AJR F and L Medical Products: Radiation Protection & More
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Taori, K. B.
Right arrow Articles by Wasnik, P. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Taori, K. B.
Right arrow Articles by Wasnik, P. N.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Hotlight (NEW!)
Right arrow
What's Hotlight?
DOI:10.2214/AJR.07.3125
AJR 2008; 191:239-242
© American Roentgen Ray Society

Clinical Observations

Renal Doppler Indices in Sickle Cell Disease: Early Radiologic Predictors of Renovascular Changes

Kishor B. Taori1, Ritu S. Chaudhary1, Vinod Attarde1, Suresh Dhakate1, Virender Sheorain1, Prashant Nimbalkar1 and Preetam N. Wasnik2

1 Department of Radiodiagnosis, Government Medical College, Hanuman Nagar, Nagpur, Maharashtra 440003, India.
2 Department of Medicine, Government Medical College, Nagpur, Maharashtra, India.

Received September 7, 2007; accepted after revision January 22, 2008.

 
Address correspondence to R. S. Chaudhary (dr_rituch{at}yahoo.com).


Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
OBJECTIVE. The purpose of our study was to detect changes in renovascular resistance through renal Doppler indexes in young sickle cell disease patients with normal routine urine laboratory tests.

CONCLUSION. Renal Doppler sonography resistive index and pulsatility index values can serve as early radiologic predictors of renovascular changes in sickle cell disease. Thereby, these findings can guide clinicians in the use of more intensive monitoring of laboratory values and initiating adequate treatment at an early stage.

Keywords: pulsatility index • renal Doppler sonography • resistive index • sickle cell disease


Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Sickle cell disease (SCD) is among the most common of inherited hemoglobinopathies. The disease has been known since James Herrick, a Chicago cardiologist, first reported it as "peculiar elongated and sickle-shaped red corpuscles in a case of severe anemia" [1]. SCD is a multisystem disorder affecting almost every tissue of the body. It is a frequent cause of renal dysfunction leading to sickle nephropathy in the later stages. Sickle cell nephropathy is indicated by sickled erythrocytes, with the consequent effects of decreased medullary blood flow, ischemia, microinfarct, and papillary necrosis [2]. Clinical features of the disease result from vasoocclusive consequences of sickled cells more than from the anemia itself. Considering the high prevalence of the disease in certain populations, it is required that renovascular changes be detected at an early stage before irreversible organ damage occurs due to chronic vasculopathy. Irreversible organ damage occurs in at least a third of patients, and thus is the most frequent cause of death beyond early childhood [3].

SCD may result in both renal function disturbances and anatomic alterations. On grayscale sonography evaluation of renal morphologic features in SCD, almost half of the patients with SCD have large kidneys, believed to be a result of increased renal blood volume from the anemia [4]. Also, the kidneys may display normal echogenicity (89% of patients); may be diffusely, mildly echogenic (5%); or may exhibit increased medullary echogenicity with normal cortical echogenicity (3%). Over time, the kidneys may shrink if renal failure ensues [5]. However, most of the gray-scale sonography morphologic features are observed in the late course of the disease.

Previous literature describes the application of Doppler sonography in the assessment of renal dysfunction in many diseases including renal artery stenosis [6], acutely obstructed kidneys [7], and acute renal failure in determining graft survival in transplanted kidneys and in SCD [8, 9]. However, to our knowledge, changes in renal Doppler indices in the early stage of the disease have not as yet been described.

The aim of this study was to determine whether the renal pulsatility index (PI) and resistive index (RI) ([peak systolic velocity-end diastolic velocity] /peak systolic velocity) would be helpful early radiologic predictors of renal dysfunction in young SCD patients with otherwise normal routine urinary laboratory tests that included urine microscopic examination for blood casts and RBCs, urinary excretion of protein (macroalbuminuria), blood urea and serum creatinine. Subsequently, we also determined the relationship between renal RI and PI in SCD patients with the number of vasoocclusive crises and the duration of history of disease.


Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
The study was performed in an area with high prevalence of SCD in the community after approval by the institutional review board and after obtaining informed consent from all subjects or a parent or guardian.

Subjects
Two groups were examined. One group consisted of patients with SCD (n = 62) attending the sickle clinic in the hospital because of various symptoms of the disease, 44 homozygous (SS pattern) and 18 heterozygous (AS pattern). All cases of SCD, both SS (homozygous) and AS (heterozygous), in the age group 7–30 years with otherwise normal routine urinary laboratory pathologic tests were included in the study. The other group was a control group (n = 50) consisting of randomly selected patients who were routinely attending the sonography department for nonrenal abdominal sonography. All control patients were age matched with the patient group (within 1 year) to remove the confounding effect of age. These patients also had no clinical, laboratory, or radiologic evidence of renal disease. Homozygous cases belonged to the age group 7–30 years, whereas heterozygous cases were in the age group of 11–28 years. All control subjects were age matched with the SCD cases and were in the age group of 7–30 years.

Doppler Sonography Examination Procedure
Doppler sonography was performed on a ProSound 4000 scanner (Aloka) with color flow Doppler facility, using 3.5-MHz sector probe. The patients were examined in the supine position: left lateral decubitus for the right kidney and right lateral decubitus for the left kidney. Doppler sonography was performed using the non compression technique and under comfortable conditions Doppler waveforms were obtained [10]. Main renal, seg mental, and interlobar arteries (adjacent to medullary pyramids) were then insonated using a 2–4 mm Doppler gate. Doppler parameters recorded were PI, RI, systolic/diastolic ratio (S/D), peak systolic velocity, and end diastolic velocity for all the subjects. All subjects were normotensive at the time of renal sonography.


Figure 1
View larger version (12K):
[in this window]
[in a new window]
[as a PowerPoint slide]
  		Fig. 1 —Flowchart shows observations of patients with sickle cell disease in this study compared with those excluded from study.

 
Doppler parameters were obtained for main renal, segmental, and interlobar arteries. Three readings from the interlobar arteries in the upper pole, interpolar, and lower pole regions were taken and average values of interlobar parameters were recorded for each kidney. The mean of the Doppler indices from main renal, segmental, and interlobar arteries of both kidneys of a patient were taken and recorded. The average time taken for Doppler assessment of both kidneys in each subject was 25 minutes. However, this was largely dependent on the cooperation of the subjects to hold their breath for required intervals. Patients who were dyspneic or unable to hold their breath as required were excluded from the study. Those patients with sickle cell crisis, tachycardia, known hypertensive disease, or who were hypertensive at the time of Doppler sonography (systolic blood pressure ≥ 120; diastolic blood pressure ≥ 80) were also excluded from the study.

Laboratory Studies
The disease status was confirmed by hemoglobin electrophoresis. All patients had normal routine urine laboratory tests including urine microscopic examination for blood casts and RBCs, urinary excretion of proteins by spot urine albumin test, blood urea, and serum creatinine. For urinary microscopic examin ation, clean catch mid stream samples were taken and centrifuged at 2,000 rpm for 5 minutes. The sediment obtained was examined under a microscope for blood casts or RBCs. Estimation of proteinuria was performed by Bayer's urine albumin strip. Patients with blood urea values < 6.4 mmol/L were included. Serum creatinine was estimated by the picric acid method and patients with normal values (< 97 µmol/L) were included. Patients with abnormal first-line investigations were excluded from the study.

Statistics
For comparison between groups (groups 1 [homozygous, SS] and 3 [control] and groups 2 [heterozygous, AS] and 3 [control]), p values ware calculated using unpaired Student's t tests. For assessing whether any positive correlation existed between PI and RI and the number of vasoocclusive crises and duration of history of the disease, the correlation coefficient (r) and p value were calculated. A p value < 0.05 was considered to be significant. A cutoff of 0.70 for RI was considered and receiver operating characteristic (ROC) curves were plotted using PI from both SS and AS groups and sensitivity and specificity thus obtained.


Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Observations were made of 62 patients with SCD (44, SS; 18, AS) in comparison with 50 control subjects, with strict exclusion criteria. The flowchart in Figure 1 shows this process. Patients in the affected groups, both homozygous (SS, group 1) and heterozygous (AS, group 2) and those of the control group (group 3) did not differ with regard to age. The mean age of the patients with SCD was 19.74 ± 5.54 years, whereas that of the control group was 19.8 ± 5.69 years.

Doppler sonography evaluation of the kidneys revealed elevated PI and RI values in the main renal, segmental, and interlobar arteries in the patients with SCD in both the homozygous (group 1) and heterozygous (group 2) patients in comparison with the control group (group 3) (Table 1 and Fig. 2). However, RI proved to be a less variable index than PI. The elevated PI was found to be highly significant when comparing group 1 and group 3 (p values 0.0001, 0.0001, 0.0001, respectively, for main renal, segmental, and interlobar arteries) and also when comparing group 2 and group 3 (p values 0.0001, 0.0001, 0.0001, respectively).


View this table:
[in this window]
[in a new window]

  		TABLE 1: Comparison of Patients with Sickle Cell Disease with Control Subjects

 

Figure 2
View larger version (83K):
[in this window]
[in a new window]
[as a PowerPoint slide]
  		Fig. 2 —10-year-old boy with homozygous sickle cell disease. Renal Doppler sonogram shows high-impedance flow represented by high pulsatility index (PI) and resistive index (RI) values (1.35 and 0.73, respectively) in interlobar artery of this sickle-affected patient.

 


Figure 3
View larger version (77K):
[in this window]
[in a new window]
[as a PowerPoint slide]
  		Fig. 3 —11-year-old boy with homozygous sickle cell disease. Renal Doppler sonogram shows high-impedance flow and early diastolic notch (arrow) in intrarenal waveform.

 
RI was also observed to be significantly elevated in both the SS and AS groups compared with the control group in the main renal, segmental, and interlobar arteries (Table 1) when comparing group 1 and group 3 (p values 0.0001, 0.0001, 0.0001, respectively) and group 2 and group 3 (p values 0.0001, 0.0001, 0.0001, respectively). An early diastolic notch was observed in 18 of the 62 patients with SCD, which further gives evidence of increased vascular resistance (Fig. 3).

The relationship between renal RI and PI in patients with SCD with the number of vasoocclusive crises and duration of disease was studied. However, there existed no significant correlation (p > 0.05). The mean number of vasoocclusive crises suffered was 6.22 ± 4.8 in group 1 and 3.6 ± 3.89 in group 2. The mean duration of disease was 11.2 ± 6.6 years in group 1 and 7.1 ± 4.9 years in group 2.

In previous studies, an RI value of < 0.70 has been regarded as the normal value [12] for differentiating patients with high and normal renal vascular resistance. Our control population showed RI values of 0.57 ± 0.04, 0.56 ± 0.04, 0.55 ± 0.04, respectively, in main renal, segmental, and interlobar arteries.

A cutoff of 0.70 for RI was considered and ROC curves plotted using PI from both the SS and AS groups (Fig. 4A, 4B). For group 1, SS patients, PI cutoff values of 1.15, 1.17, and 1.19 showed 100% and 66.7%, 97.1% and 77.8%, and 94.3% and 89% sensitivity and specificity, respectively. For group 2, AS patients, PI cutoff values of 1.15 and 1.16 showed 100% and 80% and 100% and 94% sensitivity and specificity, respectively. Thus, considering cutoff values of 0.70 for RI and 1.15 for PI, Doppler sonography is found to be 100% sensitive and 66.7% specific for the SS group and 100% sensitive and 80% specific for the AS group in detecting increased intrarenal resistance in patients with SCD.


Figure 4
View larger version (11K):
[in this window]
[in a new window]
[as a PowerPoint slide]
  		Fig. 4A —Receiver operating characteristic (ROC) curves for both groups of patients with sickle cell disease. Green = reference line; red = pulsatility index. ROC curve for group 1 (homozygous, SS) patients (A) shows cutoff considered to be 0.70 for resistive index (RI). Area under curve = 0.98. ROC curve for group 2 (heterozygous, AS) patients (B) shows cutoff considered to be 0.70 for resistive index (RI). Area under curve = 0.97.

 

Figure 5
View larger version (10K):
[in this window]
[in a new window]
[as a PowerPoint slide]
  		Fig. 4B —Receiver operating characteristic (ROC) curves for both groups of patients with sickle cell disease. Green = reference line; red = pulsatility index. ROC curve for group 1 (homozygous, SS) patients (A) shows cutoff considered to be 0.70 for resistive index (RI). Area under curve = 0.98. ROC curve for group 2 (heterozygous, AS) patients (B) shows cutoff considered to be 0.70 for resistive index (RI). Area under curve = 0.97.

 

Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Renal Doppler sonography was first introduced in the mid 1980s for the screening of renovascular disease [6]. Since then, many studies have been published indicating the potential of Doppler sonographic assessment of various renal diseases. The application of renal Doppler sonography in detection of renal artery stenosis in hypertensive patients is well documented [6]. Our study finds the use of renal RI and PI to be radiologic predictors of renovascular changes at an early stage, when renal changes are reversible using transfusion treatment.

Our study revealed a significant increase in the PI and RI in patients with SCD compared with the control group. This phenomenon may be a result of the increased renal vascular tone due to various vascular occlusive mechanisms occurring in sickle-affected kidneys. These mechanisms include vascular intimal hyperplasia, thrombosis, altered vascular reactivity, and frank vasospasm. These various mechanisms identify the multifactorial nature of the disease other than just microvascular occlusion by sickled RBC. The mechanisms of vascular intimal hyperplasia and thrombosis in turn are related to the abnormal adhesive and procoagulant properties of sickled RBC [12].

The microcirculatory flow disturbances leading to altered vascular hemodynamics have also been proven previously in experimental studies on β-thalassemic mice using noninvasive ultrasonic approaches [13]. However, overenthusiasm for the use of renal Doppler sonography in renal diseases has been questioned, considering the impact of various nonrenal factors affecting the renal waveform, including heart rate, blood pressure, effect of transducer compression, and atherosclerosis (distensibility or stiffness of the arteries) [10]. Utmost care has been taken in this study to minimize the effects of nonrenal factors that are known to affect the parameters of renal vascular flow. This includes examining patients under comfortable conditions, excluding subjects with tachycardia or hypertension, and examining young patients in the age range of 7–30 years. The noncompression sonographic technique was used to avoid an undue false increase in RI (by diminishing the end-diastolic velocity).

Thus, our study helps us to draw the conclusion that in renal Doppler sonography, RI and PI values can serve as early radiologic predictors of renovascular changes in SCD. Doppler sonography can thereby guide clinicians in the use of more intensive monitoring of other laboratory values and initiating adequate treatment at an early stage when the consequences of the disease are still reversible.


References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Herrick JB. Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. Arch Int Med1910; 6:517 –520
  2. Pham PT, Pham PC, Wilkinson AH, Lew SQ. Renal abnormalities in sickle cell disease. Kidney Int 2000;57 : 1–8[Medline]
  3. Powars D, Chan L, Schroeder W. The variable expression of sickle cell disease is genetically determined. Semin Hematol1990; 27:360 –376[Medline]
  4. Walker TM, Beardsall K, Thomas PW, Serjeant GR. Renal length in sickle cell disease: observations from a cohort study. Clin Nephrol 1996; 46:384 –388[Medline]
  5. Harrow BR, Sloane JA, Liebman NC. Roentgenologic demonstration of renal papillary necrosis in sickle cell trait. N Engl J Med 1963; 268:969 –976[Medline]
  6. Avasthi PS, Voyles WF, Greene ER. Noninvasive diagnosis of renal artery stenosis by echo-Doppler velocimetry. Kidney Int 1984; 25:824 –829[Medline]
  7. Rodgers PM, Bates JA, Irving HC. Intrarenal Doppler ultrasound studies in normal and acutely obstructed kidneys. Br J Radiol 1992; 65:207 –212[Abstract/Free Full Text]
  8. Aikimbaev KS, Oguz M, Guvenc B, Baslamisli F, Kocak R. Spectral pulsed Doppler sonography of renal vascular resistance in sickle cell disease: clinical implications. Br J Radiol 1996;69 :1125 –1129[Abstract/Free Full Text]
  9. Guvenc B, Aikimbaev K, Unsal C, et al. Renal vascular resistance in sickle cell painful crisis. Int J Hematol2005; 82:127 –131[CrossRef][Medline]
  10. Krumme B, Hollenbeck M. Doppler sonography in renal artery stenosis: does the resistive index predict the success of intervention? (editorial) Nephrol Dial Transplant 2007;22 : 692–696[Free Full Text]
  11. Becker JA. Evaluation of renal function. Radiology 1991;179 : 419–423[Abstract/Free Full Text]
  12. Francis RB Jr, Johnson CS. Vascular occlusion in sickle cell disease: current concepts and unanswered questions Blood 1991; 77:1405 –1414[Free Full Text]
  13. Stoyanova E, Trudel M, Felfly H, Garcia D, Cloutier G. Characterization of circulatory disorders in beta-thalassemic mice by noninvasive ultrasound biomicroscopy. Physiol Genomics2007; 29:84 –90[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Taori, K. B.
Right arrow Articles by Wasnik, P. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Taori, K. B.
Right arrow Articles by Wasnik, P. N.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Hotlight (NEW!)
Right arrow
What's Hotlight?

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS