Page 721 - TNFlipTest

Toronto Notes 2019
Parenchymal Kidney Diseases
Nephrology NP21
Proteinuria
(loss of large proteins [albumin])
Secondary
• Systemic disease SLE, DM, vasculitis
Pathologic Proteinuria
Tubulointerstitial
• Normally low molecular weight proteins
(<60 kDa) pass through glomerular filtration barrier and are reabsorbed in proximal tubule
• Proximal tubule dysfunction causes impaired reabsorption and increased excretion of low molecular weight proteins
• Albumin (>60 kDa) is not affected; thus, edema is partly secondary to salt and water retention
Physiologic
• Orthostatic
Absence of proteinuria overnight Usually resolves spontaneously
• Transient (exercise, fever, CHF)
Tubulointerstitial
(impaired resorption)
• <2 g/d
• e.g. Fanconi’s syndrome
Primary
• Minimal change GN
• Membranous GN
• FSGS
• Membranoproliferative GN • Post-streptococcal GN
• IgA nephropathy
Figure 13. Classification of proteinuria Table 10. Daily Excretion of Protein
Daily Excretion
<150 mg total protein (and <30 mg albumin) 30-300 mg albumin
>3500 mg total protein/1.73m2 body surface area Variable amount of proteinuria
Up to 2000 mg per d
Investigations
Pathologic
Glomerular
Overflow
(overproduction of low molecular
weight proteins)
• e.g. multiple myeloma, amyloidosis, Glomerular
Waldenstrom’s macroglobulinemia
• Normally, the filtration barrier is selectively permeable to size (<60 kDa) and charge (repels negative particles); thus, albumin is filtered to a very limited extent through a normal glomerulus
• Damage to any component of the glomerular filtration barrier results in loss
of albumin and other high molecular weight proteins; thus, edema is secondary to hypoalbuminemia (low oncotic pressure), but also due to enhanced renal tubular reabsorption of filtered sodium and water (possibly due to filtered proteins stimulating the action of cortical collecting duct epithelial sodium channel)
Overflow
• Increased production of low molecular weight proteins which exceeds the reabsorptive capacity of the proximal tubule
• Plasma cell dyscrasias: produce light chain Ig (multiple myeloma, Waldenstrom’s macroglobulinemia, monoclonal gammopathy of undetermined significance)
• Infectious disease
HIV, hepatitis B and C, bacterial endocarditis
• Hereditary/metabolic
Alport’s, Fabry’s, sickle cell, PCKD
• Medications
NSAIDs, gold, heavy metals
• Cancer
Lymphoma, solid tumour
• Others
Cryoglobulinemia, hypertensive nephrosclerosis
• urea, creatinine, ACR
• urineR&M,C&S
• furtherworkup(ifdegreeofproteinuria>0.5g/d,casts,and/orhematuria)
Stage of Nephropathy
Normal
Microalbuminuria
Nephrotic range proteinuria
Can be seen with glomerular disease
Possible tubular disease because of failure to reabsorb filtered proteins
ACR
<2.0 mg/mmol >2.0 mg/mmol >220 mg/mmol
■ CBC, glucose, electrolytes, 24 h urine protein, and Cr
■ urine and serum immunoelectrophoresis, abdominal/pelvic U/S
■ serology: ANA, RF, p-ANCA (MPO), c-ANCA (PR3), C3, C4, Hep B, Hep C, HIV, ASOT
• considerurologyconsultandpossiblecystoscopyifnotclearlyanephrologicsourceforhematuriaorif >50 yr of age
Glomerular Syndromes
1 . ASYMPTOMATIC URINARY ABNORMALITIES
Clinical/Lab Features
• oftenhaverapiddeclineinGFR,anemia,elevatedinflammatorymarkers,ECFvolumerepleteormildly overloaded
• proteinuria(usually<2g/d)and/ormicroscopicormacroscopichematuria ■ isolated proteinuria
◆ can be postural
◆ occasionally can signal beginning of more serious GN (e.g. FSGS, IgA nephropathy, amyloid,
diabetic nephropathy)
■ hematuria with or without proteinuria
◆ IgA nephropathy (Berger’s disease): most common type of primary glomerular disease worldwide, usually presents after viral upper respiratory tract infection
– more common in Caucasian and Asian populations, and in the 2nd and 3rd decades of life
– associated with cirrhosis, HIV infection, celiac disease
– treated with RAAS blockers if proteinuria, steroids, and steroid sparing agents (azathioprine,
cyclophosphamide, mycophenolate mofetil, and biologics such as rituximab)