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ORIGINAL ARTICLE
Year : 2010  |  Volume : 31  |  Issue : 1  |  Page : 16-21
 

Association of visceral adiposity with increased intrarenal artery resistive index in HIV-1-infected patients receiving highly active antiretroviral therapy


1 Division of Infectious Diseases, HIV Center, "S.Caterina Novella" Hospital, Galatina, Italy
2 Institute of Clinical Physiology, National Research Council, Lecce, Italy
3 Laboratory of Hygiene, Department of Biological and Environmental Sciences and Technologies, Di.S.Te.B.A., Faculty of Sciences, University of Salento, Lecce, Italy

Date of Web Publication3-Sep-2010

Correspondence Address:
Pierfrancesco Grima
Division of Infectious Diseases, HIV Center, "S.Caterina Novella" Hospital, Via Roma 73100 Galatina
Italy
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7184.68995

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   Abstract 

Purpose: The aim of our study was to evaluate whether perirenal fat thickness (PRFT), a parameter of central obesity, is related to kidney function and intrarenal artery resistive index (IARI) in human immunodeficiency virus (HIV)-1-infected patients. Materials and Methods: We enrolled 102 consecutive HIV-1-infected patients receiving highly active antiretroviral therapy for more than 12 months in a prospective cohort study. Echographically, the PRFT and IARI were measured and the serum metabolic parameters were evaluated. PRFT and IARI were measured using a 3.75 MHz convex linear probe. Results: The mean of PRFT and IARI in HIV-1-infected patients with visceral obesity was considerably higher than that in patients without it (P <0.001 and <0.01, respectively). Using the average IARI as the dependent variable, age (odds ratio, 1.07; 95% confidence interval [CI], 1.01-1.14; P < 0.5) and PRFT (odds ratio, 1.28; 95% CI, 1.08-1.51; P<0.01) were independent factors associated with IARI. Conclusion: Our data indicate that ultrasonographic assessment of PRFT may have a potential to be a marker of increased endothelial damage with specific involvement of the renal vascular district in HIV-1-infected patients.


Keywords: HIV infection, intrarenal artery resistive index, kidney function, visceral obesity


How to cite this article:
Grima P, Zizza A, Guido M, Tundo P, Chiavaroli R. Association of visceral adiposity with increased intrarenal artery resistive index in HIV-1-infected patients receiving highly active antiretroviral therapy. Indian J Sex Transm Dis 2010;31:16-21

How to cite this URL:
Grima P, Zizza A, Guido M, Tundo P, Chiavaroli R. Association of visceral adiposity with increased intrarenal artery resistive index in HIV-1-infected patients receiving highly active antiretroviral therapy. Indian J Sex Transm Dis [serial online] 2010 [cited 2019 Oct 21];31:16-21. Available from: http://www.ijstd.org/text.asp?2010/31/1/16/68995



   Introduction Top


The introduction of highly active antiretroviral therapy (HAART) has dramatically changed the prognosis of human immunodeficiency virus (HIV) infection, with a significant decline in morbidity and mortality. [1] However, prolonged treatment with combination regimens can be difficult to sustain because of problems with compliance and toxic effects. Treatment with antiretroviral agents has uncovered a syndrome of abnormal fat redistribution, impaired glucose metabolism, insulin resistance and dyslipidemia, collectively termed lipodystrophy syndrome, [2],[3],[4] and predisposes to an increased risk of cardiovascular disease. [5],[6] Visceral obesity, more than overall obesity, plays a key role in the development of cardiovascular disease. [7] Thus, estimating visceral fat distribution is important to identify subjects with a high risk for cardiovascular disease. It is known that there is a good correlation between intraabdominal fat distribution and ultrasonographic measurement of fat thickness and between perirenal fat thickness (PRFT) and central obesity. [8],[9],[10],[11],[12]

In addition, individuals with visceral obesity are at increased risk for progressive loss of renal function. [13] Chen et al.[14] demonstrated that increased waist circumference significantly correlated with microalbuminuria and glomerular filtration rate (GFR) decline, suggesting that obesity may be an independent risk for chronic kidney disease.

It is important to determine which group of HIV-1-infected patients is at an increased risk for impairment of renal function in consideration of the potential nephrotoxic action of antiretroviral drugs such as Tenofovir. The identification of predictive factors for the development of renal complication would be very useful because preventive interventions and optimized treatment could be undertaken for HIV-1- infected patients.

We performed a prospective cohort study to identify the role of visceral fat distribution on endothelial damage and risk. The objective of our study was to evaluate whether ultrasonographic parameters of visceral obesity could be associated with renal blood flow and renal function, playing a role as a possible surrogate marker of reduced renal function risk in HIV-1-infected patients.


   Materials and Methods Top


This study was approved by the local institutional Ethics Committee and all patients approached for the study gave written consent for participation in the study.

Study population

HIV-1-infected patients of Santa Caterina Novella's Hospital (Galatina, Italy) were considered for this study. All patients had documented HIV-1 infection, had been receiving HAART for 12 months and were older than 18 years of age. An in-depth assessment was performed, including HIV disease history, other co-morbid conditions, medication exposure and measurement of blood pressure (determined by using a sphygmomanometer with the subjects in a sitting position at rest). Smokers were defined as individuals smoking more than 5 cigarettes/day at least during the past year (in our cohort all the patients who smoke, declared to smoke >5 cigarettes/day). Subjects were excluded from participation if they had any of the following clinical conditions: active acquired immunodeficiency syndrome-defining illness, diabetes mellitus or current use of oral hypoglycemic agents, family history of myocardial infarction (prior to age 55 years for first-degree male relatives and prior to age 65 years for first-degree female relatives), a history of coronary heart disease or stroke, uncontrolled hypertension, active drug abuse, alcohol abuse (defined as alcohol consumption >30 g/day), untreated hypothyroidism and chronic kidney disease. Patients requiring systemic chemotherapy, radiation therapy or systemic steroids were excluded. Two groups of patients were consecutively selected. The first group comprised of HIV-1-infected patients with a diagnosis of visceral obesity. The second group included HIV-1-infected patients for whom the diagnosis of visceral obesity had been excluded. Diagnoses of visceral obesity were based on an ultrasound-measured PRFT/body mass index ratio >0.22. Grima et al. [10] observed that this value could be considered a potential parameter to assess a visceral fat accumulation in HIV-1-infected patients.

General metabolic assessment

CD4+ cells counts, HIV ribonucleic acid (RNA) load, total serum cholesterol level, high-density lipoprotein (HDL) cholesterol level, triglycerides and creatinine levels were evaluated at baseline after a 12-h overnight fast. Creatinine-based GFR was determined by the four-variable Modification of Diet in Renal Disease equation. [15]

Ultrasonographic measurement of visceral fat and intrarenal artery resistive index (IARI)

A Logiq 5 ultrasound scanner (General Electrics Medical Systems, CT, USA) equipped with a 3.75 MHz convex probe was employed. The visceral fat thickness was determined with a 3.75-MHz convex transducer at a specific referee point as PRFT (longitudinal scan along the right mid clavicular line, from the border of the right liver lobe to the border of the inferior pole of the right kidney [Figure 1]), with the patient in the supine position. IARI was measured with the patient lying supine, using an ultrasound frequency of 3.75 mHz. In each kidney, intrarenal Doppler spectra were obtained at three representative locations from the interlobar arteries along the border of the medullary pyramids. The resistive index (RI) was calculated according to the following formula:

RI = 100 Χ (1-maximum end diastolic velocity/maximum systolic velocity)
Figure 1 :Assessment of perirenal fat diameter. Longitudinal scan (3.75 mHz) along the right midclavicular line, from the border of the right liver lobe to the border of the inferior pole of the right kidney. Arrows, limits
of perirenal fat thickness


Click here to view


Mean RI values were calculated as the average of six RI measurements [Figure 2]. Sonographic evaluation of visceral obesity and renal artery blood flow were always performed by a single trained sonographer-blinded to the patients' data. The reproducibility of PRFT and IARI measurement was evaluated by triple determinations in 15 subjects other than the enrolled patients. A clinically significant increase of IARI was defined as a value >0.69 according to previous observations. [16],[17]
Figure 2 :Assessment of intrarenal artery resistive index with patient lying supine using an ultrasound frequency of 3.75 mHz

Click here to view


Statistical analysis

continuous variables were reported as the mean ± standard deviation (SD) and categorical factors were reported as percentages. Demographic characteristics and metabolic variables were compared between the patient groups by analysis of variance (ANOVA) of successive measurements.

Multiple regression analysis was used to assess the independent association between the renal artery RI and PRFT, adjusting for various risk factors. The most discriminant cut-offs were calculated by receiver operating characteristic (ROC) curves. Statistical calculations were performed with MedCalc software, version 9.6.0.0. A P-value < 0.05 was considered to be statistically significant.


   Results Top


Study population

One hundred and two patients were recruited during 2009. A total of 53 patients (35 men and 18 women) were in the visceral obesity group and 49 (33 men and 16 women) were in the control group. All subjects were of Caucasian race. [Table 1] shows the patient demographic and clinical characteristics.

There were no differences between the two groups with regard to age, gender ratio, smoking status, risk factors, metabolic parameters, CD4 cells count, viral load and . The triglycerides plasmatic levels and HAART duration were higher in patients with visceral obesity, although without statistical significance. Patients with diagnosis of central obesity had lower levels of creatinine clearance than that in patients without clearance (84.5 ± 18.6 vs. 98.5 ± 26 ml/min/1.73m 2 ; P < 0.01). All HIV-1-infected patients had a backbone of Tenofovir/Emtricitabine. Protease inhibitors (PI) had been prescribed in 33 (32.3%) patients (16 with visceral obesity and 17 without obesity), without statistically significant differences between the two groups. All patients exposed to PIs received a ritonavir-boosted PI. Non-nucleoside reverse-trascriptase inhibitor had been prescribed in 69 (67.6%) patients (33 with visceral obesity and 36 without obesity).
Table 1 :Demographic and clinical characteristics of HIV-1 infected patients receiving highly active
antiretroviral therapy


Click here to view


The sonographic assessment of PRFT and IARI provided a good reproducibility, with an intraobserver variability of 6.2% and 7.4%, respectively.

At baseline, the mean of PRFT and IARI in HIV-1-infected patients with visceral obesity was considerably higher (8.1 ± 2.6 vs. 3.2 ± 0.9 mm; P < 0.0001, and 0.66 ± 0.05 vs. 0.63 ± 0.04; P < 0.001, respectively) than that in patients without visceral obesity [Table 2].
Table 2 :Ultrasonographic PRFT and IARI measurement values in HIV-1 infected patients receiving highly active antiretroviral therapy

Click here to view


For all 102 HIV-1-infected patients, ultrasound-measured PRFT correlated well with IARI (r +0.35; P < 0.001) and with creatinine clearance (r -0.29; P < 0.01) [Figure 3] and [Figure 4].
Figure 3 :Linear regression curve of relation between echographicmeasured perirenal fat thickness and intrarenal artery resistive index in 102 human immunodefi ciency virus-1-infected patients. Dotted line, 95% confi dence interval; PRFT, perirenal fat thickness; RI, resistive index

Click here to view
Figure 4 :Linear regression curve of relation between echographicmeasured perirenal fat thickness (PRFT) and creatinine clearance in 102 human immunodefi ciency virus-1-infected patients. Dotted line, 95%
confi dence interval; PRFT, perirenal fat thickness


Click here to view


ROC indicated that the most discriminant PRFT value for predicting an IARI >0.69 was 5 mm (sensitivity 71.7%, specificity 70%, AUC 0.72, P < 0.001) [Figure 5]. Using the average IARI as the dependent variable, age (odds ratio, 1.07; 95% CI, 1.01-1.14; P < 0.05) and PRFT (odds ratio, 1.28; 95% CI, 1.08-1.51; P < 0.01) were independent factors associated to it.
Figure 5 :Receiver operating characteristics curves of perirenal fat thickness (PRFT) considering intrarenal artery resistive index >0.69 as status variable. The area under the curve was 0.72 (95% confi dence
interval, 0.62– 0.80; P < 0.001)


Click here to view



   Discussion Top


The introduction of HAART has induced the development of short- and/or long-term side-effects. Several reports have demonstrated that HIV-1-infected patients could have an abnormality of kidney function. [18],[19],[20] HAART has altered the spectrum of renal disease: the incidence of HIV-associated nephropathy has declined whereas the burden of chronic renal disease associated with diabetes, hypertension and antiretroviral therapy-induced nephrotoxicity has increased. [21],[22] Moreover, many studies have shown increased visceral fat accumulation to be an independent risk factor for cardiovascular diseases, such as coronary artery disease, stroke and hypertension. [20],[22] These clinical findings are also observed in kidney diseases, [23],[24],[25] signifying a potential synergistic relation with cardiovascular outcome.

Obesity has been associated with secretion of inflammatory mediators and activation of inflammation-associated signalling pathways, [26],[27] with a significant role of specific mediators such as leptin, interleukin (IL)-6, tumor necrosis factor (TNF)-a and adiponectin. [28] Because many of these cytokines have been suggested to mediate renal pathophysiology, [29] it could be speculated that progressive kidney disease could also be regulated by pro-inflammatory cytokines in the context of metabolic syndrome.

From recent data, it seems that central fat distribution may be of more importance for endothelial damage than overweight by itself, confirming previous study results that demonstrated that visceral fat accumulation itself played a role as a risk factor for atherosclerosis. [11],[29]

Moreover, truncal adiposity could be a significant source of TNF-a, with a direct stimulation of IL-6 followed by hepatic release of fibrinogen, C-reactive protein and plasminogen activator inhibitor-1. [25]

It was demonstrated that renal artery RI is associated with inflammation and may be a useful marker, together with albuminuria, in hypertensive patients when evaluating hypertensive renal damage. [30] Moreover, it was assessed that a significant correlation exists between RI and severity of renal disease. [31] Other studies evaluating RI in chronic renal failure have demonstrated a correlation of this index to the level of serum creatinine. [32],[33]

In our study, we observed that HIV-1-infected patients with a diagnosis of visceral obesity had an increased IARI with a statistically significant reduction of creatinine clearance compared to patients without central obesity. The demonstration that PRFT in addition to age is the only independent factor associated with IARI could be considered a proof that visceral fat tissue must be considered an endocrine organ with a role in the production of atherosclerotic vascular disease.

To our knowledge, this is the first study to have demonstrated a statistically significant effect of visceral fat on renal arterial blood flow in HIV-1-infected patients, finding a reproducible tool and objective parameter for the monitoring of renal function. As a consequence, a periodic screening for visceral obesity should be considered mandatory in the HIV-1-infected patients receiving HAART.

 
   References Top

1.Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV outpatient Study Investigators. N Engl J Med 1998;338:853-60.  Back to cited text no. 1      
2.Behrens G, Dejam A, Schmidt H, Balks HJ, Brabant G, Kφrner T, et al. Impaired glucose tolerance, beta cell function and lipid metabolism in HIV patients under treatment with protease inhibitors. AIDS 1999;13:F63-70.  Back to cited text no. 2      
3.Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet 2000;356:1423-30.  Back to cited text no. 3      
4.Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1988;12:F51-8.  Back to cited text no. 4      
5.Sekhar RV, Jahoor F, Pownall HJ, Ballantyne CM, Balasubramanyam A. Cardiovascular implications of HIV-associated dyslipidemic lipodystrophy. Curr Atheroscler Rep 2004;6:173-9.  Back to cited text no. 5      
6.Grinspoon S, Carr A. Cardiovascular risk and body fat abnormalities in HIV-infected adults. N Engl J Med 2005;352:48-62.  Back to cited text no. 6      
7.Depres JP. Is visceral obesity the cause of the metabolic sindrome? Ann Med 2006;38:52-63.  Back to cited text no. 7      
8.Martνnez E, Bianchi L, Garcνa-Viejo MA, Bru C, Gatell JM. Sonographic assessment of regional fat in HIV-1-infecvted people. Lancet 2000;356:1412-3.  Back to cited text no. 8      
9.Asensi V, Martνn-Roces E, Carton JA, Collazos J, Maradona JA, Alonso A, et al. Perirenal fat diameter measured by echography could be an early predictor of lipodystrophy in HIV Type 1-infected patients receiving highly active antiretroviral therapy. Clin Infect Dis 2004;39:240-7.  Back to cited text no. 9      
10.Grima PF, Chiavaroli R, Grima P. Ultrasonographic assessment of lipodystrophy in HIV-1-infected patients. Radiol Med 2009;114:141-51.   Back to cited text no. 10      
11.Grima P, Guido M, Zizza A, Chiavaroli R. Sonographically measured perirenal fat thickness: An early predictor of atherosclerosis in HIV-1-infected patients receiving highly active antiretroviral therapy? J Clin Ultrasound. 2010;38:190-5.   Back to cited text no. 11      
12.Kawasaki S, Aoki K, Hasegawa O, Numata K, Tanaka K, Shibata N, et al. Sonographic evaluation of visceral fat by measuring para- and perirenal fat. J Clin Ultrasound. 2008;36:129-33.  Back to cited text no. 12      
13.Schelling JR, Sedor JR. The metabolic syndrome as a risk factor for chronic kidney disease: More than a fat chance? J Am Soc Nephrol 2004;15:2773-4.  Back to cited text no. 13      
14.Chen J, Muntner P, Hamm LL, Jones DW, Batuman V, Fonseca V, et al. The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med 2004;140:167-74.  Back to cited text no. 14      
15.National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification and stratification. Am J Kidney Dis 2002;39:S1-266.  Back to cited text no. 15      
16.Platt J, Ellis J, Rubin J. Examination of native kidneys with duplex doppler ultrasound. Semin Ultrasound CT MR 1991;12:308-18.  Back to cited text no. 16      
17.Platt JF. Doppler evaluation of native kidney dysfunction: Obstructive and nonobstructive disease. AJR Am J Roentgenol 1992;158:1035-42.  Back to cited text no. 17      
18.Gupta SK, Mamlin BW, Johnson CS, Dollins MD, Topf JM, Dubι MP. Prevalence of proteinuria and the development of chronic kidney disease in HIV-infected patients. Clin Nephrol 2004;61:1-6.  Back to cited text no. 18      
19.Szczech LA, Hoover DR, Feldman JG, Cohen MH, Gange SJ, Goozι L, et al. Association between renal disease and outcomes among HIV-infected women receiving or not receiving antiretroviral therapy. Clin Infect Dis 2004;39:1199-206.  Back to cited text no. 19      
20.Gupta SK, Eustace JA, Winston JA, Boydstun II, Ahuja TS, Rodriguez RA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: Recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2005;40:1559-85.  Back to cited text no. 20      
21.Lucas GM, Eustace JA, Sozio S, Mentari EK, Appiah KA, Moore RD. Highly active antiretroviral therapy and the incidence of HIV-1-assocated nephropathy: A 12-year cohort study. AIDS 2004;18:541-6.  Back to cited text no. 21      
22.De Silva TI, Post FA, Griffin MD, Dockrell DH. HIV-1 infection and the kidney: An evolving challenge in HIV Medicine. Mayo Clin Proc 2007;82:1103-16.  Back to cited text no. 22      
23.Wahba IM, Mak RH. Obesity and obesity-initiated metabolic syndrome: Mechanism links to chronic kidney disease. Clin J Am Nephrol 2007;2:550-62.  Back to cited text no. 23      
24.Young JA, Hwang SJ, Sarnak MJ, Hoffmann U, Massaro JM, Levy D, et al. Association of visceral and subcutaneous adiposity with kidney function. Clin Am Soc Nephrol 2008;3:1786-91.  Back to cited text no. 24      
25.Chalmers L, Laskel FJ, Bamgbola O. The role of obesity and its bioclinical correlates in the progression of chronic kidney disease. Adv Chronic Kidney Dis 2006;13:352-64.  Back to cited text no. 25      
26.Hirosumi J, Tuncman G, Chang L, Gφrgόn CZ, Uysal KT, Maeda K, et al. A central role for JNK in obesity and insulin resistance. Nature 2002;420:333-6.  Back to cited text no. 26      
27.Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M, et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ. Science 2001;293:1673-7.  Back to cited text no. 27      
28.Wisse BE. The inflammatory syndrome: The role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol 2004;15:2792-800.  Back to cited text no. 28      
29.Wolf G, Chen S, Han DC, Ziyadeh FN. Leptin and renal disease. Am J Kidney Dis 2002;39:1-11.  Back to cited text no. 29      
30.Ozelsancak R, Torun D, Koc Z, Sezer S, Ozdemir FN, Niron EA. Relationship between renal resistive index and inflammation in untreated hypertensive patients. Int Heart J 2009;50:753-61.  Back to cited text no. 30      
31.Petersen LJ, Petersen JR, Talleruphuus U, Ladefoged SD, Mehlsen J, Jensen HA. The pulsatility index and the resistive index in renal arteries. Associations with long-term progression in chronic renal failure. Nephro Dial Transplant 1997;12:1376-80.  Back to cited text no. 31      
32.Kim SH, Kim WH, Choi BI, Kim CW. Duplex Doppler ultrasound in patients with medical renal disease: Resistive index vs creatinine serum level. Clin Radiol 1992;45:85-7.  Back to cited text no. 32      
33.Platt JF, Ellis JH, Rubin JM, DiPietro MA, Sedman AB. Intrarenal arterial Doppler sonography in patients with nonob- structive renal disease: Correlation of resistive index with biopsy findings. Am J Radiol 1990;154:1223-7.  Back to cited text no. 33      


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]



 

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