Renal Medicine 2 Flashcards
Describe the the ways diabetes can affect the kidneys?
Direct glomerular damage: there is basement membrane thickening, leading to increased leakiness of the capillary wall and proteinuria, with eventual glomerular hyalinisation leading to CKD
Ischaemia due to arterial disease: atherosclerosis extends further into the small arteries to cause reduced eGFR and glomerular ischameia
Ascending infection: more common in DM
What is the cause of PKD?
AD or AR inheritance
Describe what PKD is?
ADPKD = more common, both kidneys are gradually replaced by enlarging fluid filled cysts, compressing the parenchyma out of existence
What is the presentation of PKD?
Systemic hypertension, CKD and abdominal swelling due to very large kidneys bilaterally
Balottable kidneys
Renal failure occurs in later life
Cysts in liver, lungs and pancreas but without symptoms
What do cysts in the liver lead to?
Portal hypertension and fibrosis
What is the management of PKD?
As per CKD and screening for berry aneurysms
How does hypertensive renal damage occur?
Long standing renal disease leads to thickening of renal artery walls, making the afferent arterioles inelastic and rigid
Chronic progressively reducing blood flow leads to chronic ischaemia, with progressive loss of glomeruli, replaced by hyaline tissue
This can be exacerbated by renal artery stenosis due to atherosclerosis
What are the two forms of chronic interstitial nephritis?
Reflux associated chronic interstitial nephritis - due to incompetent vesicoureteric valves, predisposing to infection and scarring
Obstructive interstitial nephritis: recurrent episodes of infection occurring due to anatomical abnormality (prostate, retroperitoneal fibrosis, genetic abnormalities or a stone)
What drugs generally require dose reduction due to decreased eGFR?
Gentamicin Cephalosporins Heparin Lithium Opiates Digoxin
What are the three layers of the glomerulus?
Fenestrated capillary epithelium
Basement membrane
Visceral layer: formed by podocytes
What is the purpose of the layered glomerulus?
Together create a sieve that allows small, charged ions through, yet will not allow transport of proteins or blood
What is the primary cause of glomerular disease?
Immunological attack by an antibody or T cell attacking an antigen in the glomerulus, which may be primary (always there) or secondary (acquired/deposited)
What are the secondary factors causing deposition of antigens in glomerular disease
NSAID HSP:
Neoplasm SLE Amyloid Infection Diabetes
HSP
What is the effect of glomerular disease on the capillary layer?
Endothelial cell proliferation: leading to bigger fenestra
Capillary wall necrosis
Glomerulosclerosis: scarring in the mesangium leading to the fenestra and capillaries being pulled apart
What is the effect of glomerular disease on the basement membrane?
Thickened membrane, leading to structural distortion and thus becomes more permeable
What is the effect of glomerular disease on the tubules?
Deposition of cells in Bowman’s space
What do the following terms mean histologically? Global segmental Diffuse Focal
Global: whole glomerulus is decreased
Segmental: small patches of one glomerulus are damaged in a ‘patchy’ fashion
Diffuse: affecting >50% of glomeruli
Focal: affecting <50% of glomeruli
What is the clinical manifestation of glomerulonephritis?
AKI CKD Asymptomatic haematuria Nephrotic syndrome Nephritic syndrome
Rapidly progressive glomerulonephritis (rare - an acute version of nephritic syndrome)
What is nephrotic syndrome?
Triad of:
Proteinuria (at least 3.5g/day)
Hypoalbuminaemia (30g/l)
Oedema (due to decreased oncotic pressure and water retention)
Renal loss of thromboregularatory proteins or liporegulatory proteins may lead to hyperlipidaemia or venous thrombosis
Where does oedema from nephrotic syndrome tend to occur?
Periorbitally and peripherally in limbs
What are the most common primary causes of nephrotic syndrome?
Minimal change nephropathy
Membranous glomerulonephritis
Proliferative glomerulonephritis
What are the secondary causes of nephrotic syndrome?
Bacterial/viral infection
drugs
neoplasm
What is the treatment of nephrotic syndrome?
Diuretics
salt/water restriction
ACEis to reduce proteinuria
Anti-coagulation If immobile due to the risk of thrombosis
Treat the cause
What is nephritic syndrome?
Tetrad of: Haematuria - plus red cell casts Oliguria Proteinuria Hypertension
Why are casts and protein seen in urine in nephritic syndrome?
Proliferative, damages to basement membrane
Blood and protein both able to leak through
What are the common primary causes of nephritic syndrome?
IgA nephropathy
Goodpasture’s disease
What are the secondary causes of nephritic disease?
SLE/HSP
What investigations can be done for glomerulonephritis?
Bloods: FBC, U&Es, CRP, culture
Urine to rule out infection
MCS to look for red cells / casts / Bence-Jones proteins
Urine protein:creatinine ratio to quantify protein loss
Nephritic screen to look for causes
Renal USS
Renal biopsy to confirm cause in all adults
Why is urine protein:creatinine ratio used instead of 24 hour urinary protein?
More convenient and equally accurate
Describe how to interpret a protein:creatinine ratio
Units are in mg (protein) and mmol (creatinine)
The amount of protein in mg per mmol of creatinine equivolates to teh amount of protein excreted in grams over 24 hours
random protein:creatinine ratios >300mg/mmol are considered nephrotic range
Urinary protein:creatinine ratios of 50-100mg/mmol are considered significant proteinuria
What is Berger’s disease?
IgA nephropathy
commonest cause of glomerulonephritis worldwide.
It classically presents as macroscopic haematuria in young people following an upper respiratory tract infection.
What is the presentation of Berger’s disease?
Affects young males 1-2 days after and URTI
They present with haematuria, usually macroscopic and nephritic syndrome
Renal biopsy shows IgA/C3 deposits
What is the management of Beurger’s disease?
Supportive
BUT ESRD over 20y
Steroids may slow the decline in renal function
What is minimal change disease?
Most common cause of glomerulonephritis in children
Normal light microscopy and negative immunoflourecence BUT electro-microscopy will show fusion of podocyte foot processes
What is minimal change disease associated with?
NSAID use
allergy
Hodgkin’s lymphoma
What is the treatment of minimal change disease?
Oral steroids
cyclophosphamide if relapsing
What does membranous nephropathy cause?
Nephrotic syndrome
Biopsy - global diffuse glomerulonephritis with IgG and C3 deposits
What is the management of membranous nephropathy?
Steroids
Chlorambucil
Describe the histological appearance of focal segmental glomerulosclerosis?
Idiopathic areas of segmental sclerosis with IgM and C3 deposits
What is the presentation of membranoproliferative glomerulonephritis?
Nephrotic or mixed nephrotic/nephritic syndrome
Biopsy shows large glomeruli with a ‘double basement membrane’ due to mesangial proliferation giving a tramline appearance
What is post-streptococcal glomerulonephritis?
How is this different from Berger’s disease?
Patients present with nephritic syndrome 1-2 weeks following a sore throat / skin infection
Biopsy shows diffuse proliferative GN with IGG and C3 deposits, although none to biopsy
Bloods - raised ASOT and anti-DNAase B and reduced complement levels
Differs from Berger’s as later onset, and shows LOW complement
What is the presentation of HSP?
children: systemic small vessel vasculitis and nephritic syndrome following URTI:
Purpuric rash on extensor surfaces Polyarthritis ABdo pain due to GI bleeding Scrotal / scalp swelling Glomerulonephritis
How is HSP diagnosed?
Clinical - confirmed with a positive immunofluorescence in skin/renal biopsy
What is the management for HSP?
Self-limiting, but if there are relapses and evidence of progressive renal involvement, then corticosteroids
What is Goodpasture’s syndrome?
Anti-GBM antibodies recognise an epitope on type IV collagen
present in the glomerular basement membrane, alveolar basement membrane and also in the eye/ear
What is teh presentation of good pasture’s syndrome?
Haematuria
RPGN with pulmonary haemorrhage leading to haemoptysis and breathlessness
What are the investigations for good pasture’s syndrome?
CXR: pulmonary shadowing
raised transfer factor secondary to pulmonary haemorrhages
renal biopsy shows linear IgG deposition along glomerular basement membrane
What is the treatment for good pasture’s syndrome?
Plasma exchange and corticosteroids +/- cytotoxics
prognosis depends on when the disease is picked up
What is the result of a systemic vasculitis on the kidneys?
Leads to focal segmental glomerulonephritis with appearance overlapping with IgA nephropathy
ANCA +ve
What is RPGN?
GN leading to ESRF over a few days - presents with signs of renal failure and systemic disease
What are the causes of RPGN?
Goodpasture’s syndrome
Wegener’s granulomatosis
others: SLE, microscopic polyarteritis
What is the management of RPGN?
Aggressive immunosuppression
(high dose steroids and cyclophosphamide)
Prognosis depends on how early treatment is initiated
What is the presentation of acute pyelonephritis?
High fever
loin pain with tenderness
Bacteriuria
Rigors, vomiting, oliguria
