College of American Pathologists
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  Q & A





December 2010

Fredrick L. Kiechle, MD, PhD

Question Q. We had a discussion about the glomerular filtration rate calculator on the National Kidney Disease Education Program’s website. The calculator gives the choices of only serum and plasma. What about whole blood? Since whole blood creatinine testing is available, what are people using to calculate the estimated glomerular filtration rate, or eGFR? Is there a difference in the results of whole blood versus serum or plasma? Is the whole blood creatinine standardized like the new serum creatinine?

A. Equations used to estimate GFR from serum or plasma are, in most cases, suitable for use with creatinine measured in whole blood. The National Kidney Disease Education Program Laboratory Working Group has recommended that creatinine concentrations measured in whole blood be adjusted and reported as equivalent creatinine concentrations measured in simultaneously collected venous serum or plasma, where the serum or plasma measurements are traceable to a high-level isotope dilution mass spectrometry (IDMS) reference measurement procedure.1

Sensors for measuring creatinine in whole blood respond to the molality of creatinine in the sample (amount of creatinine per unit mass of water in the sample). The molality of creatinine in erythrocyte fluid is equal to molality in plasma,2, 3 and creatinine is transported by passive diffusion through the lipid bilayer of the erythrocyte membrane.4 Consequently, the measured quantity in whole blood and its separated plasma should be identical. The presence of erythrocytes may affect the whole blood measurement in other ways, for example, by hindering diffusion of analyte from bulk sample to the surface of the sensor or by affecting the electrical conductivity between different elements of the electrochemical cell. Therefore, in practice, results obtained with whole blood and simultaneously collected serum or plasma may differ and are usually sensitive to hematocrit, and it may be necessary to correct for the presence of erythrocytes to force agreement between the whole blood and serum or plasma measurements. The National Kidney Disease Education Program Web site provides more detail on whole blood creatinine measurements.1


2. Miller BF, Dubos R. Studies on the presence of creatinine in human blood. J Biol Chem. 1937;121:447–456.
3. Nolph K, Felts J, Moore R, et al. Differences in the distribution of urea and creatinine between red cells and plasma in normal and azotemic blood as assessed by autoanalyzer and manual chemical methods. Int Urol Nephrol. 1978;10:59–64.
4. Langsdorf LJ, Zydney AL. Effect of solution environment on the permeability of red blood cells. Biotechnol Bioeng. 1994;43:115–121.

Greg Miller, PhD
Professor of Pathology
Virginia Commonwealth University

Consultant, CAP Chemistry
Resource Committee

Question Q. Acute prostatitis is diagnosed primarily on the basis of clinical symptoms, rectal-prostate exam, or a finding of white cells in seminal fluid, or a combination of these. Seminal fluid sent for culture is often negative. Treatment is often empirical: fluoroquinolones (levofloxacin or ciprofloxacin) for weeks or months. After antibiotic treatment is completed, it’s not uncommon for prostatitis to recur. Sometimes the prostatitis resolves with a resumption of the same antibiotics; other times it does not. Sometimes a change in antibiotic therapy is the answer (for example, trimethoprim-sulfamethoxazole), sometimes not. Could some of the causative organisms be obligate anaerobes (which may explain an occasional response to metronidazole), Chlamydia, Ureaplasma, viral? Would PCR be of value in identifying the organism? Could recurrences of prostatitis be related to an allergic or autoimmune etiology (and thus possibly respond to corticosteroids)? What is the cause of an infiltration of eosinophils in some prostate biopsies in areas of chronic prostatitis?

A. According to a recent review1 of genitourinary pain syndromes and pro-stati-tis, prostatitis results from acute bacterial infection in two percent to five percent of cases and chronic bacterial infection in another two to five percent of cases. A bacterial pathogen can be demonstrated in these cases. On the other hand, 90 percent to 95 percent of prostatitis cases are chronic nonbacterial prostatitis (also known as chronic pelvic pain syndrome or prostatodynia). A few may result from yeast infections Candida2,3 or Cryptococcus4,5 species. But in most cases there is no demonstrable uropathogen or infectious cause, and though many men are receiving antibiotics, treatment often fails to alleviate the symptoms. This category is divided into inflammatory and noninflammatory prostatitis based on the presence or absence of leukocytes in expressed prostatic fluid. It would be logical, especially in the inflammatory category, to think that obligate anaerobic bacteria, other difficult-to-culture bacteria, other yeasts, or viruses could be the causative agent, and a response to antibiotics in some cases suggests that organisms such as Ureaplasma urealyticum, Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Corynebacteria, or anaerobic bacteria may play a role. However, this has not been demonstrated conclusively.

PCR might be of value if a target were known, and, using a broad-spectrum 16S rRNA reverse transcriptase approach, Shoskes and Shahed6 and others (see discussion in reference 7) have proposed that a positive signal could identify patients who may bene-fit from antibiotics. However, others7 have disputed their findings, so this approach remains controversial.

Currently, interstitial cystitis is thought to be a cause of the pain previously diagnosed as chronic nonbacterial prostatits/chronic pelvic pain syndrome.8 This could be another reason why no pathogen is identified. Obviously, more investigation is needed to discover the etiology of chronic nonbacterial prostatitis/chronic pelvic pain syndrome.

Class II prostatitis recurs in about 30 percent of treated patients.9 It has been suggested10 that prostatic calculi may play a role in recurrences, but a specific etiology, and whether allergic or autoimmune conditions play a role, is not known.

Eosinophilic prostatitis can be found in patients with allergies and parasitic infections and in some patients with systemic vasculitides.11 It may also be seen after transurethral resections and needle biopsies of the prostate.11,12


1. Le BV, Schaeffer AJ. Genitourinary pain syndromes, prostatitis, and lower urinary tract symptoms. Urol Clin North Am. 2009;36(4):527–536, vii.
2. Wise GJ, Shteynshlyuger A. How to diagnose and treat fungal infections in chronic prostatitis. Curr Urol Rep. 2006; 7(4):320–328.
3. Mahlknecht A, Pecorari V, Richter A. Sepsis due to asymptomatic Candida prostatitis. Arch Ital Urol Androl. 2005; 77(3):155–156.
4. Seo IY, Jeong HJ, Yun KJ, et al. Granulomatous cryptococcal prostatitis diagnosed by transrectal biopsy. Int J Urol. 2006; 13(5):638–639.
5. Siggiqui TJ, Zamani T, Parada JP. Primary cryptococcal prostatitis and correlation with serum prostate specific antigen in a renal transplant recipient. J Infect. 2005;51(3):e153–157.
6. Shoskes DA, Shahed A. Presence of bacterial signal by 16S rRNA polymerase chain reaction in expressed prostatic secretions predicts response to antibiotic therapy in men with the chronic pelvic pain syndrome. Tech Urol. 2000;6(3):240–242.
7. Leskinen MJ, Rantakokko-Javala K, Manninen R, et al. Negative bacterial polymerase chain reaction (PCR) findings in prostate tissue from patients with symptoms of chronic pelvic pain syndrome (CPPS) and localized prostate cancer. Prostate. 2003;55:105–110.
8. Forrest JB, Nickel JC, Moldwin RM. Chronic prostatitis/chronic pelvic pain syndrome and male interstitial cystitis: enigmas and opportunities. Urology. 2007;69(4 Suppl):60–63.
9. Habermacher GM, Chason JT, Schaeffer AJ. Prostatitis/chronic pelvic pain syndrome. Annu Rev Med. 2006;57:195–206.
10. Doble A. Chronic prostatitis. Br J Urol. 1994;74:537–541.
11. Prostatitis with eosinophils. Path Consult Web site. Accessed March 22, 2010.
12. Ohtsuki Y, Terao N, Kuwahara M, et al. Eosinophil infiltration in posttransurethral resection prostatitis and cystitis with special reference to sequential changes of eosinophilia. Med Mol Morphol. 2007;40(1):29–33.

Christina M. Wojewoda, MD
University Hospitals of Cleveland
Anatomic and Clinical Pathology Resident, PGY4

Member, CAP Microbiology
Resource Committee

Dr. Kiechle is medical director of clinical pathology, Memorial Healthcare, Hollywood, Fla.