Thin basement membrane disease (TBMD) is one of the inherited disorder of kidney affecting glomeruli. It is also known as Thin basement membrane nephropathy (TBMN) or thin membrane nephropathy or thin GBM syndrome or benign familial hematuria or benign familial essential hematuria or congenital hereditary hematuria or hereditary hematuria or familial hematuric nephritis or benign hereditary nephritis. Being the most frequent cause of familial hematuria TBMD is affecting 1% of population.^[1] 40% of TBMD is caused by germline mutation in COL4A3, COL4A4 genes, but female carrier with COL4A5 mutation may develop TBMD. ^[2]

Thin basement membrane disease is the most common cause of Persistent recurrent hematuria. A form of Benign hemorrhagic nephritis is first noted in 1926 by Goerge Baehr. ThenPersistent recurrent hematuria is first observed in seven out of eight siblings in a family by Melvin I. Marks and Keith N. Drummond in 1969. P. W. Rogers was the first one to analyse the association between recurrent asymptomatic hematuria and thin glomerular basement membrane in 1973. The association between the COL4A3, COL4A4 and COL4A5 gene mutation in long q arm of chromosome 2 and the recurrence of X-linked and autosomal alport syndrome in several studies conducted in 1990-1994. In 1996, it was demonstrated that the cause of Benign familial hematuria is Mutation in COL4A3 and COL4A4.

There is no distinctive classification on Thin basement membrane disease.

Thin basement membrane disease is usually caused by Heterozygous mutation in COL4A3 and COL4A4 gene in autosomal nonprogressive dominant pattern and heterozygous mutation in COL4A5 gene in X-chromosome may cause Thin basement membrane disease in female.. Alport syndrome, IgA nephropathy are among the most common to have association with Thin basement membrane disease. Gross pathology usually shows no distinctive features although Diffuse thinning of GBM in electron microscopy, Erythrocytes in between renal tubules ad bowman’s membrane, Minimal glomerular change or mesangial expansion on light microscopy are seen on microscopic histopathological analysis.

Thin basement membrane disease is an inherited disorder caused by mutation in COL4A3, COL4A4 and rarely COL4A5 gene mutation. Some form of TBMD are due to ‘De novo‘ mutation.

As a common cause of several glomerulopathies, Persistent hematuria must be differentiated as benign cause of thin basement membrane disease from other life threatening caueses of glomerular bleeding including Alport syndrome, IgA nephropathy, lupus nephritis, postinfectious glomerulonephritis.

The incidence of thin basement membrane disease is 1%-2% based on data available in 2006. The prevalence of thin basement membrane disease is 1%.Thin basement membrane disease affects children and adult equally with more predominance in female. According to available data most cases are reported in developed countries specially in Europe where majority of patient are of Caucasians race. Chinese, Indians, Africans are less commonly affected.

There are no established risk factors for Thin basement membrane disease.

According to the most physicians, screening for thin basement membrane disease by Renal function test is recommended every 1-2 years among patients with Hypertension, Proteinuria, and Renal impairment. Family members of a patient with thin basement membrane disease should also be evaluated for early diagnosis of TBMD.

TBMD is may developed or found incidentally in first decade of life in symptomatic patient, may present symptoms later in third decade in asymptomatic patient. If left untreated, adult TBMD patients with proteinuria may develop hypertension, renal impairment leading to renal insufficiency. Prognosis is usually good in patient with isolated hematuria in TBMD.

Renal biopsy is the gold standard test for Thin basement membrane disease showing diffuse thinning of glomerular basement membrane, RBCs in between renal tubules ad bowman’s membrane, Minimal glomerular change or mesangial expansion on light microscopy are seen on microscopic histopathological analysis.

Obtaining complete history both for the patient and family is an important aspect of diagnosing TBMD. The hallmark of TBMD is benign hematuria. A positive family history of incidental finding of intermittent or persistent hematuria is suggestive of TBMD. TBMD is mostly asymptomatic. Microscopic hematuria is found incidentally.

A complete medical and family history and comprehensive renal exam must be performed to help identify and properly diagnose Thin basement membrane disease. Patient is mostly asymptomatic.

Laboratory findings consistent with the diagnosis of TBDM include asymptomatic benign microscopic hematuria with normal renal function test.

There are no ECG findings associated with Thin basement membrane disease.

There are no X-ray findings associated with Thin basement membrane disease.

There are no echocardiography/ultrasound findings associated with thin basement membrane disease.

There are no CT scan findings associated with thin basement membrane disease.

There are no MRI findings associated with thin basement membrane disease.

There are no findings associated with thin basement membrane disease in other imaging procedures.

DNA sequencing of COL4A3,COL4A4, COL4A5 is needed for differentiating TBMD and Alport syndrome in specialized laboratory.

There is no treatment for Thin basement membrane disease; the mainstay of therapy is supportive care.

There are no other interventions associated with thin basement membrane disease.

There is no surgical procedure required for Thin basement membrane disease; the mainstay of therapy is supportive care.

There are no established measures for the primary prevention of TBMD as it is a hereditary disease.

Effective measures for the secondary prevention of TBMD is Health education to patients and their family members. Patients and their family members should be educated on sign and symptoms of proteinuria, hypertension, renal dysfunction. Patient along with affected family members should be monitored regularly for the development of hypertension , persistent proteinuria and progression to renal impairment.

Thin basement membrane disease is the most common cause of Persistent recurrent hematuria. A form of Benign hemorrhagic nephritis is first noted in 1926 by Goerge Baehr. ThenPersistent recurrent hematuria is first observed in seven out of eight siblings in a family by Melvin I. Marks and Keith N. Drummond in 1969. P. W. Rogers was the first one to analyse the association between recurrent asymptomatic hematuria and thin glomerular basement membrane in 1973. The association between the COL4A3, COL4A4 and COL4A5 gene mutation in long q arm of chromosome 2 and the recurrence of X-linked and autosomal alport syndrome in several studies conducted in 1990-1994. In 1996, it was demonstrated that the cause of Benign familial hematuria is Mutation in COL4A3 and COL4A4.

Thin basement membrane disease is the most common cause of Persistent recurrent hematuria besides other cause for example alport syndrome or IgA nephropathy. A form of Benign hemorrhagic nephritis is first noted in 1926 by Goerge Baehr.^[1] In 1969, Melvin I. Marks and Keith N. Drummond published an article showing that seven out of eight siblings were having persistent hematuria for 6 months to 8 years duration without experiencing any symptoms. They did not find any abnormalities in renal biopsy, light microscopy, immunofluoroscence. ^[2] Then P. W. Rogers used electron microscopy to analyse the association between recurrent asymptomatic hematuria and thin glomerular basement membrane is discovered in 1973. ^[3] From 1990-1994 several studies were conducted to find out the association between the COL4A3, COL4A4 and COL4A5 gene mutation in long q arm of chromosome 2 and the recurrence of X-linked and autosomal alport syndrome.^{[4] [5] [6][1]} Mutation in COL4A3 and COL4A4 was found to cause Benign familial hematuria in 1996.^[7]

There is no established system for the classification of Thin Basement Membrane Disease.

There is no established system for the classification of Thin Basement Membrane Disease.

Thin basement membrane disease is usually caused by Heterozygous mutation in COL4A3 and COL4A4 gene in autosomal nonprogressive dominant pattern and heterozygous mutation in COL4A5 gene in X-chromosome may cause Thin basement membrane disease in female.. Alport syndrome, IgA nephropathy are among the most common to have association with Thin basement membrane disease. Gross pathology usually shows no distinctive features although Diffuse thinning of GBM in electron microscopy, Erythrocytes in between renal tubules ad bowman’s membrane, Minimal glomerular change or mesangial expansion on light microscopy are seen on microscopic histopathological analysis.

Physiology

Glomerular Basement membranee consists of laminin, Type 4 collagen, heparan sulfate proteoglycan and nidogen. Type 4 collagen is generally composed of Gly-X-Y amino acids rich in six alpha chains (alpha 1-6) that gives type 4 collagen a trimeric shape. The nascent GBM is made up of alpha 1 and 2 initially, then alpha 3-4 trimers are secreted after glomerular capillaries formation which becomes the major component of type 4 collagen and giving the GBM its stability.^[1]

Pathology

Heterozygous mutation in COL4A3 and COL4A4 gene is responsible for causing autosomal dominant pattern of 40-50% of Thin basement membrane disease in which people have defective alpha 3, alpha 4 , alpha 5 chains. ^[1] And heterozygous mutation in COL4A5 gene in X-chromosome may cause Thin basement membrane disease in female..

Genetics

Thin basement membrane disease is an inherited pattern disease affecting successive generations. It may be due to-

• Autosomal dominant inheritance due to heterozygous mutation in COL4A3 and COL4A4 gene
• Heterozygous mutation in COL4A5 gene in X-chromosome causing Thin basement membrane like disease in female
• ‘De novo‘ mutation.^[2]

Associated condition

Condition associated with Thin basement membrane disease include:

• Alport syndrome
  • Alport syndrome is caused by homozygous or heterozygous mutation of both or either COL4A3, COL4A4 and COL4A5 gene, thus 36% of cases of TBMD with COL4A3, COL4A4 mutation are shown to be associated with Alport syndrome.^[3]
• IgA nephropathy.

Gross pathology

On gross pathology, there is no distinctive features suggesting TBMD.

Microscopic pathology

On microscopic histopathological analysis, the followings features are noted:

• Erythrocytes in between renal tubules ad bowman’s membrane^[4]
• Diffuse thinning of GBM in electron microscopy in around 50% of population with TBMD.^[5] Occassionally, segmental thinning of GBM is present in TBMD.^[6]
• Minimal glomerular change or mesangial expansion may be present on light microscopy.^[7]

Thin basement membrane disease is an inherited disorder caused by mutation in COL4A3, COL4A4 and rarely COL4A5 gene mutation. Some form of TBMD are due to ‘De novo‘ mutation.

Most common cause of TBMD may include:

• Autosomal dominant inheritance due to heterozygous mutation in COL4A3 and COL4A4 gene.

Less common causes of TBMD include:

• Heterozygous mutation in COL4A5 gene in X-chromosome causing Thin basement membrane like disease in female
• ‘De novo‘ mutation.^[1]

As a common cause of several glomerulopathies, Persistent hematuria must be differentiated as benign cause of thin basement membrane disease from other life threatening caueses of glomerular bleeding including Alport syndrome, IgA nephropathy, lupus nephritis, postinfectious glomerulonephritis.

Persistent hematuria is present in several glomerulopathies. Benign cause of thin basement membrane disease should be differentiated from life threatening causes of glomerular bleeding. Moreover, there are found to have association of Thin basement membrane disease with Alport syndrome, IgA nephropathy, thus it is important to distinguish these diseases. The various types of glomerular diseases should be differentiated from each other based on associations, presence of pitting edema, hematuria, hypertension, hemoptysis, oliguria, peri-orbital edema, hyperlipidemia, type of antibodies, light, electron microscopic features and genetic analysis. The following table differentiates between various types of glumerular diseases:

Glomerular diseases	Disease		History and Symtoms									Laboratory Findings		Pathology
			History	Systemic symptoms	Hemeturia	Proteinuria	Hypertension	Pitting edema	Oliguria	Nephrotic features	Nephritic features	Hyperlipidemia and hypercholesterolemia	Auto-antibodies, Complements	Light microscope	Electron microscope	Immunoflourescence pattern
Acute Nephritic Syndromes	Poststreptococcal Glomerulonephritis[1][2][3]		Streptococcal skin infections Streptococcal pharyngitis 2-3 weeks after infection	Fever Fatigue Skin rash	+/-	+	+/-	+/-	+/-	+/-	+/-	+/-	Anti-dsDNA antibodies Anti-C1q antibodies Antineutrophil cytoplasmic antibodies (ANCA)	Hypercellular and inflamed glomeruli	Sub-epithelial immune complex deposits Obliteration of epithelial cell foot processes	Immune complex GN Granular deposit
	Renal disease due to Subacute Bacterial Endocarditis, or cardiac shunt (Atrioventricular)[4][5]		History of infective endocarditis mostly due to S. aureus Cardiac shunt	Fever Fatigue Weight loss	+/-	+	+/-	+/-	+/-	+/-	+/-	+/-	ANCA (myeloperoxidase) positive in 1/3 Activation of the alternative complement pathway (Decreased C3, C4) Positive RF Positive anti-GBM autoantibodies	Crescentic GN is the most common pathological features Diffuse membranoproliferative glomerulonephritis features Focal proliferative GN Mesangial proliferative GN	Mesangial deposits, Subendothelial deposits Subepithelial “humps,” in minority of cases	Pauci-immune GN
	Lupus Nephritis[6]		History of SLE features	Lupus criteria: Malar rash Arthritis Arthralgia Anemia Easy bruising	+/-	+	+/-	+/-	+/-	+/-	+/-	+/-	Anti-C1q antibodies Anti-dsDNA	Differs based on the disease classification	Differs based on the disease classification	Differs based on the disease classification, mostly immune complex GN Granular deposit
	Antiglomerular Basement Membrane Disease (Goodpasture’s syndrome)[7][8]		Young adults	Dry cough Hemoptysis Malaise  Fever and chills Arthralgia  Fatigue Lethargy Pallor Anorexia Easy bruising	+	+	+	+	+	+	–	–	ANCA (myeloperoxidase) Positive anti-GBM autoantibodies	Hypercellular and inflamed glomeruli (Crescent formation)	Diffuse thickening of the glomerular basement membrane with absence of sub-epithelial and sub-endothelial deposits	Immune complex GN Linear deposit
	IgA Nephropathy[9][10]		Young children History of mucosal infections (e.g. gastroenteritis) and upper respiratory tract infection 2-3 days after infection (synpharyngitic)	Low grade fever Flank pain	+	+/-	+	+/-	+	–	+	–	Immune complex deposition	Crescent formation	Mesangial proliferation	Immune complex GN, granular deposite
	Disease		History	Systemic symptoms	Hemeturia	Proteinuria	Hypertension	Pitting edema	Oliguria	Nephrotic features	Nephritic features	Hyperlipidemia and hypercholesterolemia	Auto-antibodies, Complements	Light microscope	Electron microscope	Immunoflourescence pattern
	ANCA Small-Vessel Vasculitis[11][12]	Granulomatosis with Polyangiitis (Wegener’s)[13][14][15]	Middle age male	Constitutional symptoms Dyspnea Purpura Arthralgias Neurologic dysfunction Sinusitis Otitis media Epistaxis.	+	+	+	+/-	+	–	+	–	ANCA	Necrotizing and crescentic glomerulonephritis	Subendothelial edema Microthrombosis Degranulation of neutrophils	Pauci-immune GN
		Microscopic Polyangiitis[16]	+/-	Constitutional symptoms Dyspnea Purpura Arthralgias Neurologic dysfunction	+	+	+	+	+	+		–	P-ANCA	Hypercellular and inflamed glomeruli (Crescent formation)	Hypercellular and inflamed glomeruli (Crescent formation)	Pauci-immune GN
		Churg-Strauss Syndrome[17]	+/-	Asthma Sinusitis Myalgia  Arthralgia Purpura Arrythmias Peripheral neuropathy	+	+	+	+	+	+		–	C-ANCA	Hypercellular and inflamed glomeruli (Crescent formation)	Hypercellular and inflamed glomeruli (Crescent formation)	Pauci-immune GN
	Membranoproliferative Glomerulonephritis[18][19]		Idiopathic Hepatitis B and C (Type 1) C3 nepritic factor (Type2)	Hematuria Oliguria Periorbital edema Hypertension	+	+	+	+/-	+	+	–	–	–	Thick glomerular basement membrane (Tram-track appearance)	Mesangial proliferation Leukocyte infiltration	Immune complex GN Granular deposite
	Henoch-Schönlein purpura [20]		Most common in young male, following upper respiratory infections	Skin manifestations- Palpable purpura on buttocks Gastrointestinal manifestations- Abdominal pain Melena Bloody diarrhea Hematemesis Joints manifestations- Arthralgia	+	+	+	+/-	+	+	–	–	–	Diffuse mesangial IgA deposits often associated with mesangial hypercellularity	Diffuse mesangial IgA deposits often associated with mesangial hypercellularity	Immune complex GN, granular deposite
	Disease		History	Systemic symptoms	Hemeturia	Proteinuria	Hypertension	Pitting edema	Oliguria	Nephrotic features	Nephritic features	Hyperlipidemia and hypercholesterolemia	Auto-antibodies, Complements	Light microscope	Electron microscope	Immunoflourescence pattern
	Cryoglobulinemia[21]		Patients having cryoglobulinemia may have positive history of: Hepatitis C infection Hepatitis B infection Leg ulcers Recurrent thrombosis	Pulmonary symptoms: Difficulty breathing Cough Cutaneous symptoms: Purpura  Skin ulcer Gastrointestinal symptoms: Abdominal pain General symptoms: Fever Arthralgia, Myalgia Fatigue Blurring/loss of vision Diplopia Confusion	+/-	+	+/-	+	+/-	+/-	+/-	+/-	+/-	Membranoproliferative glomerulonephritis	Mesangial and subendothelial deposits	Prominent IgM and C3
Nephrotic Syndrome	Minimal Change Disease[22][23]		Young children Recent infection and immunization Atopy Hodgkin lymphoma Thrombosis (due to urinary loss of antithrombin-III)		–	+	–	+	+/-	+	–	+		Normal	Fusion of podocytes	–
	Focal Segmental Glomerulosclerosis[24][25][26]		Idiopathic HIV Heroine use Sickle cell disease Interferon Severe obesity Mixed cryoglobulinemia (Hepatitis C)		–	+	–	+	+/-	+	–	+		Focal (some glomeruli) and segmental (only part of glomerulus)	Effacement of podocytes	–
	Membranous Glomerulonephritis[27][28]		Idiopathic Hepatitis B and C Solid tumors Systemic lupus erythematosus Drugs (NSAIDS, pencilamine, gold, captopril)		–	+	–	+	+/-	+	–	+	Immune complex deposition	Thick glomerular basement membrane	Sub-epithelial immune complex depositis with ‘spike and dome’ appearance	Immune complex GN, granular deposite
	Diabetic Nephropathy[29][30][31][32][33][34][35][36][37][38]		For more information on diabetes click here.		–	+	–	+	+/-	+	–	+		Diffuse mesangial matrix expansion (nodular glomerulosclerosis) Increased mesangial hypercellularity Prominent glomerular basement membranes Thick basement membrane without any deposit	Nodular glomerulosclerosis	–
	Disease		History	Systemic symptoms	Hemeturia	Proteinuria	Hypertension	Pitting edema	Oliguria	Nephrotic features	Nephritic features	Hyperlipidemia and hypercholesterolemia	Auto-antibodies, Complements	Light microscope	Electron microscope	Immunoflourescence pattern
	Glomerular Deposition Diseases	Light Chain Deposition Disease[39]	Occurs in the setting of high tumor burden	–	–	+	–	+	+/-	+	–	+	–	Light-chain deposits	Granular deposits on electron microscopy	Detection of light chain deposits using anti–light chain antibody
		Renal Amyloidosis[40][41][42][43]	For the secondary causes of amloidosis: Tuberculosis Familial Mediterranean fever Rheumatoid arthritis Multiple myeloma	Dyspnea Lethargy Weight loss Bleeding tendency	–	+	–	+	+/-	+	–	+	–	Diffuse glomerular deposition of amorphous hyaline material (nodular pattern), in mesangium (weakly staining with periodic acid-Schiff (PAS)	Nodular deposit	AA amyloidosis type: negative for immunoglobulins and complement AL amyloidosis type: Positive for lambda or kappa light chains
		Fibrillary-Immunotactoid Glomerulopathy[44]	Malignancy Monoclonal gammopathy Autoimmune disease	–	+/-	+	+/-	+/-	+/-	+	+/-	+/-	–	Diffuse sclerosing glomerulonephritis Diffuse proliferative glomerulonephritis Membranoproliferative glomerulonephritis Mesangioproliferative/sclerosing disease Membranous glomerulonephritis	Large fibrillar deposits in the mesangium randomly Glomerular capillary walls different from amloidosis No staining with Congo red or thioflavine-T or with antibodies to a specific type	Positive for immunoglobulin G (IgG), C3 Kappa and lambda (ie, polyclonal) light chains
		Fabry’s Disease[45][46][47]	Family history suggestive of the disorder	Anhidrosis or decreased sweating Fatigue Angiokeratomas Burning pain of the extremities Corneal opacities. Dysphagia Abdominal pain Steatorrhea Delayed puberty Raynaud’s phenomenon Hearing loss Telangiectasis Ataxia	–	+	–	+	+/-	+	–	+	–	Vacuolization of visceral glomerular epithelial cells (podocytes) and distal tubular epithelial cells Glycolipid accumulation	Myeloid or zebra bodies: Gb3 deposition within enlarged secondary lysosomes as lamellated membrane structures Inclusions, composed of concentric layers (onion skin appearance)	–
Basement Membrane Syndrome	Alport’s Syndrome[48][49][50][51][52][53]		Positive family history	Auditary: Early Tinnitus Vertigo High-frequency progressive bilateral hearing loss Occular problems: Refractory Error Arcus Glaucoma Band Keratopathy Lenticonus Spherophakia Cataracts	–	+	–	+	+/-	+	–	+	–	Early stage: unremarkable Late stages: glomerulosclerosis, interstitial fibrosis, and interstitial foam cells (due to prolonged proteinuria).	Within glomerular basement membrane (GBM): longitudinal splitting of the lamina densa	Absence of staining of the alpha-3, alpha-4, and alpha-5 (IV) chains in the glomerular basement membrane Minimal binding to a glomerulus in indirect immunofluorescence microscopy with anti-glomerular basement membrane antibodies
	Disease		History	Systemic symptoms	Hemeturia	Proteinuria	Hypertension	Pitting edema	Oliguria	Nephrotic features	Nephritic features	Hyperlipidemia and hypercholesterolemia	Auto-antibodies, Complements	Light microscope	Electron microscope	Immunoflourescence pattern
	Thin Basement Membrane Disease[54][55]		Positive family history Gross hematuria following upper respiratory tract infection	–	–	+	-/+	–	-/+	–	-/+	–	–	–	Diffuse thinning of the glomerular basement membranes (GBM)	–
	Nail-Patella Syndrome[56][57]		Positive family history	Poorly developed fingernails, toe nails, and patellae (kneecaps). Elbow deformities Abnormally shaped pelvis bone (hip bone) Knee may be small, deformed or absent	+	+	–	–	–	–	–	–	–	Mostly unremarkable changes Secondary FSGS Late stages: Global glomerulosclerosis, Tubulointerstitial fibrosis	Glomerular basement membranes (GBMs): Focal or diffuse irregular thickening with electron-lucent areas (moth-eaten appearance) containing type III collagen bundles. Similar collagen fibrils can be seen in mesangial matrix. Podocytes: Segmental effacement of foot processes.	Immunofluorescence studies are typically negative. Nonspecific IgM and C3 deposition may be seen in sclerotic glomeruli.
Glomerular-Vascular Syndromes	Hypertensive Nephrosclerosis[58]		Chronic hypertension	Hypertensive retinal changes. High jugular venous pressure Rales from pulmonary edema on auscultation .Signs of left ventricular hypertrophy Left ventricular heave Shifting of apex towards the left S3 and gallop rhythm Loud S2 Ascites Paralysis from stroke secondary to hypertension Inferior limb edema	+/-	+/-	+	+/-	+/-	+/-	–	+/-	–	Interstitial fibrosis and atrophy Medial thickening and intimal fibrosis of medium-sized and larger vessels Arteriolar thickening, and hyalinosis Chronic stages: Global sclerosis Focal segmental sclerosis
	Cholesterol Emboli[59]		Atherosclerotic cardiovascular disease Anticoagulation therapy Cardiopulmonary resuscitation Hypertension Aortic aneurysm Hypercholesterolemia Smoking history Male sex Age over 55 years Vascular procedures Invasive angiography Aortic aneurysm rupture or surgery Vascular surgery	Depends on the organ involved	+/-	+/-	+	+/-	+/-	+/-	–	+/-	–	Atheroemboli are seen in interlobular and arcuate arteries, as lance-shaped clefts, due to dissolution of cholesterol crystals Acute lesions: Atheroemboli are surrounded by red blood cells, fibrin, and leukocytes, with multinucleated giant cell reactions Chronic lesions: Cholesterol clefts are surrounded by intimal fibrosis Vessel recanalization of chronic lesions can occur. Global and segmental sclerosis of glomeruli may be present.	Extensive foot process effacement can be seen	Not specific changes
	Disease		History	Systemic symptoms	Hemeturia	Proteinuria	Hypertension	Pitting edema	Oliguria	Nephrotic features	Nephritic features	Hyperlipidemia and hypercholesterolemia	Auto-antibodies, Complements	Light microscope	Electron microscope	Immunoflourescence pattern
	Sickle Cell Disease[60]		Positive family history	Pain and/or bone pain Dactylitis Blurry vision Persistent and painful erection Numbness Tingling Motor skill loss Speech deficits Gait disturbance Leg ulceration Jaundice	+/-	+/-	+/-	–	–	–	–	–	–	Glomerular hypertrophy Hemosiderin deposits Focal areas of hemorrhage or necrosis Chronic stage: interstitial inflammation, edema, fibrosis, tubular atrophy, and papillary infarcts Glomerular enlargement and focal segmental glomerulosclerosis (FSGS)
	Thrombotic Microangiopathies[61]		Click for more information on Thrombotic Microangiopathies.		+	+/-	+	+/-	+/-	+/-	–	–	–	Acute stage: Inravasculr fibrin thrombi Chronic stage: Endocapillary hypercellularity. Intimal proliferation of arterioles	Swollen glomerular endothelial cells with loss of fenestrations Chronic stage: interposed cells with new GBM matrix material deposition.	Thrombi stain positive for fibrinogen
	Antiphospholipid Antibody Syndrome [62][63][64]		Thrombosis Miscarriage  History of nephropathy History of hematologic abnormalities Nonthrombotic neurologic symptoms, such as migraine headaches Pulmonary hypertension	Fatigue Fever Weight loss Venous thrombosis Arterial thrombosis Thrombocytopenia Recurrent fetal loss	+	+/-	+	+/-	+/-	+/-	–	–	–	Acute stage: Inravasculr fibrin thrombi Chronic stage: Endocapillary hypercellularity. Intimal proliferation of arterioles	Swollen glomerular endothelial cells with loss of fenestrations Chronic stage: interposed cells with new GBM matrix material deposition.	Thrombi stain positive for fibrinogen

Some infectious diseases such as HIV, HBV, HCV, syphilis, leprosy, malaria, and schistosomiasis may cause glomerular diseases.

References

1. ↑ GERMUTH FG (1953). “A comparative histologic and immunologic study in rabbits of induced hypersensitivity of the serum sickness type”. J Exp Med. 97 (2): 257–82. PMC 2136196. PMID 13022878.CS1 maint: PMC format (link)
2. ↑ Germuth FG, Senterfit LB, Dreesman GR (1972). “Immune complex disease. V. The nature of the circulating complexes associated with glomerular alterations in the chronic BSA-rabbit system”. Johns Hopkins Med J. 130 (6): 344–57. PMID 5031005.CS1 maint: Multiple names: authors list (link)
3. ↑ Radhakrishnan J, Cattran DC (2012). “The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines–application to the individual patient”. Kidney Int. 82 (8): 840–56. doi:10.1038/ki.2012.280. PMID 22895519.
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7. ↑ Bolton WK (November 1996). “Goodpasture’s syndrome”. Kidney Int. 50 (5): 1753–66. PMID 8914046.
8. ↑ Mathew TH, Hobbs JB, Kalowski S, Sutherland PW, Kincaid-Smith P (February 1975). “Goodpasture’s syndrome: normal renal diagnostic findings”. Ann. Intern. Med. 82 (2): 215–8. PMID 1090223.
9. ↑ Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB, Wyatt RJ, Scolari F, Mestecky J, Gharavi AG, Julian BA (October 2011). “The pathophysiology of IgA nephropathy”. J. Am. Soc. Nephrol. 22 (10): 1795–803. doi:10.1681/ASN.2011050464. PMC 3892742. PMID 21949093.
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11. ↑ Higgins RM, Goldsmith DJ, Connolly J, Scoble JE, Hendry BM, Ackrill P, Venning MC (January 1996). “Vasculitis and rapidly progressive glomerulonephritis in the elderly”. Postgrad Med J. 72 (843): 41–4. PMC 2398323. PMID 8746284.
12. ↑ Jennette JC (March 2003). “Rapidly progressive crescentic glomerulonephritis”. Kidney Int. 63 (3): 1164–77. doi:10.1046/j.1523-1755.2003.00843.x. PMID 12631105.
13. ↑ Renaudineau Y, Le Meur Y (October 2008). “Renal involvement in Wegener’s granulomatosis”. Clin Rev Allergy Immunol. 35 (1–2): 22–9. doi:10.1007/s12016-007-8066-6. PMID 18172777.
14. ↑ Weiss MA, Crissman JD (October 1984). “Renal biopsy findings in Wegener’s granulomatosis: segmental necrotizing glomerulonephritis with glomerular thrombosis”. Hum. Pathol. 15 (10): 943–56. PMID 6384024.
15. ↑ Pagnoux C (March 2008). “[Wegener’s granulomatosis and microscopic polyangiitis]”. Rev Prat (in French). 58 (5): 522–32. PMID 18524109.CS1 maint: Unrecognized language (link)
16. ↑ Chung SA, Seo P (August 2010). “Microscopic polyangiitis”. Rheum. Dis. Clin. North Am. 36 (3): 545–58. doi:10.1016/j.rdc.2010.04.003. PMC 2917831. PMID 20688249.
17. ↑ Sinico RA, Di Toma L, Maggiore U, Tosoni C, Bottero P, Sabadini E, Giammarresi G, Tumiati B, Gregorini G, Pesci A, Monti S, Balestrieri G, Garini G, Vecchio F, Buzio C (May 2006). “Renal involvement in Churg-Strauss syndrome”. Am. J. Kidney Dis. 47 (5): 770–9. doi:10.1053/j.ajkd.2006.01.026. PMID 16632015.
18. ↑ Alchi B, Jayne D (August 2010). “Membranoproliferative glomerulonephritis”. Pediatr. Nephrol. 25 (8): 1409–18. doi:10.1007/s00467-009-1322-7. PMC 2887509. PMID 19908070.
19. ↑ Davis AE, Schneeberger EE, Grupe WE, McCluskey RT (May 1978). “Membranoproliferative glomerulonephritis (MPGN type I) and dense deposit disease (DDD) in children”. Clin. Nephrol. 9 (5): 184–93. PMID 657595.
20. ↑ Jennette JC, Falk RJ (July 1994). “The pathology of vasculitis involving the kidney”. Am. J. Kidney Dis. 24 (1): 130–41. PMID 8023818.
21. ↑ Fogo AB, Lusco MA, Najafian B, Alpers CE (February 2016). “AJKD Atlas of Renal Pathology: Cryoglobulinemic Glomerulonephritis”. Am. J. Kidney Dis. 67 (2): e5–7. doi:10.1053/j.ajkd.2015.12.007. PMID 26802335.
22. ↑ Saha TC, Singh H (November 2006). “Minimal change disease: a review”. South. Med. J. 99 (11): 1264–70. doi:10.1097/01.smj.0000243183.87381.c2. PMID 17195422.
23. ↑ Saleem MA, Kobayashi Y (2016). “Cell biology and genetics of minimal change disease”. F1000Res. 5. doi:10.12688/f1000research.7300.1. PMC 4821284. PMID 27092244.
24. ↑ Rosenberg AZ, Kopp JB (March 2017). “Focal Segmental Glomerulosclerosis”. Clin J Am Soc Nephrol. 12 (3): 502–517. doi:10.2215/CJN.05960616. PMC 5338705. PMID 28242845.
25. ↑ Jefferson JA, Shankland SJ (September 2014). “The pathogenesis of focal segmental glomerulosclerosis”. Adv Chronic Kidney Dis. 21 (5): 408–16. doi:10.1053/j.ackd.2014.05.009. PMC 4149756. PMID 25168829.
26. ↑ Gephardt GN, Tubbs RR, Popowniak KL, McMahon JT (October 1986). “Focal and segmental glomerulosclerosis. Immunohistologic study of 20 renal biopsy specimens”. Arch. Pathol. Lab. Med. 110 (10): 902–5. PMID 2429634.
27. ↑ Lai WL, Yeh TH, Chen PM, Chan CK, Chiang WC, Chen YM, Wu KD, Tsai TJ (February 2015). “Membranous nephropathy: a review on the pathogenesis, diagnosis, and treatment”. J. Formos. Med. Assoc. 114 (2): 102–11. doi:10.1016/j.jfma.2014.11.002. PMID 25558821.
28. ↑ Wasserstein AG (April 1997). “Membranous glomerulonephritis”. J. Am. Soc. Nephrol. 8 (4): 664–74. PMID 10495797.
29. ↑ Drummond K, Mauer M, International Diabetic Nephropathy Study Group (2002). “The early natural history of nephropathy in type 1 diabetes: II. Early renal structural changes in type 1 diabetes”. Diabetes. 51 (5): 1580–7. PMID 11978659.CS1 maint: Multiple names: authors list (link)
30. ↑ Hørlyck A, Gundersen HJ, Osterby R (1986). “The cortical distribution pattern of diabetic glomerulopathy”. Diabetologia. 29 (3): 146–50. PMID 3699305.CS1 maint: Multiple names: authors list (link)
31. ↑ Alpers CE, Hudkins KL (2011). “Mouse models of diabetic nephropathy”. Curr Opin Nephrol Hypertens. 20 (3): 278–84. doi:10.1097/MNH.0b013e3283451901. PMC 3658822. PMID 21422926.CS1 maint: PMC format (link)
32. ↑ Kimmelstiel P, Wilson C (1936). “Intercapillary Lesions in the Glomeruli of the Kidney”. Am J Pathol. 12 (1): 83–98.7. PMC 1911022. PMID 19970254.CS1 maint: PMC format (link)
33. ↑ Alpers CE, Biava CG (1989). “Idiopathic lobular glomerulonephritis (nodular mesangial sclerosis): a distinct diagnostic entity”. Clin Nephrol. 32 (2): 68–74. PMID 2766585.
34. ↑ Toyoda M, Najafian B, Kim Y, Caramori ML, Mauer M (2007). “Podocyte detachment and reduced glomerular capillary endothelial fenestration in human type 1 diabetic nephropathy”. Diabetes. 56 (8): 2155–60. doi:10.2337/db07-0019. PMID 17536064.CS1 maint: Multiple names: authors list (link)
35. ↑ Najafian B, Crosson JT, Kim Y, Mauer M (2006). “Glomerulotubular junction abnormalities are associated with proteinuria in type 1 diabetes”. J Am Soc Nephrol. 17 (4 Suppl 2): S53–60. doi:10.1681/ASN.2005121342. PMID 16565248.CS1 maint: Multiple names: authors list (link)
36. ↑ Najafian B, Kim Y, Crosson JT, Mauer M (2003). “Atubular glomeruli and glomerulotubular junction abnormalities in diabetic nephropathy”. J Am Soc Nephrol. 14 (4): 908–17. PMID 12660325.CS1 maint: Multiple names: authors list (link)
37. ↑ Najafian B, Alpers CE, Fogo AB (2011). “Pathology of human diabetic nephropathy”. Contrib Nephrol. 170: 36–47. doi:10.1159/000324942. PMID 21659756.CS1 maint: Multiple names: authors list (link)
38. ↑ Najafian B, Alpers CE, Fogo AB (2011). “Pathology of human diabetic nephropathy”. Contrib Nephrol. 170: 36–47. doi:10.1159/000324942. PMID 21659756.CS1 maint: Multiple names: authors list (link)
39. ↑ Hutchison CA, Cockwell P, Stringer S, Bradwell A, Cook M, Gertz MA, Dispenzieri A, Winters JL, Kumar S, Rajkumar SV, Kyle RA, Leung N (June 2011). “Early reduction of serum-free light chains associates with renal recovery in myeloma kidney”. J. Am. Soc. Nephrol. 22 (6): 1129–36. doi:10.1681/ASN.2010080857. PMC 3103732. PMID 21511832.
40. ↑ Baker KR, Rice L (2012). “The amyloidoses: clinical features, diagnosis and treatment”. Methodist Debakey Cardiovasc J. 8 (3): 3–7. PMC 3487569. PMID 23227278.
41. ↑ Gillmore JD, Hawkins PN (October 2013). “Pathophysiology and treatment of systemic amyloidosis”. Nat Rev Nephrol. 9 (10): 574–86. doi:10.1038/nrneph.2013.171. PMID 23979488.
42. ↑ Jerzykowska S, Cymerys M, Gil LA, Balcerzak A, Pupek-Musialik D, Komarnicki MA (2014). “Primary systemic amyloidosis as a real diagnostic challenge – case study”. Cent Eur J Immunol. 39 (1): 61–6. doi:10.5114/ceji.2014.42126. PMC 4439975. PMID 26155101.
43. ↑ Pepys MB (2006). “Amyloidosis”. Annu. Rev. Med. 57: 223–41. doi:10.1146/annurev.med.57.121304.131243. PMID 16409147.
44. ↑ Korbet SM, Schwartz MM, Lewis EJ (March 1991). “Immunotactoid glomerulopathy”. Am. J. Kidney Dis. 17 (3): 247–57. PMID 1996564.
45. ↑ Alroy J, Sabnis S, Kopp JB (June 2002). “Renal pathology in Fabry disease”. J. Am. Soc. Nephrol. 13 Suppl 2: S134–8. PMID 12068025.
46. ↑ Meikle PJ, Hopwood JJ, Clague AE, Carey WF (1999). “Prevalence of lysosomal storage disorders”. JAMA : the Journal of the American Medical Association. 281 (3): 249–54. PMID 9918480. Unknown parameter |month= ignored (help)CS1 maint: Multiple names: authors list (link)
47. ↑ Branton MH, Schiffmann R, Sabnis SG; et al. (2002). “Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clinical course”. Medicine. 81 (2): 122–38. PMID 11889412. Unknown parameter |month= ignored (help)CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
48. ↑ McCarthy PA, Maino DM (2000). “Alport syndrome: a review”. Clin Eye Vis Care. 12 (3–4): 139–150. PMID 11137428.
49. ↑ Chugh KS, Sakhuja V, Agarwal A, Jha V, Joshi K, Datta BN; et al. (1993). “Hereditary nephritis (Alport’s syndrome)–clinical profile and inheritance in 28 kindreds”. Nephrol Dial Transplant. 8 (8): 690–5. PMID 8414153.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
50. ↑ Chugh KS, Sakhuja V, Agarwal A, Jha V, Joshi K, Datta BN; et al. (1993). “Hereditary nephritis (Alport’s syndrome)–clinical profile and inheritance in 28 kindreds”. Nephrol Dial Transplant. 8 (8): 690–5. PMID 8414153.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
51. ↑ McCarthy PA, Maino DM (2000). “Alport syndrome: a review”. Clin Eye Vis Care. 12 (3–4): 139–150. PMID 11137428.
52. ↑ Amari F, Segawa K, Ando F (1994). “Lens coloboma and Alport-like glomerulonephritis”. Eur J Ophthalmol. 4 (3): 181–3. PMID 7819734.CS1 maint: Multiple names: authors list (link)
53. ↑ Govan JA (1983). “Ocular manifestations of Alport’s syndrome: a hereditary disorder of basement membranes?”. Br J Ophthalmol. 67 (8): 493–503. PMC 1040106. PMID 6871140.CS1 maint: PMC format (link)
54. ↑ Savige J, Rana K, Tonna S, Buzza M, Dagher H, Wang YY (2003). “Thin basement membrane nephropathy”. Kidney Int. 64 (4): 1169–78. doi:10.1046/j.1523-1755.2003.00234.x. PMID 12969134. Unknown parameter |month= ignored (help)CS1 maint: Multiple names: authors list (link)
55. ↑ Hou P, Chen Y, Ding J, Li G, Zhang H (2007). “A novel mutation of COL4A3 presents a different contribution to Alport syndrome and thin basement membrane nephropathy”. Am. J. Nephrol. 27 (5): 538–44. doi:10.1159/000107666. PMID 17726307.CS1 maint: Multiple names: authors list (link)
56. ↑ Najafian B, Smith K, Lusco MA, Alpers CE, Fogo AB (October 2017). “AJKD Atlas of Renal Pathology: Nail-Patella Syndrome-Associated Nephropathy”. Am. J. Kidney Dis. 70 (4): e19–e20. doi:10.1053/j.ajkd.2017.08.001. PMID 28941488.
57. ↑ Guidera KJ, Satterwhite Y, Ogden JA, Pugh L, Ganey T (1991). “Nail patella syndrome: a review of 44 orthopaedic patients”. J Pediatr Orthop. 11 (6): 737–42. PMID 1960197.
58. ↑ Hughson MD, Puelles VG, Hoy WE, Douglas-Denton RN, Mott SA, Bertram JF (July 2014). “Hypertension, glomerular hypertrophy and nephrosclerosis: the effect of race”. Nephrol. Dial. Transplant. 29 (7): 1399–409. doi:10.1093/ndt/gft480. PMC 4071048. PMID 24327566.
59. ↑ Lusco MA, Najafian B, Alpers CE, Fogo AB (April 2016). “AJKD Atlas of Renal Pathology: Cholesterol Emboli”. Am. J. Kidney Dis. 67 (4): e23–4. doi:10.1053/j.ajkd.2016.02.034. PMID 27012950.
60. ↑ Wesson DE (June 2002). “The initiation and progression of sickle cell nephropathy”. Kidney Int. 61 (6): 2277–86. doi:10.1046/j.1523-1755.2002.00363.x. PMID 12028473.
61. ↑ Lusco MA, Fogo AB, Najafian B, Alpers CE (December 2016). “AJKD Atlas of Renal Pathology: Thrombotic Microangiopathy”. Am. J. Kidney Dis. 68 (6): e33–e34. doi:10.1053/j.ajkd.2016.10.006. PMID 27884283.
62. ↑ Jayakody Arachchillage D, Greaves M (2014). “The chequered history of the antiphospholipid syndrome”. Br J Haematol. 165 (5): 609–17. doi:10.1111/bjh.12848. PMID 24684307.
63. ↑ Jayakody Arachchillage D, Greaves M (2014). “The chequered history of the antiphospholipid syndrome”. Br J Haematol. 165 (5): 609–17. doi:10.1111/bjh.12848. PMID 24684307.
64. ↑ Popa A, Voinea L, Pop M, Stana D, Dascalu AM, Alexandrescu C; et al. (2008). “[Primary antiphospholipid syndrome]”. Oftalmologia. 52 (1): 13–7. PMID 18714484.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)

The incidence of thin basement membrane disease is 1%-2% based on data available in 2006. The prevalence of thin basement membrane disease is 1%.Thin basement membrane disease affects children and adult equally with more predominance in female. According to available data most cases are reported in developed countries specially in Europe where majority of patient are of Caucasians race. Chinese, Indians, Africans are less commonly affected.

• In 2006, the incidence of TBMD was estimated to be 1%-2% cases per 3471 TBMD cases on renal biopsy.^[1]

• The prevalence of TBMD is approximately 1%.^[2]

• There is no sufficient data available on case fatality rate or mortality rate.

• Patients of all age groups may develop Thin basement membrane disease. The median age of children is 7 years whereas in adult it is 37 years of age.^[3]

• Thin basement membrane disease usually affects individuals of the Caucasians according to available data. Chinese, Indians and African individuals are less likely to develop TBMD.

• Thin basement membrane diseaseaffects all ages of men and women equally.
• Some studies presented data showing women are more affected with TBMD than male.^[4]

• The majority of thin basement membrane disease cases are reported in Europe.

• The majority of TBMD cases are reported in Developed countries.

• There are no distinctive data showing the association of thin basement membrane disease with developing countries.

There are no established risk factors for Thin basement membrane disease.

There are no established risk factors for Thin basement membrane disease.

TBMD is may developed or found incidentally in first decade of life in symptomatic patient, may present symptoms later in third decade in asymptomatic patient. If left untreated, adult TBMD patients with proteinuria may develop hypertension, renal impairment leading to renal insufficiency. Prognosis is usually good in patient with isolated hematuria in TBMD.

Natural History

• The symptoms of TBMD are usually developed in first decade of life and start with symptoms such as recurrent hematuria. It occurs rarely after age 50 years.
• The symptoms of TBMD typically are not present initially, are found incidentally as microscopic hematuria, mild proteinuria in routine urine analysis and macroscopic hematuria rarely.^[1]
• If left untreated, adult TBMD patients with proteinuria may develop hypertension, renal impairment leading to renal insufficiency. ^[2]

Complication

Common complications of TBMD include^[2]:

• Hypertension.
• Proteinuria.
• Renal impairment.
• Renal failure.
• Anxiety.

Prognosis

• Prognosis is good in patient with isolated hematuria.
• The presence of proteinuria or other glomerulopathy is associated with a particularly poor prognosis among patients with TBMD.^[3][4]