Anti-inflammatory effects of diet and caloric restriction in metabolic syndrome.

BACKGROUND: Weight loss in patients with metabolic syndrome has positive effects on cardiovascular and type 2 diabetes risks, but its effects on peripheral cytokines and lipid profiles in patients are still unclear. AIM: To determine the effects of diet-induced weight loss on metabolic parameters, lipids and cytokine profiles. METHODS: Eighteen adult males with metabolic syndrome (defined according to IDF 2009) and Body Mass Index (BMI) between 25 and 35 kg/m2 were subjected to a balanced hypocaloric diet for 6 months to reach at least a 5% body weight loss. RESULTS: After weight loss, a significant improvement in BMI, waist circumference, insulin, fasting blood glucose and HOMA-IR (homeostasis model assessment of insulin resistance) was observed. The analysis of LDL (low-density lipoprotein cholesterol) and HDL (high-density lipoprotein cholesterol) lipoproteins showed a change in their composition with a massive transfer of triacylglycerols from HDL to LDL. This was associated with a significant reduction in peripheral pro-inflammatory cytokines such as IL-6, TNF-α, IL-8 and MIP-1ß, leading to an overall decreased inflammatory score. An interesting positive correlation was also observed among peripheral cytokines levels after diet and peripheral levels of CETP (cholesteryl ester transfer protein), an enzyme with a key role in lipid change. CONCLUSION: Weight loss through caloric restriction is associated with an improvement in peripheral lipid and cytokine profiles that may play a major role in improving cardiovascular risk.

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%).

Nephrological indications in combined liver-kidney transplantation.

In isolated liver transplantation pretransplant renal failure is a major mortality risk, there are no guidelines at the moment to establish the indications for a combined liver-kidney transplantation (LKT). In irreversible chronic renal failure (CRF) not on dialysis, nephrological evaluation is required to assess the need for a simultaneous kidney transplantation. There are no experiences about the functional contribution of native kidneys post-LKT. Herein we have reported the case of two patients who underwent LKT in 2004 due to CRF, not yet on dialysis. At the moment of LKT, the first patient (polycystic kidney disease) had a glomerular filtration rate (GFR) = 29 mL/min, and the second recipient (vascular nephropathy and diabetes), a GFR = 33 mL/min. In both cases we did not observe delayed graft function. At discharge the serum creatinine was 1.1 and 1.0 mg/dL, respectively, which was maintained during follow-up. In both cases renal scintigraphy with Tc-99 DMSA was performed to evaluate the functional contributions of transplanted versus native kidneys. In the first case scintigraphy at 9 months after LKT demonstrated an 81% contribution from the transplanted kidney, 9% from the right and 10% from the left native kidneys. In the second case, at 3 months after LKT, the functional contributions were 76%, 10%, and 14%, respectively. The transplanted kidney nephron mass may avoid the need for hemodialysis in the early posttransplant period; in the midterm it may help to maintain residual renal function. As in other combined transplant programs (heart-kidney, kidney-pancreas) with irreversible CRF, a GFR < or = 30 to 35 mL/min may be an indication for LKT, but we need more experience.

Platelet activation and PDGF-AB release during dialysis.

During hemodialysis the blood-membrane contact causes a release of platelet granule content, which contains Platelet Derived Growth Factor (PDGF-AB). In view of its possible role in accelerated atherosclerotic processes, we evaluated the intra- and post-dialytic changes in PDGF-AB serum levels during hemodialysis sessions performed with Hemophan and Polysulfone membranes. PDGF-AB, PF4, betaTG and MPV levels were determined in the peripheral blood in 30 patients each of whom underwent 6 dialysis sessions: 3 with Hemophan (HE) membrane and 3 with Polysulfone (PS) membrane, interpolated by a wash out session with PS membrane. Blood samples were taken at times 0', 30', 120', 180', 240' during dialysis sessions and at 1, 4 and 20 hours after the end of the session. Statistical analysis was done using the ANOVA one way test and Student's t test PDGF-AB serum levels initially increased and, except for a sharp fall at 120', remained constantly high during HD with both membranes tested, not returning to basal values until 20 hours after the end of the session. PF4, betaTG and MPV all showed a similar trend to PDGF. No statistically significant difference was found between the two membranes tested. PDGF-AB, a powerful growth factor in cells of mesenchymal origin, is released during dialysis mainly as a result of the blood-membrane contact. This we found regardless of the type of dialyzer we tested, and, above all, proved to return very slowly to basal values. We speculate that the release of PDGF-AB could play a part like other atherosclerosis risk-factors in the appearance and worsening of atherosclerotic lesions in hemodialysis patients.

[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.