[Familial membranoproliferative glomerulonephritis].
BACKGROUND
Idiopathic membranoproliferative (mesangiocapillary) glomerulonephritis (MPGN) is a chronic, often progressive renal disease with variable clinical expression divided into three distinct morphological formes, now designated types I, II, and III, on the basis of immunofluorescent (IF) and ultrastructural appearances and complement profiles [1-5]. Several lines of evidences suggest a genetic basis for at least some cases of MPGN I and III. The extended haplotypes HLA-B8, DR3, SCO1, GLO2 were found to constitute 13% of the disease-associated haplotypes and 1% of control hyplotypes [8]. Significantly high percentage of those with MPGN I and III have inherited defects of the complement system [9]. Additional evidence for genetic factors is the rarity of the disease in blacks [10] and examples of MPGN occurring in families. The disease has been reported in siblings as well as in families with affected members spanning more than one generation [11-16]. Here we describe clinical and morphological features in two siblings affected by MPGN and present complement and HLA typing studies done in patients and their parents. A review of familial MPGN I and III cases reported between 1981 and 1996 is made, and genetic susceptibility factors for MPGN are discussed.


METHODS
Between 1976 and 1996 diagnosis of idiopathic MPGN was made in 24 patients, aged 516.5 years. The diagnosis was established after excluding systemic, liver and infectious disorders and malignant neoplasms. The MPGN type was confirmed by light microscopy, IF and electron microscopy studies of the renal biopsy tissues processed by standard techniques. One family with two siblings having MPGN was identified in our series. This family was examined for the presence of renal disease and an inherited complement defect. Laboratory evaluations of the patients and parents included complete urinalysis, serum protein, albumin, urea, creatinine and cholesterol levels and glomerular filtration rate (GFR) estimation. ANA, rheumatoid factors, cryoglobulins, immune complexes, HBV antigens and antibodies and anti-HCV antibodies were also determined. Haemolytic tests for CHSO (classical and alternative pathways) were carried out using standard techniques. The measurement of the various complement factors was carried out using a radial immunodiffusion technique with monospecific antisera (CIq, C2, C4, C3, C5, B, H). HLA-A, B, DR and DQ haplotypes were determined by microcytotoxicity assay of peripheral blood lymphocytes.


RESULTS
Patient 1 (SC, male). Renal disease presented at the age of his five years with nephrotic syndrome resistant to corticosteroid treatment. Morphological features and serum complement profile suggested type I MPGN. Treatment consisted of alternate-day prednisone, followed by cyclosporine and then by cyclophosphamide. At the end of the follow-up lasting 5.5 years he had only moderate proteinuria. Patient 2 (MC, female). Proteinuria was revealed at the age of 3 years becoming progressive and leading to the nephrotic syndrome resistant to corticosteroids at the age of 6 years. Electronmicroscopy features were consistent with type III MPGN, although serum C3 and C4 levels remained normal all the time. The same treatment as in her brother was given but she remained persistently nephrotic and anaemic; hypertension developed when she was 6 years old and her renal function became to declaine at the age of 7.5 years. Detailed family studies failed to reveal any evidence of complement deficiencies or secondary cause of MPGN. Siblings had in common HLA-A24, B27, Bw4, DRI1, DRS2, and DQ3 antigens.


CONCLUSIONS
In our patients clinical and morphological features are very similar and are consistent with diagnosis of MPGN, i.e. probably type I in the boy and type III in the girl. Although some extended haplotypes HLA-B8, DR3, SCO1, GLO2, were significantly more frequent (13%) than in controls (1%), and the patients with MPGN having this extended haplotype had
Bogdanović
R M
RM
Institute of Mother and Child Health of Serbia, Belgrade.
Dimitrjević
J Z
JZ
Nikolić
V N
VN
Ognjanović
M V
MV
Rodić
B D
BD
Slavković
B V
BV
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D007668:Kidney / Q000473:pathology; D008297:Male