title: Fractional urinary excretion of IgG is the most powerful predictor of renoprotection by ACE inhibitors in IgA nephropathy.
abstract: BACKGROUND
  Several aspects of renoprotection by angiotensin-converting enzyme inhibitors (ACEi) in IgA nephropathy (IgAN) are poorly defined: factors affecting responsiveness, role of proteinuria components and histological lesions, and criteria to identify patients who may benefit from ACEi.
  
  
  METHODS
  In an observational study of 140 IgAN patients (follow up 62 +/- 36 months), 73 untreated and 67 ACEitreated for 53 +/- 28 months, 9 baseline risk factors (RFs) (blood pressure, serum creatinine, proteinuria/day, fractional excretion of IgG [FEIgG] and alpha1-microglobulin, global and segmental [SS] glomerular sclerosis, tubulointerstitial damage and arteriolar hyalinosis [AH] score), each divided into 2 subgroups according to a cutoff with the highest sensitivity and specificity for progression, were evaluated for ability to predict renoprotection. Primary end point: end-stage renal disease (ESRD) and doubling of serum creatinine (sCr); secondary end point: increase >or=25% of sCr with last sCr >or=1.58 mg/dL; total progression: sum of end points.
  
  
  RESULTS
  Patients with RFs below cutoffs did not benefit from ACEi. All clinical and proteinuric and 2 histological RFs (SS, AH score) with values above cutoffs showed significant reduction of progression in ACEitreated vs. untreated patients; FEIgG showed the highest prediction of renoprotection: ESRD/sCrx2: 20% vs. 62% (p=0.0004); total progression: 40% vs. 85% (p=0.0003). By multivariate analysis, independent predictors of progression were FEIgG, sCr and no ACEi treatment. Proteinuria reduction from -100% to -30%, spontaneous or after ACEi treatment, did not affect progression in treated vs. untreated patients (19% vs. 13%, p=0.85). Patients with proteinuria increased or reduced <30% showed a reduction of total progression if ACEi-treated (15% vs. 77%, p=0.0002). Presence of 1 clinical or proteinuric RF above the cutoff may be a criterion to identify patients who may benefit from ACEi.
  
  
  CONCLUSIONS
  Renoprotection by ACEi is a multifactorial phenomenon: the best predictor of renoprotection is FEIgG, a marker of disruption of glomerular barrier to proteins; renoprotection depends not only on ability to reduce proteinuria, but probably also on antiinflammatory and antifibrotic activity.
authors: Fondazione D'Amico per la Ricerca sulle Malattie Renali, Milan - Italy. claudio.bazzi@alice.it
authors: Claudio
authors: C
authors: Bazzi
authors: Virginia
authors: V
authors: Rizza
authors: Maria
authors: M
authors: Paparella
authors: Daniela
authors: D
authors: Casellato
authors: Pietro
authors: P
authors: Napodano
authors: Giulia
authors: G
authors: Olivieri
authors: Giuseppe
authors: G
authors: D'Amico
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001706:Biopsy; D002648:Child; D018450:Disease Progression; D005260:Female; D005922:Glomerulonephritis, IGA / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D006801:Humans; D007074:Immunoglobulin G / Q000652:urine*; D007668:Kidney / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000517:prevention & control; D012307:Risk Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007074:Immunoglobulin G