Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE), an autoimmune disease where the body’s immune system mistakenly attacks its own tissues and organs. When SLE affects the kidneys, it causes inflammation and damage. This condition can hinder the kidneys’ ability to filter waste and regulate fluids, potentially leading to kidney failure if not properly managed. Medical guidelines provide evidence-based recommendations for diagnosis, treatment, and long-term management, aiming to mitigate disease progression and preserve kidney function.
What Lupus Nephritis Is and How It Is Diagnosed
Lupus nephritis involves inflammation and damage to the kidneys, impairing their ability to filter waste and maintain fluid balance. This damage can worsen, potentially leading to kidney failure. Approximately half of adults and many children with SLE develop LN, sometimes as the initial sign of lupus.
Common signs and symptoms of LN include swelling in the hands, face, feet, or ankles, often with weight gain due to fluid retention. Individuals might also notice foamy urine, indicating high protein, or brown-colored urine, suggesting blood. Fatigue and uncontrolled high blood pressure can also indicate kidney involvement.
Diagnosis begins with evaluating symptoms and medical history, followed by specific tests. Urine tests detect protein (proteinuria) and blood (hematuria), with a 24-hour urine collection or urine albumin-creatinine ratio (uACR) providing precise protein loss measurement. Blood tests assess kidney function by measuring creatinine levels and estimating the glomerular filtration rate (eGFR). Specific autoantibodies, such as anti-dsDNA, and complement levels (C3 and C4) are also checked, as these are often abnormal in active SLE and LN.
The definitive diagnostic step is a kidney biopsy, where a small tissue sample is removed and examined under a microscope. This biopsy confirms LN and helps classify the specific type of kidney damage based on the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification system. This system categorizes LN into six classes (I-VI) based on observed changes in kidney tissue. The classification guides treatment choice, as different classes respond best to different therapies.
Treatment Recommendations from Guidelines
Treatment strategies for lupus nephritis are individualized, based on the specific class of LN and disease activity. The goal of treatment is to reduce inflammation, decrease immune system activity, and prevent further kidney damage. Treatment is divided into two main phases: induction therapy and maintenance therapy.
Induction therapy is an intensive period to bring the disease under control and achieve remission. Corticosteroids, such as prednisone or methylprednisolone, are commonly used, often administered as intravenous pulses followed by oral doses. These anti-inflammatory agents are combined with immunosuppressants to suppress the overactive immune system. Mycophenolate mofetil (MMF) and cyclophosphamide are frequently prescribed. MMF has shown similar efficacy to intravenous cyclophosphamide in inducing remission, with a potentially reduced risk of side effects like ovarian failure. Cyclophosphamide can be administered in a low-dose “Euro-Lupus” regimen or a higher-dose “NIH” regimen. Newer therapies, including calcineurin inhibitors like tacrolimus or voclosporin, and biologics such as belimumab, are also incorporated into induction regimens, particularly for certain LN classes or when conventional therapies are not fully effective.
Following successful induction, maintenance therapy aims to prevent disease flares, sustain remission, and preserve long-term kidney function. This phase involves lower doses of immunosuppressants, often continued for at least three years, or longer for many patients with proliferative forms of LN. Mycophenolate mofetil is often preferred for maintenance, as studies suggest it is associated with a lower risk of renal relapse compared to azathioprine. Azathioprine remains an alternative, especially for those who received cyclophosphamide during induction. Hydroxychloroquine, an antimalarial drug, is also a standard component of maintenance therapy due to its immunomodulatory effects and benefits in reducing flare rates and slowing kidney disease progression.
Major guidelines from the American College of Rheumatology (ACR), Kidney Disease: Improving Global Outcomes (KDIGO), and European Alliance of Associations for Rheumatology/European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) provide recommendations for these treatment phases. While there are commonalities, specific preferences for drug combinations or dosing may vary slightly between guidelines, reflecting evolving evidence and expert consensus. For instance, KDIGO guidelines for active class III or IV LN recommend either low-dose intravenous cyclophosphamide or MMF with glucocorticoids for induction. These guidelines also emphasize tailoring steroid doses, recognizing that lower doses can be effective while minimizing side effects.
Living with Lupus Nephritis and Ongoing Care
Living with lupus nephritis requires continuous monitoring and long-term management to maintain kidney health and overall well-being. Regular follow-up appointments with healthcare providers assess disease activity and treatment effectiveness. These appointments include ongoing laboratory tests to track kidney function, such as urine protein levels (e.g., proteinuria, uACR), serum creatinine, and eGFR. Monitoring blood pressure is also important, as hypertension can further damage the kidneys.
Managing potential medication side effects is part of ongoing care. Immunosuppressants can increase infection risk, so patients are advised on preventive measures and prompt reporting of symptoms. Bone health is a consideration, as corticosteroids can contribute to bone density loss; strategies to support bone health may be recommended. Individuals with LN also face an increased risk of cardiovascular disease, making monitoring and management of factors like cholesterol levels and blood pressure important.
Lifestyle recommendations play a role in managing lupus nephritis. Adopting a healthy diet, which may involve limiting protein and salt intake to reduce kidney workload, can contribute to better kidney function. Regular exercise, maintaining a healthy weight, and avoiding smoking and excessive alcohol consumption are beneficial for overall health and can help protect the kidneys. Consistent adherence to prescribed medications and open communication with the healthcare team are important for achieving the best outcomes and addressing concerns promptly.
Understanding Different Guideline Sources
Multiple major organizations publish guidelines for lupus nephritis management, including the American College of Rheumatology (ACR), Kidney Disease: Improving Global Outcomes (KDIGO), and the European Alliance of Associations for Rheumatology/European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA). These separate guidelines reflect the complex nature of LN and the evolving medical knowledge. While all guidelines aim to provide evidence-based recommendations for patient care, they may present slight variations.
These differences can arise from factors like the timing of evidence review, new research, and differing expert interpretations. Regional healthcare practices and patient populations also influence guideline development. For example, EULAR/ERA-EDTA guidelines often focus on European populations, while KDIGO aims for a global reach. Despite variations, there are common themes across guidelines regarding indications for kidney biopsy, interpretation of results, treatment targets, and first-line immunosuppressive therapies for active proliferative LN.
Guidelines are regularly updated to incorporate the latest research and advancements. This refinement ensures recommendations remain current and effective. Healthcare providers consider these various guidelines, alongside individual patient characteristics and preferences, to formulate a personalized treatment plan for the best outcomes.