CME Renal Medicine
on therapy in renal disease. Arch Intern Med
1981;141:1039–41.
Richard S, Jothy S. A prospective study on
Liam Plant MB MRCPI FRCPE, Consultant
the impact of the renal biopsy in clinical
Renal Physician, Department of Renal
management. Clin Nephrol 1986;26:217–21.
5 Cohen AH, Nast CC, Adler SG, Kopple JD. Medicine, Cork University Hospital, Cork,
Clinical utility of kidney biopsies in the
ing directly inhibits sodium and chloride
diagnosis and management of renal disease. Am J Nephrol 1989;9:309–15. Clin Med 2003;3:517–20
6 Farrington K, Levison DA, Greenwood RN,
What are diuretics?
concentrating and diluting mechanisms.
ment and normal kidney size. Q J Med
1989;70: 221–33. How do they work?
Diuretics are widely used in clinical med-
Michael J. Knowledge of renal histologyalters patient management in over 40% of
1994;9:1255–9.
reabsorption at different sites along the
8 Tomson C, Porter T. Asymptomatic micro-
which investigations for which patients? A
Thiazide and related diuretics1–3
review of the evidence. BJU Int 2002;90:
Diuretics of another class, the thiazides
9 McGregor DO, Lynn KL, Bailey RR, Robson
RA, Gardner J. Clinical audit of the use of
used agents (Table 1).1–3 Although most
renal biopsy in the management of isolated
microscopic hematuria. Clin Nephrol 1998; 49:345–8.
zone), are also organic anions secreted in
10 Nakao N, Yoshimura A, Morita H, Takada
this site (eg acetazolamide) are of rela-
distal tubule and connecting segment.
in non-diabetic renal disease (COOP-ERATE): a randomised controlled trial. Lancet 2003;361:117–24.
11 Feehally J. Treating IgA Nephropathy –
principle applies to the proximal tubular
Who, When and How? Nephron Clin Pract
2003;93:C47–8.
12 Iseki K, Iseki C, Ikemiya Y, Fukiyama K.
Risk of developing end-stage renal disease
nation of these classes can be especially
in a cohort of mass screening. Kidney Int
1996;49:800–5.
13 Kasiske BL. Relationship between vascular
disease and age-associated changes in the
human kidney. Kidney Int 1987;31:1153–9.
14 Ball S, Cook T, Hulme B, Palmer A, Taube
D. The diagnosis and racial origin of 394
patients undergoing renal biopsy: an associ-ation between Indian race and interstitialnephritis. Nephrol Dial Transplant 1997;
12:71–7. Diuretics cause natriuresis in oedematous and hypertensive states Dietary salt intake restriction is essential with diuretic use Rapid adaptation by the tubule blunts the initial response to diuretic therapy Application of pharmacokinetic and pharmacodynamic principles improves the achievement of clinical objectives Sequential nephron blockade is effective in advanced chronic renal failure and heart failure KEY WORDS: diuretics, heart failure, kidney, nephron, oedema, pharmacodynamics, pharmacokinetics, potassium, sodium Clinical Medicine Vol 3 No 6 November/December 2003 CME Renal Medicine
prescribe a reduction in dietary salt intake
difficult to achieve. Unfortunately, many
channels of the principal cells in the cor-
inhibits the effect of aldosterone on the
intake occurs because of addition in food
Low glomerular filtration rate (GFR):
but not losing weight is likely to have an
When are diuretics indicated? How are they most effectively used?1–3
pathophysiological states (renal failure,
Pharmacokinetics are important in initi-
cardiac failure, hepatic failure, nephrotic
ating natriuresis, pharmacodynamics in
increased natriuresis until the patient has
is excreted in the tubular fluid, consider-
proximal tubule: many organic ions
new desired steady state, particularly if
threshold may be difficult in the presence
Decreased bioavailability: furosemide
and water requires an excess of excretion
over intake. Dietary salt intake frequently
exceeds 100 mmol/day (~6 g salt/day).
diuretic is not active. For example, to lose
650 mmol over and above that needed to
balance daily intake. It is irrational not to
Table 1. Diuretic agents. Diuretic class Examples Principal site of action Comments
**Indicated if sulphonamide hypersensitivity
due to combination of loop and thiazide diuretics
Consider in severe heart failure+Specific benefits in advanced heart failure
Clinical Medicine Vol 3 No 6 November/December 2003 CME Renal Medicine Are there other specific
more frequently will not help. In difficult
indications?
patients, but not all patients benefit.
effect. This is principally a local response
greater than three litres per day, restric-
Metabolic alkalosis due to chloride
Use of adequate dose more frequently:
furosemide acts for about six hours. Hyperuricaemia – tubular handling
with heart failure, particularly with more
acute renal failure (ARF),11 and are in fact
more likely to increase the frequecy with
Hypersensitivity reactions such as
response to loop diuretics declines.
to diminish anticipated nephrotoxicity.
skin rashes and interstitial nephritis. What are the side effects of diuretics? urea concentrations because of renal
may cause fetal electrolyte disturbances.
mised, and diuretics enter breast milk. References Electrolyte disturbances, for example:
2 Brater DC. Pharmacology of diuretics.
3 Ellison DH. Diuretic drugs and the treat-
Clinical Medicine Vol 3 No 6 November/December 2003 CME Renal Medicine
Bischoff I et al. Coadministration ofalbumin and furosemide in patients with
5 Agarwal R, Gorski JC, Sundblad K, Brater
John Main MB ChB FRCP MD, Consultant
affect response to furosemide in patients
Nephrologist, James Cook University
with nephrotic syndrome. J Am Soc Nephrol
2000;11:1100–5.
6 Rudy DW, Voelker JR, Greene PK, Esparza
FA, Brater DC. Loop diuretics for chronic
Clin Med 2003;3:520–5
renal insufficiency: a continuous infusion is
7 Fliser D, Schroter M, Neubeck M, Ritz E.
Coadministration of thiazides increases the
15–30% of otherwise unselected patients
efficacy of loop diuretics even in patients
vascular disease.1 It is easy to find; in our
unit, about 75% of cases selected only on
treatment in severe heart failure: a ran-
efferent arteriolar constriction which is
9 Cooper HA, Dries DL, Davis CE, Shen YL,
Domanski MJ. Diuretics and risk ofarrhythmic death in patients with left ven-
sure is reduced. This loss of GFR is inde-
10 Pitt B, Zannad F, Remme WJ, Cody R et al.
The effect of spironolactone on morbidity
and mortality in patients with severe heartfailure. Randomized Aldactone Evaluation
stenosis. The effect of these drugs is dose
ered with a view to revascularisation.
11 Mehta RL, Pascual MT, Soroko S, Chertow
mortality, and nonrecovery of renal func-tion in acute renal failure.
Atheromatous renal artery stenosis (ARAS) is common in arteriopaths All the clinical manifestations of ARAS have more common causes in arteriopaths ARAS and chronic renal failure (CRF) often co-exist, but the CRF is not usually due to the ARAS (and therefore not improved by revascularisation) The role of intervention in preventing end-stage renal failure remains unclear The response to intervention in hypertension is usually no better than mild improvement When pulmonary oedema is due to ARAS, the response to intervention can be dramatic When acute oliguric renal failure occurs as a consequence of renal artery occlusion, excellent renal recovery can occur after intervention KEY WORDS: atheromatous renal artery stenosis, ischaemic nephropathy, athero-embolic nephropathy, renovascular hypertension Clinical Medicine Vol 3 No 6 November/December 2003
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