Lupus nephritis

Lupus nephritis is an inflammation of the kidneys caused by systemic lupus erythematosus (SLE), an autoimmune disease. It is a type of glomerulonephritis in which the glomeruli become inflamed. As the result of SLE, the cause of glomerulonephritis is said to be secondary and has a different pattern and outcome from conditions with a primary cause originating in the kidney.

Classification

Class I disease (minimal mesangial glomerulonephritis) in its histology has a normal appearance under a light microscope, but mesangial deposits are visible under an electron microscope. At this stage urinalysis is normal.

Class II disease (mesangial proliferative glomerulonephritis) is noted by mesangial hypercellularity and matrix expansion. Microscopic haematuria with or without proteinuria may be seen. Hypertension, nephrotic syndrome, and acute kidney injury are very rare at this stage.

Class III disease (focal glomerulonephritis) is indicated by 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. Under the electron microscopy, subendothelial deposits are noted, and some mesangial changes may be present. Immunofluorescence reveals positively for IgG, IgA, IgM, C3, and C1q. Clinically, haematuria and proteinuria are present, with or without nephrotic syndrome, hypertension, and elevated serum creatinine.

Diffuse proliferative lupus nephritis as seen in a pathology specimen

Class IV disease (diffuse proliferative nephritis) is both the most severe, and the most common subtype. 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, subendothelial 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.

Class V disease (membranous glomerulonephritis) is characterized by diffuse thickening of the glomerular capillary wall (segmentally or globally), with diffuse membrane thickening, and subepithelial deposits seen under the electron microscope. Clinically, stage V presents with signs of nephrotic syndrome. Microscopic haematuria and hypertension may also been seen. Stage V can also lead to thrombotic complications such as renal vein thromboses or pulmonary emboli.

Class VI, or advanced sclerosing lupus nephritis. a final class which is included by most practitioners. It is represented by 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. 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. It is thought to be due to the chronic interferon exposure.

Signs and symptoms

General symptoms of lupus nephritis include

• Fever
• Edema
• High blood pressure
• Joint pain
• Muscle pain
• Malar rash
• Foamy urine

Cause

The cause of lupus nephritis, a genetic predisposition, plays role in lupus nephritis. Multiple genes, many of which are not yet identified, mediate this genetic predisposition.

The immune system protects the human body from infection, with immune system problems it cannot distinguish between harmful and healthy substances. Lupus nephritis affects approximately 3 out of 10,000 people.

Pathophysiology

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.

Diagnosis

Membranous nephropathy

The diagnosis of lupus nephritis depends on blood tests, urinalysis, X-rays, ultrasound scans of the kidneys, and a kidney biopsy. On urinalysis, a nephritic picture is found and red blood cell casts, red blood cells and proteinuria is found. The World Health Organization has divided lupus nephritis into five stages based on the biopsy. This classification was defined in 1982 and revised in 1995.

• Class I is minimal mesangial glomerulonephritis which is histologically normal on light microscopy but with mesangial deposits on electron microscopy. It constitutes about 5% of cases of lupus nephritis. Kidney failure is very rare in this form.
• Class II is based on a finding of mesangial proliferative lupus nephritis. This form typically responds completely to treatment with corticosteroids. It constitutes about 20% of cases. Kidney failure is rare in this form.
• Class III is focal proliferative nephritis and often successfully responds to treatment with high doses of corticosteroids. It constitutes about 25% of cases. Kidney failure is uncommon in this form.
• Class IV is diffuse proliferative nephritis. This form is mainly treated with corticosteroids and immunosuppressant drugs. It constitutes about 40% of cases. Kidney failure is common in this form.
• Class V is membranous nephritis and is characterized by extreme edema and protein loss. It constitutes about 10% of cases. Kidney failure is uncommon in this form.

Treatment

Cyclophosphamide

Drug regimens prescribed for lupus nephritis include mycophenolate mofetil (MMF), intravenous cyclophosphamide with corticosteroids, and the immune suppressant azathioprine with corticosteroids. MMF and cyclophosphamide with corticosteroids are equally effective in achieving remission of the disease. 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).

See also

• Glomerulus (kidney)

External links

Classification	ICD-10: M32.1 +N08.5 ICD-9-CM: 583.81 MeSH: D008181
External resources	MedlinePlus: 000481 eMedicine: med/1597

Lupus nephritis

• Minimal mesangial glomerulonephritis Class I (Minimal mesangial glomerulonephritis Minimal mesangial glomerulonephritis)
• Mesangial proliferative lupus nephritis Class II (Mesangial proliferative lupus nephritis Mesangial proliferative lupus nephritis)
• Focal proliferative nephritis Class III (Focal proliferative nephritis Focal proliferative nephritis)
• Diffuse proliferative nephritis Class IV (Diffuse proliferative nephritis Diffuse proliferative nephritis)
• Membranous glomerulonephritis Class V (Membranous glomerulonephritis Membranous nephritis)
• Glomerulosclerosis Class VI (Glomerulosclerosis Glomerulosclerosis)

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