Multifaceted relationship between diabetes and kidney diseases: Beyond diabetes

Table 1 Elements for the differential diagnosis between diabetic kidney disease and nondiabetic kidney disease

	DKD	NDKD	Ref.
Clinical characteristics			[57,71,72]
	Diabetic retinopathy	Microhematuria; active urinary sediment
	Longer diabetes duration (> 5 yr)	Acute onset of nephrotic proteinuria
		Acute kidney injury
		Positive autoimmunity
Histopathological elements			[27,29]
Light microscopy
Diffuse glomerulosclerosis	Thickening of the GBM; mesangial expansion; mesangiolysis	Reduced vascular involvement and arteriolar hyalinosis
Nodular glomerulosclerosis	Mesangial expansion with nodular glomerular sclerosis (“Kimmelstiel-Wilson nodules”)
	Nodules are PAS-positive, silver and Congo red negative	Amyloidosis: Congo red positive staining
Immunofluorescence	Linear staining of the GBM and tubular basement membrane for IgG and albumin; no other specific stainings	MIDD: Light-chain and/or heavy-chain deposits; IgAN: Predominant or codominant mesangial staining for IgA with or without C3; Cryoglobulinaemia and MPGN: Mesangial and GBM staining for IgM, IgG and C3
Electron microscopy	Diffuse GBM thickening; diabetic fibrillosis; podocytopenia	Fibrillar and Immunotactoid glomerulonephritis: Microfibrillar and microtubules deposition; cryoglobulinaemia and MPGN: Mesangial, subendothelial and subepithelial electron-dense deposits, intracapillary thrombi and leucocytic infiltrate
Radiological features	Higher renal arterial resistance index (> 0.66)		[78]
Biomarkers	Higher uNGAL/creatinine ratio (cutoff = 60.85 ng/mg)		[75]
Omic sciences	Specific biomolecular signatures in urine and plasma; proteomic analysis of extracellular vesicles		[79,80,81,83]
Other techniques	Evaluation of urine samples by Raman spectroscopy and chemometric analysis		[82]

DKD: Diabetic kidney disease; NDKD: Nondiabetic kidney disease; MIDD: Monoclonal immunoglobulin deposition disorder; IgAN: IgA nephropathy; GBM: Glomerular basal membrane; MPGN: Membranoproliferative glomerulonephritis; uNGAL: Urinary neutrophil gelatinase-associated lipocalin.