Biochemical composition of the glomerular extracellular matrix in patients with diabetic kidney disease

Table 1 Major components of the glomerular basement membrane and the mesangial matrix in normal human glomeruli

	Glomerular basement membrane	Mesangial matrix
Heparan sulfate proteoglycan	Abundant	Abundant
Laminin	Major component	Minor component
Fibronectin	Minor component	Major component
Type I collagen	Absent in most studies	Absent in most studies
Type III collagen	Absent in most studies	Absent in most studies
Type IV collagen	Major component	Present (inconsistent amounts)
Type V collagen	Present	Present
Type VI collagen	Present	Present
Type XVII collagen	Present	Unknown
Type XVIII collagen	Present	Present
Tubulointerstitial nephritis antigen-like-1	Low abundance	High abundance
Nidogen / Entactin	Present	Low abundance
Fibulin-1	Present	Present
Fibrillin-1	Present	Present
Nephronectin	Present	Present
Vitronectin	Absent	Present
Microfibril-associated proteins	Absent	Present

Table 2 Staining characteristics of the mesangial deposits in diabetic kidney diseases, fibronectin-1 nephropathy, and type III collagen glomerulopathy

	Periodic acid Schiff	Methenamine silver	Congo red	Specific analysis
Diabetic kidney disease	Positive	Positive	Negative	Unknown material
Fibronectin-1 nephropathy	Positive	Negative	Negative	Fibronectin-1
Type III collagen nephropathy	Negative	Negative	Negative	Type III collagen

Table 3 Type IV collagen-related kidney disease

	Gene/location	Protein	Mutation	Risk of progression to end-stage kidney disease
X-linked Alport syndrome	COL4A5/X chromosome	α5 chain of type IV collagen	Hemizygous (males) or heterozygous (females) mutations	Hemizygous: 100%; Heterozygous: 25%
Autosomal recessive Alport syndrome	COL4A4 or COL4A3/2q36-37	α4 and α3 chains of type IV collagen	Biallelic (homozygous or compound heterozygous) mutations	100%
Autosomal dominant Alport syndrome	COL4A4 or/COL4A32q36-37	α4 and α3 chains of type IV collagen	Heterozygous mutations in the α4 or α3 chains	20% in patients with risk factors for progression
Digenic Alport syndrome	Two of the COL4A3-5 genes	Two of the α3-5 chains

Table 4 Different composition of glomerular extracellular matrix (glomerular basement membrane and mesangial matrix) in normal subjects and patients with diabetes

	Normal glomeruli	Diabetic kidney disease
Heparan sulfate proteoglycans	GBM and mesangial matrix	Decreased amount
Laminin	Predominantly in the GBM	Inconsistent
Fibronectin-1	Mainly in the mesangial matrix	It varies according to DKD stage
Type I collagen	Inconsistent	No detectable
Type III collagen	Absent	Abundant
Type IV collagen	Abundant in the GBM	Reduced GBM amount
Type V collagen	Similar to type IV collagen	Increased mesangial amount
Type VI collagen	GBM and mesangial matrix	Increased mesangial amount

GBM: Glomerular basement membrane; DKD: Diabetic kidney disease.