Lupus Nephritis: An Overview
AUTHOR:
Amanda Balbi
Senior managing editor, Consultant360
CITATION:
Balbi A. Lupus nephritis: an overview. Consultant360. Published online May 27, 2021.
Lupus nephritis is a serious kidney complication caused by systemic lupus erythematosus (SLE). SLE is most common among women, especially during the childbearing years, as well as people of African or Asian descent. In the United States, about 5 out of 10 adults with SLE will develop lupus nephritis.1 Among children, about 8 out of 10 with SLE will develop lupus nephritis.1
Moreover, the development of lupus nephritis is a major predictor of poor prognosis among patients with SLE.2 It is estimated that 25% of patients who develop lupus nephritis will develop end-stage renal disease, with a 5-year survival rate ranging from 83% to 93%.2
Screening
The American College of Rheumatology (ACR) defines lupus nephritis as persistent proteinuria with a level of 0.5 g/d or greater than 3+ by dipstick, and/or cellular casts including red blood cells, hemoglobin, granular, tubular, or mixed.3
To screen for lupus nephritis, the ACR recommendations conducting a spot urine protein/creatinine ratio test, results of which should show 0.5 for the first 24-hour measurement, as well as an active urinary sediment test to evaluate for cellular casts.3 Renal biopsy sampling is also recommended, results of which should show immune complex–mediated glomerulonephritis to confirm the diagnosis.
Diagnosis
According to the ACR recommendations, a diagnosis of lupus nephritis should be made clinically via laboratory testing and renal biopsy. However, a diagnosis could also be made based on the opinions of a rheumatologist or nephrologist.3
For patients with SLE, a renal biopsy should be conducted to diagnose lupus nephritis. Patients with SLE who have an increasing serum creatinine level without an alternative cause, those who have confirmed proteinuria of 1.0 g or more per 24 hours, or those who have a combination of proteinuria of 0.5 g or more per 24 hours plus hematuria of 5 or more red blood cells per high power field or proteinuria of 0.5 g or more per 24 hours plus cellular casts should receive a renal biopsy.3
Moreover, the Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA–EDTA) also support performing a renal biopsy in patients with SLE who show any signs of renal involvement.4
Although performing renal biopsies in patients with SLE has been controversial, a biopsy is necessary to make the diagnosis of lupus nephritis and to stage the renal involvement.5 Staging of lupus nephritis can range from Class I (minimal mesangial lupus nephritis) to Class VI (advanced sclerosing lupus nephritis).6
Induction Treatment
The goal of treatment is to stop or slow the progression of renal disease at 12 months.4,5 Immunosuppression therapy and glucocorticoids are typically the gold standard of treatment. However, aggressive therapy is not recommended until Class III or IV lupus nephritis is diagnosed.5 Adequate duration of therapy has been controversial, but the overall 5-year survival rates have improved because of induction and maintenance therapies.5
For patients with Class III and IV staging, the ACR recommends aggressive treatment with glucocorticoids to control inflammation and immunosuppressive medications to control inflammation and autoimmunity.3,5
For patients with Class V staging—in the setting of Class III or IV—the ACR recommends aggressive treatment similar to that for Class III or IV. When Class V is solely present, oral prednisone (0.5 mg/kg/d) plus mycophenolate mofetil (2 to 3 g/d) is recommended.3 EULAR/ERA–EDTA supports this recommendation:
- Mycophenolate mofetil (2-3 g/d) or mycophenolic acid (equivalent dose) plus glucocorticoids (pulses of intravenous methylprednisolone, then oral prednisone 0.3-0.5 mg/kg/d) or
- Low-dose intravenous cyclophosphamide (500 mg, 6 biweekly doses) plus glucocorticoids (pulses of intravenous methylprednisolone, then oral prednisone 0.3–0.5 mg/kg/d)4
For patients with Class VI staging, the ACR recommends renal replacement therapy over immunosuppression therapy. Similarly, EULAR/ERA–EDTA recommends renal transplantation plus immunosuppression therapy based on transplantation outcomes and extrarenal cormorbidities.4
Conclusions
These protocols are similar for both adults and children with lupus nephritis. Management of lupus nephritis and its comorbidities is lifelong and may include repeat biopsy if complete response is not achieved or if nephritic flares are reported.4
More research is needed to update the guidelines and provide updated treatment options for patients with lupus nephritis.
References
1. Lupus and Kidney Disease (Lupus Nephritis). National Institute of Diabetes and Digestive and Kidney Diseases. Reviewed January 2017. Accessed May 27, 2021. https://www.niddk.nih.gov/health-information/kidney-disease/lupus-nephritis
2. Anaya JM, Rojas-Villarraga A, García-Carrasco M. The autoimmune tautology: from polyautoimmunity and familial autoimmunity to the autoimmune genes. Autoimmune Dis. 2012;2012:297193. https://doi.org/10.1155/2012/297193
3. Hahn BH, McMahon MA, Wilkinson A, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken). 2012;64(6):797-808. https://doi.org/10.1002/acr.21664
4. Fanouriakis A, Kostopoulou M, Cheema K, et al. 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(6):713-723. https://doi.org/10.1136/annrheumdis-2020-216924
5. Almaani S, Meara A, Rovin BH. Update on lupus nephritis. Clin J Am Soc Nephrol. 2017;12(5):825-835. https://doi.org/10.2215/cjn.05780616
6. Markowitz GS, D'Agati VD. The ISN/RPS 2003 classification of lupus nephritis: an assessment at 3 years. Kidney Int. 2007;71(6):491-495. https://doi.org/10.1038/sj.ki.5002118