Excessive diagnostic testing in acute kidney injury

We conducted a retrospective cohort study among inpatients at Brigham and Women’s Hospital (BWH). All protocols were approved by the BWH Institutional Review Board.

BWH is a 777-bed tertiary care academic medical center that provides care to an ethnically and socioeconomically diverse population. We analyzed all hospitalizations of adult patients (age ≥ 18) who were admitted in 2010 and developed AKI. While participants could only be considered to have a single episode of AKI per admission, AKI during subsequent admissions was also included and considered a separate AKI event. Thus, data were analyzed at the AKI-event level. We excluded patients with end-stage renal disease (ESRD) on maintenance hemo- or peritoneal dialysis and those who had undergone kidney transplantation.

We obtained data through the Research Patient Data Registry, a central clinical data warehouse maintained by Partners Healthcare System, of which BWH is a member. We obtained information on patient demographics (age, gender, race, comorbidities) and on patterns of diagnostic testing for AKI, including urine, blood, and radiology testing, as well as renal biopsy.

We defined and staged AKI according to the serum creatinine (SCr)-based criteria established by the Kidney Disease Improving Global Outcomes (KDIGO) Work Group [12]. Urine output data were not available. AKI was defined as an increase in SCr ≥0.3 mg/dl over any 48 h time period during hospitalization or ≥50 % increase in SCr over baseline known or presumed to have occurred within 7 days. For patients meeting criteria for AKI, we identified the AKI stage based on the ratio of maximum SCr during hospitalization divided by the baseline SCr, according to consensus criteria [12]. Baseline SCr was defined as the mean of all available outpatient SCr measurements obtained 7 to 365 days prior to admission, a validated approach described previously [13]. If no outpatient SCr values were available, the lowest SCr measurement during hospitalization was used as the baseline.

We manually reviewed the electronic medical record (EMR) of 100 randomly-selected patients and recorded the AKI etiology where it was known or suspected. In cases where AKI etiology was suspected to be multi-factorial, we recorded the two etiologies judged to be of primary importance.

The following urine, blood, radiology, and pathology tests were included as AKI diagnostic tests: urine tests – urinalysis, sediment, sodium, creatinine, urea, eosinophils, total protein, and protein electrophoresis (UPEP); blood tests – anti-neutrophil cytoplasmic antibody (ANCA), anti-glomerular basement membrane (anti-GBM) antibody, cryoglobulins, complement component 3 (C3), complement component 4 (C4), free light chains, and protein electrophoresis (SPEP); radiology tests – renal ultrasound and computerized tomography of the abdomen/pelvis (CTAP); pathology test – renal biopsy.

Urine and blood test results were determined to be normal or abnormal based on reference ranges provided by the BWH central laboratory. However, some tests such as urine sodium have normal physiologic variation and thus reference ranges are not applicable. These tests were therefore not categorized as normal or abnormal.

We manually reviewed all radiology reports. We considered CTAP tests as an AKI diagnostic test only if the indication for the test specifically mentioned AKI, acute renal failure, elevated SCr, decreased urine output, or concern for hydronephrosis. We categorized renal ultrasound and CTAP tests as abnormal if any abnormality was documented except simple cysts and non-obstructing stones and masses noted on prior imaging and found to be stable in size.

We evaluated the diagnostic yield of one urine test (eosinophils), four blood tests (SPEP, free light chains, ANCA, and cryoglobulins), and two radiology tests (renal ultrasound and CTAP). To evaluate diagnostic yield of urine and blood tests, we manually reviewed the EMR of patients with abnormal test results to determine whether the test affected the patient’s AKI diagnosis or management during that hospitalization or within 30 days of discharge. For example, for patients with an abnormal SPEP or serum free light chain test result we determined from progress notes and discharge summaries whether they were subsequently diagnosed with a plasma cell dyscrasia likely to be contributing to their AKI (e.g., cast nephropathy) or whether the test affected their subsequent management (e.g., intravenous fluids, chemotherapy, or additional testing such as renal biopsy or bone marrow biopsy). Additional examples are provided in Table 1. Since radiology tests often reveal abnormal findings that appear chronic or otherwise have limited immediate clinical relevance, we assessed the diagnostic yield of radiology tests based on whether an abnormal test resulted in a subsequent procedural intervention. For renal ultrasonography, abnormalities other than hydronephrosis (e.g., atrophy, cortical thinning, and other chronic changes) were not included in this analysis, since interventions are not typically performed for these findings.

Some diagnostic tests commonly ordered for the work-up of glomerulonephritis (ANCA, anti-GBM, and complement levels) and paraproteinemias (SPEP, UPEP, and serum free light chains) may also be ordered for purposes unrelated to AKI. We therefore manually reviewed the EMR of 50 randomly-selected patients who were tested for one of the above glomerulonephritis labs and 50 randomly-selected patients who were tested for one of the above paraproteinemia labs, and we determined the approximate frequency with which these tests were obtained for purposes related or unrelated to AKI. We classified each test into one of three categories: 1) obtained for AKI evaluation; 2) not obtained for AKI evaluation; 3) unable to determine whether ordered for AKI evaluation.

To evaluate the appropriateness of testing for glomerulonephritis and paraproteinemias in AKI, we manually reviewed the EMR of the same 100 patients above. We developed criteria to evaluate appropriateness of testing (Table 2) and applied those criteria to each patient. Further, we evaluated whether appropriateness of testing differed based on patient location (floor vs. ICU), ordering team (primary team vs. renal consult), and AKI stage.

The study cohort included 4903 patients with 5731 episodes of AKI (70.8 % of which were stage 1, 17.1 % stage 2, and 12.1 % stage 3). The number of patients admitted 1, 2, or ≥ 3 times with AKI was 4323 (75 %), 471 (8 %), and 109 (2 %), respectively. Additional baseline characteristics are shown in Table 3.

The major etiologies of AKI determined in a random subset of 100 AKI episodes were ischemic acute tubular necrosis (24 %), pre-renal azotemia (21 %), nephrotoxic acute tubular necrosis (10 %), cardiorenal syndrome (8 %), glomerulonephritis (5 %), obstruction (3 %), and hepatorenal syndrome (2 %). AKI etiology was unknown in 22 % of episodes. Etiologies for the remaining 5 % included acute interstitial nephritis (AIN), rhabdomyolysis, and tumor lysis syndrome.

The most commonly ordered tests in AKI were urinalysis and automated urine sediment examination (Fig. 1). Blood tests for vasculitis, glomerulonephritis, and paraproteinemias were ordered in fewer than 10 % overall, and more frequently for higher stages of AKI. Radiology testing with renal ultrasonography or CTAP was obtained in 10 % and 1 %, respectively. Kidney biopsies were performed in 28 patients (0.5 % of all AKI episodes).

Not all diagnostic tests during the course of AKI are obtained specifically for clarification of the cause or treatment of AKI (e.g., automated urinalysis, urine sodium, urine total protein). We therefore focused on those tests used most commonly to diagnose specific causes of AKI such as interstitial nephritis, paraprotein-related kidney disease, glomerulonephritides, and obstructive uropathy. Data on the number of tests performed, the number that were abnormal, and the number that affected AKI diagnosis or management are shown in Fig. 2. Additional data on frequency of abnormal results by AKI stage are shown in Table 4.

We conducted the following sensitivity analyses among 50 randomly selected patients who were tested for one of the “glomerulonephritis” labs (ANCA, anti-GBM, or complements), and an additional 50 randomly selected patients who were tested for one of the “paraproteinemia” labs (SPEP, UPEP, and serum free light chains):

Among the patients who were tested for one of the glomerulonephritis labs, 46 % were ordered specifically for AKI, 12 % were ordered for reasons unrelated to AKI, and 42 % were ordered for reasons which were not clearly documented. Among the 50 patients who were tested for one of the paraproteinemia labs, 44 % were ordered specifically for AKI, 6 % were ordered for reasons unrelated to AKI, and 50 % were ordered for reasons which were not clearly documented.

Using prespecified criteria (Table 2), we determined appropriateness of glomerulonephritis and paraproteinemia testing in AKI. Overall, glomerulonephritis and paraproteinemia testing was appropriate in 50 % and 54 % of tests, respectively (Fig. 3). When testing was ordered by the renal consult team compared to the primary team, appropriateness of testing was higher for glomerulonephritis testing (P=0.047), and showed a similar trend that did not reach statistical significance for paraproteinemia testing (P=0.09, Fig. 3). Similarly, when testing was ordered in patients with higher AKI stages, we found that appropriateness of testing was higher for paraproteinemia testing (P=0.04) but not for glomerulonephritis testing (P=0.13, Fig. 3).

Among the patients who underwent one of the glomerulonephritis tests, testing was normal in 45 out of 50 (90 %) tests, and affected AKI diagnosis or management in only 1 out of the 45 (2.2 %) normal tests (and in 0 out of the 5 abnormal tests). Specifically, in one case a negative ANCA test resulted in discontinuation of immunosuppressive medications. Among the patients who underwent one of the paraproteinemia tests, testing was normal in 39 out of 50 (78 %) tests, and affected AKI diagnosis or management in 0 out of the 39 normal tests (and in 4 out of the 11 abnormal tests).