Dr. Shivnarayan .J. Acharya MD, DNB (Nephrology) Consultant Nephrologist Acharya Dialysis Centre & Kidney Hospital, Nagpur
Introduction
An autoimmune disease is a condition when your immune system does not distinguish between healthy tissue and potentially harmful antigens. Through the exact cause of the autoimmune disorder is unknown, it is observed in people who have genes that make them more prone to autoimmune conditions. Lupus is a chronic, autoimmune disease that can cause inammation and pain in any part of your body. Lupus affects everyone difierently. Some people have only a few mild symptoms and others have many, more severe ones. It most commonly affects your skin, joints, internal organs like kidneys and heart. And, lupus nephritis occurs when lupus autoantibodies affect the kidneys. In this article, we will discuss in detail the cause, diagnosis, and treatment of lupus nephritis from a renowned expert Dr. S J Acharya. Dr. Acharya is a consultant nephrologist at the Acharya dialysis center and kidney hospital in Nagpur. He is affached to the Meditrina Institute of Medical Sciences and Orange city hospital and research institute and Kingsway hospital. Dr.Acharya is widely acknowledged as an expert in the field of nephrology.
Systemic Lupus Erythematosus is a long-term condition that affects various parts of the body. What are some signs and symptoms of lupus?
SLE can cause infiammation of multiple organs or organ systems in the body, either acutely or chronically. The seriousness of SLE can range from mild to life threatning. In this disease, the immune system of the body mistakenly affacks healthy tissue. It can affect the skin, joints, kidneys, brain, and other organs. Though the cause of SLE is not clearly known, it may be linked to genetic, environmental, or hormonal factors. People with SLE may experience a variety of symptoms that include fatigue, skin rashes, fevers, and pain or swelling in the joints. Some adults have a period of SLE symptoms called flares, which may happen offen or sometimes-even years apart, and go away at other times, called remission. However, some adults may experience SLE flares more frequently throughout their life. Other symptoms can include sun sensitivity, oral ulcers, arthritis, lung problems, heart problems, kidney problems, seizures, psychosis, and blood cell and immunological abnormalities. There is no complete cure for lupus, but early treatment can help to keep symptoms under control.
It is clinically evident that 50-60% of patients with systemic lupus erythematosus (SLE) have lupus nephritis. How would you define lupus nephritis (LN)?
Lupus nephritis is glomerulonephritis caused by systemic lupus erythematosus (SLE). Lupus nephritis is diagnosed in about 50% of patients with SLE and typically develops within 1 year of diagnosis. Evaluating renal function in SLE patients is important because early detection and treatment of renal involvement can significantly improve renal outcomes. However, it is vital to note that Lupus nephritis is a major risk factor for overall morbidity and mortality in SLE, and despite potent anti-inflammatory and immunosuppressive therapies still ends in CKD or ESRD for too many patients.
Are there any stages or classification of Lupus Nephritis?
Newer classification levels were established in 2003 by the International Society of Nephrology and the Renal Pathology Society. The new classification eliminated the original class I that had no evidence of disease and added a sixth class. The classification is as follows:
Class I: Minimal mesangial lupus nephritis
Class II: Mesangial proliferative lupus nephritis
Class III: Focal lupus nephritis (active and chronic, proliferative and sclerosing)
Class IV: Di use lupus nephritis (active and chronic, proliferative and sclerosing, segmental and global)
Class V: Membranous lupus nephritis
Class VI: Advanced sclerosis lupus nephritis
What kind of diagnosis is required to understand Lupus and are there any particular tests specific to Lupus Nephritis that need to be carried out?
Lupus nephritis is diagnosed through urine and blood tests and a kidney biopsy. Diagnosis is suspected in all patients with SLE, particularly in patients who have proteinuria, microscopic hematuria, red blood cell (RBC) casts, or hypertension. Diagnosis is also suspected in patients with unexplained hypertension, elevated serum creatinine levels, or abnormalities on urinalysis who have clinical features suggesting SLE. The tests used in the diagnosis of Lupus nephritis are:
Urine Test
A urine sample to look for blood and protein in your urine. A high level of protein or a high number of red blood cells in the urine means kidney damage. e urine will also be examined under a microscope to look for kidney cells.
Blood Test
The blood test measures creatinine, a waste product from the normal breakdown of muscles in your body. The amount of creatinine in your blood is used to estimate the glomerular filtration rate (GFR). As kidney disease gets worse, the level of creatinine goes up.
Renal Biopsy
If either is abnormal, a renal biopsy is usually done to confirm the diagnosis and classify the disorder histologically. A kidney biopsy can also help in understanding how far the disease has progressed which further helps to determine prognosis and direct treatment.
As the diagnosis of lupus includes a combination of tests, what are the medications or therapies available for Lupus Nephritis?
Treatment is based on the type of lupus nephritis, which is determined by the biopsy. Since symptoms and severity vary from person to person, treatments are individually tailored to meet a person’s particular circumstances.
Corticosteroids: These strong anti-inammatory drugs can decrease inammation. Doctors may prescribe these until the lupus nephritis improves. Because these drugs can cause a variety of potentially serious side effects, they must be monitored carefully. Doctors generally taper down the dosage once the symptoms start to improve.
Immunosuppressive drugs: For severe lupus nephritis, you might take drugs that slow or stop the immune system from afacking healthy cells, such as steroids, such as prednisone, Cyclosporine, Tacrolimus, Cyclophosphamide, Azathioprine (Imuran), Mycophenolate (CellCept), Rituximab (Rituxan). Medications to prevent blood clots or lower blood pressure if needed.
How effective is immunosuppressive therapy in the management of Lupus Nephritis?
Immunosuppressive therapy in the management of lupus nephritis aims to induce and maintain disease remission, to maximize patient and renal survival while minimizing complications or treatment-related adverse effects. The induction phase of therapy usually lasts six to 12 months. Common immunosuppressive agents in induction therapy include corticosteroid and an anti‐proliferative agent such as cyclophosphamide, mycophenolate mofetil (MMF), or azathioprine. Less commonly used treatments that are added to corticosteroids include tacrolimus, cyclosporin, plasma exchange or plasmapheresis, or a biologic therapy such as rituximab. Intravenous (IV) cyclophosphamide in combination with corticosteroids became standard of care therapy for inducing remission based on a landmark National Institutes of Health (NIH) trial that showed cyclophosphamide was superior over corticosteroids alone in preventing renal flares and kidney failure. The dose of corticosteroid is tapered as the disease activity is controlled and the antiproliferative therapy is replaced with a less toxic alternative once remission is induced. Maintenance therapy aims to maintain remission and potential treatments include azathioprine, MMF, tacrolimus, and cyclosporin.
What are the factors to be considered before starting with the medications for Lupus Nephritis?
According to the guidelines of the American College of Rheumatology, patients with clinical evidence of active, previously untreated lupus nephritis should have a renal biopsy to classify the disease according to the International Society of Nephrology/Renal Pathology Society criteria. And, the EULAR/E -EDTA revised recommendations suggests that Kidney biopsy should be considered when there is evidence of kidney involvement, especially in the presence of persistent proteinuria ≥ 0.5 g/24 hours (or UPCR ≥ 500mg/g in morning rst void urine), and/or an unexplained decrease in glomerular ltration rate (GFR).
As the treatments differ for each class of lupus nephritis, are there any guidelines set up for the dosage and treatment of lupus nephritis?
There are several guidelines set up by the American College of Rheumatology and European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/E -EDTA) for the dosage and treatment of lupus nephritis. According to these guidelines, in all LN patients, Hydroxychloroquine (HCQ) should be co-administered at a dose not to exceed 5 mg/kg/day and adjusted for the GFR, in the absence of contraindications. The guidelines also suggest that patients with ISN/RPS class I and II nephritis do not require immunosuppressive therapy. It is recommended that Glucocorticoids plus either cyclophosphamide intravenously (IV) or mycophenolate mofetil should be induced orally in patients with ISN class III and IV disease. An Alternative option for class III-IV disease includes combination therapy of mycophenolate mofetil with a calcineurin inhibitor, especially tacrolimus, particularly in patients with nephrotic-range proteinuria. Further, the Initial treatment for pure class V disease with nephrotic-range proteinuria, Mycophenolate mofetil in combination with methylprednisolone followed by oral prednisone is recommended. Alternate options for class V disease include cyclophosphamide or calcineurin inhibitors, especially tacrolimus, as monotherapy or in combination with mycophenolate mofetil/mycophenolic acid.
How long should we continue with the treatment of lupus nephritis? When can the treatment be withdrawn?
Patients who improve after initial treatment should receive mycophenolate mofetil/mycophenolic acid, especially if it was the initial treatment or azathioprine in combination with low-dose prednisone when needed to control disease activity. Gradual withdrawal of treatment glucocorticoids first, then immunosuppressive drugs can be aflempted after at least 3 to 5 years of therapy in patients with complete clinical response. HCQ should be continued long-term. However, continuation, switching to, or addition of calcineurin inhibitors, especially tacrolimus, can be considered in pure class V nephritis at the lowest effective dose and aer considering nephrotoxicity risks. Patients in whom initial therapy fails should be switched to one of the alternative initial therapies or rituximab.
On an endnote, what are your thoughts on the challenges of lupus nephritis as there is no complete cure. How do these treatments help patients?
It is important to note that the major goals of the treatments include patient survival, long-term preservation of kidney function, prevention of disease flares, prevention of organ damage, management of comorbidities, and improvement in disease-related quality of life.
