Urinary Excretion of β2-Microglobulin and IgG Predict Prognosis in Idiopathic Membranous Nephropathy

Abstract

An accurate prediction of the prognosis of patients with idiopathic membranous nephropathy (iMN) should allow restriction of immunosuppressive treatment to patients who are at highest risk for ESRD. On the basis of retrospective studies, it has previously been suggested that the urinary excretions of ␤2-microglobulin (U␤2m) and IgG (UIgG) are useful predictors of renal insufficiency in patients with iMN. The threshold values of 0.5 g/min (U␤2m) and 250 mg/24 h (UIgG) have been validated in a new and larger patient cohort. From 1995 onward, 57 patients with iMN (38 men, 19 women; age 48 ؎ 16 yr), a nephrotic syndrome, and a serum creatinine level <1.5 mg/dl were studied prospectively. At baseline, a standardized measurement was carried out to determine renal function and protein excretion. The end point renal death was defined as a serum creatinine exceeding 1.5 mg/dl or a rise of serum creatinine of >50%. Mean (؎SD) follow-up was 53 ؎ 23 mo. Thus far, 25 (44%) of the patients have reached the end point renal death. Multivariate analysis confirmed U␤2m as the strongest independent predictor for the development of renal insufficiency. Sensitivity and specificity were 88 and 91%, respectively, for U␤2m, and both were 88% for UIgG. When the excretions of both proteins were combined, specificity improved to 97%. It is concluded that the present data validate the accuracy of U␤2m and of UIgG in predicting renal outcome in patients with iMN. These markers can be used to guide decisions on the start of immunosuppressive treatment.

Rituximab-based novel strategies for the treatment of immune-mediated glomerular diseases

“…There is ongoing research into whether additional factors, such as urinary biomarkers, may help predict the course of the disease and/or who will respond to therapy. Several authors have examined whether the measurement of low and high molecular weight urinary proteins may be helpful in determining prognosis, rate of progression and response to therapy in membranous nephropathy [72], [73], [74] and [75]. Bazzi et al [76] published a study in 2001 looking at the excretion of urinary proteins in 78 patients with membranous nephropathy.…”

Glomerular and Tubular Damage Markers in Individuals with Progressive Albuminuria

“…Recently, it has become possible to measure markers in urine samples that represent damage to different parts of the nephron (12). These damage markers initially drew much attention as possible early predictors of AKI, but have also recently been reported as predictors for progressive CKD (13)(14)(15)(16). In these studies, progressive CKD was defined as loss of GFR.…”

Prognostic Value of Risk Score and Urinary Markers in Idiopathic Membranous Nephropathy

“…Alternatively, urinary markers have been suggested to predict progression in iMN (5)(6)(7)(8)(9). We showed that urinary excretion of b2-microglobulin (ub2m) or a1-microglobulin (ua1m) accurately predicted progressive loss of kidney function (10,11). When re-evaluated, both markers showed somewhat lower sensitivity and specificity than before.…”

“…Immunosuppressive therapy was advised only in patients with evidence of deteriorating kidney function or severe untreatable nephrotic syndrome. Data of 46 patients were also used in our previous study of low-molecular weight proteins (10).…”

“…Details of our protocol for the evaluation of patients with iMN were described elsewhere (10). In summary, patients were instructed to fast overnight, omit the use of diuretics, and take sodium bicarbonate on the evening before and on the morning of the urinary analysis to raise urinary pH, because ub2m degrades in acidic urine.…”