Radiol Oncol 1995 ; 29: 102-6. Age-related changes of renal vascular resistance in normal native kidneys: color duplex Doppler ultrasound assessment Boris Brkljacic,1 Ivan Drinkovic,1 Diana Delic-Brkljacic,2 Andrija Hebrang1 1 Department of Radiology, Ultrasonic Center, University Hospital "Merkur" and 2 Department of Medicine, University Hospital "Sestre Milosrdnice", Croatia. Purpose: To evaluate age-related changes of renal vascular resistance (RVR) in normal native kidneys. Materials and methods. lntrarenal arteries were insonated in 180 kidneys of 90 examinees and Doppler sonographic resistive indexes (RIs) were measured. Examinees were classified into three age groups: the first consisted of subjects < = 30 years old, the second of subjects between 31 and 54 years and the third of subjects 55 years of age and older. Results: Mean Ris were 0.57 in the first group, 0.598 in the second group, and 0.621 in the third group. Ris were found to be age dependent, with significant elevation observed with increasing age (group I vs. group II, P < .01; group II vs. group III, P = .03; group I vs. group III, P < .01). Conclusion: Doppler sonographic resistive indexes reflect elevation of RVR with aging. Key words: kidney, blood, renal artery-ultrasonography; ultrasonography, supply, Doppler, color; age factors. Introduction Extensive research has been performed during the last decade in Doppler assessment of intra-renal blood flow in transplanted kidneys.1"3 In the last few years Doppler studies were performed in native kidneys, as well.4-6 Normal values have been established in a few studies and Doppler indexes have been correlated with renal functional tests and blood pressure values in several renal diseases.7-13 In most of these studies age-dependent changes of renal vascular resistance were neglected, although some authors referred to age-related changes of Dop-pler inexes in large series of patients.10 The purpose of this study was to evaluate age-related changed of renal vascular resistance, reflected in values of Doppler sonographic resistive indexes (RIs), in normal native kidneys. Correspondence to: Boris Brkljacid, M. D., Ph. D., Department of Radiology, Ultrasonic Center, University Hospital "Merkur", Zajceva 19, Zagreb, Croatia. Phone/Fax: + 385-1-2331440. UDC: 611.611:611.136.7:534-8 Materials and methods Between November 1991 and November 1994 color-duplex Doppler sonography of intrarenal arteries was performed in 180 kidneys of 90 Age-related changes of renal vascular resistance 103 subjects without renal impairment. There were 39 men, and 51 women, aged 18-55 years (mean 44.6 ± 14.6 years). Twenty six were healthy volunteers and 64 were studied in the course of nonrenal abdominal, thyroid or breast US examinations. The inclusion criteria for the examination were abscence of a history of kidney disease; absence of systemic, chronic or malignant diseases that might affect renal function; absence of hypertension; absence of history of congenital or acquired heart disease; normal conventional US finding of kidneys; and normal urinalyisis findings prior to Doppler US examination. Twenty eight subjects had findings of normal serum creatinine, tested within 30 days prior to Doppler US examination. Informed consent was obtained from all examinees. All subjects were older than 18 years, to avoid variations in Rls values noted in childhood.14' 15 The examinees were arbitrarily classified into three age groups (< = 30 years old, 31-54 years, > = 55 years) to evaluate age dependence of RI values in healthy adult subjects. Real-time and color duplex-Doppler US examinations were performed with a Radius CF color Doppler scanner (GE-CGR, Buc, France), with a curved-array 3.75-MHz transducer. After color-Doppler identified flow in intrare-nal vessels, a sample-volume was positioned in segmental, interlobar and arcuate arteries in their typical positions. Spectral analysis was performed and Rls measured using existing software capabilities of the scanner. Mean RI values for each kidney were calculated from all measurements. Wall-filter of 50 Hz and minimal PRFs were used to obtain optimal spectral waveforms in all cases. Sample-volume was set at 2-4 mm. Examination was technically successful and adequate spectra obtained in all subjects. The RI was measured with the formula (peak systolic frequency shift - minimum diastolic frequency shift)/mean frequency shift during the cardiac cycle.16 Subjects were examined in supine and decubitus positions; the duration of the examination per person was 30-40 minutes. All the examinations were performed by the first author (B. B). Mean RI values were compared between different age groups of examines. "Goodness-of-fit test" (Kolmogornov-Smirnov) was used to test whether the distribution of RI values was normal. The statistical significance of observed differences was calculated with the MannWhitney U test. The Pearson method was used to estimate the correlation between Rls and age of the age of the whole group of examinees. Results The mean RI ± SD in 180 kidneys of 90 subjects with normal native kidneys was 0.596 ± 0.038 (range 0.535 - 0.685). All Rls were below 0.70. There were 23 examinees 30 years old or younger (group 1), 46 subjects were in the range of 31 - 54 years of age (group II), and 21 examinees were 55 years old or older (group III). The distribution of Rls by these three age groups is shown in Figure l. The age distribution, as well as distribution of Rls within each age group was normal. Statistical significance of differences of Rls between different age groups (Mann-Whitney U-test) was observed between the age groups I and II (P < .01), between the age groups II and III (P = .03; 95 % confidence level), and between the age groups I and III (P < .01). RI 0.7-------------------------- MEAN 0.621 0'65 " MEAN 0.598 MEAN 0.570 0.6 - _ 0.55 - 0.5--1-----1-------'----- <• 30 YEARS 31-54 YEARS >• 55 YEARS n-23 n-46 n-21 Figure 1. The distribution of mean RI values and 1 S. D. in three age-groups of examinees with normal native kidneys. n = number of patients within the particular age-group. 104 Brkljacic B et al. The typical Doppler spectra from intrarenal arteries with high continuous diastolic flow and low resistive index are shown in the Figure 2. The Pearson lienar correlation method showed high and statistically significant correlation between Rls and age of the whole group of examinees with normal native kidneys. The Pearson correlation coefficient (r) between age of examinees and RI was 0.5172 (P< .001). The Pearson method showed lack of correlation between Rls and renal length and between Rls and renal parenchymal thickness in subjects with normal native kidneys. Correlation coefficients between Rls and renal lenght were: r = -0.053 for the right kidney (P = NS) and r = -0.061 for the left kidney (P = NS). Coefficients between Rls and renal parenchymal thickness were: r = --0.078 for the right kidney and r = — 0.086 (P = NS) for the left kidney (P = NS). Discussion Doppler sonographic studies of renal vascular resistance in renal parenchymal diseases have shown complex interrelations of several para- Figure 2. The normal spectral waveforms of intrarenal arteries in normal native kidney; continuous high diastolic flow with low resistive index. meters affecting values of Doppler sonographic indexes.10'17 A few studies have analyzed relation between RI and renal biopsy findings. It appears that the site of the pathologic alterations within the kidney is very important in measurement and interpretation of Doppler so-nographic indexes.1318 Doppler analysis seems to be particularly useful in disease affecting tubulointerstitial and vascular compartments of kidneys. In diabetic nepropathy Doppler indexes reflect elevated renal vascular resistance.10,17 In unilateral pyelocalicectasis Doppler seems to be very accurate in distinguishing between obstructive and non-obstructive collecting system dilatation.1''12 In addition to pathologic alterations within the kidney and hypertension, age has emerged in large studies as a significant covariable, affecting RVR and Doppler indexes values.10'17 The present study has shown a high and significant correlation of Doppler sonogra-phic resistive index and age of examinees with normal native kidneys. It has also shown age-dependance of Rls values, which tend to increase with aging. In a literature a RI value of 0.70 has been generally accepted as a threshold value for pathological renal vascular resistance, and Rls of 0.70 and higher are considered abnormally elevated. This threshold RI value has been introduced by Platt5'17'18 and other groups ' of investigators have accepted it.10-13 This study has shown that it is reasonable to take into account age-related dependence of Doppler indexes in interpretation of their values and in comparison with the control groups. Statistically significant differences of Rls values were observed in the present study between arbitrarily chosen age-groups of examinees. It was noted that all the examinees had Rls below 0.70, and even in the oldest age-group the mean RI of 0.621 was far below the threshold value of 0.70. The mean RI value of 0.596 ± 0.038 observed in this study was similar to other studies where mean intrarenal Rls in normal native kidneys ranged from 0.58 to 0.64.5. 7, 9, 10 There are several limitations in the golden standard reference method for normal renal Age-related changes of renal vascular resistance 10,5 status. It is known that serum creatinine levels may be normal while even a 50 % decrease in renal function may exist simultaneously. 19 Therefore, it is hard to prove normal renal status when a study is performed in a usual clinical setting. An analysis of creatinine clearance rates has to take in account potential error from inaccurate urine collection.15 In the present study, small proportion of control subjects had serum creatinine levels tested and we had to rely in the majority of subjects on absence of history of renal disease, normal conventional US findings and urin analysis findings for inclusion of examinees in the control group. Although some persons with renal functional impairment may have been included in the control group using such criteria, we believe that the relevance of obatined data is not essentially decreased. This study shows that elevation of Rls with aging does not represent false variations or variability of these values. A few studies about physiology of aging suggest that the loss of renal function related with aging is hemodina-mically mediated (elevated renal vascular resistance). 2023 The present study confirms those results. Some authors think that elevation of Doppler indexes that occurs with aging reflects the loss of functioning nephrons, observed in the senescent kidney, that is not reflected by serum creatinine elevation.5' 19'24 In pediatric population higher Rls were observed in comparison with adults. I4' 5 Only subjects older than 18 years were included in the present study, so the changes of Rls in childhood need not to be accounted for. Rls values did not show significant correlation with renal length and parenchy-mal thickness of our examinees, which is not surprising for normally functioning kidneys. Doppler US imaging has the most important potential for the diagnosis of parenchymal renal diseases in the longitudinal follow-up of patients with renal disease to provide predictive clinical information on the recovery of renal function or the progression of renal disease. Results of the present study indicate that elevation of Rls with increasing age has to be taken into account in such longitudinal studies, and that it is accep- table to consider RT of 0.70 as a threshold value for pathologic elevation of renal vascular resistance. References 1. Pelling, M, Dubbins PA. Doppler and color Doppler imaging in acute transplant failure. J Clin Ultrasound 1992; 20; 507-11. 2. Deane C. Doppler and color Doppler ultrasonography in renal transplants: chornic rejection. .1 Ciin Ultrasound; 20: 539-42. 3. Becker JA. Role of radiology in evaluation of the failing renal transplantation. Radiol Clin Norih Am 1991; 29: 511-5. 4. Sauvain JL, Bourschcid D, Picrrat V, et al. Duplex Doppler ultrasonography of intra-renal arteries. Normal and pathological aspects. Ann Radiol 1991; 34; 237-46. 5. Platt JF. Duplex Doppler evaluation of native kidney dysfunction: obstructive and nonobstructive disease. AJR 1992; 158: 1035-42. 6. Scheidegger JR, Werlen S. Spektral und Farbdop-plersonographie: Technik, Moglichkeit und Grenzen in der Uroradiologie. Schweiz Med Wo-chenschr; 1991; 121 (9): 292-8. 7. Gottlieb RH, Luhmann K IV, Oatcs RP. Duplcy ultrasound evaluation of normal native kidneys and native kidneys with urinary tract obstruction. J Ultrasound Med 1989; 8: 609-11. 8. Rodgers PM, Bates JA, Irving HC. Intrarenal Doppler ultrasound studies in normal and acutely obstructed kidneys. Br J Radiol 1992; 65: 207. 9. Kim SH, Kim WH, Choi BI, et al. Duplex sonography of the native kidney - Resistive index vs. serum creatinine. J Ultrasound Med 1990; 9: 25-9. 10. Brkljacic B, Mrzljak V, Drinkovic I, Soldo D, Sabljar-Matovinovic M, Hebrang A. Renal vascular resistance in diabetic nephropathy: duplex Doppler US evaluation. Radiology 1994; 192: 54954. 11. Brkljacic B, Drinkovic I, Sabljar-Matovinovic M. et al. Intrarenal duplex-Doppler sonographic evaluation of unilateral native kidney obstruction. J Ultrasound Med 1994: 13: 197-204. 12. Brkljacic B, Drinkovic I, Soldo D, Vidjak V, Odak D, Hebrang A. Pulsedwave and color-Dop-pler in the assessment of nalive kidneys with urinary tract obstruction. Radiol Oncol 1993: 27: 21-6. 13. Mostbeck GH, Kain R, Mallek R, et al. Duplex Doppler sonography in renal parenchimal disease. Histopathologic correlation. J Ultrasound Med 1991; 10 (4): 189-94. 106 Brkljacic B et al. 14. Wong SN, Lo RNS, Yu ECL. Renal blood flow pattern by non-invasive Doppler ultrasound in normal children and acute renal failure patients. J Ultrasound Med 1989; 8: 135-43. 15. Keller MS. Renal Doppler sonography in infants and children. Radiology 1989; 172: 603-4. 16. Pourcelot L. Applications cliniques de l'examen Doppler transcutane. In Peronneau P ed Veloci-metrie ultrasonare Doppler Seminaire INSERM. Paris, 1974; 34: 213-30. 17. Platt JF, Rubin JM, Ellis JH. Diabetic nephropathy: evaluation with renal duplex Doppler US. Radiology 1994; 190: 343-6. 18. Platt JF, Ellis JH, Rubin JM, Di Pietro MS, Sedman AB. Intrarenal arterial Doppler sono-graphy in patients with nonobstructive renal disease: correlation of resistive index with biopsy findings. AJR 1990; 154: 1223-7. 19. Becker JA Evaluation of renal function. Radiology 1991; 179: 337-8. 20. Hollenberg NK, Adams DF, Solomon HS, Rashid A, Abrams HL, Merrill JP. Senescence and the renal vasculature in normal man. Circ Res 1974; 34: 309-14. 21. Epstein M. Effects of aging on the kidnes. Fed Proc 1979; 38: 169-72. 22. Anderson S, Brenner BM. Effects of aging on the renal glomerulus. Am J Med 1986 ; 80: 435-42. 23. Cody RJ, Torre S, Clark M, Pondolfino K. Age-related hemodynamic, renal and hormonal differences among patients with congestive heart failure. Arch Intern Med 1989; 149: 1023-8. 24. Riehl J, Clasen W, Schmitt H, KierdorfH, Siebert HG. Altersabhaengige veraendenrungcn der renal haemodynamik. Untersuchungen untells duplex-sonographie (DS). Ultraschall Klin Prax 1989: 4(1): 129.