Week 6 Flashcards
Functions of the kidneys
Homeostasis:
-water/fluid
-electrolytes
-acid-base
-blood pressure
-elimination of waste
-excretion of drugs and drug metabolites
Metabolic/endocrine:
-synthesis of hormones
— vitamin D
— erythropoietin
—renin
Measurement of glomerular filtration rate
Gold standards but not used clinically
Exogenous filtration markers:
-e.g inulin, 51Cr-EDTA
-require injection or infusion
-require multiple sample collection
-cumbersome, intrusive
Endogenous filtration markers:
-eg urinary clearance of creatinine
-requires accurate timed urine collection and matched serum sample
-cumbersome and error prone
Only used rarely for specific purposes when clinical decisions depend on accurate knowledge of GFR
Estimation of GFR from serum creatinine
Creatinine from breakdown of muscle and gets cleared by kidneys
Limitation 1:
-Non linear relationship between serum creatinine and GFR. Small changes in serum creatinine value can mean large changes in GFR
Non renal determinants of serum creatinine include:
-age
-sex
-ethnicity
-body habitus
-diet
Limitation 2:
-creatinine is an end product of muscle turnover, creatinine generation is proportional to muscle mass
-creatinine can also be derived from dietary meat or creatinine supplements
Quantification of proteinuria
Injured, inflamed or damaged glomerulus/kidneys will leak protein
Bad prognostic factor in terms of progression of cKD, increase risk CVD and mortality
Concentration of any analyte in urine is heavily influenced by concentration or urine
Measure total amount: protein excretion in 24 hrs urine sample
Measure ratio to reference analyte (known conc.): protein:creatinine ratio or albumin:creatinine ratio to estimate protein in urine
Definition of chronic kidney disease
CKD is defined as abnormalities of kidney structure or function, present for> 3 months with implications for health
Albuminuria
Urine sediment abnormalities- blood or RBC casts
Structural abnormalities etc
Decreased GFR
Classification of CKD
Stage 1: normal kidney function GFR>90ml/min but proteinuria or blood etc
When estimating GFR with creatinine cant go up to 120 as EGFR increases confidence of measurement decreases
Moderate stage 3A 3B- CKD with reduced renal function
Severe stage 5 GFR<15
Irreversible loss of renal filtration function (loss of nephrons)
Progressive loss of renal filtration function if untreated irreversible damage
Stage 5 CKD end stage renal failure
Insufficient renal function to sustain life/health
Haemodialysis, peritoneal dialysis
Kidney transplantation
Death
Relative risks for adverse outcomes
Knowing if someone has proteinuria helps determine the cause
Helps narrow down investigations and find cause CKD, do biopsy because we’re looking to see the type of inflammatory disease so can treat appropriately
Proteinuria increases rate at which CKD progresses
Who has renal disease
Common with Uk population
Significant proportion unrecognised
Important risk factors are:
-age
-social deprivation
-black or south Asian ethnicity
-hypertension
-diabetes
-smoking
Causes of CKD
Diabetes- diabetic kidney disease
Hypertension/ischaemic
Glomerulonephritis
Genetic
Other
Diabetic nephropathy
Diabetic kidney disease
Renal disease occur 40% patients with type I and 2 diabetes
40% patients with ESRF in US and 20% in Europe
Associated with poor diabetes control and hypertension
Characterised by proteinuria
Correlation with diabetic retinopathy
If you have microvascular disease elsewhere likely to get it in kidneys
Pathology of diabetic nephropathy
Thickening of basement membrane
Mesangial expansion . Get collagen deposits and fibrosis
-hyperglycaemia stimulates increased matrix production by mesangial cells
-stimulation of TGF-beta release
Glomerulosclerosis due to intraglomerular hypertension or ischaemic damage
Hyperglycaemia causes vasodilation of afferent arterioles increasing glomerular pressure (so people with diabetic KD at first hyperfiltrate slight increase in GFR) then causes damage with time starts to develop proteinuria and reduce kidney function
Natural history of diabetic nephropathy
Onset of diabetes:
-increased GFR
-reversible albuminuria
-increased kidney size
After ~5 years :
-increased glomerular basement membrane thickness
-mesangial expansion
Mircoalbuminuria and rising blood pressure
11-23 years: onset proteinuria
13-25 years: rising serum creatinine
15-27 years: ESRF
Inevitable decline in renal function over 7-10 years
Treatment diabetic nephropathy
Treat underlying cause: good blood sugar control (diet and medications)
Reduce proteinuria: ACE inhibition and SGLT2 inhibitor
Limit cardiovascular risk: control blood pressure, treat hyperlipidaemia stop smoking etc
Hypertensive nephropathy
Vascular remodelling (atherosclerosis, intimal thickening) leading to narrowing of blood vessels and glomerular ischaemia
Glomerular hypertension causing injury and sclerosis over prolonged periods
Progressive kidney disease, progressive fibrosis
Thickened intima
Segmented sclerosis scarring glomeruli more lesions, more scarring nephrons, lose functional nephrons progressive CKD
Renovascular disease
Because of atherosclerosis can disrupt blood supply to kidneys
Renal artery stenosis
Likely to have hypertension and CVD cKD due to other reasons as well
Glomerulonephritis
Immune mediated injury to glomeruli
Characteristic changes in kidney histology and immunohistochemistry
Typically blood and/or protein in urine
Immunocomplex formation and deposition in glomeruli that causes damage
Many different disease processes:
-e.g IgA nephropathy (most common)
-can be associated with infection (e.g streptococcus, HIV)
-can be part of systemic disease process (e.g systemic lupus erythematosus, vasculitis)
Autosomal dominant polycystic kidneys
Most common genetic cause
Autosomal dominant most common manifests in adulthood
There are recessive forms too that manifest in childhood
Large cysts, large kidneys, very painful. Cysts can rupture- painful can cause haematuria
Loss nephrons due to cysts displacing functional tissue
Affects ~1 in 1000 people
Other causes of CKD
-Medications (NSAIDs, chemotherapy, others)
-recurrent urinary tract infection
-urinary outflow obstruction- common, benign hyperplasia
-trauma uncommon
-interstitial nephritis
-recurrent/persistent acute kidney injury
Complications related to CKD
Increased mortality, cardiovascular disease and hypertension. Altered drug handling
Anaemia, vitamin D, phosphate and parathyroid disturbance
Acidosis, hyperkalaemia
Fluid retention, uraemia
Cardiovascular risk in CKD
Traditional risks: diabetes, hypertension, dyslipidaemia, smoking
Non classical risks: endothelial dysfunction, inflammation, oxidative stress, catabolic state
CKD-related risks: fluid retention, anaemia, hyperparathyroidism, vascular calcification
Hypertension
Multiple mechanisms:
-sodium retention
-volume expansion
-renin-angiotensin-system activation
-sympathetic nervous system activation
-endothelial dysfunction
Accelerates decline of kidney function
Contributes to cardiovascular risk (stroke, myocardial infarction, heart failure)
Management:
-moderate salt intake
-RAS blockade
-diuretics
-other anti-hypertensive medications
Vitamin D, calcium and parathyroid hormone in renal failure
Vitamin D not activated in kidneys
So serum calcium not increased
Constant secretion of PTH and bone resorption
Cycle repeats not corrected autonomous production PTH by parathyroid glands. Secondary and tertiary hyperparathyroidism
Major risk factor for calcium deposition in blood vessels
Renal bone disease
Brown tumour
Rugger jersey spine
Ectopic calcification
Calcium depositions in blood vessels
Risk factor of CVD
How to manage mineral bone disease
Correct global vitamin D deficiency if present (colecalciferol, ergocalciferol)
Supplement activated vitamin D (Alfacalcidol, calcitriol)
Control high phosphate levels (dietary restriction, phosphate binders)
Offer calcimimetics -stop producing PTH
Last resort: parathyroidectomy
Anaemia
Impact:
-impaired quality of life
—reduced exercise capacity
—impaired cognition
-increase risk of left ventricular hypertrophy
-increase CV disease in patients with CKD and anaemia vs those with CKD without anaemia
Management:
-correct iron deficiency if present, helps RBC production
-recombinant erythropoietin: supplement what kidneys cant produce stimulate bone marrow to produce RBCs
Bicarbonate- carbonic acid buffer system
PH= pK+logHCO3-/H2CO3-
With progressive kidney disease you fail to excrete H+, reabsorb serum HCO3- and metabolic acidosis
Increase CO2 removed by lungs to maintain pH
Metabolic acidosis
Impact:
-increased respiratory rate
-acute-life threatening metabolic dysfunction
-chronic- loss of bone and muscle mass
Management :
- sodium bicarbonate
-dialysis (or transplantation)
Hyperkalaemia
Enormous functional reserve to excrete potassium
Severe hyperkalaemia when GFR<10ml.min
Due to:
-excessive load
-interference with potassium excretion
— acidosis with volume contraction
— diabetic nephropathy
Alterations in membrane excitability
Cardiac arrhythmias
ECG changes:
-tall T waves
- long QRS interval
-long PR interval
-cardiac arrest
How to manage hyperkalaemia
Input side:
-dietary potassium restriction
-potassium binders- dont use in clinical practice
Output side:
-dialysis (or transplantation)
Determinants on when to start:
-how patient feels- degree of uremia
-losing weight, vomiting etc
-EGFR<10ml/min
Sodium and fluid retention
Loss of nephrons reduces ability to excrete salt and water
Major cause of hypertension and fluid overload
Sodium must be within normal range for normal neurological function
High or low sodium leads to confusion, fits and coma
Failure of fluid homeostasis
Inability to concentrate urine (early):
-loss of diurnal rhythm of urine excretion
Inability to excrete water load:
-dilutional hyponatraemia
-oedema- pitting oedema, painful
-hypertension
How to manage fluid overload
Input side:
-salt restriction
-fluid restriction
Output side:
-diuretics
-dialysis or transplant
