To the Editor:
In their research letter, de Rosa et al.1 present important data in a cohort of patients with lupus nephritis (LN) with low-grade proteinuria. They demonstrate that a significant proportion of patients requiring intensive immunosuppressive therapy may be missed with a threshold of 500 mg/24 hours of proteinuria as an indication for renal biopsy, as suggested in the latest European League Against Rheumatism guideline.2 They show that 46 of 228 patients who underwent a renal biopsy had low-grade proteinuria and microscopic hematuria. Of these, 84.8% had proliferative LN.
In our cohort, 10 of 58 patients (17.2%) received a biopsy with low-grade proteinuria. Of these, 5 had LN class III/IV and subsequently received mycophenolate mofetil or cyclophosphamide. The remaining patients had nonproliferative or non–lupus-related renal pathology (biopsies were performed for declining renal function, protocol biopsy, or hematuria). There were statistically significant differences between patients with proliferative or nonproliferative LN: the former were younger and had higher serological activity (high anti–double-stranded DNA antibodies, low complement levels) (Table 1). de Rosa et al.1 reported an even higher frequency of class III/IV (almost 85% compared with 50%).
Table 1.
Characteristics of patients with LN with low-grade proteinuria
| Lupus nephritis III or IV n = 5 | Lupus nephritis non-III non-IV n = 5 |
||
|---|---|---|---|
| Epidemiologic data | |||
| Female gender, n (%) | 3 (60) | 4 (80) | ns |
| Age at LN diagnosis (y) | 26 (16–48) | 67 (34–78) | 0.0317 |
| Urinary findings | |||
| Creatinine (mg/dl) | ns | ||
| Proteinuria (mg/g Creatinine) | 343.0 (229–483) | 195 (77–391) | ns |
| Hematuria, n (%) | 3 (60) | 1 (20) | ns |
| Serology | |||
| dsDNA | 379 (231–413) | 7.5 (0.7–28) | 0.0357 |
| C3 | 0.47 (0.3–0.54) | 1.005 (0.78–1.310) | 0.0159 |
| C4 | 0.03 (0–0.06) | 0.18 (0.08–0.24) | 0.0159 |
| Renal findings, n (%) | |||
| LN class I | - | 2 (40) | |
| LN class II | - | 1 (20) | |
| LN class III | 2 (40) | - | |
| LN class IV | 3 (60) | - | |
| LN class V | - | - | |
| LN class VI | - | - | |
| TMA | - | 1 (20) | |
| Non-lupus pathology | 1 (20) | ||
| Immunosuppressive therapy | |||
| MMF | 4/5 (80%) | 1/5 (20%), non-nephritis indication | ns |
| CYC | 1/5 (20%) | ns |
C3/4, complement factor C3/C4; CYC, cyclophosphamide; dsDNA, anti–double-stranded DNA antibody; LN, lupus nephritis; MMF, mycophenolate mofetil; ns, not significant; TMA, thrombotic microangiopathy.
Considering the aggregated data by de Rosa et al.1 and our data, we suggest that in younger patients early in their disease course with high levels of anti–double-stranded DNA antibodies and low complement, renal biopsies should be considered despite low-grade proteinuria, as these patients may harbor more aggressive lesions of LN. We suggest further analyses of additional cohorts to corroborate these findings.
References
- 1.De Rosa M., Rocha A.S., De Rosa G. Low-grade proteinuria does not exclude significant kidney injury in lupus nephritis. Kidney Int Rep. 2020;5:1066–1068. doi: 10.1016/j.ekir.2020.04.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Fanouriakis A., Kostopoulou M., Cheema K. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis. 2020;79:713–723. doi: 10.1136/annrheumdis-2020-216924. [DOI] [PubMed] [Google Scholar]