3 Nephritis and nephrotic syndrome Flashcards
what is nephrotic syndrome characterised by ?
maassive proteinurea >3.5g a day
and hypoalbuminemia
and edema
what is the pathophysiology of nephritic syndrome
loss of negative charge in glomerular basement membrane = loss of selective barrier esp negatively charged albumin
podocyte damage and fusion - non selective porteinurea - except in minimal change disease manifest with selective glomerular proteinuria
what is a compensatory mechanism to the protein loss we see in nephrotic syndrome and also useful for the diagnosis of nephrotic syndrome
plasma levels of cholesterol , LDL , triglycerides and lipoproteins increase
what are the typical clinical features of nephritic syndrome ?
decrease in osmotic pressure - leading to PITTING edema starts in the periorbital lung pleural edema ascitis
weight gain , lower metabolic rate , muscle stiffness = loss of thyroglobulin transport protein leading to thyroxine deficient
vit D deficicny = hypocalcemia = tetany , paresthesia and muscle spasms
symptoms of underlying disease
frothy urine - protein high
lipid urea - fatty casts
what do nephrotic syndrome people have a higher risk for ? and why ?
rena vein thrombosis
higher risk for hypercogulability
because anti thrombin 3 , protein C and S = will cause hypercoaguble site
= pulmonary embolism = dyspnea
higher risk for infection because loss of immunoglobulins
what are the initial evaluation we do for nephrotic syndrome ?
CONFIRM NEPHROTIC RANGE PROTEINUREA
qualitative
urine dipstick
hematurea indicate concomitant glomerulonephritis
quantitative
24hr urine protein
pot urin protein / creatnine ratio
===========
Urine sediment microscopy
Nephrotic sediment :
Lipiduria, fatty casts with Maltese cross appearance under polarized light
Renal tubular epithelial cell casts
microscopic Hematuria with acanthocytes
and/or
RBC casts may indicate concomitant glomerulonephritis
===========
additional lab
hb/ hct high - indicate hemoconcentration
creatinine high
SODIUM COMMONLY LOW (RASS AND ADH)- HYPERVOLEMIC HYPONATREMIA
= sometimes lead to hypertension
coagulation factors - fibrinogen and d dimer is high
vit D levels
=========
renal ultrasound
what diseases are associated with nephrotic syndrome ?
minimal change disease / lipid nephrosis
focal segmental glomerulosclerosis
membranous glomerulonephritis
diabetic nephropathy = secondary
amyloid nephropathy = secondary
lupus nephritis = secondary
membranoproliferative glomerulonephritis
what is the definition of nephritic syndrome ?
inflammatory process that is defined as the presence of one or more of the following
macroscopic hematuria with acanthocytes
RBC casts in urine
proteinurea but less than 3.5g a day
hypertension
mild to moderate edema
sterile pyuria
oliguria
azotemia
what is the pathophysiology of nephritis syndrome ?
usually due to inflammation of the glomerulus
1) inflammation leading to cytokine release - white blood cells accumulate in the bowman capsule
the glomerular basement membrane is also porous - leaking protein and RBC
oliguria is because the inflammatory infiltrates in the bowman capsule and the capillaries red fluid across the membrane reduction in GFR
there is SALT retention - leading to intravascular volume expansion = hypertension and edema
2) membranoproliferazive glomerulonephritis
depostion of antibodies between the podocytes and basement membrane
type 1 : sub endothelial immune complex deposition
type 2 (dense deposit disease) : intramembranous deposition of complement C3 C3 nephritic factor - autoantibody which stabilises C3 converts - leading to continuous activation and depletion of C3
what are the clinical features of nephritic syndrome ?
intermittent hematurea - red/ brown coloured urine
hypertension
pitting edema
decrease gfr and oligourea leading to uremic symptoms :
= fatigue , weakness , loss of appetite ,
uremic fector
pruritus
uremic pericarditis
encephalopathy - seizures and coma
parethesia
how do we diagnose nephritic syndrome ?
hematuria ancanthocytes RBC casts mild to moderate porteinurea sterile pyuria - sometimes abc casts
blood test
creatinine high
azotemia with BUN high
ANA , ANCA and anti-GBM pantibodies
renal biopsy
how is non glomerular hematurea characterised ?
BRIGHT RED
occurrence of blood clots
normal RBC morphology
ABCENCE OF RBC CASTS
what are the diseases associated with nephritic syndrome ?
post strep glomerulonephritis
IgA nephropathy - berger disease
small vessel vasculitis -wegner granulomatosis -microscopic polyangitis -eosinophilic granulomatosis with polyangitis (charge strauss syndrome)
good pasture syndrome
thin basement membrane hematurea
alport syndrome
diffusive proliferative glomerulonephritis
rapidly progressive glomerulonephritis
membranoproliferazive glomerulonephritis
what is the etiology of ALPORT SYNDROME ?
x linked recessive inheritance = therefore more severe in males
sometimes autosomal recessive
what is the pathophysiology of aport syndrome ?
genetic defect in type 4 collagen - which is a component of the basement membrane of the kidneys , eyes , and chochlea
what are the clinical features of aport syndrome ?
age of onset day from infancy to late adulthood
often asymtomatic
intermittent macroscopic hematurea
SENSORINEURAL HEARING LOSS - high freq
ocular 0 anterior lenticonus , retinopathy
as glomerular damage progresses - nephritic syndrome and chronic kidney disease and end stage renal disease
(cant pee , cant see , cant hear a bee)
what is the confirmatory test of aport syndrome other than nephritic syndrome diagnostics ?
skin biopsy - absence if collagen 4 alpha 5 chants
======
kidney biopsy
LM = mesangial cell proliferation and sclerosis
EM = splitting and thickening of the glomerular basement membrane - basket weave appearance
immunostaining - absence of type 4 collagen in basement membrane
======
molecular genetic testing
what is the treatment for aport syndrome ?
proteinurea - ACE inhibitors / arb
chronic kidney disease treatment )sodium restriction and diuretics)
hearing aid
ocular surgery
the only definitive treatment is kidney transplant
what is a complication of aport syndrome after kidney transplant ?
good pasture disease can occur due to newly developed collage type 4 antigens
what is the treatment of nephrotic syndrome ?
Edema
Dietary sodium restriction
Fluid restriction: < 1.5 liters/day
Diuretic therapy
High diuretic doses often required because of diuretic resistance.
First-line: oral loop diuretic
Second-line:
Add oral thiazide
OR switch to IV loop diuretic
Consider adjunctive IV albumin 30–60 minutes prior to intravenous loop diuretic.
================
Proteinuria
Elimination or reduction of proteinuria is a major treatment goal for nephrotic syndrome and lead to increased serum albumin, decreased edema, hyperlipidemis, reduction in risk of thromboembolism and infection, and slowing of the progression of chronic kidney disease.
RAAS inhibitor: ACEI or ARB are commonly used.
Effects
Reduces proteinuria
Treats hypertension
Avoid in patients with AKI, hyperkalemia, or abrupt onset of nephrotic syndrome.
Other measures that may be beneficial in combination with an ACEI or ARB:
Thiazide diuretic (e.g., hydrochlorothiazide )
Mineralocorticoid receptor antagonist (e.g., spironolactone )
Dietary protein: avoid very high-protein diet but ensure adequate protein intake (0.8–1.0 g/kg daily).
=============
Dyslipidemia
atorvastatin
========
Hypercoagulability
All patients with nephrotic syndrome are at increased risk of thromboembolism, and this risk becomes progressively higher as serum albumin drops below 3.0 g/L.
The following parameters should be taken into account to decide whether prophylactic anticoagulation is indicated:
Serum albumin level: when serum albumin is < 2–2.5 g/dL.
Histological diagnosis: VTE risk is higher in primary membranous nephropathy
Immobility due to edema, obesity, malignancy,
thrombophilic state
Previous history of thromboembolic events
Proteinuria > 10 g/day
Body mass index > 35 kg/m2
Recent abdominal or orthopedic surgery
New York Heart Association class III to IV congestive heart failure
Options
Unfractionated heparin
Low molecular weight heparin
Oral warfarin (target INR 2.0–3.0)
=============
Infectious risk
Screening: Consider screening for hepatitis B,
HIV,
latent TB,
syphilis
Preventive measures :
Pneumococcal vaccination
Annual vaccination for influenza
Consider monthly IV immunoglobulin in patients with repeated bacterial infections and serum IgG < 600 mg/dL.
Consider pneumocystis pneumonia prophylaxis (e.g., trimethoprim-sulfamethoxazole ) in patients receiving high-dose steroids and/or other immunosuppressive therapy
what re the complications of nephrotic syndrome ?
Venous thromboembolism deep vein thrombosis, pulmonary embolism
Arterial thromboembolism
Renal vein thrombosis:
Cause: hypercoagulable state (e.g., malignancies, antiphospholipid syndrome, nephrotic syndrome)
Manifestations: flank pain, anuria
Atherosclerotic complications
Chronic kidney disease: FSGS and membranous nephropathy in particular may progress to chronic kidney disease and ESRD.
treatment of nephritic syndrome :
Supportive therapy
Low-sodium diet
Water restriction
Medical therapy
If proteinuria and/or hypertension: angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers
If severe hypertension and/or edema: diuretics
