Year
1977
1983
1985
1988–1989
1997
2005
2006
Author [Ref]
Ueda [1]
Kitajima [2]
Glassock [3]
Yoshikawa [4]
Koyama [5]
Nozawa [9]
Wakai [7]
Source of patients
Tokyo Jikei U
Nationwide
Tokyo Jikei U
Chiba Shakai Hoken Hospital
Kobe University or Tokyo Metropolitan Children’s Hospital
Nationwide
Fukushima Medical University School of Medicine
Nationwide
No. of patients (%)
85/306 Bx (28 %)
500 children
2,175 adults
243
244
258 children
502/1063 Primary GN (47 %)
181 children
2,269
Male (%)
55 (65 %)
304 (61 %)
1,157 (53 %)
67 %
60 %
53 %
59 %
1,104 (49 %)
Age
=<19 y.o. 10 (12 %)
20–24 y.o. 520 (19 %)
<29 y.o. 65 %
Mean age of onset
120 (25 %)
Mean age of onset
526 (23 %)
20–29 y.o.55 (65 %)
15–29 y.o. 1,381 (52 %)
A peak at 20–30 y.o.
9.3 ± 2.8 y.o. in boys
178 (37 %)
11.0 ± 2.3 y.o.
500 (22 %)
30–39 y.o. 18 (21 %)
10.3 ± 2.4 y.o. in girls
129 (27 %)
367 (16 %)
>=40 y.o. 2 (2 %)
58 (12 %)
40–49 y.o. 456 (20 %)
50–59 y.o. 289 (13 %)
60 y.o.- 131 (6 %)
Mode of onset
Chance proteinuria and/or hematuria
47 (55 %)
371 (74 %)
1,408 (65 %)
60 %
158 (61 %)
332 (68 %)
147 (81 %)
Acute nephritic syndrome
32 (6 %)
206 (9 %)
46 (9 %)
8 (4 %)
Gross hematuria
15 (18 %)
70 (14 %)
280 (13 %)
18 %
68 (26 %)
36 (7 %)
26 (14 %)
Nephrotic syndrome
7 %
5 %
32 (12 %)
16 (3 %)
9 (5 %)
76 (3 %)
Clinical manifestation at the time of biopsy
Hypertension
8 (9 %)
10 %
18 (10 %)
414 (18 %)
Renal dysfunction
Ccr<80 9 (11 %)
Ccr<80 13 %
21 %
Cr=>1.25 mg/dl 388 (17 %)
High serum IgA
28 %
46 %
73 %
16 %
Pathology
Minimal
18 (21 %)
23 %
19 %
29 %
16 %
34 (7 %)
123 (68 %)
Grade Ia 514 (24 %)
Focal
19 (22 %)
28 %
27 %
Without C 4 %
Without C 31 %
114 (23 %)
Grade IIa 698 (33 %)
With C 20 %
With C 28 %
Diffuse
Without C 33 (39 %)
50 %
53 %
Without C 16 %
Without C 10 %
311 (63 %)
58 (32 %)
Grade IIIa 688 (33 %)
With C 15 (18 %)
With C 31 %
With C 15 %
Grade IVa 212 (10 %)
Follow-up data
481 children
1,349 adults
Follow-up duration
3 y (1y–8y 9 mo)
29 mo
39 mo
11.8 ± 6.3 y
7.3 ± 3.1 y
77 mo
Remission
20 %
7 %
13 %
71 % for 15 years
91 (50 %)
Nephrotic syndrome
5 %
4 %
3.5 %
Hypertension
4 %
11 %
22.5 %
12 (7 %)
Renal failure
13 %
26 %
20 %
11 %
14 %
ESRF
1 (1 %)
5 %
20 %
7 (4 %)
207 (9 %)
Renal survival 5 years
95 %
96 %
10 years
94 %
85 %
92 %
15 years
89 %
75 %
20 years
61 %
90 %
11.1.2 The Incidence and Prevalence of IgA Nephropathy in Japan
In 1981, the incidence of IgA nephropathy in patients with chance proteinuria and hematuria was examined by a joint effort of many institutions and supported by the National Ministry of Health and Welfare [3]. Among 335 patients (138 children and 197 adults) who received kidney biopsy because of chance proteinuria and hematuria, 33 % of children and 63 % of adult patients were IgA nephropathy [3]. Although the exact incidence or prevalence of IgA nephropathy in Japan is not known, it can be estimated that as much as 0.3 % of the population or approximately 0.3 million Japanese are suffering from IgA nephropathy, based on the data obtained on the occasion of urinary examination in school children, students, and employees [3]. According to the survey from 1993 to 1995 by the Research Committee on the Epidemiology of Intractable Diseases with the financial supports from the Ministry of Health, Labour and Welfare of Japan, the estimated annual numbers of patients treated for IgA nephropathy in 1994 were 24,000 patients (95 % confident interval 21,000–27,000) [6]. In 1996, Yamagata et al. reported a unique prospective long-term follow-up studies of 805 patients (1.4 %) with asymptomatic proteinuria and/or hematuria (478 patients with pure hematuria, 150 with hematuria and proteinuria, and 177 with proteinuria) selected in the mass screening of 56,269 adults between 1983 and 1992 [10]. Renal biopsy was performed in 151 patients in the study population and 68.2 % of these patients had IgA nephropathy. High prevalence of IgA nephropathy in the adult patients with asymptomatic proteinuria and/or hematuria selected in the mass screening was confirmed in their study. In 2002, Yamagata et al. reported a further long-term follow-up study (6.35 years, range 1.03–14.6 years) on Japanese working men to elucidate prognosis and prevalence of chronic renal diseases among proteinuric and/or hematuric subjects found in mass screening [11]. A total of 772 subjects (1.5 %) selected from 50,501 Japanese men aged 15–62 years were found to have asymptomatic hematuria (n = 404), hematuria and proteinuria (n = 155), and proteinuria (n = 213) during their annual urine examination and five consecutive urinalyses. Renal biopsy was performed in 168 patients and 60.7 % of these patients had IgA nephropathy. The incidence of IgA nephropathy in the present subjects was estimated to be as high as 143 cases per one million per year [11]. In 2007, the Committee for the Standardization of Renal Pathological Diagnosis and the Working Group for Renal Biopsy Database of the Japanese Society of Nephrology started the first nationwide, web-based, and prospective registry system, the Japan Renal Biopsy Registry (J-RBR), to record the pathological, clinical, and laboratory data of renal biopsies. Sugiyama reported the results of a cross-sectional study using the pathological diagnoses registered on the J-RBR in 2007 and 2008 [12]. Data were collected from 818 patients from 18 centers in 2007 and 1582 patients from 23 centers in 2008. Renal biopsies were obtained from 726 native kidneys and 92 from renal grafts in 2007 and 1,400 native kidneys and 182 renal grafts in 2008 [12]. Of the native kidneys, the most frequent pathological diagnosis was IgA nephropathy both in 2007 (32.9 %) and 2008 (30.2 %) [12]. In 2013, Sugiyama reported the registered data from 3,336 cases in 2009 and 4,106 cases in 2010 [13]. The percentages of IgA nephropathy were 31.6 % and 30.4 %, in 2009 and 2010, respectively.
11.2 The Etiology of IgA Nephropathy Investigated by Japanese Researchers
Although the pathogenesis of IgA nephropathy is not fully determined, they include the genetic factors, abnormality of IgA molecule, abnormality of mucosal immune system such as the tonsil and intestine, infectious antigen, and food antigen. Obviously, it is not known whether the etiology of IgA nephropathy differs among different parts of the world. There has been much works done in Japan concerning the pathogenesis of IgA nephropathy. Here, investigations by Japanese researchers concerning an abnormality of IgA molecule, tonsillar abnormality, infectious antigen, and food antigen are described.
11.2.1 Abnormality of IgA1 Molecule
The accumulated evidences of a pathogenetic significance of IgA1 molecule abnormality in IgA nephropathy investigated by Hiki et al. include the existence of the dimeric form of IgA class anti-IgA antibody in the circulation [14], the increased reactivity of O-glycan(s) in the IgA1 hinge region to jacalin due to an unusual glycosylation of serum IgA1 [15], the unusual glycosylation on the hinge region of jacalin-binding IgA1 due to an insufficient conformational stiffness to the hinge peptide, resulting in the aggregation of the IgA1 molecule [16], the presence of a defect in the Gal and/or GalNAc residues in the IgA1 hinge glycopeptides [17], the aberrant exposure of the peptide core of the IgA1 hinge region by a defective N-acetylgalactosaminylation [18], the underglycosylated hinge glycopeptide of IgA1 molecules in the glomerular accumulation of IgA1 [19], and a possibility of induction of the humoral immune response due to the peptide epitope of the IgA1 hinge region aberrantly exposed by underglycosylation [20].
11.2.2 Tonsillar Abnormality
In Japan, a number of investigations of the tonsillar abnormality in IgA nephropathy have been reported.
The reports of the histochemical investigations of tonsillar abnormality in patients with IgA nephropathy include the presence of IgA1 subclass in follicular dendritic cells (FDC) of the tonsil [21], a decreased reticulization of tonsillar crypt epithelium [22], an increase in CD5+ B cells (B-1 cell) numbers in the germinal center of tonsils [23], and an increase of CD208(+) dendritic cells [24].
The reports of the studies of IgA produced in tonsil in patients with IgA nephropathy include an overproduction of asialo IgA1 in the tonsils [25], an increase in the percentage of asialo-agalacto type O-glycans in IgA1 produced by tonsillar lymphocytes [26], and a significant increase in asialo-agalacto type O-glycans in the tonsillar IgA1 hinge in IgA nephropathy [27].
The reports for the production of cytokines by tonsillar mononuclear cells or gene expression of tonsillar cells in IgA nephropathy include increased IFN-gamma production [28], increased MCP-1, IL-8 incubation with staphylococcus enterotoxin-B or lipopolysaccharide [29], an elevated frequency of T cell receptor variable (TCR V) beta 6 in tonsils [30, 31], an increase in the proportions of TCR V beta 6-positive cells in peripheral blood T cells and an enhanced expression of TCR V beta 6 in tonsillar T cells in vitro stimulation with Haemophilus parainfluenzae antigen [31], a high intercellular expression of IFN-gamma on the T cells isolated from tonsils, higher spontaneous productions of IgA and IFN-gamma of tonsillar mononuclear cells (TMCs), a significantly higher productions of IgA, B cell activation factor BAFF and IFN-gamma of TMCs under stimulation with unmethylated deoxycytidyl-deoxyguanosine oligodeoxynucleotide, a high BAFF expression on the CD1c cells and the BAFF production of TMCs [32], an elevated gene expression of the APOBEC2 in the tonsils [33], a decreased gene expression of beta1,3-galactosyltransferase (beta3GalT) and the core 1 beta3GalT-specific molecular chaperone, Cosmic, UDP-N-acetyl-alpha-D-galactosamine, polypeptide N-acetylgalactosaminyltransferase 2 in tonsillar CD19-positive B lymphocytes, decreased protein expression of beta3GalT in the tonsils [34], a high expression of tonsillar mucosal toll-like receptor 9 (TLR9) in 23 % of the patients with IgA nephropathy and well correlation between tonsillar TLR9 and TLR9 SNP and the efficacy of tonsillectomy with steroid pulse therapy [35], and upregulated muscle-related genes and immune-related genes and downregulated polymeric Ig receptor [36].
11.2.3 Infectious Antigen
The viruses which have been reported in relation to IgA nephropathy include adeno, herpes simplex, varicella-zoster or parainfluenza 3 [37], retrovirus [38], and enteroviruses [39]. However, Kunimoto et al. reported that they could not detect the presence of herpes simplex virus 1 and 2, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus (EBV) 1 and 2 in tonsils, renal tissues, and mouth washings from patients with IgA nephropathy [40].
The bacteria which have been reported as a candidate of the pathogenesis of IgA nephropathy include Haemophilus parainfluenzae [41–48], Streptococcus [49, 50], Escherichia coli [51], Haemophilus influenzae [51], Staphylococcus aureus [52, 53], and Helicobacter pylori [54, 55] and periodontal disease bacteria such as Treponema sp., Haemophilus segnis, and Campylobacter rectus [56].
11.2.4 Food Antigen
Only few reports concerning the food antigen in relation to the pathogenesis of IgA nephropathy have been published between 1988 and 1991 in Japan. Yagame et al. reported no increase in the levels of IgA-circulating immune complexes (IgA-CIC) 2 weeks after the gluten-rich diet and suggested that the short-term gluten-rich diet might not increase the levels of IgA-CIC in Japanese patients with IgA nephropathy [57]. Kuramoto et al. reported no difference in the serum level of IgG, IgA, and IgM antibody titers against six food-derived antigens (rice, soybean paste, soy sauce, egg yolk, egg white, and gluten) between the patients with IgA nephropathy and healthy controls and suggested that food antigens appear to have little relation to IgA nephropathy [58]. The glomerular deposition of food antigens was investigated in two reports; 39.3 % and 25 % of patients were positive with casein [59, 60], 69 % and 75.0 % with soybean protein [59, 60], and 3.6 % with rice protein [59].
In 1991, Coppo et al. reported a comparative investigation concerning geographical difference in the importance of food antigen as a pathogenesis of IgA nephropathy [61]. Serum IgA as antibodies to dietary antigens (Ag), as lectin-binding molecules, and as conglutinin-binding immune complexes (IgA IC) was studied in people from Italy, Australia, and Japan. Increased values of IgA IC were detected in 42.8 % of Italian patients, in 23.8 % of Australian, and in only 8 % of Japanese patients. IgA antibodies against dietary Ag were detected in 19–28.5 % of Italian patients, 0–38 % of Australians, and 0–16 % of Japanese. The relationship between IgA IC and serum concentration to alimentary component was particularly evident for Italian and Australian IgA nephropathy patients [61].
These results suggest that the dietary antigen as a pathogenesis might be less important in Japanese patients with IgA nephropathy.
11.3 The Treatment of IgA Nephropathy in Japan
11.3.1 Overview of the Treatment of IgA Nephropathy in Japan
The most conspicuous treatment of the patients with IgA nephropathy in Japan includes steroid therapy, tonsillectomy, and tonsillectomy with steroid pulse therapy.
Kobayashi et al. firstly reported a significant effect of steroids on the amount of proteinuria and prevention of progression of renal deterioration in series of retrospective studies [62–66]. Since then, Japanese nephrologists began to use steroid in patients with progressive IgA nephropathy. Although there have been many retrospective studies concerning the efficacy of steroid therapy [67–78], only a few randomized control trials have been reported in adult patients with IgA nephropathy [79–81].
The effect of tonsillectomy has been reported in patients with IgA nephropathy especially in those with chronic tonsillitis [82–89]. In 2001, Hotta et al. reported the impact of tonsillectomy and steroid pulse therapy on the remission of urinary abnormality in patients with IgA nephropathy [90]. Since then, there have been many reports published about the efficacy of such therapy [91–100], and tonsillectomy with steroid pulse therapy has been widely spread throughout Japan as the first line of treatment of adult patients with IgA nephropathy [101, 102]. However, the tonsillectomy with steroid pulse therapy was not accepted as a standard treatment of IgA nephropathy internationally due to the lack of high-level evidence of the effect of such therapy. The recent Kidney Disease: Improving Global Outcomes clinical guideline for glomerulonephritis suggests that tonsillectomy not be performed for IgA nephropathy, because no randomized controlled trial of tonsillectomy has been performed [103]. Recently, Kawamura et al. reported the results of a multicenter, randomized, controlled trial (RCT) of tonsillectomy combined with steroid pulse therapy in patients with IgA nephropathy versus steroid pulse monotherapy conducted by the Special IgA Nephropathy Study Group of the Progressive Glomerular Diseases Study Committee organized by the Ministry of Health, Labour and Welfare of Japan [104]. Although they found a significantly greater antiproteinuric effect in combined therapy, the difference was marginal. Thus, they concluded that the impact of tonsillectomy combined with steroid pulse therapy on the renal functional outcome remains to be clarified. The details of this randomized controlled trial will be described in Chap. 19.
In contrast to the treatment of the adult patients with IgA nephropathy in Japan, the treatment of Japanese pediatric patients with IgA nephropathy has been determined in evidence-based method by the Japanese pediatric IgA nephropathy treatment group. They performed several RCTs or pilot studies in the different subset of children with IgA nephropathy [105–110].
In this part, the major clinical investigations of treatment of IgA nephropathy in Japan will be described, in adult patients and pediatric patients, separately.
11.3.2 The Treatment of Adult Patients with IgA Nephropathy in Japan
11.3.2.1 Steroid Therapy
Main results of a series of the retrospective studies by Kobayashi et al., case series by Yoshimura et al., and three RCTs are summarized in Table 11.2.
Table 11.2
Steroid treatment of adult patients with IgA nephropathy in Japan
1st author | Year | Study design | Inclusion criteria | No. of patients | No. of controls | Initial dose of steroid (mg/day) | Duration of steroid treatment | Follow-up duration | Main results | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Kobayashi [62] | 1986 | R | UP 1–2 g/day | 14 | 29 | PSL40 mg | 19 mo | 60–80 mo | Steroid group | Control | |||
Initial | Last | Initial | Last | ||||||||||
UP (g/day) | 1.2 | 0.7* | 1.3 | 1.3 | |||||||||
Ccr (ml/min) | 86 | 78* | 86 | 45 | |||||||||
Progressive | 21 % | 69 % | |||||||||||
ESRF | 7 % | 31 % | |||||||||||
Kobayashi [64] | 1988 | R | UP >= 2 g/day | 29 | – | PSL40 mg | 12–36 mo | 68–93 mo | Initial Ccr | >= 70 | < 70 | ||
n | 15 | 14 | |||||||||||
Initial | Last | Initial | Last | ||||||||||
UP (g/day) | 3.3 | 1.5 | 3.1 | 1.7 | |||||||||
Ccr (ml/min) | 83 | 62 | 51 | 18 | |||||||||
Progressive | 7 (47 %) | 5 (36 %) | |||||||||||
ESRF | 1 (7 %) | 8 (57 %) | |||||||||||
Kobayashi [65] | 1989 | R | UP 1–2 g/day and followed up >= 4 years | 18 | 42 | PSL40 mg | 18 mo | 73–79 mo | Steroid group | Controls | |||
Ccr >= 70 | 15 cases | 31 cases | |||||||||||
Stable | 11 (73 %) | 12 (39 %) | |||||||||||
Progressive | 3 (20 %) | 10 (32 %) | |||||||||||
ESRF | 1 (7 %) | 9 (29 %) | |||||||||||
Ccr < 70 | 3 cases | 11 cases | |||||||||||
Stable | 0 (0 %) | 0 (0 %) | |||||||||||
Progressive | 2 (67 %) | 0 (0 %) | |||||||||||
ESRF | 1 (33 %) | 11 (100 %) | |||||||||||
Kobayashi [66] | 1996 | R | UP 1–2 g/day and Ccr 70 or more and histological score >=7 and followed up >=10 years | 20 | 26 | PSL40mg | 18 mo | 10 years | Steroid group | Controls | |||
Initial data | |||||||||||||
Proteinuria (g/day) | 1.4 ± 0.4 | 1.3 ± 0.3 | |||||||||||
Ccr (ml/min) | 85 ± 14 | 88 ± 13 | |||||||||||
Hypertension (%) | 25 | 38 | |||||||||||
Histological score | 10.7 ± 2.5 | 11.0 ± 3.0 | |||||||||||
Kidney survival | |||||||||||||
5 years | 100 % | 84 %* | |||||||||||
10 years | 80 % | 34 %* | |||||||||||
Yoshimura [67] | 1992 | Cases | UP >= 2+ and cellular crescent >=10 % of glomeruli | 8 | – | 2 courses of mPSL 1 g/day for 3 days | 3–5 mo | 3–5 mo | Pre-treatment | Post-treatment | |||
UP | 2.3 ± 0.5 | 1.1 ± 0.3** | |||||||||||
GFR | 83 ± 11 | 96 ± 10** | |||||||||||
Crescent (%) | 25 ± 6 | 16 ± 5 | |||||||||||
Shoji [79] | 2000 | RCT | UP<1.5 g/day and Scr <1.5 mg/dl and diffuse mesangial proliferation (Mes pro) | 11 | 10 | PSL 0.8 mg/kg | 12 mo | 13.4 mo | Steroid group | Controls | |||
Initial | Last | Initial | Last | ||||||||||
UP | 0.75 | 0.29** | 0.73 | 0.71 | |||||||||
Mes pro (%) | 65 | 42.7** | 59.3 | 50.7 | |||||||||
Increase in mm (%) | 62 | 45.2** | 63.4 | 56.9 | |||||||||
Cellular crescent (%) | 7.6 | 0.9** | 1.9 | 2.5 | |||||||||
αSMA (grade) | 2.1 | 1.2** | 1.8 | 1.6 | |||||||||
Katafuchi [80] | 2003 | RCT | Glomerular score 4~7 | 43 | 47 | PSL20 mg | 24 mo | 64–65 mo | Steroid group | Controls | |||
ΔUP/UCR | −0.84 ± 1.78* | 0.26 ± 1.65 | |||||||||||
ESRF: n, (%) | 3 (5.7) | 3 (6.4) | |||||||||||
Koike [81] | 2008 | RCT | Mild histological activities | 24 | 24 | PSL 0.4 mg/kg | 24 mo | 24 mo | Steroid group | Controls | |||
Scr (mg/dl) | 0.92 ± 0.26* | 1.15 ± 0.35 | |||||||||||
Vascular changes | 0.63 ± 0.73* | 1.08 ± 0.88 | |||||||||||
Initial | Last | Initial | Last | ||||||||||
UP (g/day) | 0.97 | 0.31** | 0.89 | 0.68 | |||||||||
U-RBC/HPF | 35.6 | 13.7** | 30.1 | 12.4** | |||||||||
In 1986, Kobayashi et al. reported the efficacy of steroid treatment in patients with IgA nephropathy, whose urinary protein was between 1.0 and 2.0 g/day [62]. A total of 14 patients were treated with steroids, and 29 patients received no steroids. They found significant reduction of urinary protein in patients with steroid treatment and deterioration of renal function in patients without steroids. The difference in the amount of proteinuria and renal function at the final observation between the patients with steroid treatment and those without it was more distinct in patients with initial creatinine clearance (Ccr) 70 ml/min or more. Thus, they concluded that treatment with steroids in IgA nephropathy may be beneficial, especially in the early stage of the disease. In 1988, Kobayashi et al. investigate the efficacy of steroids in 29 patients with IgA nephropathy whose proteinuria is 2.0 g/day or more and found that steroids were effective in patients with initial Ccr greater than 70 ml/min [64]. They suggested that steroid therapy in IgA nephropathy may be able to stabilize a progressive course, especially in the early stage of the disease. In 1989, Kobayashi et al. further investigated the efficacy of steroid therapy in IgA nephropathy patients with proteinuria between 1.0 and 2.0 g/day in the follow-up of more than 4 years and confirmed the efficacy of steroid treatment in the reduction of the amount of proteinuria and stabilization of renal function in patients with initial Ccr 70 ml/min or more [65]. In 1996, Kobayashi et al. confirmed the efficacy of steroid therapy on 10-year kidney outcome in patients with proteinuria 1–2 g/day and Ccr 70 ml/min or more [66].
The report by Yoshimura et al. in Japanese article is worthy to introduce here because it is the first one concerning the effect of steroid pulse therapy in IgA nephropathy [67]. They reported a significant decrease in urinary protein and a significant increase in glomerular filtration rate (GFR) after the methylprednisolone pulse therapy in eight patients with progressive IgA nephropathy, defined as 2+ or more urinary protein and crescents in 10 % or more glomeruli. They also found a significant reduction in the percentage of cellular crescent in the second biopsy after the treatment compared to the first biopsy. Thus, they suggested that the methylprednisolone pulse therapy significantly reduced urinary protein excretion and improved renal function through suppression of new crescent formation as well as transformation of cellular crescents to fibrocellular or fibrous crescents.
In 2000, Shoji et al. reported the result of the first RCT in Japanese patients with IgA nephropathy [79]. Inclusion criteria were diffuse mesangial proliferation, the duration of abnormal urinalysis less than 36 months, proteinuria less than 1.5 g/day, and serum creatinine level less than 1.5 mg/dL. A total of 21 patients were randomly assigned to the corticosteroid group (11 patients) and the antiplatelet group (10 patients). They found a significant reduction in proteinuria and a significant improvement of histological findings in the corticosteroid group and concluded that early treatment with corticosteroids for adult diffuse proliferative IgA nephropathy is effective in reducing renal injury.
In 2003, Katafuchi et al. reported the results of RCT of low-dose prednisolone therapy in patients with IgA nephropathy with moderate histological severity [80]. A total of 43 patients in the steroid group and 47 patients in the control group were included in their study and found a significant antiproteinuric effect of steroids, but there was no effect of steroid treatment on kidney outcome. Thus, they suggested that an insufficient dose of prednisolone in their protocol may be the reason for the discrepancy between the effect on proteinuria and kidney survival.
In 2008, Koike et al. reported the result of RCT in patients with IgA nephropathy with mild histological activities [81]. A total of 24 patients in the steroid group and 24 patients in the control group were included in their study. They found a significant decrease in the amount of proteinuria and the grade of hematuria in steroid group compared to controls and concluded that low-dose steroid therapy for IgA nephropathy patients with mild inflammatory lesions could reduce the amount of urinary protein excretion and prevent deterioration of renal function.
11.3.2.2 Tonsillectomy
The results of reports that concern the efficacy of tonsillectomy in a large number of patients with IgA nephropathy are summarized in Table 11.3.
Table 11.3
Tonsillectomy with or without steroid treatment of adult patients with IgA nephropathy in Japan
1st author | Year | Study design | Inclusion criteria | Patients | Controls | Follow-up period | UP Remission (%) | OB Remission (%) | CR (UP+OB remission, %) | Long-term kidney survival | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Tonsillectomy | |||||||||||||||||||||
Tomioka [83] | 1996 | R | TX+ | 104 TX+ | – | 1 year | 38 | ||||||||||||||
Xie [85] | 2003 | R | Followed up >= 5 years | 48 TX+ | 70 TX− | 193 mo | TX+ | TX− | |||||||||||||
ESRF (%) | 10.4* | 25.7 | |||||||||||||||||||
20 year renal survival (%) | 89.6* | 63.7 | |||||||||||||||||||
Akagi [86] | 2004 | R | Followed up >=10 years | 41 TX+ | 30 TX− | 151–159 mo | TX+ | TX− | TX+ | TX− | |||||||||||
24.4 | 13.3 | Renal survival rate (%) | 95.1* | 73.3 | |||||||||||||||||
Maeda [89] | 2012 | Cohort | Scr <2.0 mg/dl and followed up >= 1 year | 70 TX+ (50 with steroids) | 130 TX− (19 with steroids) | 7 years | Multivariate-adjusted HR of TX for CR | Multivariate-adjusted HR of TX for decline GFR | |||||||||||||
Model | HR (95 % CI) | Model | HR (95 % CI) | ||||||||||||||||||
Age and gender adjusted | 3.90* (2.46–6.18) | Age and gender adjusted | 0.14* (0.02–1.03) | ||||||||||||||||||
Clinical factor adjusted | 4.03* (2.52–6.44) | Clinical factor adjusted | 0.12* (0.02–0.89) | ||||||||||||||||||
Histological factor adjusted | 3.71* (2.30–5.98) | Histological factor adjusted | 0.12* (0.02–0.89) | ||||||||||||||||||
Treatment factor adjusted | 3.06* (1.74–5.40) | Treatment factor adjusted | 0.10* (0.01–0.85) | ||||||||||||||||||
Tonsillectomy plus steroid therapy | |||||||||||||||||||||
Hotta [90] | 2001 | R | Followed up >= 36 mo | 250 TX+ | 79 TX− | 82.3 mo | 48 | Probability of progressive deterioration at 10 year | |||||||||||||
CR+ | CR− | ||||||||||||||||||||
0 | 21 ± 5 % | ||||||||||||||||||||
Sato [91] | 2003 | R | Scr >= 1.5 | 70 | 70.3 mo | Total | TSP | S | C | ||||||||||||
n | 70 | 30 | 25 | 15 | |||||||||||||||||
ESRF (%) | 41.4 < div class='tao-gold-member'>
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