The kidney is vulnerable to damage by the immune system [1]. The high blood flow rate through glomeruli exposes them to immunologically active cells. Antibodies and lymphocytes can attack vascular endothelial cells. Antigen-antibody complexes and complement molecules are trapped within the filtration barrier and taken up into mesangial cells and podocytes by endocytosis. Antibodies can be generated against antigens expressed in the glomerular basement membrane or on podocytes. Cell injury, inflammation and repair responses cause a wide range of kidney diseases.

Immunological tests on serum can help distinguish between conditions with clinically similar presentations. It is tempting to tick a number of boxes on the blood test request form to check for immune-mediated disease – a kidney disease ‘immunology screen’. However, this may not be a wise move.

There is a danger of a false positive result with all screening tests. The likelihood that a positive result will be ‘false’ is dependent upon the pre-test probability – the prior odds – that the patient actually has the disease in question.

For example, the chances of an anti-nuclear antibody (ANA) test being positive in a healthy older person can be as high as one in five. The chances that someone with slowly progressive chronic kidney disease with minimal proteinuria has systemic lupus erythematosus (SLE) are perhaps one in a thousand. So a positive ANA test in such a person has a 1000/5 = 200 to 1 chance of being a false positive.

Similarly, serum IgA levels are elevated in a high proportion of patients with IgA nephropathy . A raised level can be useful supportive evidence in a patient with other typical features of IgA nephropathy. However, serum IgA is elevated in many other conditions including chronic infection and so on its own is not diagnostically specific [2].

The risk of ignoring these laws of probability is that you will be led along a path of ever-more invasive tests to exclude a serious cause for the abnormal result. For example, immunoglobulins and a protein electrophoresis are often assayed in patients with chronic kidney disease to ‘exclude’ multiple myeloma. The finding of a monoclonal paraprotein raises the possibility that the paraprotein is the cause of the kidney disease and the patient would benefit from chemotherapy. In reality, it is more likely that the paraprotein is unrelated to the kidney disease, a monoclonal protein of undetermined significance (MGUS). You may be left with the dilemma of whether to exclude monoclonal protein-related kidney disease by performing a renal biopsy.

The following sections describe the most commonly used immunological tests with the clinical features that indicate when they are likely to have diagnostic value.

Clinical features:

Free lights chains are smaller than albumin and freely filtered by glomeruli. Their serum concentration is therefore dependent upon GFR and patients with reduced GFR have increased serum levels of polyclonal free light chains. The levels are further increased by inflammation and are associated with an increased risk of progression of chronic kidney disease and of mortality [3].

The ratio of kappa to lambda light chain concentrations is used to identify a monoclonal excess of one type of chain. An abnormal ratio is not proof of clonality; further tests are needed to prove a monoclonal plasma cell disorder.

Monoclonal free light chains in the urine (Bence Jones protein) are not detected by dipstick testing but the laboratory urine protein assay does detect them. A specific test for free light chain is the most sensitive.

About half of people with SLE have kidney involvement, this proportion being higher in men and in black races. The pattern of kidney disease is very variable, ranging from asymptomatic urine abnormalities to acute nephritis and nephrotic syndrome . A biopsy is required to characterise the type of kidney disease.

Histological appearances are grouped into six classes, each associated with different clinical features and requiring different treatment [6].

Components of the complement cascade (Fig. 14.4) are consumed in a range of auto-immune disorders.

Immune complexes of antibody and antigen are deposited in the glomeruli where they can fix complement and cause glomerulonephritis. Deposits of the C3 component of complement are the common feature in a recently characterised category of glomerulonephritis [7].

Serum C3 and C4 levels are reduced in patients with nephritis associated with SLE and cryoglobulinaemia . This suggests activation of the classical and alternative pathways. C4 levels may be unreliable for monitoring SLE nephritis because genetic deficiencies of C4 are relatively common and cause a low C4 without disease.

C3 is usually decreased more than C4 in patients with C3 glomerulopathy , Dense Deposit Disease , post-streptococcal glomerulonephritis , bacterial endocarditis glomerulonephritis and cholesterol crystal embolism . This suggests activation of the alternative pathway.

The drop in C3 found in children with post-streptococcal glomerulonephritis is usually short lasting. If the level of C3 remains low for longer than eight weeks, the autoantibody ‘C3 nephritic factor’ that blocks the regulation of C3 activation may be present [8].