N13 - Glomerular Diseases Flashcards
Types of nephritis syndromes
- acute nephritis syndrom
- rapid progressive glomerulonephritis
- chronic (asymptomatic) nephritis
Types of nephrosis syndrome
asympomatic urinary disorders: isolated hematuria, isolated proteinuria
Types of proteinuria
- tubular proteinuria: low molecular weight proteins filtered through the glomerulus are not fully reabsorbed in the renal tubules
- overflow proteinuria: overproduction of low molecular weight proteins
- postrenal proteinuria: typically associated with UTI and leukocyturia
Proteinuria in nephrosis syndrome
- protein in urine >3.5 g/day
- serum albumin <3.5 g/dl
Characteristics of acute nephritis syndrome
- eGFR: decreases significantly in a few days
- urine volume: oliguria
- hematuria: microscopic or macroscopic, dysmorphic RBC, acanthrocytes, RBC cylinders
- proteinuria: subnephrotic (typically 1-3g/day)
- serum albumin: normal/slightly low
- edema: generalized, caused by volume retention
- blood pressure: can be high, very high
- systemic symtoms: headache, anorexia
sudden onset, usually spontaneous improvement
Characteristics of rapid progressive glomerulonephritis (RPGN) syndrome
- eGFR: decreases significantly in a few days or 1-2 months
- urine volume: can be oliguria
- hematuria: mostly microscopic, dysmorphic RBC, acanthrocytes, RBC cylinders
- proteinuria: subnephrotic (typically 1-3g/day)
- serum albumin: normal/slightly low
- edema: not typical but can be mild
- blood pressure: not necessarily high
- systemic symptoms: fever, weight loss, join pain, muscle pain, weakness, palpable purpura
sudden onset, rapid progression of uremia
Characteristics of chronic (asymptomatic) nephritis
- eGFR: can be maintained and decreases over years/decades
- urine volume: normal
- hematuria: mostly microscopic, sometimes macroscopic, dysmorphic RBC, acanthrocytes
- proteinuria: subnephrotic (typically less than 3g/day)
- serum albumin: mostly normal
- blood pressure: often high
- systemic symptoms: not characteristic
asymptomatic onset, slow progression of uremia
General treatment of nephritis syndromes
- fluid status
- reduce table salt intake (≤ 5g/day) and fluid intake (500-1000 mL/day)
- furosemide: 40-160 mg/day (po. or iv.)
- for dehydration: iv 0.9% NaCl infusion
- regulation of blood pressure: ß-blocker, CCB, ACEi/ARB (↓eGFR) (infection control)
Characteristics of nephrosis syndrome
- eGFR: normally maintained, but may decrease slowly with persistent and severe proteinuria
- urine volume: normal
- hematuria: not typical
- proteinuria: nephrotic (>3g/day)
- serum albumin: low
- edema: pronounced (face + limbs)
- blood pressure: normal or low systemic
- systemic symptoms: not characteristic
Consequences of proteinuria in nephrosis syndrome
- Generalized edema: oncotic pressure decreases so there is loss of tissue fluid and plasma volume decreases, leading to increased aldosterone levels and Na-retention
- Hyperlipidemia: protein
- Other possible effects:
- venous thromboembolism due to ↓AT III
- increased infection due to ↓IgG
- osteomalacia due to ↓25(OH)D (calcediol)
- ↓TBG, ↓T3 and T4
- increased TSH (normal T3 and T4!!)
General treatment of nephrotic syndromes
- weight loss (0.5 - 1kg/day)
- liquid and salt restriction (<5g/day)
- furosemide 40 - 250 mg/day (po. or iv.)
- +/- Hypothiazid 25 mg/Tag (po.)
- +/- Aldosterone antagonist 25-100mg/day (po/iv.)
- 20% albumin, 100mL - proteinuria reducing
- ACEi/ARB
- blood pressure ≤ 125/75 Hgmm
- 0.8 g/kg/day protein restriction - anticoagulant treatment
- ASA
- when serum albumin <20 g/L : LMWH!! - lipid lowering drugs:
- normal kidney function in addition to fibrates, otherwise statins (infection control)
Serum investigaion of glomerulopathies
- creatinine
- urea
- ions
- albumin
- CRP
- AST
Immunoglobulin investigation of glomerulopathies
IgA, IgG, IgM, cryoglobulin
Complement investigation of glomerulopathies
C3, C4
Serum light chain investigation of glomerulopathies
- Serum ELFO
- λ
- κ
Antibodies investigation of glomerulopathies
- ANA
- anti-dsDNA
- ANCA
- antiPLA2R
- antiC1q
Histological investigation of glomerulopathies
blood count, hand swab, reticulocytes
Protein excretion investigation of glomerulopathies
- in mg/24h or mg/mmol
- albumin/creatinine or total protein/creatinine
Urine investigation of glomerulopathies
- urine sediment test
- Stix
- protein ELFO
Microbiological investigation of glomerulopathies
- culture tests: urine, stool, respiratory secretions, or hemoculture
- serological tests
- bacterial or viral detection
Imaging for glomerulopathies
- chest Rtg
- abdominal ultrasound (kidney size, parenchyma)
Types of proliferation in proliferative glomerular diseases
- endocapillary: endothelial cells
- mesangio capillary: mesangial and endothelial cells
- mesangial: mesangial cells
- extracapillary: podocytes and parietal epithelial cells
Characteristics of ANCA vasulitis
- rapidly progressing glomerulonephritis; proliferative
- special labs: increase anti-MPO or anti-PR3, possibly eosinophilia, normal complement values
- relatively common disease in middle-aged/elderly patients
- consequences: pulmonary-kidney syndrome, symptoms of upper resp. tract (GPA), asthma, chronic rhinorrhea (EGPA), purpura, necrotizing vasculitis on skin
Histology
LM: extracapillary proliferation w/ crescent formation
IF: pauci-immune
EM: basement membrane rupture, no immune complex
Characteristics of goodpasture syndrome
- rapidly progressing glomerulonephritis; proliferation
- special labs: increased anti-GBM, possible ANCA positivity, normal complement values
- extremely rare disease
- lung and kidney syndrome, no systemic symptoms
Histology
- LM: extracapillary proliferation w/ crescent formation
- IF: linear IgG deposition
- EM: basement membrane rupture
Characteristics of SLE nephritis
- can be any nephritis syndrome
- proliferative or basement membrane damage or both
- special labs: ANA-screen positive, elevated anti-dsDNA and anti-C1q, decreased C3 and C4, possibly accompanied by pancytopenia
- young or middle age patients
- other symptoms: skin, mucous membranes, serous membranes of nervous system, heart etc.
Histology
- LM: mild mesangial proliferation; or endocapillary proliferation ± crescent formation; or basement membrane thickening
- IF: grainy IgG, A, M, C3, C1q (“full house”!!)
- EM: subendothelial electron-dense deposits
Characteristics of IgA nephropathy
- 50% isolated macroscopic hematuria; 40% chronic nephritis
- proliferative
- special labs: increased IgA, normal complement values (essentially negative lab results)
- common disease of youth
- symptoms: hematuria w/ upper resp. tract infection; screened patient (hematuria + proteinuria + hypertension) sometimes with very low eGFR
Histology
- LM: mesangial hypercellularity
- IF: granular IgA, C3, C5b-9
- EM: mesangial electron-dense deposits
Characteristics of Schönlein-Enoch Purpura
- 80% nephritis with systemic symptoms; 20% nephroso-nephritis
- proliferative
- special labs: possibly increased IgA; normal complement values (essentially negative lab results)
- young patients (90% child)
- symptoms: palpable purpura + no thrombopenia/coagulopathy; joint pain; abdominal pain; bleeding in lower GI; hematuria/deteriorating eGFR
Histology
- IgA is indistinguishable from nephropathy
Characteristics of membranoproliferative/mesangiocapillaris glomerulonephritis
- most often nephroso-nephritis of nephrosis syndrome, but can be anything
- proliferative and non-proliferative (mixed)
- special labs: ↑cryoglobulin
- immune complex-mediated MCGN: low C4 + normal C3
- complement-mediated MCGN: low C3 + normal C4 - rare disease, heterogenous etiology
Histology
- mesangial and endocapillary proliferation
- thickening/doubling of the basement membrane
-IF: granular deposition
- EM: subendothelial immune complexes, double basement membrane
Characteristics of minimal change disease
- nephrosis syndrome
- non-proliferative
- special labs: none
- often in childhood, the second form can occur in Hodgkin’s disease
Histology
- not required in childhood; excellent response to corticosteroid therapy
- FM: normal
- IF: negative
- EM: merging of podocyte foot extensions
Characteristics of focal segmental glomerulosclerosis
- nephrotic syndrome ± decreasing GFR
- non-proliferative
- special labs: none
- more common in black people
- second form can be: HIV, heroine abuse, extremely low birth weight, extreme obesity, bodybuilding, obstructive uropathy
Histology
- FM: ECM accumulation, collapsed capillaries, capillary adhesion near intact glomeruli (focal) and glomerular parts (segmental)
- IF: IgM and C3 positivity
- EM: confluence of podocyte foot extensions, crumpled basement membrane, subendothelial hyaline
Characteristics of membranous nephropathy
- nephrosis syndrome
- non-proliferative
- special labs: positivity of the anti-phospholipase A2 receptor (PLA2R) in 70% of primary form
- more common in the elderly
- thrombosis is a common complication
- second form can be: solid tumor, chronic infection, autoimmune disease
Histology
- FM: thickening of the basement membrane with tip-like protrusions
- IF: granular deposition of IgG4 and C3
- EM: subepithelial electron-dense deposits
Characteristics of diabetic nephropathy
- nephrotic syndrome/isolated proteinuria ± decreasing GFR
- non-proliferative
- special labs: none, persistently high HbA1c for long time
- usually due to a long-term, undertreated DM
- retinopathy also exists with T1DM, not necessarily with T2DM
- kidneys checked with abdominal ultrasound; slow progression
Histology
- FM: mesangial expansion, nodular glomerulosclerosis (Kimmelstiel-Wilson syndrome)
- IF: no typical deviation
- EM: basement membrane thickening, podocyte death, mesangial expansion
Characteristics of amyloidosis
- nephrotic syndrome ± decreasing GFR
- non-proliferative abnormalities
- special labs: may contain monoclonal protein in serum/urine (electrophoresis + immunofixation)
- rare disese, elderly patients
- enlarged kidneys with abdominal ultrasound, organomegaly, purpura
Histology
- increased risk of bleeding
- FM: mesangial expansion, nodular glomerulosclerosis; congo staining (painted red in light apple green birefringence)
- IF: AL for amyloid kappa or lambda positivity
- EM: fibrils in the mesangium
Treatment options for acute nephritis
Poststreptococcal GN (supportive therapy)
- volume and salt absorption control
- loop diuretic (furosemide 1x40mg)
- antihypertensive therapy (CCB, ACE inhibitors or ARB only with caution)
- renal replacement therapy
Treatment options for chronic nephritis
IgA nephropathy:
- antihypertensive and anti-proteinuria therapy (ACE inhibitors/ARB)
- fish oil
- depending on the tissue p.o. steroid (for 1/2 year, gradually downwards)
Treatment options for rapid progressive glomerulonephritis
SLE nephritis / goodpasture syndrome / ANCA vasculitis
- aggressive immunosuppression is required
- induction (3-6 months): iv. then po. steroid + cyclophosphamide/rituximab/MMF
- plasmapheresis
- maintenace therapy (1-2 years): azathioprine, MMF, rituximab, or methotrexate
Treatment options for minimal change
- usually a good response to steroids
- cyclosporine if steroid dependence or steroid resistance occurs
Treatment options for focal segmental glomerulosclerosis
- longer-term steroid therapy is required
- cyclosporine or MMF is common in case of steroid resistance/dependence
Treatment options for membranous nephropathy
- steroid + cyclophosphamide/cyclosporine
- rituximab in case of therapy resistance
- spontaneour remission may occur
Treatment options for diabetic nephropathy
- adequate blood sugar control
- ACE inhibitors or ARB to control blood pressure and reduce proteinuria
- reduction of salt intake
Treatment options for amyloid
hematological treatment
