A report of fever and chills, flank pain, and irritative voiding symptoms (e.g., urgency, frequency, and dysuria) should prompt a workup. Other key symptoms include nausea, vomiting, and dehydration. It is also critical to be aware of signs of sepsis (e.g., tachycardia, tachypnea, hypotension, fever or hypothermia, poor capillary refill, mottled or ashen skin, cyanosis, newly altered mental state, or reduced urine output).[32]National Institute for Health and Care Excellence. Suspected sepsis: recognition, diagnosis and early management. Mar 2024 [internet publication].
https://www.nice.org.uk/guidance/ng51
The triad of flank pain, fever, and nausea and vomiting occurs much more often in patients with pyelonephritis than in those with cystitis.[33]Fairley KF, Carson NE, Gutch RC, et al. Site of infection in acute urinary-tract infection in general practice. Lancet. 1971 Sep 18;2(7725):615-8.
http://www.ncbi.nlm.nih.gov/pubmed/4105942?tool=bestpractice.com
Physical exam
Temperature greater than 100.4ºF (38.0ºC) is a key finding supporting the diagnosis. In one study, temperature greater than or equal to 100ºF (37.8ºC) was strongly correlated with acute pyelonephritis.[34]Pinson AG, Philbrick JT, Lindbeck GH, et al. Fever in the clinical diagnosis of acute pyelonephritis. Am J Emerg Med. 1997 Mar;15(2):148-51.
http://www.ncbi.nlm.nih.gov/pubmed/9115515?tool=bestpractice.com
Tachycardia and hypotension may be present. Costovertebral angle tenderness may be pronounced.
Laboratory tests
Initial laboratory tests in all patients with suspected pyelonephritis are urinalysis and urine culture.[5]Czaja CA, Scholes D, Hooton TM, Stamm WE. Population-based epidemiologic analysis of acute pyelonephritis. Clin Infect Dis. 2007 Aug 1;45(3):273-80.
http://www.ncbi.nlm.nih.gov/pubmed/17599303?tool=bestpractice.com
[35]European Association of Urology. Guidelines on urological infections. 2024 [internet publication].
https://uroweb.org/guidelines/urological-infections
Urinalysis shows pyuria, bacteriuria, and varying degrees of hematuria. Do not define microhematuria by positive dipstick testing alone. Microhematuria is defined as three or more red blood cells per high-powered field on microscopy of a properly collected urinary specimen.[36]American Urological Association. Fifteen things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. Jul 2022 [internet publication].
https://web.archive.org/web/20230307140800/https://www.choosingwisely.org/societies/american-urological-association
[37]Barocas DA, Boorjian SA, Alvarez RD, et al: Microhematuria: AUA/SUFU guideline. J Urol. 2020 Oct;204(4):778-86.
https://www.auajournals.org/doi/10.1097/JU.0000000000001297
http://www.ncbi.nlm.nih.gov/pubmed/32698717?tool=bestpractice.com
Pyuria is almost invariably present; in fact, its absence should prompt consideration of an alternative diagnosis. WBC casts, if present, suggest a renal origin for the pyuria. A Gram stain performed on spun urine can sometimes help distinguish gram-negative from gram-positive organisms, thus influencing the choice of therapy. The specificity of these tests in patients with acute pyelonephritis is less than 28% with a misdiagnosis rate (with regard to specific site of infection) of 55% of cases.[38]Garin EH, Olavarria F, Araya C, et al. Diagnostic significance of clinical and laboratory findings to localize site of urinary infection. Pediatr Nephrol. 2007 Jul;22(7):1002-6.
http://www.ncbi.nlm.nih.gov/pubmed/17375337?tool=bestpractice.com
Urine culture (from a clean-catch or catheterized specimen) shows heavy growth of the causative pathogen (classically ≥100,000 colony-forming units [CFUs] per milliliter of voided urine).[39]Miller JM, Binnicker MJ, Campbell S, et al. Guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2024 update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). Clin Infect Dis. 2024 Mar 5:ciae104.
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciae104/7619499
http://www.ncbi.nlm.nih.gov/pubmed/38442248?tool=bestpractice.com
Blood cultures are indicated in more severely ill patients. Blood cultures are positive for the causative pathogen in approximately 10% to 20% of women with acute uncomplicated pyelonephritis.
Other initial laboratory tests indicated in the initial workup are complete blood count, erythrocyte sedimentation rate, and serum C-reactive protein.[40]Masajtis-Zagajewska A, Kurnatowska I, Wajdlich M, et al. Utility of copeptin and standard inflammatory markers in the diagnostics of upper and lower urinary tract infections. BMC Urol. 2015 Jul 8;15:67.
https://bmcurol.biomedcentral.com/articles/10.1186/s12894-015-0061-2
http://www.ncbi.nlm.nih.gov/pubmed/26152182?tool=bestpractice.com
Procalcitonin (a propeptide produced by the monocytes-macrophage cells during bacterial infections) is a more specific diagnostic marker of bacterial infection and values appear to correlate with severity.[41]Xu RY, Liu HW, Liu JL, et al. Procalcitonin and C-reactive protein in urinary tract infection diagnosis. BMC Urol. 2014 May 30;14:45.
https://bmcurol.biomedcentral.com/articles/10.1186/1471-2490-14-45
http://www.ncbi.nlm.nih.gov/pubmed/24886302?tool=bestpractice.com
[42]Simon L, Gauvin F, Amre DK, et al. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis. 2004 Jul 15;39(2):206-17.
http://www.ncbi.nlm.nih.gov/pubmed/15307030?tool=bestpractice.com
Do not perform procalcitonin testing without an established, evidence-based protocol.[43]American Society for Clinical Pathology. Thirty five things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. Jul 2021 [internet publication].
https://web.archive.org/web/20230316185857/https://www.choosingwisely.org/societies/american-society-for-clinical-pathology
Interleukins (IL-6, IL-32), as acute-phase reactants, are also being evaluated as possible markers to distinguish lower urinary tract infections from pyelonephritis.[44]Azab S, Zakaria M, Raafat M, et al. The combination of urinary IL-6 and renal biometry as useful diagnostic tools to differentiate acute pyelonephritis from lower urinary tract infection. Int Braz J Urol. 2016 Jul-Aug;42(4):810-6.
http://www.intbrazjurol.com.br/pdf/vol42n04/Azab_810_816.pdf
http://www.ncbi.nlm.nih.gov/pubmed/27564295?tool=bestpractice.com
Copeptin is a C-terminal part of pro-vasopressin (CT-pro-AVP) that is released along with vasopressin and has been investigated for use as a diagnostic tool in bacterial infections and sepsis.[40]Masajtis-Zagajewska A, Kurnatowska I, Wajdlich M, et al. Utility of copeptin and standard inflammatory markers in the diagnostics of upper and lower urinary tract infections. BMC Urol. 2015 Jul 8;15:67.
https://bmcurol.biomedcentral.com/articles/10.1186/s12894-015-0061-2
http://www.ncbi.nlm.nih.gov/pubmed/26152182?tool=bestpractice.com
Imaging studies
Additional imaging is not usually necessary for diagnosis but can often be useful when patients are not responding to treatment as expected or after 72 hours.[45]American College of Radiology. ACR Appropriateness Criteria®. Acute pyelonephritis. 2022 [internet publication].
https://acsearch.acr.org/docs/69489/Narrative
In patients with complicated infections, renal ultrasound may aid diagnosis by identifying hydronephrosis from a stone or other source of obstruction or show intra- or perirenal fluid collections and cysts.[46]Stunell H, Buckley O, Feeney J, et al. Imaging of acute pyelonephritis in the adult. Eur Radiol. 2007 Jul;17(7):1820-8.
http://www.ncbi.nlm.nih.gov/pubmed/16937102?tool=bestpractice.com
[47]Garcia-Ferrer L, Primo J, Juan Escudero JU, et al. The use of renal ultrasound for adult acute pyelonephritis. Arch Esp Urol. 2007 Jun;60(5):519-24.
http://www.ncbi.nlm.nih.gov/pubmed/17718205?tool=bestpractice.com
Contrast-enhanced spiral computed tomography (CECT) and/or magnetic resonance imaging of the abdomen can further delineate structural abnormalities to help guide therapy. Computed tomography of the abdomen can expose subjects to considerable radiation, but may be easier to schedule and is less expensive than magnetic resonance imaging.[45]American College of Radiology. ACR Appropriateness Criteria®. Acute pyelonephritis. 2022 [internet publication].
https://acsearch.acr.org/docs/69489/Narrative