L24 Chronic kidney disease and renal replacement therapy Flashcards
What is the definition of chronic kidney disease?
3
Progressive, irreversible impariment of renal function > 3 months, as evidenced by
- GFR <60ml/min/1.73^2
- Albuminuria - albumin excretion rate (AER) > 30mg/24h OR
urine albumin:creatinine ratio (UACR) >3mg/mmol
When 24h collection of urine may not be possible in oliguric patients, what is used as a parameter of creatinine clearance?
eGFR
(estimated glomerular filtration rate)
*for chronic renal failure only
Which of the following are limitations of eGFR?
A. Unacconted factors like muscle mass B. Extreme ages/ Extreme BMI C. Pregnancy D. Amputees, multiple-comorbidities E. not valid in Chinese population
All of the above
eGFR can be used for the assessment of AKI.
T/F?
F!!!
What are the aetiologies for chronic kidney disease? (5)
- Diabetic nephropathy (30%)
- Hypertension (25%)
- Glomerulonephritis (15%)
- Cystic diseases (3%)
- Others (5%): interstitial nephritis, analgesic nephropathy, reflux nephropathy
(refer to ACP for details if don’t remember)
Adapations of the kidney of solute handling:
- response of the surviving nephrons to continue excrete the daily load of a given substance with the intact nephron hypothesis - what is that?
When will this adaptation fail?
as CKD advances, kidney function is supported by a diminishing pool of functioning (or hyper-functioning) nephrons, rather than a relatively constant number of nephrons each with diminished function
其他手足會努力
occurs in CKD stages 3 and 4, fails in stage 5
List 4 adaptation mechanisms in CKD.
- Hypertrophy: whole kidney vs individual nephrons
- Increased renal blood flow by mild volume overload and hypertension
- Increased GFR per residual nephron
- Alterations in tubular reabsorption and/or secretion
Name the curves A-C in notes page 38.
Done? :) add oil!
What would be the adaptations of major solutes in plasma in CKD?
(a) creatinine
(b) amino acids, glucose
(c) Sodium
(a) creatitine
- no active homeostasis, therefore plasma [Cr] as indicator of CKD
(b) plasma concentration remains unchanged when GFR changes
(c) Na: reduced reabsorption: FENa rises to >5%, process promoted by ANP
- in CKD, patients generally retains their ability to maintain Na balance until GFR falls to <10
- +ve Na balance > fluid retention and worsening hypertension
What would be the adaptations of major solutes in plasma in CKD?
(d) Potassium
(d) Potassium
- increases, promoted by aldosterone
- failed in ESRF: secretion limited by very low tubular flow rate
- normal [K+] until ESRF
What would be the adaptations of major solutes in plasma in CKD?
(e) H+
(e) H+
- increases secretion: down to pH4.5
(In CRF, metabolic acidosis does not usually appear until renal function declines to 20-25% of normal.
With further progression of CRF, acid excretion by the kidney fails to keep pace with H+ production and metabolic acidosis ensues due to positive H+ balance.)
- increases regeneration of HCO3 by 2 buffering systems:
1. phosphate: reduced reabsorption (H+ + HPO42- > H2PO4 > excreted)
2. NH3: increase production, but will be limited by reduced kidney mass in CKD
What are the important acid base problems due to chronic renal disease?
NAGMA at earlier stage;
HAGMA at ESRF due to retention of unfiltered organic anions
(due to retention of phosphate, sulphate and other undetermined anions)
What are the impacts of metabolic acidosis in chronic renal failure? (3)
- Adaptive increase in NH3 production per nephron, leads to tubulointerstitial damage
- Bone buffering: osteodystrophy
(Intracellular buffering by absorption of hydrogen atoms by various molecules, including proteins, phosphates and carbonate in bone.)
- Skeletal muscle breakdown (protein catabolism), decreased albumin synthesis
NH3 production by nephrons are proportional to?
Kidney mass , thus NH3 production will be limited by reduced kidney mass in CKD
Decreased nephron mass in CKD would lead to ___________ and ___________ thus causing abnormalities to calcium and phosphate homeostasis.
- Decreased 1alpha-hydroxylation of vitamin D
- phosphate retention
Phosphate retention suppresses 1alpha hydroxylase > decreased formation of 1,25(OH)2D > reduced intestinal calcium absorption
+ increased serum phosphate
> > increased PTH = secondary hyperparathyroidism
____________ is a bone-derived hormone that functions as the central endocrine factor that regulates phosphate balance.
Fibroblast growth factor 23 (FGF23)
State the changes of [Ca] and [PO4] in plasma in early and late CKD.
(4)
Early:
- [Ca] and [PO4] are maintained by persistent increase in PTH
Late:
1. Hyperphosphatemia: phosphate reabsorption has reached the minimum of 15%
- Hypocalcemia: increased phosphate causes precipitation of Ca + reduced calcitriol (which increases both Ca and Phosphate)
- Renal osteodystrophy
Describe what is happening in renal osteodystrophy. (3)
i. Osteomalacia: defective mineralisation
ii. Osteitis fibrosa cystica: PTH-stimulated osteoclastic activity; patch osteolytic lesions on X-ray
iii. Osteosclerosis: metastatic calcification; patchy increased bone density on X-ray
Normally, kidney has minimus daily urine output of ___L/day with obligatory solutes of __________mmol/day.
> The maximum urine concentration is 1200mmol/L.
0.5;
600
In CKD, the concentrating ability is impaired by? (3)
- reduced medullary hypertonicity
- medullary fibrosis
- collecting tubule resistance to ADH
Which of the following about the urine osmolality in CKD is correct?
A. It approaches isotonic (300 mmol/L), causing a minimum daily urine output of 2L/day
B. Isosthenuria: excretion of urine with specific gravity of 1
C. Polyuria
D. Nocturia
E. Edema and volume expansion
All of the above
A: the maximal urine conc. in CKD patient approaches 300 mmol/L, but still 600 mmol of solutes have to be secreted, thus the minimal daily UOP is 2L/day
B: Isosthenuria refers to the excretion of urine whose specific gravity (concentration) is neither greater (more concentrated) nor less (more dilute) than that of protein-free plasma, typically 1.008-1.012.
The kidneys lack the ability to concentrate or dilute the urine and so the initial filtrate of the blood remains unchanged despite the need to conserve or excrete water based on the body’s hydration status.
At ESRF, maximum urine output is limited by?
GFR (<10ml/min)
Which of the following is incorrect regarding GFR?
A. There is reduced renal reserve (50-75%) of normal RFT and no detectable azotaemia in asymptomatic patients
B. Renal insufficiency means 25-50% of normal RFT with mild azotaemia
C. Renal insufficiency is associated with HT, anemia and defective urine concentration
D. Hypercalcemia, hyperphophatemia and mild metabolic acidosis can be seen in renal failure stage (12-25% of normal RFT, 15-30ml/min)
E. Uremia is the latest stage of CKD with GFR <15ml/min, marked azotaemia and electrolyte imbalance, acidosis
D is incorrect
- should be hypocalcemia and hyperphosphatemia
C: anemia due to reduced erythropoietin
E: uremic syndrome (multisystem disorders)
What are the indications for renal replacement therapy? (4)
differential transfer of solutes and water, by diffusion/osmosis/ultrafiltration, through a semi-permeable membrane
- ESRF - GFR <10ml/min
- Unable to control volume status or BP
- Progressive deterioration in nutritional status refractory to dietary intervention
- Cognitive impairment
What are the 4 main renal replacement therapy available?
- Hemodialysis
- Peritoneal dialysis
- Hemofiltration
- Renal transplant
What is the mechanism of hemodialysis?
diffusion through an artificial membrane
(convection and diffusion)
Rate: 80-160ml/min
Which of the following regarding hemodialysis is incorrect?
A. Blood flow is >200ml/min
B. Arteriovenous fisula is surgically created for permanent and easily accessible insertion site
C. Anti-coagulated by heparin during treatment because contact of blood with foreign surfaces activates clotting cascade
D. Is is more efficient than peritoneal dialysis in small molecules <300Da
E. It requires longer time of dialysis compared to peritoneal dialysis.
E
Shorter period of dialysis compared to peritoneal dialysis
Compared to PD, hemodialysis has low _______ and _______, high required in PD for effective filtration of fluid by osmosis.
dextrose and osmolality
Summary of differences:
- as above
- Hemo has shorter time of dialysis
- Hemo is more efficient in small molecules <300Da
What is the possible complication of hemodialysis?
Hypotension
- partly due to excessive removal of ECF
Mechanism of peritoneal dialysis?
Peritoneum as a semi-permeable membrane
- diffusion/osmotic ultrafiltration of solute and osmosis of water
Rate: 15-20ml/min
(hemodialysis: 80-160ml/min)
Which of the following is incorrect in peritoneal dialysis?
A. Tenckhoff catheter placed into peritoneal cavity via a subcutaneous tunnel
B. Continous ambulatory peritoneal dialysis (CAPD) allows patient to be mobile during dialysis
C. It may cause bacterial peritonitis by Staph aureus
D. Osmotic agents like glucose is added to achieve ultrafiltration
E. Solutes diffuse slowly across from capillaries to the peritoneal cavity when fluid infused
C Staph. epidermidis
___________ is the convection through a highly permeable membrane and replaced by fluid of desired composition.
When is it used?
Hemofiltration
- large amount of fluid and solute can be reoved
- used in intensive care in management of AKI
Remarks for renal transplant? (1)
Possible complications? (4)
Long-term immunosuppressant
- Opportunistic infections
- Hypertension
- Tumor
- Recurrence (e.g. Goodpasture syndrome)
In hemodialysis, small solutes like urea are removed by _________________;
water and large solutes are removed by _________________.
diffusion (down the concentration gradient);
Ultrafiltration
- convective transport: creates negative transmembrane pressure where solvent drags solute across membrane
Hemodialysis regime?
_____ times/week, _______per hour?
2-3 times/week;
4-5 times per hour
