Rituximab in relapsing and de novo MPO ANCA-associated vasculitis with severe renal involvement: a case series.

BACKGROUND: Antineutrophil cytoplasmic antibody associated vasculitis (AAV) is a group of diseases associated in most cases with the presence of anti-neutrophil cytoplasmic antibodies (ANCAs). Rituximab- based remission induction has been proven effective in ANCA associated vasculitis but scarce data exist in forms with severe renal involvement. In this case series, we report the outcomes in patients with de novo or recurrent MPO-AAV and severe renal involvement treated with rituximab without cyclophosphamide (CYC). METHODS: In this single centre retrospective study, we analysed patients with a clinical diagnosis of de novo or recurrent AAV who met the following criteria: detection of P-ANCA, creatinine clearance lower than 30 ml/min, induction of remission therapy with rituximab without concomitant CYC and a follow up period of at least 6 months. The primary outcomes were complete remission after induction therapy, renal function recovery and mortality after the induction treatment. RESULTS: Eight patients met the inclusion criteria. The M:F ratio was 1:7, the average age was 54 years old and the median follow up was 10 months (7-72); in 2 patients there was a MPA renal limited vasculitis. A renal biopsy was performed in 7 patients. The median BVAS score at rituximab induction was 14(range 6-21). Two patients required haemodialysis before the induction treatment. Four patients developed end stage renal disease (ESRD) that required haemodialysis. These data show a remission of the disease, associated with a stabilization of the kidney function in 50% of patients. In 3 patients who did not show a response, there was also no response to CYC. CONCLUSIONS: This study shows a partial efficacy of rituximab in renal function recovery and a low risk of infectious complications in patients with MPO vasculitis with severe renal involvement, in particular in the short term. The optimal treatment in this subgroup of patients still has to be established because data are lacking.

Renin angiotensin system blockade and activated vitamin D as a means of preventing deep vein thrombosis in renal transplant recipients.

BACKGROUND: Venous thromboembolism (VTE) is one of the thrombotic complications that occur in renal transplant recipients (RTR). The observation that vitamin D receptor activators, angiotensin-converting enzyme inhibitors (ACEi), and angiotensin receptor blockers (ARBs) have a protective effect against protrombotic state suggests that their possible combination could reduce the incidence of VTE in RTR. OBJECTIVES: to evaluate the incidence of VTE in RTR and the timing of occurrence after renal transplantation (Tx); to compare the incidence of VTE in our RTR and RTR on calcitriol, ACEi, ARBs and their combination therapy. Risk factors were also evaluated. RESULTS: During follow-up, 96 of 769 RTRs, 73 males 23 females, developed a first episode of VTE: 23 in the first 3 months after Tx; 15 from 3 to 6 months; 9 from 6 to 12 months; 13 from 12 to 48 months and 36 after more than 48 months. The incidence was significantly lower in RTR on treatment with a combination of calcitriol 0.25 µg/day, an ACEi and an ARB and in RTR on treatment with only calcitriol 0.5 µg/day (9.4% and 9%, respectively, vs. 14.5% (p < 0.05)). However, the most decreased rate (5.6% vs. 14.5% (p < 0.01)) was in patients treated with a combination of calcitriol 0.5 µg/day, an ACEi and an ARB. CONCLUSION: A combination therapy with calcitriol 0.5 µg/day, ACEi, and ARB is associated with a 60% lower rate risk of VTE.

Kidney graft survival rates do not improve by era: the impact of the age factor.

We performed this study to evaluate whether older ages of donors and recipients negatively affected long-term graft survival. We compared 5-year graft survival rates of 89 recipients transplanted between 1991 and 1995 (period A) versus 221 recipients transplanted between 1996 and 2000 (period B). Acute rejection rates and the number of donors and recipients >50 years of age were compared in the two periods. The 5-year graft survival rate in period B was 76.3% versus 82% in period A. In period B, the acute rejection incidence was 18% versus 40% in period A (P < .001). The overall 5-year graft survival was 86.2% for donors aged 21-50 years and 65.7% for donor's aged >50 years (P < .0001) in period A versus 84.1% and 68%, respectively, in period B (P = .0023). In period A, 23.6% of donors and 35.9% of recipients were >50 years old, versus 50.2% and 42.9%, respectively, in period B. The graft survival rate in period B was worse than in period A, although the acute rejection rate was lower. The older age of both donors and recipients in period B seemed to be an important cause of worse outcomes.

Subcutaneous nodules and infectious complications in renal allograft recipients.

Renal transplant recipients are at increased risk of infectious diseases and subject to cutaneous infections because of the effects of immunosuppressive therapy. Some long-term descriptive follow-up studies confirm that skin infections are common among renal transplant recipients. We report the development of subcutaneous nodules among patients receiving renal transplantations from 1991 to 2009. Transplant recipients were followed by the Nephrology Unit at control visits according to the American Society Nephrology guidelines. Between 1991 to 2009, subcutaneous nodules were identified in 7 out of 774 renal transplant recipients. The male:female ratio was 5:2; median age at renal transplantation was 52 years (range 28-59). Subcutaneous nodules were identified at a median 3 years after transplantation. The 7 patients had the following diagnoses: systemic scedosporiasis (n = 1); Mycobacterium avium complex infection (n = 2) disseminated tuberculosis (n = 2) Sporothrix schenckii infection (n = 1); Trichophyton rubrum infection (n = 1). Four patients died due to sepsis from disseminated infection. Subcutaneous nodules may reflect a systemic infectious pathology. In some cases, the investigation of cutaneous lesions is important to reach a definitive diagnosis for possible future disseminated infections.

Reticulated platelets and platelet reactivity in renal transplant recipients receiving antiplatelet therapy.

INTRODUCTION: Renal transplant recipients are at increased risk of cardiovascular morbidity and mortality. We assessed platelet reactivity and reticulated platelets (RPs) in 90 recipients, 51 (56.6%) of whom were not receiving acetylsalicylic acid (ASA) therapy (group A) and 39 (43.3%) who were receiving ASA therapy, 100 mg (group B), and in 60 healthy controls (group C). METHODS: Reticulated platelets were measured using a hematology automated analyzer (XE-2100; Sysmex Corp, Kobe, Japan) and were expressed as the percentage of RPs in the total optical platelet count (immature platelet fraction [IPF]), as the percentage of highly fluorescent RPs, and as the absolute number of RPs (IPF#). Platelet function was assessed using optical aggregometry (platelet aggregation) induced using 1 mmol/L of arachidonic acid, 2 or 10 micromol/L of adenosine diphosphate, or 2 microg/mL of collagen. RESULTS: Group A demonstrated significantly higher values of RP compared with group B or group C. Group B demonstrated a substantially higher percentage of RPs compared with group C, which was significant only for the IPF parameter. Multiple regression analysis demonstrated that IPF and IPF# were significantly and positively related to collagen-induced platelet aggregation. CONCLUSION: We documented the presence of higher concentrations of RPs in transplant recipients compared with a control population, and a significant association between RPs and platelet function.

Lower homocysteine levels in renal transplant recipients treated with everolimus: a possible link with a decreased cardiovascular risk?

Cardiovascular disease (CVD) is the main cause of morbidity and mortality in renal transplant recipients. The incidence of CVD in this setting is approximately 5-fold greater than in age- and and gender-matched subjects. This excess cardiovascular risk is not completely explained by traditional cardiac risk factors. It has been well documented that these patients show greatly increased prevalence of both fasting and postmethionine-loading hyperhomocysteinemia (hHcy) compared with the general population. An immunosuppressive therapy based on everolimus has been demonstrated to reduce the incidence major adverse coronary events at 4 years compared with azathioprine among heart transplant recipients. In contrast, scarce data are available on the impact of everolimus on emerging risk factors, such as homocysteine (Hcy), in renal transplant recipients. The aim of this study was to evaluate the possible impact of everolimus compared with other immunosuppressive regimes among 132 stable recipients, including 91 men and 41 women who were at least 1 year after transplant with stable renal function and no clinical evidence of acute or chronic renal graft rejections. We compared 31 subjects on everolimus immunosuppressive therapy (group A) versus 101 on immunosuppressive therapy based on cyclosporine, steroids, and mycophenolate. The Hcy levels were significantly lower among group A patients compared with group B: 16.5 +/- 5 micromol/L vs 21.2 +/- 11 micromol/L; P < .005. Hyper-Hcy, defined as Hcy levels >15 micromol/L, was diagnosed in 18 out of 31 patients (51%) of group A and in 82 out of 101 patients (81%) of group B. This preliminary study demonstrates a favorable impact of everolimus on a marker of atherothrombosis which is associated with a worse vascular prognosis.

Blood rheology and renal transplantation: an intriguing relationship for assessing cardiovascular risk.

Renal transplant recipients (RTRs) are at increased risk of cardiovascular complications. An altered hemorheological profile may determine both cardiovascular complications and progression of renal failure in RTRs. We performed this study to evaluate the rheologic status in 239 RTRs at least 12 months after transplantation with stable and normal renal function compared with 90 control subjects. In RTRs, a significantly higher hematocrit-adjusted, but not native, whole blood viscosity was found (P < .0001). Moreover, plasma viscosity and red blood cell deformability were significantly higher in patients than in control subjects (P < .0001), whereas no difference in erythrocyte aggregation between patients and control subjects was observed (P = .5). Fibrinogen, but not hematocrit, significantly increased in RTRs (P = .001). This preliminary study provides evidence of an altered hemorheologic profile in RTRs.