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Rapidly Recurrent Renal Calculi Caused by Ureaplasma Urealyticum: A Case Report
Vol. Printed in
T'iE JOiJRNAL OF UROLOGY
Ccpyright © 1986 by The \./VilE.ams & ~Ni:kins Co.
RAPIDLY RECURRENT RENAL CALCULI CAUSED BY UREAPLASMA UREAL YTICUM: A CASE REPORT L. GRENABO, G. CLAES, H. HEDELIN AND S. PETTERSSON From the Department of Urology, Sahlgrenska sjukhuset, Goteborg and Department of Surgery, Centrallasarettet, Baras, Sweden
ABSTRACT
We report on a patient operated upon 8 times for recurrent bilateral struvite stones. Multiple conventional bacterial cultures had been negative. No etiological agent for the rapidly recurring concrements could be detected until Ureaplasma urealyticum cultures were performed at the time of the seventh operation. Ureaplasma urealyticum was found in the bladder and renal pelvic urine, and in the stones. That operation was followed by appropriate antibiotic treatment (doxycycline), which eradicated the microorganism and no stones recurred for 6 months. The urinary pH, which constantly had been highly alkaline before treatment, was normal as was the ammonium loading test. However, 1 year after the seventh operation the Ureaplasma infection recurred, probably due to sexual transmittance, and a new renal stone was discovered. These findings strongly suggest that U reaplasma urealyticum can induce the formation of infection concrements. Infection with urease-producing bacteria can induce the formation of renal infection concrements, that is calculi composed of stmvite (magnesium ammonium phosphate) and carbonateapatite.1· 2 Such stones often are bilateral, grow rapidly and frequently recur after surgical removal. Although Prnteus species or other urease-producing bacteria are mostly detected in the urine or the stones of patients with infection concrements, this is not always the case. 3 • 4 In a recent study an association between the presence of Ureaplasma urealyticum in the upper urinary tract and infection concrements was found. 5 To illustrate the importance of this etiology we describe the history of a patient with bilateral, rapidly recurring multiple renal stones, for which U. urealyticum was the probable etiological agent. CASE REPORT
A 45-year-old male accountant, with normal dietary habits, had suffered an episode of left renal colic in 1963. An excretory urogram (IVP) showed no concrements, no morphological abnormalities and no outflow obstruction. Thereafter, the patient was free of pain until December 1972, when he complained of right renal colic. An IVP showed bilateral renal pelvic concrements, including a 2 x 3.5 cm. stone on the right side and a 3 x 4 cm. stone on the left side (fig 1, A). Pyelolithotomy was through a conventional flank performed on both sides in incision. Some minute aa.;,,u,cu 'Nere left in the left kidney, completely. Following treatwhile the right side vvas ment new stones to form at a high rate, and between 1973 and 1977 the passed millimeter-sized concrements each month. In 1977 an IVP revealed multiple lai·ge calculi on the left side occupying most of the pelviocaliceal system and a 4 x 2 cm. large calculus in the right pelvis (fig 1, B). Left pyelolithotomy was performed in 1977 and right pyelolithotomy was performed in 1977 and 1978, In April 1978 plain x-ray films showed no residual concrements. Chemical analysis of all concrements revealed pure struvite. Repeated bacterial urinary cultures, including examination for bacterial counts in low numbers (10 to 20 colony-forming units x ml.- 1) when the patient was off antimicrobial treatment, were negative. Tests for hyperparathyroidism were negative. Urinary excretion of calcium, magnesium, phosphate and urate was within normal limits on repeated analyses. The fasting morning Accepted for publication November 12, 1985.
urine pH was between 8 and 9, and the ammonium chloride loading test was interpreted as indicating an incomplete distal renal tubular acidification deficiency. Despite repeated ammonium chloride loads of 0.1 gm. x kg.- 1 body weight, the urinary pH remained alkaline. Although no bacterial infection had been verified the patient received nitrofurantoin and trimethoprimsulfamethoxazole for long periods. He was treated with bendmflumethiazide for 5 years in a futile attempt to prevent recurrence. Magnesium oxide was given concomitantly for 2 years for the same reason. The patient continued to pass millimeter-sized concrements frequently and in October 1979 an IVP showed multiple small stones in the left kidney and 2 stones in the right kidney (20 x 10 and 5 X 5 mm.) (fig. 2, A). No operation was performed and the concrements in the right kidney grew rapidly to a staghorn stone within the next 2 years (fig. 2, B). In November 1981 the right kidney was explored extracorporeally and the concrements were removed. To facilitate future stone passage the kidney was autotransplanted into the ipsilateral iliac fossa with a wide direct anastomosis between the renal pelvis and the bladder, according to a method previously described. 6 The renal artery and vein were anastomosed end-to-side to the external iliac vessels. The left kidney was operated on percutaneously in February 1983, with removal of about 250 stones up to 2 cm. large. Analysis of the stones by infrared spectroscopy and optical crystallography showed the stone composition to be 20 per cent struvite, 65 per cent hydroxyapatite and 15 per cent carbonate apatite. Postoperative plain films revealed 3 millimeter-sized residual fragments in the left kidney and an autotransplanted right kidney free of concrements. Culture for U. urealyticum was now performed for the first time. The microorganism was detected in voided urine in a concentration of 5 X 104 colony-forming units x m1.- 1 and cultures from the pelvic urine, aspirated percutaneously, and from the stones were positive for U. urealyticum. The concentration of U. urealyticum in the pelvic urine was 2 x 104 colonyforming units X mL- 1 and in the stones (after 4 washings in saline and crushing) 102 colony-forming units X mL- 1 • Immediately postoperatively 100 mg. doxycycline were given daily for 6 weeks. The fasting morning urinary pH, which preoperatively had been between 8 and 9, decreased to less than 6 after the start of antibiotic treatment (fig 3). The ammonium chloride loading test also was normal. The serum antibody titer against U. urealyticum, measured with an indirect immunofluorescent technique, had been increased before antibiotic treat-
995
996
GRENABO AND ASSOCIATES
FIG. 1. A, IVP in January 1973 shows bilateral renal pelvic concrements, including 2 X 3.5 cm. stone on right side and 3 X 4 cm. stone on left side. B, IVP in September 1977 reveals multiple large calculi on left side occupying most of pelviocaliceal system and 4 X 2 cm. large calculus in right pelvis.
FIG. 2. A, IVP in October 1979 shows multiple small stones in left kidney and 2 stones in right kidney (20 August 1981 reveals multiple small stones in left kidney and staghorn calculus in right kidney.
pH 10 9 8 7 6 5 4
3 2
-2 -1 0 1 2 3 4 5 6 7 8 9 10
+
Days
FIG. 3. Fasting morning urinary pH. On day O renal stones were removed percutaneously and doxycycline treatment was instituted.
ment (1/128 to 1/256), and 1 and 3 months later it was normal (less than or equal to 1/64). During the first 6 months after the percutaneous operation and the doxycycline treatment repeated urinary cultures for
X
10 and 5
X
5 mm.). B, IVP in
bacteria and U. urealyticum were negative. An IVP revealed that the residual stones had not grown and no new stones could be detected. However, after another 6 months, urine cultures for U. urealyticum were again positive and multiple stones had recurred in the left kidney. The patient's sexual partner also had a positive urine culture for U. urealyticum. Therefore, both subjects were treated with 100 mg. doxycycline daily for 4 weeks. The stones were removed percutaneously without residual fragments. The composition of the stone was 100 per cent struvite according to chemical analysis. The patient remained free of infection according to urine culture, and no new stones were detected 4 months after antibiotic treatment. He and his partner will be examined at short intervals in the future to prevent recurrent infection. After the last operation an immunological investigation revealed essentially normal conditions, except for slightly impaired reactivity of the lymphocytes to mitogens and a low lgG3 fraction; 0.28 gm. X 1-1 (reference range 0.41 to 1.29 gm. X 1-1 ). DISCUSSION
Our patient had suffered from rapidly recurring struvite stones, although all bacterial urinary cultures had been negative. He had been operated on 8 times during a 12-year period because of renal stones. Extensive metabolic evaluation had demonstrated nothing but highly alkaline urine and abnormal ammonium chloride loading tests interpreted as indicating an
RAPIDLY RECURRENT RENAL STONES CAUSED BY UREAPLASMA UREALYTICUM
incomplete distal renal tubular acidification defect. At the seventh operaton U. urealyticum was cultured from all levels of the urinary tract, including the concrements. Antibiotic treatment was instituted, whereupon the pH of the urine neutralized and no new stones developed for 6 months, during which time the urinary cultures were negative. In view of the rapid development of recurrent concrements seen before U. urealyticum was detected, this microorganism must be strongly suspected to be of etiological importance in this case. Further evidence is the fact that new stones developed when the ureaplasma infection recurred. It is noteworthy that the appearance of an incomplete tubular renal acidification defect was normal when U. urealyticum was eradicated from the urinary tract. It is known that infection with urease-producing bacteria may cause a false positive renal acidification test7 but U. urealyticum has not been considered in this context. Since U. urealyticum is not detected with ordinary cultures, it is possible that a urease-producing organism can be present in the urine despite negative conventional cultures, producing an alkaline urine misinterpreted as an incomplete tubular acidification defect. Serum antibodies against U. urealyticum were elevated before treatment with doxycycline but they were normal at followup, when cultures for U. urealyticum were negative. Thus, an antibody response to U. urealyticum was seen, which may be another diagnostic tool in patients with U. urealyticuminduced stone formation. It should be noted in this context that a serum antibody response to U. urealyticum has been demonstrated recently in patients with nongonococcal urethritis compared to asymptomatic U. urealyticum-positive controls.8 The significance of the relative lgG3 deficiency is unclear. Apart from recurrent urinary infections with U. urealyticum, the patient had no history of other recurrent infections. In an attempt to improve the immunological defense, prophylaxis with gamma globulins in a dose of 25 mg. x kg.- 1 body weight weekly has been instituted. · Because U. urealyticum is not identified by conventional bacterial culture methods, special media and techniques are required for its isolation and identification.9 It is a common inhabitant of the lower urogenital tract in asymptomatic male and female patients. It is cultured from the urethra in about half of all sexually active men10 and in similar frequency from the lower urogenital tract in women of child-bearing age 11 but it is not ordinarily found in the upper urinary tract. 12 The history of our patient strongly suggests that infection with U. urealyticum can induce rapid recurrence of infection stones. Therefore, we suggest that in addition to conventional bacterial cultures specific cultures for U. urealyticum should be performed in patients with infection stones, especially if no other urease-producing microorganism has been detected. The presence of U. urealyticum in voided urine often is due to urethral contamination, and to be assured of its presence in the upper urinary tract cultures of renal pelvic urine or of the stone are
997
recommended. When infection recurs culture should be obtained also from the sexual partner, as illustrated by our case. U. urealyticum is resistant to penicillins, cephalosporins, sulfonamides and other antibiotics that act by interfering with cell wall formation or folic acid synthesis but it usually can be treated with tetracyclines (doxycycline), erythromycin or aminoglycosides. 13 Dr. Hakan Gnarpe, Department of Microbiology, Gii.vle Hospital, Gii.vle, Sweden, performed the measurements of serum antibody titers against U. urealyticum. REFERENCES
1. Griffith, D. P.: Struvite stones. Kidney Int., 13: 372, 1978. 2. Stamey, T. A.: Infection stones. In: Pathogenesis and Treatment of Urinary Tract Infections. Baltimore: The Williams & Wilkins Co., chapt. 8, pp. 430-474, 1980. 3. Thompson, R. B. and Stamey, T. A.: Bacteriology of infected stones. Urology, 2: 627, 1973. 4. Lewi, H.J. E., White, A., Hutchinson, A. G. and Scott, R.: The bacteriology of the urine and renal calculi. Urol. Res., 12: 107, 1984. 5. Hedelin, H., Brorson, J.-E., Grenabo, L. and Pettersson, S.: Ureaplasma urealyticum and upper urinary tract stones. Brit. J. Urol., 56: 244, 1983. 6. Pettersson, S., Brynger, H., Henriksson, C., Nilson, A. E. and Ranch, T.: Autologous renal transplantation with direct pyelocystostomy in the treatment of recurrent renal calculi. Brit. J. Urol., 55: 154, 1983. 7. Schloeder, F. X., Griffith, D. P. and Stinebaugh, B. J.: Evaluation of renal acidification in patients with urea-splitting organisms. Invest. Urol., 15: 299, 1978. 8. Brown, M. B., Cassel, G. H., Taylor-Robinson, D. and Shepard, M. C.: Measurement of antibody to Ureaplasma urealyticum by an enzyme-linked immunosorbent assay and detection of antibody responses in patients with nongonococcal urethritis. J. Clin. Microbiol., 17: 288, 1983. 9. Shepard, M. C. and Lunceford, C. D.: Urease color test medium U9 for the detection and identification of "T"-Mycoplasmas in clinical material. Appl. Microbiol., 20: 539, 1970. 10. Bowie, W.R., Wang, S.-P., Alexander, E. R., Floyd J., Forsyth, P. S., Pollock, H. M., Lin, J.-S. L., Buchanan, T. M. and Holmes, K. K.: Etiology of nongonococcal urethritis. Evidence for Chlamydia trachomatis and ureaplasma urealyticum. J. Clin. Invest., 59: 735, 1977. 11. Mardh, P.-A., Westrom, L. and Colleen, S.: Infections of the genital and urinary tracts with Mycoplasmas and Ureaplasmas. In: Proceedings of the Symposium on Genital Infections and Their Complications. Edited by D. Danielsson, L. Juhlin and P.-A. Mardh. Stockholm: Almqvist & Wiksell International, pp. 5362, 1975. 12. Thomsen, A. C.: Occurrence of Mycoplasmas in urinary tracts of patients with acute pyelonephritis. J. Clin. Microbiol., 8: 84, 1978. 13. Shepard, M. C. and Masover, G. K.: Special features of ureaplasmas. In: The Mycoplasmas. Edited by M. F. Barile and S. Razin. New York: Academic Press, Inc., vol. 1, chapt. 17, pp. 451-494, 1979.
T'iE JOiJRNAL OF UROLOGY
Ccpyright © 1986 by The \./VilE.ams & ~Ni:kins Co.
RAPIDLY RECURRENT RENAL CALCULI CAUSED BY UREAPLASMA UREAL YTICUM: A CASE REPORT L. GRENABO, G. CLAES, H. HEDELIN AND S. PETTERSSON From the Department of Urology, Sahlgrenska sjukhuset, Goteborg and Department of Surgery, Centrallasarettet, Baras, Sweden
ABSTRACT
We report on a patient operated upon 8 times for recurrent bilateral struvite stones. Multiple conventional bacterial cultures had been negative. No etiological agent for the rapidly recurring concrements could be detected until Ureaplasma urealyticum cultures were performed at the time of the seventh operation. Ureaplasma urealyticum was found in the bladder and renal pelvic urine, and in the stones. That operation was followed by appropriate antibiotic treatment (doxycycline), which eradicated the microorganism and no stones recurred for 6 months. The urinary pH, which constantly had been highly alkaline before treatment, was normal as was the ammonium loading test. However, 1 year after the seventh operation the Ureaplasma infection recurred, probably due to sexual transmittance, and a new renal stone was discovered. These findings strongly suggest that U reaplasma urealyticum can induce the formation of infection concrements. Infection with urease-producing bacteria can induce the formation of renal infection concrements, that is calculi composed of stmvite (magnesium ammonium phosphate) and carbonateapatite.1· 2 Such stones often are bilateral, grow rapidly and frequently recur after surgical removal. Although Prnteus species or other urease-producing bacteria are mostly detected in the urine or the stones of patients with infection concrements, this is not always the case. 3 • 4 In a recent study an association between the presence of Ureaplasma urealyticum in the upper urinary tract and infection concrements was found. 5 To illustrate the importance of this etiology we describe the history of a patient with bilateral, rapidly recurring multiple renal stones, for which U. urealyticum was the probable etiological agent. CASE REPORT
A 45-year-old male accountant, with normal dietary habits, had suffered an episode of left renal colic in 1963. An excretory urogram (IVP) showed no concrements, no morphological abnormalities and no outflow obstruction. Thereafter, the patient was free of pain until December 1972, when he complained of right renal colic. An IVP showed bilateral renal pelvic concrements, including a 2 x 3.5 cm. stone on the right side and a 3 x 4 cm. stone on the left side (fig 1, A). Pyelolithotomy was through a conventional flank performed on both sides in incision. Some minute aa.;,,u,cu 'Nere left in the left kidney, completely. Following treatwhile the right side vvas ment new stones to form at a high rate, and between 1973 and 1977 the passed millimeter-sized concrements each month. In 1977 an IVP revealed multiple lai·ge calculi on the left side occupying most of the pelviocaliceal system and a 4 x 2 cm. large calculus in the right pelvis (fig 1, B). Left pyelolithotomy was performed in 1977 and right pyelolithotomy was performed in 1977 and 1978, In April 1978 plain x-ray films showed no residual concrements. Chemical analysis of all concrements revealed pure struvite. Repeated bacterial urinary cultures, including examination for bacterial counts in low numbers (10 to 20 colony-forming units x ml.- 1) when the patient was off antimicrobial treatment, were negative. Tests for hyperparathyroidism were negative. Urinary excretion of calcium, magnesium, phosphate and urate was within normal limits on repeated analyses. The fasting morning Accepted for publication November 12, 1985.
urine pH was between 8 and 9, and the ammonium chloride loading test was interpreted as indicating an incomplete distal renal tubular acidification deficiency. Despite repeated ammonium chloride loads of 0.1 gm. x kg.- 1 body weight, the urinary pH remained alkaline. Although no bacterial infection had been verified the patient received nitrofurantoin and trimethoprimsulfamethoxazole for long periods. He was treated with bendmflumethiazide for 5 years in a futile attempt to prevent recurrence. Magnesium oxide was given concomitantly for 2 years for the same reason. The patient continued to pass millimeter-sized concrements frequently and in October 1979 an IVP showed multiple small stones in the left kidney and 2 stones in the right kidney (20 x 10 and 5 X 5 mm.) (fig. 2, A). No operation was performed and the concrements in the right kidney grew rapidly to a staghorn stone within the next 2 years (fig. 2, B). In November 1981 the right kidney was explored extracorporeally and the concrements were removed. To facilitate future stone passage the kidney was autotransplanted into the ipsilateral iliac fossa with a wide direct anastomosis between the renal pelvis and the bladder, according to a method previously described. 6 The renal artery and vein were anastomosed end-to-side to the external iliac vessels. The left kidney was operated on percutaneously in February 1983, with removal of about 250 stones up to 2 cm. large. Analysis of the stones by infrared spectroscopy and optical crystallography showed the stone composition to be 20 per cent struvite, 65 per cent hydroxyapatite and 15 per cent carbonate apatite. Postoperative plain films revealed 3 millimeter-sized residual fragments in the left kidney and an autotransplanted right kidney free of concrements. Culture for U. urealyticum was now performed for the first time. The microorganism was detected in voided urine in a concentration of 5 X 104 colony-forming units x m1.- 1 and cultures from the pelvic urine, aspirated percutaneously, and from the stones were positive for U. urealyticum. The concentration of U. urealyticum in the pelvic urine was 2 x 104 colonyforming units X mL- 1 and in the stones (after 4 washings in saline and crushing) 102 colony-forming units X mL- 1 • Immediately postoperatively 100 mg. doxycycline were given daily for 6 weeks. The fasting morning urinary pH, which preoperatively had been between 8 and 9, decreased to less than 6 after the start of antibiotic treatment (fig 3). The ammonium chloride loading test also was normal. The serum antibody titer against U. urealyticum, measured with an indirect immunofluorescent technique, had been increased before antibiotic treat-
995
996
GRENABO AND ASSOCIATES
FIG. 1. A, IVP in January 1973 shows bilateral renal pelvic concrements, including 2 X 3.5 cm. stone on right side and 3 X 4 cm. stone on left side. B, IVP in September 1977 reveals multiple large calculi on left side occupying most of pelviocaliceal system and 4 X 2 cm. large calculus in right pelvis.
FIG. 2. A, IVP in October 1979 shows multiple small stones in left kidney and 2 stones in right kidney (20 August 1981 reveals multiple small stones in left kidney and staghorn calculus in right kidney.
pH 10 9 8 7 6 5 4
3 2
-2 -1 0 1 2 3 4 5 6 7 8 9 10
+
Days
FIG. 3. Fasting morning urinary pH. On day O renal stones were removed percutaneously and doxycycline treatment was instituted.
ment (1/128 to 1/256), and 1 and 3 months later it was normal (less than or equal to 1/64). During the first 6 months after the percutaneous operation and the doxycycline treatment repeated urinary cultures for
X
10 and 5
X
5 mm.). B, IVP in
bacteria and U. urealyticum were negative. An IVP revealed that the residual stones had not grown and no new stones could be detected. However, after another 6 months, urine cultures for U. urealyticum were again positive and multiple stones had recurred in the left kidney. The patient's sexual partner also had a positive urine culture for U. urealyticum. Therefore, both subjects were treated with 100 mg. doxycycline daily for 4 weeks. The stones were removed percutaneously without residual fragments. The composition of the stone was 100 per cent struvite according to chemical analysis. The patient remained free of infection according to urine culture, and no new stones were detected 4 months after antibiotic treatment. He and his partner will be examined at short intervals in the future to prevent recurrent infection. After the last operation an immunological investigation revealed essentially normal conditions, except for slightly impaired reactivity of the lymphocytes to mitogens and a low lgG3 fraction; 0.28 gm. X 1-1 (reference range 0.41 to 1.29 gm. X 1-1 ). DISCUSSION
Our patient had suffered from rapidly recurring struvite stones, although all bacterial urinary cultures had been negative. He had been operated on 8 times during a 12-year period because of renal stones. Extensive metabolic evaluation had demonstrated nothing but highly alkaline urine and abnormal ammonium chloride loading tests interpreted as indicating an
RAPIDLY RECURRENT RENAL STONES CAUSED BY UREAPLASMA UREALYTICUM
incomplete distal renal tubular acidification defect. At the seventh operaton U. urealyticum was cultured from all levels of the urinary tract, including the concrements. Antibiotic treatment was instituted, whereupon the pH of the urine neutralized and no new stones developed for 6 months, during which time the urinary cultures were negative. In view of the rapid development of recurrent concrements seen before U. urealyticum was detected, this microorganism must be strongly suspected to be of etiological importance in this case. Further evidence is the fact that new stones developed when the ureaplasma infection recurred. It is noteworthy that the appearance of an incomplete tubular renal acidification defect was normal when U. urealyticum was eradicated from the urinary tract. It is known that infection with urease-producing bacteria may cause a false positive renal acidification test7 but U. urealyticum has not been considered in this context. Since U. urealyticum is not detected with ordinary cultures, it is possible that a urease-producing organism can be present in the urine despite negative conventional cultures, producing an alkaline urine misinterpreted as an incomplete tubular acidification defect. Serum antibodies against U. urealyticum were elevated before treatment with doxycycline but they were normal at followup, when cultures for U. urealyticum were negative. Thus, an antibody response to U. urealyticum was seen, which may be another diagnostic tool in patients with U. urealyticuminduced stone formation. It should be noted in this context that a serum antibody response to U. urealyticum has been demonstrated recently in patients with nongonococcal urethritis compared to asymptomatic U. urealyticum-positive controls.8 The significance of the relative lgG3 deficiency is unclear. Apart from recurrent urinary infections with U. urealyticum, the patient had no history of other recurrent infections. In an attempt to improve the immunological defense, prophylaxis with gamma globulins in a dose of 25 mg. x kg.- 1 body weight weekly has been instituted. · Because U. urealyticum is not identified by conventional bacterial culture methods, special media and techniques are required for its isolation and identification.9 It is a common inhabitant of the lower urogenital tract in asymptomatic male and female patients. It is cultured from the urethra in about half of all sexually active men10 and in similar frequency from the lower urogenital tract in women of child-bearing age 11 but it is not ordinarily found in the upper urinary tract. 12 The history of our patient strongly suggests that infection with U. urealyticum can induce rapid recurrence of infection stones. Therefore, we suggest that in addition to conventional bacterial cultures specific cultures for U. urealyticum should be performed in patients with infection stones, especially if no other urease-producing microorganism has been detected. The presence of U. urealyticum in voided urine often is due to urethral contamination, and to be assured of its presence in the upper urinary tract cultures of renal pelvic urine or of the stone are
997
recommended. When infection recurs culture should be obtained also from the sexual partner, as illustrated by our case. U. urealyticum is resistant to penicillins, cephalosporins, sulfonamides and other antibiotics that act by interfering with cell wall formation or folic acid synthesis but it usually can be treated with tetracyclines (doxycycline), erythromycin or aminoglycosides. 13 Dr. Hakan Gnarpe, Department of Microbiology, Gii.vle Hospital, Gii.vle, Sweden, performed the measurements of serum antibody titers against U. urealyticum. REFERENCES
1. Griffith, D. P.: Struvite stones. Kidney Int., 13: 372, 1978. 2. Stamey, T. A.: Infection stones. In: Pathogenesis and Treatment of Urinary Tract Infections. Baltimore: The Williams & Wilkins Co., chapt. 8, pp. 430-474, 1980. 3. Thompson, R. B. and Stamey, T. A.: Bacteriology of infected stones. Urology, 2: 627, 1973. 4. Lewi, H.J. E., White, A., Hutchinson, A. G. and Scott, R.: The bacteriology of the urine and renal calculi. Urol. Res., 12: 107, 1984. 5. Hedelin, H., Brorson, J.-E., Grenabo, L. and Pettersson, S.: Ureaplasma urealyticum and upper urinary tract stones. Brit. J. Urol., 56: 244, 1983. 6. Pettersson, S., Brynger, H., Henriksson, C., Nilson, A. E. and Ranch, T.: Autologous renal transplantation with direct pyelocystostomy in the treatment of recurrent renal calculi. Brit. J. Urol., 55: 154, 1983. 7. Schloeder, F. X., Griffith, D. P. and Stinebaugh, B. J.: Evaluation of renal acidification in patients with urea-splitting organisms. Invest. Urol., 15: 299, 1978. 8. Brown, M. B., Cassel, G. H., Taylor-Robinson, D. and Shepard, M. C.: Measurement of antibody to Ureaplasma urealyticum by an enzyme-linked immunosorbent assay and detection of antibody responses in patients with nongonococcal urethritis. J. Clin. Microbiol., 17: 288, 1983. 9. Shepard, M. C. and Lunceford, C. D.: Urease color test medium U9 for the detection and identification of "T"-Mycoplasmas in clinical material. Appl. Microbiol., 20: 539, 1970. 10. Bowie, W.R., Wang, S.-P., Alexander, E. R., Floyd J., Forsyth, P. S., Pollock, H. M., Lin, J.-S. L., Buchanan, T. M. and Holmes, K. K.: Etiology of nongonococcal urethritis. Evidence for Chlamydia trachomatis and ureaplasma urealyticum. J. Clin. Invest., 59: 735, 1977. 11. Mardh, P.-A., Westrom, L. and Colleen, S.: Infections of the genital and urinary tracts with Mycoplasmas and Ureaplasmas. In: Proceedings of the Symposium on Genital Infections and Their Complications. Edited by D. Danielsson, L. Juhlin and P.-A. Mardh. Stockholm: Almqvist & Wiksell International, pp. 5362, 1975. 12. Thomsen, A. C.: Occurrence of Mycoplasmas in urinary tracts of patients with acute pyelonephritis. J. Clin. Microbiol., 8: 84, 1978. 13. Shepard, M. C. and Masover, G. K.: Special features of ureaplasmas. In: The Mycoplasmas. Edited by M. F. Barile and S. Razin. New York: Academic Press, Inc., vol. 1, chapt. 17, pp. 451-494, 1979.