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Evan AP et al, 2015: MECHANISM BY WHICH SHOCK WAVE LITHOTRIPSY CAN PROMOTE FORMATION OF HUMAN CALCIUM PHOSPHATE STONES.

Evan AP, Coe FL, Connors BA, Handa RK, Lingeman JE, Worcester EM.
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana; International Kidney Stone Institute, Methodist Hospital, Indianapolis, Indiana.
Nephrology Section, University of Chicago, Chicago, Illinois.
International Kidney Stone Institute, Methodist Hospital, Indianapolis, Indiana.
Nephrology Section, University of Chicago.

Abstract

Human stone calcium phosphate (CaP) content correlates with higher urine CaP supersaturation (SS) and urine pH as well as with the number of shock wave lithotripsy (SWL) treatments. SWL does damage medullary collecting ducts and vasa recta, sites for urine pH regulation. We tested the hypothesis that SWL raises urine pH and therefore Cap SS resulting in CaP nucleation and tubular plugging. Left kidney (T) of nine farm pigs was treated with SWL and metabolic studies were performed using bilateral ureteral catheters for up to 70 days post-SWL. Some animals were given an NH4Cl load to sort out effects on urine pH of CD injury vs. increased HCO3- delivery. Histopathologic studies were performed at the end of the functional studies. The mean pH of the T kidneys exceeded that of the control (C) kidneys by 0.18 units in 14 experiments on 9 pigs. Increased HCO3- delivery to CD is at least partly responsible for the pH difference because NH4Cl acidosis abolished it. The T kidneys excreted more Na, K, HCO3-, water, Ca, Mg, and Cl than C kidneys. A single nephron site that could produce losses of all of these is thick ascending limb. Extensive injury was noted in medullary thick ascending limbs and collecting ducts. Linear bands showing nephron loss and fibrosis were found in the cortex and extended into the medulla. Thus, SWL produces tubule cell injury easily observed histopathologically that leads to functional disturbances across a wide range of electrolyte metabolism including higher than control urine pH. 

Am J Physiol Renal Physiol. 2015 Feb 4:ajprenal.00655.2014. doi: 10.1152/ajprenal.00655.2014. [Epub ahead of print]

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Comments 2

Guest - peter.alken on Thursday, 27 October 2016 16:04

It is difficult to understand why this abstract and the review with conflicting views on the question if ESWL provokes brushite stone formation got nearly 4000 hits and nobody had an idea for a comment and thought it necessary to start a discussion.

It is difficult to understand why this abstract and the review with conflicting views on the question if ESWL provokes brushite stone formation got nearly 4000 hits and nobody had an idea for a comment and thought it necessary to start a discussion.
Hans-Göran Tiselius on Friday, 03 July 2015 10:23

Does SWL induce formation of calcium phosphate (calcium hydrogen phosphate; brushite) stones? Of all reasons presented with the aim of disqualifying SWL as a safe and appropriate method for stone removal, the hypothesis that shockwaves cause kidney damage with subsequent alteration in urine composition leading to calcium phosphate precipitation, seems to be one of the most serious potential side effects. Not only are brushite stones more difficult to disintegrate (with all available methods), but it is also the calcium crystal phase that is associated with highest recurrence rate.
In this article the authors have used an experimental approach to test the hypothesis that SWL converts calcium oxalate stone disease to calcium phosphate stone disease. For this purpose they treated pigs with 4 x 2000 electrohydraulic shock waves (Unmodified Dornier HM3 lithotripter) at 24 kV and with a frequency of 2 Hz. The pH and composition were measured in urine collected through ureteral catheters. Not unexpectedly this tough treatment resulted in considerable injuries to the treated kidney.
The major effects on urine were increased pH and increased excretion of HCO3- when a comparison was made with urine from the untreated kidney in the same animal. In summary the average increment in pH was 0.18 pH-units, an effect that was explained by increased concentrations of HCO3- in collecting ducts. Although the authors claim that no single zone of the kidney received more than 2000 shockwaves this is of course impossible to know because also outside the defined focal volume will tissues be exposed to a significant shockwave energy. The treatment given to these kidneys will likely cause a trauma at a level not encountered clinically. That slight acidification defects appeared in the pig kidneys is therefore not surprising.
Irrespective of the interesting findings presented in this article, the fundamental question is which evidence there is for increased risk of brushite precipitation and stone formation as a result of SWL? The authors mainly support this assumption by a substantial number of patients with brushite stones referred to their clinic and with the observation that 78% of these patients previously had been treated with SWL. The explanation for that might most certainly be that these patients have a particularly problematic disease with frequent recurrences. This observation does not directly mean that SWL was the cause of brushite stone formation. It is emphasized that approximately 20% of these patients had a history of non-brushite stones [1]. It needs to be pointed out that conversion from CaOx to CaP also was recoreded after PNL.
Also Knoll and coworkers [2] recorded an increasing number of brushite stones during the period 1980-2004, but the percentage of brushite stones nevertheless remained at a low level. Apatite stones increased temporarily but subsequently returned to almost the same level as 1980, but a peak between 1989 and 1994 deserves some attention.
Increased occurrence of calcium phosphate stones from 19 to 27% was recorded in children between two periods 1992-2000 and 2001-2010. Interestingly the frequency of brushite stone formation increased from 3.7 to 11.1% in 27 children with recurrent stone formation. Any relation to SWL was not presented in this material but it is not likely that SWL had played a role for the altered stone composition [3].
Stone analysis carried out in USA 1989 and 2003 disclosed an increased occurrence of brushite from 1.4 to 4.1%. Also the frequency of CaOx increased but HAP remained constant. They noted a conversion of CaOx to Cap in 3.2% but a reverse conversion in 7.6%. On the other hand mixed CaOxCaP were converted to pure CaP in 18% [4].
The conclusion that can be drawn from these and other similar studies is that CaP (brushite) apparently has become more common during recent decades, although the fraction of brushite stones still remain small. This alteration in stone composition seems to have a more general explanation than just SWL. During the same period of time alkaline citrate as a recurrence preventive tool has been extensively used. Previous restrictions in calcium intake has been replaced by a more generous recommendations and it is of note that hypercaliuria is one important risk factor for brushite stone formation. Whether a minor increment in urine pH, as demonstrated in the SWL treated pig kidneys, can explain this altered stone pattern remains to be demonstrated.
In view of the hypothesis of a possible relationship between SWL and subsequent brushite stone formation, this field should apparently be given high research priority with both stone and urine analysis at first as well as at late stone removing procedures, and not only with SWL.
References
1. Krambeck AE, Handa SE, Evan AP, Lingeman JE. Profile of the brushite stone former. J Urol. 2010; 184: 1367-1371.
2.Knoll t, Schubert G, Fahlenkamp D, Leusmann DB. Urolithiasis through the ages: data on more than 200 000 urinary stone analyses. J Urol 2011; 185: 1304-1311
3. Wood KD, Stanasel IS, Koslov DS, Muffarij PW, Mc Lorie, Assimos D. Changing stone composition profile in children with nephrolithiasis. Urology 2013;82: 210-213
4. Mandel N, Mandel I, Fryjoff K, Rejniak T, Mandel G. Conversion of calcium oxalate to calcium phospahte with recurrent stone episodes. J Urol 2003; 169; 2026-2029

Does SWL induce formation of calcium phosphate (calcium hydrogen phosphate; brushite) stones? Of all reasons presented with the aim of disqualifying SWL as a safe and appropriate method for stone removal, the hypothesis that shockwaves cause kidney damage with subsequent alteration in urine composition leading to calcium phosphate precipitation, seems to be one of the most serious potential side effects. Not only are brushite stones more difficult to disintegrate (with all available methods), but it is also the calcium crystal phase that is associated with highest recurrence rate. In this article the authors have used an experimental approach to test the hypothesis that SWL converts calcium oxalate stone disease to calcium phosphate stone disease. For this purpose they treated pigs with 4 x 2000 electrohydraulic shock waves (Unmodified Dornier HM3 lithotripter) at 24 kV and with a frequency of 2 Hz. The pH and composition were measured in urine collected through ureteral catheters. Not unexpectedly this tough treatment resulted in considerable injuries to the treated kidney. The major effects on urine were increased pH and increased excretion of HCO3- when a comparison was made with urine from the untreated kidney in the same animal. In summary the average increment in pH was 0.18 pH-units, an effect that was explained by increased concentrations of HCO3- in collecting ducts. Although the authors claim that no single zone of the kidney received more than 2000 shockwaves this is of course impossible to know because also outside the defined focal volume will tissues be exposed to a significant shockwave energy. The treatment given to these kidneys will likely cause a trauma at a level not encountered clinically. That slight acidification defects appeared in the pig kidneys is therefore not surprising. Irrespective of the interesting findings presented in this article, the fundamental question is which evidence there is for increased risk of brushite precipitation and stone formation as a result of SWL? The authors mainly support this assumption by a substantial number of patients with brushite stones referred to their clinic and with the observation that 78% of these patients previously had been treated with SWL. The explanation for that might most certainly be that these patients have a particularly problematic disease with frequent recurrences. This observation does not directly mean that SWL was the cause of brushite stone formation. It is emphasized that approximately 20% of these patients had a history of non-brushite stones [1]. It needs to be pointed out that conversion from CaOx to CaP also was recoreded after PNL. Also Knoll and coworkers [2] recorded an increasing number of brushite stones during the period 1980-2004, but the percentage of brushite stones nevertheless remained at a low level. Apatite stones increased temporarily but subsequently returned to almost the same level as 1980, but a peak between 1989 and 1994 deserves some attention. Increased occurrence of calcium phosphate stones from 19 to 27% was recorded in children between two periods 1992-2000 and 2001-2010. Interestingly the frequency of brushite stone formation increased from 3.7 to 11.1% in 27 children with recurrent stone formation. Any relation to SWL was not presented in this material but it is not likely that SWL had played a role for the altered stone composition [3]. Stone analysis carried out in USA 1989 and 2003 disclosed an increased occurrence of brushite from 1.4 to 4.1%. Also the frequency of CaOx increased but HAP remained constant. They noted a conversion of CaOx to Cap in 3.2% but a reverse conversion in 7.6%. On the other hand mixed CaOxCaP were converted to pure CaP in 18% [4]. The conclusion that can be drawn from these and other similar studies is that CaP (brushite) apparently has become more common during recent decades, although the fraction of brushite stones still remain small. This alteration in stone composition seems to have a more general explanation than just SWL. During the same period of time alkaline citrate as a recurrence preventive tool has been extensively used. Previous restrictions in calcium intake has been replaced by a more generous recommendations and it is of note that hypercaliuria is one important risk factor for brushite stone formation. Whether a minor increment in urine pH, as demonstrated in the SWL treated pig kidneys, can explain this altered stone pattern remains to be demonstrated. In view of the hypothesis of a possible relationship between SWL and subsequent brushite stone formation, this field should apparently be given high research priority with both stone and urine analysis at first as well as at late stone removing procedures, and not only with SWL. References 1. Krambeck AE, Handa SE, Evan AP, Lingeman JE. Profile of the brushite stone former. J Urol. 2010; 184: 1367-1371. 2.Knoll t, Schubert G, Fahlenkamp D, Leusmann DB. Urolithiasis through the ages: data on more than 200 000 urinary stone analyses. J Urol 2011; 185: 1304-1311 3. Wood KD, Stanasel IS, Koslov DS, Muffarij PW, Mc Lorie, Assimos D. Changing stone composition profile in children with nephrolithiasis. Urology 2013;82: 210-213 4. Mandel N, Mandel I, Fryjoff K, Rejniak T, Mandel G. Conversion of calcium oxalate to calcium phospahte with recurrent stone episodes. J Urol 2003; 169; 2026-2029
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