Successful heart transplantation following melphalan plus dexamethasone therapy in systemic AL amyloidosis.

Recurrence in the allograft and progression in other organs increase mortality after cardiac transplantation in AL amyloidosis. Survival may be improved after suppression of monoclonal light chain (LC) production following high dose melphalan and autologous stem cell transplantation (HDM/ASCT). However, because of high treatment related mortality, this tandem approach is restricted to few patients without significant extra-cardiac involvement. A diagnosis of systemic AL amyloidosis was established in a 45-year old patient with congestive heart failure related to restrictive cardiomyopathy, nephrotic syndrome, peripheral neuropathy, postural hypotension, macroglossia, and lambda LC monoclonal gammopathy. After melphalan and dexamethasone (M-Dex) therapy, which resulted in 80% reduction of serum free lambda LC, he underwent orthotopic cardiac transplantation. Two years later, he remains in a sustained hematologic remission, with no evidence of allograft or extra-cardiac amyloid accumulation. M-Dex should be considered as an alternative therapy in AL amyloid heart transplant recipients ineligible for HDM/ASCT.

Early loss of two renal grafts obtained from the same donor: role of ecstasy?

Early loss of renal grafts is generally caused by vascular or immunologic complications. We describe two patients who received a kidney transplant from the same donor and lost their grafts during the first posttransplant week. Both cases presented necrotizing graft vasculopathy without inflammatory element. The donor was a 21-year-old woman who regularly used "ecstasy" over a 2-year period. After an extensive work-up to investigate the potential causes of graft loss, we considered the possibility of ecstasy being the cause of these two renal-graft losses.

Recurrence of ANCA-positive glomerulonephritis immediately after renal transplantation.

Recurrence of crescentic necrotizing glomerulonephritis after renal transplantation is rare. Successful renal transplantation in patients with antineutrophil cytoplasmic autoantibody (ANCA) glomerulonephritis has been reported. The presence of ANCA at transplantation does not appear to increase the rate of relapse after kidney allografting. Therapy with cyclophosphamide and corticoids usually is effective. We report a case of recurrent perinuclear ANCA crescentic necrotizing glomerulonephritis immediately after renal transplantation that was treated successfully by cyclophosphamide, plasma exchange, and intravenous polyvalent immunoglobulin.

[Virological, epidemiological and pathogenic aspects of human polyomaviruses]. / Caractères virologiques, épidémiologiques et pathogéniques des polyomavirus humains.

VIROLOGICAL ASPECTS: Human polyomaviruses (BK virus and JC virus), together with simian polyomaviruses (SV40 virus) share 75% of genomic homology. Their in vivo and in vitro genomes vary. Molecular analyses have identified several genotypes, some of which appear related to the development of viral diseases. Genomic modifications of the regulation area might provide the BKv with a pathogenic aspect thus enhancing the induction of tubulo-interstitial nephropathies in renal transplant recipients. EPIDEMIOLOGY: Human polyomaviruses are ubiquitous and exhibit a sero-prevalence of 60 to 80% in adults. Following a primary infection via the respiratory tract in childhood, these viruses are diffused in the blood using the B-lymphocytes during their latent stage in the urogenital tract. The reactivation that occurs after several years is asymptomatic and urinary excretion of BKv is observed in 4 to 6% of immunocompetent patients. PATHOGENIC POTENTIAL: Human polyomaviruses have a cytopathogenic effect on the urothelium and epithelium of renal transplant recipients. Infection by BKv may provoke hemorrhagic cystitis or urethral stenosis. The JCv is the cause of progressive multifocal leuko-encephalitis. The BKv (and less frequently the JCv) is responsible for tubulo-interstitial nephritis possible leading to renal transplant loss. They also have an oncogenic effect and their implication in the origin of tumours is the subject of many studies.

[Therapeutic possibilities for polyomavirus infections in renal transplantation]. / Possibilités thérapeutiques des infections à polyomavirus humains en transplantation rénale.

TO IMPROVE THERAPEUTIC MANAGEMENT: The aim is the early detection of polyomavirus infection, before the onset of tubulo-interstitial nephritic lesions, and to reduce viral replication. AT THE STAGE OF POLYOMAVIRUS INFECTION: Treatment relies on the reduction of immunosuppression. Efficacy is controlled by monitoring the decoy cells in the urine and the detection and quantification of the DNA of polyomaviruses in the plasma and urine. AT THE STAGE OF POLYOMAVIRUS DISEASE: The aim is to reduce the viral replication by further decreasing immunosuppression to stabilize renal function and avoid graft rejection. When signs of rejection and viral infection co-exist, cidofovir could be a therapeutic alternative. However, the use of cidofovir remains in the field of clinical research and requires the further development of therapeutic protocols.

[Clinical aspects of human polyomaviruses in renal transplantation]. / Manifestations cliniques des polyomavirus humains en transplantation rénale.

A THREAT FOR RENAL ALLOGRAFT: Human polyomavirus infections (BK virus, JC virus), known for the past 30 years, were considered as common in renal transplantation until the recently reported studies describing the responsibility of BKv (and less JCv) in the occurrence of tubulo-interstitial nephritis in around 5% of renal transplant recipients, with worsening of the renal function leading to graft failure in 10 to 45% of infected patients. Their description coincided with the use of new immunosuppressors (tacrolimus and mycophenolate mofetil) without, however, their responsibility clearly incriminated. EARLY DIAGNOSIS FOR EFFICIENT TREATMENT: The presence of cells infected by the polyomavirus ("decoy cells") in the urine and the detection of BKv or JCv DNA by PCR in the plasma and urine are viral replication markers which strongly suggest the possibility of a polyomavirus nephropathy. TWO CLINICAL VARYING FORMS: Polyomavirus infection is frequent and often asymptomatic. The diagnosis requires the detection of large nucleus "decoy cells" in fresh urine. Polyomavirus renal allograft disease is characterised by the association of decoy cells and renal failure related to a tubulo-interstitial nephropathy and the presence of DNA of the virus in the plasma. The diagnosis requires identification of intra-nuclear viral inclusions in epithelial cells using immunohistochemistry, in situ hybridisation, or electron microscopy techniques. A DIFFICULT DIAGNOSIS: Confusion between interstitial nephritis and acute cellular rejection is the major risk leading to therapeutic error. Risk factors include over-immunosuppression and/or treatment of rejection episodes which could increase viral replication as well as the emergence of mutant BKv strains at the origin of tubulo-interstitial nephritis, leading to acute and chronic dysfunction of the renal transplantation.