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NP20 Nephrology
Parenchymal Kidney Diseases
Toronto Notes 2019
Parenchymal Kidney Diseases
Glomerular Diseases
HISTOLOGICAL TERMS OF GLOMERULAR CHANGES
Extent of Changes
• histologicaltermdescribingthenumberofglomeruliaffectedinagivencondition: ■ diffuse: majority of glomeruli abnormal
■ focal: some glomeruli affected
• histologicaltermdescribingtheextenttowhichindividualglomeruliareaffectedinagivencondition ■ global: entire glomerulus abnormal
■ segmental: only part of the glomerulus abnormal
Types of Changes
• proliferation:hyperplasiaofoneoftheglomerularcelltypes(mesangial,endothelial,parietalepithelial), with or without inflammatory cell infiltration
■ crescent formation: parietal epithelial cell proliferation and mononuclear cell infiltration form crescent-shape in Bowman’s space
• membranouschanges:capillarywallthickeningduetoimmunedepositsoralterationsinbasement membrane
CLINICAL PRESENTATION OF GLOMERULAR DISEASE
Important Points to Remember
• glomerulardiseaseshavediverseclinicalpresentationsincludinghematuria,proteinuria,HTN,edema, and decreased GFR
■ eachglomerulopathypresentsasoneoffourmajorglomerularsyndromes(theseareNOTdiagnoses) 1. asymptomatic urinary abnormalities
– proteinuria
– hematuria
2. nephritic syndrome
– acute GN
– rapidly progressive GN
3. nephrotic syndrome
4. ESRD
• glomerulopathiescanbecausedbyaprimarydiseaseorcanoccursecondarytoasystemicdisease
• someglomerulopathiescanpresentasmorethanonesyndromeatdifferenttimes
The Nephritic-Nephrotic Spectrum
• glomerularpathologycanpresentwithaclinicalpictureanywhereonaspectrumwithpurenephritic and pure nephrotic syndromes at the extremes
Nephrotic Proteinuria
FSGS
Membranous glomerulopathy Minimal change
Figure 12. Spectrum of glomerular pathology
PROTEINURIA
Intermediate
Membranoproliferative GN Focal proliferative GN
• IgA nephropathy
• Idiopathic membranoproliferative GN • Hepatitis B, hepatitis C
• SLE
• Cryoglobulinemia
Nephritic Hematuria,  GFR
Diffuse proliferative GN Crescentic GN
• hallmarkofnephroticsyndromes
• compositionofnormalurineprotein:albumin,lowermolecularproteins(suchasimmunoglobulin
light chain), or proteins secreted by the tubular epithelial cells (e.g. Tamm-Horsfall mucoprotein)
• 24hurineprotein:goldstandardtoassessdegreeofproteinuria
• urineACR:usedtoscreenfordiabeticnephropathy
• microalbuminuria:ACR≥2.0mg/mmol
■ marker of vascular endothelial function
■ an important prognostic marker for kidney disease in DM and HTN (see Diabetes, NP31) ■ microalbuminuria is the earliest sign of diabetic nephropathy
• compositionofnormaltotalurineprotein
• upperlimitofnormaldailyexcretionoftotalproteinis150mg/d
• upperlimitofnormaldailyexcretionofalbuminis30mg/d
• theothernormallyexcretedproteinsareeitherfilteredlowmolecularweightproteins(suchas
immunoglobulin light chains or β-2 microglobulin) or proteins secreted by the tubular epithelial cells (e.g. Tamm-Horsfall mucoprotein)