Is beta2-microglobulin-related amyloidosis of hemodialysis patients a multifactorial disease? A new pathogenetic approach.

PURPOSE: Beta2-microglobulin amyloidosis (Abeta(2)M) is one of the main long-term complications of dialysis treatment. The incidence and the onset of Abeta(2)M has been related to membrane composition and/or dialysis technique, with non-homogeneous results. This study was carried out to detect: i) the incidence of bone cysts and CTS from Abeta(2)M; ii) the difference in Abeta(2)M onset between cellulosic and synthetic membranes; iii) other risk factors besides the membrane. METHODS: 480 HD patients were selected between 1986 to 2005 and grouped according to the 4 types of membranes used (cellulose, synthetically modified cellulose, synthetic low-flux, synthetic high-flux). The patients were analyzed before and after 1995, when the reverse osmosis treatment for dialysis water was started at our center, and the incidence of Abeta(2)M was compared between the two periods. Routine plain radiography, computer tomography (CT) and nuclear magnetic resonance imaging (MRI) as well as electromyography were used to investigate the clinical symptoms. RESULTS: Bone cysts occurred in 29.2% of patients before 1995 vs. 12.2% after 1995 (p<0.0001). CTS occurred in 24% of patients before 1995 vs. 7.1% after 1995 (p<0.0001). Bone cysts and CTS occurred in older patients, who began dialysis at a late age, with high CRP, low albumin, low residual GFR, and low Hb. Cox regression analysis showed that the risk factor for bone cysts was high CRP (RR 1.3, p<0.01), while albumin (RR 0.14, p<0.0001) and residual GFR (RR 0.81, p<0.0001) were revealed to be protective factors. Cox analysis for CTS confirmed CRP as a risk factor (RR 1.2, p<0.01), and albumin (RR 0.59, p<0.0001) and residual GFR (RR 0.75, p<0.0001) as protective factors. The comparison obtained between membranes did not suggest any protective effect on Abeta(2)M. CONCLUSIONS: The findings that the inflammatory status as well as low albumin and the residual GFR of the uremic patient are predictive of Abeta(2)M lesions suggests that Abeta(2)M has a multifactorial origin rather than being solely a membrane- or technique-related side effect.

Combined liver-kidney transplantation--S. Orsola experience: nephrological aspects.

Combined liver kidney transplantation (LKT) has the potential to provide a complete recovery of liver and kidney failure; the literature reports an increase in LKT in the last few years and an improvement in patient and graft survival. In our experience 15 patients underwent LKT from 1997 to 2005. The mean age was 50 +/- 9 years (range 34 to 63). The patients were affected by viral (n = 9), alcoholic (n = 1), polycystic (n = 2), cholangitis (n = 1), cholestatic (n = 1), or amyloidotic (n = 1) chronic hepatopathy. Chronic renal failure (CRF) was due to polycystic kidney disease (n = 4), IgA (n = 2), interstitial nephropathy (n = 2), glomerulonephritis (n = 4), amyloidosis (n = 1), vascular nephropathy (n = 1), of unknown end-stage renal disease (n = 1). Twelve of 15 patients were on renal dialysis treatment, three patients had moderate/severe CRF. Two patients had previously been transplanted (kidney). All patients were selected based upon blood group identity and negative cross-match before kidney transplant. Histocompatibility matching (HLA) was not included in the selection criteria. We did not observe delayed graft function. After a mean follow-up was 23 +/- 32 months (range 5 to 99), 12 subjects show, normal hepatic and renal function. At the beginning of our experience two patients in bad clinical condition died within 3 months because of sepsis, and one died because of a malignancy after 7 years. Both organs were functioning well in the deceased patients. Survival analysis confirms LKT efficacy: at 5 years follow-up patient survival is 86%, graft survival censored for death 100%. Only two subjects had an acute rejection episode in the first year; the kidney rejection incidence was lower than that reported for an isolated kidney transplant (13% vs 21%).

[Renal transplantation and malignancies: A single-centre experience (25 years)]. / Trapianto renale e neoplasie maligne: esperienza a lungo termine (25 anni) di un singolo centro.

BACKGROUND: The prevalence of post-transplant malignancies, in renal transplant recipients, is higher than that expected in age and sex-matched controls from the general population, and there is a markedly increased incidence of certain cancers. METHODS: In 1137 renal transplant recipients (1020 from cadaveric and 117 from living donors, M/F 771/366) performed at the S. Orsola Renal Transplantation Centre since 10/1976 to 9/2001, we studied the post-transplant cancer prevalence, the correlation between cancer prevalence and population characteristics, the risk factors (smoke, cancer history, positive HBsAg and antiHCV infection) and the immunosuppressive therapy. RESULTS AND CONCLUSIONS: The prevalence of malignancies was 3.86% (52 malignancies in 44 patients). The period between transplant and diagnosis of malignant disease was 59 +/- 85 months. Skin cancer was the most common (n=16; 30.7%), followed by lymphoproliferative disorders (n=8; 15.4%), Kaposi s sarcoma (n=6; 11.5%), uterine cancer (n=6; 11.5%), renal carcinoma of native kidney (n=5; 9.6%), cancer of breast/stomach/pancreas and urinary bladder (n=2; 3.8%) and other cancers (n=5; 9.6%). The mean duration of dialysis before transplantation was longer in cancer patients (41+/- 32.1 vs. 33.5 +/- 32.4 months). We found a correlation between types of malignancies and viral infection in NH-lymphoma (EBV positive 4/4) and skin cancer (HZV positive 13/16). We also detected a correlation between Aza and skin cancer (16/22) and CyA and lymphoproliferative disorders (7/8).

[Late onset immunodeficiency with hypo-IgG and hyper-IgM, T CD4+ lymphocytopenia and vitiligo]. / Immunodeficienza ad insorgenza tardiva con ipo-IgG e iper-IgM, linfocitopenia T CD4+ e vitiligo.

The Authors report the clinical case of a patient with a deficit of humoral immunity who developed infections since puberty. The serum levels of IgG and IgA decreased progressively in the fourth decade of life, while serum IgM increased. Moreover, the patient developed a marked CD4+ T lymphocytopenia and a meager B lymphocytopenia, vitiligo, positivity for anti-SSA/Ro autoantibodies and granulomatous phlogosis of the knee. The heterogeneity of the clinical and laboratory data suggests that this patient might present an overlap immunodeficiency syndrome with some of the clinical and immunological features typical of the hyper-IgM syndrome (in the X-linked or autosomal forms) and others that can be referred to a nosologically distinct humoral immunodeficiency such as the common variable immunodeficiency.