Diuretics and the kidney

Question 1

Key points

Answer 1

Diuretics work in various ways, often interacting
with different ion transport systems throughout
the nephron to influence renal tubular sodium
and water reabsorption.
Diuretic resistance in heart failure or chronic
kidney disease may result in larger doses of
diuretic drugs being needed to achieve the same
effect.
Acute kidney injury is not a contraindication to
the use of diuretics.
Fluid overload causes harm.
Diuretics can be beneficial for critically ill patients
who have excess extracellular fluid

Question 2

Renal anatomy and physiology

Answer 2

The average kidney contains between 800,000 and 1,000,000
nephrons, with each nephron supplied with blood by an
afferent arteriole

The afferent arteriole forms a
glomerulus, which is a bundle of capillaries situated within
the Bowman’s capsule. The glomerulus acts as the filtering
unit of the kidney. Under normal conditions, in healthy individuals
the kidneys can generate a glomerular filtration rate
(GFR) up to 125 ml min1 of ultrafiltrate into the Bowman’s
capsule.1

The formed ultrafiltrate passes through the fenestrated
endothelium of glomerular capillaries, the glomerular basement
membrane and visceral epithelial cells (podocytes).2
These layers act as a semipermeable membrane allowing
the passage of fluid, solutes and proteins of <70 kDa, whereas
the negatively charged glycocalyx limits the filtration of
negatively charged proteins such as albumin. Starling forces
are responsible for the formation of the ultrafiltrate and

Question 3

Proximal convoluted tubule and reabsorption

Answer 3

Up to 70% of the ultrafiltrate is reabsorbed in the proximal
convoluted tubule (PCT), which is the site of numerous
adenosine triphosphate (ATP)-driven processes. The Naþ/Kþ-
ATPase pump within the basolateral proximal tubule epithelial
cells is responsible for the reabsorption of sodium ions
(Naþ) and water. Other solutes, including amino acids, bicarbonate
(HCO3
e), organic cations, anions, glucose and phosphate
(PO43e) are, to a degree, reabsorbed in the PCT through
ATP-dependent processes.

Question 4

Loop of Henle and further concentration of the
ultrafiltrate

Answer 4

Solute and water reabsorption continues in the loop of Henle,
which is responsible for further concentrating the urine
through its counter-current multiplier system. Up to 20e25% of filtered solutes and water are reabsorbed here through the
thin descending, thin ascending and the thick ascending
limbs of the loop

Answer 5

Diuretics are widely used in patients encountered in the
perioperative setting and critical care. For critically ill patients
it is recognised that fluid overload is harmful and timely
evacuation of fluid or ‘deresuscitation’ is an important therapy,
which requires both water and total body Naþ loss. There
is potential benefit from a combination of different diuretic
agents in order to minimise electrolyte disturbances, but there
remains a lack of robust evidence on which diuretic combinations
produce optimal fluid and solute removal in such
patients. Awareness of common drug interactions is important
in the perioperative period.