Dr.

Dalya Shakir

PhD.Clinical Biochemistry

4\5\2020

Tests of tubular function

Renal tubular disorders may be congenital or acquired.Specific disorders affecting

the renal tubules may affect the ability to concentrate urine or to excrete an
appropriately acidic urine, or may cause impaired reabsorption of amino acids,
glucose, phosphate, etc.

1. Urine osmolality

Urine osmolality in health between 50 and 1250 mmol/kg, depending upon the
body's requirement to produce a maximally dilute or a maximally concentrated
urine. The failing kidney loses its capacity to concentrate urine at a relatively late
stage. A patient with polyuria due to chronic kidney disease is unable to produce
either a dilute or a concentrated urine. Instead, urine osmolality is generally within
50 mmol/kg of the plasma osmolality (i.e. between about 240 and 350 mmol/kg).
To excrete the obligatory daily solute load of about 600 mmol requires
approximately 2 L of water at a maximum urine osmolality of 350 mmol/kg,
compared with 500 mL of the most concentrated urine achieved by the normal
kidney. Hence, patients with CKD require a daily water intake of at least 2 L to
maintain their water balance. Urine osmolality is directly proportional to the
osmotic work done by the kidney, and is a measure of concentrating power. Urine
specific gravity, which can be estimated using urinalysis dipsticks, is usually
directly proportional to osmolality, but gives spuriously high results if there is
significant glycosuria or proteinuria. In patients with polyuria, measurement of
the osmolality of early morning urine specimens should be made before proceeding
to formal concentration tests. If urinary osmolality greater than 800 mmol/kg is
observed in any specimen, as should be the case in most patients who can
concentrate urine normally, there is no need to perform further tests of
concentrating ability.

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2. renal concentration tests

Renal concentration tests are not normally required in patients with established
chronic kidney disease, Causes of kidney failure to concentrate urine are shown in

1) Causal mechanism Examples of causes Insufficient secretion of vasopressin

(e.g. trauma, neoplasm)
2) Inhibition of vasopressin release Psychogenic polydipsia, lesions of the
thirst centre causing polydipsia
3) Inability to maintain renal medullary hyperosmolality (Chronic kidney
disease, , lithium toxicity, hypokalaemia, hypercalcaemia, renal papillary
necrosis (e.g.analgesic nephropathy)
4) Inability to respond to vasopressin Renal tubular defects (e.g. nephrogenic
diabetes insipidus, Fanconi syndrome)
5) Increased solute load per nephron (Chronic kidney disease, diabetes
mellitus)

Formal tests of renal concentrating power measure the concentration of urine

produced in response either to fluid deprivation or to intramuscular (IM) injection
of 1-deamino, 8-D-arginine vasopressin (DDAVP), a synthetic analogue of
vasopressin. If the patient is receiving drugs that affect the renal concentrating
ability (e.g. carbamazepine, chlorpropamide, DDAVP), these should be stopped for
at least 48 h before testing. A fluid deprivation test is performed first. If the patient
is unable to concentrate the urine adequately following fluid deprivation, then a
DDAVP test follows immediately.

A. Fluid deprivation test

This test is effectively a bioassay of vasopressin.

1) For instance, beginning at 10 pm, the patient is told not to drink overnight, and
urine specimens are collected while the patient continues not to drink between 8
am and 3 pm the next day.
2) During the test, the patient should be weighed every 2 h, and the test should be
stopped if weight loss of 3-5% of total body weight occurs.
3) Blood and urine specimens are collected for measurement of osmolality.

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 Normally, there is no increase in plasma osmolality (reference range 285-
295 mmol/kg) over the period of water deprivation, whereas urine
osmolality rises to 800 mmol/kg or more. A rising plasma osmolality and a
failure to concentrate urine are consistent with either a failure to secrete
vasopressin or a failure to respond to vasopressin at the level of the distal
nephron. When this pattern of results is obtained, it is usual to proceed
immediately to perform the DDAVP test.
B. DDAVP test
1) The patient is allowed to drink a moderate amount of water at the end of the
fluid deprivation test, to alleviate thirst.
2) An IM injection of DDAVP is then given, and urine specimens are collected
at hourly intervals for a further 3 h and their osmolality measured.

Interpretation of tests of renal concentrating ability

a) Patients with diabetes insipidus of hypothalamic- pituitary origin produce
insufficient vasopressin; they should therefore not respond to fluid deprivation,
but should respond to the DDAVP. As a rule, these patients show an increase
in plasma osmolality during the fluid deprivation test, to more than 300
mmol/kg, and a low urine osmolality (200-400 mmol/kg). There is a marked
increase in urine osmolality, to 600 mmol/kg or more, in the DDAVP test.

b) Polyuria of renal origin may be due to inability of the renal tubule to respond
to vasopressin, as in nephrogenic diabetes insipidus. In this condition, there is
failure to produce a concentrated urine in response either to fluid deprivation
or to DDAVP injection, the urinary osmolality usually remaining below 400
mmol/kg; in these patients,
plasma osmolality increases as a result of fluid deprivation.

c) Patients with psychogenic diabetes insipidus should respond to both fluid

deprivation and DDAVP. In practice, however, renal medullary hypo-
osmolality often prevents the urine osmolality from reaching 800 mmol/kg
after fluid deprivation or DDAVP injection in these tests, as normally
performed. These patients have a plasma osmolality that is initially low, but
which rises during the tests. However, fluid deprivation may have to be
continued for more than 24 h in these patients before medullary
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hyperosmolality is restored; only then do they show normal responses to fluid
deprivation or to DDAVP injection.