renal disease Flashcards
prevalence of kidney disease
Up to 10% pop have some aspect of kidney disease
it is part of other conditions - HTN, dm
UTI
o Really common o Kidney tract problem o Usually just infection in bladder o E coli bacteria line bladder wall Lifetime risk for females 10-30% • Lead to 3 million GP visits per year in UK
ways renal disease can present
• Haematuria • Proteinuria • Nephrotic syndrome • Nephritic syndrome • Hypertension • Acute kidney injury • Chronic kidney disease Urinary tract infection • Abdominal pain • Complications of hypertension (esp malignant hypertension) • Oliguria or anuria • Polyuria, nocturia - often a metabolic problem – nothing wrong with kidneys
how long are the kidneys
about 3 vertebral bodies
dark white in kidney in CT
excreting contrast in collecting system
summarise anatomy of the kidney and tubule
• Glomerulus fed by arteriole – comprises of capillary tuft
o Blood leaving glomerulus is blood supplies around tubules
o Filtrate goes through the tubules
o Cortex contains glomerula
o Medulla – loop of henle and collecting duct
what is the renal parenchyma made of
cortex and medulla
summarise the anatomy and the function of the glomerulus
it is the filtering unit of the kidney
blood enters cap tuft through afferent arteriole
under high pressure the fluid is pushed out of the blood vessel - ceels and proteins are retained in the capillary lumen
specialised filtration to allow this:
Endothelial cell layer of capillaries has pores
–Glomerular basement membrane
–Epithelial cells (podocytes) with slit membranes
blood leaves glomerulus by efferent arteriole
filtrate passes into Bowman’s capsule and into tubule,
becoming urine
role of podocytes
allow you to filtrate the blood but maintain blood cells and protein in blood
functions of the kidney
Filtration and excretion of waste products
Electrolyte homeostasis
Blood pressure control via renin/angiotensin/aldosterone axis
prostagladins and bradykinin
Acid Base homeostasis
what hormones does the kidney produce
Erythropoietin (epo) – red blood cell production
1,25 Calcitriol (active vitamin D) – calcium, phosphate and
bone metabolism
what are the manifestations in patients when kidney function goes wrong
anaemia - because not making epo, cause fatigue acidosis bone fractures poor clearance of waste = fatigue reduced excretion of many drugs electrolyte abnormalities eg high potassium, low calcium, low or high sodium… impaired fluid balance high blood pressure
treatability of manifestations of when kidney func goes wrong
anaemia - treatable with epo replacement
acidosis - treatable with bicarbonate
bone fractures- treatable by lowering serum phosphate,
replace active vitamin D, suppress PTH
poor clearance of waste - when v poor only
replaceable by dialysis or a transplant
reduced excretion of many drugs - avoid nephrotoxic
drugs and amend drug doses
electrolyte abnormalities - need correcting
impaired fluid balance - oedema usually (excess fluid)
high blood pressure - needs treatment
why not just use creatinine to assess kidney ‘cleaning’ func
a product of metabolism of muscle creatine and
phosphocreatine – so muscle mass make big diff to blood creatinine levels
sex difference
so having same blood creatinine doesnt mean have same kidney function
Freely filtered and not reabsorped but there is tubular
secretion
what is glomerular filtration
Most common test of kidney function
• Determines the clearance of a substance from the plasma
• Does not determine the cause for kidney disease
what is GFR
• Sum of the filtration rates of all functioning nephrons
• Normal 120-130ml/min/1.73m2
• Depends on age, sex, body size, muscle mass
• Reduced GFR means loss of filtering capacity and
accumulation of waste products
how do you measure GFR
No direct measurement
• Estimated from urinary clearance of an ideal filtration marker
from the plasma per unit time
what is an ideal marker for measuring GFR
freely filtered solute, not secreted or
reabsorbed by the kidney, not metabolised by the kidney
ie it is only removed from the body by the kidney - see how fast this happens
markers used for measuring GFR
• Inulin – best molecule, but too complex to use in practice - not used Radioactive markers (eg EDTA, iothalamate, iohexol) – expensive, low dose radioactivity, takes 2-4h and iv injection, need blood test, or radioactive body count? - cant do it regularly Creatinine – good endogenous substance • Cystatin c – probably best marker but not widely available - not affected by muscle mass
summarise eGFR
GFR determined from serum Creatinine or Cystatin C is an
ESTIMATED GFR
how is creatinine used to determine eGFR
Used to be common to collect 24 hour urine samples to
measure Creatinine clearance as measure of GFR (from urine
creatinine, serum, urine volume)- not now (– difficult to do – people forget some samples)
based on mathematical eqn
Cockcroft Gault: includes body weight and creatinine
eGFR from MDRD or CKD-EPI or other Equations: uses serum
creatinine and age only
problems with eGFR
still uses creatinine
Only relevant in stable patients, not for AKI, dependant on
muscle mass
USEFUL if have serial measurements
urine dip
helps tell where the problem is and guides investigations Especially if protein or blood bedside investigation
causes of red/brown urine
– myoglobinuria (from rabdomyolysis - muscle crushing trauma) or haemoglobinuria
– food dyes or beetroot ingestion
– porphyria
– rifampicin
causes of white urine
pyuria, phosphate crystals, chyluria
causes of black urine
haemoglobinuria , alkaptonuria
what does proteinuria indicate
glomerular problem/damage (usually)
Can be a benign variant (Orthostatic proteinuria)
how do you assess proteinuria
urine dipstick tells you that it is present
need to quantitate
spot urine Protein:creatinine ratio (PCR) or
albumin:creatinine ration (ACR)
?? normal up to 30 - low level protein excretion
what is AKI
A rapid decline in renal function over hours or days
with:
Accumulation of (nitrogenous) waste products
Potentially life threatening metabolic consequences
With or without reduction in urine output.
definition of AKI
Serum creatinine rise by greater than 26 umol/L within 48 hrs
OR
Serum creatinine rise 1.5 x from the reference value which is
known or presumed to have occurred within one week
OR
Urine output is less than 0.5ml/kg/hr for 6 consecutive hours
what reference serum creatinine should be used
lowest creatinine
value recorded within 3 months of the event
different stages of AKI
1 - Serum creatinine rise by greater than 26 umol/L within 48 hrs, Urine output is less than 0.5ml/kg/hr for 6 consecutive hours
2 - SCr increase >=2-2.9 fold from baseline, <0.5mL/Kg/h for 12hr
3 - SCr increase >=3 fold from baseline, or >=354umol/L or initiated on RRT, Urine output is less than 0.5ml/kg/hr for 24 consecutive hours or anuria for 12hr
is minor AKI fine
no - can be critical
associated with significant
increase in mortality from other conditions
seeing AKI as a spectrum of disease
normal - increased risk - damage - reduced GFR - kidney failure - death
o Want to recognise people at increased risk – flag to minimise risk they progress down route
o Route reversible in most pts but not always
why is it important to recognise RF for AKI
occurs most commonly in patients who are at risk, who
either are acutely ill or have had major surgery
allows simple preventative
measures, eg ensuring adequate hydration, consideration of drugs, regular blood tests
RF for AKI
Age >75 years
• Pre-existing CKD (eGFR <60 mL/kg/1.73 m2)
• Previous episode of AKI
• Debility and dementia
• Heart failure
• Liver disease
• Diabetes mellitus
• Hypotension (Mean arterial pressure <65mmHg, systolic BP <90mmHg)
• Sepsis
• Hypovolaemia
• Nephrotoxins, eg gentamicin, NSAIDs, iodinated contrast
• Continued antihypertensives in setting of hypotension, eg ACE
inhibitors, loop diuretics
3 categories of causes of AKI
pre-renal - blood flow into the kidney, all about volume - check BP, JVP and vol
intrinsic renal
post-renal - obstruction to outflow, need US
epidemiology
o 20% pre-renal – low bp, vol depletion
o 13% obstruction
o 45% intrinsic – acute tubular necrosis – multiple insult- sepsis, low bp, drugs = damage to kidney – tubules fallen apart, but reversible just need to get everything else right – vol and stop nephrotoxic agents
pre-renal causes of AKI
Hypovolaemia
low cardiac output
Hypotension
Renal artery thrombosis
renal
Acute tubular necrosis Glomerulonephritis Vasculitis Nephrotoxins, contrast, rhabdomyolysis Interstitial nephritis HUS/TTP Malignant hypertension Myeloma
post-renal
Ureteric obstruction Urethral obstruction Blocked urinary catheter Bladder tumour
difference between AKI and CKD
AKI - potentially reversible
CKD - impaired kidney function, usually
progressive, and potentially resulting in end
stage kidney disease (ESKD) over months to
years, often multifactorial. Not reversible
thought process when see high serum creatinine/reduced eGFR
is it acute/chronic
if acute - what is the cause? Is it treatable?
if chronic - can you identify cause, can progression be slowed, control and treat complications, plan for ESKD (dialysis, transplant, conservative care)
AKI presentation
Commonly non-specific symptoms
• Symptoms of uraemia (nausea, vomiting, anorexia)
• Features of the underlying disease
• Decreased urine output
• Systemic features (rash, myalgia, arthralgia, headaches)
• Abnormal biochemistry (rise in serum urea and creat)
• Acidosis, hyperkalaemia, salt and water retention
what are you looking for in AKI history
Duration
• Systemic features
• Past history, especially vascular, childhood renal disease,
UTI’s, diabetes, hypertension
• Family history, inc early death & strokes
• Drugs, inc herbals, over-the-counter medications (not
“drugs” esp analgesics), recreational drugs - – ketamine causes kidney problem
what are you looking for in AKI examination
For any features indicating cause • For features of systemic disease • Bladder? Palpable kidneys? • For complications • Volume status of patient • URINE analysis, microscopy
urine analysis in AKI
glomerular disease -Red cells, red cell casts,
proteinuria (often heavy)
tubular disease - minimal blood, small protein, granular or white cell casts - – nothing going down the tubule so no blood leaking from glomerulus – no blood in urine
pre-renal causes - no blood or protein. no casts
common causes of AKI
ATN ⧫ Functional - low BP and low flow ⧫ Myeloma ⧫ ATIN - inflammation in kidney caused by drugs ⧫ Athero-embolic ⧫ Rhabdomyolysis
exotic causes of AKI
⧫ Systemic vasculitis ⧫ Acute GN ⧫ Lupus Nephritis ⧫ Anti-GBM disease (Goodpasture’s disease)
what do you want to know when someone comes in with high creatinine
previous renal func ABG for hypoxia and acidosis Ca, phos US - see obstruction and size of kidneys CXR - for fluid overload, chest infection assessment of volume status urinalysis
investigations for AKI
volume status (for ATN) • Urine microscopy and dipstick • Imaging (U/S) *** Obstruction *** • ANCA, Anti-GBM, SLE immunology (ANA, dsDNA, complements) - if worried about glomerular disease • Creatinine kinase • FBC, clotting • Inflammatory markers • Myeloma screen (protein electrophoresis, urine BJP) - in older pts • May need biopsy
steps in AKI management
What is the cause? • What needs treating NOW? • Reverse underlying factors • Treat the cause if possible • Prevent and manage complications
complications in AKI that need managing
Potassium (kills) • Pulmonary oedema (kills) • Acidosis • Hypertension • Uraemia (brain, nerves, heart)
management of hyperkalaemia
Intravenous calcium • Insulin and dextrose • Nebulised salbutamol • Calcium resonium or newer binding agents eg SZC or patiromer • Dialysis
what are you thinking AKI wise if see purpuric rash o/e
need to consider immunology
if see small scarred kidneys on US what does this suggest
CKD
if in young person: either congenital o Or childhood reflux nephropathy and UTIs - asymptomatic mostly
means dont have to start dialysis straight away
what is CKD
• A “syndrome” for which there is a cause, although
often not identified
Often first presentation is at end stage
• Kidneys may be normal size, but often small
what is the aim of management for CKD
identify cause if possible,
treat and prevent complications, slow progression,
plan for future ESKD
how is CKD defined
by GFR:
GFR 60-90 and no other evidence- not CKD, if do have other evidence- could be chronic eg on US
as albuminuria gets worse = worse outcomes overall = higher death rate and risks of CVS complications
prevalence of CKD
high - increasing by age
most common in elderly with comorbidities
RF for chronic kidney disease
Elderly Hypertension Diabetes IHD Family History CKD African American Obesity
causes of CKD
Diabetes (~30%)
• Chronic glomerulonephritis (~30%)
• Vascular diseases including hypertension, ischaemic heart
disease (~15%)
• Autosomal dominant polycystic kidney disease (~10%)
•Congenital/reflux/childho0d infections
• Genetic risks .. with another insult (eg ApoL1 risk variants
in black patients)
investigating CKD
Identify cause - important for progression, systemic
features, recurrence after transplant …. This might
be treatable
• Ensure patient understanding
• Ensure regular follow-up
• Investigate for complications (metabolic, CV, BP,
proteinuria)
complications of CKD
AKI
CVS mortality
kidney failure
preventing progression of CK D
BP control, ACEi/ARB and reducing proteinuria, SGLTi drugs - slows down eGFR decline (irbesartan reduces incidence of dm nephropathy)
minimise other CV risks - smoking
encouraging exercise, low salt and low protein, measure BP, take med even when asymptomatic
effect of SGLT2 inhibitors in CKD
slow progression of renal disease in CKD, reduce deaths, reduce CV morbidity, reduce hospitalisations
management of CKD
Encourage/support /activate patients to understand this
BP < 125-130/75-80 (usually 3+ drugs), lower BP target
if proteinuria
ACEi/ARB .. More ACEi/ARB … Maximal doses
• Second and third line agents for BP and proteinuria
• Reduce proteinuria as much as possible
• CV risks (aspirin, statins, ezetimibe ..)
• Stop smoking, encourage exercise, healthy diet, avoid
nephrotoxins eg NSAIDs
avoid dehydration
how does CKD affect bv
calcification of bv = CVS, atheroma = narrowing of vessels
treat calcification by treating the BP
what is nephrotic syndrome
(heavy proteinuria, oedema, hypoalbuminaemia)
proteinuria
Incidental finding to full blown nephrotic syndrome
pt concern is swollen legs, painful, limit walking
Normal protein < 300 mg/day (U PCR < 30 mg/mmol)
• Nephrotic > 3 g/day (Urine PCR > 300 mg/mmol)
• Urine Protein:creatinine ratio < 30 “normal”
100 ~ 1 g/day
300 ~ 3 g/day
o Albumin creatinine ratio in urine – if >3 seen as abnormal – sign of microalbuminae in dm. could still be normal if not dm
what is the most useful investigation for proteinuria
kidney biopsy
Quantitate proteinuria (urine protein:creatinine
ratio)
• Serum albumin and cholesterol
• Serum creatinine, U+Es
• Glucose, SLE tests, virology - can cause nephrotic syndrome (Hep B,C and HIV),
myeloma screen
causes of proteinuria
ALWAYS indicated glomerular pathology • Diabetes • Minimal change (glomerular) disease (and FSGS) • Membranous nephropathy • Amyloid • SLE
management of proteinuria
Control oedema – low salt diet, diuretics
• ACEi/ARB (reduce proteinuria)
• Treat the cause ! (if possible)
• Sometimes steroids or immunosuppression
• Uncontrolled proteinuria is a major risk for
progressive CKD and ultimate ESKD
do you need to do a cystoscopy for people with haematuria
not gor everyone
Look in bladder if worry had bladder cancer – but only 24yr, unless other RF
Has a kidney problem
If he were 50yr – would defo need cystoscopy
approach to haematuria
With pain – think urological cause ie stones or cancers
(kidneys, ureter, bladder, prostate)
• Age > 40 years, must exclude cancer in urinary tract
• BUT age < 40 or protein also present, most likely
intrinsic microscopic renal (glomerular) cause
may need kidney biopsy
glomerular injury causing haematuria
Thin glomerular basement membrane disease or
variant eg Alport’s syndrome
IgA nephropathy
investigations for haematuria
If “surgical” or cancer/stone most likely – start
with imaging (US, CT) and cystoscopy
If cause within kidney glomerulus most likely –
check urine for protein, eGFR, then blood tests for
underlying systemic or immune disease, then
possibly renal biopsy.
management of end stage kidney disease
No recovery possible
• Need dialysis or a transplant or decide not to do
either and treat symptoms (conservative care)
