Polyclonal free light chains in IgA-nephropathy: correlation with clinical and morphological parameters and prognostic significance

Abstract

BACKGROUND. Mechanisms of the initiation of renal interstitial inflammation and fibrosis caused by immunoglobulin monoclonal free light chains (mFLC) in monoclonal gammopathy are well established. As far as these damage pathways are considered to be universal we hypothesize that polyclonal free light chains (pFLC) could have a similar effect on tubular and interstitial tissue and lead to chronic kidney disease (CKD) progression in primary glomerulopathies. THE AIM of this retrospective study was to analyze the association of pFLC kappa (pFLC-κ) and lambda (pFLC-λ) assessed in serum by Freelite® with clinical and morphological parameters and CKD progression in IgA-nephropathy (IgAN) cohort.PATIENTS AND METHODS. In this retrospective study, we enrolled 24 patients with IgAN proven by kidney biopsy (KBx). pFLC-κ and pFLC-λ levels were assessed in all cases at the time of KBx by Freelite® method (N pFLC-κ=3.3-19.4 mg/l, N pFLC-λ=5.7-26.3 mg/l). The normal κ/λ ratio was the inclusion criterion. In all cases, we determined serum creatinine, estimated glomerular filtration rate by CKD-EPI method (eGFRCKD-EPI), and daily proteinuria. Morphological findings were defined semiquantitatively by light and immunofluorescence microscopy. Oxford MEST-C score was evaluated as well as % of glomerulosclerosis. Correlation between parameters was assessed by Spearman’s coefficient. Cox proportional hazards regression was used to analyze the association of parameters with the progression of CKD estimated as an elevation of serum creatinine ≥25 % from the initial level or the initiation of renal replacement therapy at the end of the follow-up period (median was 28 (7; 37) months).RESULTS. Median of pFLC-κ 30.2 (6.1; 67.5) mg/l, median of pFLC-λ 27.6 (11.1; 92.1) mg/l. Levels of pFLC-κ and pFLC-λ were increased in 66.7 % and 50 % of patients, respectively. eGFR CKD-EPI median was 41 (26; 65) ml/min/1.73m2. Serum creatinine correlates with pFLC-κ (R=0.62, p<0.01) and pFLC-λ (R=0.45, p=0.03). Among morphological parameters pFLC-κ correlates with interstitial inflammation (R=0.47, p=0.02), tubular atrophy (R=0.54, p<0.01), interstitial fibrosis (R=0.44, p=0.03), peritubular capillaritis (R=0.42, p=0.04), T-score (R=0.66, p<0.01) and combined MEST-C score (R=0.45, p=0.03). For pFLC-λ the correlations with tubular atrophy (R=0.45, р=0.03) and Т-score (R=0.56, p<0.01) were shown. In Univariate Cox regression analysis pFLC-κ and pFLC-λ were associated with CKD progression (Exp(ß)=1.053; 95,0 %CI 1.003-1.105; p=0.038 and Exp(ß)= 1.041; 95,0 %CI 1.002-1.082; p=0.038, respectively) CONCLUSION. Polyclonal FLC, mostly pFLC-κ, were associated with tubulointerstitial inflammation and fibrosis in patients with IgAN. Increased levels of either pFLC-κ or λ could be proposed as a predictor of CKD progression in patients with IgAN.