Relationship between serum IgA/C3 ratio and progression of IgA nephropathy

OBJECTIVE: The serum IgA/C3 ratio might be considered to serve as a diagnostic marker for patients with IgA nephropathy (IgAN), but its value as a marker of the severity of histological lesions or prognosis is unknown. METHODS: We studied the serum IgA/C3 ratio, using standardized reference material, in 86 patients with IgAN and in 32 with non-IgAN. The patients with IgAN were divided according to the severity of histological lesions (mild IgAN, n=29 and severe IgAN, n=57) based on Japanese clinical guidelines. RESULTS: The serum IgA level was significantly higher, while its C3 level was lower in patients with severe IgAN compared to those with non-IgAN. However, these levels were not different between patients with mild IgAN and non-IgAN. In contrast, the serum IgA/C3 ratio obviously differed among the three groups (2.47+/-0.96 vs. 3.63+/-1.44 vs. 4.72+/-1.86; p<0.01, ANOVA). Kaplan-Meier analysis of the patients with IgAN classified according to the mean serum IgA/C3 ratio revealed that the group with high serum IgA/C3 (4.5 and above) had a significantly poorer renal outcome (p<0.05, log-rank test), since the cumulative renal survival rate at 5 years was 84.4% vs. 100%. The ratio (%) of patients with severe IgAN in whom hematuria disappeared, was significantly higher in the low, than in the high serum IgA/C3 group (41.9% vs. 15.4%; p<0.05, t-test). CONCLUSION: The serum IgA/C3 ratio appears to reflect the histological severity of IgAN and could serve as a marker of the progression of IgAN.     

Reduced expression of heme oxygenase-1 in patients with coronary atherosclerosis.

Heme oxigenase-1 (HO-1) is known to be an inducible cytoprotective enzyme that copes with oxidative stress. However, changes in HO-1 expression and their association with human diseases have not been studied. To test the hypothesis that the capacity to upregulate HO-1 in response to oxidative stress is an intrinsic marker for susceptibility to coronary atherosclerosis, we assessed stimulation-induced change in HO-1 expression in blood cells in 110 patients who underwent coronary angiography, comparing the results with the extent of coronary atherosclerosis and (GT)(n) repeat polymorphism in the HO-1 gene promoter region, which is believed to affect the gene expression level. The extent of coronary atherosclerosis was assessed by coronary score. Mononuclear cells were incubated with 10 micromol/l hemin or vehicle for 4 h to maximally stimulate HO-1 expression, then the HO-1 expression level was determined by real-time polymerase chain reaction (PCR). The difference between the HO-1 mRNA levels of hemin- and vehicle-treated cells (DeltaHO-1 mRNA) was taken as an index of the capacity to upregulate HO-1 mRNA. The coefficient of variance of DeltaHO-1 mRNA was 7.2%. Consistent with previous studies, DeltaHO-1 mRNA was significantly lower in patients carrying a long (GT)(n) repeat. DeltaHO-1 mRNA negatively and significantly correlated with the coronary score (r(2)=0.50, p<0.01). In conclusion, the capacity to upregulate HO-1 expression may be determined, at least in part, by genetics, and reduced ability to induce HO-1 may be involved in the mechanism of coronary atherosclerosis.     

Anteroposterior and varus–valgus laxity of the knee increase after stair climbing in patients with mild osteoarthritis

The aim of this study was to measure exercise-induced changes in knee joint laxity in patients with knee osteoarthritis (OA). The study subjects were 46 female patients with OA and 22 age- and sex-matched normal controls. Radiographs of the knee were taken in all subjects, and the disease severity was graded according to the Kellgren and Lawrence (K-L) grading system. The K-L grade of the control subjects (non-OA group) was 0-1. The OA patients were divided into those with mild OA (K-L grade 2, n = 20) and advanced OA (K-L grade 3-4, n = 26). The subject climbed up and down 8 steps on a staircase apparatus over a period of 10 min. The anteroposterior (A-P) translation was measured with KT2000 arthrometer, and varus-valgus (V-V) rotation was measured on stress radiographs before and after the stair climbing. The Δchange in A-P translation after the exercise was significantly larger in mild OA group than other groups (P < 0.005). The Δchange in V-V rotation after exercise was significantly larger in mild and advanced OA groups than the control (P < 0.003). There were no significant differences in A-P laxity and V-V laxity before exercise among the non-OA, mild OA and advanced OA groups. Exercise resulted in significant changes in A-P knee joint laxity in patients with mild OA relative to the control. The results suggest that daily physical activities (e.g., knee bending or squatting) play a role in the development of knee laxity, particularly in patients with mild OA, and that progression of knee OA seems to correlate with increments of A-P knee joint laxity.