PROTEINURIA &

7/29/2019 PROTEINURIA &

http://slidepdf.com/reader/full/proteinuria- 1/38

PROTEINURIA &

NEPHROTIC SYNDROME







Glomerular anatomy & filtration barrier







Proteinuria

• Normal urine < 150 mg/day in adults

– Small MW proteins filtered across GCW

– Tamm-Horsfall proteins secreted by tubular

cells• Abnormal proteinuria

– Failure of the GCW filtration barrier – glomerular proteinuria

– Decreased reabsorption into, or increasedrelease from, tubular cells – tubular proteinuria



• Tubular proteinuria – Low MW proteins, (generally < 40,000 D)

– Amounts < 1 g/day

• Glomerular proteinuria – Proteins of greater molecular size

– May be up to many grams per day

• Selective proteinuria – Proteins much larger then albumin are excluded, e.g.

MCD where the injury is of limited nature

• Non-selective proteinuria

– More extensive damage – Immunoglobulins & larger proteins

• Glomerular disease – Primary

– Secondary to systemic diseases







Case

• 6 y/o girl with progressive swelling on her

face, ankles, BP 95/60, otherwise normal.

PMHx (-). UA: protein++++

• Cr=0.5 mg/dl, Alb 1.3 g/dl,

urine microscopy: many hyaline casts,

24h U protein =6g, cholesterol elevated

• Patient was referred to a nephrologist for a

possible renal biopsy



• Percutaneous renal biopsy can be performed toestablish the correct diagnosis & prognosis in patients

with suspected parenchymal renal disease.• It is usually a safe procedure, but bleeding complications

can occur.

• It may not be used

– when the diagnosis is In little doubt, – when it is unlikely to lead to a change in therapy,

– when the chance for complication is greater than usual

• Abnormalities may be – Segmental, involving part of a glomerulus only

– Global, the whole glomerulus

– Focal, involving a few glomeruli only

– Diffuse, involving most glomeruli



.





Treatment

• In general, the primary forms of GN causing NSare treated with corticosteroids; which have anti-inflammatory action

• In some cases immunosuppressive drugs are

used – Cyclophosphamide

– Azathioprine / Imuran

– Mycophenolic acid / MMF

– Cyclosporin• With secondary GN, treatment is directed

towards the primary disease



GLOMERULONEPHRITIS

&

ACUTE NEPHRITICSYNDROME



Acute glomerulonephritis

• Inflammatory renal disease involving theglomeruli of all or some of the millionnephrons of each kidney

• Classification based on pathologicalappearance of glomeruli, and other components of the nephron; blood

vessels, interstitium• Primary or idiopathic

• Secondary to a another (systemic) disease



• To confirm the presence of renal inflammation, urine

sediment examination should be performed on acentrifuged sample of fresh urine (casts may breakdownwithin 1-2h)

• When cells or cellular debris aggregate in the tubular lumen, they may form casts of the tuble

• Granular or cellular casts (epithelial, red, or white cells)indicate the presence of renal parenchymal disease

• Hyaline – proteinaceous – casts are found withproteinuria

• An active sediment contains elements consistent withrenal inflammation and/or cell necrosis

• A benign sediment may contain a few cells and onlyhyaline casts.





Nephritic Syndrome

• Hematuria, Hypertension, reduced GFR

• Active urinary sediment and Hematuria areindicative of renal inflammation

• Oliguria & renal impairment are aconsequence of glomerular infiltration withinflammatory cells & release of vasoactive

hormones & cytokines• Hypertension is the result of salt & water

retention & vasoactive hormone release



Consequences of glomerular disease

• Proteinuria; due to impaired filtration barrier of GCW

• Hematuria; due to leak into Bouwman’s space acrossGCW or into tubular lumen

• Renal impairment; multifactorial – Acute inflammatory process

• Proliferation intrinsic glomerular cells

• Glomerular infiltration with leukocytes• Haemodynamic changes induced by vasoactive hormones &

cytokines

– Chronic renal scarring• Caused by continuing inflammation,hypertension, proteinuria &

other factors

– Structural and/or functional damage of glomeruli andtubulointerstitium

• Hypertension – Salt and water retention

– Glomerular capillary & arteriolar scarring

– Neurohumoral changes, in particular activation of Renin- Angiotensin system



Diagnosis of glomerular disease /

nephritic syndrome• Combination of clinical features, serologic tests, and

renal biopsy

• A positive test result suggest the primary diagnosis, butdoes not prove that it is the cause of the renal disease

• Renal biopsy usually establishes the diagnosisdefinitively

• GN may occur in isolation or as part of a multisystemdisease

• Acute nephritic syndrome can occur either restricted tothe kidney or involve multiple organ (systemic disease)

• Without rapid treatment, irreversible renal failure maydevelop over a short period



Respiratory & skin, other postinfectios GN



• IgA nephropathy: – Acute nephritis

– Macroscopic hematuria occurring at the time or within a few days of (a viral) soar throat

– Shorter prodrome & recurrent distinguishes it from poststreptococcal GN







Pathologenesis of acute glomerulonephritis

• GN may be initiated by an immune response to – An exogenous antigen, e.g. streptococcal

– An endogenous antigen, e.g. DNA in SLE

– Autoimmune response to a renal antigen, e.g. GBM in Goodpasteur’ssyndrome

• The antibodies involved in these responses form the basis for diagnostic serological tests

• Ag is part of a circulating IC , or is deposited in the kidney to form anIC in situ – the IF pattern is discontinues or granular

– Corresponding electron-dense deposits are seen wit EM

– E.g. membranous GN, post-streptococcal GN, and SLE

• If the AB is directed against an intrinsic renal Ag – IF pattern is continuous / linear

– No electron-dense deposits on EM

– E.g. Goodpasteur’s syndrome





Pathology of acute GN

• The glomerulus may be altered in a # of ways in GN – Intrinsic cells – endothelial, mesangial, epithelial – may

proliferate

– Circulating leukocytes may infiltrate

– Platelets may accumulate mesangial matrix may expand

– The GBM may change

– Scarring may develop

• Hallmark of severe disease is development of aglomerular crescent

– A cellular, fibrinous, and later, fibrous lesion in Bouwman’sspace

– The greater the size, and the number of crescents, the moresevere the disease













• Fig 3. The thickened capillary wall shows numerous "holes" in tangential sections,indicating deposits. (Deposits do not take up the silver stain.) Well-developed spikesaround the deposits are not present in this early stage II membranousglomerulonephritis, but segmental, small nubs of silver-stained basement membrane

material protruding from the basement membrane contour on the epithelial side canbe seen (Jones' silver stain, original magnification x400).



• Diffuse coarsely granular capillary wall IgG deposits in stage II-III membranous

glomerulonephritis (immunofluorescence with anti-IgG, original magnification x100).



• Diffuse proliferative acute postinfectious glomerulonephritis with numerous

PMNs with PAS-positive cytoplasm and endocapillary proliferation (periodicacid-Schiff; original magnification x400).



• Acute postinfectious glomerulonephritis by immunofluorescence typically shows

i l ill l d it t i i f I G h C3 i Fi 6(i fl ith ti I G i i l ifi ti 400)

Documents

PROTEINURIA &