A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

CHAPTER 36
NEPHROLOGICAL AND RELATED
ASPECTS
● Introduction 273
● Volume overload (salt and water excess) 273
● Diuretics 274
● SIADH: overhydration 276
● Volume depletion 277
● Disordered potassium ion balance 278
● Drugs that alter urine pH 279
● Drugs that affect the bladder and genito-urinary
system 279
INTRODUCTION
The ‘internal environment’ is tightly controlled so that plasma
concentrations of electrolytes remain within narrow limits
despite substantial variations in dietary intake, as a result of
renal processes that ensure that the amounts excreted balance
those taken in. Fluid and electrolyte disturbances are important
in many diseases (e.g. heart failure, see Chapter 31). In the
present chapter, we consider general aspects of their management.
This usually involves dietary restriction and the use of
drugs that act on the kidney – especially various diuretics.
Additionally, we consider briefly drugs that act on the bladder
and other components of the genito-urinary system.
VOLUME OVERLOAD (SALT AND WATER
EXCESS)
Volume overload is usually caused by an excess of sodium
chloride with accompanying water. Effective treatment is
directed at the underlying cause (e.g. heart failure or renal failure),
in addition to improving volume status per se by reducing
salt intake and increasing its elimination by the use of
diuretics. Limiting water intake is seldom useful in patients
with volume overload, although modest limitation is of value
in patients with ascites due to advanced liver disease and in
other patients with hyponatraemia.
Diuretics increase urine production and Na excretion.
They are of central importance in managing hypertension
(Chapter 28), as well as the many diseases associated with
oedema and volume overload, including heart failure, cirrhosis,
renal failure and nephrotic syndrome, where it is important
to assess the distribution of salt and water excess
in different body compartments. Glomerular filtrate derives
from plasma, so diuretic treatment acutely reduces plasma
volume. It takes time for tissue fluid to re-equilibrate after an
acute change in blood volume. Consequently, attempts to
produce a vigorous diuresis are inappropriate in some oedematous
states and may lead to cardiovascular collapse and
‘prerenal’ renal failure – i.e. caused by poor renal perfusion,
often signalled by an increase in serum urea disproportionate
to the creatinine concentration. The principles of using diuretics
in the management of hypertension (Chapter 28) and heart
failure (Chapter 31) are described elsewhere. Here, we
describe briefly the management of hypoalbuminaemic states:
nephrotic syndrome and cirrhosis. Hypoalbuminaemia affects
the kinetics of several drugs through its effects on protein
binding (Chapter 7) and causes an apparently inadequate
intravascular volume in the face of fluid overload in the body
as a whole. This results in an increased risk of nephrotoxicity
from several common drugs, particularly non-steroidal antiinflammatory
drugs (NSAIDs, Chapter 26). Particular caution
is needed when prescribing and monitoring the effects of therapy
for intercurrent problems in such patients.
NEPHROTIC SYNDROME
The primary problem in nephrotic syndrome is impairment of
the barrier function of glomerular membranes with leakage of
plasma albumin into the urine. Plasma albumin concentration
falls together with its oncotic pressure and water passes from the
circulation into the tissue spaces, producing oedema. The fall in
effective blood volume stimulates the renin–angiotensin–aldosterone
system, causing sodium retention. Depending on the
nature of the glomerular pathology, it may be possible to reduce
albumin loss with glucocorticosteroid or other immunosuppressive
drugs (Chapter 50). However, treatment is often only symptomatic.
Diuretics are of limited value, but diet is important.
Adequate protein intake is needed to support hepatic synthesis
of albumin. Salt intake should be restricted.