Lupus nephritis: Difference between revisions
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| Caption = [[Micrograph]] of diffuse proliferative lupus nephritis showing increased mesangial matrix and mesangial hypercellularity. [[Kidney biopsy]]. [[PAS stain]]. |
| Caption = [[Micrograph]] of diffuse proliferative lupus nephritis showing increased mesangial matrix and mesangial hypercellularity. [[Kidney biopsy]]. [[PAS stain]]. |
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| ICD10 = {{ICD10|N|08|5|n|00}} |
| ICD10 = {{ICD10|M|32|1|m|32}}+{{ICD10|N|08|5|n|00}}* |
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| ICD9 = {{ICD9|583.81}} |
| ICD9 = {{ICD9|583.81}} |
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Revision as of 15:21, 13 June 2012
| Lupus nephritis | |
|---|---|
| Specialty | Nephrology  |
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.
Signs and symptoms
General Symptoms of Lupus include: Malar Rash, Discoid rash, photosensitivity, oral ulcers, nonerosive arthritis, pleuropericarditis, renal disease, neurologic manifestaions, and hematologic disorders.
Clinically, SLE is manifested by: Fever, weight loss (100%), Arthralgias, synovitis, arthritis (95%), Pleuritis, pericarditis (80%), Malar facial rash, photodermatosis, alopecia (75%), Anemia, leukopenia, thrombocytopenia, thromboses (50%).
About half of cases of SLE demonstrate signs of Lupus Nephritis at one time or another. Renal specific signs: Proteinuria (100%), Nephrotic Syndrome (55%), Granular casts (30%), Red Cell Casts (10%), Microhematuria (80%), Macrohematuria (2%), Reduced Renal Function (60%), RPGN (30%), ARF (2%), Hypertension (35%), Hyperkalemia (15%), Tubular Abnormalities (70%).
In histology, Stage I (Minimal Mesangial) disease looks normal under light microscopy, but mesangial deposits are noted in Electron Microscopy. In this stage urinalysis is typically normal.
Stage II disease (Mesangial Proliferative) is noted by mesangial hypercellularity and matrix expansion. Microscopic hematuria with or without proteinuria may be seen. Hypertension, Nephrotic Syndrome, and Acute Renal Insufficiency are rare at this stage.
Stage III Disease (Focal Lupus Nephritis) is indicated by Sclerotic lesions of <50% of the glomeruli, which can be segmental or global, and active or chronic, with endocapillary or extracapillary proliferative lesions. In Electron Microscopy, subendothelial deposits are noted, and some mesangial changes may be present. Immunofluorescence reveals the so called "Full House" stain, staining positively for IgG, IgA, IgM, C3, and C1q." Clinically, Hematuria and Proteinuria is present, with or without Nephrotic Syndrome, Hypertension, and elevated Serum Creatinine.
Stage IV Lupus Nephritis (Diffuse Proliferative) is both the most severe, and the most common subtype. In it, >50% of glomeruli are involved which can be segmental or global, and active or chronic, with endocapillary or extracapillary proliferative lesions. In Electron Microscopy, subendothelial deposits are noted, and some mesangial changes may be present. Immunofluorescence reveals the so called "Full House" stain, staining positively for IgG, IgA, IgM, C3, and C1q." Clinically, Hematuria and Proteinuria is present, frequently with Nephrotic Syndrome, Hypertension, Hypocomplementemia, elevated anti-dsDNA titers and elevate Serum Creatinine.
A wire-loop lesion may be present in stages III and IV. The wire loop lesion is a glomerular capillary loop with subendothelial immune complex deposition that is circumferential around the loop. Stage V is denoted by an uniformly thickened, eosinophilic basement membrane. Stage III and IV are differentiated only by the number of glomeruli involved (which is subject to inherent sample bias), but clinically the presentation and prognosis are both expected to be more severe in Stage IV versus Stage III.
Stage V (Membranous Lupus Nephritis) is characterized by diffuse thickening of the glomerular capillary wall (segmentally or globally), with diffuse membrane thickening, and supepithelial (note the -epi-) deposits seen in Electron Microscopy. Note that the Stages in Lupus Nephritis are not chronological in the traditional sense, meaning they do not imply a progression from stage I - IV. In addition, stage V can occur in combination with other stages, e.g. Stage III + V, or Stage IV + V, or on its own. Suspect a combination diagnosis when subepithelial and subendothelial deposits are both present on Electron Microscopy. Clinically, Stage V presents with signs of Nephrotic Syndrome; microscopic hematuria and hypertension may also been seen. Plasma Creatinine is usually normal or slightly elevated, and stage V may not present with any other clinical/serologic manifestations of SLE (complement levels may be normal; anti-DNA Ab may not be detectable). Stage 5 is also predisposed to thrombotic complications (renal vein thrombosis, pulmonary embolus).
A final stage is usually included by most practitioners, Stage VI, or Advanced Sclerosing Lupus Nephritis. It is represented by Global sclerosis >90% of glomeruli, and represents healing of prior inflammatory injury, as well as chronic class III, IV, V. Active glomerulonephritis should not be observed. This stage is clinically observed as slowly progressive renal dysfunction, with relatively bland urine sediment and is unlikely to respond to immunosuppressive therapy.
A Tubuloreticular inclusion is also characteristic of Lupus Nephritis, and can be seen by Electron Microscopy in all stages. It is not diagnostic however, as it exists in other conditions. It is thought to be due to chronic Interferon exposure.
Diagnosis
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 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.[1]
- 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.[2] Renal failure is very rare in this form.[2]
- 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.[2] Renal failure is rare in this form.[2]
- Class III is focal proliferative nephritis and often successfully responds to treatment with high doses of corticosteroids. It constitutes about 25% of cases.[2] Renal failure is uncommon in this form.[2]
- Class IV is diffuse proliferative nephritis. This form is mainly treated with corticosteroids and immunosuppressant drugs. It constitutes about 40% of cases.[2] Renal failure is common in this form.[2]
- Class V is membranous nephritis and is characterized by extreme edema and protein loss. It constitutes about 10% of cases.[2] Renal failure is uncommon in this form.[2]
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 mofetil and intravenous cyclophosphamide. One recent study compared these two drugs.[3] 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 [1]. 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.[4] 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.
References
- ^ Weening JJ, D'Agati VD, Schwartz MM; et al. (2004). "The classification of glomerulonephritis in systemic lupus erythematosus revisited". J. Am. Soc. Nephrol. 15 (2): 241–50. doi:10.1097/01.ASN.0000108969.21691.5D. PMID 14747370.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b c d e f g h i j Table 6-4 in: Elizabeth D Agabegi; Agabegi, Steven S. (2008). Step-Up to Medicine (Step-Up Series). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7153-6.
{{cite book}}: CS1 maint: multiple names: authors list (link) - ^ Ginzler EM, Dooley MA, Aranow C; et al. (2005). "Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis". N. Engl. J. Med. 353 (21): 2219–28. doi:10.1056/NEJMoa043731. PMID 16306519.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Appel GB, Contreras G; et al. (2009). "Oral Mycophenolate Mofetil is not Superior to Intravenous Cyclophosphamide as Induction Therapy for Lupus Nephritis". J Am Soc Nephrol. 20 (5): 1103–12. doi:10.1681/ASN.2008101028. PMC 2678035. PMID 19369404.
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