Many clinicians opt not to perform a kidney biopsy if proteinuria doesn’t fall above a certain level. However, Dr. Appenzeller shared results from a cross-sectional study of 222 patients demonstrating that some important kidney pathology could be seen via histology in patients with lupus who had active urine sediment but low levels of proteinuria (<0.5 g/ day). Thus, she recommended considering kidney biopsy even in patients with low-grade proteinuria.9
Histological Patterns
Lupus is a notoriously heterogenous disease, and lupus nephritis displays varying histological patterns as classified by the International Society of Nephrology/ Renal Pathology Society (ISN/ RPS). Patients with class I (minimal mesangial) and class II (mesangial proliferative) lupus nephritis typically have mild or absent clinical features. Patients with class III (focal disease) and class IV (diffuse disease) lupus nephritis have comparatively more acute injury, hematuria, proteinuria and chronic disease. Patients with class V (membranous disease) lupus nephritis have the highest rate of nephrotic syndrome, and class VI represents rare and advanced sclerosing disease.10
Dr. Appenzeller shared that biopsy patterns can also give clinicians helpful prognostic information. For example, a retrospective study of 382 patients with childhood lupus of class III or higher showed that patients with class III disease achieved complete remission more often than those with class IV or V disease.4
This same study highlighted the room for improvement in remission rates for childhood lupus: At a 24-month follow-up, 57% of patients had achieved complete remission and 34% had achieved partial remission. Patients with severe disease at diagnosis had the highest risk of not achieving remission.4
Maintenance Therapy
Kidney biopsy can also enrich our understanding of true disease activity. For many years, researchers assumed that a complete clinical remission in lupus nephritis would be reflected in histological remission. But several studies have demonstrated this is not the case. Histologic findings may reveal ongoing inflammation not yet clinically apparent.11
“Repeat renal biopsy can help us identify complete remission more reliably,” explained Dr. Appenzeller. Because the optimal duration of maintenance immunosuppressive therapy for lupus nephritis is not clear, kidney biopsy can be an important tool in deciding whether to continue therapy. Biopsy helps clinicians balance the risks of ongoing immunosuppression vs. the risks of flare, which further increase the risks of chronic and end-stage kidney disease.11
Dr. Appenzeller discussed one prospective study of 75 patients during the maintenance phase of treatment for lupus nephritis. Roughly one-third of patients had histologic disease activity even though they had been in clinical remission for at least 12 months. The researchers continued maintenance immunosuppression in these patients, but allowed those with both ongoing clinical remission and histologic remission to stop their immunosuppression therapy. This approach seemed to decrease flare rates (1.5/year) compared with standard rates in the literature.11
