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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2019  |  Volume : 30  |  Issue : 1  |  Page : 62-67
Association of insulin growth factor-1 and growth hormone levels in elderly renal transplant recipients with cardiac dysfunction


1 Department of Internal Medicine, Kasr Al-Aini School of Medicine, Cairo University, Cairo, Egypt
2 Department of Nephrology, Kasr Al-Aini School of Medicine, Cairo University, Cairo, Egypt

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Date of Submission29-Sep-2017
Date of Decision19-Dec-2017
Date of Acceptance19-Dec-2017
Date of Web Publication26-Feb-2019
 

   Abstract 


Insulin growth factor-1 (IGF-1) and growth hormone (GH) have cardiac protective effects through many mechanisms; they can directly oppose endothelial dysfunction in a number of ways. Many studies assessed the effect of GH or IGF-like growth factor 1 in patients with cardiac dysfunction, but no previous study assessed the GH and insulin-like growth factor-1 in renal transplant recipients with and without cardiac dysfunction, especially elderly. Eighty patients with renal transplantation and age limit above 75 years. They were subdivided into two groups according to the presence or absence of cardiac dysfunction based on medical history, clinical findings, electrocardiogram, and echocardiography. Serum GH and insulin-like growth factor-1 were studied by immunoradiometric assay. The echocardiography study was performed. M-mode two-dimensional and Doppler measurements were taken to obtain the four- and five-chamber views, chambers' dimensions, left ventricular end-diastolic dimensions, left ventricular end-systolic dimensions, septal wall thickness (SWT), distance between leading edges of the endocardial and pericardial echoes of left ventricular posterior wall (posterior wall thickness), aortic root and left atrial dimensions (LAD), fractional shortening and ejection fraction. IGF-1 is lower in patients with cardiac dysfunction with renal transplantation with mean value of 61 ± 30.05 than those control group with mean value 145.52 ± 70.5. Level of human growth factor is higher in patients with dysfunction with renal transplantation with mean value 2.62 ± 3.05 than those control group after renal transplantation with mean value 0.85 ± 0.9. No correlations were found between IGF-1 and various echocardiographic parameters. Only SWT and LAD were negatively correlated with GH, r = −0.08, P <0.02, r = −0.37, P <0.03, respectively. No correlation was found between IGF-1 and various echocardiographic parameters. Only SWT and LAD were negatively correlated with GH.

How to cite this article:
Soliman AR, Soliman MA, Sadek KM. Association of insulin growth factor-1 and growth hormone levels in elderly renal transplant recipients with cardiac dysfunction. Saudi J Kidney Dis Transpl 2019;30:62-7

How to cite this URL:
Soliman AR, Soliman MA, Sadek KM. Association of insulin growth factor-1 and growth hormone levels in elderly renal transplant recipients with cardiac dysfunction. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 May 19];30:62-7. Available from: http://www.sjkdt.org/text.asp?2019/30/1/62/252934



   Introduction Top


The insulin growth factor-1 (IGF-1) and growth hormone (GH) axis system are dynamic and complex, by which cells use to communicate with their local environment to help regulate normal physiology and in number of other pathological states.[1],[2]

IGF-1 has cardiac protective effects by preventing endothelial dysfunction in a number of ways, some of which include by interacting with high-affinity endothelial binding sites that lead to nitric oxide production,[3] by promoting insulin sensitivity[4] and potassium-channel opening,[5] and by preventing postprandial dyslipidemia.[6]

Many studies assessed the effect of GH or IGF-like growth factor 1 in patients with and without cardiac dysfunctions,[7] but no previous study assessed the GH and insulin-like growth factor-1 in elderly renal transplant recipients with and without cardiac dysfunction.


   Materials and Methods Top


This study was conducted on 53 consecutive from January 1995 to December 2014 subjects who were status postrenal transplant and were 75 years or older. The exclusion criterion included patients with diabetes mellitus, creatinine (Cr) above 2 mg/dL, liver cell failure, collagen vascular disease, and myocardial infarction were excluded. Total patients identified before exclusion criterion was applied were 80 [Table 1] and [Table 2].
Table 1: Transplantation details of elderly renal transplant recipients with and without cardiac dysfunction.

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Table 2: Demographic data of elderly renal transplant recipients with and without cardiac dysfunction.

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They were then subdivided into two groups according to the presence or absence of cardiac dysfunction based on medical history, clinical findings, electrocardiogram (ECG), and echocardiography. Including the history of previous ischemic heart disease or heart failure and by detection of the clinical finding of heart failure or chamber enlargement, and ECG and echocardiographic finding of any chamber enlargement and low ejection fraction. The two groups were subjected to laboratory investigations including blood sugar (fasting and 2 h postprandial), serum Cr and blood urea, serum albumin. Bilirubin, aspartate transaminase, alanine transaminase, serum cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels using autoanalyzer. Blood samples for lipid parameters were collected after more than 12 h fasting. Lipoprotein (a) was also estimated.[8] Serum GH and insulin-like growth factor-1 were studied by immunoradiometric assay.[9] Echocardiography study was performed using Interspec, Ambler, PA Machine (Apogee CX, Serial number 7294 model). M-mode two-dimensional and Doppler measurements were taken to obtain the four-and five-chamber views, chambers' dimensions, left ventricular end-diastolic dimensions, left ventricular end-systolic dimensions, septal wall thickness (SWT), distance between leading edges of the endocardial and pericardial echoes of left ventricular posterior wall [posterior wall thickness, aortic root and left atrial dimensions (LAD), fractional shortening, and ejection fraction].


   Statistical Analysis Top


Statistical Package for the Social Science (SPSS) (version 17.0) software (SPSS Inc., Chicago, IL, USA). was used for data analysis. Mean and standard deviation were used for quantitative data description, median and range for nonnormally distributed data. Wilcoxon test was used for comparison of two independent groups. Comparison and coefficient correlation between groups were done using r value. P-value is statistically significant if <0.05 level.


   Results Top


Fifty-three elderly renal transplant recipients fulfilled the inclusion criteria. They were 40 males and 13 females with age ranging from 75 to 88 with mean 78.4 ± 6.7.

Clinical data of group 1 with cardiac dysfunction (28 subjects) most of them showed clinical features of volume overload included nine subjects with ascites, 12 with congested hepatomegaly, 18 with bilateral basal crepitations, 28 with bilateral pedal edema, 27 with congested neck veins and three with jaundice. On the other hand, the control group with satisfactory cardiac function (25 subjects) showed negative findings as regard ascites, lung bases, and neck veins. Two subjects showed pedal edema (probably due to amlodipine intake) and three had noncongested hepatomegaly.

Laboratory investigations of subjects and control groups are shown in [Table 3].
Table 3: Laboratory data of elderly renal transplant recipients with and without cardiac dysfunction.

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Main serum Cr of subjects with cardiac dysfunctions (Group 1) was 1.6 ± 0.4 while in the control group (Group 2) was 1.5 ± 0.2 (NS). Blood urea of subjects with cardiac dysfunction group (group 1) was 62.4 ± 35.3 while in control group was 27.5 ± 6.45, P <0.001. Human GH of cardiac dysfunction subjects (Group 1) was 2.62 ± 3.05, whereas in control group (Group 2) was 0.85 ± 0.9 (NS). IGF-1 of cardiac dysfunction subjects (Group 1) was 61.10 ± 30.05, whereas in control group (Group 2) was 145.52 ± 70.5, P<0.001. Serum albumin of cardiac dysfunction group was 3.1 ± 0.51 while in the control group (group 2) was 3.95 ± 0.3, P<0.001.

Echocardiographic finding showed that LAD of cardiac dysfunction subjects (Group 1) was 5.12 ± 0.92, whereas in control group (Group 2) was 3.62 ± 0.34, P<0.001.

Other echocardiographic findings in both groups are shown in [Table 4].
Table 4: Echocardiographic parameters in elderly renal transplant recipients with and without cardiac dysfunction.

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IGF-1/human GH ratio in cardiac renal transplant study patients was 160.12 ± 215 and in control group was 428.5 ± 440 (P<0.02) while IGF-1/human GH log ratio in cardiac renal transplant study patients was 1.68 ±0.72 and in control group was 2.42 ± 0.41 P <0.02 shown in [Table 5].
Table 5: IGF-1/Human growth hormone ratio and log ratio in cardiac renal transplant patients and control group.

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Correlation between GH and echocardiographic parameters shown in [Table 6].
Table 6: Correlation between growth hormone and echocardiographic parameters.

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   Discussion Top


There is no previous study assessed the effect of GH and insulin-like growth factor 1 in renal transplantation, especially in those elderly persons with cardiac dysfunction.

The salient findings of the present study are GH has protective cardiac effects in elderly after renal transplantation, negative correlation between LAD, SWT with the GH, no correlation between IGF-1 and various echocardiographic finding.

In our study, we studied 53 subjects with renal transplantation and age limit above 75 years, they were subdivided into two groups according to presence or absence of cardiac dysfunction based on medical history, clinical finding, ECG and echocardiography.

We found level of IGF-1 is lower in subjects with cardiac dysfunction postrenal transplantation with mean value of 61 ± 30.05 than those control group with mean value 145.52 ± 70.5. We found the level of human growth factor is higher in patients with cardiac dysfunction postrenal transplantation with mean value 2.62 ± 3.05 than those control group after renal transplantation with mean value 0.85 ± 0.9.

All assessment of echocardiography for both groups was posttransplantation and unfortunately we did not have pretransplantation echocardiography details to compare between them before and after transplantation.

This result is supported with Spallarossa et al in 1996,[10] they studied of 122 young subjects, they assessed the level of IGF-1 in comparison with the risk of coronary artery disease as documented angiographically. They found low circulating IGF-1 associated with angiographically documented coronary artery disease.

In our study, we also found that EDV in patients with cardiac dysfunction postrenal was higher with a mean value of 6.82 ± 0.9 than those control group after renal transplantation with mean value 4.40 ± 0.5. Furthermore, ESV in patients with cardiac dysfunction postrenal was higher with mean value 5.93 ± 0.9 than those control group after renal transplantation with mean value 2.75 ± 0.4.

Regression analysis was performed regarding blood urea, albumin, bilirubin, and cholesterol in both groups and it showed no significant effect on echocardiographic changes or any association with level of GH of IGF-1.

No significant correlation was found between duration after renal transplantation and the value of GH and IGF-1. Furthermore, the regimen of immunosuppression was not found to affect the level of either GH or IGF-1.

Our study founded that there is no correlation between IGF-1 and various echocardiographic finding.

In our study, we found that IGF-1 is lower in subjects with cardiac dysfunction postrenal with mean value of 61 ± 30.05 than those control group after renal transplantation with mean value 145.52 ± 70.5. Furthermore, the level of human growth factor is higher in subjects with cardiac dysfunction postrenal with mean value 2.62 ± 3.05 than those control group after renal transplantation with mean value 0.85 ± 0.9. No correlation was found between IGF-1 and various echocardiographic parameters. Only SWT and LAD were negatively correlated with GH, r = − 0.08, P <0.02, r = −0.37, P<0.03, respectively.

We also found that EDV in patients with cardiac dysfunction postrenal was higher with mean value 6.82 ± 0.9 than those control group after renal transplantation with mean value 4.40 ± 0.5, also ESV in patients with cardiac dysfunction postrenal was higher with mean value 5.93 ± 0.9 than those control group after renal transplantation with mean value 2.75 ± 0.4.


   Conclusion Top


GH is protective against cardiac changes in elderly patients after renal transplantation. Negative correlation between LAD and SWT with the GH level. No correlation between IGF 1 and various echocardiographic finding.

Impaired IGF/GH axis may play a role in renal transplant recipients patients with cardiac dysfunction and further studies are required to see if correction will help improve cardiac function.


   Acknowledgment Top


Thanks to ALLAH, the most merciful and gracious.

Thinks is one emotion that flows directly from the heart into a heart and it's a very wonderful feeling that never goes away.

Thanks to Prof. Dr. Amin Roshdi, Professor of Internal Medicine and Nephrology, Cairo University, I owe him a great deal of gratitude, his wide horizon of kindness has helped me in this work. He provides me with graceful guidance and support as a professor and a father.

Conflict of interest:

None declared.



 
   References Top

1.
Hwa V, Oh Y, Rosenfeld RG. The insulin-like growth factor-binding protein (IGFBP) superfamily. Endocr Rev 1999;20:761-87.  Back to cited text no. 1
    
2.
Conti E, Pitocco D, Capoluongo E, et al. IGF-1 and macrovascular complications of diabetes: Alternative interpretations of recently published data. Diabetes Care 2003;26:1653-4.  Back to cited text no. 2
    
3.
Schini-Kerth VB. Dual effects of insulin-like growth factor-I on the constitutive and inducible nitric oxide (NO) synthase-dependent formation of NO in vascular cells. J Endocrinol Invest 1999;22:82-8.  Back to cited text no. 3
    
4.
Conti E, Andreotti F, Sestito A, et al. Reduced levels of insulin-like growth factor-1 in patients with angina pectoris, positive exercise stress test, and angiographically normal epicardial coronary arteries. Am J Cardiol 2002; 89:973-5.  Back to cited text no. 4
    
5.
Oltman CL, Kane NL, Gutterman DD, Bar RS, Dellsperger KC. Mechanism of coronary vasodilation to insulin and insulin-like growth factor I is dependent on vessel size. Am J Physiol Endocrinol Metab 2000;279:E176-81.  Back to cited text no. 5
    
6.
Twickler MT, Cramer MJ, Koppeschaar HP. Unraveling reaven's syndrome X: Serum insulin-like growth factor-I and cardiovascular disease. Circulation 2003;107:e190-2.  Back to cited text no. 6
    
7.
Arcopinto M, Salzano A, Giallauria F, et al. Growth hormone deficiency is associated with worse cardiac function, physical performance, and outcome in chronic heart failure: Insights from the T.O.S.CA. GHD study. PLoS One 2017;12:e0170058.  Back to cited text no. 7
    
8.
Labeur C, Michiels G, Bury J, Usher DC, Rosseneu M. Lipoprotein(a) quantified by an enzyme-linked immunosorbent assay with monoclonal antibodies. Clin Chem 1989;35: 1380-4.  Back to cited text no. 8
    
9.
Underwood LE, D'Ercole AJ, Copeland KC, Van Wyk JJ, Hurley T, Handwerger S. Development of a heterologous radioimmunoassay for somatomedin C in sheep blood. J Endocrinol 1982;93:31-9.  Back to cited text no. 9
    
10.
Spallarossa P, Brunelli C, Minuto F, et al. Insulin-like growth factor-I and angiographically documented coronary artery disease. Am J Cardiol 1996;77:200-2.  Back to cited text no. 10
    

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Correspondence Address:
Khaled M Sadek
Department of Internal Medicine and Nephrology, Kasr Al-Aini School of Medicine, Cairo University, Cairo
Egypt
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DOI: 10.4103/1319-2442.252934

PMID: 30804268

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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    Abstract
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    Materials and Me...
   Statistical Analysis
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