Membranous glomerulonephritis

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Membranous glomerulonephritis
Other namesMembranous glomerulopathy, membranous nephritis, (epi)membranous nephropathy, extramembranous glomerulopathy, and perimembranous nephropathy. [1]
Membranous nephropathy - mpas - very high mag.jpg
Micrograph of membranous nephropathy showing prominent glomerular basement membrane spikes. Jones' stain.
Specialty Nephrology   OOjs UI icon edit-ltr-progressive.svg

Membranous glomerulonephritis (MGN) is a slowly progressive disease of the kidney affecting mostly people between ages of 30 and 50 years, usually white people (i.e., those of European, Middle Eastern, or North African ancestry.)[ citation needed ].

Contents

Video explanation

It is the second most common cause of nephrotic syndrome in adults, with focal segmental glomerulosclerosis (FSGS) recently becoming the most common. [2]

Signs and symptoms

Most people will present as nephrotic syndrome, with the triad of albuminuria, edema and low serum albumin (with or without kidney failure). High blood pressure and high cholesterol are often also present. Others may not have symptoms and may be picked up on screening, with urinalysis finding high amounts of protein loss in the urine. A definitive diagnosis of membranous nephropathy requires a kidney biopsy, though given the very high specificity of anti-PLA2R antibody positivity this can sometimes be avoided in patients with nephrotic syndrome and preserved kidney function [3]

Causes

Traditional definitions split membranous nephropathy into 'primary/idiopathic' or 'secondary'. It is likely that instead the field will move to novel classification on the basis of the specific autoantigen detected, though given the current lack of clinical assays (other than for PLA2R autoantibodies) this may be several years off still.

Primary/idiopathic

Traditionally 85% of MGN cases are classified as primary membranous glomerulonephritis—that is to say, the cause of the disease is idiopathic (of unknown origin or cause). This can also be referred to as idiopathic membranous nephropathy. [ citation needed ]

Antibodies to an M-type phospholipase A2 receptor [4] are responsible around 60% of cases of membranous nephropathy. Testing for these anti-PLA2R has revolutionised diagnosis and treatment of this disease in antibody positive patients, and tracking titre level over time allows you to predict risk of disease progression and chance of spontaneous remission [5] There is little secondary disease association with PLA2R autoantibodies.

In 2014, a second autoantigen was discovered, the thrombospondin type 1 domain-containing 7A (THSD7A) system that might account for an additional 1% of membranous nephropathy cases, and appears to be associated with malignancies. [6]

Further studies have identidied more novel auto-antigens responsible for causing a membranous nephropathy pattern of injury continue to be published, with antibodies discovered against:

Secondary

We include the traditional list of secondary causes, though as above nomenclature is moving towards an autoantibody specific approach. Membranous nephropathy is associated with the following:

Pathogenesis

Immune complexes (black) are deposited in a thickened basement membrane creating a "spike and dome" appearance on electron microscopy. Membranous Nephropathy Pathology Diagram.svg
Immune complexes (black) are deposited in a thickened basement membrane creating a "spike and dome" appearance on electron microscopy.

MGN is caused by immune complex formation in the glomerulus. The immune complexes are formed by binding of antibodies to antigens in the glomerular basement membrane. The antigens may be part of the basement membrane, or deposited from elsewhere by the systemic circulation.[ citation needed ]

The immune complex serves as an activator that triggers a response from the C5b - C9 complements, which form a membrane attack complex (MAC) on the glomerular epithelial cells. This, in turn, stimulates release of proteases and oxidants by the mesangial and epithelial cells, damaging the capillary walls and causing them to become "leaky". In addition, the epithelial cells also seem to secrete an unknown mediator that reduces nephrin synthesis and distribution.[ citation needed ]

Within membranous glomerulonephritis, especially in cases caused by viral hepatitis, serum C3 levels are low. [17]

Similar to other causes of nephrotic syndrome (e.g., focal segmental glomerulosclerosis or minimal change disease), membranous nephropathy is known to predispose affected individuals to develop blood clots such as pulmonary emboli. Membranous nephropathy in particular is known to increase this risk more than other causes of nephrotic syndrome though the reason for this is not yet clear.[ citation needed ]

Morphology

The defining point of MGN is the presence of subepithelial immunoglobulin-containing deposits along the glomerular basement membrane (GBM).[ citation needed ]

Although it usually affects the entire glomerulus, it can affect parts of the glomerulus in some cases. [19]

Treatment

Treatment of secondary membranous nephropathy is guided by the treatment of the original disease. For treatment of idiopathic membranous nephropathy, the treatment options include immunosuppressive drugs and non-specific anti-proteinuric measures such as ACE inhibitors or angiotensin II receptor blockers. Given spontaneous remission is common, international guidelines recommend a period of watchful waiting before considering immunosuppressive treatment. [20] Likelihood of achieving spontaneous remission is much higher if anti-proteinuric therapy with ace inhibitors or angiotensin II receptor blockers is commenced.[ citation needed ]

Recommended first line immunosuppressive therapy often includes: cyclophosphamide alternating with a corticosteroid, [21] also known as the Ponticelli regime.

Immunosuppressive therapy options

  1. Corticosteroids: They have been tried with mixed results, with one study showing prevention of progression to kidney failure without improvement in proteinuria.
  2. Chlorambucil
  3. Cyclosporine [22]
  4. Tacrolimus
  5. Cyclophosphamide
  6. Mycophenolate mofetil
  7. Rituximab

Perhaps the most difficult aspect of membranous glomerulonephritis is deciding which people to treat with immunosuppressive therapy as opposed to simple "background" or anti-proteinuric therapies. A large part of this difficulty is due to a lack of ability to predict which people will progress to end-stage kidney disease, or kidney disease severe enough to require dialysis. Because the above medications carry risk, treatment should not be initiated without careful consideration as to risk/benefit profile. Of note, corticosteroids (typically Prednisone) alone are of little benefit. They should be combined with one of the other 5 medications, each of which, along with prednisone, has shown some benefit in slowing down progression of membranous nephropathy. It must be kept in mind, however, that each of the 5 medications also carry their own risks, on top of prednisone.[ citation needed ]

The twin aims of treating membranous nephropathy are first to induce a remission of the nephrotic syndrome and second to prevent the development of end-stage kidney failure. A meta-analysis of four randomized controlled trials comparing treatments of membranous nephropathy showed that regimes comprising chlorambucil or cyclophosphamide, either alone or with steroids, were more effective than symptomatic treatment or treatment with steroids alone in inducing remission of the nephrotic syndrome.[ citation needed ]

Prognosis

About a third of untreated patients have spontaneous remission, another third progress to require dialysis and the last third continue to have proteinuria, without progression of kidney failure.[ citation needed ]

Terminology

The closely related terms membranous nephropathy (MN) [23] and membranous glomerulopathy [24] both refer to a similar constellation but without the assumption of inflammation.

Membranous nephritis (in which inflammation is implied, but the glomerulus not explicitly mentioned) is less common, but the phrase is occasionally encountered. [25] These conditions are usually considered together.

By contrast, membranoproliferative glomerulonephritis has a similar name, but is considered a separate condition with a distinctly different causality. Membranoproliferative glomerulonephritis involves the basement membrane and mesangium, while membranous glomerulonephritis involves the basement membrane but not the mesangium. (Membranoproliferative glomerulonephritis has the alternate name "mesangiocapillary glomerulonephritis", to emphasize its mesangial character.)

Related Research Articles

<span class="mw-page-title-main">Proteinuria</span> Presence of an excess of serum proteins in the urine

Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein;less than 150 mg/day,an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy. Severe proteinuria can cause nephrotic syndrome in which there is worsening swelling of the body.

<span class="mw-page-title-main">Nephrotic syndrome</span> Collection of symptoms due to kidney damage

Nephrotic syndrome is a collection of symptoms due to kidney damage. This includes protein in the urine, low blood albumin levels, high blood lipids, and significant swelling. Other symptoms may include weight gain, feeling tired, and foamy urine. Complications may include blood clots, infections, and high blood pressure.

<span class="mw-page-title-main">Kidney disease</span> Damage to or disease of a kidney

Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can be diagnosed by blood tests. Nephrosis is non-inflammatory kidney disease. Nephritis and nephrosis can give rise to nephritic syndrome and nephrotic syndrome respectively. Kidney disease usually causes a loss of kidney function to some degree and can result in kidney failure, the complete loss of kidney function. Kidney failure is known as the end-stage of kidney disease, where dialysis or a kidney transplant is the only treatment option.

<span class="mw-page-title-main">IgA nephropathy</span> Disease of the kidney

IgA nephropathy (IgAN), also known as Berger's disease, or synpharyngitic glomerulonephritis, is a disease of the kidney and the immune system; specifically it is a form of glomerulonephritis or an inflammation of the glomeruli of the kidney. Aggressive Berger's disease can attack other major organs, such as the liver, skin and heart.

<span class="mw-page-title-main">Podocyte</span> Type of kidney cell

Podocytes are cells in Bowman's capsule in the kidneys that wrap around capillaries of the glomerulus. Podocytes make up the epithelial lining of Bowman's capsule, the third layer through which filtration of blood takes place. Bowman's capsule filters the blood, retaining large molecules such as proteins while smaller molecules such as water, salts, and sugars are filtered as the first step in the formation of urine. Although various viscera have epithelial layers, the name visceral epithelial cells usually refers specifically to podocytes, which are specialized epithelial cells that reside in the visceral layer of the capsule. One type of specialized epithelial cell is podocalyxin.

<span class="mw-page-title-main">Goodpasture syndrome</span> Rare autoimmune disease

Goodpasture syndrome (GPS), also known as anti–glomerular basement membrane disease, is a rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs, glomerulonephritis, and kidney failure. It is thought to attack the alpha-3 subunit of type IV collagen, which has therefore been referred to as Goodpasture's antigen. Goodpasture syndrome may quickly result in permanent lung and kidney damage, often leading to death. It is treated with medications that suppress the immune system such as corticosteroids and cyclophosphamide, and with plasmapheresis, in which the antibodies are removed from the blood.

<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">Lupus nephritis</span> Inflammation of the kidneys

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. 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 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.

<span class="mw-page-title-main">Minimal change disease</span> Medical condition

Minimal change disease is a disease affecting the kidneys which causes nephrotic syndrome. Nephrotic syndrome leads to the loss of significant amounts of protein in the urine, which causes the widespread edema and impaired kidney function commonly experienced by those affected by the disease. It is most common in children and has a peak incidence at 2 to 6 years of age. MCD is responsible for 10–25% of nephrotic syndrome cases in adults. It is also the most common cause of nephrotic syndrome of unclear cause (idiopathic) in children.

<span class="mw-page-title-main">Nephritic syndrome</span> Medical condition

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.

<span class="mw-page-title-main">Focal segmental glomerulosclerosis</span> Kidney disease

Focal segmental glomerulosclerosis (FSGS) is a histopathologic finding of scarring (sclerosis) of glomeruli and damage to renal podocytes. This process damages the filtration function of the kidney, resulting in protein loss in the urine. FSGS is a leading cause of excess protein loss—nephrotic syndrome—in children and adults. Signs and symptoms include proteinuria, water retention, and edema. Kidney failure is a common long-term complication of disease. FSGS can be classified as primary versus secondary depending on whether a particular toxic or pathologic stressor can be identified as the cause. Diagnosis is established by renal biopsy, and treatment consists of glucocorticoids and other immune-modulatory drugs. Response to therapy is variable, with a significant portion of patients progressing to end-stage kidney failure. FSGS is estimated to occur in 2–3 persons per million, with males and African peoples at higher risk.

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

Acute proliferative glomerulonephritis is a disorder of the small blood vessels of the kidney. It is a common complication of bacterial infections, typically skin infection by Streptococcus bacteria types 12, 4 and 1 (impetigo) but also after streptococcal pharyngitis, for which it is also known as postinfectious glomerulonephritis (PIGN) or poststreptococcal glomerulonephritis (PSGN). It can be a risk factor for future albuminuria. In adults, the signs and symptoms of infection may still be present at the time when the kidney problems develop, and the terms infection-related glomerulonephritis or bacterial infection-related glomerulonephritis are also used. Acute glomerulonephritis resulted in 19,000 deaths in 2013, down from 24,000 deaths in 1990 worldwide.

Podocin is a protein component of the filtration slits of podocytes. Glomerular capillary endothelial cells, the glomerular basement membrane and the filtration slits function as the filtration barrier of the kidney glomerulus. Mutations in the podocin gene NPHS2 can cause nephrotic syndrome, such as focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD). Symptoms may develop in the first few months of life or later in childhood.

<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 complement and damaging the glomeruli.

<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.

Glomerulonephrosis is a non-inflammatory disease of the kidney (nephrosis) presenting primarily in the glomerulus as Nephrotic Syndrome. The nephron is the functional unit of the kidney and it contains the glomerulus, which acts as a filter for blood to retain proteins and blood lipids. Damage to these filtration units results in important blood contents being released as waste in urine. This disease can be characterized by symptoms such as fatigue, swelling, and foamy urine, and can lead to chronic kidney disease and ultimately end-stage renal disease, as well as cardiovascular diseases. Glomerulonephrosis can present as either primary glomerulonephrosis or secondary glomerulonephrosis.

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

Monoclonal gammopathy of renal significance (MGRS) are a group of kidney disorders that present with kidney damage due to nephrotoxic monoclonal immunoglobulins secreted by clonal plasma cells or B cells. By definition, people with MGRS do not meet criteria for multiple myeloma or other hematologic malignancies. The term MGRS was introduced in 2012 by the International Kidney and Monoclonal Gammopathy Research Group (IKMG). MGRS is associated with monoclonal gammopathy of undetermined significance (MGUS). People with MGUS have a monoclonal gammopathy but does not meet the criteria for the clonal burden nor the presence of end organ damage seen in hematologic malignancies. In a population based study based on the NHANES III health survey; 6% of patients with MGUS were subsequently classified as having MGRS. The prevalence and incidence of MGRS in the general population or in specific populations is not known but it is more prevalent in those over the age of 50 as there is a monoclonal protein (M-protein) present in 3% of those 50 and years older and 5% of those 70 years and older, placing those 50 and older at increased risk of MGRS.

References

  1. ↑ Bruijn, Jan A. (2007), Fogo, Agnes B.; Cohen, Arthur H.; Jennette, J. Charles; Bruijn, Jan A. (eds.), "Membranous Glomerulopathy", Fundamentals of Renal Pathology, New York, NY: Springer, pp. 21–29, doi:10.1007/978-0-387-31127-2_2, ISBN   978-0-387-31127-2 , retrieved 2021-05-16
  2. ↑ Membranous Glomerulonephritis at eMedicine
  3. ↑ Bobart, Shane A.; Vriese, An S. De; Pawar, Aditya S.; Zand, Ladan; Sethi, Sanjeev; Giesen, Callen; Lieske, John C.; Fervenza, Fernando C. (2019-02-01). "Noninvasive diagnosis of primary membranous nephropathy using phospholipase A2 receptor antibodies". Kidney International. 95 (2): 429–438. doi: 10.1016/j.kint.2018.10.021 . ISSN   0085-2538. PMID   30665573.
  4. ↑ Sethi, Sanjeev (2021). "New 'Antigens' in Membranous Nephropathy". Journal of the American Society of Nephrology. 32 (2): 268–278. doi:10.1681/ASN.2020071082. PMC   8054892 . PMID   33380523.
  5. ↑ Logt, Anne-Els van de; Fresquet, Maryline; Wetzels, Jack F.; Brenchley, Paul (2019-12-01). "The anti-PLA2R antibody in membranous nephropathy: what we know and what remains a decade after its discovery". Kidney International. 96 (6): 1292–1302. doi: 10.1016/j.kint.2019.07.014 . ISSN   0085-2538. PMID   31611068.
  6. ↑ Tomas NM, Beck LH, Meyer-Schwesinger C, Seitz-Polski B, Ma H, Zahner G, Dolla G, Hoxha E, Helmchen U, Dabert-Gay AS, Debayle D, Merchant M, Klein J, Salant DJ, Stahl RA, Lambeau G (December 2014). "Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy". The New England Journal of Medicine. 371 (24): 2277–2287. doi:10.1056/NEJMoa1409354. PMC   4278759 . PMID   25394321.
  7. ↑ Sethi, Sanjeev; Debiec, Hanna; Madden, Benjamin; Charlesworth, M. Cristine; Morelle, Johann; Gross, LouAnn; Ravindran, Aishwarya; Buob, David; Jadoul, Michel; Fervenza, Fernando C.; Ronco, Pierre (2020-01-01). "Neural epidermal growth factor-like 1 protein (NELL-1) associated membranous nephropathy". Kidney International. 97 (1): 163–174. doi: 10.1016/j.kint.2019.09.014 . ISSN   0085-2538. PMID   31901340.
  8. ↑ Sethi, Sanjeev (2022). "The Many Faces of NELL1 MN". Clinical Kidney Journal. 16 (3): 442–446. doi:10.1093/ckj/sfac237. PMC   9972807 . PMID   36865014.
  9. ↑ Sethi, Sanjeev; Madden, Benjamin J.; Debiec, Hanna; Charlesworth, M. Cristine; Gross, LouAnn; Ravindran, Aishwarya; Hummel, Amber M.; Specks, Ulrich; Fervenza, Fernando C.; Ronco, Pierre (2019-06-01). "Exostosin 1/Exostosin 2–Associated Membranous Nephropathy". Journal of the American Society of Nephrology. 30 (6): 1123–1136. doi:10.1681/ASN.2018080852. ISSN   1046-6673. PMC   6551791 . PMID   31061139.
  10. ↑ https://www.kidney-international.org/article/S0085-2538(20)31180-7/fulltext
  11. ↑ Al-Rabadi, L. F.; Caza, T.; Trivin-Avillach, C.; Rodan, A. R.; Andeen, N.; Hayashi, N.; Williams, B.; Revelo, M. P.; Clayton, F.; Abraham, J.; Lin, E.; Liou, W.; Zou, C. J.; Ramkumar, N.; Cummins, T.; Wilkey, D. W.; Kawalit, I.; Herzog, C.; Storey, A.; Edmondson, R.; Sjoberg, R.; Yang, T.; Chien, J.; Merchant, M.; Arthur, J.; Klein, J.; Larsen, C.; Beck Jr, L. H. (2021). "Serine Protease HTRA1 as a Novel Target Antigen in Primary Membranous Nephropathy". Journal of the American Society of Nephrology. 32 (7): 1666–1681. doi:10.1681/ASN.2020101395. PMC   8425645 . PMID   33952630.
  12. ↑ "Renal Pathology" . Retrieved 2008-11-25.
  13. ↑ "UpToDate". www.uptodate.com. Retrieved 2019-05-11.
  14. ↑ "UpToDate". www.uptodate.com. Retrieved 2019-05-11.
  15. ↑ "UpToDate". www.uptodate.com. Retrieved 2019-05-11.
  16. ↑ Ziakas PD, Giannouli S, Psimenou E, Nakopoulou L, Voulgarelis M (July 2004). "Membranous glomerulonephritis in chronic lymphocytic leukemia". American Journal of Hematology. 76 (3): 271–4. doi:10.1002/ajh.20109. PMID   15224365. S2CID   35937418.
  17. ↑ Menon S, Valentini RP (August 2010). "Membranous nephropathy in children: clinical presentation and therapeutic approach". Pediatric Nephrology. 25 (8): 1419–28. doi:10.1007/s00467-009-1324-5. PMC   2887508 . PMID   19908069.
  18. ↑ "Renal Pathology" . Retrieved 2008-11-25.
  19. ↑ Obana M, Nakanishi K, Sako M, Yata N, Nozu K, Tanaka R, Iijima K, Yoshikawa N (July 2006). "Segmental membranous glomerulonephritis in children: comparison with global membranous glomerulonephritis". Clinical Journal of the American Society of Nephrology. 1 (4): 723–9. doi: 10.2215/CJN.01211005 . PMID   17699279.
  20. ↑ "KDIGO GN guidelines" (PDF).
  21. ↑ von Groote TC, Williams G, Au EH, Chen Y, Mathew AT, Hodson EM, Tunnicliffe DJ (November 2021). "Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome". The Cochrane Database of Systematic Reviews. 2021 (11): CD004293. doi:10.1002/14651858.CD004293.pub4. PMC   8591447 . PMID   34778952.
  22. ↑ Goumenos DS, Katopodis KP, Passadakis P, Vardaki E, Liakopoulos V, Dafnis E, Stefanidis I, Vargemezis V, Vlachojannis JG, Siamopoulos KC (2007). "Corticosteroids and ciclosporin A in idiopathic membranous nephropathy: higher remission rates of nephrotic syndrome and less adverse reactions than after traditional treatment with cytotoxic drugs". American Journal of Nephrology. 27 (3): 226–31. doi:10.1159/000101367. PMID   17389782. S2CID   1475371.
  23. ↑ Passerini P, Ponticelli C (July 2003). "Corticosteroids, cyclophosphamide, and chlorambucil therapy of membranous nephropathy". Seminars in Nephrology. 23 (4): 355–61. doi:10.1016/S0270-9295(03)00052-4. PMID   12923723.
  24. ↑ Markowitz GS (May 2001). "Membranous glomerulopathy: emphasis on secondary forms and disease variants". Advances in Anatomic Pathology. 8 (3): 119–25. doi:10.1097/00125480-200105000-00001. PMID   11345236. S2CID   39640332.
  25. ↑ Hallegua D, Wallace DJ, Metzger AL, Rinaldi RZ, Klinenberg JR (2016). "Cyclosporine for lupus membranous nephritis: experience with ten patients and review of the literature". Lupus. 9 (4): 241–51. doi:10.1191/096120300680198935. PMID   10866094. S2CID   20048968.
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