AKI

Question 1

What is Bartter’s syndrome?

Answer 1

Bartter’s syndrome is a rare autosomal recessive disorder, caused by one of three mutations of the ion transporter/channel present in the thick ascending limb of the loop of Henle.

Question 2

What heavy metal poisoning is associated with proximal renal tubular acidosis?

Answer 2

Lead

Question 3

What are the physiological changes that occur in HRS?

Answer 3

The key physiological changes include, increased cardiac output, reduced systemic vascular resistance and renal vasoconstriction.

Question 4

What are the criteria for the diagnosis of HRS?

Answer 4

Cirrhosis or fulminant hepatic failure from other causes with ascites

Serum creatinine > 133 μmol/L (1.5 mg/dL).

No improvement in serum creatinine (decrease to a level of ≤ 133 μmol/L) after ≥ 2 days with diuretic withdrawal and volume expansion with albumin; the recommended dose of albumin is 1 g/kg of body weight/day up to a maximum of 100 g/day

Absence of shock

No current or recent treatment with nephrotoxic drugs.

Absence of intrinsic kidney disease as indicated by proteinuria > 500 mg/day, microscopic haematuria (>50 red blood cells per high power field), and/or abnormal renal ultrasonography

Question 5

What is Liddle syndrome?

Answer 5

Liddle’s syndrome is a congenital form of salt-sensitive hypertension characterised by a very high rate of renal sodium uptake, despite low levels of aldosterone, secondary hypokalaemia and metabolic alkalosis. (Bartter’s is associated with acidosis)

It is caused by a congenital mutation, which causes a constitutive hyper-reactivity in the epithelial sodium channel (ENaC). The increased sodium uptake is accompanied by an increased water uptake, leading to an increase in blood volume and secondary hypertension.

Question 6

What is the difference between Liddle and Bartter syndrome?

Answer 6

Liddle Syndrome

• Hypertension
• Low levels of aldosterone
• Increased ENaC activity
• Low Urinary Na+

Bartter Syndrome

• Hypotension
• High levels of aldosterone (and renin)

Question 7

What is the main difference on biochemistry between type 1 and type 2 RTA?

Answer 7

Type 2 RTA is associated with less severe hypokalaemia

Question 8

What is type 1 RTA?

Answer 8

Type 1 or distal renal tubular acidosis is associated with failure of distal H+ ion secretion. It leads to:

• normal anion gap metabolic acidosis
• hypokalaemia
• urinary stone formation (related to alkaline urine, hypercalciuria, and low urinary citrate)
• nephrocalcinosis, and
• bone demineralisation.

Question 9

How would you differentiate between central and nephrogenic DI?

Answer 9

• Central DI urine becomes more conc. after adm. of desmopressin
• Nephrogenic DI urine does not respond to desmopressin

Question 10

Which renal tubular acidosis is associated with renal calculi?

Answer 10

Type 1 (distal) RTA

Question 11

What should you check for before administering rasburicase?

Answer 11

Check for G6PD

Question 12

What is the time to CIN (contrast)?

Answer 12

3-5 days

Question 13

What are the features of Bartter’s syndrome?

Answer 13

• Hypokalaemia and metabolic acidosis
• High urinary potassium excretion

Question 14

How high is urinary Na+ loss in ATN?

Answer 14

It tends to be >60mmol/L

Question 15

What are the main features of Liddle syndrome?

Answer 15

• Autosomal Dominant
• GOF mutation in beta and gamma subunits of ENaC
• Reduced recognition for internalisation and degradation by Nedd4-2
• Hyporeninism and hypoadrenalism
• Hypokalaemia and metabolic alkalosis
• Treatment with amiloride

Question 16

How many types of Bartter syndrome are there?

Answer 16

• 5
  
  • Types 1-4 AR
  • Type 5 AD
  • Transient X linked
  • Type 1
    
    • Mutation in NKCC
  • Type 2
    
    • ROMK mutation
  • Type 3
    
    • ClC-Kb mutation
  • Type 4 (associated with SND)
    
    • 4a mutation of Barthin in ClC-Kb (associated with SND)
    • 4b mutation in ClC-Ka and ClC-Kb
  • Type 5
    
    • GOF in the Ca2+ sensing receptor

Question 17

What drugs can cause “drug-induced” Bartter syndrome?

Answer 17

• Aminoglycosides
• Calcimimetics
• Amphotericin B
• Heavy metal intoxication

Question 18

What are the features of Bartter syndrome?

Answer 18

• Hypokalaemia
• Metabolic alkalosis
• Hypercalciuria
• Nephrocalcinosis (less common in T3 and T4)
• High urinary PGE2
• Secondary FSGS

Question 19

What nephron segment is affected by Bartter syndrome?

Answer 19

Thick Ascending Limb of LoH

Question 20

What nephron segment is affected by GS?

Answer 20

Distal convoluted tubule

Question 21

What mutations cause GS?

Answer 21

• LOF mutation in Na Cl
• Mutation in the Transient Receptor Action Potential Cation Channel V (TRPV5)
  *

Question 22

What drug is associated with GS?

Answer 22

Cisplatin

Question 23

Why might patients with GS develop hypertension later on?

Answer 23

Chronic activation of RAAS without the countereffect of PGE2 as occurs in BS

Question 24

What effect does GS have on calcium metabolism?

Answer 24

Increased re-uptake of Ca2+ leads to hypocalciuria and chondrocalcinosis

Question 25

Which hypotensive, hypokalaemic and alkalotic genetic disorder is associated with a hypo-osmolar urine relative to the serum?

Answer 25

Bartter syndrome

GS may be associated with euosmolar urine

Question 26

What metabolic complications are associated with some urinary diversions?

Answer 26

Ileal conduit

• Met acidosis and hypokalaemia

Uterosigmoid anastamosis

• Met acidosis and hypokalaemia

Jejenoureterostomy

• Met acidosis and hyperkalaemia and hyponatraemia

Gastric segment (used in bladder augmentation)

• Met alkalosis, hypokalaemia, and hyponatraemia