Nephrotic Syndrome Flashcards
Investigations of glomerular disease.
Urine microscopy - red cells
Urinary proteins
Serum urea
Serum creatinine
Culture - throat, ear, skin swab
CXR
Renal imaging
Renal biopsy
Antistreptolysin-O titre
C3 and C4 levels
ANA, ANCA, Anti-GBM, Cryoglobulins
What is nephrotic syndrome characterised by?
Oedema
Hypoalbuminaemia
> 3.5g proteinuria in a day
Hyperlipidaemia
What causes hyperlipidaemia in nephrotic syndrome?
Increased synthesis of lipoproteins due to low albumin.
LDL increases partly due to upregulation of PCSK9 causing internalisation of LDL receptors.
Pathophysiology of nephrotic syndrome.
Podocyte pathology -> proteinuria
Membranous nephropathy
Management of oedema in nephrotic syndrome.
Fluid (1L/day) and salt restriction. Give furosemide (if gut oedema give IV) Daily weights for guidance.
Aim for 0.5kg to 1kg weight loss per day.
Thiazide if resistant oedema.
Management of proteinuria in nephrotic syndrome.
ACEi or ARBs.
Common complications in nephrotic syndrome.
Thromboembolism
Infection
Hyperlipidaemia
Progression of CKD
Hypertension
Cause of thromboembolism in nephrotic syndrome and treatment.
Hypercoagulable due to more clotting factors, less anti-thrombin III, and patelet abnormalities.
This leads to increased of VTE, DVT and PE and renal vein thrombosis.
Treated with LMWH and warfarin.
What predisposes nephrotic syndrome patients to infection?
Urine losses of immunoglobulins and immune mediators.
This leads to increased risk of urinary, resp and CNS infections.
Primary causes of nephrotic syndrome.
Minimal change disease
Focal segmental glomerulosclerosis (FSGS)
Membranous nephropathy
Membranoprolfierative glomerulonephritis
Secondary causes of nephrotic syndrome.
DM
Lupus nephritis of SLE
Myeloma
Amyloid
Pre-eclampsia
Give examples of conditions that may have nephrotic range proteinuria but not necessarily other nephrotic features.
Amyloidosis
Diabetes
Myeloma
Epidemiology of MCD.
Most common form of GN in children.
Condition accounts for 20-25% of cases of adult nephrotic syndrome.
Oedema usually present predominantly around face as a child.
Causes of MCD.
Idiopathic most common
Drugs such as NSAIDs and lithium
Paraneoplastic due to haematological malignancy like Hodgkin’s lymphoma
Does not cause renal failure
Diagnosis of MCD.
Light microscopy is normal and is why it is called minimal change.
Electron microscopy shows effacement of podocyte foot processes.
Treatment of MCD.
Prednisolone 1mg/kg for 4-16 weeks.
75% of adults will respond and > 50% will relapse.
If there are frequent relapses try increased dose of prednisolone or try a DMARD like cychlophosphamide or calcineurin inhibitors.
Rituximab can be tried.
What is the most common glomerulonephritis seen on renal biopsy?
FSGS
Causes of FSGS.
Primary (idiopathic)
Secondary such as HIV, Heroin, lithium, lymphoma, other scarring.
Complications of FSGS.
Risk of progressive CKD and kidney failure.
Increased proteinuria worsens prognosis.
Diagnosis of FSGS.
Glomeruli have scarring of certain segments. Scerotic glomerular lesions that affects some but not all glomeruli as well as segments of each tuft.
May miss early disease if < 10 glomeruli in biopsy sample.
Treatment of FSGS.
ACEi/ARBs and BP control in all.
Corticosteroids only in primary disease.
Remission in around 25% and partial remission in up to 50%.
Calcineurin inhibitors can be considered as second line.
Plasma exchange and rituximab in reccurence in transplants.
Epidemiology of membranous nephropathy.
25% of adult nephrotic syndrome.
Causes of membranous nephropathy.
Primary (idiopathic)
Secondary:
Lung, breast, GI, prostate haematological malignancy
Infection such as hep B and C, Streptococcus, malaria and schistosomiasis
Immunological disease like SLE, RA, Sarcoidosis and Sjögren’s
Drugs like gold and penicillamine
Diagnosis of membranous nephropathy.
Anti-phospholipase A2 receptor antibody for idiopathic
Diffusely thicked GBM due to subepithelial depsotis (IgG4 dominant in idiopathic and IgGS in secondary)
Spikes on silver stain
Treatment of membranous nephropathy.
ACEi/ARBs and BP control in all.
Immunosuppression only in those with high risk of progression ( >4g proteinuria without response to ACEi/ARBs)
Treatment of underlying cause in secondary
Epidemiology of membranoproliferative glomerulonephritis.
10% of adult nephrotic syndrome.
Types of membranoproliferative GN.
Immune-complex associated
C3 glomerulopathy
Explain immune-complex associated membranoproliferative GN.
Driven by increased or abnormal immune complexes which deposit in the kidneys and activate complement.
There is usually an underlying cause such as infection, cryoglobulinaemia, monoclonal gammopathy or autoimmunity.
Explain C3 glomerulopathy
Genetic or acquired defect in the alternative complement pathway.
Diagnosis of membranoproliferative GN.
Proliferative glomerulonephritis with electron dense deposits.
Immunoglobulin deposition distinguishes between immuno-complex associated and C3 glomerulopathy.
Treatment of membranoproliferative GN.
ACEi/ARBs and BP control.
Treat underlying cause.
Trial of immunosupp if no underlying cause is found or if there is progressive decline.
What is amyloidosis?
A group of disorders characterised by extracellular deposits of a protein in abnormal fibrillar form, resistant to degradation.
The ones discussed in this session are systemic forms, it can however also be seen in Alzheimer’s, T2DM and haemodialysis related amyloidosis.
Give examples of types of systemic amyloidosis.
AL amyloidosis
AA amyloidosis
Familial amyloidoses
What is AL amyloidosis?
There is proliferation of plasma cell clones related to multiple myeloma.
This leads to amyloidogenic monoclonal immunoglobulins leading to fibrillar light chain protein deposition.
Depositions lead to organ failure and ultimately death.
Associations of AL amyloidosis.
Myleoma
Waldenström’s
Lymphoma
Organs involved in AL amyloidosis
Kidneys - glomerular lesions, proteinuria and nephrotic syndrome
Heart - restrictive cardiomyopathy
Nerves - peripheral and autonomic neuropathy + carpal tunnel
Gut - macroglossia, malabsorption, weight loss, perforation, hepatomegaly
Vascular - purpura (periorbital)
Treatment of AL amyloidosis.
Optimise nutrition, PO melphalan and prednisolone to extend survival.
Stem cell transplant
What is AA amyloidosis?
Secondary amyloidosis where the amyloid is derived from serum amyloid A.
It is an acute phase protein associated with chronic inflammation in RA, UC/Crohn’s and untreated familial mediterranean fever.
Also with chronic infections such as TB, bronchiectasis and osteomyelitis.
Organ involves in AA amyloidosis.
Kidneys - proteinuria and nephrotic syndrome may be present
Liver - hepatomegaly
Spleen - splenomegaly
No macroglossia
Cardiac is rare
Treatment of AL amyloidosis.
Manage underlying condition
What is familial amyloidosis?
Autosomal dominant from mutation in transthyretin. This is a transport protein produced in the liver.
Usually causes senosry or autonomic neuropathy.
Renal involvment
Cardiac involvment
No macroglossia
Treatment of familial amyloidosis.
Liver transplant can cure it.
Diagnosis of amyloidosis.
Biopsy of affected tissue.
Positive congo red staining with apple-green birefringence under polarised light microscopy.
Rectum or subcut fat is +ve in 80% of cases.
Prognosis of amyloidosis.
Median survival is 1-2 years.
Patients with myeloma and amyloidosis have a shorter survival than those with myeloma alone.
