#5414 clinical utility of serological test at time of biopsy

Abstract Background and Aims It is common practice to order serological tests at time of renal biopsy, but the diagnostic value in different clinical settings is largely unknown. We utilized data from the national Swedish Renal Biopsy Registry to analyze the positive and negative post-test likelihood of four common diagnoses depending on the results of frequently used serological tests. Method Data on all biopsies performed during the period 2015-01-01 – 2020-12-31 was retrieved from the Swedish Renal Biopsy Registry. All biopsies are classified into one of the following five biopsy indications: the nephrotic syndrome (nephrosis), acute/subacute nephritic syndrome (nephritis), other acute kidney injury (AKI), chronic kidney disease stage 1-2 (CKD 1-2), and CKD 3-5. Biopsy results are given as SNOMED codes by the pathologist and a clinical diagnosis using the ERA coding system by the nephrologist. Results from the following serological tests were analyzed: C3, C4, ANA, anti-dsDNA, ANCA (PR3 and/or MPO-ANCA) and anti-phospholipid antibodies. Pre-test likelihood, positive post-test (PPL) and negative post-test likelihood (NPL) for the diagnoses IgA nephropathy (IgAN), diabetic nephropathy (DN), ANCA-associated vasculitis (AAV) and lupus nephritis (LN) were analyzed. The diagnostic yield was defined as the ratio between the PPL and NPL. Results Out of a total of 3165 individuals that had undergone kidney biopsy, there were 694 (21.9%) patients assigned a diagnosis of IgAN, 378 (11.9%) with DN, 342 (10.8%) with AAV and 117 (3.7%) with LN. The proportion of patients being tested varied from 17% for anti-phospholipid antibodies to 77% for ANCA. The highest diagnostic yield was found for ANCA in AAV were the PPL/NPL ratio was 154. In patients with nephrosis the ratio went up to 290 mainly because of a very low NPL (0.2%). The next best diagnostic yield was seen in SLE were both ANA and anti-dsDNA exhibited a PPL/NPL ratio of 26. The best yield for ANA was found when the biopsy indication was nephrosis where the PPL was 33% and the NPL 0.54% and the ratio 61. For anti-dsDNA the best yield was in AKI with a ratio of 46 (PPL 55%, NPL 1.1%). The best test to make a diagnosis less likely was anti-phospholipid antibodies in diabetic nephropathy. The test was never positive in any of the 42 patients with this diagnosis, however the same result slightly increased the likelihood of AAV. A positive result for C3(reduced levels) also reduced the likelihood av diabetic nephropathy, the PPL / NPL ratio was 13. C4 and ANCA being, on the other hand, reduced the likelihood for IgAN with a ratio in the same range. Conclusion While the utility of ANCA, ANA and anti-dsDNA is well known, it is less known when a positive test substantially reduced the likelihood of a disease. Here we present data showing that a positive test for C3 decreases the likelihood of DN, while the likelihood is much less affected by C4. The opposite Is seen for IgAN.