ARTICLE IN PRESS Rev Esp Med Nucl. 2010;29(1):20–24
Clinical note
Captopril renography as a prognostic factor in obstructive hydronephrosis with preserved renal function S. Ajmi , K. Ben Ali, M. Guezguez, R. Sfar and M. Nouira Department of Nuclear Medicine, Sahloul’s Hospital, Sousse, Tunisia
ARTICLE INFO
A B S T R A C T
Article history: Received 11 May 2009 Accepted 29 September 2009 Available online 10 December 2009
Hydronephrotic kidney with a differential renal function greater than 55% is defined as supranormal. The signification of this finding remains controversial. In this article, the authors reported a case of supranormal function in obstructive hydronephrosis. Differential renal functions were evaluated after administration of captopril and after pyeloplasty. The role of captopril renography as a prognostic factor for surgery is discussed. ˜ a, S.L. y SEMNIM. All rights reserved. & 2009 Elsevier Espan
Keywords: Hydronephrosis Kidney function tests Captopril renography Renin-angiotensin system
Renografı´a con captopril como factor prono´stico en hidronefrosis obstructivo con funcio´n renal intacta R E S U M E N
Palabras clave: Hidronefrosis ˜ o´n Pruebas funcionales del rin Renografı´a con captopril Sistema renina-angiotensina
˜ o´n hidronefro´tico con una funcio´n renal diferencial mayor del 55% se define como supranormal. El El rin significado de este hallazgo sigue siendo controvertido. En este artı´culo, los autores comunican un caso de funcio´n supranormal dentro de una hidronefrosis obstructiva. Se evaluaron las funciones diferenciales del ˜ o´n despue´s de la administracio´n de captropril y despue´s de una pieloplastia. Se examina el papel de la rin renografı´a con captopril como un factor de prognosis para la cirugı´a. ˜ a, S.L. y SEMNIM. Todos los derechos reservados. & 2009 Elsevier Espan
Introduction
Case report
Pelviureteral junction obstruction in children is the most common cause of hydronephrosis and its management requires a multidisciplinary diagnostic approach to avoid unnecessary pyeloplasty or renal function loss. Actually, important controversies still exist on the need and the timing of surgery. Diuretic renography is considered as a reliable method to investigate hydronephrosis and monitor renal function. Differential renal function is one of the most important parameter in clinical management of patients with hydronephrosis.1 For most experts surgical intervention is indicated only if there are signs of reduced function of the obstructed kidney. Paradoxally, the obstructed kidney occasionally has better function than the morphologically normal contralateral kidney (Z 55%). This finding, known as supranormal renal function, is reported in 0–22% of cases.2 The true significance and prognostic value of this finding remain controversial.3 In this article we present a case of supranormal function in obstructive hydronephrosis and we evaluate renal function after administration of captopril and after pyeloplasty.
A 17-year-old boy presented with a several week history of right-sided flank pain. There was no relevant past medical history and the patient was taking no medication. Physical examination was unremarkable. Abdominal ultrasound examination showed a marked dilatation of the right pyelocaliceal system and the left kidney showed normal appearance. He was then referred to our department for dynamic renal scintigraphy. After intravenous injection of 370 MBq (10 mCi) of Tc99 m DTPA, posterior sequential images were obtained over 30 min. In the 15th min, 30 mg of furosemide was administered intravenously. Visual analysis of the images showed normal uptake and excretion of the left kidney. On the right side, dynamic images visualized normal uptake and continual parenchymal uptake and delayed visualization of radioactivity in the dilated pyelocaliceal collecting system. Background subtracted time-activity curves (Renograms) showed a normal pattern with timely emptying on the left side and a frankly obstructed nephrogram without any response to diuretic administration on the right side. The split renal functions calculated using uptake values of the 2–3-min images were 45% on the left and 55% on the right (fig. 1). To study the signification of the supranormal function observed in the obstructed kidney, a captopril Tc99m-DTPA renography was performed 4 days later. The scan was started one hour after oral administration of 25 mg of captopril and showed a continued accumulation without identification of an excretory phase on the right kidney. No
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˜ a, S.L. y SEMNIM. All rights reserved. 0212-6982/$ - see front matter & 2009 Elsevier Espan doi:10.1016/j.remn.2009.09.004
ARTICLE IN PRESS S. Ajmi et al. / Rev Esp Med Nucl. 2010;29(1):20–24
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Figure 1. Preoperative dynamic diuretic renography with Tc-99 m DTPA shows normal uptake and excretion of the left kidney and an obstructed pattern on the right side.
radioactivity was seen in the collecting system until the end of the study (30 min). The scan showed unchanged findings on the left kidney. Evaluation of the relative uptake showed a significant
reduction in function of the right kidney of 40% (fig. 2). The patient underwent pyeloplasty via lumbotomy and his postoperative course was unremarkable. A repeat Tc99m DTPA
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Figure 2. A repeated Tc 99 m DTPA renal scintigraphy performed one hour after oral administration of 25 mg of captopril shows a significant reduction of the right renal function (40%). There is no significant modification of the left renogram. Note that there is no activity appearing in the right collecting system until the end of the examination.
S. Ajmi et al. / Rev Esp Med Nucl. 2010;29(1):20–24
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Figure 3. Tc-99 m DTPA dynamic diuretic renography performed one month after pyeloplasty showing a normal uptake and excretion in both kidneys. Differential renal function calculation reveals symmetric function.
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scintigraphy performed one month after pyeloplasty showed a normal uptake and excretion in both kidneys. The split renal functions were symmetrical (fig. 3).
Discussion The significance of increased function in obstructive hydronephrosis is controversial. For some authors, this finding is probably artifactual due to inadequate choice of a perirenal background area, calculation of the split function or a reservoir effect of the dilated renal cavities.3,4 For others authors, supranormal renal function is real and probably related to a glomerular and tubular hypertrophy in response to an increase in the hydrostatic pressure in renal cavities.5,6 Activation of the rennin angiotensin system in obstructive uropathy has been linked to many of the pathophysiologic processes including modification of renal hemodynamics, tubulointerstitial fibrosis and apoptotic renal cell death.7 During initial stage of obstruction, the glomerular filtration rate is maintained within normal limits by vasoactive mechanisms.8 Indeed, following the onset of renal obstruction angiotensin II production is rapidly stimulated leading to a vasoconstriction of the glomerular artery and allowing normal glomerular filtration rate. This compensatory response may explain the increase of the renal function in the obstructed kidney noted in our patient. The significant decrease of renal function after captopril administration and the normalization of glomerular function after pyeloplasty support this hypothesis. A peristaltic effect of angiotensin II is also cited in the literature. It seems that angiotensin II has a critical role in the development of the pelvic pacemaker and in stimulating the renal excretory compartment.9 On the other hand, it has been demonstrated that prolonged activation of the rennin angiotensin system contributes to the deterioration of function of the obstructed kidney. An increase in renal angiotensin II triggers a cascade of events ultimately leading to renal fibrosis. This action is mediated essentially by transforming growth factor-beta (TGF-b) which stimulates extracellular matrix accumulation leading to tubulointerstitial fibrosis. Others intrinsic and extrinsic cellular factors are also stimulated including notably tumor necrosis factor-alpha (TNF-a) and nuclear factor-kB (NF-kB).7,10 In the literature there is considerable controversy on the management of children with hydronephrosis and essentially the need and the appropriate timing of surgery. Because of obstruction may resolve spontaneously and not all obstructive kidneys experienced improved function after pyeloplasty, many studies have proposed morphologic and functional parameters to identify kidney at risk to develop function loss and, therefore, needing surgery. Rodriguez in a study about 81 cases have demonstrated that comparison of parenchymal-to-pelvic area ratio determined on serial ultrasound is useful for evaluating children with hydronephrosis to predict those needing surgery. He also demonstrated that on initial ultrasound a parenchymal-to-pelvic area ratio of 1.6 or less is predictive of a future need for pyeloplasty in 96% of cases.11 Hafez have demonstrated that progression of hydronephrosis in two consecutive ultrasound studies could serve as an indication for surgery. Using this criterion he noted an improvement or stabilization of renal function in all operated kidneys.12 During the last few years, MRI has become more widely used as an imaging modality of the urinary tract providing highquality anatomic images and quantitative functional evaluation of each kidney.13 Kaneyama used a morphologic MRI pelvic index ratio as an indicator of pyeloplasty or conservative management. He found that 88% of hydronephrosis with a pelvic index ratio greater than 0.3 needed surgery.14 Diuretic renography is a useful exploration to differentiate between obstructed and
non-obstructed hydronephrosis but it is not accurate for identifying kidneys that are at risk for future functional deterioration. Some studies have focused on predictive scintigraphic parameters to identify kidneys at risk to manifest deterioration of their function. Schlotmann, in an animal experimental study, have demonstrated that delayed tissue tracer transit of Tc99 m MAG3 is associated with deterioration of renal function and histomorphologic restructuring of the renal parenchyma.15 These results were confirmed on clinical study. Delayed tissue tracer transit predicts functional improvement following surgery in 80% of cases and 85% of non operative kidneys maintained their function.16 The hypothesis of an activation of the system in obstructive kidneys as the cause of these modifications was suggested.15,16 The prognostic significance of activation of renin-angiotensin system as demonstrated by captopril renography, is well documented by Bajpai. In this study, it has been demonstrated that during a mean follow up period of 30 months, 75% of obstructive hydronephrosis with activation of the renin-angiotensin system required surgery and none of patients with no activation needed surgery.17 In conclusion, captopril renography can be used to evaluate in a non-invasive manner the activation of the rennin angiotensin system. This parameter may be of value in detecting hydronephrotic kidney at risk for renal deterioration. Conflict of interest The authors have no conflict of interest to declare. References 1. He W, Fischman AJ. Nuclear imaging in the genitourinary tract: recent advances and future directions. Radiol Clin North Am. 2008;46:25–43. 2. Oh SJ, Moon DH, Kang W, et al. Supranormal differential renal function is real but may be pathological: assessment by 99 m technetium mercaptoacetyltriglycine renal scan of congenital unilateral hydronephrosis. J Urol. 2001;165: 2300–2304. 3. Inanir S, Biyikli N, Noshari O, et al. Contradictory supranormal function in hydronephrotic kidneys: fact or artifact on pediatric MAG-3 renal scans? Clin Nucl Med. 2005;30:91–6. 4. Khan J, Charron M, Hickeson MP, et al. Supranormal renal function in unilateral hydronephrotic kidney can be avoided. Clin Nucl Med. 2004;29: 410–414. 5. Steckler RE, McLorie GA, Jayanthi VR, et al. Contradictory supranormal differential renal function during nuclear renographic investigation of hydroureteronephrosis. J Urol. 1994;152:600–2. 6. Song C, Park H, Park S, et al. The change in renal function in the supranormal hydronephrotic kidney after pyeloplasty. BJU Int. 2007;99:1483–6. 7. Misseri R, Rink RC, Meldrum DR, et al. Inflammatory mediators and growth factors in obstructive renal injury. J Surg Res. 2004;119:149–59. 8. Klahr S, Pukerson ML. The pathophysiology of obstructive nephropathy: the role of vasoactive compounds in the hemodynamic and structural abnormalities of the obstructed kidney. Am J Kidney Dis. 1994;23:219–23. 9. Zucchetta P, Carasi C, Marzola MC, et al. Angiotensin converting enzyme inhibition worsens the excretory phase of diuretic renography for obstructive hydronephrosis. J Urol. 2001;165:2296–9. 10. Klahr S, Morrissey J. Obstructive nephropathy and renal fibrosis. Am J Physiol Renal Physiol. 2002;283:F861–75. 11. Rodrı´guez LV, Lock J, Kennedy WA, et al. Evaluation of sonographic renal parenchymal area in the management of hydronephrosis. J Urol. 2001;165: 548–551. 12. Hafez AT, McLorie G, Bagli D, et al. Analysis of trends on serial ultrasound for high grade neonatal hydronephrosis. J Urol. 2002;168:1518–21. 13. Kirsch AJ, Grattan-Smith JD, Molitierno Jr JA. The role of magnetic resonance imaging in pediatric urology. Curr Opin Urol. 2006;16:283–90. 14. Kaneyama K, Yamataka A, Someya T, et al. Magnetic resonance urographic parameters for predicting the need for pyeloplasty in infants with prenatally diagnosed severe hydronephrosis. J Urol. 2006;176:1781–4. 15. Schlotmann A, Clorius JH, Rohrschneider WK, et al. Diuretic renography in hydronephrosis: delayed tissue tracer transit accompanies both functional decline and tissue reorganization. J Nucl Med. 2008;49:1196–203. 16. Schlotmann A, Clorius JH, Clorius SN. Diuretic renography in hydronephrosis: renal tissue tracer transit predicts functional course and thereby need for surgery. Eur J Nucl Med Mol Imaging. 2009 [Epub ahead of print]. 17. Bajpai M, Puri A, Tripathi M, et al. Prognostic significance of captopril renography for managing congenital unilateral hydronephrosis. J Urol. 2002; 168:2158–61.