Progressive improvement of patient and renal survival and reduction of morbidity over time in patients with lupus nephritis (LN) followed for 20 years.

Whether the long-term patient and renal survival of those diagnosed with lupus nephritis (LN) has improved over the decades is still debated. Eighty-nine patients diagnosed between 1968 and 1990 entered this study and their outcome was evaluated after 20 years. At presentation 54% of patients had class IV LN, 39.3% had renal insufficiency and 59.5% had nephrotic syndrome. Patients were divided into two groups: Group 1 consisted of 30 patients diagnosed between 1968 and 1980; Group 2 consisted of 59 patients diagnosed between 1981 and 1990. In Group 1 patient survival at 20 years was 84% versus 95% in Group 2 (p=0.05). Survivals without end-stage renal failure were respectively 75% and 84% at 20 years (p=0.05). Survivals without severe infection at 20 years were 44% in Group 1 and 66.5% in Group 2 (p=0.02). Survivals without cardiovascular events at 20 years were: 53% in Group 1 and 90% in Group 2 (p=0.005). At presentation, patients in Group 1 had higher serum creatinine (1.96 vs 1.15 mg/dl, p=0.01), higher activity index (8 vs 5.5, p=0.01), lower hematocrit (31% v s6%, p=0.008) and lower serum C4 levels (p=0.04) than Group 2 patients. Patients in Group 1 also received less frequent methylprednisolone pulses (43% vs 81%, p=0.0006). In Italian patients with LN, long-term life expectancy and renal survival progressively improved over the decades, while morbidity progressively declined. An earlier referral and refinement of therapy achieved this goal.

Oxidative stress and homocysteine metabolism in patients with lupus nephritis.

The objective of this study was to compare oxidative status and homocysteinemia in patients with lupus nephritis (LN) and in controls. Total antioxidant capacity (TAC), reactive oxygen species (ROS), homocysteine and related vitamins were measured in 68 patients with LN and in 50 controls. LN patients had lower TAC (p = 0.05) and higher ROS and homocysteinemia (p = 0.01) than controls. TAC, significantly lower in active than in quiescent LN (p = 0.01), was correlated with albuminemia (p = 0.02), inversely with proteinuria (p = 0.01) and anti-DNA antibodies (p = 0.004). ROS values, higher both in active and in inactive LN, correlated with age (p = 0.02), C-reactive protein (CRP) (p = 0.0005) and inversely with prednisone dosage (p = 0.05). At multivariate analysis, CRP (p = 0.04) and age (p = 0.005) were independent ROS predictors. Homocysteine, higher in active than in quiescent LN (p = 0.016) and in patients with antiphospholipid antibodies (p=0.05), correlated with serum creatinine (p = 0.00001) and proteinuria (p = 0.015). At multivariate analysis serum creatinine (p = 0.006) and active nephritis (p = 0.003) were independent predictors of hyperhomocysteinemia. Patients with LN showed impaired oxidative status, even without clinical signs of renal activity. ROS production may be counterbalanced by adequate antioxidant capacity in some patients with quiescent LN. The association of hyperhomocysteinemia and antiphospholipid antibodies positivity may increase the risk of cardiovascular and/or thrombotic events in LN patients.

Are laboratory tests useful for monitoring the activity of lupus nephritis? A 6-year prospective study in a cohort of 228 patients with lupus nephritis.

OBJECTIVES: To evaluate the role of immunological tests for monitoring lupus nephritis (LN) activity. METHODS: C3, C4, anti-dsDNA and anti-C1q antibodies were prospectively performed over 6 years in 228 patients with LN. RESULTS: In membranous LN only anti-C1q antibodies differentiated proteinuric flares from quiescent disease (p = 0.02). However, in this group 46% of flares occurred with a normal value of anti-C1q antibodies versus 20% in proliferative LN (p = 0.02). In patients with antiphospholipid antibodies (APL), 33% of flares occurred with normal levels of anti-C1q antibodies versus 14.5% in patients that were APL-negative (p = 0.02). In proliferative LN, anti-C1q antibodies showed a slightly better sensitivity and specificity (80.5 and 71% respectively) than other tests for the diagnosis of renal flares. All four tests had good negative predictive value (NPV). At univariate analysis anti-C1q was the best renal flare predictor (p<0.0005). At multivariate analysis, the association of anti-C1q with C3 and C4 provided the best performance (p<0.0005, p<0.005, p<0.005 respectively). CONCLUSIONS: Anti-C1q is slightly better than the other tests to confirm the clinical activity of LN, particularly in patients with proliferative LN and in the absence of APL. All four "specific" tests had a good NPV, suggesting that, in the presence of normal values of each, active LN is unlikely.

The long-term prognosis of renal transplant in patients with systemic vasculitis.

Little information is available about the long-term outcome of renal transplantation in patients with systemic vasculitis (SV). We compared the outcomes of 19 renal transplant recipients with SV with those of 38 controls matched for time of transplantation, age, gender and source of donor. The mean post-transplant follow-up was 58 +/- 57 months for vasculitic patients and 61 +/- 49 months for controls. The actuarial 10-year patient survival was 87% in vasculitic patients and 90% in controls, death-censored graft survival were 84% and 100%, respectively. The risks of acute and chronic rejection, and arterial hypertension were not significantly different between the two groups. Infection was significantly more frequent in vasculitic patients (74% vs. 34%; p = 0.01). Seven patients (36.8%) had a recurrence of vasculitis in mean 45 months after renal transplant (0.076/patients/year). After recurrence, one patient had an irreversible humoral rejection, another died from hemophagocytosis and another restarted dialysis 1 year later. Long-term patient and renal allograft survival in vasculitic patients was good. Although graft function recovered in most relapsers after reinforcement of immunosuppression, one patient died and two lost graft function.

[SLE: Extra-renal clinical manifestations and lupus nephritis]. / LES: Manifestazioni cliniche extra-renali E nefrite lupica.

Systemic Lupus Erythematosus (SLE) is a chronic inflammatory autoimmune disease affecting multiple organ systems, skin and joints the most involved. Lupus Nephritis occurs in Approximately 50% of patients, sometimes it may be the first manifestation of SLE. Clinical features range from asymptomatic urinary abnormalities to full-blown nephrotic syndrome or rapidly progressive renal failure. Because of the heterogeneity of clinical renal manifestations, renal biopsy plays an important role in the management of patients with SLE: it provides information about the class, severity, activity and chronicity of the renal disease that cannot be accurately predicted on the basis of clinical parameters. The complexity of protean renal manifestation of SLE can be approached using the original WHO classification (1982), recently revised (2004).