-mediated afferent arteriolar constriction which cannot be prevented by concomitant theophylline administration.

[Bullous cutaneous mastocytosis revealed by acute disease secondary to morphine administration]. / Mastocytose cutanée bulleuse révélée par un malaise grave secondaire à la prise de morphinique.

UNLABELLED: Mastocytosis in children shows in three clinical forms. The rarest is the diffuse or bullous form. CASE REPORT: Since one month of age an infant showed a diffuse erythema and vesicle rash. At four months of age, serious discomfort after morphinic absorption led to the diagnosis of bullous cutaneous mastocytosis. Histologic examination confirmed this diagnosis. The clinical severity led to intravenous corticosteroid and antihistamine therapy. COMMENTS: Bullous cutaneous mastocytosis is unusual in children. However, it should be considered if there are any doubts because of its serious complications and iatrogenic therapeutic risks. Some serious cases require intravenous corticosteroid therapy. Appropriate care enables a normal development with a disappearance of the disease before the teenage years.

Endothelin, angiotensin II and adenosine in acute cyclosporine A nephrotoxicity.

We previously developed a model of acute cyclosporine A (CsA)-induced vasomotor nephrotoxicity in rabbits. In the present study, we evaluated the role of endothelin (ET), angiotensin II (AII) and adenosine in this experimental model. All animals received CsA (25 mg/kg/day) for 5 days. Renal function parameters were first measured in a 30-min period, showing renal insufficiency in all animals. Then, rabbits were administered bosentan (10 mg/kg; antagonist of ET(AB) receptors), perindopril (20 microg/kg; angiotensin-converting enzyme inhibitor), or theophylline (1 mg/kg; adenosine receptor blocker at micromolar concentrations). After a 40-min equilibration period, renal function was assessed again for 30 min. Bosentan, perindopril and theophylline significantly reduced renal vascular resistance (-28+/-5%, -39+/-7% and -8+/-3%, respectively), and improved renal blood flow (+38+/-15%, +66+/-16% and +20+/-5%), glomerular filtration rate (+33+/-9%, +52+/-13% and +50+/-8%) and diuresis (+48+/-9%, +76+/-19% and +73+/-14%). Filtration fraction was unchanged with bosentan, decreased with perindopril (-10+/-9%) and increased with theophylline (+24+/-5%). The overall results suggest that ET, AII and adenosine are involved in the acute renal failure induced by CsA. We conclude that CsA administration for 5 days induced a vasomotor nephropathy with ET- and adenosine-mediated afferent arteriolar constriction as well as ET- and AII-mediated efferent arteriolar constriction.

Acute cyclosporine A-induced nephrotoxicity: a rabbit model.

Chronic cyclosporine A (CsA) nephrotoxicity has been widely assessed but only few studies have described acute nephrotoxicity. As CsA is now used for short periods, we developed an experimental model of acute CsA-induced nephrotoxicity. Renal clearances of inulin and para-aminohippurate were assessed in 35 New Zealand rabbits. Group 1: control, no treatment; group 2: CsA 25 mg/kg per day in 0.5 ml/kg per day for 5 days; group 3: vehicle Cremophor-EL, 0.5 ml/kg per day for 5 days; group 4: follow-up, the same as group 2, then CsA discontinuation for 31 days. Compared with group 1, CsA significantly decreased glomerular filtration rate (GFR), renal blood flow (RBF), and diuresis, with a significant increase in renal vascular resistance (RVR). The proportional fall in GFR (-32.3%) and RBF (-33.1%) suggests both pre- and postglomerular vasoconstriction. Discontinuation of CsA in group 4 led to normalization of RVR with improvement of other renal function parameters. Compared with group 1, Cremophor-EL induced no significant changes but an increased RBF. Microvacuolization of proximal tubule epithelial cells was the sole histological abnormality observed only in group 2. The overall results suggest that CsA induced a vasomotor acute renal failure which was not due to Cremophor-EL. This effect was partly reversible after discontinuation of treatment.

[Cronkhite-Canada syndrome and arsenic poisoning: fortuitous association or new etiological hypothesis?]. / Syndrome de Cronkhite-Canada et intoxication à l'arsenic: association fortuite ou nouvelle hypothèse étiologique?

We report a case of Cronkhite-Canada syndrome in a 66 year-old man, particular by an association with arsenism. Both arsenism and the Cronkhite-Canada syndrome are a cause of ectodermal and mucosal lesions. The persistence of physical, biological and endoscopic manifestations associated with disappearance of arsenic intoxication signs allowed us to make the diagnosis. The search of arsenic in blood, nail and hair must complete the investigations in case of acquired pseudopolyposis and ectodermal changes.

Foscarnet-induced crystalline glomerulonephritis with nephrotic syndrome and acute renal failure after kidney transplantation.

Foscarnet nephrotoxicity has been reported to be associated with acute tubulointerstitial nephritis. Crystals in glomerular capillary lumens have also been observed in patients with acquired immunodeficiency syndrome who were treated with foscarnet for cytomegalovirus disease. We describe a kidney transplant recipient who developed a nephrotic syndrome with microscopic hematuria and nonoliguric acute renal failure within 15 days after starting foscarnet therapy for cytomegalovirus infection. A kidney biopsy specimen showed the presence of crystals in all glomeruli and in proximal tubules. Fourier transform infrared microscopy analysis demonstrated that crystals were made from several forms of foscarnet salts: mixed calcium and sodium salts, and unchanged trisodium foscarnet salts. Renal function and proteinuria spontaneously improved, and a second transplant biopsy performed 8 months after the first one revealed fibrotic organization of half of the glomeruli and of interstitial tissue, and crystal vanishing. We were thus able to provide proof of the possible precipitation of foscarnet in a transplanted kidney.