Glomerular Disease

and Christopher Isles²

(1)

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK

(2)

Dumfries and Galloway Royal Infirmary, Dumfries, UK

Q1 What does the term glomerular disease mean?

Glomerular disease is a general term for a group of disorders affecting both kidneys in which there is usually, but not always, immunologically mediated injury to glomeruli, with renal interstitial damage a regular accompaniment. The clinical hallmark of glomerular disease is proteinuria.

Q2 Describe the pathophysiology of glomerular disease

The immunological insult is either by antigen antibody complexes deposited or formed on the glomerular basement membrane (GBM) or by antibodies directed towards the GBM. Antigen antibody complex deposition is thought to be the more common of the two mechanisms. The term ‘glomerulonephritis’ is often used to describe this group of disorders even if not all of them are due to inflammation.

Q3 How might you classify glomerular disease?

This is an area that medical students and junior doctors often find confusing. Glomerular disease can be classified by presentation, by cause and by pathology. The difficulty is that a particular presentation may have more than one cause and more than pathology. We have adopted a workable but simplified approach here.

Q4 How does glomerulonephritis present?

The glomerulus has a limited number of ways of responding to a variety of different stimuli. The following five clinical presentations of glomerular disease are recognised:

Box 21.1 Five presentations of glomerular disease

Asymptomatic urinary abnormality i.e. proteinuria, haematuria or both

Acute nephritis

Nephrotic syndrome

Rapidly progressive renal failure

Chronic kidney disease

Q5 What is meant by asymptomatic urinary abnormalities?

The term describes patients whose only presenting features are asymptomatic proteinuria (i.e. not associated with oedema) or haematuria (which may be visible or non visible) or both. The detection and measurement of proteinuria and haematuria have been described in an earlier chapter

Q6 What do you understand by the term acute nephritis?

This is the name given to a syndrome that is no longer very common but usually occurs 10–14 days after an infection, classically a streptococcal sore throat. The features of acute nephritis are malaise, oliguria, hypertension, proteinuria (but not usually nephrotic range), haematuria (urine is often described as ‘smoky’ or ‘coke coloured’), mild oedema and impaired renal function. Acute nephritis usually settles rapidly, although proteinuria and microscopic haematuria may persist for years. In a small proportion of patients the disease may become chronic, leading to renal failure.

Q7 What do you understand by the term nephrotic syndrome?

Nephrotic syndrome, which is more common in children than in adults, is characterised by the five features shown in Box 21.2. The cutpoints for proteinuria and hypoalbuminaemia required for diagnosis vary slightly depending on the textbook or guideline you happen to be reading – we have chosen urine PCR 350 mg/mmol and serum albumin 35 g/l because they are easy to remember.

Box 21.2 Five features of nephrotic syndrome

Oedema

Proteinuria with urine PCR >350 mg/mmol (equivalent to proteinuria >3.5 g/day).

Hypoalbuminaemia <35 g/l.

Prothrombotic tendency.

Hyperlipidaemia.

Patients with nephrotic syndrome can present with venous thrombo-embolism which occurs because their urinary protein loss includes fibrinolytic factors e.g. anti-thrombin III (see case history). They may also be hyperlipidaemic because their livers produce more lipoproteins as part of a generalised increase in protein synthesis to make up for the loss of protein in the urine.

Case Report

A 68 year old man presented with a swollen left leg and pleuritic chest pain. Ultrasonongraphy confirmed a recent thrombus in the superficial femoral vein. He had dipstick urine of ++++ protein and a serum albumin of 24 g/l, both of which were overlooked at the time. Renal function was normal. The patient represented 2 months later with swelling of both legs while on warfarin with an INR of 1.3. Doppler showed a resolving DVT in the left superficial femoral vein but no DVT in the right leg. Urinalysis was not carried out on this occasion and a low serum albumin of 20 g/l was again overlooked. Three weeks later the general practitioner referred the patient for a third time as both legs were by now swollen to the upper thigh. A degree of redness led to a diagnosis of cellulitis and treatment with benzylpenicillin and flucloxacillin. Once again urinalysis was not performed and the serum albumin of 22 g/l was ignored. After discharge his GP noted heavy proteinuria and referred the patient directly to the Renal Unit where urine protein was quantified at 12.3 g/24 h and a diagnosis of nephrotic syndrome was confirmed. Renal biopsy showed that this was caused by membranous nephropathy.Ambler B et al. Nephrotic syndrome presenting as deep vein thrombosis or pulmonary embolism. Emergency Med J. 2008;25:241–42; with permission from BMJ Publishing Group Ltd.

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