The kidneys 54 Negative pressure on the dialysate side of the membrane - PowerPoint Presentation

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The kidneys

54

Negative pressure on the dialysate side of the membrane

- a high rate of excretion of the metabolic

can be varied to adjust the amount of water removed.

product forming the stone, due either to

In intermittent and continuous ambulatory

high plasma and therefore ?ltrate levels or to

peritoneal dialysis, the folds of the peritoneum are

impairment of normal tubular reabsorption

used as the dialysing membrane with capillaries

from the ?ltrate.

on one side, and an appropriate fluid of higher

Changes in pH of the urine, often due to bacterial

osmolality is infused into the peritoneal cavity on the

infection, which favour precipitation of different

other. After a suitable time to allow for equilibration

salts at different hydrogen ion concentrations.

of diffusible solutes, depending on the type of

Urinary stagnation due to obstruction to urinary

peritoneal dialysis, the peritoneal cavity is drained

outflow or renal tract structural abnormality.

and the cycle is repeated.

Lack of normal inhibitors: urine normally contains

inhibitors, such as citrate, pyrophosphate and

Dialysis is used in some cases of acute kidney injury

glycoproteins, which inhibit the growth of calcium

until renal function improves, or as a regularly repeated

phosphate and calcium oxalate crystals respectively.

procedure in suitable cases of end-stage kidney disease.

Hypocitraturia may partly explain the renal calculi

It may also be used to prepare patients for renal

found in distal or type 1 renal tubular acidosis (see

transplantation.

Chapter 4).

RENAL CALCULI

Constituents of urinary calculi

Renal calculi are usually composed of products of

metabolism present in normal glomerular filtrate, often at

Renal calculi may consist of the following (Box 3.3):

concentrations near their maximum solubility (Fig. 3.8).

calcium-containing salts:

Conditions favouring renal calculus

- calcium oxalate,

formation

- calcium phosphate,

urate,

A high urinary concentration of one or more

cystine,

constituents of the glomerular filtrate, due to:

xanthine.

- a low urinary volume with normal renal

function, because of restricted ?uid intake or

excessive ?uid loss over a long period of time

Calculi composed of calcium salts

(particularly common in hot climates) - this

About 80 per cent of all renal stones contain calcium.

favours formation of most types of calculi,

Precipitation is favoured by hypercalciuria, and the type

especially if one of the other conditions listed

of salt depends on urinary pH and on the availability

below is also present,

of oxalate. Any patient presenting with calcium-

containing calculi should have plasma calcium and

phosphate estimations performed, and, if the results are

normal, they should be repeated at regular intervals to

exclude primary hyperparathyroidism.

Hypercalcaemia causes hypercalciuria if glomerular

function is normal. The causes and differential

Box 3.3 Some causes of renal calculi

cm

Calcium phosphate or oxalate

Triple phosphate stones

1

Urate

Cystine

Figure 3.8 A renal calculus. Reproduced with

Complex/mixture stones

permission from Nyhan WL and Barshop BA. Atlas of

Rarities, e.g. xanthine, dihydroxyadenine or indinavir

Inherited Metabolic Diseases , 3rd edition. London:

Artefacts, e.g. ?brin/clots/Munchausen's syndrome

Hodder Arnold, 2012.

Renal calculi

55

diagnosis of hypercalcaemia are discussed in Chapter

by treating hypercalcaemia if present,

6. In many subjects with calcium-containing renal

if this is not possible, by reducing dietary calcium

calculi the plasma calcium concentration is normal.

(although this alone may exacerbate hyperoxaluria)

Any increased release of calcium from bone (as

and oxalate intake,

in actively progressing osteoporosis, in which loss

by maintaining a high fluid intake, unless there is

of matrix causes secondary decalci?cation, or in

glomerular failure.

prolonged acidosis, in which ionization of calcium

Thiazide diuretics reduce urinary calcium excretion,

is increased) causes hypercalciuria; hypercalcaemia

and treatment of urinary tract infection may reduce the

is unusual in such cases. In distal renal tubular

risk of calculi formation.

acidosis there is an increased calcium load and,

because of the relative alkalinity of the urine, calcium

Struvite (magnesium ammonium phosphate)

precipitation in the kidney and renal tract may occur

These stones (about 10 per cent of all renal calculi)

- nephrocalcinosis.

are associated with chronic urinary tract infections by

Hypercalciuria has been de?ned as a daily urinary

organisms such as Proteus species capable of splitting

calcium excretion of more than 6.2 mmol in adult

ammonium. The urinary pH is usually greater than 7.

females and 7.5 mmol in adult males.

These urease-containing bacteria convert urea to

A signi?cant proportion of cases remain in which

ammonia and bicarbonate.

there is no apparent cause for calcium precipitation.

A common cause is hypercalciuria despite

Uric acid stones

normocalcaemia (see Chapter 6).

About 8 per cent of renal calculi contain uric acid; these

Hyperoxaluria favours the formation of the very

are sometimes associated with hyperuricaemia, with or

poorly soluble calcium oxalate, even if calcium

without clinical gout. In most cases, no predisposing

excretion is normal. The source of the oxalate may be

cause can be found. Precipitation is favoured in an acid

derived exogenously from the diet. Oxalate absorption

urine. Uric acid stones are usually small, friable and

is increased by fat malabsorption: calcium in the bowel

yellowish brown, but can occasionally be large enough

is bound to fat instead of precipitating with oxalate,

to form `staghorn' calculi. They are radiolucent but

which is then free to be absorbed. Foods rich in oxalate

may be visualized by ultrasound or by an intravenous

include rhubarb, chocolate, beetroot, spinach, nuts

pyelogram.

and tea.

The treatment of hyperuricaemia is discussed

Primary hyperoxaluria, a rare inborn error, should

in Chapter 20. If the plasma urate concentration is

be considered if renal calculi occur in childhood.

normal, ?uid intake should be kept high and the urine

There are two main types, 1 and 2, the former being

alkalinized. A low-purine diet may help to reduce urate

more common. Type 1 is due to de?ciency of alanine

production and excretion.

glyoxylate aminotransferase, and type 2 is due to

de?cient D -glycerate dehydrogenase. Hyperoxaluria

Cystine stones

(urinary oxalate greater than 400 æmol/24 h) is a more

Cystine stones are rare. In normal subjects the

important risk factor for formation of renal stones than

concentration of cystine in urine is soluble, but in

is hypercalciuria.

homozygous cystinuria this may be exceeded and the

Calcium-containing calculi are usually hard, white

patient may present with radio-opaque renal calculi.

and radio-opaque. Calcium phosphate may form

Like urate, cystine is more soluble in alkaline than in

`staghorn' calculi in the renal pelvis, while calcium

acidic urine; the principles of treatment are the same as

oxalate stones tend to be smaller and to lodge in the

for uric acid stones. Penicillamine can also be used to

ureters, where they are compressed into a fusiform

treat the condition (see Chapter 27).

shape. Alkaline conditions favouring calcium phosphate

precipitation and stone formation are particularly

Miscellaneous stones

common in patients with chronic renal infection.

Xanthine stones

The treatment of calcium-containing calculi depends

Xanthine stones are very uncommon and may be the

on the cause. Urinary calcium concentration should be

result of the rare inborn error xanthinuria.

reduced:

The kidneys

56

Indinavir stones

Exclude hypercalcaemia (see Chapter 6) and

hyperuricaemia (see Chapter 20).

These are seen in patients with human immuno-

Collect a 24-h specimen of urine for urinary volume,

deficiency virus (HIV) infection who have been treated

calcium and oxalate estimations. These tests will help

with the protease inhibitor indinavir. The stones are

to detect hypercalciuria or hyperoxaluria.

composed of pure protease inhibitor.

If all these tests are negative, and especially if there

Other stones

is a family history of calculi, screen the urine for

cystine. If the qualitative test is positive, the 24-h

Other rare stones may consist of dihydroxyadenine (due

excretion of cystine and basic amino acids should be

to adenine phosphoribosyltransferase deficiency) or

estimated.

poorly calcified mucoproteinaceous material associated

If fresh uninfected urine is alkaline despite a

with chronically infected kidneys (matrix stone). Some

systemic metabolic acidosis, the diagnosis of renal

stones may be factitious, as sometimes found in patients

tubular acidosis is likely (see Chapter 4). A pH more

with Munchausen's syndrome, who may add `stones' to

than 7 is suggestive of a urinary infection with a

their urine.

urea-splitting organism such as Proteus vulgaris , in

Investigation of a patient with renal calculi

which case consider struvite calculi. A midstream

If the stone is available, send it to the laboratory for

urine specimen is useful to exclude infection before

analysis (Fig. 3.9).

diagnosing renal tubular acidosis.

Evidence of renal calculi

Is stone fragment available for analysis?

No

Yes

Evidence of hyperuricaemia?

No

Yes

Evidence of hypercalcaemia and/or hypercalciuria?

No

Yes

Assess 24-h

urine oxalate

Low/normal

High

Hyperoxaluria

Measure

urine cystine

Low/normal

High

Cystinuria

Consider

rare calculi

(see Box 3.3)

Figure 3.9 Algorithm for the investigation of renal calculi.