L24 Chronic kidney disease and renal replacement therapy

Question 1

What is the definition of chronic kidney disease?

3

Answer 1

Progressive, irreversible impariment of renal function > 3 months, as evidenced by

1. GFR <60ml/min/1.73^2
2. Albuminuria - albumin excretion rate (AER) > 30mg/24h OR

urine albumin:creatinine ratio (UACR) >3mg/mmol

Question 2

When 24h collection of urine may not be possible in oliguric patients, what is used as a parameter of creatinine clearance?

Answer 2

eGFR
(estimated glomerular filtration rate)

*for chronic renal failure only

Question 3

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

Answer 3

All of the above

Question 4

eGFR can be used for the assessment of AKI.

T/F?

Answer 4

F!!!

Question 5

What are the aetiologies for chronic kidney disease? (5)

Answer 5

1. Diabetic nephropathy (30%)
2. Hypertension (25%)
3. Glomerulonephritis (15%)
4. Cystic diseases (3%)
5. Others (5%): interstitial nephritis, analgesic nephropathy, reflux nephropathy

(refer to ACP for details if don’t remember)

Question 6

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?

Answer 6

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

Question 7

List 4 adaptation mechanisms in CKD.

Answer 7

1. Hypertrophy: whole kidney vs individual nephrons
2. Increased renal blood flow by mild volume overload and hypertension
3. Increased GFR per residual nephron
4. Alterations in tubular reabsorption and/or secretion

Question 8

Name the curves A-C in notes page 38.

Answer 8

Done? :) add oil!

Question 9

What would be the adaptations of major solutes in plasma in CKD?

(a) creatinine
(b) amino acids, glucose
(c) Sodium

Answer 9

(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

Question 10

What would be the adaptations of major solutes in plasma in CKD?
(d) Potassium

Answer 10

(d) Potassium
- increases, promoted by aldosterone
- failed in ESRF: secretion limited by very low tubular flow rate
- normal [K+] until ESRF

Question 11

What would be the adaptations of major solutes in plasma in CKD?

(e) H+

Answer 11

(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

Question 12

What are the important acid base problems due to chronic renal disease?

Answer 12

NAGMA at earlier stage;
HAGMA at ESRF due to retention of unfiltered organic anions

(due to retention of phosphate, sulphate and other undetermined anions)

Question 13

What are the impacts of metabolic acidosis in chronic renal failure? (3)

Answer 13

1. Adaptive increase in NH3 production per nephron, leads to tubulointerstitial damage
2. Bone buffering: osteodystrophy

(Intracellular buffering by absorption of hydrogen atoms by various molecules, including proteins, phosphates and carbonate in bone.)

3. Skeletal muscle breakdown (protein catabolism), decreased albumin synthesis

Question 14

NH3 production by nephrons are proportional to?

Answer 14

Kidney mass , thus NH3 production will be limited by reduced kidney mass in CKD

Question 15

Decreased nephron mass in CKD would lead to ___________ and ___________ thus causing abnormalities to calcium and phosphate homeostasis.

Answer 15

1. Decreased 1alpha-hydroxylation of vitamin D
2. 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

Question 16

____________ is a bone-derived hormone that functions as the central endocrine factor that regulates phosphate balance.

Answer 16

Fibroblast growth factor 23 (FGF23)

Question 17

State the changes of [Ca] and [PO4] in plasma in early and late CKD.

(4)

Answer 17

Early:
- [Ca] and [PO4] are maintained by persistent increase in PTH

Late:
1. Hyperphosphatemia: phosphate reabsorption has reached the minimum of 15%

2. Hypocalcemia: increased phosphate causes precipitation of Ca + reduced calcitriol (which increases both Ca and Phosphate)
3. Renal osteodystrophy

Question 18

Describe what is happening in renal osteodystrophy. (3)

Answer 18

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

Question 19

Normally, kidney has minimus daily urine output of ___L/day with obligatory solutes of __________mmol/day.
> The maximum urine concentration is 1200mmol/L.

Answer 19

0.5;

600

Question 20

In CKD, the concentrating ability is impaired by? (3)

Answer 20

1. reduced medullary hypertonicity
2. medullary fibrosis
3. collecting tubule resistance to ADH

Question 21

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

Answer 21

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.

Question 22

At ESRF, maximum urine output is limited by?

Answer 22

GFR (<10ml/min)

Question 23

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

Answer 23

D is incorrect
- should be hypocalcemia and hyperphosphatemia

C: anemia due to reduced erythropoietin

E: uremic syndrome (multisystem disorders)

Question 24

What are the indications for renal replacement therapy? (4)

differential transfer of solutes and water, by diffusion/osmosis/ultrafiltration, through a semi-permeable membrane

Answer 24

1. ESRF - GFR <10ml/min
2. Unable to control volume status or BP
3. Progressive deterioration in nutritional status refractory to dietary intervention
4. Cognitive impairment

Question 25

What are the 4 main renal replacement therapy available?

Answer 25

1. Hemodialysis
2. Peritoneal dialysis
3. Hemofiltration
4. Renal transplant

Question 26

What is the mechanism of hemodialysis?

Answer 26

diffusion through an artificial membrane
(convection and diffusion)

Rate: 80-160ml/min

Question 27

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.

Answer 27

E

Shorter period of dialysis compared to peritoneal dialysis

Question 28

Compared to PD, hemodialysis has low _______ and _______, high required in PD for effective filtration of fluid by osmosis.

Answer 28

dextrose and osmolality

Summary of differences:

1. as above
2. Hemo has shorter time of dialysis
3. Hemo is more efficient in small molecules <300Da

Question 29

What is the possible complication of hemodialysis?

Answer 29

Hypotension

- partly due to excessive removal of ECF

Question 30

Mechanism of peritoneal dialysis?

Answer 30

Peritoneum as a semi-permeable membrane
- diffusion/osmotic ultrafiltration of solute and osmosis of water

Rate: 15-20ml/min
(hemodialysis: 80-160ml/min)

Question 31

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

Answer 31

C Staph. epidermidis

Question 32

___________ is the convection through a highly permeable membrane and replaced by fluid of desired composition.

When is it used?

Answer 32

Hemofiltration

• large amount of fluid and solute can be reoved
• used in intensive care in management of AKI

Question 33

Remarks for renal transplant? (1)

Possible complications? (4)

Answer 33

Long-term immunosuppressant

1. Opportunistic infections
2. Hypertension
3. Tumor
4. Recurrence (e.g. Goodpasture syndrome)

Question 34

In hemodialysis, small solutes like urea are removed by _________________;
water and large solutes are removed by _________________.

Answer 34

diffusion (down the concentration gradient);

Ultrafiltration
- convective transport: creates negative transmembrane pressure where solvent drags solute across membrane

Question 35

Hemodialysis regime?

_____ times/week, _______per hour?

Answer 35

2-3 times/week;

4-5 times per hour