A. KIDNEY DISEASE Flashcards
what is AKI
- an abrupt decrease in kidney function that occurs within 7 days (no structural abnormalities)
- an increase in SCr by 50% within 7 days or
- an increase in SCr by 0.3mg/dl (26.5 micromol/l) within 2 days or
- oliguria for ≥6 hours
*included in AKD and CKD
what is AKD
- patients who have functional/structural abnormalities with implications for health
- ≤ 3 months
- AKI or
- GFR <60ml/min/1.73m2 or
- decrease in GFR by ≥35% or
- increase in SCr by >50%
- marker of kidney damage (albuminuria, hematuria, pyuria)
what is CKD
- abnormalities in kidney structure or function that persists for >3 months
- GFR < 60ml/min/1.73m2
- marker of kidney damage (albuminuria)
- can include AKI and AKD
*classified according to CGA classification
kidney disease progression
- AKI to AKD (both can have recovery)
- AKD to CKD to (AKI-on-CKD during progression) ESRD which requires renal replacement therapy (dialysis, transplant)
what is maladaptive repair
- development of fibrosis
- delayed resolution of pathology/inflammation
what is adaptive repair
- clear debris by macrophages
- proliferation to restore tubular epithelial cell layer
- resolution of pathology/inflammation
what risk factors contribute to progression
- severity/frequency of AKI (AKI-on-CKD if have a number of times)
- age
- sex (males have faster rate)
- pre-existing CKD
- albuminuria
- hypoalbuminaemia
- hypertension
- obesity
- DM
AKI
- rapid loss of kidney function
- sudden onset of renal impairment – (within 7 days)
- range from mild renal dysfunction to the need for renal replacement therapies (RRTs)
- outcomes: recovery, AKD with recovery, CKD (possibly to ESRD), ESRD or death
what are the 3 types of causes of AKI
- pre-renal: occurs before the kidney - reduced perfusion to kidney (80%)
- intrinsic (or intrarenal): nephrons
- post-renal: ureter, bladder, urethra
main causes of pre-renal AKI
- low renal perfusion
- dehydration (esp elderly)
- medicines which can impact on hydration, will further decrease perfusion (diuretics, antihypertensives, laxatives) - withhold if have AKI
what drugs exacerbate AKI or are unsafe to use and so should be withheld
DAMN
- Diuretics
- ACE inhibitors, AIIRAs
- Metformin
- NSAIDs
CANDA
- Contrast media
- ACE inhibitors
- NSAIDs
- Diuretics
- AIIRAs
*dose adjustment guided by clinical judgement and drug monitoring
definition of CKD
- long-term, progressive, irreversible loss of nephrons
- either through disease/damage or ageing
clinical definition of CKD
- presence of kidney damage or
- GFR < 60 m L/min/1.73m2
- persisting for ≥ 3 months
- irrespective of cause
prevalence of CKD in UK
- 13-14% adults (age ≥16)
- 6% UK (age ≥16) with CKD stages 3-5
- higher prevalence in males
difference in CKD vs AKI
- long duration of symptoms
- absence of acute illness
- anaemia
- hyperphosphataemia, hypocalcaemia (but similar laboratory findings may complicate AKI)
- reduced renal size and cortical thickness on renal ultrasound (but renal size is typically preserved in patients with diabetes)
causes of CKD
- DM (1 - most common cause to ESKD), hypertension (2), obesity
- renal vascular disorders: atherosclerosis, nephrosclerosis
- immunological disorders: SLE, glomerulonephritis (3)
- infections: pyelonephritis, TB
- nephrotoxins (NSAIDs, heavy metals)
- UT obstruction (kidney stones, hypertrophy of prostate)
- polycystic kidney disease (4)
cycle of how CKD leads to ESRD
- primary kidney disease
- decreased nephron number
- hypertrophy and vasodilation of surviving nephrons (surviving nephrons adapt as there is an increase in structural features) ADAPTIVE CHANGES
- increased glomerular pressure and/or filtration
- maintain excretion of water/solutes (near normal function)
*over time these functional changes may lead to further injury
how is an asymptomatic patient with CKD diagnosed (adaptation)
- blood/urine tests
when do clinical symptoms show with CKD
- 75%-80% nephron loss
- stage 4/5 (near ESKD)
how can CKD lead to ESKD
- primary kidney disease
- decreased nephron number
- increased arterial pressure caused by decreased fluid excretion
- hypertrophy and vasodilation of surviving nephrons (surviving nephrons adapt as there is an increase in structural features) ADAPTIVE CHANGES
- increased glomerular pressure and/or filtration
- glomerular sclerosis (stress on capillaries and scarring, less elastic and able to cope with pressures)
- decreased nephron number
- ESRD
what drugs slow down progressive loss of kidney function (by decreasing glomerular pressure)
- ACEIs
- AIIRAs (renoprotective)
- SGLT2 inhibitors (dapagliflozin)
how is angiotensin II converted to angiotensin I IN RAAs
- renin from JG cells
how is angiotensin I converted to angiotensin II
- angiotensin-converting enzyme (ACE)
what does angiotensin II trigger
- vasoconstriction
- aldosterone release from adrenal cortex
what does vasoconstriction cause
- efferent arteriole being narrower than afferent arteriole
- increased filtration pressure and GFR
what effect does aldosterone cause
- increased Na+ and water reabsorption
- increased K+ (from P-cells) and H+ secretion (from H+ cells)
how do ACEIs act as renoprotective agents
- block ACE
- hence decreases angiotensin II levels
- decreases vasoconstriction at efferent arteriole
- decrease in blood pressure, renal blood flow, GFR
- decreased intraglomerular pressure and glomerular sclerosis
- decreases aldosterone levels
- decreased Na+ and water reabsorption
- decreased K+ and H+ secretion so get a decreased blood volume and hyperkalaemia
ACEIs causing renal impairment
- patients with reduced renal perfusion such as renal vascular disease, bilateral renal artery stenoses
- get a further decrease in GFR ie further ischaemia of kidney
how do SGLT2 inhibitors work in CV
- mild natriuresis and glucose-induced osmotic diuresis
- decrease in blood volume and blood pressure
- decrease in intraglomerular pressure
- decrease in glomerular sclerosis
*Cardiovascular & renal benefits manifest rapidly, unlikely to be related to improvement in glycaemic control
*SGLT2 inhibitors are used in the management of T2DM, CHF and CKD
how do SGLT2 inhibitors work in renal impairment (flozins - dapagliflozin, canagliflozin, empagliflozin)
- reversibly inhibit SGLT2 in renal PCT to reduce glucose reabsorption and increase urinary glucose excretion so there is a decrease in blood glucose
signs and symptoms of CKD
- none, often asymptomatic (stages 1-3)
- nausea, vomiting (acidosis)
- loss of appetite and weight loss
- itching
- confusion, seizures
*uraemic toxins - ankle swelling (oedema)
- shortness of breath (oedema, anaemia, acidosis)
- weakness, fatigue (anaemia)
- altered urine output
what factors cause progression of chronic renal disease and how can we control the modifiable risks
- advancing age
- sex (male, AMAB>female, AFAB)
- race (black African/caribbean, asian)
- socio-economic status (if lower, faster rate)
- hypertension: blood pressure control
- proteinuria: ACEIs or AIIRAs by decreased intraglomerular pressure and hence the rate
- obesity: weight loss
- dyslipidaemia; statins
- smoking: smoking cessation
- diabetes control: good glycemic control
what are the aims of management
- identify patients with CKD
differentiate from AKI
establish aetiology if possible
establish severity - treat underlying reversible causes
- reduce CV risk (controlling modifiable risk factors)
- delay or prevent progression (controlling modifiable risk factors)
- treat complications
- dialysis preparation for those with progressive disease
how do you treat renal anaemia
- supplemental iron (and folate) may be required
- erythropoiesis-stimulating (RBC production) agents (ESA) such as epoetin alfa, beta
how do you treat renal bone disease
- vitamin D analogues (alfacalcidol and calcitriol)
- phosphate binders (e.g. calcium carbonate, sevelamer)
- dietary restriction of high phosphate foods (low protein, low dairy)
what is alfacalcidol
- l-hydroxy attached to vitamin D so need metabolism to get 25-hydroxy added to make it calcitriol
how do phosphate binders work
- collate phosphate in stomach and gut to decrease absorption from food substances
- if you have hyperphosphatemia or if you break down bone to get calcium you get increased phosphate levels)
how do you treat CV disease
statins
what are renal replacement therapies
- long term dialysis: haemodialysis (connected to machine) and peritoneal dialysis (in patients own body to remove toxins) which relieves uraemia symptoms and detoxify
- kidney transplantation: therapy of choice for ESRD - cadaveric or living donor transplantation
what substances are affected by altered glomerular filter integrity and what are the consequences
- protein: proteinuria
- RBCSs: haematuria
what substances are affected by decreased excretion and what are the consequences
- creatinine: increased serum creatinine conc and decreased eGFR
- uraemia toxins: excess of amino acids and protein metabolic end-products: uraemia
- salt/water: hypertension, oedema
- acid: metabolic acidosis
- potassium: hyperkalaemia
- phosphate: hyperphosphatemia
what substances are affected by decreased biosynthesis (stages 4/5) and what are the consequences
- EPO: anaemia
- activation of vitamin D: osteodystropy (hypocalacaemia)
how does erythropoietin work
- decreased oxygen delivery to the kidney
- peritubular fibroblast-like cells produce EPO (interstitium of cortex/outer medulla)
- EPO stimulates erythropoiesis by the bone marrow stem cells
- increased red blood cell production restores oxygen levels back to normal (homeostasis)
how is EPO production affected in chronic renal failure
- decreased
- leads to renal anaemia due to insufficient production of RBCs
how is activated vitamin D made
- vitamin D3 (cholecalciferol) from skin (made from radiation) and diet (egg yolk, fish, fortified cereals)
- converted to 1,25-dihydroxycholecalciferol (1,25-dihydroxyvitamin D3, calcitriol)
- by the liver (25alpha-hydroxylase) then the kidney (1alpha-hydroxylase)
what homeostatic mechanism is activated vitamin D involved in
calcium homeostasis
what effect does activated vitamin D have on the body
- intestines: increased calcium and phosphate absorption (from digested foods)
- kidneys (weak): increased calcium and phosphate reabsorption
what effect does PTH have on actions of vitamin D
- permissive actions
- 1alpha-hydroxylase synthesis and activity (and hence synthesis of calcitriol) requires PTH
how can we elevate plasma calcium levels
- increase in intestinal calcium absorption by vitamin D
- increase in renal calcium reabsorption by PT§H and vitamin D
- increase resorption of calcium and phosphate from bone by PTH
how is vitamin D synthesis affected in advanced CKD (chronic renal failure)
- low levels of calcitriol as not a lot of 1alpha-hydroxylase activity
- hence decreased plasma calcium leads to increased PTH secretion (acts to increase calcium levels)
how does decreased calcitriol levels in chronic renal failure
- hypocalacaemia leads to hyperparathyroidism
- increased PTH leads to: resorption of bone and calcium release and hence impaired bone mineralisation
(renal osteodystrophy/renal bone disease - bone pain, joint pain, bone deformation, bone fracture, poor mobility)
