A. KIDNEY DISEASE Flashcards
(51 cards)
1
Q
what is AKI
A
- 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
2
Q
what is AKD
A
- 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)
3
Q
what is CKD
A
- 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
4
Q
kidney disease progression
A
- AKI to AKD (both can have recovery)
- AKD to CKD to (AKI-on-CKD during progression) ESRD which requires renal replacement therapy (dialysis, transplant)
5
Q
what is maladaptive repair
A
- development of fibrosis
- delayed resolution of pathology/inflammation
6
Q
what is adaptive repair
A
- clear debris by macrophages
- proliferation to restore tubular epithelial cell layer
- resolution of pathology/inflammation
7
Q
what risk factors contribute to progression
A
- 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
8
Q
AKI
A
- 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
9
Q
what are the 3 types of causes of AKI
A
- pre-renal: occurs before the kidney - reduced perfusion to kidney (80%)
- intrinsic (or intrarenal): nephrons
- post-renal: ureter, bladder, urethra
10
Q
main causes of pre-renal AKI
A
- low renal perfusion
- dehydration (esp elderly)
- medicines which can impact on hydration, will further decrease perfusion (diuretics, antihypertensives, laxatives) - withhold if have AKI
11
Q
what drugs exacerbate AKI or are unsafe to use and so should be withheld
A
DAMN
- Diuretics
- ACE inhibitors, AIIRAs
- Metformin
- NSAIDs
CANDA
- Contrast media
- ACE inhibitors
- NSAIDs
- Diuretics
- AIIRAs
*dose adjustment guided by clinical judgement and drug monitoring
12
Q
definition of CKD
A
- long-term, progressive, irreversible loss of nephrons
- either through disease/damage or ageing
13
Q
clinical definition of CKD
A
- presence of kidney damage or
- GFR < 60 m L/min/1.73m2
- persisting for ≥ 3 months
- irrespective of cause
14
Q
prevalence of CKD in UK
A
- 13-14% adults (age ≥16)
- 6% UK (age ≥16) with CKD stages 3-5
- higher prevalence in males
15
Q
difference in CKD vs AKI
A
- 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)
16
Q
causes of CKD
A
- 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)
17
Q
cycle of how CKD leads to ESRD
A
- 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
18
Q
how is an asymptomatic patient with CKD diagnosed (adaptation)
A
- blood/urine tests
19
Q
when do clinical symptoms show with CKD
A
- 75%-80% nephron loss
- stage 4/5 (near ESKD)
20
Q
how can CKD lead to ESKD
A
- 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
21
Q
what drugs slow down progressive loss of kidney function (by decreasing glomerular pressure)
A
- ACEIs
- AIIRAs (renoprotective)
- SGLT2 inhibitors (dapagliflozin)
22
Q
how is angiotensin II converted to angiotensin I IN RAAs
A
- renin from JG cells
23
Q
how is angiotensin I converted to angiotensin II
A
- angiotensin-converting enzyme (ACE)
24
Q
what does angiotensin II trigger
A
- vasoconstriction
- aldosterone release from adrenal cortex
25
what does vasoconstriction cause
- efferent arteriole being narrower than afferent arteriole
- increased filtration pressure and GFR
26
what effect does aldosterone cause
- increased Na+ and water reabsorption
- increased K+ (from P-cells) and H+ secretion (from H+ cells)
27
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
28
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
29
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
29
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
30
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
31
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
32
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
33
how do you treat renal anaemia
- supplemental iron (and folate) may be required
- erythropoiesis-stimulating (RBC production) agents (ESA) such as epoetin alfa, beta
34
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)
35
what is alfacalcidol
- l-hydroxy attached to vitamin D so need metabolism to get 25-hydroxy added to make it calcitriol
36
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)
37
how do you treat CV disease
statins
38
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
39
what substances are affected by altered glomerular filter integrity and what are the consequences
- protein: proteinuria
- RBCSs: haematuria
40
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
41
what substances are affected by decreased biosynthesis (stages 4/5) and what are the consequences
- EPO: anaemia
- activation of vitamin D: osteodystropy (hypocalacaemia)
42
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)
43
how is EPO production affected in chronic renal failure
- decreased
- leads to renal anaemia due to insufficient production of RBCs
44
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)
45
what homeostatic mechanism is activated vitamin D involved in
calcium homeostasis
46
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
47
what effect does PTH have on actions of vitamin D
- permissive actions
- 1alpha-hydroxylase synthesis and activity (and hence synthesis of calcitriol) requires PTH
48
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
49
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)
50
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)
