Relationship between Kidney Size, Renal Injury, and Renal Impairment Induced by Shock Wave Lithotripsy : Journal of the American Society of Nephrology

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Pathophysiology of Renal Disease

Relationship between Kidney Size, Renal Injury, and Renal Impairment Induced by Shock Wave Lithotripsy

WILLIS, LYNN R.*; EVAN, ANDREW P.; CONNORS, BRET A.; BLOMGREN, PHIL; FINEBERG, NAOMI S.; LINGEMAN, JAMES E.§

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Journal of the American Society of Nephrology 10(8):p 1753-1762, August 1999. | DOI: 10.1681/ASN.V1081753
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Abstract

More than 15 yr of clinical experience with shock-wave lithotripsy (SWL) as treatment for renal calculi leaves no doubt that high-energy shock waves can permanently damage renal tissue and, at least acutely, impair renal function (1, 2). Gross hematuria consistently occurs after SWL, and magnetic resonance imaging reveals kidney damage after SWL in 63 to 85% of human patients (3). Histologic studies in experimental animals show that shock waves injure all tissues within the focal region (F2) of the shock waves. Vascular injury is most severe in this region, with veins and small arteries showing varying degrees of damage. The tubular injury induced by SWL involves disruption of the tubular epithelium and associated basement membrane.

SWL also typically promotes transient impairment of GFR and renal plasma flow (RPF) in human patients (4,5,6,7,8,9,10) and experimental animals (11,12,13). Results of longer-term studies suggest that the impairment of renal hemodynamics may be permanent (2), and at least one clinical report links SWL-induced renal injury to the development of irreversible acute renal failure (14). Other reports link shock-wave-induced injury to the subsequent development of new-onset hypertension (3, 9, 15, 16) or worsened preexisting hypertension. (3, 15). Indeed, elderly patients may be especially susceptible to impairment of renal hemodynamics and/or hypertension after SWL (17, 18).

Implicit in the notion that renal hemodynamics may be permanently impaired after SWL is the possibility that at least some of the tissue injury caused by the shock waves is irreversible. Clinical doses of shock waves applied to pig kidneys, which model human kidneys in size, morphology, and function (19), severely damage renal tissue within F2. Although some healing of the injury occurs, a substantial fraction of the damaged tissue becomes fibrotic and nonfunctional (20). Because the size of F2 is fixed for most lithotripters (F2 approximates a cylinder 8 cm long by 1.5 cm in diameter in the unmodified Dornier HM3 lithotripter), the lesion should encompass a greater fraction of the functional mass of a small kidney than of a large one. Accordingly, the resulting lesion and the extent to which renal function may be impaired should vary with the size of the kidney. In addition, the extent to which SWL-induced renal injury impairs renal function may also be related to the extent to which renal function may have been compromised by preexisting renal disease or injury. In this context, attention has increasingly been drawn to the possibility that risk factors may exist for SWL (2), and there has been longstanding concern that renal impairment after SWL may be greater in pediatric patients than in mature patients (21, 22), presumably because pediatric patients have smaller kidneys. There has also been speculation and concern that the seemingly higher susceptibility of older patients to greater renal impairment and incidence of hypertension (23, 24) after SWL may likewise be attributable to risk factors associated with reduced functional renal mass. The present studies were conceived with this view of risk factors for SWL in mind. The experiments tested the hypothesis that SWL-induced impairment of renal function is greater in small kidneys than in large kidneys.

Materials and Methods

Animal Protocols

Renal Clearance Experiments. Thirty-three female farm pigs were used in the clearance studies. All pigs were obtained from the same supplier (Hardin Farms) in the Indianapolis area. Sixteen pigs were 6 to 7 wk of age and 17 were 9 to 10 wk of age. Kidneys from the older pigs are similar in size to kidneys from mature adult human beings. The kidneys of the younger pigs contain a full complement of nephrons but have only about two-thirds the mass of the kidneys in the older pigs. Overall, kidney sizes in the two groups of pigs were approximately the same as in pediatric and adult human subjects.

On the day of each experiment, a pig was assigned either to a group that was to receive SWL or to a sham-control group. Each pig was anesthetized with ketamine (15 to 20 mg/kg, intramuscularly), intubated, and given a mixture of isoflurane (0.8 to 1.5%) and oxygen to breathe. Respiration was spontaneous. Catheters were placed in a marginal ear vein (Angiocath, 22-gauge, 1 inch) for infusion of fluids, in a femoral artery for monitoring BP and sampling of blood (Intercath, 19-gauge, 8 inches), and in both renal veins via the femoral veins (7F “Cobra,” Cook Inc.) for sampling of renal venous blood. Both ureters were cannulated with balloon catheters (7F, 65 cm, Medi-Tech) via a small midline incision immediately superior to the urinary bladder. Each catheter was visualized fluoroscopically and advanced with the aid of a flexible guide wire to the renal hilus where the balloons were inflated. Positioning of the renal venous catheters well into the renal veins was verified by fluoroscopy and injections of small volumes (approximately 0.5 ml) of dilute contrast medium. Body temperature was monitored throughout the experiment and maintained at 38 to 39°C with the aid of a warming pad.

Isotonic saline was infused intravenously in amounts ranging between 1 and 3% body weight during the 90 min preceding the start of sample collection. Subsequent infusion rates were adjusted to reflect changes in urine production.

Polyfructosan (Inutest, Henstettler, Austria) and para-aminohippurate (PAH) were infused intravenously in isotonic saline at 1 ml/min to establish and maintain (by continuous infusion) near-steady-state concentrations of each marker. Forty-five minutes into the infusion, the first of three consecutive 15-min collections of urine from each kidney was begun. Femoral arterial and bilateral renal venous blood samples were drawn at the midpoint of each collection period. After the third urine collection had been obtained, all infusions were stopped and the pigs were taken, still anesthetized and with all catheters in place, to the lithotripsy suite, where they were positioned in the treatment gantry and lowered into the water bath (maintained at 39°C). A small volume of contrast medium, sufficient to fill the renal pelvis, was injected retrograde into the right ureteral catheter to facilitate the fluoroscopic placement of the lower pole calyx of the right kidney at F2. Isotonic saline was infused intravenously at approximately 1 ml/min to maintain urine flow. Once placed, the targeted region of the kidney was subjected to SWL (2000 shocks, 24 kV, unmodified Dornier HM3). The shock waves were administered at a frequency of 2 Hz, and the electrode was replaced after each 1000 shocks (replacement takes about 1 min). A fluoroscopic image was generated after every 500 shocks to verify that F2 was still on target. After all of the shocks had been administered (usually after about 18 to 20 min), the pigs were returned to the laboratory where the sustaining infusion of PAH and polyfructosan was restarted and all monitors were reconnected. Sets of three 15-min samples of urine, with midpoint arterial and renal venous blood samples, were then obtained beginning at 1 and 4 h after SWL. At the completion of these collections, both kidneys were fixed in situ (see below) and removed for morphologic analysis.

Sham treatment initially included all procedures except SWL, but when it was subsequently realized that data obtained from pigs that were not transported to the lithotripsy suite did not differ from data obtained from pigs that were, transport, immersion, and contrast injections were not always included in subsequent sham experiments. Time equivalent to that required for the transportation and shockwave treatment was always included as part of this protocol.

Double Renal Vein Determination of PAH Extraction. In the course of fluoroscopically positioning the renal vein catheters, one of us (B.A.C.) noticed that in some pigs the right renal vein divided into at least two branches and that one branch appeared to drain the upper pole of that kidney while the other appeared to drain the lower pole. This anatomical feature of the renal veins of the pig is well documented, a and after validating our observation, we conducted six additional experiments in which double renal veins were identified for the right kidney. In those experiments, each renal vein catheter was positioned in one of those branches of the renal vein (Figure 1). No renal venous blood was collected from the left kidneys of those pigs. All other surgical preparations, subsequent treatment with SWL, and clearance determinations were identical to those for the pigs described above except that renal venous blood was not obtained from the contralateral unshocked kidneys of those pigs, and PAH extractions were determined only for the upper and lower poles of the shocked kidneys.

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Figure 1:
Diagram showing placement of catheters in double renal veins and in ureter for the Double-Vein series of experiments (aorta and renal artery not shown). The circle labeled F2 denotes the site at which the shock waves were targeted.

Tissue Preparation and Morphologic Analysis

At the completion of the clearance studies, all animals were prepared for vascular perfusion of both kidneys according to our previously published technique (25). The kidneys were then embedded and sectioned. Computer-assisted segmentation techniques were applied to serial sections of the kidneys, according to our recently developed protocol, to determine the size of the lesions produced by SWL (26). Four treated kidneys from each group were analyzed in this way.

Analytical Procedures

Urine and plasma samples were analyzed for polyfructosan and PAH according to standard methods (27, 28). Clearances of each were calculated as estimates, respectively, of GFR and RPF. The concentration of PAH in renal venous blood was used to calculate the extraction of PAH (EPAH) according to the equation: EPAH = {([PAH]arterial - [PAH]renal venous)} ÷ ([PAH]arterial). EPAH provides an estimate of the efficiency of renal tubular PAH secretion and is used to calculate “true” RPF (RPF = CPAH/EPAH). Filtration fraction (FF) was calculated as FF = GFR/RPF. Because of the variability encountered between pigs within each group, the GFR and RPF data were factored by kidney weight and are expressed per gram of kidney weight.

Statistical Analyses

Mean values were calculated for each set of three determinations and were analyzed by repeated-measures ANOVA (RM ANOVA). Shocked and unshocked kidneys were analyzed separately. Size and treatment were used as grouping factors, while time was treated as the repeated measure. When significant changes over time were found in the RM ANOVA, one-way RM ANOVA and the Newman-Keuls test were used to determine changes from baseline. The criterion for statistical significance was set at P < 0.05. The protocol was reviewed and approved by the Institutional Animal Care and Use Committees for Indiana University and Methodist Hospital.

Results

Morphologic Analysis and Quantification of Lesion

At the time of autopsy, the gross morphologic appearance of the SWL-treated kidneys from younger and older pigs was strikingly different (Figure 2). Subcapsular hematomas generally encased the entire 6- to 7-wk-old kidney (both anterior and posterior surfaces), whereas the 9- to 10-wk-old kidneys had much smaller sites of hemorrhage (about 1.5 cm in diameter) on either the anterior or posterior surfaces.

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Figure 2:
The gross morphology of the anterior surface of shock-wave lithotripsy (SWL)-treated kidneys (2000 shocks at 24 kV) from a 6-wk-old and a 9-2k-old pig (the 6-wk-old kidney is on the right). A subcapsular hematoma (noted as the dark region) completely surrounds the small kidney while the larger 9-wk-old kidney contains a small (1.5 cm) hematoma (arrow).

Examination of the treated kidneys by light microscopy revealed multiple sites of hemorrhage within the region of the lower pole corresponding to F2 (Figure 3). Each contained ruptured veins and/or arteries. Figure 3 shows a mid-coronal section from 6- and 10-wk-old kidneys illustrating the location and size of the SWL-induced damage. The lesions occupied 6.1 ± 1.7 and 1.5 ± 0.2 volume percent, respectively, of the younger and older kidneys. The difference between the two means is statistically significant (P < 0.05).

F3-14
Figure 3:
Digitized image (mid-coronal plane) of a 6- and 10-wk-old pig kidney after SWL (2000 shocks at 24 kV to the lower pole calyx). The large circle at the lower pole defines F2. The dark material within the circles (arrows) represents sites of intraparenchymal hemorrhage. The series of dark arrowheads lining the lower pole of the 6-wk-old kidney shows subcapsular hematomas resulting from intraparenchymal bleeding.

Renal Clearance Experiments

Mean body weights, kidney weights, and BP for younger and older pigs in the SWL and sham-SWL groups are summarized in Table 1. Mean body weights did not differ significantly between the SWL and sham-SWL subgroups within either age group, but the younger pigs in both subgroups weighed significantly less, by more than half, than their older counterparts (P > 0.001).

T1-14
Table 1:
Summary of mean body weights, kidney weights, and blood pressure in small and large, SWL-treated and control pigsa

Kidneys in the younger, smaller pigs of both subgroups weighed significantly less than those in the two subgroups of older, larger pigs, but right and left kidney weights within each age group were not significantly different from each other. Even so, SWL-treated kidneys tended to weigh, on average, about 10% more than the contralateral untreated kidneys in each group. This difference probably reflected the extravasation and subcapsular bleeding caused by the shock waves. Since the clearance data obtained for each kidney were factored by kidney weight, the weight discrepancy in shocked kidneys would be expected to underestimate the size of the change in clearance function occurring in those kidneys after SWL. As will be evident below, this difference has not affected the interpretation of these data.

Mean BP fell to similar degrees in all groups during the 6-h course of the experiments. As is evident from Figure 4, which plots BP for the individual pigs in each group, BP changes from pig to pig were generally consistent over the time course of the experiments.

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Figure 4:
Individual mean BP measured in all pigs in the small and large, SWL- and sham-treated groups. SWL treatment consisted of 2000 shocks at 24 kV to the lower pole calyx of right kidneys. Sham groups received identical treatment as SWL groups except that they did not receive SWL. Each treatment lasted approximately 20 min (see SWL designation on the x-axis).

Baseline urine flow rates were, with some exceptions, comparable in all four groups of pigs (Figure 5). No significant differences in baseline urine flow between or within groups were detected. SWL caused no detectable alteration of urine flow in either group of pigs. Post-SWL urine flow rates in both groups of SWL-treated pigs did not differ significantly from corresponding values in the sham groups of pigs.

F5-14
Figure 5:
Mean urine flow rates in shocked and contralateral unshocked kidneys of small and large pigs. For details, see legend of Figure 4.

Blood was always evident in urine collected from the shocked kidneys of both SWL-treated subgroups at the 1-h post-SWL collection, but was generally not evident, except in barely visible amounts, during the subsequent 4-h collections. Hematuria was never observed in urine obtained from the contralateral unshocked kidneys of either SWL-treated subgroup, nor was it evident in urine from either kidney of the sham-SWL subgroups.

The effect of SWL and sham-SWL on RPF in shocked and unshocked kidneys of younger and older pigs is summarized in Figure 6. Expressed per gram kidney weight, baseline RPF in both subgroups of 6- to 7-wk-old pigs did not differ significantly from baseline RPF in the corresponding subgroups of older pigs. A size-related difference in baseline RPF was evident, however, when absolute values were compared between older and younger pigs (baseline RPF in older pigs exceeded that in younger pigs) (data not shown).

F6-14
Figure 6:
Mean renal plasma flow (RPF) in shocked and contralateral unshocked kidneys of SWL-treated small and large pigs. For treatment details, see legend of Figure 4. Asterisks denote statistically significant changes from baseline. P values are provided in the text.

SWL applied to the same region of right kidneys of the younger pigs reduced RPF in those kidneys in all nine animals studied (Figure 6A). The mean reduction for this group was statistically significant at the 1-h post-SWL determination (P < 0.003), and was sustained below baseline through the 4-h period of observation. This response was significantly different from that of the right kidneys in the sham-SWL group of young pigs for the same period of time (P < 0.02, Figure 6A).

Mean RPF was also reduced by SWL in the shocked kidneys of the older pigs (P < 0.05, Figure 6B), but the individual responses in those larger kidneys were more variable than those in the small kidneys, and, on average, RPF fell to a lesser extent than in the small kidneys. The reduction of RPF in the large shocked kidneys was evident only at the 1-h post-SWL determination and had returned to baseline by the 4-h determination. By comparison, RPF did not change significantly over the course of the experiment in right kidneys of shamtreated older pigs (Figure 6B).

RPF was reduced significantly and to similar degrees in the contralateral unshocked kidneys of both subgroups of SWL-treated pigs (P < 0.025, Figure 6C; P < 0.05, Figure 6D). These reductions were evident only at the 1-h post-SWL determination, but the overall responses were significantly different from the corresponding values in the large and small sham-SWL pigs (P < 0.002).

The effect of SWL and sham-SWL on GFR (expressed per gram kidney weight) in large and small pigs is summarized in Figure 7. Mean baseline GFR did not differ significantly among any of the subgroups. Sham pigs showed no consistent changes in GFR in either kidney over the time course of the study, whereas SWL reduced GFR to similar and statistically significant degrees in both shocked and unshocked kidneys of large and small pigs at 1 h post-SWL (P < 0.001). At the 4-h post-SWL determination, GFR had returned to or exceeded baseline values in both kidneys of large and small pigs. FF data are summarized in Figure 8. There were no significant changes in FF in any of the subgroups of pigs.

F7-14
Figure 7:
GFR in shocked and contralateral unshocked kidneys of small and large pigs. For treatment details, see legend of Figure 4. Asterisks denote statistically significant changes from baseline. P values are provided in the text.
F8-14
Figure 8:
Filtration fraction in shocked and contralateral unshocked kidneys of small and large pigs. For treatment details, see legend of Figure 4.

Figure 9 summarizes the PAH extraction data for both groups of small and large pigs. Baseline extractions for right and left kidneys in large and small pigs were not significantly different from each other. SWL reduced EPAH to similar and statistically significant degrees in the shocked kidneys of large and small pigs at the 1-h post-SWL determination (-9.41 ± 2.03% in small pigs, P < 0.002, versus -10.3 ± 2.13% in large pigs, P < 0.007) (Figure 9, A and B). PAH extraction by the small shocked kidneys remained significantly below baseline throughout the 4-h post-SWL period (P < 0.002), whereas it had returned to baseline by the 4-h determination in the large shocked kidneys. In contrast, PAH extraction by the contralateral unshocked kidneys in each of the SWL-treated subgroups showed no significant change from baseline over the 4-h post-SWL period. No significant changes in PAH extraction were evident in either kidney of both subgroups of sham-SWL pigs. The post-SWL pattern of PAH extraction seen in both groups of SWL-treated kidneys was significantly different from the corresponding patterns in each respective group of sham-controls (P < 0.005).

F9-14
Figure 9:
Para-aminohippurate (PAH) extraction in SWL-treated, sham-treated, and contralateral unshocked kidneys of small and large pigs. For details, see legend of Figure 4.

Double Renal Vein Determination of PAH Extraction

In this series of experiments, samples of renal venous blood were obtained from the upper and lower poles of the same kidney in each of six pigs (6 to 7 wk old) through catheters placed in branches of the renal vein originating from each pole of that kidney. As is evident from the data shown in Figure 10, SWL to the lower pole of those kidneys caused a statistically significant reduction of EPAH in that pole at each posttreatment determination (from 76.6 ± 7.2% to 70.6 ± 6.7% at 1 h post-SWL, P < 0.005, and to 71.6 ± 6.7% at 4 h post-SWL, P < 0.05). In contrast, treatment of the lower pole with shock waves had no detectable effect on PAH extraction in the upper pole of the same kidneys. The overall hemodynamic responses (GFR and PAH clearance) of the shocked and unshocked kidneys in these double-vein experiments are summarized in Figure 11, and were similar to those that occurred in shocked and unshocked kidneys of the small pigs in the first series of experiments.

F10-14
Figure 10:
PAH extraction in shocked lower poles and unshocked upper poles of one kidney in six pigs with double renal veins to those kidneys. For treatment details, see legend of Figure 4. Asterisks denote statistically significant changes from baseline. P values are provided in the text.
F11-14
Figure 11:
GFR and PAH clearance in right and left kidneys after SWL (2000 shocks at 24 kV) to the lower pole calyx of the right kidneys in six pigs with double renal veins to those kidneys. For treatment details, see legend of Figure 4. Asterisks denote statistically significant changes from baseline. P values are provided in the text.

Discussion

In our experience, the application of 2000 shocks at 24 kV to one kidney consistently reduces renal blood flow and GFR in that kidney (13, 29). The results of the current study, which involved the same treatment protocol as in our earlier studies, confirm and extend these findings by demonstrating that small kidneys exhibited greater reductions of blood flow during the first 4 h after SWL than did large kidneys. To the extent that an acute reduction of renal blood flow represents an undesirable and potentially harmful effect of SWL, and if SWL causes greater reductions of renal blood flow in small kidneys, kidney size appears to qualify as a risk factor for SWL-induced impairment of renal hemodynamics.

Mostafavi et al. (30) have recently observed substantial reductions of renal cortical blood flow in human patients during the first 4 h after SWL (1800 to 2200 shocks at 18 to 20 kV). These observations, which were obtained under treatment conditions similar to those used in our current and earlier animal studies (13, 31, 32), corroborate, and extend to human patients, our findings that SWL acutely reduces renal blood flow. Mostafavi et al. (30) also detected an SWL-induced increase of medullary blood flow. They attributed that increase to a compensatory response intended to prevent potential cellular damage from hypoxia threatened by an overall reduction of renal blood flow (29).

Another consistent finding in our earlier studies has been that SWL always causes severe and localized injury to renal tissue within and near F2 (26). The injury primarily involves vascular tissue (26), but it also affects all other types of renal tissue within and near F2. Because F2 is of relatively fixed dimensions, the tissue damage induced at F2 should comprise a greater proportion of the renal mass of a small kidney than of a large one. The current findings support this hypothesis.

The possibility that small kidneys may be at increased risk for adverse consequences of SWL has been of concern to some pediatric urologists for several years (22). Although pediatric SWL is generally considered safe and effective (33,34,35), it has not been known whether SWL-induced renal damage may impair renal growth (36, 37) or otherwise adversely affect longterm renal function (37). The present findings support the theoretical basis for these concerns by demonstrating that the acute tissue damage caused by the shock waves affects a much larger fraction of a smaller, and in this case, immature, kidney than of a larger, more mature one. It remains to be determined whether greater initial renal injury from SWL compromises renal growth or long-term renal function.

The fourfold difference in fractional lesion size observed between small and large kidneys in these studies is substantial. Nevertheless, and kidney size aside, these lesions occupied only a relatively small fraction of the total functional mass of each kidney. Accordingly, the large average reductions of RPF in the SWL-treated kidneys of each group (50% in small kidneys and 27% in large kidneys; Figure 6) seem out of proportion to the size of the lesions. Moreover, it cannot be determined from the current results whether the renal vasoconstriction induced by SWL was generalized for the whole kidney or was specifically localized within or near F2. This is because the classic clearance method for determining RPF or GFR provides only an indication of integrated clearance for the whole kidney. In that regard, the present finding of such large reductions of whole-kidney RPF, especially in the small kidneys, supports the view that if blood flow was severely reduced within F2, it was probably also reduced throughout the rest of the cortex. The findings of Mostafavi et al. (30) that blood flow was reduced throughout the cortex after SWL supports this interpretation, but they do not rule out the possibility of an even greater reduction within F2.

If the impairment of renal hemodynamics or tubular function associated with SWL is related to the size of the lesion caused by the shock waves, it is reasonable to expect that the resulting impairment will be greatest in the smaller kidneys. This expectation was borne out for RPF in the present experiments, but it did not hold for GFR or PAH extraction. One implication behind the failure to detect size-related differences in the latter two variables may be that kidney size does not determine the extent to which SWL alters GFR or PAH extraction. Alternatively, given the relatively small post-SWL reductions of GFR and PAH extraction that were evident in both groups of pigs, the whole-kidney clearance methods may simply not have been sensitive enough to detect a difference in the magnitude of the responses between large and small kidneys.

PAH extraction was significantly reduced, and to similar degrees, in shocked kidneys of large as well as small pigs in these studies. Because this effect did not occur in the contralateral unshocked kidneys of these pigs, we can safely assume that the reduced extraction was directly related to the SWL, and probably reflects the result of tubular damage inflicted by the shock waves. Moreover, since the reduced extraction in the small kidneys was sustained throughout the entire 4-h period after SWL, whereas that in the large kidneys was no longer evident at the 4-h determination, it seems reasonable to think that the small kidneys sustained the greatest injury from the shock waves. This suggestion is supported by the presence of the larger lesion in the small kidneys. It is possible, as well, that our failure to find a greater absolute depression of PAH extraction in the small kidneys after SWL, despite the more severe injury, was also due to the localized nature of that effect. This possibility is clearly supported by the results obtained from the double-vein experiments. What may have been a case of severely impaired PAH extraction within a relatively small zone of injury, even in the large kidneys, would have been diluted and obscured by the much larger fraction of the renal parenchyma that had not been directly affected by the shock waves and in which PAH extraction could be expected to have been normal. Thus, the double-vein experiments demonstrated that the shock waves did not reduce PAH extraction uniformly throughout the kidney. Indeed, the notion that SWL-induced tubular impairment would be confined mainly (if not entirely) to the damaged tissue is not unreasonable. We and others (1,2,3, 38, 39) have clearly shown that the morphologic damage caused by SWL in renal tissue is confined to the immediate vicinity in which the shock waves were applied.

Post-SWL GFR and RPF were also reduced in the contralateral kidneys, which had not been treated with shock waves, and there was no indication that kidney size contributed to the size of these reductions. Moreover, since these kidneys were not exposed to the shock waves, there is no reason to suspect that the reductions were not uniform within those kidneys. Accordingly, there are at least two explanations for the reduction of blood flow and GFR in the unshocked contralateral kidneys. In one instance, renal vasoconstrictor nerves may have been activated by the shock waves. In another, there may have been the local or systemic release of a vasoconstrictor substance. It is not possible to identify the cause of the vasoconstriction in either kidney from the data at hand, and in any case there exist several possible candidates. Nevertheless, because RPF was reduced to a greater degree in the shocked kidneys than in the contralateral kidneys, the greater reduction in the shocked kidneys may reflect the additive effects of localized and systemically mediated vasoconstriction, whereas the lesser reduction in the unshocked kidneys may reflect only a systemic vasoconstricting influence. The lack of any apparent change in FF in either kidney after SWL suggests that the vasoconstrictor influence, whatever its origin, was likely not selective for the efferent arteriolar vasculature, nor detectably reduced the glomerular filtration coefficient.

A significant conclusion to be drawn from the data provided by these experiments is that the morphologic and acute hemodynamic effects of SWL are intensified in small kidneys. The intensification may be related to the larger fraction of the functional renal mass that is affected by the shock waves in small versus large kidneys. If functional renal mass indeed is an important factor in determining the extent to which SWL impairs renal hemodynamics or tubular function, then the results of the present experiments can reasonably be extrapolated to patients who may come to SWL with a preexisting reduction of functional renal mass, such as the elderly. In that regard, Janetschek et al. (24) have observed apparently permanent reductions of renal blood flow and increased incidence or hypertension in such patients after SWL. Their data, considered together with those reported in this article, support the notion that small kidney size, or reduced functional renal mass, may represent a potentially serious risk factor for SWL.

Acknowledgments

This project was supported in part by the Institute for Kidney Stone Disease, Methodist Hospital of Indiana, and by United States Public Health Service Grant PO1-DK43881. The authors are indebted to Anne Trout and Valerie Westmoreland for their expert technical assistance.

American Society of Nephrology

aWrobel K-H: Das Blutgefabsystem der Niere von Sus scrofa dom. unter besonderer Berucksichtigung des fur die menschlide Niere beschriebenen Abkurzungskrelislaufes. Inaugural Dissertation, Aus dem Veterinar-Anatomischen Institut der Justus Liebig, Universitat zu Gleieben, 1961.
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