Renal involvement in systemic amyloidosis: an Italian collaborative study on survival and renal outcome.

BACKGROUND: Few data are available from large population-based studies on survival and renal outcome of patients with renal involvement and different types of systemic amyloidosis. METHODS: Two hundred and ninety of over 373 patients affected from systemic amyloidosis with renal involvement diagnosed in Italy between January 1995 and December 2000 were followed from diagnosis to death or until the last available clinical control. Eighty-three patients were excluded from analysis either because the amyloid type remained undetermined or they were lost at follow-up. Clinical and laboratory information was collected according to the different types of amyloidosis using a specific form which included renal function with 24 h proteinuria at diagnosis and at the end of follow-up, the type and the date of onset of dialysis and the kind of treatment they underwent. RESULTS: The median time of follow-up was 24 months in primary (AL) amyloidosis (range: 1-88 months), 16 months in AL with associated multiple myeloma (MM + AL: range 1-76 months), 30 months in reactive (AA) amyloidosis (range: 1-99 months) and 52 months in patients with familial forms (AF: range 14-82 months). Patients with AL showed a significantly shorter survival than AA. Despite no significant differences of renal outcome or survival on dialysis being observed between the two groups, a lower renal survival with a higher number of patients who progressed to end-stage renal disease (ESRD) was observed in patients with AA. Overall survival was markedly improved in patients with AL who underwent a specific therapy (conventional chemotherapy or autologous stem cell transplantation (ASCT)) even in the absence of a positive kidney response. Multivariate analysis showed cardiac involvement and specific therapy to significantly influence survival in AL whereas age, serum creatinine (sCr) and heart involvement significantly affected survival in AA. In both groups, sCr and heart involvement were the most relevant predictors for renal outcome, together with urinary protein excretion, in patients with AA. CONCLUSIONS: Our results show a worse survival in AL due to the higher prevalence of heart involvement in this group and emphasize that a specific therapy significantly prolongs survival and slows the progression of renal disease in patients with AL. We suggest that a late nephrological referral is likely the cause of the higher sCr found at presentation in patients with AA and probably accounts for the lower renal survival observed in the short term in these patients. At the time being, renal transplantation and ASCT are still rare therapeutic options for renal patients affected from systemic amyloidosis.

Acute renal and hepatic failure associated with allopurinol treatment.

Hyperuricemia is present in about 5% of the population, and allopurinol is frequently used to treat it. The use of this drug can be associated with a number of side effects, indicating allergic reactions, such as skin rash, reversible after its withdrawal. In some cases more severe hypersensitivity reactions may be seen, such as erythema multiforme exudativum, or Steven-Johnson Syndrome (SJS). Reversible clinical hepatotoxicity, as well as acute renal failure, may also develop after allopurinol therapy. We describe here the case of a 74-year-old woman with chronic renal failure who was admitted to hospital after 1 week of sore throat and fever, presenting mucous membrane lesions, widespread blistering of the skin, evolving to flaccid vesicles and bullae, and extensive epidermal detachment associated with acute renal failure and cholestatic jaundice. A diagnosis of allopurinol-induced toxic epidermal necrolysis (TEN) was established. Allopurinol was discontinued, and intensive care management was required: the patient was successfully treated by using intravenous immunoglobulin (IVIg), standard hemodialysis, and albumin dialysis (Molecular Adsorbents Recirculating System - MARS, Teraklin AG, Rostock, Germany). Allopurinol-induced TEN is extremely rare, however, the survival rate is extremely low. Clinicians should be aware of this potentially severe adverse effect. This report emphasizes the importance of an aggressive pharmacological and dialysis treatment in the case of TEN.

Diagnostic specificity of autoantibodies to M-type phospholipase A2 receptor (PLA2R) in differentiating idiopathic membranous nephropathy (IMN) from secondary forms and other glomerular diseases.

Autoantibody against phospholipase A2 receptor (anti-PLA2R) is a sensitive and specific biomarker of idiopathic membranous nephropathy (iMN), being found in approximately 70% of iMN patients and only occasionally in other glomerular diseases. However, whereas its diagnostic specificity vs. normal controls and other glomerulonephritides (GN) has been firmly established, its specificity vs. membranous nephropathy associated with various diseases (sMN) has given inconsistent results. The aim of our study was to evaluate the prevalence of anti-PLA2R antibodies in iMN in comparison with various control groups, including sMN. A total of 252 consecutive iMN patients, 184 pathological and 43 healthy controls were tested for anti-PLA2R antibody using indirect immunofluorescence (PLA2R IIFT, Euroimmun). Anti-PLA2R autoantibodies were detectable in 178/252 iMN patients, 1/80 primary GN, 0/72 secondary GN, 9/32 sMN and 0/43 healthy controls, with a diagnostic sensitivity of 70.6%. The diagnostic specificity of anti-PLA2R antibody vs. normal and pathological controls was 100 and 94.6% respectively. However, when the diagnostic specificity was calculated only vs. secondary forms of MN, it decreased considerably to 71.9%. Interestingly enough, 9 out of 10 anti-PLA2R positive patients in the disease control groups had membranous nephropathy associated with various diseases (7 cancer, 1 Crohn's disease, 1 scleroderma). In conclusion, anti-PLA2R positivity in a patient with MN, should not be considered sufficient to abstain from seeking a secondary cause, especially in patients with risk factors for neoplasia. The causal relationship between tumors and anti-PLA2R-induced MN remains to be established, as well as the possible mechanisms through which malignancies provoke autoimmunity.

IgM nephropathy: is it closer to minimal change disease or to focal segmental glomerulosclerosis?

Immunoglobulin (Ig)M nephropathy (IgMN), known since 1978, is a very controversial clinicopathological entity characterized by IgM diffuse deposits in the mesangium at immunofluorescence whereas light microscop identifies minimal glomerular lesion, hypercellularity and expansion of the mesangium or sclerotic focal, segmental lesion. Clinically, it is a nephrotic syndrome, especially in pediatric patients, or asymptomatic proteinuria and/or isolated hematuria. These characteristics narrowly define IgMN between minimal change disease and focal segmental glomerulosclerosis, so it is not often recognized as a separate pathology. Homogeneous epidemiologic, pathogenetic, clinical or histological data are not available. Recent research on the pathogenetic role of mesangial IgM has, however, renewed interest in IgMN and naturally the controversies.

Biofiltration with buffer-free dialysate.

The presence of acetate in the dialysate appears to be superfluous in the new depurative technique indicated as biofiltration, which consists in a standard hemodialysis with high ultrafiltration combined with the reinfusion of 3-4 1/2 liters of solution containing bicarbonate. The presence of acetate could in fact be contraindicated by a number of potential side effects, metabolic, cardiovascular and biological. Hence, starting from the consideration that in standard biofiltration a buffer is already infused directly as bicarbonate, we tried to overcome the potential hazards of the acetate-containing bath simply by using a dialysate without acetate and by increasing the concentration of bicarbonate in the reinfusate. A cumulative clinical experience of 20 months in 4 patients proved the feasibility and safety of the technique and suggests further advantages over standard biofiltration (better control of acid-base equilibrium, better cardiovascular stability.

Renal funtional reserve in kidney transplant recipients.

In the last few years different authors have observed that kidney transplant recipients with good organ function do not have a renal functional reserve (RFR). This condition is accompained by a high glomerular filtration rate (GFR). We studied RFR in patients with very good organ function under different immunosuppressive therapies, who were divided into groups based on the presence or absence of RFR.

Antibodies against hepatitis C virus in hemodialysis patients in the central Italian region of Umbria: evaluation of some risk factors.

The epidemiology of non-A, non-B hepatitis (NANBH) is still incomplete. To define the prevalence of antibodies against the main causative agent of NANBH, the hepatitis C virus (HCV) and the role of some risk factors, we tested sera from 269 patients on chronic dialysis at the hemodialysis units in our region in central Italy. We utilized the recently developed serological assay. Twenty-nine hemodialysis patients (13.3%) and 3 peritoneal dialysis patients (4.8%) were anti-HCV positive. Of these, 13 (40.6%) had antibodies to hepatitis B core antigen (anti-HBc) indicating prior hepatitis B infection. The anti-HCV seropositive patients had been on dialysis longer than the seronegative ones; they had received more transfusions than the others but without a significant difference. The prevalence rate of anti-HCV was statistically significantly higher among hemodialysis patients utilizing the same dialysis equipment for the previous 12 months.