Glomerular disease Flashcards
(40 cards)
Clinical Px of glomerular disease in general
• glomerular disease has diverse clinical presentations including hematuria, proteinuria,hypertension, edema and decreased GFR
• each glomerulopathy presents as one of four major glomerular syndromes (these are NOTdiagnoses):
○ acute nephritis
○ rapidly progressive glomerulonephritis
○ nephrotic
○ asymptomatic urinary abnormalities
• glomerulopathies can be caused by a primary disease OR can occur secondary to a systemic disease
• some glomerulopathy can present as more than one syndrome at different times
What is Protein-creatinine ratio
relates to concentration of urine sample. Has good correlation (1g=100)
Albumin makes about 1/3 of protein that’s being leaked.
How is urine albumin-to-creatinine ratio (ACR) helpful?
to early diagnose kidney problems especially diabetic nephropathy (they selectively have albuminuria instead of general proteinuria)
used to screen for diabetic nephropathy
- microalbuminuria - defined as ACR ≥2.8 mg/mmol (female) or ≥2.0 mg/mmol (male) - marker of vascular endothelial function - an important prognostic marker for kidney disease in diabetes and hypertension (see Diabetes, NP28) - an elevated ACR ≥2.0 or 2.8 mg/mmol is the earliest sign of diabetic nephropathy
What amount of protein excretion is ‘abnormal’ and hence proteinuria?
3500mg total protein/1.73m^2 per day = nephrotic range proteinuria
- upper limit of normal daily excretion of total protein is 150 mg/d
- upper limit of normal daily excretion of albumin is 30 mg/d
the other normally excreted proteins are either filtered low molecular weight proteins (such as immunoglobulin, light chains or β-2 microglobulin) or proteins secreted by the tubular epithelial cells (e.g. Tamm-Horsfall mucoprotein)
Ix for proteinuria
• urine R&M, C&S, urea, Cr
• further workup (if degree of proteinuria >0.5 g/d, casts and/or hematuria)
- CBC, glucose, electrolytes, 24-h urine protein and Cr
- urine and serum immunoelectrophoresis, abdominal/pelvic ultrasound
- serology: ANA, RF, p-ANCA (MPO), c-ANCA, (PR3) Hep B, Hep C, HIV, Antisteptolysin-O (ASOT)
• indications for nephrology referral
- generally, if there is “heavy” proteinuria, should refer to nephrologist
- heavy proteinuria is ACR >30 mg/mmol
• definitely if there is nephrotic syndrome: marked proteinuria >3.5g/1.73m2/d with hypoalbuminemia (
Definen haematuria
• hallmark of nephritic syndromes
• presence of blood or RBCs in urine
- gross hematuria: pink, red, or tea-coloured urine
- in gross hematuria, the urine should be centrifuged:
○ if the sediment is red, true hematuria.
○ if the supernatant is red, test for heme with a dipstick
○ if supernatant +ve for heme: myoglobinuria or hemoglobinuria
○ if –ve for heme: pseudohematuria. Consider medications (e.g. rifampin), food dyes (e.g. beets) or metabolites (e.g. porphyria)
• microscopic hematuria: normal coloured urine, >2-3 RBCs/HPF on microscopy
Normally there should be no RBC
Ix of haematuria
- Hx and Px: family history of nephrolithiasis, hearing loss (Alport’s), cerebral aneurysm (PCKD), diet, recent URTI, irritative and obstructive urinary symptoms (UTI)
- urine R&M, C&S, urea, Cr
- renal ultrasound
- 24-h urine stone workup if there is a history of stone formation or if there is a stone noted on imaging: calcium, oxalate, citrate, magnesium, uric acid, cysteine
- further workup (if casts and/or proteinuria): CBC, electrolytes, 24-h urine protein and Cr, serology (ANA, RF, C3, C4, p-ANCA, c-ANCA, ASOT)
- consider urology consult and possible cystoscopy if not clearly a nephrologic source for hematuria or if >50 yr of age
Causes of isolated proteinuria in asymptomatic urinary abnormalities
- can be postural
- occasionally can signal beginning of more serious GN (e.g. FSGS, IgA nephropathy, amyloid, diabetic nephropathy)
Causes of hematuria with or without proteinuria in asymptomatic urinary abnormalities
- IgA nephropathy (Berger’s disease): most common type of primary glomerular disease worldwide, usually presents after viral URTI
- hereditary nephritis (Alport’s disease): X-linked nephritis often associated with sensorineural hearing loss; proteinuria
What is a Bence-Jones protein?
a monoclonal globulin protein or immunoglobulin light chain found in the urine
Detection of Bence Jones protein may be suggestive of multiple myeloma or Waldenström’s macroglobulinemia
Describe amyloidosis as a secondary cause of glomerular disease
- nodular deposits of amyloid in mesangium, usually related to amyloid light chain (AL)
- presents as nephrotic range proteinuria with progressive renal insufficiency
- can be primary or secondary
- secondary causes: multiple myeloma, TB, rheumatoid arthritis, malignancy
Describe Lupus as a secondary cause of glomerular disease
- lupus nephritis can present as any of the glomerular syndromes
- nephrotic syndrome with an active sediment is most common presentation
- glomerulonephritis caused by immune complex deposition in capillary loops and mesangium with resulting renal injury
- serum complement levels are usually low during periods of active renal disease
- children and males with SLE are more likely to develop nephritis
Describe Henoch-Schonlein purpura as a secondary cause of glomerular disease
HSP is a systemic vasculitis (inflammation of blood vessels) and is characterized by deposition of immune complexes containing the antibody IgA; the exact cause for this phenomenon is unknown. It usually resolves within several weeks and requires no treatment apart from symptom control, but may relapse in a third of the cases and cause irreversible kidney damage in about one in a hundred cases
- seen more commonly in children
- purpura on buttocks and legs, abdominal pain, arthralgia and fever
- glomeruli show varying degrees of mesangial hypercellularity
- IgA and C3 staining of mesangium
- usually benign, self-limiting course, 10% progress to CKD
Describe Goodpasture’s disease as a secondary cause of glomerular disease
- antibodies against type IV collagen present in lungs and GBM
- more common in 3rd and 6th decades of life, men slightly more affected than females
- present with RPGN type I and hemoptysis/dyspnea
- pulmonary hemorrhage more common in smokers and males
- treat with plasma exchange, cyclophosphamide, prednisone
Describe ANCA associated vasculitis as a secondary cause of glomerular disease
- pr3-ANCA (c-ANCA) most commonly associated with the clinical picture of granulomatosis with polyangiitis (previously called Wegener’s granulomatosis)
- mpo-ANCA (p-ANCA) most commonly associated with the clinical picture of microscopic polyangiitis
- renal involvement very common
- focal segmental necrotizing RPGN with no immune staining (pauci-immune)
- may be indolent or fulminant in progression
- vasculitis and granulomas rarely seen on renal biopsy
- treating typically involves cyclophosphamide and prednisone
Describe cryoglobulinemia as a secondary cause of glomerular disease
- cryoglobulins: monoclonal IgM and polyclonal IgG
- presents as purpura, fever, Raynaud’s phenomenon and arthralgias
- at least 50% of patients have hepatitis C
- renal disease seen in 40% of patients (isolated proteinuria/hematuria progressing to nephritic syndrome)
- most patients have decreased serum complement (C4 initially)
- treat hepatitis C, plasmapheresis
- overall prognosis: 75% renal recovery
Describe shunt nephritis as a secondary cause of glomerular disease
- immune-complex mediated nephritis associated with chronically infected ventriculoatrial shunts inserted for treatment of hydrocephalus
- presents as acute nephritic syndrome with decreased serum complement
- nephrotic range proteinuria in 25% of patients
Describe HIV as a secondary cause of glomerular disease
- direct nephrotoxic effect of HIV infection, antiretroviral drugs (e.g. tenofovir, indinavir) and other drugs used to treat HIV-associated infections
- HIV-associated nephropathy (HIVAN)
- histology: focal and segmental glomerular collapse with mesangial sclerosis, “collapsing FSGS”
- tubular cystic dilation and tubulo-reticular inclusions
- clinical features: predominant in black men, heavy proteinuria, progressive renal insufficiency
- prognosis: kidney failure within 1 yr without treatment
- therapy: short-term, high dose steroids, ACEI, HAART
Describe infective endocarditis as a secondary cause of glomerular disease
- manifests as mild form of acute nephritic syndrome with decreased serum complement
- S. aureus is most common infecting agent
- treatment with appropriate antibiotics usually resolves GN
Describe Hep B & C as a secondary cause of glomerular disease
Hep B: can result in membranous nephropathy, polyarteritis nodosa, membranoproliferative GN
Hep C: can result in membranoproliferative GN, cryoglobulinemia and membranous nephropathy
Describe syphilis as a secondary cause of glomerular disease
can result in membranous GN
Px of nephrotic syndrome (4)
HELP
Hypoalbuminemia
Edema
Lipid abnormalities
Proteinuria
Px of nephritic syndrome (6)
PHAROH
Proteinuria Hematuria Azotemia RBC casts Oliguria Hypertension
(2) types of GN that is nephritic
IgA GN
Post infectious GN - although rare now
