Medical Hypotheses 82 (2014) 691–693

Contents lists available at ScienceDirect

Medical Hypotheses

journal homepage: www.elsevier .com/locate /mehy

Are we estimating the adverse effects of shock-wave lithotripsyon a faulty scale?

http://dx.doi.org/10.1016/j.mehy.2014.03.0050306-9877/� 2014 Elsevier Ltd. All rights reserved.

⇑ Corresponding author. Address: Department of Nuclear Medicine, UniversityHospital Split, Spinciceva 1, 21000 Split, Croatia. Tel.: +385 21 556 818; fax: +385 21556 955.

E-mail address: davor.eterovic@mefst.hr (D. Eterovic).

Davor Eterovic a,⇑, Marijan Šitum b, Vinko Markovic c, Krunoslav Kuna d, Ante Punda c

a Department of Nuclear Medicine, University Hospital Split and Department of Medical Physics, University of Split School of Medicine, Croatiab Department of Urology, University Hospital Split and University of Split School of Medicine, Croatiac Department of Nuclear Medicine, University Hospital Split and University of Split School of Medicine, Croatiad Department of Gynecology and Obstetrics, University Hospital Sisters of Charity, Zagreb, Croatia

a r t i c l e i n f o

Article history:Received 23 April 2013Accepted 5 March 2014

a b s t r a c t

The adverse effect of shock-wave lithotripsy (SWL) for renal stones on blood pressure is currently definedas its post-treatment increase. On the contrary, we hypothesize that even mild, unilateral renal obstruc-tion initiates an increase in blood pressure. Then, in absence of treatment-induced injury, the stoneremoval should decrease the blood pressure. We derived the formula to assess the expected change inthe mean arterial pressure following relief of renal obstruction without affecting the kidney functions.The predictions were well replicated in the cohort of patients with renal stone treated with paren-chyma-saving open surgery, with 6.4 mmHg decrease at 3 months. On the contrary, in SWL cohort,instead of the expected 4.7 mmHg decrease, the blood pressure was unchanged. In conclusion, theabsence of decrease in blood pressure is a very common adverse effect of SWL, leading to an epidemio-logically significant increase in the risk of arterial vascular events.

� 2014 Elsevier Ltd. All rights reserved.

Introduction

Despite growing evidence that shock-wave lithotripsy (SWL) in-duces both acute and permanent damage to renal tissue, there is alack of consensus whether this has implications on renal controlfunctions. Specifically, the initial observations on association ofSWL with the new onset hypertension have not been recently cor-roborated [1].

We offer an explanation for this apparent controversy. First, oneshould realize that even unilateral, relatively mild renal obstruc-tion can elicit a rise in blood pressure.

If so, there is no real difference in reports showing unchanged orslightly increased arterial pressure following SWL. By redefiningthe adverse effect of SWL as an absence of a decrease in arterialpressure, all these reports demonstrate that SWL related renaldamage offsets the beneficial effects of relief of obstruction.

However, it is hard to provide hard data on the hypothesis thatrenal obstruction in a typical SWL patient is sufficient to alterhemodynamics. The problem is that we do not know what theblood pressure was before the patient developed the obstructive

kidney disease. Still, if our hypothesis was true, the removal of kid-ney stone without collateral damage to kidney should reestablishthe pre-obstructive state and thus lower the blood pressure. Unfor-tunately, the reported comparisons of SWL with competitive non-invasive or minimally invasive techniques have not addressed theissue of chronic changes in blood pressure [2]. We reported a mean6.4 mmHg decrease in the mean arterial pressure (MAP) in the co-hort of patients with unilateral renal stone treated with paren-chyma-saving open surgery and unchanged arterial pressures inSWL cohort, at 3 months after treatment [3]. However, one can ar-gue that the degree of obstruction in SWL patients was insufficientto elicit the hemodynamic changes. To circumvent this problem,we propose the use of hemodynamic modeling to predict a changein blood pressure following relief of unilateral renal obstruction,assessed by comparing the renal vascular resistances of the twokidneys.

Hemodynamic modeling

Recall that MAP equals the product of cardiac output (CO) andtotal peripheral vascular resistance (TPR):

MAP ¼ CO � TPR

692 D. Eterovic et al. / Medical Hypotheses 82 (2014) 691–693

Denote by TPRobstruction and TPRno obstruction the total peripheralresistances of the same person in the states with and without uni-lateral renal obstruction, respectively. Assuming unchanged ve-nous return, and relatively small differences in afterload, thecardiac output is preserved, and:

MAPno obstruction ¼MAPobstruction �TPRno obstruction

TPRobstruction

Next, in normal renal hemodynamic conditions (non-obstruc-tive state) the kidneys accommodate about one fifth of cardiac out-put. Since the blood flow to an organ is proportional to its vascularconductance (inverse of vascular resistance), it follows that thetotal peripheral vascular conductance (TPCno obstruction) is com-prised from renal vascular conductance (RVCno obstruction) and thevascular conductance of the rest of periphery, which is thus about4 � RVCno obstruction:

TPCno obstruction ¼ RVCno obstruction þ 4� RVCno obstruction

The above equation does not hold when the kidney is ob-structed; then RVC may decrease well below one fifth of TPC.Assuming that unilateral renal stone does not affect non-renalvasculature:

TPC obstruction ¼ RVCobstruction þ 4� RVCno obstruction

Combining the above three equations and reverting back to useof the more common concept of vascular resistance:

MAPno obstruction ¼MAPobstruction �15

4þ RVRno obstruction

RVRobstruction

� �

Thus, one can estimate the chronic effect of unilateral renalobstruction on MAP from the ratio of renal vascular resistances be-tween the states with and without obstruction.

The above equation can be written in terms of vascular resis-tance of the lithiatic kidney (LKVR) and the vascular resistance ofthe non-lithiatic kidney (NLKVR). Since the two kidneys are alignedin parallel:

MAPno obstruction ¼MAPobstruction

� 15

4þ ðLKVR � NLKVRÞno obstruction

ðLKVR � NLKVRÞobstruction

�

� ðLKVR � NLKVRÞobstruction

ðLKVR þ NLKVRÞno obstruction

�ð1Þ

One usually does not know what MAP was before a persondeveloped the obstructive kidney disease. However, one can com-pare the states before and after stone removal. Then the model canbe simply tested by comparing the expected with measured valuesof MAP. If the method of relief of obstruction does not interfere

Table 1Hemodynamic effects of unilateral renal stone removal (mean values ± SD).

Open surgery (n = 30)

At baseline At 3

Renal vascular resistance (mmHg/ml/min)Obstructed kidney 0.52 ± 0.32 0.22Non-obstructed kidney 0.26 ± 0.12 0.21Total 0.17 ± 0.08 0.11

Mean arterial pressure (mmHg)*

Observed 104.2 ± 13.8 97.8Expected by Eq. (1) (bias ± precision)** 97.6Expected by Eq. (2) 97.3

* (2/3) � diastolic pressure + (1/3) � systolic pressure.** Observed-expected: mean ± SD.

with kidney function, the pre-obstructive MAP and RVR shouldbe reproduced by the post-treatment values, at a time when stea-dy, chronic conditions are restored.

If, however, the post-treatment RVR remains elevated, MAP willnot decrease and we may ascribe (within the framework of ourmodel) the lack of decrease in MAP as an adverse effect of themethod.

Moreover, we can assess the adverseness by comparing the ob-served MAP with the value that would occur if the stone removalleft the kidney blood pressure regulating function intact (hypothet-ical MAPno obstruction). To do so, in patients with unilateralobstruction, the post-treatment vascular resistance of non-lithiatickidney (NLKVRno obstruction) can be taken as a reference for the ex-pected post-treatment vascular resistance of the lithiatic kidney(LKVRno obstruction). Under this assumption Eq. (1) becomes:

hypothetical MAPno obstruction ¼MAPobstruction

� 15

�4þ 0:5 NLKVRno obstruction

� ðLKVR þ NLKVRÞobstruction

ðLKVR � NLKVRÞobstruction

�ð2Þ

Evaluation

We applied Eqs. (1) and (2) to our data on the cohorts ofpatients with unilateral renal stone treated with pyelolithotomyor SWL [3]. In comparison with non-lithiatic kidney, vascular resis-tance of the obstructed kidney was on average 100 and 86% greaterin the pyelolitotomy and SWL cohorts, respectively. At 3 months, inthe pyelolithotomy cohort, vascular resistance of the lithiatic kid-ney completely normalized and MAP decreased for 6.4 mmHg, al-most exactly as predicted by Eq. (1). However, in SWL patients,relief of obstruction did not affect either vascular resistance ofthe lithiatic kidney or MAP, so that about 5 mmHg decrease inMAP, as predicted by Eq. (2), did not occur. However, even small,apparently random changes in MAP following SWL can be ex-plained by the respective changes in renal vascular resistance, aspredicted by Eq. (1) (Table 1).

Discussion

It is well known that shock-wave lithotripsy (SWL) may induceserious acute lesions to renal tissue. However these effects are rareand often resolve without sequelae. Since SWL is the most preva-lent method of treating the symptomatic renal stones, the eventualcommon chronic effects are much more important. Moreover, gi-ven the sharp increase in the risk of adverse vascular events withrising arterial pressure, [4] even the subclinical effects on renalcontrol of blood pressure are epidemiologically important. Thus,

SWL (n = 29)

months At baseline At 3 months

± 0.1 0.41 ± 0.38 0.39 ± 0.29± 0.11 0.22 ± 0.06 0.23 ± 0.08± 0.05 0.13 ± 0.04 0.13 ± 0.05

± 10.2 102.8 ± 7.9 103.4 ± 7.7± 12 (0.23 ± 7.3) 103.2 ± 9 (�0.02 ± 5.6)± 12.6 98.1 ± 8.6

D. Eterovic et al. / Medical Hypotheses 82 (2014) 691–693 693

the issue of SWL related blood pressure changes is the importantone and should not be addressed only in terms of induction ofblunt hypertension, as done in some previous studies.

The reports on SWL related chronic effects on arterial pressureappear as conflicting ones, which actually might not be the case.We offer an alternate scale for assessing the adverse effect ofSWL, arguing that the post-treatment observations should bejudged according to the expected improvements in renal functions.On that scale all reports, those showing a small increase, and thoseshowing no change, demonstrate the absence of lowered bloodpressure following SWL.

The cause of elevated RVR in patients with renal stone at base-line is not known. Possibilities include an altered vasomotor tone,which is abolished by relief of obstruction, as might be the case inour open surgery cohort [3]. The hard evidence that SWL induceschronic renal lesions is the persistence of elevated RVR, despite re-lief of obstruction. Thus the adverse effects of shock waves on renalvasculature are not only acute [5], but persist and probably sup-press the blood pressure decreasing effect of relief of obstruction.

The Eq. (1) rests on conservation of cardiac output between thestates with and without unilateral renal obstruction andthe assumption that this obstruction may affect vascular resistanceof the contralateral kidney, but not the rest of periphery. Theseassumptions proved to be the robust ones, since the predictionswere well met in both cohorts. Eq. (2) further assumes that reliefof obstruction leaves the renal control of blood pressure unaffectedand neglects the eventual impact of obstruction on contralateralkidney. This model also worked well in parenchyma saving opensurgery cohort, but not in SWL cohort, which indicates that litotri-psy affects adversely the renal control functions. In our SWL cohortthe degree of renal obstruction corresponded to 5 mmHg increasein MAP, as assessed by Eq. (2). Our sample may not be representa-tive to all SWL patients, which can be more or less obstructed. Thismay limit our conclusions, but the model should predict the effectof renal obstruction on blood pressure in any patient with renal

obstruction. If stone removal does not lower the blood pressurearound the value expected by the Eq. (2), one can suspect a collat-eral lesion, with adverse effect on renal control function.

We used the radionuclide measurement of renal blood flow toassess RVR [3]; alternatively, one can use the Doppler ultrasound,making the use of Eq. (2) to predict the expected decrease inMAP following relief of unilateral renal obstruction a simpleprocedure.

Thus, we may not be using the proper scale in assessing the ad-verse effects of SWL on blood pressure and possibly other renalcontrol functions, like erythropoiesis [6]. Randomized comparisonof SWL with kidney parenchyma safe treatments could providemore direct answers.

Conflict of interest

The authors have no conflict of interest to declare.

References

[1] Pearle MS. Shock wave lithotripsy for renal calculi. N Engl J Med 2012;367:50–7.

[2] Srisubat A, Potisat S, Lojanapiwat B, Setthawong V, Laopaiboon M.Extracorporeal shock wave lithotripsy (ESWL) versus percutaneousnephrolithotomy (PCNL) or retrograde intrarenal surgery (RIRS) for kidneystones. Cohrane Database Syst Rev 2009;4:CD007044.

[3] Eterovic D, Šitum M, Juretic-Kušcic L, Dujic Z. A decrease in blood pressurefollowing pyelolithotomy but not extracorporeal lithotripsy. Urol Res2005;33:93–8.

[4] Verdecchia P, Gentile G, Angeli F, Mazzotta G, Mancia G, Reboldi G. Influence ofblood pressure reduction on composite cardiovascular endpoints in clinicaltrials. J Hypertens 2010;28:1356–65.

[5] Eterovic D, Juretic-Kušcic L, Capkun V, Dujic Z. Pyelolithotomy improves whileextracorporeal lithotripsy impairs kidney function. J Urol 1999;161:39–44.

[6] Eterovic D, Šitum M, Punda A, Markovic V, Kokic S. Urinary obstructiondepresses erythropoiesis which recovers after parenchyma-saving surgery butnot SWL. Urol Res 2010;38:51–6.