Biochemistry of Renal Failure

Question 1

Functions of the Kidney →

Answer 1

Excretion/Homeostasis

Endocrine functions

Question 2

Excretion/Homeostasis

Answer 2

• Waste products of metabolism
• Fluid/electrolyte balance
• Acid-base balance
• Removal of drugs and toxins

Question 3

Endocrine functions

Answer 3

• Renin Angiotensin Aldosterone system
• Erythropoietin production
• Hydroxylation of Vitamin D

Question 4

Inadequate renal blood flow

Answer 4

the same blood supply supplies pressure and oxygenation of the tubules and therefore important to address quickly.

Question 5

Acute Kidney Injury →Definition

Answer 5

Any physical, chemical toxic, or ischaemic insult causing rise in creatinine OR fall in urine output over timescale of hours to days (don’t need both).

Question 6

Acute Kidney Injury → Epi

Answer 6

• Common – 8% (of all creatinine measurements) – fit the criteria above
• Often missed – 40% of those developing after submission
• Doubles length of stay (stage 1,2,3)
• Increases mortality – 2,4,6x @ 1 year in stage 1,2,3

Question 7

Stage 1
Serum creatinine (SCr) criteria
Urine output criteria

Answer 7

Increase >26 umol/L within 48 hrs or
Increase >1.5 to 1.9 X reference SCr

6 consecutive hrs

Question 8

Stage 2
Serum creatinine (SCr) criteria
Urine output criteria

Answer 8

Increase >2 to 2.9 X reference SCr 12 hrs

Question 9

Stage 3
Serum creatinine (SCr) criteria
Urine output criteria

Answer 9

Increase >3 X reference SCr or increase >354 umol/L or commenced on renal replacement therapy (RRT) irrespective of stage 24 hrs or anuria for 12 hrs

Question 10

Aetiology of AKI → Pre-Renal (most common)

Answer 10

Hypovolemia
• Haemorrhage
• Sepsis
Pump Failure

Question 11

Aetiology of AKI → Renal (tubular damage)

Answer 11

Ischaemia – not correcting pre-renal
Nephrotoxins
•	Drugs, poisons, metals, myoglobin* (monomeric protein carrying oxygen in tisssues), paraproteins
Glomerulonephritis
Interstitial nephritis

Question 12

Aetiology of AKI → Post-Renal

Answer 12

Stones
Tumour
Prostate

Question 13

• Myoglobin significance

Answer 13

can filter as its smaller. If too excessive can crystallise from reduced urinary output i.e. during haemorrhage. Following major trauma there is lots o f myoglobin release and so important to think of in these patients.

Question 14

Biochemical vs. clinical features: of AKI

Answer 14

• Biochemical changes occur early but are eventually life-threatening (High K+, acidosis)
• Clinical features are non-specific and occur late

Question 15

Biochemical vs. clinical features: of AKI

Due to:

Answer 15

• Failure to remove
o Nitrogenous waste products
o Fluid, electrolytes
o Acids

Question 16

Biochemical vs. clinical features: of AKI Outcome:

Answer 16

• Retain nitrogenous waste products
o Nausea; malaise; confusion
• Reduced GFR → fluid overload
• Retain acidic waste products of metabolism
o 100 mmol/day from metabolism
o Life threatening once plasma pH >7.0 ([H+] = 10-7)
• Retain Potassium
o Life threatening once [K+] >8mmol/L
• Don’t see endocine problems in AKI – not enough time to cause morbidity

Question 17

Disproportionate increase of urea compared to creatinine 2 reasons

Answer 17

Urea rise explanation 1:
• Urea and creatinine are both markers of Renal function as both freely filtered at glomerulus. Degree of clearance reflects kidney function.
• Creatinine – freely filtered but no reabsorption
• Urea is filtered by glomerulus and reabsorbed at PT.
• The lower renal blood flow the lower the GFR the more opportunity there is for Urea to be reabsorbed,
• Low renal blood flow lower UO and more urea reabsorption so Urea is higher than creatinine

Urea rise explanation 2:
Hematemesis (Upper GI bleed) production of creatinine is proportional to muscle mas, Urea proportional to diet protein (hepatic function influential). ‘Large protein meal’ because of bleed and therefore will increase urea regardless of renal function.

Question 18

Treatment of acute renal Failure →

Answer 18

Correct life threatening abnormalities
→ Fluid (for renal perfusion_
•	Maintain fluids
•	Replace fluids
•	Resuscitate fluids
→ Electrolyte
→ Acid/base
Restore renal perfusion if possible
Support renal function if not
→ Dialysis/hemo-filtration – restoring function

Question 19

High and Low urea caused by

Answer 19

High:
Protein load
Dehydration

Low:
Low protein diet
Anorexia

Question 20

High and low creatinine caused by

Answer 20

High:
Muscle breakdown
Low:
Small muscle mass

Question 21

Who is at risk of AKI

Answer 21

75+; Hypertension; CKD; Diabetes; Chronic Liver Disease; CCF; Myeloma; Sepsis; Drugs (what has changed)

Question 22

Causes of CKD

Answer 22

o Diabetes Mellitus (most common because better survival), Hypertension
o Polycystic Kidney Disease
o Glomerulonephritis, Pyelonephritis, Interstitial nephritis
o Multisystem disease
o Drugs

Question 23

Serum Creatinine and GFR: (why creatinine isn’t used really)

Answer 23

• Need to loose the equivalent of half the renal function before the Serum creatinine rises significantly.
• Low muscle mass (elderly) curve shift downwards and therefore lost 1 2/3 of renal function before the creatinine is above the normal range.

Question 24

Biochemical changes in CKD

Answer 24

• Elevated Urea/Creatinine
• Acidosis (dissolving buffers primarily form bone – backfires on bone health)
• Hyperkalaemia – offset by increased gut losses
• High phosphate (main cause of morbidity)
• Low calcium – causes secondary hyperparathyroidism
• Endocrine changes
o Reduced 1α hydroxylation of Vitamin D -
o Reduced Erythropoietin, causing anaemia
• Lipids
o Elevated Cholesterol and Triglyceride, accounts for increased risk of CHD
• Impaired immune function

Question 25

Water balance in renal disease:

glomerular damage

Answer 25

Little glomerular filtrate

Oliguria

Question 26

Water balance in renal disease Healthy nephron in diseased kidney

Answer 26

Osmotic diuresis

Polyuria

Question 27

Water balance in renal disease Tubular damage

Answer 27

Ineffective water reabsorption

Polyuria

Question 28

Mechanisms of renal bone disease:

Answer 28

Disease of Hydroxylation Process →

1. Decreased 1α hydroxylation
2. Decreased 1,25 Vit D
3. Decreased gut absorption of Ca++
4. Reduced plasma Ca++
5. Increased PTH – increased bone resorption

Question 29

Decreased Plasma Ca ++

Answer 29

Osteomalacia

Question 30

Increased PTH (drop in plasma calcium)

Answer 30

Increased Bone resorption

Osteitis fibrosa

Question 31

Increased Calcium/ Phosphate product

Answer 31

Metastatic Calcification

Question 32

Dissolved bone buffers from metabolic acidosis

Answer 32

Bone decay

Osteoporosis

Question 33

Treatment: of metabolic renal disease

Answer 33

• Active Vitamin with the aim of keeping PTH in the normal range= confirmation that process is in homeostatic balance.
• Phosphate binders – keeps phosphate down
• Bicarb – to mitigate the acidosis

Question 34

Renal Tubular Disorders:

Answer 34

Transport Defects
•	Glucose (exceed threshold (capacity) for reabsorption)
o	Renal Glycosuria
o	Pregnancy – increased filtration rate
•	Amino acid
o	Selective e.g. Cystinuria
o	Generalized
•	Phosphate
o	Hypophosphataemic rickets
Globular tubular defect – Fanconi Syndrome – multiple defects across multiple transporters.

Question 35

Renal Tubular Acidosis: Type 1 (Distal)

Answer 35

Failure to excrete H+ → acidosis
Excess K+ loss in exchange for NA → low K+
Can’t acidify urine

Question 36

Renal Tubular Acidosis:Treatment of Type 1

Answer 36

Bicarbonate and K+

Question 37

Renal Tubular Acidosis: Type II (Proximal)

Answer 37

Bicarbonate ‘leak’ – no plug in bath

Question 38

Renal Tubular Acidosis: Treatment of Type II

Answer 38

Bicarbonate

Question 39

Renal Tubular Acidosis: Type IV

Answer 39

Description: (low renin, low aldosterone)
Both H+ and K+ excretion from DCT defective
Often asymptomatic, sometime high K+