FACTORS ASSOCIATED WITH RENAL RESPONSE ACHIEVEMENT IN MONOCLONAL IMMUNOGLOBULIN RELATED GLOMERULOPATHIES

Introduction:

The therapeutic strategy in monoclonal immunoglobulin related glomerulopathies (mIgGP) relies the clone-directed treatment (CDT) aiming at eradication of malignant cells population. Progression of kidney dysfunction may also have a significant impact on survival, and the renal response to treatment (RR) was suggested to be a crucial factor for better renal outcomes. The study aimed to evaluate the difference in clinical and morphological features between responders and non-responders (NRs) and to define factors associated with the achievement of RR in mIgGP.

Methods:

We included 116 patients with morphologically proven mIgGP, who undergone at least 4 cycles of any CDT and had follow-up (FUP) ≥ 6 months. Decrease in 24h proteinuria <3.5 g and by 50% from the baseline with stable eGFR (no decline >25%) was considered as RR. Baseline clinical parameters, renal histology, type of treatment, and hematologic response (HR) were analysed. Composite renal outcome was defined as initiation of renal replacement therapy or eGFR<15 ml/min/1.73m2 at the end of FUP. Death-censored renal survival was analysed by the Kaplan-Meier method, and Cox regression was used to determine factors independently associated with RR. Differences or regression coefficients were considered significant at p-values <0.05.

Results:

Median FUP was 38 (12; 71) months. The RR was achieved in 50% of patients. Overall and complete HRs were more common in renal responders (p<0.001). Significant proportion of hematologic responders did not have RR (Fig.1). Baseline parameters in responders and NRs are presented in the figure 1. Proteasome inhibitor-, lenalidomide-, melphalan-, rituximab-, daratumumab-based CDT were applied in 91%, 22%, 26%, 10%, 19% of NRs and 88%, 17%, 21%, 5%, 10% of responders, respectively. Autologous stem cell transplantation was performed in responders (n=16) more often than in NRs (n=6, p=0.018). Specific sub-types of mIgGP did not differ between groups except C3-glomerulopathy (p=0.012) (Fig.2). The cumulative renal survival was lower in NRs (Fig.3A) and in those without HR (Fig.3B). In multivariable Cox regression model adjusted for age, gender, malignant vs non-malignant disease, and nephrotic syndrome baseline eGFR (Exp(β) 0.95 (95% CI 0.93; 0.97)), RR (Exp(β) 0.008 (95% CI 0.01; 0.109)) and HR (Exp(β) 0.32 (95% CI 0.13; 0.77)) were independently associated with the renal outcome. In univariate Cox regression analysis 24h-proteinuria (Exp(β) 0.95 (95% CI 0.92; 0.99)), serum albumin (Exp(β) 1.051 (95% CI 1.021; 1.082)), nephrotic syndrome (Exp(β) 0.54 (95% CI 0.31; 0.95)), eGFR (Exp(β) 0.98 (95% CI 0.97; 0.99)), malignant B-cell clone vs non-malignant (Exp(β) 2.2  (95% CI 1.2; 3.9)), and HR (Exp(β) 3.51 (95% CI 1.26; 9.76)) were associated with the RR occurrence. In a multivariable Cox regression model adjusted for nephrotic syndrome and eGFR at baseline and malignant vs non-malignant clonal disease, only HR was independently associated with increased probability of RR (Exp(β) 3.28 (95% CI 1.2; 8.7)).

Conclusions:

Achievement of HR seems to be crucial in the treatment of mIgGP. Considering the significant proportion of those not having RR despite HR and an overall impact of RR on renal survival, further studies are needed to define mechanisms of progressive glomerular injury and explore other therapeutic approaches aiming at improving renal outcomes in specific sub-types of mIgGP.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.