Fractional excretion of IgG predicts renal outcome and response to therapy in primary focal segmental glomerulosclerosis: a pilot study.
BACKGROUND
Prolonged treatment with steroids and/or cyclophosphamide improves the prognosis of primary focal segmental glomerulosclerosis (FSGS). In nephrotic patients, no clinical or histological feature predicts responsiveness to therapy.


METHODS
In 50 patients with FSGS, fractional excretion (FE) of immunoglobulin G (IgG), albumin, transferrin, and alpha(1)-microglobulin (alpha(1)m) was calculated. The aim of the study is to assess whether FE IgG and FE alpha(1)m: (1) correlate with histological lesions, (2) predict outcome, and (3) may be useful to guide therapy.


RESULTS
The association of FE IgG with percentage of glomeruli with segmental sclerosis was at the limit of significance (P = 0.01). FE alpha(1)m was associated with extent of tubulointerstitial damage (P = 0.008). By multiple regression analysis, FE alpha(1)m was dependent on FE IgG (R(2) = 0.76; P = 0.000). The predictive value of proteinuric variables on outcome was evaluated in 29 patients with nephrotic syndrome and baseline normal renal function (serum creatinine level, 1.04 +/- 0.22 mg/dL [92 +/- 19 micromol/L]; follow-up, 50 +/- 33 months); remission rates were 91% and 0% in patients with FE IgG less than versus greater than 0.140 (P = 0.0009). By multiple logistic regression analysis, only FE IgG was associated with remission (P = 0.043). Proteinuria less than versus greater than 7.5 g/d of protein predicted end-stage renal failure (0% versus 36%; P = 0.004); the predictive value of FE IgG less than versus greater than 0.140 was higher (0% versus 71%; P = 0.0000). Patients with FE IgG less than 0.025 were responsive to steroids alone (70%) or steroids and cyclophosphamide (20%); patients with FE IgG greater than 0.025 and less than 0.140 were responsive to steroids alone (20%) or steroids and cyclophosphamide (80%); and 100% of patients with FE IgG greater than 0.140 were unresponsive to therapy (P = 0.000).


CONCLUSIONS
In FSGS, FE IgG is at the limit of statistically significant association with segmental sclerosis, and FE alpha(1)m is associated with extent of tubulointerstitial damage. FE IgG shows the best predictive value for remission, progression, and response to therapy and may be useful to guide treatment. Am J Kidney Dis 41:328-335.
Bazzi
Claudio
C
Division of Nephrology and Dialysis, Biochemical Laboratory, San Carlo Borromeo Hospital, Milan, Italy.
Petrini
Concetta
C
Rizza
Virginia
V
Napodano
Pietro
P
Paparella
Maria
M
Arrigo
Girolamo
G
Pisano
Lucia
L
D'Amico
Giuseppe
G
D058186:Acute Kidney Injury / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology / Q000652:urine; D000328:Adult; D000510:Alpha-Globulins / Q000652:urine; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications / Q000188:drug therapy* / Q000652:urine*; D006801:Humans; D007074:Immunoglobulin G / Q000652:urine*; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000652:urine; D008297:Male; D009404:Nephrotic Syndrome / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000652:urine; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011379:Prognosis; D011507:Proteinuria / Q000188:drug therapy / Q000473:pathology; D012074:Remission Induction / Q000379:methods; D016896:Treatment Outcome
D000510:Alpha-Globulins; D007074:Immunoglobulin G; C016001:alpha-1-microglobulin; D003520:Cyclophosphamide