MULTIELEMENT ANALYSIS OF KIDNEY TISSUE WITH RENAL CALCULI ISAO KIRIYAMA, M.D. HIROMICHI ISHIKAWA, M.D. KENKICHI KOISO, M.D.
TSUNETADA YAZAKI, M.D. TOMOKAZU UMEYAMA, M.D. SHOJI KANEKO, M.D.
From the Departments of Urology, Teikyo University School of Medicine, Tokyo; Gunma University School of Medicine, Gunma; and Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan
ABSTRACT--Tissue distribution and concentration gradients of macro- and micro-elements in the papilla, medulla, and cortex of human kidney with renal calculi were measured with spectrometer. An uninvolved portion of the hypernephroma kidney was used as control. Cadmium (Cd), cobalt (Co), and molybdenum (Mo) were least in amount in renal papilla as compared with the cortex and medulla in renal stone kidney. Overall there was less Mo in stone kidney tissue, and also significantly less when comparedwith that of control renal papilla. Considering the reported fact that Mo was found in high concentrations in urinary tract stones and our data that Mo was less in stone kidney, it is speculated that Mo may play some unexplained but significant role in certain stage(s) of the stone formation.
Despite the extensive clinical and investigative r e s e a r c h , the p a t h o g e n e s i s of c a l c i u m containing urolithiasis remains obseure to date. Various approaches such as epidemiology, analysis of stone components, and chemical analysis of blood and urine are included. Knowledge of the role of micro-elements in the biologic system is beginning to focus on their place in human metabolism.1 However, reports on chemical analysis of micro- and macro-elements in stone-containing kidney are few.~-5 The purpose of this study is to elucidate the role of microand macro-elements in formation of stone in renal tissue. As a preliminary study we measured the tissue distribution and concentration gradients of multielements in papilla, medulla, and cortex of human kidney with stone and have compared these results with those of uninvolved portion of the hypernephroma kidney.
290
Material and Methods Fresh human renal tissue operation (nephrectomy or tomy) from 9 patients with c renal calculi. Control specim from uninvolved portion of~ 12 patients with renal cell thickness sections were excise medulla, and papilla of each rated and stored at - 20 ° C 1 The tissue specimen was nearest 0.1 mg wet weight. was then cleaned with a pre distilled deionized water to face contamination. Seven: acid were added to the speci ture was allowed to stand fo~ at 48 ° C. The mixture spec
UROLOGY
/
SEPTEMBER 1991
/
VOLUM
T~LE I.
A I• Be Ca Cd Co Cr Fe
Multielements in renal stone kidney (ppm)
Cortex
Medulla
(n---9)
(n=9)
0.000 ± 0.000 0.118±0.119 105.499± 66. 088 88.783:1:72.353~*~ 0.056±0.0?0 * * 0.419±0.874 28.830±14.425 98.871±25.409 0.843±0.422 Q. 022± 0.05? 0.058±0.04? 4840.000± 3202.050 0.198±0.180 -I0.093±0.188 1.514±1.028 2.021 ± 0. ?3?
Mg
Mn Sn Sr Zn Mo Pb Se Cu
Papilla (n=8)
0.054 ± 0.152 0.070±0.10'7 135.813± 71.9?9 07.887±140.991 0.072±0.136 0.523±0.905 30.832±25.363 112.208±75.884 0.841±1.012 0.000 ± 0.000 0.06?±0.053 2363.000 ± 1020.583 0.135±0.288 0.081±0.228 0.880±0.9?3 2.021 ± 1. 812
0. 000± 0.000 0.000 ±0.000 421. 560± 345.694 ?.883±5.982 0.008±0.021 0.130±0.120 18.998±3.077 82.681±15.849 2.515±5.922 0.000 ± 0.000 0.219±0.171 1386.288 ± 501.899 0.004±0.011 0.144±0.217 3.221±3.188 0. ?22± 0.319
P < 0.05 P < 0.02 -I- P < 0.01 • *
• **
i!]~e times by thrice deionized distilled water i ~ : w a s placed in the Plasma AtomComp ~i~e&'Reading Spectrometer (Fisher Scientific !$~ MA). Some specimens of either cortex, me'~i~!a, or papilla, when inappropriately proc~8)~' were omitted for analysis. Results multielement analyses for the 9 kidneys ~:h calculi are presented in Table I. Calcium ~ i manganese (Mn), strontium (Sr), and !~:iiPb) were abundantly contained in papilla nedulla or cortex. Meanwhile dmium (Cd) (p < 0.02), cobalt , and molybdenum (Mo) (p < )ilia than in the cortex or me1 (Be), tin (Sn), and zinc (Zn) in the renal cortex. Overall, i n e d elements m o d e r a t e in )ared with those of papilla and analyses of papilla in stone control kidney (n = 8) are [. Ca and magnesium (Mg) buted in the two groups. < 0.01) was contained in n in renal stone papilla. o, Zn, and Pb were distriblla, and Mn was contained La.
........
3ER 1991
/
TAZLEII.
Mulaeleraents in renal papilla (ppm)
Renal Stone Kidneys
(n = 8)
AI Be Ca Cd Co Cr Fe
Mg Mn Sn Sr Zn Mo Pb Se Cu
0.000±0.000 0.000±0.000 421.560±345.694 7.863±5.962 0.008±0.021 0.130±0.120 18.998±3.077 82.681±15.849 2.515±5.922 0.000±0.000 0.219±0.171 1386.288±501. 899 0.004±0.011 0.144±0.217 3.221±3.188 0.722±0.319
Uninvolved Portion of Hypernephroma Kidneys
(n = 8)
0.038±0.099 0.161±0.209
426.813±668.081 28.125±31.995 0.025±0.066 0.231±0.398 40.574±28.650 98.908±26.086 0.417±0.343 0.157±0.415 0.210±0.386 3066.375±2052.824 0.252±0.176 * 0.530±0.798 6.098±6.893 1.641±0.530 *
P< 0.001
Results of analyses in renal medulla are shown in Table III. Amounts of Ca and Zn were distributed equally in the two groups, while there was slightly more Mg in medulla with calculi. Cd, chromium (Cr), and copper (Cu) were contained in larger amounts in medulla
VOLUME XXXVIII, NUMBER 3
291
TABLEIII.
Renal Stone Kidneys
(n= 9) AI
0.054±0.152
Be
0.070±0.107
Ca Cd Co Cr Fe Mg Mn Sn Sr Zn Mo Pb Se Cu
135.813±71.879 67.087±140.991 0.072±0.138 0.523±0.995 30.832±25.363 112.208±75.664 0.841±1.012 0.000±0.000 0.067±0.053 2363.000±1020. 583 0.135±0.268 0.081±0.228 0.680±0. 973 2.021±1.812
UninvolvedPortion of Hypernephroma Kideneys ( n = 11) 0.000±0.000 0.106±0.180 160.220±190.142 25.g21±13.417 0.941±2.865 0.112±0.047 30.154±20.908 78.755±16.498 0.824±0.864 0.000~0.000 0.056±0.099 2954.900±1165.390 8.2?2±25.269 0.053±0.116 3.438~2.884 * * * 1.238±0.433 *** P < 0.02
TABLEIV. Multielements in renal cortex (ppm) Renal Stone Kidneys (n=0) AI
Be Ca Cd Co Cr Fe Mg Mn Sn Sr Zn Mo Pb Se Ca
0. 000 ± 0.000
0.118±0.119 105.49g • 66.088 68.783 ± 72. 353 0.056 ± 0.070 0.419 ± 0.674 26,630 ± 14.425 98.671 ± 25.409 0. 843 ± 0. 422 0.022 ± 0.057 0.058 ± 0.047 4840.000± 3202.050 0.196±0.180 0.093±0.188 1. 514 ± 1. 026 2.021 ± 0. 737
Uninvolved Portion of
Hypernephroma Kidneys (n=12) 0.000 ± 0.000
0.1?2±0.151 136.700 • 102.700 63.121 ± 39.05? 0.057 ± 0.070 0.144 ± 0. 096 31. 308 ± 9.929 101. 140 ± 20.9?6 0. 959 ± 0.286
0.000 ± 0.000 0. 051 ± 0.048 50?3.100± 2111. g00 0.402±0.182 0.298±0.642 4.327 ± 2.362 2. 036 ± 0. 655
with calculi, whereas there was more Be, Co, Mo, and Se (p < 0.02) in control medulla, The multielement analyses of cortex in stone kidney (n = 9) and control kidney (n = 12) are shown in Table IV. Ca, Mg, and Zn were distributed equally in the two groups• Chromium and Sn were distributed more in stone kidney cortex, while Mo and Se were contained more in control renal cortex• 292
Comment
Multielements in renal medulla (ppm)
The method of analyses for miero-element~ has improved remarkably in recent years.!.~ The role of micro-elements in urinary stone disi,i ease has been under discussion for some time. 7-1° Little definitive information, however, has been presented linking the presence or ab senee of selected micro-elements in the urine 0 patients with various forms of the disease to ttil pathogenesis of the disease. In vitro experiment have shown that certain micro-elements ha~i an effect on the crystallization of calcium ox~ late and calcium phosphate? Concentrations ~ micro-elements used in the test system were ot ten unphysiologic. ..... ~?:~; In 1987 and 1940 RandalP ~82 pubhshed art,s!: cles in which he depieted the early developme~ii of attached renal ealeuli within and on the } ~ nal papilla. His results were substantiated ~N other investigators during the next decade a ~ then were largely ignored. 5 At present it is w ~ i recognized that ealeific deposits occur a n ~"~:~ ' neys and have been identified as either e a l e ~ phosphate 13 or calcium oxalate. 14 Oliver et d i ~ found that the stones of rats invariably wer~ ~0~ eated near the bend of loop of Henle. H ~ N mann, Lehmaim, and Komor ~ tissue concentration of oxalate a the papilla, medulla, and torte: compared these with the eoncent late and calcium in urine. Signif concentrations of calcium and ox served in the papilla compared dulla. The medulla, in turn, eor eoncentrations than the cortex. T that the observed intrarenal eal~ late coneentration gradients appeared t01 significant mechanism in the pathogene~i papillary calcification and strong indicati~ renal stone formation to start from fixedil talluric particles in the papilla. Depending on the method of fixing th e and the source of the tissue the incidei0t calcified deposits in the kidney is variaf most series, however, the spatial frec uei i ealeium deposits increases as the papillarytl approached. The results of these investig~ support that the renal papilla may be th4 stone formation in its early stage. Therefi studied the tissue concentration and di! tion gradient of multielements in c~i! containing kidney stone qf man at thi~:~ ferent portions, namely papilla, medul~t eortex, and compared these results with tJ:] involved counterpart with hypernephr0~
UROLOGY / SEPTEMBER1991
/ VOLUMEXXXVIII, N ~
Our s t u d y o n m u l t i e l e m e n t analyses in r e n a l 0~e k i d n e y r e v e a l e d t h a t C d , C o , a n d M o w e r e iund least in a m o u n t in r e n a l p a p i l l a as c o m ired w i t h t h e c o r t e x a n d m e d u l l a . M e a n w h i l e ere w e r e n o e l e m e n t s w h i c h w e r e s i g n i f i c a n t amounts in t h e c o n t r o l k i d n e y tissue. W h e n ultielements in r e n a l p a p i l l a , m e d u l l a , a n d irtex of s t o n e k i d n e y tissue w e r e c o m p a r e d ]th those of t h e r e s p e c t i v e c o u n t e r p a r t s in t h e ntrol k i d n e y t i s s u e , M o in r e n a l p a p i l l a a n d in r e n a l m e d u l l a w e r e s i g n i f i c a n t l y least in n0unt. M e a n w h i l e h i g h e r c o n c e n t r a t i o n s a n d ,latively h i g h f r e q u e n c y rates of Mo, Sr, a n d a w e r e f o u n d in u r i n a r y stones i n c l u d i n g calam oxa late.x°'la U m e y a m a a n d O g a w a 1° reirked t h a t N a , K, a n d M g w e r e also f o u n d in gh c o n c e n t r a t i o n s in u r i n a r y stones. T h u s ey s p e c u l a t e d t h a t these s u b s t a n c e s m a y b e in,fred in t h e process of stone f o r m a t i o n . W h y hibitors s u c h as M g a n d Z n w e r e f o u n d in gti c o n c e n t r a t i o n s in u r i n a r y stones is n o t Overall M o w a s less in a m o u n t in r e n a l p a !1a, m e d u l l a , a n d c o r t e x in stone k i d n e y tissue an c o n t r o l c o u n t e r p a r t s , a n d M o in r e n a l p a llia was least in a m o u n t as c o m p a r e d w i t h m e ilia a n d c o r t e x in e i t h e r stone k i d n e y or con3I k i d n e y tissue. To d a t e f u n c t i o n of M o in iman m e t a b o l i s m is n o t k n o w n , 6 a n d t h u s its ie i n t h e f o r m a t i o n of u r i n a r y stones is n o t ~eidated. H o w e v e r c o n s i d e r i n g t h e r e p o r t e d ct that M o w a s f o u n d in h i g h c o n c e n t r a t i o n in inary stones a n d less in s t o n e k i d n e y tissue, peeially r e n a l p a p i l l a , it is r e a s o n a b l e to specate t h a t M o m a y p l a y s o m e u n e x p l a i n e d b u t ~ificant role in c e r t a i n stage(s) of stone forafion A m o n g v a r i o u s a p p r o a c h e s to e l u c i d a t e e:mechanism of stone formation, micro-
GY,
e l e m e n t analysis of stone k i d n e y tissue in addit i o n to u r i n a r y s t o n e a n d u r i n e is necessary. 2-11-1 Kaga, Itabashi-Ku Tokyo, 173 Japan (DR. YAZAKI) References 1. Sehroeder HA, and Nason AP: Trace-element analysis in clinical chemistry; Clin Chem 17:461 (1971). 2. Gains NA, Miehaels CW, Thwaites MZ, and Trounce JR: Calcium concentration in the kidney, Nephron 5:352 (1968). 3. CookeSAR: The distribution of calcium in the human kidney: method and results, Br J Urol 43:130 (1971). 4. Wright RJ, and Hodgkinson A: Oxalic acid, ealeium, and phosphorus in the renal papilla of normal and stone forming rats, Invest Urol 9:369 (1972). 5. Hautmann R, Lehmann A, and Komor S: Calcium and oxalate concentrations in human renal tissue: the key to the pathogenesis of stone formation? J Urol 123:317 (1980). 6. Gemba A: An analytical signifieanees and its determinations of the trace elements in human, Igaku No Ayumi 120; 369 (1982). 7. Eusebio E, and Elliot JS: Effect of trace metals on the crystallization of calcium oxalate, Invest Urol 4:431 (1967). 8. Meyer JL, and Angio EE: The role of trace metals in calcium urolithiasis, Invest Urol 14:347 (1977). 9. ScottR, et al: Concentration and distribution of some minor and trace elements in urinary tract stones: a preliminary report, Urol Res 8:167 (1980). 10. Umeyama T, and Ogawa Y: Studies on trace element in urinary tract stones, Jpn J Urol 75:1038 (1984). 11. Randall A: The origin and growth of renal calculi, Ann Surg 105:1009 (1937). 12. Randall A: Papillary pathology as a precursor of primary renal calculus, J Urol 44:580 (1940). 13. Haggit RC, and Pitcock JA: Renal medullary calcifications', a light and electron microscopic study, J Urol 106:342 (1971). 14. Bennington JL, Haber SL, Smith JV, and Warner NE: Crystals of calcium oxalate in the human kidney. Studies by means of electromicroprobe and x-ray diffraction, Am J Clin Pathol 41.' 8 (1964). 15. OliverJ, MacDowell M, Whang R, and Welt LG: The renal lesions of electrolyte imbalance.IV. The intranephronic calculosis of experimental magnesium depletion, J Exp Med 124:263 (1966). 16. LevinsonAA, Nosal M, and Davidman RG: Traceelements in kidney stones from three areas in the United States, J Urol 15: 270 (1978).
/ SEPTEMBER 1991 / VOLUME XXXVIII, NUMBER 3
293
TSUNETADA YAZAKI, M.D. TOMOKAZU UMEYAMA, M.D. SHOJI KANEKO, M.D.
From the Departments of Urology, Teikyo University School of Medicine, Tokyo; Gunma University School of Medicine, Gunma; and Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan
ABSTRACT--Tissue distribution and concentration gradients of macro- and micro-elements in the papilla, medulla, and cortex of human kidney with renal calculi were measured with spectrometer. An uninvolved portion of the hypernephroma kidney was used as control. Cadmium (Cd), cobalt (Co), and molybdenum (Mo) were least in amount in renal papilla as compared with the cortex and medulla in renal stone kidney. Overall there was less Mo in stone kidney tissue, and also significantly less when comparedwith that of control renal papilla. Considering the reported fact that Mo was found in high concentrations in urinary tract stones and our data that Mo was less in stone kidney, it is speculated that Mo may play some unexplained but significant role in certain stage(s) of the stone formation.
Despite the extensive clinical and investigative r e s e a r c h , the p a t h o g e n e s i s of c a l c i u m containing urolithiasis remains obseure to date. Various approaches such as epidemiology, analysis of stone components, and chemical analysis of blood and urine are included. Knowledge of the role of micro-elements in the biologic system is beginning to focus on their place in human metabolism.1 However, reports on chemical analysis of micro- and macro-elements in stone-containing kidney are few.~-5 The purpose of this study is to elucidate the role of microand macro-elements in formation of stone in renal tissue. As a preliminary study we measured the tissue distribution and concentration gradients of multielements in papilla, medulla, and cortex of human kidney with stone and have compared these results with those of uninvolved portion of the hypernephroma kidney.
290
Material and Methods Fresh human renal tissue operation (nephrectomy or tomy) from 9 patients with c renal calculi. Control specim from uninvolved portion of~ 12 patients with renal cell thickness sections were excise medulla, and papilla of each rated and stored at - 20 ° C 1 The tissue specimen was nearest 0.1 mg wet weight. was then cleaned with a pre distilled deionized water to face contamination. Seven: acid were added to the speci ture was allowed to stand fo~ at 48 ° C. The mixture spec
UROLOGY
/
SEPTEMBER 1991
/
VOLUM
T~LE I.
A I• Be Ca Cd Co Cr Fe
Multielements in renal stone kidney (ppm)
Cortex
Medulla
(n---9)
(n=9)
0.000 ± 0.000 0.118±0.119 105.499± 66. 088 88.783:1:72.353~*~ 0.056±0.0?0 * * 0.419±0.874 28.830±14.425 98.871±25.409 0.843±0.422 Q. 022± 0.05? 0.058±0.04? 4840.000± 3202.050 0.198±0.180 -I0.093±0.188 1.514±1.028 2.021 ± 0. ?3?
Mg
Mn Sn Sr Zn Mo Pb Se Cu
Papilla (n=8)
0.054 ± 0.152 0.070±0.10'7 135.813± 71.9?9 07.887±140.991 0.072±0.136 0.523±0.905 30.832±25.363 112.208±75.884 0.841±1.012 0.000 ± 0.000 0.06?±0.053 2363.000 ± 1020.583 0.135±0.288 0.081±0.228 0.880±0.9?3 2.021 ± 1. 812
0. 000± 0.000 0.000 ±0.000 421. 560± 345.694 ?.883±5.982 0.008±0.021 0.130±0.120 18.998±3.077 82.681±15.849 2.515±5.922 0.000 ± 0.000 0.219±0.171 1386.288 ± 501.899 0.004±0.011 0.144±0.217 3.221±3.188 0. ?22± 0.319
P < 0.05 P < 0.02 -I- P < 0.01 • *
• **
i!]~e times by thrice deionized distilled water i ~ : w a s placed in the Plasma AtomComp ~i~e&'Reading Spectrometer (Fisher Scientific !$~ MA). Some specimens of either cortex, me'~i~!a, or papilla, when inappropriately proc~8)~' were omitted for analysis. Results multielement analyses for the 9 kidneys ~:h calculi are presented in Table I. Calcium ~ i manganese (Mn), strontium (Sr), and !~:iiPb) were abundantly contained in papilla nedulla or cortex. Meanwhile dmium (Cd) (p < 0.02), cobalt , and molybdenum (Mo) (p < )ilia than in the cortex or me1 (Be), tin (Sn), and zinc (Zn) in the renal cortex. Overall, i n e d elements m o d e r a t e in )ared with those of papilla and analyses of papilla in stone control kidney (n = 8) are [. Ca and magnesium (Mg) buted in the two groups. < 0.01) was contained in n in renal stone papilla. o, Zn, and Pb were distriblla, and Mn was contained La.
........
3ER 1991
/
TAZLEII.
Mulaeleraents in renal papilla (ppm)
Renal Stone Kidneys
(n = 8)
AI Be Ca Cd Co Cr Fe
Mg Mn Sn Sr Zn Mo Pb Se Cu
0.000±0.000 0.000±0.000 421.560±345.694 7.863±5.962 0.008±0.021 0.130±0.120 18.998±3.077 82.681±15.849 2.515±5.922 0.000±0.000 0.219±0.171 1386.288±501. 899 0.004±0.011 0.144±0.217 3.221±3.188 0.722±0.319
Uninvolved Portion of Hypernephroma Kidneys
(n = 8)
0.038±0.099 0.161±0.209
426.813±668.081 28.125±31.995 0.025±0.066 0.231±0.398 40.574±28.650 98.908±26.086 0.417±0.343 0.157±0.415 0.210±0.386 3066.375±2052.824 0.252±0.176 * 0.530±0.798 6.098±6.893 1.641±0.530 *
P< 0.001
Results of analyses in renal medulla are shown in Table III. Amounts of Ca and Zn were distributed equally in the two groups, while there was slightly more Mg in medulla with calculi. Cd, chromium (Cr), and copper (Cu) were contained in larger amounts in medulla
VOLUME XXXVIII, NUMBER 3
291
TABLEIII.
Renal Stone Kidneys
(n= 9) AI
0.054±0.152
Be
0.070±0.107
Ca Cd Co Cr Fe Mg Mn Sn Sr Zn Mo Pb Se Cu
135.813±71.879 67.087±140.991 0.072±0.138 0.523±0.995 30.832±25.363 112.208±75.664 0.841±1.012 0.000±0.000 0.067±0.053 2363.000±1020. 583 0.135±0.268 0.081±0.228 0.680±0. 973 2.021±1.812
UninvolvedPortion of Hypernephroma Kideneys ( n = 11) 0.000±0.000 0.106±0.180 160.220±190.142 25.g21±13.417 0.941±2.865 0.112±0.047 30.154±20.908 78.755±16.498 0.824±0.864 0.000~0.000 0.056±0.099 2954.900±1165.390 8.2?2±25.269 0.053±0.116 3.438~2.884 * * * 1.238±0.433 *** P < 0.02
TABLEIV. Multielements in renal cortex (ppm) Renal Stone Kidneys (n=0) AI
Be Ca Cd Co Cr Fe Mg Mn Sn Sr Zn Mo Pb Se Ca
0. 000 ± 0.000
0.118±0.119 105.49g • 66.088 68.783 ± 72. 353 0.056 ± 0.070 0.419 ± 0.674 26,630 ± 14.425 98.671 ± 25.409 0. 843 ± 0. 422 0.022 ± 0.057 0.058 ± 0.047 4840.000± 3202.050 0.196±0.180 0.093±0.188 1. 514 ± 1. 026 2.021 ± 0. 737
Uninvolved Portion of
Hypernephroma Kidneys (n=12) 0.000 ± 0.000
0.1?2±0.151 136.700 • 102.700 63.121 ± 39.05? 0.057 ± 0.070 0.144 ± 0. 096 31. 308 ± 9.929 101. 140 ± 20.9?6 0. 959 ± 0.286
0.000 ± 0.000 0. 051 ± 0.048 50?3.100± 2111. g00 0.402±0.182 0.298±0.642 4.327 ± 2.362 2. 036 ± 0. 655
with calculi, whereas there was more Be, Co, Mo, and Se (p < 0.02) in control medulla, The multielement analyses of cortex in stone kidney (n = 9) and control kidney (n = 12) are shown in Table IV. Ca, Mg, and Zn were distributed equally in the two groups• Chromium and Sn were distributed more in stone kidney cortex, while Mo and Se were contained more in control renal cortex• 292
Comment
Multielements in renal medulla (ppm)
The method of analyses for miero-element~ has improved remarkably in recent years.!.~ The role of micro-elements in urinary stone disi,i ease has been under discussion for some time. 7-1° Little definitive information, however, has been presented linking the presence or ab senee of selected micro-elements in the urine 0 patients with various forms of the disease to ttil pathogenesis of the disease. In vitro experiment have shown that certain micro-elements ha~i an effect on the crystallization of calcium ox~ late and calcium phosphate? Concentrations ~ micro-elements used in the test system were ot ten unphysiologic. ..... ~?:~; In 1987 and 1940 RandalP ~82 pubhshed art,s!: cles in which he depieted the early developme~ii of attached renal ealeuli within and on the } ~ nal papilla. His results were substantiated ~N other investigators during the next decade a ~ then were largely ignored. 5 At present it is w ~ i recognized that ealeific deposits occur a n ~"~:~ ' neys and have been identified as either e a l e ~ phosphate 13 or calcium oxalate. 14 Oliver et d i ~ found that the stones of rats invariably wer~ ~0~ eated near the bend of loop of Henle. H ~ N mann, Lehmaim, and Komor ~ tissue concentration of oxalate a the papilla, medulla, and torte: compared these with the eoncent late and calcium in urine. Signif concentrations of calcium and ox served in the papilla compared dulla. The medulla, in turn, eor eoncentrations than the cortex. T that the observed intrarenal eal~ late coneentration gradients appeared t01 significant mechanism in the pathogene~i papillary calcification and strong indicati~ renal stone formation to start from fixedil talluric particles in the papilla. Depending on the method of fixing th e and the source of the tissue the incidei0t calcified deposits in the kidney is variaf most series, however, the spatial frec uei i ealeium deposits increases as the papillarytl approached. The results of these investig~ support that the renal papilla may be th4 stone formation in its early stage. Therefi studied the tissue concentration and di! tion gradient of multielements in c~i! containing kidney stone qf man at thi~:~ ferent portions, namely papilla, medul~t eortex, and compared these results with tJ:] involved counterpart with hypernephr0~
UROLOGY / SEPTEMBER1991
/ VOLUMEXXXVIII, N ~
Our s t u d y o n m u l t i e l e m e n t analyses in r e n a l 0~e k i d n e y r e v e a l e d t h a t C d , C o , a n d M o w e r e iund least in a m o u n t in r e n a l p a p i l l a as c o m ired w i t h t h e c o r t e x a n d m e d u l l a . M e a n w h i l e ere w e r e n o e l e m e n t s w h i c h w e r e s i g n i f i c a n t amounts in t h e c o n t r o l k i d n e y tissue. W h e n ultielements in r e n a l p a p i l l a , m e d u l l a , a n d irtex of s t o n e k i d n e y tissue w e r e c o m p a r e d ]th those of t h e r e s p e c t i v e c o u n t e r p a r t s in t h e ntrol k i d n e y t i s s u e , M o in r e n a l p a p i l l a a n d in r e n a l m e d u l l a w e r e s i g n i f i c a n t l y least in n0unt. M e a n w h i l e h i g h e r c o n c e n t r a t i o n s a n d ,latively h i g h f r e q u e n c y rates of Mo, Sr, a n d a w e r e f o u n d in u r i n a r y stones i n c l u d i n g calam oxa late.x°'la U m e y a m a a n d O g a w a 1° reirked t h a t N a , K, a n d M g w e r e also f o u n d in gh c o n c e n t r a t i o n s in u r i n a r y stones. T h u s ey s p e c u l a t e d t h a t these s u b s t a n c e s m a y b e in,fred in t h e process of stone f o r m a t i o n . W h y hibitors s u c h as M g a n d Z n w e r e f o u n d in gti c o n c e n t r a t i o n s in u r i n a r y stones is n o t Overall M o w a s less in a m o u n t in r e n a l p a !1a, m e d u l l a , a n d c o r t e x in stone k i d n e y tissue an c o n t r o l c o u n t e r p a r t s , a n d M o in r e n a l p a llia was least in a m o u n t as c o m p a r e d w i t h m e ilia a n d c o r t e x in e i t h e r stone k i d n e y or con3I k i d n e y tissue. To d a t e f u n c t i o n of M o in iman m e t a b o l i s m is n o t k n o w n , 6 a n d t h u s its ie i n t h e f o r m a t i o n of u r i n a r y stones is n o t ~eidated. H o w e v e r c o n s i d e r i n g t h e r e p o r t e d ct that M o w a s f o u n d in h i g h c o n c e n t r a t i o n in inary stones a n d less in s t o n e k i d n e y tissue, peeially r e n a l p a p i l l a , it is r e a s o n a b l e to specate t h a t M o m a y p l a y s o m e u n e x p l a i n e d b u t ~ificant role in c e r t a i n stage(s) of stone forafion A m o n g v a r i o u s a p p r o a c h e s to e l u c i d a t e e:mechanism of stone formation, micro-
GY,
e l e m e n t analysis of stone k i d n e y tissue in addit i o n to u r i n a r y s t o n e a n d u r i n e is necessary. 2-11-1 Kaga, Itabashi-Ku Tokyo, 173 Japan (DR. YAZAKI) References 1. Sehroeder HA, and Nason AP: Trace-element analysis in clinical chemistry; Clin Chem 17:461 (1971). 2. Gains NA, Miehaels CW, Thwaites MZ, and Trounce JR: Calcium concentration in the kidney, Nephron 5:352 (1968). 3. CookeSAR: The distribution of calcium in the human kidney: method and results, Br J Urol 43:130 (1971). 4. Wright RJ, and Hodgkinson A: Oxalic acid, ealeium, and phosphorus in the renal papilla of normal and stone forming rats, Invest Urol 9:369 (1972). 5. Hautmann R, Lehmann A, and Komor S: Calcium and oxalate concentrations in human renal tissue: the key to the pathogenesis of stone formation? J Urol 123:317 (1980). 6. Gemba A: An analytical signifieanees and its determinations of the trace elements in human, Igaku No Ayumi 120; 369 (1982). 7. Eusebio E, and Elliot JS: Effect of trace metals on the crystallization of calcium oxalate, Invest Urol 4:431 (1967). 8. Meyer JL, and Angio EE: The role of trace metals in calcium urolithiasis, Invest Urol 14:347 (1977). 9. ScottR, et al: Concentration and distribution of some minor and trace elements in urinary tract stones: a preliminary report, Urol Res 8:167 (1980). 10. Umeyama T, and Ogawa Y: Studies on trace element in urinary tract stones, Jpn J Urol 75:1038 (1984). 11. Randall A: The origin and growth of renal calculi, Ann Surg 105:1009 (1937). 12. Randall A: Papillary pathology as a precursor of primary renal calculus, J Urol 44:580 (1940). 13. Haggit RC, and Pitcock JA: Renal medullary calcifications', a light and electron microscopic study, J Urol 106:342 (1971). 14. Bennington JL, Haber SL, Smith JV, and Warner NE: Crystals of calcium oxalate in the human kidney. Studies by means of electromicroprobe and x-ray diffraction, Am J Clin Pathol 41.' 8 (1964). 15. OliverJ, MacDowell M, Whang R, and Welt LG: The renal lesions of electrolyte imbalance.IV. The intranephronic calculosis of experimental magnesium depletion, J Exp Med 124:263 (1966). 16. LevinsonAA, Nosal M, and Davidman RG: Traceelements in kidney stones from three areas in the United States, J Urol 15: 270 (1978).
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