To the Editor:
In a recent retrospective study, Lee et al.1 demonstrated the interest of serum albumin (sAlb) as a prognostic marker of outcome in primary membranous nephropathy. The most significant limitation of their study was the absence of information about patients’ phospholipase A2 receptor (PLA2R) status. Indeed, during the past decade, accumulating evidence suggested that clinical remission is preceded by immunological remission2,3 and PLA2R serology has become an essential tool for primary membranous nephropathy monitoring. Whether sAlb remains a useful marker in the era of PLA2R is unknown. To investigate this question, we retrospectively analyzed 46 cases of PLA2R-related primary membranous nephropathy. Forty-one patients reached immunological remission after rituximab therapy with a median delay of 4.8 months. The evolution of patients with immunological remission and normal sAlb (>3.5 g/dl) was compared with that of patients with immunological remission and low sAlb (Table 1). The outcome of patients with immunological remission and normal sAlb was better than that of patients with low sAlb, that is, higher sAlb and lower proteinuria at 12 months and at last follow-up. Moreover, patients with normal sAlb had a higher probability to reach complete remission (log-rank test P < 0.001) (Figure 1).
Table 1.
Characteristics of patients with IR and normal sAlb (>3.5 g/dl) versus IR and low sAlb (≤3.5 g/dl)
| Variables | IR and normal sAlb (n = 17) | IR and low sAlb (n = 24) | P |
|---|---|---|---|
| At diagnosis | |||
| Age, yr | 53 (42–66) | 53 (39–68) | 0.98 |
| Sex, male, % | 12 (71) | 14 (58) | 0.52 |
| eGFR (MDRD), ml/min per 1.73 m2 | 75 (55–104) | 71 (41–93) | 0.21 |
| sAlb, g/dl | 2.2 (1.9–3.0) | 2.0 (1.6–2.5) | 0.1 |
| Proteinuria, g/mmol | 0.55 (0.35–1.13) | 0.85 (0.60–1.26) | 0.15 |
| PLA2R-Ab titer (ELISA), RU/ml | 95 (27–264) | 89 (20–310) | 0.89 |
| At IR | |||
| Delay between diagnosis and IR, mo | 14.2 (9.0–31.1) | 10.2 (9.0–7.1–19.9) | 0.11 |
| Delay between RTX and IR, mo | 7.3 (3.8–14.5) | 4.2 (3.1–6.4) | 0.10 |
| eGFR (MDRD), ml/min per 1.73 m2 | 91 (61–105) | 57 (47–87) | 0.08 |
| sAlb, g/dl | 3.8 (3.7–4.3) | 3.1 (2.8–3.3) | <0.01 |
| Proteinuria, g/mmol | 0.09 (0.03–0.15) | 0.35 (0.18–0.64) | <0.01 |
| 12 mo after RTX | |||
| eGFR (MDRD), ml/min per 1.73 m2 | 75 (56–103) | 65 (44–94) | 0.45 |
| sAlb, g/dl | 4.2 (4.0–4.5) | 3.5 (2.8–4.1) | <0.01 |
| Proteinuria, g/mmol | 0.05 (0.02–0.09) | 0.16 (0.05–0.26) | <0.01 |
| PLA2R-Ab titer (ELISA), RU/ml | 0 (0–0) | 0 (0–0) | 0.18 |
| Immunological relapse, n (%) | 1 (6) | 4 (17) | 0.38 |
| Complete remission, n (%) | 9 (53) | 8 (33) | 0.21 |
| At last follow-up | |||
| Follow-up, mo from diagnosis | 29.4 (18.0–50.2) | 38.4 (28.5–61.8) | 0.12 |
| eGFR, ml/min per 1.73 m2 | 75 (56–108) | 67 (54–100) | 0.54 |
| sAlb, g/dl | 4.2 (4.0–4.4) | 3.8 (3.4–4.1) | <0.01 |
| Proteinuria, g/mmol | 0.03 (0.02–0.05) | 0.14 (0.02–0.3) | 0.04 |
| PLA2R-Ab titer (ELISA), RU/ml | 0 (0–0) | 0 (0–29) | 0.04 |
| Immunological relapse, n (%) | 1 (6) | 6 (25) | 0.21 |
| Clinical relapse, n (%) | 2 (12) | 6 of 22 (27) | 0.43 |
| Complete remission, n (%) | 14 (82) | 10 (42) | 0.01 |
eGFR, estimated glomerular filtration rate; ELISA, enzyme-linked immunosorbent assay; IR, immunological remission defined as negative PLA2R serology by indirect immunofluorescence assay; MDRD, modification of diet in renal disease; PLA2R-Ab, phospholipase A2 receptor antibody; RTX, rituximab; sAlb, serum albumin.
Data are reported as medians and interquartile ranges and were analyzed using unpaired t test or Mann–Whitney test as appropriate. Categorical data are presented as absolute values and percentages and were analyzed using Fisher’s Exact test or χ2 test.
Figure 1.
Rates of complete remission over time in patients with IR and normal sAlb (>3.5 g/dl) versus IR and low sAlb (≤3.5 g/dl). IR, immunological remission defined as negative phospholipase A2 receptor serology by indirect immunofluorescence assay; sAlb, serum albumin.
In conclusion, in 2017, the GEMRITUX trial suggested that sAlb appeared to be an earlier predictor of remission of nephrotic syndrome than proteinuria.4 Recently, Lee et al.1 confirmed that sAlb was an interesting and probably underestimated prognostic biomarker. Our results indicate that sAlb remains a useful tool to predict the outcome of patients with primary membranous nephropathy, in combination with PLA2R serology.
References
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