Long-Term Follow-Up Study oflgMAssociated Nephrotic Syndrome Patients : Clinical Outcome and Prognostic Indicators
PATHRA KURATHONG,M.D.*, SOMNUEK JESDAPATARAKUL, M.D.**
Affiliation : KURATHONG P & JESDAPATARAKUL S J Med Assoc Thai 2000; 83: 315-324 IgM nephropathy is the most common primary glomerular disease in Thailand0,2). IgM nephropathy was first reported independently in 1978 by Cohen et al(3), and Bhasin et al(4). Histo- logically, IgM nephropathy is characterized by generalized and diffuse deposition of immunoglo- bulin M (IgM) more prominently than any other type of immunoglobulin in the renal mesangium. There may or may be no associated staining with C3. Diagnosis of IgM nephropathy is established by ex- amination of renal-biopsy tissue with light micro- scopy and with immunofluorescent stain. Clinically, IgM nephropathy may be associated with edema (as found in patients with nephrotic syndrome) or with- out edema. There are controversies whether IgM nephropathy is a new entity(5) as reported by Cohen et a!, and Bhasin et a!, or it is merely an intermediate stage of minimal change disease and focal segmen- tal glomerulosclerosis(6). There were reports of finding IgM deposits in the renal mesangium of normal persons; others attached it to progressive glomerular disease(?). There were reports of the effects of mesangial IgM deposits on the clinical features, on response to corticosteroid, and on prog- nosis(5,7,8). Other reports showed no evidence of the specific role of IgM in mesangial prolifera- tion(9, 1 0). In Thailand, clinical studies on adult idio- pathic or primary nephrotic syndrome (PNS) re- vealed IgM nephropathy is the most common cause of PNSOl-14), while in the West, membranous nephropathy is the most common cause of PNS(l5). The etiology and pathogenesis of IgM nephropathy remain unknown. There have been a few reports on the clinical course and prognosis of IgM nephro- pathy(I6-18). There have been reports of a high incidence of renal failure when IgM nephropathy was associated with hypertension( 16), or when it was resistant to corticosteroid therapy( 17, 18 l. In some reports, the presence of hematuria had no effect on the prognosis, and subsequent renal failure in patients with IgM nephropathy(7,8, 17). How- ever, in one report07), when it was associated with renal insufficiency, IgM nephropathy responded poorly to therapy, and progressed to renal failure. The purposes of this long-term follow-up study were to determine the (I) responsiveness to prednisolone therapy, (2) long-term clinical and laboratory outcomes, and (3) prognosti.: indicators to prednisolone therapy of IgM associated PNS patients. PATIENTS AND METHOD All patients diagnosed as IgM associated PNS, and follow-up at Vajira Hospital from 1978 to 1996, were included in this study. Inclusion criteria Patients with PNS associated with (I) proteinuria > 3 g/D, (2) serum albumin < 3 g/dl, (3) edema, (4) renal-biopsy proved IgM nephropathy, and (5) follow-up for more than 3-consccutive months were included in the study. Exclusion criteria Patients with PNS who (I) were < 15 years old, or (2) had no renal biopsy, or (3) received no prednisolone treatment, or ( 4) were followed-up for less than 3 months after prednisolone therapy, were excluded from the study.
Rationale: Even though it is the most common primary glomerular disease, the natural
history and prognosis of lgM associated nephrotic syndrome have not been well established.
Objectives : To determine the (1) responsiveness to prednisolone therapy, (2) long-term
clinical and laboratory outcomes, and (3) prognostic indicators to prednisolone therapy in patients
with IgM associated nephrotic syndrome.
Study design : Clinical descriptive, longitudinal study.
Subjects : Seventy two biopsy-proved IgM associated nephrotic syndrome patients,
diagnosed between 1978-1996 at Vajira Hospital, Bangkok, were included in the study.
Method : Clinical parameters with age, sex, duration of edema, blood pressure and labo-
ratory findings such as hematuria, BUN, creatinine, albumin, and cholesterol, 24-hour urine protein,
and stool examination, were collected pre-renal biopsy. Each patient was treated with 45-60 mg of
prednisolone according to body weight, for up to 8 weeks. Each patient was followed-up every
4-weeks for clinical and laboratory evaluations, and for adjusting the steroid dosage. Clinical
responses were stratified into 3 groups as steroid responsive (SRP), steroid dependent (SD), and
steroid resistant (SRS).
Main outcome measures : (I) Frequency and types of steroid responsiveness. (2) Inci-
dence of hypertension, hematuria, renal insufficiency, end-stage renal disease, and survival during
the follow-up. (3) Prognostic indicators for initial clinical response to prednisolone, and for
long-term morbidity and mortality.
Results : Forty eight of the 72 patients (66.67%) were responsive to prednisolone at
8-weeks, the 24 remaining patients (33.33%) were nonresponsive. High proteinuria of 7.66 ± 4.14
g/D was the only good prognostic indicator to initial prednisolone therapy (p < 0.03). During the
follow-up, 42(58.33% ), 26(36.11% ), and 4(5.56%) patients were SRP, SD, and SRS, respectively.
There were no prognostic indicators associated with long-term steroid responsiveness. Of the 60
patients followed-up for more than one year; 34, 15 and 11 patients were followed-up for 1-5,
* Department of Medicine,
** Department of Pathology, Bangkok Metropolitan Administration Medical College, and Vajira Hospital, Bangkok
1 0300, Thailand.
>5-1 0 and > 10 years, respectively. Hematuria and proteinuria were more frequent among the SRS
group (p < 0.01 and 0.02, respectively) during the follow-up. Only one patient, initially in the SD
group, and later on became SRS, died.
Conclusion : Patients with IgM associated nephrotic syndrome had very good response
to prednisolone therapy. It had a very slow progressive course, with low morbidity and mortality.
Keywords : IgM Associated Nephrotic Syndrome, Long-term Follow-up, Steroid Responsive- ness, Prognostic Indicators
