Abstract The number of patients with membranoprolif-erative glomerulonephritis(MPGN) diagnosed in our in-stitution and the incidence of hypocomplementemia asdetermined by school urinary screening programs in Ja-pan were investigated retrospectively. Fifty-seven chil-dren were diagnosed as having MPGN between 1974and 1997. Of these, 13 patients were diagnosed duringperiod 1 (1974–1979) and 25 during period 2 (1980–1985). A decreasing trend was observed during periods 3(1986–1991) (12 patients) and 4 (1992–1997) (7 pa-tients) compared with period 2 (P<0.05 and P<0.01, re-spectively). A significant difference was also noted whenMPGN was compared between periods 1 and 2 (1974–1985) and periods 3 and 4 (1986–1997) (P<0.01). SerumC3 was measured in 1,282 school children with abnor-mal urinary findings between 1980 and 1997. Thirtychildren had hypocomplementemia. The incidence of hy-pocomplementemia was significantly lower in period 3 (1986–1991) (9 children) and period 4 (1992–1997) (2 children) compared with period 2 (1980–1985) (19children) (P<0.05 and P<0.01, respectively). New casesof MPGN in our institution and the incidence of hypo-complementemia as determined by school urinaryscreening programs are decreasing in Japan. The reasonfor this trend is unknown.

Key words Membranoproliferative glomerulonephritis ·Hypocomplementemia · School urinary screening

Introduction

The relationship between the light microscopic appear-ance of renal biopsy of idiopathic membranoproliferativeglomerulonephritis(MPGN) and a low serum level of C3was reported by West et al. [1] in 1965. In Japan, MPGNhas been detected in many children by school urinaryscreening. Most of these children had low serum C3 lev-els [2]. In Europe and Canada, a decreasing number ofpatients with MPGN has been reported [3, 4]. However,other groups have reported conflicting results [5, 6].

In this paper, we report our experience and observa-tions on the number of patients with MPGN diagnosed atKitasato University Hospital between 1974 and 1997,and also the incidence of hypocomplementemia as deter-mined by school urinary screening in Kanagawa Prefec-ture between 1980 and 1997.

Patients and methodsBetween 1974 and 1997, 57 children were diagnosed as having id-iopathic MPGN at our hospital. Of these, 47 had typical MPGN and10 had focal segmental MPGN (FSMPGN). The average age ofthese patients at the time of presentation was 9.5 (3–15) years. De-tails of the pathological studies have been described elsewhere [2].

Between 1974 and 1997, a total of 547 children, presenting atless than 15 years with primary glomerular disease, were biopsiedat Kitasato University Hospital, one of the referral centers for pe-diatric renal diseases in Kanagawa Prefecture. Transplant biopsieswere not included.

A total of 992,346 urine specimens from 153,908 children inelementary and junior high school were examined between 1980and 1997. Serum C3 was measured in 1,282 children with abnor-mal urinary findings. The screening methods and the method formeasuring serum C3 levels have also been described elsewhere[7]. Initially, the normal range for serum C3 was 53.0–97.0 mg/dl,but this was changed to 50.0–90.0 mg/dl in 1992. The chi-squaredtest was used for statistical analysis.

Results

Among 547 children who had a renal biopsy at KitasatoUniversity Hospital between 1974 and 1997, 57 patients(10.4%) had idiopathic MPGN. Ten patients had

K. IitakaYamato City Hospital, Japan

K. IitakaKitasato University School of Medicine, Japan

T. SakaiChildren’s Kidney Center, Kanagawa, Japan

K. Yagisawa · Y. AokiKanagawa Health Service Association, Kanagawa, Japan

K. Iitaka (✉ )8-3-6 Fukaminishi Yamato-shi, Kanagawa 242–8602 Japane-mail: iitaka@wd5.so-net.ne.jpTel.: +81-0462-600111, Fax: +81-0462-603366

Pediatr Nephrol (2000) 14:794–796 © IPNA 2000

O R I G I N A L A RT I C L E

Kikuo Iitaka · Tadasu Saka · Katsumi YagisawaYoshikazu Aoki

Decreasing hypocomplementemia and membranoproliferative glomerulonephritis in Japan

Received: 10 August 1999 / Revised: 22 November 1999 / Accepted: 23 November 1999

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Table 1 New cases ofmembranoproliferative glomer-ulonephritis (MPGN) duringfour 6-year periods between1974 and 1997. Numbers of pa-tients with focal segmentalMPGN are in parentheses

Period 1 2 3 4 Total1974–1979 1980–1985 1986–1991 1992–1997

Number of biopsied patients 136 139 139 133 547Number of 13 (0) 25 (3) 12 (5) 7 (2) 57 (10)MPGN patients 9.6% 18.0% 8.6% 5.3% 10.4%Number of MPGN 2.2 4.2 2.0 1.2 2.4patients per year

Table 2 Incidence of hypocomplementemia in schoolchildren between 1980 and1997a, b

Period 2 3 4 Total1980–1985 1986–1991 1992–1997

Number of school children screened 386,796 332,334 273,216 992,346Number of school children with complement 468 495 319 1,282measurementsNumber of children with hypocomplementemiac 19 (5) 9 (6) 2 (1) 30 (12)

4.1% 1.8% 0.6% 2.3%

a Normal range of C3: 53.0–97.0 mg/dl, 1980–1991b Normal range of C3: 50.0–90.0 mg/dl, 1992–1997c Numbers of children with serum C3 below 30 mg/dl are in parentheses

Table 3 Number of patients with MPGN in biopsy populations from various countries

Country Population Incidence Reference

Number of patients/institute/year

1972–1975 1976–1979 1980–1983 1985 [3]Italy Adult 95 (21%) 71 (14%) 38 (6%)

7.9 5.9 3.11971–1976 1977–1983 1985 [8]

France Adult 105 (16%) 46 (8%)17.5 6.6

1977–1981 1981–1985 1986 [10]Spain Adult 26 (17%) 10 (8%)

6.5 2.51976–1980 1981–1985 1987 [9]

France Adult 20 (10%) 5 (2%)4.0 1.0

1966–1980 1981–1985 1987 [4]Canada Children 39 6

2.6 1.21972–1976 1977–1981 1982–1986 1990 [11]

Spain Children 27 (11%) 40 (7%) 32 (5%)0.4 0.6 0.5

1965–1969 1970–1974 1975–1979 1980–1984 1985–1989 1992 [5]USA Children 2.6 2.0 4.1 2.2 1.6

1981–1984 1985–1988 1988–1992 1994 [6]Turkey Children 19 (14%) 21 (14%) 20 (13%)

4.8 5.3 5.01974–1979 1980–1985 1986–1991 1992–1997

Japan Children 13 (10%) 25 (18%) 12 (9%) 7 (5%) (Present2.2 4.2 2.0 1.2 study)

FSMPGN. The number of MPGN patients diagnosedduring each 6-year period is listed in Table 1.

The number of MPGN patients increased during pe-riod 2 (1980–1985) and decreased during periods 3(1986–1991) and 4 (1992–1997). The number of patients

with MPGN was significantly smaller in periods 3 and 4compared with period 2 (P<0.05 and P<0.01, respective-ly). The difference was also significant when comparingperiods 1 and 2 (1974–1985) (38 patients) with periods 3and 4 (1986–1997) (19 patients) (P<0.01).

1992 [6]. We observed a similar trend as West [5] butwith a greater recent decrease.

Data for school screening in Tokyo in 1992 reportedby Murakami et al. [12] appear to corroborate the presentresults. Of 326,257 children screened, C3 was measuredin 2,669 children with urinary abnormalities, and only 3had low levels (3, 40, and 44 mg/dl). MPGN was diag-nosed in 1, and the other 2 were not biopsied.

In conclusion, our study indicates that new cases ofMPGN in our institution and the incidence of hypocom-plementemia as determined by school urinary screeningprograms are decreasing in Japan. The reason for thistrend is not known.

Acknowledgements We would like to thank Dr. Clark D. Westand Dr. Nobuo Matsuura for their critical review of this manu-script. This study was supported by the Ishii Fund of the Ka-nagawa Study Group for school urinary screening and renal dis-ease.

References

1. West CD, McAdams AJ, McConville JM, Davis NC, HollandNH (1965) Hypocomplementemic and normocomplementemicpersistent (chronic) glomerulonephritis: clinical and patholog-ic characteristics. J Pediatr 67:1089–1112

2. Iitaka K, Ishidate T, Hojo M, Kuwao S, Kasai N, Sakai T (1995)Idiopathic membranoproliferative glomerulonephritis in Japa-nese children. Pediatr Nephrol 9:272–277

3. Barbiano di Belgiojosa G, Baroni M, Pagliari B, Lavagni MG,Porri MT, Banfi G, Colasani G, Confalonieri R (1985) Ismembranoproliferative glomerulonephritis really decreasing?A multicenter study of 1,548 cases of primary glomerulone-phritis. Nephron 40:380–381

4. Arbus G, Getu H, Baumal R, Mraz V, Jabs D, Eddy A (1987)Long-term follow-up, including renal transplantation, of chil-dren with membranoproliferative glomerulonephritis. In:Murakami K, Kitagawa T, Yabuta K, Sakai T (eds) Recent ad-vances in pediatric nephrology. Excerpta Medica, Amsterdam,pp 242–346

5. West CD (1992) Idiopathic membranoproliferative glomerulo-nephritis in childhood. Pediatr Nephrol 6:96–103

6. Yalcinkaya F, Tumer N, Cakar N, Ekim M (1994) Paediatricmembranoproliferative glomerulonephritis is not decreasing inTurkey! Pediatr Nephrol 8:131–132

7. Iitaka K, Igarashi S, Sakai T (1994) Hypocomplementemiaand membranoproliferative glomerulonephritis in school uri-nary screening in Japan. Pediatr Nephrol 8:420–422

8. Jungers P, Forget D, Droz D, Noel LH, Grunfeld JP (1985)Reduction in the incidence of membranoproliferative glomeru-lonephritis in France. Proc Eur Dial Transplant Assoc 22:730–735

9. Simon P, Ramee MP, Ang KS, Cam G (1987) Variations ofprimary glomerulonephritis incidence in a rural area of400,000 inhabitants in the last decade. Nephron 45:171

10. Burgos RR, Novoa (1986) Incidence of membranoproliferativeglomerulonephritis in a Spanish population. Clin Nephrol26:161

11. Study Group of the Spanish Society of Nephrology (1990) De-creasing incidence of membranoproliferative glomerulonephri-tis in Spanish children. Pediatr Nephrol 4:266–267

12. Murakami M, Tatsuma N, Tsugu H, Ambo K, Tsuchiya M,Yamamoto M, Yamauchi K (1997) Incidence of hypocomple-mentemia in elementary and junior high school children withurinary abnormalities. Acta Paediatr Jpn 39:413–415

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Annual urinary screening started in 1980 in Chi-gasaki and Hiratsuka City, Kanagawa Prefecture. Thenumber of school children screened, the number of chil-dren with abnormal urinary findings who had their se-rum complement measured, and the number of childrenwith hypocomplementemia during the three 6-year peri-ods are shown in Table 2. The overall number of schoolchildren has gradually decreased in Japan, however theincidence of hypocomplementemia was significantlylower during periods 3 (1986–1991) (9 children) and 4(1992–1997) (2 children) compared with period 2(1980–1985) (19 children) (P<0.05 and P<0.01, respec-tively). Among the 30 hypocomplementemic patients,12 had serum C3 levels below 30 mg/dl. Of these 12children, 7 had a renal biopsy and were diagnosed ashaving MPGN.

Discussion

This study shows a decreasing trend of MPGN and hy-pocomplementemia in Japanese school children duringthe past 24 and 18 years, respectively. Many children(71%) with a diffuse proliferative form of MPGN hadtheir urinary abnormalities detected by school urinaryscreening. Most (95%) had persistently low levels of C3over 3 months in our experience [2].

The number or percentage of MPGN cases in the bi-opsy population in other countries is summarized inTable 3. A significant drop in the number of patients withMPGN has also been reported in Europe and Canada [3,4]. In Italy, the frequency of MPGN decreased from 21%to 6% of biopsied patients over a 10-year period [3]. InFrance, the frequency of new cases of MPGN droppedby 50% or more over a 10-year period [8, 9]. In Spain,the percentage of cases in the biopsy population was17% between 1977 and 1981, and 8% between 1981 and1985 [10]. These were reports on adult populations. Inthe late 1980s and early 1990s, decreasing numbers ofchildren with MPGN were reported. In Canada, the num-ber of new cases per year decreased from 2.6 between1966 and 1980, to 1.2 between 1981 and 1985 [4]. InSpain, a multicenter study showed a decreasing percent-age of MPGN in the biopsy population, from 10.9% be-tween 1972 and 1976, to 6.6% between 1977 and 1981and 5.4% between 1982 and 1986 [11].

In contrast, West [5] showed that, when patients re-ferred from outside their catchment area were eliminat-ed, the frequency of new cases was fairly constant over10-year periods between 1965 and 1974, and between1980 and 1989, but there was a definite increase over the5-year period between 1975 and 1979. However, theyobserved an approximate 50% decrease between 1980and 1984, suggesting that the decrease represented a re-turn to a baseline frequency, defined as that existing be-tween 1965 and 1974 [5]. In Turkey, a stable MPGN fre-quency of 14% in children was noted between 1981 and