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Lupus nephritis (LN) is an inflammation of the caused by systemic lupus erythematosus (SLE) and childhood-onset systemic lupus erythematosus which is a more severe form of SLE that develops in children up to 18 years old; both are autoimmune diseases. It is a type of glomerulonephritis in which the glomeruli become inflamed. Since it is a result of SLE, this type of glomerulonephritis is said to be secondary, and has a different pattern and outcome from conditions with a primary cause originating in the kidney. The diagnosis of lupus nephritis depends on , urinalysis, X-rays, ultrasound scans of the kidneys, and a kidney biopsy. On urinalysis, a nephritic picture is often seen with presence of red blood cell casts, red blood cells and proteinuria however a nephrotic picture may also be seen depending on the classification of lupus nephritis present. New therapies for LN are being developed and tested with significantly improved morbidity and mortality in the past 4 decades.
The pathophysiology of lupus nephritis has autoimmunity contributing significantly. Autoantibodies direct themselves against nuclear elements. The characteristics of nephritogenic autoantibodies (lupus nephritis) are antigen specificity directed at nucleosome, high affinity autoantibodies form intravascular immune complexes, and autoantibodies of certain isotypes activate complement.
A tubuloreticular inclusion within capillary endothelial cells is also characteristic of lupus nephritis and can be seen under an electron microscope in all stages. It is not diagnostic however, as it exists in other conditions such as HIV infection.
Class IV disease (Diffuse proliferative nephritis) is both the most severe, and the most common subtype, involving greater than 50% of glomeruli. Class V disease (Membranous glomerulonephritis) can present on its own, or be seen alongside Class III or IV disease. Class VI (Advanced sclerosing lupus nephritis) is a final class which is included by most practitioners. It is thought to be due to the chronic interferon exposure.
| + !Order !Name !IncidenceTable 6-4 in: !Light microscopy !Electron microscopy !Clinical findings and other tests !Treatment | ||||||
| Class I | Minimal mesangial glomerulonephritis | 5% | Normal appearance. | Mesangial immune complex deposits are visible under an electron microscope | Kidney failure is very rare in this form. Normal urinalysis, normal or minimal proteinuria, normal serum Cr. | Normally no specific treatment for class I lupus nephritis is needed, however the patient may require active management of SLE. |
| Class II | Mesangial proliferative glomerulonephritis | 20% | Mesangial hypercellularity and matrix expansion. | Mesangial immune complex deposition as seen in Class I LN | Microscopic haematuria with or without proteinuria may be seen. Hypertension, nephrotic syndrome, and acute kidney injury are very rare at this stage. | Responds to high doses of corticosteroids. |
| Class III | Focal glomerulonephritis | 25% | Sclerotic lesions involving less than 50% of the glomeruli, which can be segmental or global, and active or chronic, with endocapillary or extracapillary proliferative lesions. | Sub endothelial deposits are noted, and some mesangial changes may be present. | Immunofluorescence reveals a "full house" stain positive for Immunoglobulin G, IgA, IgM, C3, and C1q. Clinically, haematuria and proteinuria are present, with or without nephrotic syndrome, hypertension, and elevated serum creatinine. | Often successfully responds to high doses of corticosteroids with immunosuppressants. |
| Class IV | Diffuse proliferative nephritis | 40% | More than 50% of glomeruli are involved. Lesions can be segmental or global, and active or chronic, with endocapillary or extracapillary proliferative lesions. | Under electron microscopy, sub endothelial deposits are noted, and some mesangial changes may be present. | Clinically, haematuria and proteinuria are present, frequently with nephrotic syndrome, hypertension, hypocomplementemia, elevated anti-dsDNA titres and elevated serum creatinine. Kidney failure is common. | Responds to high dose corticosteroids and immunosuppressant drugs. |
| Class V | Membranous glomerulonephritis | 10% | Diffuse thickening of the glomerular capillary wall (segmentally or globally), with diffuse membrane thickening, and subepithelial deposits seen under the electron microscope. | Sub epithelial deposits are seen on electron microscopy, a key distinction from other classes of LN. | Signs of nephrotic syndrome. Microscopic haematuria and hypertension may also be seen. Can also lead to thrombotic complications such as renal vein thromboses or pulmonary emboli. Kidney failure is uncommon. | Responds to high dose corticosteroids and immunosuppressant drugs. |
| Class VI | Advanced sclerosing lupus nephritis. | Global sclerosis involving more than 90% of glomeruli, and represents healing of prior inflammatory injury. | Active glomerulonephritis is not usually present. This stage is characterised by slowly progressive kidney dysfunction, with relatively bland urine sediment. | Response to immunotherapy is usually poor. |
Triple immunosuppressive therapy includes a corticosteroid and one of the following combinations of medications:
MMF and cyclophosphamide with corticosteroids are equally effective in achieving remission of the disease, however the results of a systematic review found that immunosuppressive drugs were better than corticosteroids for renal outcomes. MMF is safer than cyclophosphamide with corticosteroids, with less chance of causing ovarian failure, immune problems or hair loss. It also works better than azathioprine with corticosteroids for maintenance therapy. A 2016 network meta-analysis, which included 32 RCTs of lupus nephritis, demonstrated that tacrolimus and MMF followed by azathioprine maintenance were associated with a lower risk of serious infection when compared to other immunosuppressants or glucocorticoids. Individuals with lupus nephritis have a high risk for B-cell lymphoma (which begins in the immune system cells). Voclosporin can also be used to treat LN. Rituximab and obinutuzumab were also tested for treatment of lupus nephritis.
After initial treatment, patients can remain on MMF or can be transitioned to the immune suppressant azathioprine for maintenance therapy. Additionally, patients with LN should also be started on maintenance therapy for SLE with hydroxychloroquine. A systematic review of 21 reviewed studies found that hydroxychloroquine therapy reduced mortality in patients with SLE. Maintenance therapy of LN also focuses on managing other conditions that may contribute to worsening kidney function. This could include managing lipid levels with statin therapy and lowering blood pressure with ACE inhibitor or angiotensin II receptor blockers. Ultimately, the goal of maintenance therapy is to reduce the frequency of SLE flairs while preserving as much kidney function as possible.
Lupus nephritis can progress to Kidney failure, a condition in which the kidneys can no longer filter blood adequately. These patients require hemodialysis or peritoneal dialysis to clean their blood of the toxic metabolites that would otherwise build up. Dialysis may be used temporarily to bridge patients to kidney transplantation, or a permanent treatment for those who are not candidates for transplant.
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