Lupus nephritis

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Lupus nephritis
Other namesSLE nephritis [1]
Diffuse proliferative lupus nephritis - high mag.jpg
Micrograph of diffuse proliferative lupus nephritis showing increased mesangial matrix and mesangial hypercellularity. Kidney biopsy. PAS stain.
Specialty Nephrology   OOjs UI icon edit-ltr-progressive.svg
Symptoms Joint pain or swelling [2]
CausesComplication of systemic lupus erythematosus. [3]
Diagnostic method Complement levels, Urinalysis [3]
TreatmentCorticosteroids may be used [3]

Lupus nephritis is an inflammation of the kidneys 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. [3] [4] 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. [5] [2] 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.

Contents

Signs and symptoms

General symptoms of lupus nephritis include [2] [6]

Cause

The cause of lupus nephritis, a genetic predisposition, plays a significant role in lupus nephritis. Multiple genes, many of which are not yet identified, mediate this genetic predisposition. [7] [8]

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

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. [7]

Diagnosis

Membranous nephropathy Membranous nephropathy - mpas - very high mag.jpg
Membranous nephropathy

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. [9]

Classification

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. [10] [11]

Class IV disease (Diffuse proliferative nephritis) is both the most severe, and the most common subtype. 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. [12]

OrderNameIncidence [13] Light microscopy Electron microscopy Clinical findings and other testsTreatment
Class I Minimal mesangial glomerulonephritis 5%Normal appearance Mesangial deposits are visible under an electron microscope Kidney failure is very rare in this form. [13] Normal urinalysis. [14]
Class II Mesangial proliferative glomerulonephritis 20%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. [14] 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.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. [14] Often successfully responds to high doses of corticosteroids
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, 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. [14] Kidney failure is common. [13]
Diffuse proliferative lupus nephritis as seen in a pathology specimen Diffuse proliferative lupus nephritis.jpg
Diffuse proliferative lupus nephritis as seen in a pathology specimen
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.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. [14] Kidney failure is uncommon. [13]
Class VIAdvanced sclerosing lupus nephritis. [7] 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.

Treatment

Cyclophosphamide Cyclophosphamide.svg
Cyclophosphamide

Drug regimens prescribed for lupus nephritis include mycophenolate mofetil (MMF), intravenous cyclophosphamide with corticosteroids, and the immune suppressant azathioprine with corticosteroids. [15] MMF and cyclophosphamide with corticosteroids are equally effective in achieving remission of the disease, however the results of a recent systematic review found that immunosuppressive drugs were better than corticosteroids for renal outcomes. [16] 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. [17] [18] 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. [19] [20] Individuals with lupus nephritis have a high risk for B-cell lymphoma (which begins in the immune system cells). [2]

Prognosis

In those who have SLE, concomitant lupus nephritis is associated with a worse overall prognosis. [21] 10-30% of people with lupus nephritis progress to kidney failure requiring dialysis, with the 5 year mortality rate of lupus nephritis being 5-25%. [21] The proliferative forms of lupus nephritis are associated with a higher risk of progression to end stage kidney disease. [21] Black and Hispanic people with lupus nephritis are more likely to present with severe disease at initial presentation (with more proteinuria and more extensive histopathologic changes) and progress to end stage kidney disease. This is thought to be due to socioeconomic factors but auto-antibodies strongly associated with lupus nephritis such as anti-Sm, anti-Ro and anti-ribonucleoprotein are also more commonly seen in Black and Hispanic people. [21] Men with SLE tend to have more aggressive forms of lupus nephritis as well with a higher risk of progression to end stage kidney disease and higher risk of concurrent cardiovascular disease. [21]

See also

Related Research Articles

<span class="mw-page-title-main">Antinuclear antibody</span> Autoantibody that binds to contents of the cell nucleus

Antinuclear antibodies are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human proteins (autoantigens). In some cases, antibodies to human antigens are produced; these are known as autoantibodies.

<span class="mw-page-title-main">Mycophenolic acid</span> Immunosuppressant medication

Mycophenolic acid is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohn's disease and lupus. Specifically it is used following kidney, heart, and liver transplantation. It can be given by mouth or by injection into a vein. It comes as mycophenolate sodium and mycophenolate mofetil.

<span class="mw-page-title-main">Glomerulonephritis</span> Term for several kidney diseases

Glomerulonephritis (GN) is a term used to refer to several kidney diseases. Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the name, but not all diseases necessarily have an inflammatory component.

<span class="mw-page-title-main">Membranous glomerulonephritis</span> Kidney disease

Membranous glomerulonephritis (MGN) is a slowly progressive disease of the kidney affecting mostly people between ages of 30 and 50 years, usually white people.

<span class="mw-page-title-main">Cyclophosphamide</span> Medication used as chemotherapy and to suppress the immune system

Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer, small cell lung cancer, neuroblastoma, and sarcoma. As an immune suppressor it is used in nephrotic syndrome, granulomatosis with polyangiitis, and following organ transplant, among other conditions. It is taken by mouth or injection into a vein.

<span class="mw-page-title-main">Nephritic syndrome</span> Symptoms resulting from kidney inflammation

Nephritic syndrome is a syndrome comprising signs of nephritis, which is kidney disease involving inflammation. It often occurs in the glomerulus, where it is called glomerulonephritis. Glomerulonephritis is characterized by inflammation and thinning of the glomerular basement membrane and the occurrence of small pores in the podocytes of the glomerulus. These pores become large enough to permit both proteins and red blood cells to pass into the urine. By contrast, nephrotic syndrome is characterized by proteinuria and a constellation of other symptoms that specifically do not include hematuria. Nephritic syndrome, like nephrotic syndrome, may involve low level of albumin in the blood due to the protein albumin moving from the blood to the urine.

Mixed connective tissue disease (MCTD) is a systemic autoimmune disease that shares characteristics with at least two other systemic autoimmune diseases, including systemic sclerosis (Ssc), systemic lupus erythematosus (SLE), polymyositis/dermatomyositis (PM/DM), and rheumatoid arthritis. The idea behind the "mixed" disease is that this specific autoantibody is also present in other autoimmune diseases such as systemic lupus erythematosus, polymyositis, scleroderma, etc. MCTD was characterized as an individual disease in 1972 by Sharp et al., and the term was introduced by Leroy in 1980.

<span class="mw-page-title-main">Rapidly progressive glomerulonephritis</span> Medical condition

Rapidly progressive glomerulonephritis (RPGN) is a syndrome of the kidney that is characterized by a rapid loss of kidney function, with glomerular crescent formation seen in at least 50% or 75% of glomeruli seen on kidney biopsies. If left untreated, it rapidly progresses into acute kidney failure and death within months. In 50% of cases, RPGN is associated with an underlying disease such as Goodpasture syndrome, systemic lupus erythematosus or granulomatosis with polyangiitis; the remaining cases are idiopathic. Regardless of the underlying cause, RPGN involves severe injury to the kidneys' glomeruli, with many of the glomeruli containing characteristic glomerular crescents.

<span class="mw-page-title-main">Membranoproliferative glomerulonephritis</span> Medical condition

Membranoproliferative glomerulonephritis (MPGN) is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane (GBM) thickening, activating the complement system and damaging the glomeruli.

<span class="mw-page-title-main">Lupus erythematosus</span> Collection of human autoimmune diseases

Lupus erythematosus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs. The most common and most severe form is systemic lupus erythematosus.

<span class="mw-page-title-main">Mesangial proliferative glomerulonephritis</span> Medical condition

Mesangial proliferative glomerulonephritis (MesPGN) is a morphological pattern characterized by a numerical increase in mesangial cells and expansion of the extracellular matrix within the mesangium of the glomerulus. The increase in the number of mesangial cells can be diffuse or local and immunoglobulin and/or complement deposition can also occur. MesPGN is associated with a variety of disease processes affecting the glomerulus, though can be idiopathic. The clinical presentation of MesPGN usually consists of hematuria or nephrotic syndrome. Treatment is often consistent with the histologic pattern of and/or disease process contributing to mesangial proliferative glomerulonephritis, and usually involves some form of immunosuppressant.

Pulmonary-renal syndrome (PRS) is a rare medical syndrome in which respiratory failure involving bleeding in the lungs and kidney failure (glomerulonephritis) occur. PRS is associated with a high rate of morbidity and death. The term was first used by Goodpasture in 1919 to describe the association of respiratory and kidney failure.

<span class="mw-page-title-main">Anti-dsDNA antibodies</span> Group of anti-nuclear antibodies

Anti-double stranded DNA (Anti-dsDNA) antibodies are a group of anti-nuclear antibodies (ANA) the target antigen of which is double stranded DNA. Blood tests such as enzyme-linked immunosorbent assay (ELISA) and immunofluorescence are routinely performed to detect anti-dsDNA antibodies in diagnostic laboratories. They are highly diagnostic of systemic lupus erythematosus (SLE) and are implicated in the pathogenesis of lupus nephritis.

<span class="mw-page-title-main">Lupus</span> Autoimmune disease in which the immune system attacks healthy tissue

Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face. Often there are periods of illness, called flares, and periods of remission during which there are few symptoms. Children up to 18 years old develop a more severe form of SLE termed childhood-onset systemic lupus erythematosus.

Diffuse proliferative glomerulonephritis (DPGN) 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. In absence of SLE, DPGN pathology looks more like Membranoproliferative glomerulonephritis

Minimal mesangial glomerulonephritis is a type of glomerulonephritis that 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.

<span class="mw-page-title-main">Anti-SSA/Ro autoantibodies</span> Type of anti-nuclear autoantibodies

Anti-SSA autoantibodies are a type of anti-nuclear autoantibodies that are associated with many autoimmune diseases, such as systemic lupus erythematosus (SLE), SS/SLE overlap syndrome, subacute cutaneous lupus erythematosus (SCLE), neonatal lupus and primary biliary cirrhosis. They are often present in Sjögren's syndrome (SS). Additionally, Anti-Ro/SSA can be found in other autoimmune diseases such as systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), rheumatoid arthritis (RA), and mixed connective tissue disease (MCTD), and are also associated with heart arrhythmia.

Autoimmune optic neuropathy (AON), sometimes called autoimmune optic neuritis, may be a forme fruste of systemic lupus erythematosus (SLE) associated optic neuropathy. AON is more than the presence of any optic neuritis in a patient with an autoimmune process, as it describes a relatively specific clinical syndrome. AON is characterized by chronically progressive or recurrent vision loss associated with serological evidence of autoimmunity. Specifically, this term has been suggested for cases of optic neuritis with serological evidence of vasculitis by positive ANA, despite the lack of meeting criteria for SLE. The clinical manifestations include progressive vision loss that tends to be steroid-responsive and steroid dependent.

<span class="mw-page-title-main">Lupus vasculitis</span> Medical condition

Lupus vasculitis is one of the secondary vasculitides that occurs in approximately 50% of patients with systemic lupus erythematosus (SLE).

Childhood-onset systemic lupus erythematosus, also termed juvenile-onset systemic lupus erythematosus, juvenile systemic lupus erythematosus, and pediatric systemic lupus erythematosus, is a form of the chronic inflammatory and autoimmune disease, systemic lupus erythematosus, that develops in individuals up to 18 years old. Early-onset systemic lupus erythematosus is often used to designate a subset of cSLE patients who are up to 5 years old. Children with early-onset SLE tend to have a more severe form of cSLE than children who develop cSLE after 5 years of age.

References

  1. ↑ Ponticelli, C.; Moroni, G. (2005-01-01). "Renal transplantation in lupus nephritis". Lupus. 14 (1): 95–98. doi:10.1191/0961203305lu2067oa. ISSN   0961-2033. PMID   15732296. S2CID   36968488.
  2. 1 2 3 4 "Lupus Nephritis". www.niddk.nih.gov. Retrieved 2015-10-31.
  3. 1 2 3 4 5 "Lupus nephritis: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-10-31.
  4. ↑ Lee WF, Fan WL, Tseng MH, Yang HY, Huang JL, Wu CY (August 2022). "Characteristics and genetic analysis of patients suspected with early-onset systemic lupus erythematosus". Pediatric Rheumatology Online Journal. 20 (1): 68. doi: 10.1186/s12969-022-00722-6 . PMC   9375402 . PMID   35964089.
  5. ↑ Saxena, Ramesh; Mahajan, Tina; Mohan, Chandra (2011-01-01). "Lupus nephritis: current update". Arthritis Research & Therapy . 13 (5): 240. doi: 10.1186/ar3378 . ISSN   1478-6354. PMC   3308062 . PMID   22078716.
  6. ↑ "Lupus Nephritis - National Library of Medicine". PubMed Health. Retrieved 2015-11-03.
  7. 1 2 3 "Lupus Nephritis: Practice Essentials, Pathophysiology, Etiology". emedicine. 30 March 2023. Retrieved 2 January 2024.
  8. ↑ Salgado, Alberto (2012). "Lupus Nephritis: An Overview of Recent Findings". Autoimmune Diseases. 2012: 849684. doi: 10.1155/2012/849684 . PMC   3318208 . PMID   22536486.
  9. ↑ Kfoury H (2014). "Tubulo-reticular inclusions in lupus nephritis: are they relevant?". Saudi Journal of Kidney Diseases and Transplantation. 25 (3): 539–43. doi: 10.4103/1319-2442.132169 . PMID   24821149.
  10. ↑ Weening JJ, D'Agati VD, Schwartz MM, et al. (February 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 . hdl: 20.500.12648/8229 . PMID   14747370.
  11. ↑ "National Guideline Clearinghouse | American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis". www.guideline.gov. Archived from the original on 2015-09-18. Retrieved 2015-11-01.
  12. ↑ Karageorgas TP, Tseronis DD, Mavragani CP (2011). "Activation of type I interferon pathway in systemic lupus erythematosus: association with distinct clinical phenotypes". Journal of Biomedicine & Biotechnology. 2011: 1–13. doi: 10.1155/2011/273907 . PMC   3227532 . PMID   22162633.
  13. 1 2 3 4 Table 6-4 in: Elizabeth D Agabegi; Agabegi, Steven S. (2008). Step-Up to Medicine (Step-Up Series) . Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN   978-0-7817-7153-5.
  14. 1 2 3 4 5 Lewis, Edmund J.; Schwartz, Melvin M. (2010-11-04). Lupus Nephritis. OUP Oxford. pp. 174–177. ISBN   9780199568055.
  15. ↑ Singh, Jasvinder A.; Hossain, Alomgir; Kotb, Ahmed; Wells, George A. (2016). "Comparative effectiveness of immunosuppressive drugs and corticosteroids for lupus nephritis: a systematic review and network meta-analysis". Systematic Reviews. 5 (1): 155. doi: 10.1186/s13643-016-0328-z . ISSN   2046-4053. PMC   5020478 . PMID   27619512.
  16. ↑ Singh, Jasvinder A.; Hossain, Alomgir; Kotb, Ahmed; Oliveira, Ana; Mudano, Amy S.; Grossman, Jennifer; Winthrop, Kevin; Wells, George A. (2016). "Treatments for Lupus Nephritis: A Systematic Review and Network Metaanalysis". The Journal of Rheumatology. 43 (10): 1801–1815. doi: 10.3899/jrheum.160041 . ISSN   0315-162X. PMID   27585688.
  17. ↑ Tunnicliffe, David J.; Palmer, Suetonia C.; Henderson, Lorna; Masson, Philip; Craig, Jonathan C.; Tong, Allison; Singh-Grewal, Davinder; Flanc, Robert S.; Roberts, Matthew A.; Webster, Angela C.; Strippoli, Giovanni Fm (29 June 2018). "Immunosuppressive treatment for proliferative lupus nephritis". The Cochrane Database of Systematic Reviews. 2018 (6): CD002922. doi:10.1002/14651858.CD002922.pub4. ISSN   1469-493X. PMC   6513226 . PMID   29957821.
  18. ↑ Masson, Philip (2011). "Induction and maintenance treatment of proliferative lupus nephritis" (PDF). Nephrology. 18: 71–72. doi:10.1111/nep.12011. S2CID   56952099 . Retrieved 4 November 2015.
  19. ↑ Singh, Jasvinder A.; Hossain, Alomgir; Kotb, Ahmed; Wells, George (2016-09-13). "Risk of serious infections with immunosuppressive drugs and glucocorticoids for lupus nephritis: a systematic review and network meta-analysis". BMC Medicine. 14 (1): 137. doi: 10.1186/s12916-016-0673-8 . ISSN   1741-7015. PMC   5022202 . PMID   27623861.
  20. ↑ Tang, Kuo-Tung; Tseng, Chien-Hua; Hsieh, Tsu-Yi; Chen, Der-Yuan (June 2018). "Induction therapy for membranous lupus nephritis: a systematic review and network meta-analysis". International Journal of Rheumatic Diseases. 21 (6): 1163–1172. doi:10.1111/1756-185X.13321. ISSN   1756-185X. PMID   29879319. S2CID   46951249.
  21. 1 2 3 4 5 Parikh, Samir V.; Almaani, Salem; Brodsky, Sergey; Rovin, Brad H. (1 August 2020). "Update on Lupus Nephritis: Core Curriculum 2020". American Journal of Kidney Diseases. 76 (2): 265–281. doi: 10.1053/j.ajkd.2019.10.017 . ISSN   0272-6386. PMID   32220510 . Retrieved 22 July 2021.

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