Lupus nephritis
Encyclopedia
Lupus nephritis is an inflammation of the kidney caused by systemic lupus erythematosus
(SLE), a disease of the immune system
. Apart from the kidneys, SLE can also damage the skin
, joints, nervous system
and virtually any organ or system in the body.
, darker foamy urine
or swelling
around the eyes, legs, ankles or fingers.
Histologically a wire-loop lesion will be present. The wire loop lesion is a glomerular capillary loop with subendothelial immune complex deposition that is circumferential around the loop.
Furthermore, patients may suffer from other symptoms of lupus unrelated to kidney function. Such symptoms can include arthritis
, fevers
, gastro-intestinal disturbances, headaches, fatigue
, and fluid in the joints.
tests, urinalysis
, X-rays, ultrasound
scans of the kidneys, and a kidney biopsy
. On urinalysis, a nephritic picture is found and RBC casts, RBCs and protenuria is found.
The World Health Organization
has divided lupus nephritis into five classes based on the biopsy. This classification was defined in 1982 and revised in 1995.
Medicines are prescribed that decrease swelling, lower blood pressure, and decrease inflammation by suppressing the immune system: Patients may need to monitor intake of protein, sodium, and potassium. Patients with severe disease should restrict their sodium intake to 2 grams per day and limit fluid as well. Depending on the histology, renal function and degree of proteinuria, patients may require steroid therapy or chemotherapy regimens such as cyclophosphamide, azathioprine, mycophenolate mofetil, or cyclosporine.
and intravenous cyclophosphamide
. One recent study compared these two drugs. The authors showed that patients with Class III or IV disease are more likely to benefit from mycophenolate mofetil
as compared to cyclophosphamide
. However, a larger study by the same authors that directly compared these therapies did not show that Mycophenolate was superiour to cyclophosphamide except in non-caucasian non-Asian patients http://www.hopkins-arthritis.org/physician-corner/education/acr2007/lupus/abstract-L13.html. In caucasian or Asian patients both treatments worked equally well. Both agents are associated with significant adverse effects; cyclophosphamide may induce permanent infertility in young women, and mycophenolate mofetil is associated with a higher risk of infection-related death. One study concluded that in cases where lupus-related thrombotic thrombocytopenic purpura is present, plasmapheresis is life-saving, and must be instituted early to avoid a poor outcome. PMID 14530532.
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
(SLE), a disease of the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
. Apart from the kidneys, SLE can also damage the skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
, joints, nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
and virtually any organ or system in the body.
Signs and symptoms
Sufferers of lupus nephritis may or may not have symptoms of kidney disease, but it can manifest itself through weight gain, high blood pressureHypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, darker foamy urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
or swelling
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
around the eyes, legs, ankles or fingers.
Histologically a wire-loop lesion will be present. The wire loop lesion is a glomerular capillary loop with subendothelial immune complex deposition that is circumferential around the loop.
Furthermore, patients may suffer from other symptoms of lupus unrelated to kidney function. Such symptoms can include arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
, fevers
Fevers
Fevers are a five-piece band formed in 2010 in Ottawa, Ontario. The band consists of Colin MacDougall , Jim Hopkins , Martin Charbonneau , Sarah Bradley and Mike Stauffer . Theirs is a fresh take on a classic genre, combining indie rock and electronic music...
, gastro-intestinal disturbances, headaches, fatigue
Fatigue (physical)
Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles...
, and fluid in the joints.
Diagnosis
The diagnosis of lupus nephritis depends on bloodBlood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
tests, urinalysis
Urinalysis
A urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...
, X-rays, ultrasound
Ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
scans of the kidneys, and a kidney biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
. On urinalysis, a nephritic picture is found and RBC casts, RBCs and protenuria is found.
The World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
has divided lupus nephritis into five classes based on the biopsy. This classification was defined in 1982 and revised in 1995.
- Class I is minimal mesangial glomerulonephritisMinimal mesangial glomerulonephritisMinimal mesangial glomerulonephritis is a type of glomerulonephritis is seen in 10% to 25% of SLE cases, and is associated with mild clinical symptoms. Immune complexes deposit in the mesangium, with a slight increase in the mesangial matrix and cellularity....
which is histologically normal on light microscopy but with mesangial deposits on electron microscopy. It constitutes about 5% of cases of lupus nephritis. Renal 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. Renal failure is rare in this form.
- Class III is focal proliferative nephritisFocal proliferative nephritisFocal proliferative nephritis is a type of glomerulonephritis seen in 20% to 35% of cases of SLE, classified as type III SLE. As the name suggests, lesions are visualized in only portions of fewer than half the glomeruli...
and often successfully responds to treatment with high doses of corticosteroids. It constitutes about 25% of cases. Renal failure is uncommon in this form. - Class IV is diffuse proliferative nephritisDiffuse proliferative nephritisDiffuse proliferative glomerulonephritis is a type of glomerulonephritis that is the most serious form of renal lesions in SLE and is also the most common, occurring in 35% to 60% of patients...
. This form is mainly treated with corticosteroids and immunosuppressant drugs. It constitutes about 40% of cases. Renal 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. Renal failure is uncommon in this form.
Medicines are prescribed that decrease swelling, lower blood pressure, and decrease inflammation by suppressing the immune system: Patients may need to monitor intake of protein, sodium, and potassium. Patients with severe disease should restrict their sodium intake to 2 grams per day and limit fluid as well. Depending on the histology, renal function and degree of proteinuria, patients may require steroid therapy or chemotherapy regimens such as cyclophosphamide, azathioprine, mycophenolate mofetil, or cyclosporine.
Treatment
The medical therapy for lupus nephritis depends on the severity of the disease. For mild disease, corticosteroids are, in general, prescribed. More severe disease requires treatment with immunosuppressant agents. The two most commonly-used agents are mycophenolate mofetilMycophenolate mofetil
Mycophenolate mofetil is an immunosuppressant and prodrug of mycophenolic acid, used extensively in transplant medicine. It is a reversible inhibitor of inosine monophosphate dehydrogenase in purine biosynthesis, which is necessary for the growth of T cells and B cells...
and intravenous cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
. One recent study compared these two drugs. The authors showed that patients with Class III or IV disease are more likely to benefit from mycophenolate mofetil
Mycophenolate mofetil
Mycophenolate mofetil is an immunosuppressant and prodrug of mycophenolic acid, used extensively in transplant medicine. It is a reversible inhibitor of inosine monophosphate dehydrogenase in purine biosynthesis, which is necessary for the growth of T cells and B cells...
as compared to cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
. However, a larger study by the same authors that directly compared these therapies did not show that Mycophenolate was superiour to cyclophosphamide except in non-caucasian non-Asian patients http://www.hopkins-arthritis.org/physician-corner/education/acr2007/lupus/abstract-L13.html. In caucasian or Asian patients both treatments worked equally well. Both agents are associated with significant adverse effects; cyclophosphamide may induce permanent infertility in young women, and mycophenolate mofetil is associated with a higher risk of infection-related death. One study concluded that in cases where lupus-related thrombotic thrombocytopenic purpura is present, plasmapheresis is life-saving, and must be instituted early to avoid a poor outcome. PMID 14530532.