Nephrotoxicity due to contrast media

Contrast media nephrotoxicity may be defined as a 25% increase in creatinine

occurring within 3 days of the intravascular administration of contrast media.
Risk factors include

known renal impairment (especially diabetic nephropathy)

age > 70 years

dehydration

cardiac failure

the use of nephrotoxic drugs such as NSAIDs

Prevention

the evidence base currently supports the use of intravenous 0.9% sodium
chloride at a rate of 1 mL/kg/hour for 12 hours pre- and post- procedure.
There is also evidence to support the use of isotonic sodium bicarbonate

N-acetylcysteine (usually given orally) has been shown to reduce the

incidence of contrast-nephropathy in some studies but the evidence base
is not as strong as for fluid therapy

1. NICE Guideline 171. Urinary incontinence. The management of urinary

incontinence in women. September 2013

Urinary incontinence
Urinary incontinence (UI) is a common problem, affecting around 4-5% of the
population. It is more common in elderly females.

Causes

overactive bladder (OAB)/urge incontinence: due to detrusor over activity

stress incontinence: leaking small amounts when coughing or laughing

mixed incontinence: both urge and stress

overflow incontinence: due to bladder outlet obstruction, e.g. due to

prostate enlargement

Initial investigation

bladder diaries should be completed for a minimum of 3 days

vaginal examination to exclude cystocele

urine dipstick and culture

Management depends on whether urge or stress UI is the predominant picture. If

urge incontinence is predominant:

bladder retraining (lasts for a minimum of 6 weeks, the idea is to gradually

increase the intervals between voiding)

bladder stabilising drugs:antimuscarinic) is first-line

surgical management: e.g. sacral nerve stimulation

If stress incontinence is predominant:

pelvic floor muscle training (for a minimum of 3 months)

surgical procedures: e.g. retropubic mid-urethral tape procedures

The patient is presenting with polyuria in the absence of other urinary symptoms
associated with diarrhoea and weight loss. There is no evidence of a 'common' (>
1 in 10) cause of polyuria, for example diuretics, caffeine or diabetes. Therefore
the most appropriate next test is thyroid function tests, particularly in the setting of
other possible symptoms of thyrotoxicosis. Hyperthyroidism is an 'infrequent'
cause of polyuria (> 1 in 100).
While paired serum and urine osmolalities may be indicated they are to detect
diabetes insipidus, a 'very rare' cause of polyuria (< 1 in 10,000) and are
therefore much less likely to make a positive diagnosis of this patient's polyuria.
Desmopressin administration is performed after identification of diabetes
insipidus to distinguish between a cranial or nephrogenic origin and would not be
appropriate at this stage.
The clinical case does not point towards pelvic floor dysfunction necessitating
urodynamic studies. While testing for coeliac disease may be indicated given
positive family history and diarrhoea, this diagnosis would not explain the
patient's polyuria.

Polyuria
A recent review in the BMJ categorised the causes of polyuria by how common
they were. This does not of course tally with how common they are in exams!
Common (>1 in 10)

diuretics, caffeine & alcohol

diabetes mellitus

lithium

heart failure

Infrequent (1 in 100)

hypercalcaemia

hyperthyroidism

Rare (1 in 1000)

chronic renal failure

primary polydipsia

hypokalaemia

Very rare (<1 in 10 000)

diabetes insipidus

The scenario highlights the candidates understanding of the approach to

the management of pre renal azotaemia. The patient described is
dehydrated, owing to her fever and insensible fluid losses, due to which
she is hypotensive. Her urinary electrolytes show that her kidneys are
functioning as one would expect them to in the face of impaired renal
perfusion, i.e. they are producing concentrated urine and retaining sodium.
The derangement of renal function is due to the impaired renal blood flow
and is pre-renal in nature.
All causes of pre-renal azotaemia may lead to acute kidney injury and by
definition, excretory function improves once normal renal perfusion has
been restored. The criteria for distinction between pre renal azotaemia and
intrinsic renal dysfunction are highlighted below:
Although she suffers from SLE and her renal impairment may be
secondary to lupus nephritis, the urinary electrolytes suggest a pre renal
component rather than an intrinsic parenchymal pathology.

Acute kidney injury: acute tubular necrosis vs. prerenal

uraemia

Prerenal uraemia - kidneys hold on to sodium to preserve volume

Pre-renal uraemia

Acute tubular necrosis

Urine sodium

< 20 mmol/L

> 30 mmol/L

Fractional sodium excretion*

< 1%

> 1%

Fractional urea excretion**

< 35%

>35%

Urine:plasma osmolality

> 1.5

< 1.1

Urine:plasma urea

> 10:1

< 8:1

Specific gravity

> 1020

< 1010

Urine

'bland' sediment

brown granular casts

Response to fluid challenge

Yes

No

fractional sodium excretion = (urine sodium/plasma sodium) / (urine *

creatinine/plasma creatinine) x 100
fractional urea excretion = (urine urea /blood urea ) / (urine **
creatinine/plasma creatinine) x 100

This patient presents with a nephrotic syndrome, characterised by oedema,

proteinuria and hypoalbuminuria. The underlying diagnosis is actually given to
you by the renal biopsy findings of podocyte fusion, pathopneumonic of minimal
change disease. His recent viral illness seems to be classical for infectious
mononucleosis, which can predispose to minimal change disease. A recent
respiratory tract infection should alert you to mesangioproliferative
glomerulonephropathy, caused by IgA deposition acutely following an upper

respiratory tract infection, and diffuse proliferative glomerulonephritis, caused by

reduced C3 and diffuse glomerular proliferation around 2 to 3 weeks after a
streptococcal infection. Both however, classically present as nephritic syndrome
or at least haematuria. Focal segmental glomerulosclerosis is a consequence of
diffuse renal damage and is linked to HIV, sickle cell anaemia and intravenous
heroin abuse, not marijuana.

Minimal change disease

Minimal change disease nearly always presents as nephrotic syndrome,
accounting for 75% of cases in children and 25% in adults.
The majority of cases are idiopathic, but in around 10-20% a cause is found:

drugs: NSAIDs, rifampicin

Hodgkin's lymphoma, thymoma

infectious mononucleosis

Pathophysiology

T-cell and cytokine mediated damage to the glomerular basement

membrane polyanion loss

the resultant reduction of electrostatic charge increased glomerular

permeability to serum albumin

Features

nephrotic syndrome

normotension - hypertension is rare

highly selective proteinuria*

renal biopsy: electron microscopy shows fusion of podocytes

Management

majority of cases (80%) are steroid responsive

cyclophosphamide is the next step for steroid resistant cases

Prognosis is overall good, although relapse is common. Roughly:

1/3 have just one episode

1/3 have infrequent relapses

1/3 have frequent relapses which stop before adulthood

only intermediate-sized proteins such as albumin and transferrin leak through the *
glomerulus
is patient has had a bowel resection for UC, both of these conditions are risk
factors for developing oxalate stones. The stone is radio-opaque which excludes
urate and xanthine stones. Magnesium pyrophosphate or 'Staghorn calculi'
involve the renal pelvis and extend into at least 2 calyces, the presence of the
stone in the ureter excludes this.

Renal stones: imaging

The table below summarises the appearance of different types of renal stone on
x-ray
Type

Frequency

Radiograph appearance

Calcium oxalate

40%

Opaque

Mixed calcium oxalate/phosphate stones

25%

Opaque

Type

Frequency

Radiograph appearance

Triple phosphate stones*

10%

Opaque

Calcium phosphate

10%

Opaque

Urate stones

5-10%

Radio-lucent

Cystine stones

1%

Semi-opaque, 'ground-glass' appeara

Xanthine stones

<1%

Radio-lucent

stag-horn calculi involve the renal pelvis and extend into at least 2 calyces. They *
develop in alkaline urine and are composed of struvite (ammonium magnesium
phosphate, triple phosphate). Ureaplasma urealyticum and Proteus infections
predispose to their formation