# Monoclonal gammopathy of renal significance in western China: A large cohort study dominated by amyloidosis with distinct clinical outcomes

## TL;DR

This study shows that amyloidosis is the main cause of kidney disease in Chinese patients with monoclonal gammopathy, and early treatment improves outcomes.

## Contribution

The study identifies amyloidosis as the dominant MGRS subtype in western China and highlights cardiac involvement and early therapy as critical prognostic factors.

## Key findings

- Renal amyloidosis is the most common MGRS subtype in the cohort (75.8%).
- Cardiac involvement is a strong predictor of end-stage kidney disease.
- Therapy response in both hematologic and renal aspects is linked to better survival.

## Abstract

•Renal amyloidosis is the dominant lesion in this Chinese MGRS cohort.•Amyloidosis MGRS shows a distinct clinical phenotype at presentation.•Cardiac involvement is a key predictor of end-stage kidney disease.•Therapy response (hematologic/renal) is linked to better survival.•Early clone-directed therapy is critical for amyloidosis MGRS.

Renal amyloidosis is the dominant lesion in this Chinese MGRS cohort.

Amyloidosis MGRS shows a distinct clinical phenotype at presentation.

Cardiac involvement is a key predictor of end-stage kidney disease.

Therapy response (hematologic/renal) is linked to better survival.

Early clone-directed therapy is critical for amyloidosis MGRS.

To characterize the epidemiology, clinicopathological features, and renal outcomes in patients with Monoclonal Gammopathy of Renal Significance (MGRS).

The authors conducted a retrospective analysis of all renal biopsy-confirmed MGRS cases diagnosed between 2010‒2020, with histopathological review by two independent pathologists. Post-hoc power analysis confirmed adequate statistical power (92 %).

Among 124 histologically confirmed MGRS cases (median age 64.0-years, IQR 52.5‒68.0), renal amyloidosis predominated (75.8 %), followed by monoclonal immunoglobulin deposition disease (MIDD, 10.5 %), cryoglobulinemic GN (4.8 %), proliferative GN with monoclonal Ig deposits (PGNMID, 2.4 %), light chain proximal tubulopathy (3.2 %), and C3 glomerulopathy with monoclonal gammopathy (1.6 %). Amyloidosis patients primarily presented with nephrotic syndrome (77.7 %), while fewer exhibited acute kidney injury (3.2 %), chronic kidney disease (16.1 %), or ESRD (6.7 %). Compared to other MGRS subtypes, amyloidosis patients demonstrated significantly lower anemia rates (p < 0.001), higher LDH (p = 0.035), preserved eGFR (p < 0.001), greater proteinuria (p = 0.037), and hypoalbuminemia (p < 0.001). The renal response rates were 26.1 % (Amyloidosis-Associated MGRS, MGRS-A) versus 33.3 % (Non-Amyloidosis MGRS, MGRS-NA), while hematologic responses were 8.7 % versus 0 %, respectively. Both hematologic (p = 0.007) and renal responses (p = 0.009) correlated with improved survival. MGRS-A showed inferior renal survival (p = 0.05). Multivariate analysis identified hypotension (p = 0.005), elevated creatinine (p = 0.002), and cardiac involvement (p = 0.022) as independent predictors of ESKD, while age (p < 0.001) and cardiac involvement (p < 0.001) predicted mortality.

MGRS represents a clinically significant cause of kidney injury in monoclonal gammopathy patients, with amyloidosis being the predominant etiology. MGRS-A portends a worse prognosis than MGRS-NA. Therapeutic responses in both hematologic and renal parameters predict survival benefits. Age and cardiac involvement emerge as key prognostic markers for both renal and patient survival.