As a primary survey, we sent a questionnaire and letter to 848 hospitals in Japan, each of which employed a Fellow of the Japanese Society of Nephrology between October and December of 2006, in order to gather information about the prevalence and efficacy of TSP
therapy for patients with
IgA nephropathy. As a secondary survey, we collected data from both low- and high-CR-rate groups to determine which factors predicted resistance to TSP
therapy.
RESULTS: A total of 2,746 patients received TSP
therapy between 2000 and 2006. The CR rates, calculated by measuring urinary criteria 6 and 12 months after TSP
therapy, were 32.0% (347/1,085) and 45.6% (452/991), respectively. Analysis of the 30 hospitals in which TSP
therapy had been performed on at least ten patients revealed that the CR rates varied from below 10% to 100%. A secondary survey of ten hospitals revealed that, after correction of the CR rate from each hospital, patients could be categorized into three groups: those with a low CR rate (122 patients in four hospitals), a middle CR rate (78 patients in four hospitals), and a high CR rate (103 patients in two hospitals). The CR rate of all patients (N = 303) was 54.1%. A comparison of patient data between the low- and high-CR-rate groups showed a significant difference in age at onset (years; P = 0.05), amount of
proteinuria (g/day; P = 0.02), total
protein (g/dl; P = 0.02), pathological grade (P = 0.009), and prognostic score as described by Wakai et al. [Nephrol Dial Transplant 21:2800-2808, 2006, (P = 0.04)]. Univariate analysis revealed that there was a significant difference between non-CR and CR subgroups in duration from diagnosis until TSP
therapy (6.9 +/- 6.8 versus 5.3 +/- 5.2 years; P = 0.02), amount of
proteinuria (1.5 +/- 1.6 versus 0.8 +/- 0.8 g/day; P < 0.0001), serum
creatinine (0.99 +/- 0.40 versus 0.87 +/- 0.34 mg/dl; P = 0.006), pathological grade (P = 0.0006), and Wakai et al.'s prognostic score (37.4 +/- 17.8 versus 28.1 +/- 15.1; P < 0.0001). A multivariate logistic analysis demonstrated that resistance to TSP
therapy depends on age at onset, amount of
proteinuria,
hematuria grade, and pathological grade, and a score predicting resistance to TSP
therapy could be derived by the formula: [(-0.0330) x (age) + (0.4772) x log (amount of
proteinuria) - (0.0273) x (
hematuria grade: 0, 1, 2, and 3) + (0.7604) x (pathological grade: 1, 2, 3, and 4) - 0.1894]. A receiver operating characteristic (ROC) curve showed that patients with a resistance score of greater than -0.02 easily resist TSP
therapy (sensitivity 69%, specificity 75%, positive likelihood ratio 2.76).
CONCLUSION: TSP
therapy shows promise as a treatment that can bring about CR of urinary abnormalities, but unfortunately the average CR rate is about 50% at 1 year
after treatment. Predictive factors for resistance to TSP
therapy are age at onset, amount of
proteinuria,
hematuria grade, and pathological grade. The present study suggests that patients with either early-stage or mild to moderate
IgA nephropathy easily achieve CR following TSP
therapy, whereas patients with late-stage or severe disease are prone to TSP
therapy resistance.