Membranoproliferative glomerulonephritis overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Ali Poyan Mehr, M.D. [2] Associate Editor(s)-in-Chief: Olufunmilola Olubukola M.D.[3]
Nazia Fuad M.D.[4] L.Farrukh [5]
Overview
Membranoproliferative glomerulonephritis or MPGN, also called mesangiocapillary glomerulonephritis is a type of glomerulonephritis caused by immune complexes depositing in the kidney glomerular mesangium and basement membrane (GBM), these immune complexes activate complement resulting in damaging the glomeruli. The GBM is rebuilt ontop of the deposits, and shows "tram-tracking" appearance under the microscope. Membranoproliferative Glomerulonephritis (MPGN) is a relatively uncommon inflammatory glomerulopathy that can cause chronic nephritis. Based on the histological pattern of glomerular injury it has been described as a chronic kidney disease found mostly in children and young adults. Like many forms of glomerulopathies, membranoproliferative glomerulonephritis (glomerulopathy) has been a diagnosis of tissue pathology rather the diagnosis of a specific disease entity. Therefore, the term membranoploriferative glomerulonephritis (MPGN) relates to a pattern of glomerular injury characterized by mesangial proliferation and expansion, lobularization of the glomerular tufts and double contours which can be caused by many disease states. Glomerular injury occurs due to deposition of immune complexes on the glomerular mesangium or on the glomerular basement membrane. MPGN has been categorized into 3 types based on the basis of histological pattern of glomerular damage. Clinically, MPGN often present with hematuria, varying degrees of proteinuria, with or without Glomerular filtration rate impairment depending on the severity of glomerular injury, and the underlying etiology. The treatment of membranoproliferative glomerulonephritis (MPGN) needs to address the underlying cause of the MPGN, eg, infection. The factors that predict renal prognosis should be assessed, and finally immunosuppressive drugs can be used when the underlying cause is autoimmune diseases.
Historical Perspective
The term membranous glomerulonephritis was used first by Bell in 1946 to describe a category of glomerular renal disease classified within the spectrum of Ellis type II glomerulonephritis. This category also included lipoid nephrosis, lobular glomerulonephritis, and chronic glomerulonephritis. In 1957, David Jones, a renal pathologist from Syracuse University in New York, separated membranous glomerulonephritis as a distinct morphologic entity. Jones fully illustrated the special features of this lesion such as lobular glomerulonephritis, lipoid nephrosis and chronic glomerulonephritis. Thickening of the capillary wall and alteration in basement membrane structure were described. Electron-dense subepithelial locations were identified by Movat and McGregor in 1959 using electron microscopic methods. Mellors in 1957 identified the unique lesion of membranous glomerulonephritis, the presence of immunoglobulin in the deposits, using the immunofluorescence technique. Thus, over the span of just 2 years, the triad of essential features of membranous glomerulonephritis were described. These are still the fundamental features used today to identify membranous glomerulonephritis, now called membranoproliferative glomerulonephritis MPGN.
Classification
Classification of MPGN based on immunofluorescence microscopy is a result of all advances in the understanding of the pathogenesis of the disease. Based on this advanced techniques, there are three types of MPGN [1]:Immune-complex-mediated MPGN (Type I) ,Complement-mediated MPGN (Type II), Non-Ig/complement-mediated MPGN (Type III)
Pathophysiology
MPGN membrano proliferative glomerulonephritis, also known as mesangiocapillary glomerulonephritis, is a glomerular injury on light microscopy that is characterized by mesangial hypercellularity, endocapillary proliferation, and double-contour formation along the glomerular capillary walls. "MPGN" includes two characteristic histologic changes:Thickened glomerular basement membrane (GBM) due to deposition of immune complexes and/or complement factors, intrusion of the mesangial cells and other cellular elements between the glomerular basement membrane and the endothelial cells, and new basement membrane formation. Mesangial and endocapillary cellularity is increased resulting in lobular appearance of the glomerular tuft. Proliferation of mesangial cells and circulating monocytes results in increased cellularity.Two mechanisms are involved in the pathogenesis of MPGN, Immune complex deposition leading to activation of complement (immune complex-mediated) and dysregulation and persistent activation of the alternative complement pathway.
Causes
The most common causes for membranoproliferative glomerulonephritis autoimmune diseases, mainly systemic lupus erythematosus (SLE), Sjögren syndrome, rheumatoid arthritis, inherited complement deficiencies (esp C2 deficiency), scleroderma, Celiac disease .Chronic infections also play major role such as viral infections like hepatitis B, hepatitis C, and cryoglobulinemia type II, bacterial infections such as endocarditis, infected ventriculoatrial (or jugular) shunt, multiple visceral abscesses, leprosy. Protozoal - malaria, schistosomiasis. Rare causes of MPGN include non-Hodgkin lymphoma, renal cell carcinoma, snake venom, splenorenal shunt surgery for portal hypertension , melanoma, alpha-1-antitrypsin deficiency, and cryoglobulinemic glomerulonephritis and Idiopathic MPGN.
Differentiating membrano proliferative glomerulonephritis from Other Diseases
There are some differential diagnosis mentioned for MPGN as they have some symptoms and signs in shared, the most relevant diseases are acute glomerulonephritis, IgA Nephropathy, LupusNephritis, poststreptococcal glomerulonephritis, and rapidly progressive Glomerulonephritis (RPGN).
Epidemiology and Demographics
Membranoproliferative glomerulonephritis (MPGN) is observed in 6-12% of US patients receiving renal biopsies. This entity accounts for 7% of children and 12% of adults with idiopathic nephrotic syndrome. MPGN causes significant proportion of the cases of nephritis among patients in nonindustrialized countries. For example, in Mexico, MPGN accounts for 40% of all patients with nephritis. Most of these patients have type I disease; MPGN type II is uncommon. However, the incidence of MPGN type I is decreasing progressively in developed countries, which may be explained by a change in environmental factors, especially a decline in infections. In an investigation of the changing patterns of adult primary glomerular disease occurrence in a single region of the United Kingdom, Hanko analyzed the results of 1844 native renal biopsies taken between 1976 and 2005 (inclusive) and found the presence of primary glomerulonephritis in 49% of the biopsies, with the most common forms being immunoglobulin A (IgA) nephropathy (38.8%). Other common forms were membranous nephropathy (29.4%), minimal-change disease (MCD) (9.8%), MPGN type 1 (9.6%), and focal segmental glomerulosclerosis (FSGS) (5.7%). The incidence of IgA nephropathy increased significantly over the study period, whereas the occurrence of membranous nephropathy decreased. In the United States, MPGN predominantly affects the white population. Type I disease affects women more often than men, whereas a nearly equal sex distribution is seen in MPGN type II. The idiopathic forms of MPGN are more common in children and young adults (range, 6-30 y). Isolated reports of involvement in patients as young as 2 years and as old as 80 years are noted in the literature. Secondary types of MPGN predominate among adults.are Nephrotic or Nephritic. The incidence of MPGN (as a lesion in renal biopsies) ranges from 1.4 to 9.3 cases per million population (pmp) per year and with few exceptions, the incidence has decreased over time.
Risk Factors
Membranoproliferative glomerulonephritis is associated with several diseases that can be categorized in to different groups. The most relevant conditions are chronic infections, autoimmune diseases, chronic liver disease (cirrhosis and alpha1-antitrypsin deficiency), chronic and recovered thrombotic microangiopathies, paraprotein deposition diseases, and malignant neoplasms genetic mutations.
Screening
Till now there is not specific screening protocols for MPGN, although it can diagnosed in the early stages by checking the proportion of urine protein to serum creatinine and 24 hour urine protein.
Natural History, Complications, and Prognosis
The natural history of membranoproliferative glomerulonephritis (MPGN) is characterised by severity of clinical features. Complete remission is seen in few cases only. Acute presentation and a slower reduction in renal function have seen more in children than adults. End stage renal disease is seen in approximately 40% of patients within 10 years of diagnosis. Features suggestive of an adverse outcome include nephrotic syndrome, renal dysfunction at onset, and persistent hypertension. Type II MPGN is associated with a worse prognosis, so is the presence of chronic interstitial damage on renal biopsy. In 20 - 30% of type I and 80 - 90 % type II MPGN, membranoproliferative glomerulonephritis may recur. Complication of MPGN is mostly based on the fact that when was the disease diagnosed and what kind of MPGN is determined in the result of kidney biopsy. The most common complications in patients who have MPGN are end-stage renal disease ESRD, edema, hypertension, Infection with encapsulated bacteriahemophilus, streptococcus, and klebsiella species, thromboembolism and hyperlipidemia, Factors that worsen the prognosis of MPGN are hypertension ,elderly individuals and low GFR at 1st year of presentation. Patients with MPGN type 1 and nephrotic syndrome have 50% vulnerability to develop end-stage renal disease (ESRD) within 10 years and 90% in 20 years. Type II MPGN is some how more aggressive and 50% of patients eventuate in ESRD after 10 years of diagnosis.
Diagnosis
Diagnostic Study of Choice
Renal biopsy is considered the gold standard diagnostic test for MPGN.Light, electron and immunoflourescnce microscopy are performed.Other diagnostic tests are doen to look for the cause of the disease.
History and Symptoms
MPGN is assessed firstly based on the symptoms and signs of patients. These signs and symptoms are mostly related and same as kidneys dysfunction such as, edema, hematuria and symptoms develop after nephrotic syndrome.
Physical Examination
Physical examination of patients with membranoproliferative glomerulonephritis is usually normal except there are signs of fluid overload if the disease progress to end-stage renal failure.
Laboratory Findings
MPGN laboratory findings include urinalysis, renal function tests, complete blood counts, complement profile and other diagnostic tests for evaluating the cause of MPGN.
Electrocardiogram
Other imaging modalities for renal scanning are DTPA and DMSA scans with no specific findings.
X-ray
Echocardiography and Ultrasound
CT scan
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Interventions
Surgery
Primary Prevention
Secondary Prevention
References
- ↑ Sethi S, Zand L, Leung N, Smith RJ, Jevremonic D, Herrmann SS; et al. (2010). "Membranoproliferative glomerulonephritis secondary to monoclonal gammopathy". Clin J Am Soc Nephrol. 5 (5): 770–82. doi:10.2215/CJN.06760909. PMC 2863981. PMID 20185597.