Could my patient with acute dysuria and less than 10,000 E. coli/ml on urine culture still have a urinary tract infection (UTI)?

Absolutely! Although historically ≥100,000 bacteria/ml has been used as a criterion for UTI based on studies of women with pyelonephritis in the 1950s,1 several studies have since found that this criterion may not be met in up to 50% of symptomatic patients with UTI. 2-6 A lower criterion of 100-1,000 bacteria/ml of urine increases the sensitivity of urine culture to ~90% or more for diagnosis of UTI (albeit with lower specificity). 2-5

A 1982 NEJM study involving UTIs due to coliforms in acutely dysuric women found that the traditional count of ≥100,000 bacteria/ml in midstream urine missed ~50% of cases based on positive bladder cultures. 2 Similarly a 2013 NEJM study reported that 40% of women with symptomatic UTI would be missed if the ≥100,000 bacteria/ml criterion for midstream urine is used. 3

Among symptomatic men, 32% have been found to have <100,000 bacteria/ml in their midstream urine 4 and a single urine specimen by urethral catheterization growing ≥ 100 bacteria/ml is consistent with bacteriuria for both men and women. 5

Since most of these studies have involved UTI caused by E. coli or other coliforms, more data are needed to find out if the same findings apply to non-coliform urinary pathogens.

Bonus Pearl: Did you know that because quantitative urine culture results are concentration dependent (ie, “per ml”), a dilute urine—as may be found in patients experiencing diuresis—will result in lower numbers of bacteria/ ml. 5

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 References

  1. Kass EH. Asymptomatic infections of the urinary tract. Trans Assoc Am Physicians 1958;69:56-74. https://pubmed.ncbi.nlm.nih.gov/13380946/
  2. Stamm WE, Counts GW, Running KR, et al. Diagnosis of coliform infection in acutely dysuric women. N Engl J Med 1982;307:463-8. https://pubmed.ncbi.nlm.nih.gov/7099208/
  3. Hooten TM, Roberts PL, Cox ME, et al. Voided midstream urine culture and acute cystitis in premenopausal women. N Engl J Med 2013;369:1883-91. https://www.nejm.org/doi/full/10.1056/NEJMoa1302186
  4. Lipsky BA, Ireton RC, Fihn SD, et al. Diagnosis of bacteriuria in men: specimen collection and culture interpretation. J Infect Dis 1987;155:847-54. https://pubmed.ncbi.nlm.nih.gov/3559288/
  5. Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America Guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005;40:643-54. https://pubmed.ncbi.nlm.nih.gov/15714408/
  6. Roberts KB, Wald ER. The diagnosis of UTI: colony count criteria revisited. Pediatrics 2018;141:e20173239. https://doi.org/10.1542/peds.2017-3239

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Could my patient with acute dysuria and less than 10,000 E. coli/ml on urine culture still have a urinary tract infection (UTI)?

Could measurement of urinary albumin-protein ratio be useful in my patient with renal insufficiency and proteinuria?

A spot urine test for determination of albumin-protein ratio (uAPR) may be useful in distinguishing glomerular vs tubulointerstitial source of proteinuria. A low (<0.4) uAPR, defined as urinary albumin to creatinine ratio(uACR)/urinary protein to creatinine ratio (uAPR) is more suggestive of a tubulointerstitial renal disease and less suggestive of glomerular pathology.1-3  

A 2012 study involving simultaneous measurements of urinary albumin and total protein in over 1000 proteinuric patients found a relatively high (0.84) area under curve (AUC) in a receiver operating characteristic curve analysis for uAPR (vs 0.74 for uACR and 0.54 for uPCR) in discriminating between tubular and non-tubular proteinuria pattern on urine protein electrophoresis and immunofixation. An uAPR cut-off of <0.4 was found to be 88% sensitive and 99% specific for the diagnosis of primary tubulointerstitial disorders on renal biopsy.1  

Due to the limitations of this study (including a relatively small subset of patient who had renal biopsy), a related editorial concluded that a low uAPR gives a “reasonable prediction of a tubular electrophoretic proteinuria”, but that it warrants further validation. Nevertheless, uAPR could potentially be useful in patients with moderate proteinuria (>300 mg/day to <3 g/day) who have not had renal biopsy and  where assessment of likelihood of tubulointerstitial vs glomerular source of proteinuria is desired.3 Interestingly, the utility of uAPR in predicting non-glomerular source of hematuria has also been reported.4

Bonus pearl: Did you know that the negatively-charged glomerular capillary wall repels negatively charged albumin thus preventing its filtration (charge-barrier) (5)?  

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References

  1. Smith ER, Cai MMX, McMahon LP, et al. The value of simultaneous measurement of urinary albumin and total protein in proteinuric patients. Nephrol Dial Transplant 2012;27:1534-41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035283/
  2. Fraser SDS, Roderick PJ, McIntyre NJ, et al. Assessment of proteinuria in patients with chronic kidney disease stage 3: albuminuria and non-albumin proteinuria. PLOS ONE 2014;9:e98261. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035283/pdf/pone.0098261.pdf
  3. Ellam T, Nahas ME. Urinary albumin to protein ratio: more of the same or making a difference. Nephrol Dial Transplant 2012;27:1293-96. https://www.ncbi.nlm.nih.gov/pubmed/22362784
  4. Ohisa N, Yoshida K, Matsuki R, et al. A comparison of urinary albumin-total protein ratio to phase-contrast microscopic examination of urine sediment for differentiating glomerular and nonglomerular bleeding. Am J Kidney Dis 2008;52:235-41. https://www.ajkd.org/article/S0272-6386(08)00828-7/pdf
  5. Venkat KK. Proteinuria and microalbuminuria in adults: significance, evaluation, and treatment. S Med J 2004;97:969-79. https://internal.medicine.ufl.edu/files/2012/07/5.18.05.04.-Proteinuria-review.pdf
Could measurement of urinary albumin-protein ratio be useful in my patient with renal insufficiency and proteinuria?