Table 1.

Recommended initial testing in the patient being evaluated for glomerular disease¹

Test	Specific Purpose	Comments
1. 24-h urine collection	Quantify proteinuria. Spot PC (protein/creatinine ratio) is not recommended for this purpose because it is unreliable in individual patients [66,85,87–89]. Measuring albuminuria is useful in monitoring low-level glomerular proteinuria. However, once the total proteinuria exceeds 500 mg/d, albuminuria is about 60–80% of total proteinuria. So, proteinuria provides the same information as albuminuria, and is less expensive [6].	Also recommended is the measurement of sodium, potassium, and urea content of the collection. If the collection is a complete or nearly 24-h collection, these are reliable estimates of 24-h intake of salt, potassium, and protein, which are important for nutrient management the CKD patient [38].
2. Serum albumin	Assess severity of the disruption of the GFB, and whether protein nutrition, and hepatic albumin synthesis is adequate.	At any given level of proteinuria, the lower the serum albumin, the greater is the glomerular permeability to albumin. The serum albumin also assesses nutritional/liver status. For example, if proteinuria is modest (e.g., 3.0 g/d) and serum albumin is low (e.g., 1.5 g/dl), this suggests that a low rate of albumin synthesis is partly to blame for the low albumin level. This may be nutritional or related to liver disease.
3. LDH	Assess for hemolysis, or damage to muscles or viscera.	In the absence of muscle injury or visceral organ necrosis, elevated LDH is evidence for hemolysis (e.g., a thrombotic microangiopathy).
4. Reticulocyte count Platelet count	Assess for increased or decreased red cell production. Assess for thrombotic microangiopathy.	If elevated reticulocyte count or decreased platelet count, do blood smear to search for schistocytes and haptoglobin to assess for intravascular hemolysis. These will assess for thrombotic microangiopathy, which can cause glomerular disease (e.g., vasculitis, antiphospholipid syndrome, TTP, HUS, aHUS, scleroderma, malignant hypertension, blood stream infection, and the cryoglobulinemias).
5. C3, C4	Test for disorders that activate the classical or alternative complement pathways.	Low C3 and C4 are characteristic of the glomerulonephritis caused by deposition of circulating immune complexes (e.g., SLE, infective endocarditis). Normal or nearly normal C3 with very low C4 is characteristic of Type 2 and Type 3 cryoglobulinemia. Very low C3 and normal C4 is characteristic of post-streptococcal glomerulonephritis. Low C3 and normal C4 is seen in HUS, aHUS, C3 glomerulopathy, and idiopathic MPGN Type 1 [50].
6. Serum protein electrophoresis (SPEP) + free light chains	Screen for monoclonal gammopathy (SPEP + free light chains), or hypogammaglobulinemia, hypergammaglobulinemia (SPEP). Serum or urine for immunofixation is not recommended for routine screening because it is much more expensive than SPEP + free light chains, which are sensitive and specific for detection of monoclonal gammopathy [90].	If monoclonal protein is present on SPEP, and/or there is an abnormal ratio of kappa/lambda light chains, serum immunofixation is indicated to characterize the monoclonal proteins [90] (see Algorithm 1). If hypogammaglobulinemia is present, measure serum IgG, IgA, IgM levels to assess for immunodeficiency. If hyperglobulinemia is present, measure serum IgG, IgA, IgM levels. If IgG is is increased, measure IgG isotypes (IgG1,2,3,4) to test for IgG4 disease.
7. Hepatitis B surface antigen, Hepatitis C antibody, and HIV (if risk factors for HIV are present)	These infections are common causes of glomerular disease.	Even if the patient’s glomerular diseases is not the result of one of these infections, it is important to know whether these infections are present, especially if immunosuppressive therapy is planned.
8. ANA	Screen for autoimmune disorders	See text for Limitations of ANA testing to identify SLE and (other autoimmune disorders)
9. ANCA	Screen for ANCA-related vasculitis	See text for Limitations of ANCA testing. If ANCA is present, test for anti-myeloperoxidase (if pANCA positive) or proteinase 3 (if c-ANCA positive).
10. Rheumatoid factor	Screen for cryoglobulinemias (Types 2 and 3), and certain autoimmune disorders.	In cryoglobulinemic glomerulonephritis, plasma cryoglobulins are often undetectable. So, the rheumatoid factor serves as a surrogate marker for Type 2 and Type 3 cryoglobulinemia. This is especially helpful in cryoglobulinemic glomerulonephritis because often the deposits are cleared rapidly and are not present in the kidney biopsy.

¹Not included in this list is testing that is routinely indicated in the CKD patient, such as intact PTH, serum creatinine, BUN, electrolytes, blood glucose, lipid panel, calcium, phosphorus, bilirubin, ALT, AST, CBC and urinalysis (as discussed above).