A Textbook of Clinical Pharmacology and Therapeutics

●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

CHAPTER 36

NEPHROLOGICAL AND RELATED

ASPECTS

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 impor-
tant in many diseases (e.g. heart failure, see Chapter 31). In the
present chapter, we consider general aspects of their manage-
ment. 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 fail-
ure), in addition to improving volume status per se by reduc-
ing 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 Naexcretion.
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, cirrho-
sis, 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 oede-

matous 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 diuret-

ics 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 anti-

inflammatory drugs (NSAIDs, Chapter 26). Particular caution

is needed when prescribing and monitoring the effects of ther-

apy 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–aldos-

terone system, causing sodium retention. Depending on the

nature of the glomerular pathology, it may be possible to reduce

albumin loss with glucocorticosteroid or other immunosuppres-

sive drugs (Chapter 50). However, treatment is often only symp-

tomatic. 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.