Mesangial hypercellularity predicts antiproteinuric response to dual blockade of RAS in primary glomerulonephritis

Abstract

The greater antiproteinuric efficacy of converting enzyme inhibitor and angiotensin II receptor blocker combination (CEI+ARB), versus monotherapy with either drug, is not a consistent finding. We evaluated the clinicopathologic predictors of response to CEI+ARB in 43 patients with primary glomerulonephritis (GN), never treated with immunosuppressive drugs, and with persistent proteinuria after CEI alone. Main histological lesions were analyzed by obtaining on 557 glomeruli and 165 arteries formal score of mesangial cellularity, glomerulosclerosis, tubulointerstitial damage, mononuclear cell infiltration, arteriosclerosis, and arteriolar hyalinosis. Duration of CEI and CEI+ARB therapy was similar (4.7+/-2.4 and 5.0+/-1.5 months). Proteinuria (g/day) decreased from 3.5+/-2.9 to 2.4+/-2.3 after CEI, and to 1.5+/-1.3 after CEI+ARB (P<0.0001). Reduction of proteinuria after CEI+ARB was greater in proliferative versus non-proliferative GN (-63.3+/-23.4 versus 42.4+/-23.7%, respectively; P=0.006). When patients were categorized in responders and non-responders to CEI+ARB, no difference between the two groups was detected in any demographic or clinical variable, whereas histology showed in responders a greater prevalence of proliferative GN (71.4 versus 31.8%, P=0.009) and higher score of mesangial cellularity (1.76+/-0.53 versus 1.20+/-0.22, P<0.0001). At multiple regression analysis (r(2)=0.476, P=0.001), response to CEI+ARB resulted independently related only to mesangial cellularity (P<0.0001). In conclusion, the best independent predictor of antiproteinuric efficacy of CEI+ARB in patients with primary GN is the degree of mesangial cellularity. This finding supports the experimental evidence that high angiotensin II contributes to proliferation of mesangial cells.

Changes in urinary angiotensinogen posttreatment in pediatric IgA nephropathy patients

“…Ang II induces mesangial cell activation, and former studies have shown that the degree of mesangial cellularity is associated with a high sensitivity to the beneficial effects of RAS blockade on glomerular structure and proteinuria [36, 37]. Minutolo et al suggested that high intrarenal Ang II production contributed to the proliferation of mesangial cells [38]. In our study, glomerular Ang II levels were correlated with mesangial hypercellularity score ( r =0.4303, P =0.0358).…”

Urine Annexin A1 as an Index for Glomerular Injury in Patients

“…We classified the patients' specimens as group 1: primary GN: nonproliferative GN, including MCD, MGN, and FSGS; group 2: primary GN: proliferative GN, including IgAN and CrGN, and group 3: secondary GN, including DN and LN, as described previously [42, 43]. As shown in Figure 7, urine ANXA1 levels were significantly increased in these three groups compared to normal control (all P < 0.005).…”

Validation of the Oxford classification of IgA nephropathy

“…Certainly others studies have shown that the effect of the renin-angiotensin system is associated with mesangial cell inhibition and prevention of renal-function decline in both human and experimental glomerulonephritis. 16,17 As in the derivation data set, we found an interaction between the E-score and the use of immunosuppressive therapy and the rate of renal-function decline in the validation cohort. In the original derivation study, because of the small number of subjects, we could not determine the independent predictive value of the E-score, given this important potential confounder of treatment effect.…”