Week 14 Flashcards
What are the functions of the kidneys?
control of solutes and fluid status blood pressure control acid /base drug metabolism / excretion endocrine functions metabolic waste excretion
What is the primary role of the kidneys?
to maintain fluid and electrolyte homeostasis in response to blood pressure and hormones
What is the function of the glomeruli?
filter plasma
not supposed to let through protein / cells / large molecules
What is the function of the tubules?
adjust filtrate content, with collecting ducts absorbing water
Describe measuring urinary protein excretion
24hr urine collection (grams/24hrs)
protein: creatinine ratio (PCR) on morning spot sample (mg/mol)
albumin: creainine ratio (mg/mol)
Describe haematuria
can be blood detectable on dipstick (non-visible haematuria)
visible haematuria-can come from anywhere in the urinary tract (kidneys, stones, infection, malignant, cysts, inflammation)
What is measured in U&Es?
sodium potassium chloride urea creatinine eGFR \+/- bicarbonate
Describe creatinine
breakdown product of muscle so plasm concentration affected by muscle mass
concentration affected by plasma volume
affected only slightly by diet
up to 15% secreted by renal tubule, so total urinary excretion = glomerular filtration + tubular secretion
Trimethprim blocks this - artificially raised
Describe urea
used less than plasma creatinine concentration because urea concentration is more affected by non kidney factors: diet dehydration tissue breakdown - e.g corticosteroid liver failure (lower levels up to 40% may be reabsorbed
What is clearance?
volume of plasma which would be cleared of the substance per unit of time
What is renal clearance?
urine concentration X urine volume
/ plasma concentration of substance
usually expressed as ml/min
usually described as glomerular filtration rate
What is used to calculate the eGFR?
plasma creatinine concentration
age (adults only)
gender
race
Describe in what way eGFR assumes stable renal function
if today’s plasma creatinine concentration = 100micromols/L, but the patent has no kidneys or is making no urine, GFR=0
important for drug dosing
not suitable for AKI
Describe the staging of chronic kidney disease
> 90 - with another abnormality otherwise regard as normal = 1
60-89 - with another abnormality otherwise regard as normal = 2
30-59 - moderate impairment - 3
15-29 severe impairment = 4
<15 advanced renal failure = 5
Describe the basics of glomerulonephritis
inflammatory diseases involving the glomerulus and tubules rare variable natural history may be primary or secondary few specific treatments
What are the targets for injury in glomerulonephritis?
mesangial cells basement membrane (collagen IV) epithelial cells (podocytes) capillary endothelial cells vasculature tubular structures integrity of glomerulus and tubules
What are the extrinsic mechanisms of glomerulonephritis?
antibodies immune complexes complement cytokines lymphocytes other infiltrating cells
What are the intrinsic mechanisms of glomerulonephritis?
cytokines growth factors TGF-beta, PDGF, IFN gamma vasoactive factors proteinuria
Describe kidney biopsy
required for clinical diagnosis of glomerulonephritis
biopsy of kidney cortex examined under:
light microscopy (glomerular and tubular structure)
immunoflourescence (looking for Ig and complement)
electron microscopy (glomerular basement membrane and deposits)
many diseases are a clinical and pathological spectrum
Describe RPGN
rapidly progressive glomerulonephritis - rapid rise in serum creatinine
crescentic damage
vasculitis / lugs. IgA: often have other clinical features
Describe nephritic syndrome
blood and protein in urine, high blood pressure, rising sCr
proliferative / acute inflammation
IgA / lupus / post-infectious
Give overview of nephrotic syndrome
> 3.5g/day proteinuria, low salt, oedema
non-proliferative, podocyte damage
minimal change/ FSGS/ membranous
Describe nephrotic syndrome
3.5g proteinuria per 24 hr
serum albumin <30
oedema
hyperlipidaemia
risk of venous thrombosis and infection also increased
Describe IgA nephropathy
infection? production of IgA
mesangial deposition of IgA
lysis of mesangium proliferation of MC, matrix production, healing or scarring
glomerulosclerosis, tubular loss, hypertensive damage
may be secondary to HSP, cirrhosis, coeliac disease
abnormal production of IgA, C3 deposition
What are the clinical features of IgA nephropathy?
haematuria proteinuria hypertension renal impairment resolve, persist, progress to ESFR
How is IgA nephropathy treated?
antihypertensives
ACE I
ARBs
Describe the pathophysiology of membranous GN
primary - production of Ab
Secondary - tumour? drugs? CTD?
deposition of, or formation of, IC in the GBM and mesangium
altered GBM charge, altered permeability, thickened GBM
glomerulosclerosis
tubular loss
hypertensive damage
Describe the clinical features of membranous GN
proteinuria
nephrotic syndrome
hypertension
renal impairment
Describe membranous GN
disease of adults
presents with the nephrotic syndrome
can be secondary to malignancy, CTD, drugs
anti-phospholipase A2 receptor antibody in 70%
IC in basement membrane / sup-epithelial space
How is membranous nephropathy treated?
treat underlying disease if secondary
supportive non -immunological - ACEi, statins, diuretics, salt and fluid restriction
specific immunotherapy - steroids, alkylating agents (cyclophosphamide), cyclosporin, alternatives (rituximab)
outcomes - complete remission, partial remission, ESRD, relapse, death
Describe minimal change disease
commonest form of GN in children
causes nephrotic syndrome
EM - foot process fusion
idiopathic but may be secondary to malignancy
acute presentation - may follow URTI
GFR - normal or reduced due to intravascular depletion
relapsing course
What is the treatment of minimal change disease?
high dose steroids (prednisalone 1mg/kg for up to 8 weeks
cyclophosphamide / calcineurin inhibitor
Describe the pathophysiology of post infectious GN
infection - streptococci, production of Ab/IC deposition of AB/IC in mesangium etc complement activation infiltration of leukocytes destruction of glomerular cells proliferation of epithelial cells crescent formation glomerulosclerosis tubular loss hypertensive damage
Describe the clinical features of post infectious GN
nephritic/ RPGN haematuria proteinuria hypertension renal impairment
Describe post-infectious glomerulonephritis
production of cross reactive Ab after group A strep infection
sub-epithelial I/C deposition
complement consumption and hypocomplementaemia
10-21 day latent period
oliguric ARF
resolves over weeks in most cases
may require dialysis
Describe crescentic GN / RPGN
a group of conditions linked by natural history./ histology
crescents on biopsy
progression to ESRF over a few weeks, untreated high mortality
What are common causes of crescentic GN / RPGN
goodpastures syndrome - anti-GBM antibody
pauci immune - microscopic polyangiits - MPO antibody (postive pANCA)
granulomatosis with polyangiitis (GPA) - PR3 antibody (positive cANCA
post infectious / bacterial endocarditis
lupus
idiopathic
rarely others - IgA nephropathy
What tests for diabetic nephropathy?
HbA1c / random glucose
What tests for vasculitis?
ANCA / anti GBM
What tests for membranous GN?
ANA/ PLA2R / virology
What tests for lupus?
complement / ANA / dsDNA
What tests for MPGN, FSGS?
complement / virology (hepB, C, HIV) Igs, RF
What tests for amyloid / light chain deposition?
SEP / BJP / SFLC
Name 4 systemic diseases associated with renal dysfunction
diabetes mellitus
atheromatous vascular disease
systemic lupus erythematosis
amyloidosis
In what 5 ways can systemic diseases manifest in the kidneys?
acute kidney injury chronic kidney disease nephritic syndrome proteinuria nephrotic syndrome
Describe the pathophysiology of diabetic nephropathy
hyperglycaemia volume expansion intra-glomerular hypertension hyperfiltration proteinuria hypertension and renal failure
Describe the structural changes the glomerulus in diabetes mellitus
thickening of the glomerular basement membrane, fusion of foot processes, loss of podocytes with denudling of the glomerular basement membrane, and mesangial matrix expansion
What does the evidence recommend for the reduction of risk of diabetic nephropathy?
Tight glycaemic control
Good BP control - ACEi /ARB, SGLT2 inhibitors
aim for BP <130/80
Describe the action of SGLT2 inhibitors
prevent reabsorption of glucose and sodium
lowers blood pressure and blood glucose
main side effect- UTIs
can’t be used in late stage kidney disease
Describe the pathogenesis of renovascular disease
progressive narrowing of renal arteries with atheroma
perfusion falls by 20%
GFR falls but tissue oxygenation of cortex and medulla maintained
RA stenosis progresses to 70%
cortical hypoxia causes microvascular damage and activation of inflammatory and oxidative pathways
parenchymal inflammation and fibrosis progress and become irreversible
restoration of blood flow provides no benefit
Describe the management of renal artery stenosis
BP control (not ACEi / ARB)
statin
if diabetic - good glycaemic control
lifestyle - smoking cessation, exercise, (low sodium diet)
angioplasty - rapidly deteriorating renal failure, uncontrolled high BP on multiple agents
flash pulmonary oedema
Describe amyloidosis
deposition of highly stable insoluble proteins material in extracellular space
kideny, heart, liver, gut
specific ultrastructural features (8-10nm fibrils)
high affinity for the constituents of the capillary wall
What is the appearance of amyloid on light microscopy?
congo red stain
apple green befreingence
What is the appearance of amyloid on electromicroscopy?
amyloid fibrils
cause mesangial expansion
What are the 2 classes of amyloid?
AA - systemic amyloidosis - (inflammatory or infection
AL - immunoglobulin fragments from haematological condition - myeloma
HOw is amyloid treated?
AA - treat the underlying source of inflammation / infection
AL - treat the underlying haematological condition
Describe systemic lupus erythematosis
auto-immune disease
immune complex mediated glomerular disease
multiple auto-ABS - directed against DNA, histones, snRNPs, transcriptional / translational machinery
Describe the pathophysiology of lupus nephritis
auto-antiboeis produced against dsDNA or nucleosomes (anti-dsDNA, anti-histone) form intravascular immune complexes or attach to GBM activate complement (low C4) renal ddadmage
Describe the diagnosis of lupus nephritis
renal biopsy to confirm diagnosis and stage disease
treatment - immunosuppresion - steroids / MMF/ cyclophosphamide / rituximab
What is a cyst?
sac like structure containing fluid
in the kidneys - these arise from the tubules
cause problems by compressing other structures, replacing useful tissue, becoming infected, bleeding, pain
Describe adult polycystic kidney disease
commonest inherited kidney disorder
autosomal dominant
PDK1 gene mutation (C16), most common and aggressive
PDK 2 gene mutations
Describe the impact of PKD1 and 2 gene mutations
code for polycystic 1 and 2
polycystins are located in the renal tubular epithelia (and in liver and pancreas ducts)
overexpressed in cyst cells
membrane proteins involved in intracellular calcium regulation
mechanism for cyst formation is poorly understood
genetic testing not routine
Describe the natural history of APKD
cysts gradually enlarge
kidney volume increases
some compensation
eGFR falls, usually 10 years before kidney fails
Describe the diagnosis of APKD
differentiate between simple renal cysts which are common as people get older
should get ultrasound at 21 if family history - 2 cysts, screened again at 30 if no cysts
no family history - 10 or more cysts on each side
CT or MRI more sensitive
What are the renal complications of APKD?
50% risk ESRD by age 50
cyst accidents 60%
What are the other complications of APKD?
hypertension intracranial aneurysms mitral valve prolapse aortic incompetence colonic diverticular disease liver / pancreas cysts hernias - volume of kidneys
What is the management of APKD?
supportive early detection and management of blood pressure treat complications manage extra renal associations renal replacement therapy
Describe Von HIppel Lindau
autosomal dominant condition causing multiple bengin and malignant neoplasms
renal cysts and multifocal renal cell carcinomas
other unusual tumours - phaechromoctytoma, haeangioblastoma, clear cell carcinoma of CNS
Describe tuberous sclerosis
autosomal dominant
benign hamartomas of multiple systems: brain, eyes, heart, lung, liver, kidney and skin
variable phenotype
up to 80% renal involvement - multiple renal cysts, renal angiomyolipomas, renal cell carcinoma
most have epilepsy, 50% have learning difficulties
Describe medullary cystic kidney disease
autosomal dominant
cysts at the corticosteroids-medullary junction
small to normal sized kidneys
hyperuricaemia and gout
Describe Alport’s syndrome
usually X-linked -
collagen 4 abnormalities - alpha 3 gene mutation, alpha 4 gene mutation or alpha 5 gene mutation
deafness and renal failure (can affect other organs including eyes)
microscopic haematuria, proteinuria, and ESRF
mainly on dialysis bu age 40
sensineural hearing loss late childhood
female aport’s carrier - 12 % ESFR by age 40
Describe Fabry’s disease
X-linked storage disorder
alpha galactosidase A deficiency resulting in accumulation of globotriaosylceramide (Gb3)
Gb3 accumulates in glomeruli, particularly podocytes causing proteinuria and ESFR - average age of onset 34
also causes neuropathy, cardiac and skin features
diagnosis - measure alpha Gal A activity in leukocytes
renal biopsy
management - enzyme replacement therapy
Describe cystitis
infection of the bladder dysuria frequency urgency suprapubic pain haematuria
Describe pyelonephritis
infection of the kidney cystitis symptoms plus fever >38 chills / riots flank pain costo-vertebral angle tenderness nausea / vomiting
What are the risk factors for UTI
infancy abnormal urinary tract female bladder dysfunction / incomplete emptying foreign body diabetes mellitus renal transplant immunosuppressants
How are UTIs diagnosed?
multisite
microscopy / flow cytometry
urine culture
Describe urine culture for UTI
obtain before starting antibiotics
clean catch supra pubic aspiration, catheter specimen
Describe antibiotics treatment of UTI
IV - ceftriaxone, gentamicin
oral - trimethoprim , cephalosporin, co-ampxiclav, nitrofurantoin
What are the pros and cons of ultrasound in UTI?
radiation free
readily available
good for dilated drainage tracts and cysts
operator dependent
less sensitive for scarring, parenchymal damage
Describe MCUG pros and cons
gold standard for VUR and PUV
radiation
invasive - UTI risk
Describe DMSA (static)
gold standard for scars ectopic - duplex differential fucntion timing - acute or chronic differentiating scars vs dysplasia radiation
Describe MAG3 indirect cystogram
used for VUR study with no catheter needed
differential function
need continence and cooperation on bladder emptying
no PUV info available
misses low grade VUR
Describe MAG3 diureses renogram
gold standard for obstruction
furosemide also needed
operator interpretation
What are the risk factors for renal scarring?
age high grade VUR anatomical obstruction dysfunctional voiding frequent episodes of APN therapeutic delay bacterial virulence factors host response low birth weight prenatal dysplasia
Name congenital abnormalities of jidey and urinary tract (CAKUT)
vesico-ureteric reflux (VUR)
obstruction of urinary drainage tracts
Describe VUR
retrograde passage of urine from the bladder to the upper urinary tract
higher risk of UTI and pyelonephritis
some will resolve spontaneously
