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International journal of endocrinology Том 13, №6, 2017

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Influence of certain components of metabolic syndrome on renal function in hypothyroidism (literature review)

Authors: O.M. Didushko
Higher State Education Institution “Ivano-Frankivsk National Medical University”, Ivano-Frankivsk, Ukraine

Categories: Endocrinology

Sections: Specialist manual

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Summary

У статті висвітлено вплив окремих компонентів метаболічного синдрому: артеріальної гіпертензії, ожиріння й дисліпідемії на функцію нирок при гіпотиреозі, причинно-наслідковий зв’язок між вказаними компонентами й гіпотиреозом та нирковою дисфункцією. Показано, що артеріальна гіпертензія, абдомінальне ожиріння, гіперлептинемія, дисліпідемія є незалежними факторами ризику розвитку порушення функції нирок при гіпо­тиреозі.

В статье освещено влияние отдельных компонентов метаболического синдрома: артериальной гипертензии, ожирения и дислипидемии на функцию почек при гипотиреозе, причинно-следственная связь между указанными компонентами и гипотиреозом и почечной дисфункцией. Показано, что артериальная гипертензия, абдоминальное ожирение, гиперлептинемия, дислипидемия являются независимыми факторами риска развития нарушения функции почек при гипотиреозе.

The article deals with the influence of certain components of the metabolic syndrome, such as arterial hypertension, obesity and dyslipidemia, on renal function in hypothyroidism, causal relationship between these components and hypothyroidism and renal dysfunction. It has been shown that arterial hypertension, abdominal obesity, hyperleptinemia and dyslipidemia are independent risk factors for renal dysfunction in hypothyroidism.


Keywords

гіпотиреоз; артеріальна гіпертензія; ожиріння; лептин; дисліпідемія; хронічна хвороба нирок; огляд

гипотиреоз; артериальная гипертензия; ожирение; лептин; дислипидемия; хроническая болезнь почек; обзор

hypothyroidism; arterial hypertension; obesity; leptin; dyslipidemia; chronic kidney disease; review

International research proves that diabetes mellitus, arterial hypertension (AH), obesity and dyslipidemia, i.e. major components of metabolic syndrome (MS), constitute an independent risk factor not only for the development of cardiovascular diseases, but also of chronic kidney disease (CKD) [1–3].
Negative influence of MS components on the functional state of kidneys is manifested at various stages: from the development of albuminuria — to progressive decrease of glomerular filtration rate (GFR), including administration of dialysis and kidney transplantation [4]. At the same time, manifestations of CKD, in addition to albuminuria and decrease in GFR, include AH and dyslipidemia, which significantly impairs the prognosis of such patients.
CKD is treated as a disease characterized by prolonged (at least three months) structural and/or functional renal changes according to clinical, laboratory, instrumental and morphological investigations, which give grounds for eliminating the acute nature of the pathological process in kidneys [5, 6].
CKD is identified as a risk factor for cardiovascular events; for example — the risk of cardiovascular mortality is 6 times higher with albuminuria threshold exceeding 300 mg/day and 5 times higher if GFR decreases to less than 70 ml/min. Therefore, experts recommend to consider CKD an independent factor of cardiovascular complications and cardiac death [7].
Stages of CKD are determined according to the level of GFR, rather than that of creatinine, since blood creatinine begins to increase when GFR is half less than its normal value, i.e. hypercreatininemia is observed in case when more than 50 % of nephrons are inactive [6]. Very high concentrations of creatinine in combination with low GFR are independently associated with mortality from all causes, while an isolated reduction of GFR is associated with death caused by cardiovascular disease [5]. In order to calculate GFR, Cockroft-Gault formula and MDRD (Modification of Diet in Renal Disease) are commonly used; they are easy to apply and validate according to standard methods for GFR evaluation. Common disadvantage of the mentioned above formulas is their inaccuracy in normal or slightly lowered GFR va–lues. CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration), a newly developed formula, which provides more accurate results, even with preserved kidney function, has been developed [5, 8].
Cystatin C measurement as a confirmatory test for the diagnosis of CKD in adult patients with reduced GFR, measured by the level of creatinine, is recommended by the work group KDIGO CKD [8, 9]. Cystatin C is a non-glycosylated protein inhibiting cysteine proteinases [10, 11]. It is formed in the body at a constant rate, is freely filtered through the glomerular membrane, and then it is completely reabsorbed by proximal tubules without further secretion [12]. Cystatin is less dependent on age, sex, race, muscle mass, drug therapy, physical activity, and diet as compared to creatinine. These enume–rated properties have made it almost an ideal candidate for assessing kidney function. Trials on humans and animals have proved that, as a rule, cystatin C levels have a tendency opposite to those of serum creatinine [13, 14]. With hypothyroidism, reduction of cystatin C level due to its lower production and further decrease in the intensity of cellular metabolism, is observed. However, there is an assumption that thyroid hormones directly affect the synthesis of cystatin C, although the exact mechanism of this action is still unknown. Thus, presented facts about the variability of this marker indicate that cystatin C cannot be used for the evaluation of GFR in patients with thyroid diseases [15, 16].
No doubt that AH plays a leading role in the deve–lopment of CKD of any genesis. Moreover, there is no fundamental difference whether AH is a separate disease, associated with the pathology of the kidneys, or is the result of nephropathy [17].
Hypertension accompanying hypothyroidism develops primarily as a result of increased peripheral vascular resistance, which is a compensatory response to the decreased total diameter of the vasculature due to a decreased cardiac output, circulating blood volume, as well as the result of mucoid edema of small vessels and reduced arterial elasticity. N.B. Zelinska [18] indicates such peculiarity of hypertension accompanying hypothyroidism as growth of diastolic blood pressure and pulmonary arterial pressure, which occurs in case of mild and moderate severity of the disease, and increase of systolic blood pressure is observed only with AH development to hypothyroidism or in patients over the age of 50. Since the highest prevalence of AH and hypothyroidism has been observed in the age group over 50, the problem of combining AH and hypothyroidism, especially in patients of older age groups, is of paramount importance nowadays.
Although most researchers consider hypertension a disease which develops regardless of the presence of hypothyroidism, all of them confirm a positive effect of substitution therapy with thyroid hormonal preparations on the level of blood pressure (BP) [19, 20]. However, there are studies that show persisting hypertension in 50 % of patients and lack of normalization of hemodynamic disorders, even after achieving a euthyroid condition. This is due to the disorder of elastic properties of the aorta and large arteries with the development of rigidity in case of hypothyroidism.
A number of authors describe significantly higher va–lues of systolic BP, diastolic BP, pulse BP in patients with hypothyroidism with obesity than in non-obese patients. Authors [18, 21] correlate such increase of blood pressure in patients with hypothyroidism and obesity with their inherent insulin resistance and hyperinsuli–nism. These changes increase the peripheral vascular resistance with further growing risk of disorders associated with insulin resistance.
In addition, prolonged increase of BP causes hypertensive changes in intrarenal arteries, their sclerosis and gyalinosis, which leads to ischemia of glomeruli and nephroangiosclerosis. But even before the manifestation of first morphological signs of renal vascular damage, high BP causes growth of intraglomerular transcaspillary pressure and leads to intraglomerular hypertension, which contributes to the development of glomerulosclerosis [22].
Numerous clinical studies show that accelerated CKD progression is influenced by AH. MDRD (Modified Diet and Renal Disease) research has stated that patients, who have managed to achieve appropriate low blood pressure values, have lower rate of glomerular filtration (especially patients with high proteinuria levels). BP is considered an important determinant of renal damage progression, both in early and late stages of CKD.
Obesity is one of the main problems of modern society [23–26]. Epidemics of obesity spreads in parallel with the increase of incidences of CKD [21, 27–31].
Hypothyroidism is traditionally referred to a condition associated with an increase in body weight. Up to 54 % of patients with primary hypothyroidism report gain of body weight. In this case, primary hypothyroidism is found in 11.8 % of patients with morbid obesity, and increase of TSH levels to the subclinical level is observed in 7.7 %. The cohort study of Norwegian Nord-Trandelag (15 020 euthyroid patients monitored for 10.5 years) demonstrated a relationship between thyroid condition, body weight, and body mass index (BMI). It has been revealed that increase of TSH by 1 mIU/l in women is accompanied by body weight gain by 0.9 kg, and BMI increase by 0.3 kg/m2, while in men — by 0.8 kg and 0.2 kg/m2, respectively.
A number of studies have proved that expression of the thyroid receptor a and cx 1 is increased in the subcutaneous fatty tissue in comparison to visceral one in obese patients, and expression of TSH receptor in the subcutaneous fatty tissue correlates with BMI [32, 33].
Recent studies indicate that excessive body weight and obesity are independent predictors of CKD deve–lopment and end-stage of renal diseases (ESRD) [25, 26, 31]. Particular attention is drawn to cardio-renal syndrome, which is frequently manifested by involvement of kidneys in the pathological process at the background of primary heart and circulatory diseases and is one of the causes of chronic renal failure [31].
The effects of excessive body weight on the functional state of kidneys are treated ambiguously nowadays. Most researchers point to a positive correlation between BMI and renal filtration capacity.
Negative effect of obesity on the structure of the kidneys is explained by the influence of hyperleptinemia, hyperinsulinemia, activation of local adipocyte renin-angiotensin-aldosterone system and hemodynamic factors (fat tissue compression, inadequacy of nephron number to body size, constriction of the efferent arterioles, hyper- and hypofiltration, intraglomerular hypertension). Studies show a cause-effect relationship between these mechanisms of damage and renal dysfunction [26]. Prolonged intraglomerular hypertension contributes to disorders of architectonics and basal membrane permeability, which ultimately leads to glomerulosclerosis and tubulointerstitial fibrosis [31].
The role of adipose tissue hormone — leptin, concentration of which significantly increases with obesity due to the development of leptin resistance [26], remains rather interesting. In case of leptin resistance, peroxide oxidation of free fatty acids is activated, which can sti–mulate the development of lipotoxic disorders: development of insulin resistance, endothelial dysfunction or oxidative stress [31]. In case of visceral obesity and leptin resistance this hormone is able to cause calcification of vessels, accumulation of cholesterol by the vascular wall cells, increased sympathetic tone [32]. According to some researchers, the content of thyroid hormones and TSH do not affect the synthesis and secretion of adipose tissue hormone (leptin) in any way [34]. Other studies reveal that there is a positive correlation between leptin levels and TSH in obese patients, which reflects a positive correlation between TSH and BMI [35]. However, a number of studies highlight that serum leptin content in patients with hypothyroidism increases, even after correction of BMI values [32]. Physiologically, leptin regulates energy homeostasis, informing the central nervous system about the stores of adipose tissue, affects neuroendocrine and behavioral responses to overeating; and TSH, in its turn, stimulates the secretion of leptin in the adipose tissue; and increase of leptin induces secretion of thyroliberin [32].
Leptin plays an important role in the development of renal pathophysiological processes. In kidneys, leptin receptors are found in the tubular epithelial cells. These receptors are responsible for diuresis and natriuresis, without changes in blood pressure and K+ excretion [31]. In the culture of endothelial cells of rats with body weight within norm, prolonged infusion of recombinant leptin of mice stimulated increase of the mRNA-transforming growth factor β1, its secretion and synthesis of type IV collagen, which was accompanied by the development of focal glomerulosclerosis and proteinuria. There is evidence that with hyperleptinemia glomerular endothelial cell damage by oxygen radicals and peroxides is increased due to activation of oxidative stress [36].
It has been proved that the condition of even “minimal thyroid insufficiency” greatly contributes to the development of hyperlipidemia, ischemic heart disease [38, 39]. It has been noted that with hypothyroidism, dyslipidemia is observed twice often in comparison to patients with euthyroidism [39].
Mechanisms of dyslipidemia development in case of hypothyroidism include a number of biochemical changes: decreased activity of cholesterol-ether-transport protein and hepatic lipase, which provide about 30 % of reverse transport of cholesterol; disorders of HDL structure; decreased number and sensitivity of LDL receptors in the liver, as well as impaired renal glomerular function (decreased GFR) and slower LDL clearance [40]. Administration of hormonal replacement therapy optimizes lipid-lowering effect of statins, but is not an alternative to lipid-lowering therapy [41]. Findings of experimental and clinical studies provide an opportunity to positively assert the significance of dyslipidemia not only in the development of atherosclerotic lesions of renal vessels, but also glomerulosclerosis [42]. Accumulation of lipid by cells or “lipotoxicity” is a well-known phenomenon that plays an important role in the process of atherosclerosis [22]. “Lipotoxicity” is associated with the damage to internal organs, including renal diseases. Autopsy data indicate a direct relationship between sclerosis of the glomerular renal apparatus and processes of atherosclerosis [43, 44]. Although some scholars believe that lipid metabolic disorders trigger kidney disease, still the overwhelming majority of scientists consider dyslipidemia a condition that only contributes to the progression of renal pathology.
In terms of CKD and associated dyslipidemia, the rate of deterioration of renal function is twice higher than in individuals with CKD and normal lipidogram parameters [6]. Negative effects of dyslipidemia on renal glomeruli are conditioned by endothelial and mesangial cell dysfunction, direct cytotoxicity, vascular wall proliferation, cytokine release, growth factors, inflammatory mediators, etc. [22].
Thus, components of MS are independent risk factors for the development of renal dysfunction in hypothyroidism. Therefore, patients with impaired renal function of non-inflammatory genesis and abdominal obesity are re–commended a comprehensive examination for the diagnosis of hypothyroidism (ultrasound examination of the thyroid gland and determination of TSH level) and administration of adequate treatment. At the same time, high le–vels of TSH can be considered a predictor of GFR decrease.
Conflicts of interests. Author declares the absence of any conflicts of interests that might be construed to influence the results or interpretation of their manuscript.

Bibliography

  1. Gerchman F, Tong J, Kristina M, et al. Body mass index is associated with increased creatinine clearance by a mechanism independent of body fat distribution. J Clin Endocrinol Metab. 2009 Oct; 94(10): 3781-8. doi:  10.1210/jc.2008-2508.
  2. Bonnet F, Marre M, Halimi JM, et al. Waist circumference and the metabolic syndrome predict the development of elevated albuminuria in non-diabetic subjects: the DESIR Study. J Hypertens. 2006 Jun;24(6):1157-63. doi: 10.1097/01.hjh.0000226206.03560.ac.
  3. Kryachkova AA, Savelyeva SA, Gallyamov MG, Shestakova MV, Kutiryna IM. The role of obesity in renal injury in patients with metabolic syndrome. Nefrologiia i dializ. 2010;12(1):34-8. (in Russian).
  4. Dobronravov VA, Smirnov AV, Kayukov IG. Manysided albuminuria: aspects of clinical value. Nephrology (Saint-Petersburg). 2009;13(3):33-38. (in Russian).
  5. Ivanov DD. Lectures on nephrology. Diabetic disease of kidneys. Hypertensive nephropathy. Chronic renal failure. Donetsk: Publisher Zaslavskyi OYu; 2010. 200 p. (in Russian).
  6. Ivanov DD, Korzh ОM. Nephrology in physician’s practice: study guide. 2nd edition. Donetsk: Publisher Zaslavskyi OYu; 2012. 384 p. (in Ukrainian).
  7. Damman K, Van Veldhuisen DJ, Navis G, et al. Tubular damage in chronic systolic heart failure is associated with reduced survival independent of glomerular filtration rate. Heart. 2010 Aug;96(16):1297-302. doi: 10.1136/hrt.2010.194878.
  8. National Kidney Foundation. KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update. Am J Kidney Dis. 2012 Nov;60(5):850-86. doi: 10.1053/j.ajkd.2012.07.005.
  9. Hojs R, Bevc S, Ekart R, Gorenjak M, Puklavec L. Kidney function estimating equations in patients with chronic kidney disease. Int J Clin Pract. 2011 Apr;65(4):458-64. doi: 10.1111/j.1742-1241.2010.02597.x.
  10. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3(1):1–150. doi: 10.1038/kisup.2012.73. 
  11. Waheed S, Matsushita K, Sang Y, et al. Combined association of albuminuria and cystatin C-based estimated GFR with mortality, coronary heart disease, and heart failure outcomes: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Kidney Dis. 2012 Aug; 60(2): 207–216. doi:  10.1053/j.ajkd.2012.03.011.
  12. Niccoli G, Conte M, Della Bona R. et al. Cystatin C is associated with an increased coronary atherosclerotic burden and a stable plaque phenotype in patients with ischemic heart disease and normal glomerular filtration rate. Atherosclerosis. 2008 Jun;198(2):373-80. doi: 10.1016/j.atherosclerosis.2007.09.022.
  13. Kravchun NO, Kryvovyaz YuO. Modern diagnostical markers of diabetic nephropathy. Problems of Endocrine Pathology. 2012;3:104-12. (in Ukrainian).
  14. Shen SJ, Hu ZX, Li QH, et al. Implications of the changes in serum neutrophil gelatinase-associated lipocalin and cystatin C in patients with chronic kidney disease. Nephrology (Carlton). 2014 Mar;19(3):129-35. doi: 10.1111/nep.12203.
  15. Helal I, Fick-Brosnahan GM, Reed-Gitomer B, Schrier RW. Glomerular hyperfiltration: definitions, mechanisms and clinical implications. Nat Rev Nephrol. 2012 Feb 21;8(5):293-300. doi: 10.1038/nrneph.2012.19.
  16. Kimmel M, Braun N, Alscher M. Influence of thyroid function on different kidney function tests. Kidney Blood Press Res. 2012;35(1):9-17. doi: 10.1159/000329354. 
  17. Mahmoodi BK, Matsushita K, Woodward M, et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis. Lancet. 2012 Nov 10;380(9854):1649-61. doi: 10.1016/S0140-6736(12)61272-0.
  18. Zelinska NB. Diagnostics of pathology of cardiovascular system in hypothyroid patients. Clinical Endocrinology and Endocrine Surgery. 2010;1(30):58-60. (in Ukrainian).
  19. Zubkova SТ. Treatment of primary hypothyroidism: ways to improve. Zdorov’ja Ukrai’ny. 2015;4(32):29-31. (in Russian).
  20. Mitchenko ОІ, Lohvynenko АО, Romanov VYu. Diurnal profile of blood pressure and structural-functional state of myocardium in patients with metabolic syndrome and thyroid dysfunction, treatment optimization. Ukrainian cardiology journal. 2010;4:70-7. (in Ukrainian).
  21. Olenych LV, Radchenko ОМ, Bek NS, Olenych LN. The peculiarities of kidney dysfunction in patients with arterial hypertension and obesity under hypothyroidism. Bukovinian Medical Herald. 2015;19(3):118-20. (in Ukrainian).
  22. Zerbino DD, Bagrij MM, Djadyk OO, et al. Vascular renal pathology: monography. Vinnycja: Nova knyga; 2015. 456 p. (in Ukrainian).
  23. Butrova SА. Visceral obesity as a key component of metabolic syndrome. Mezhdunarodnyi Endokrinologicheskii Zhurnal. 2009;2(20):82-4. (in Russian).
  24. Marusyn ОV, Bociurko VІ. Obesity and leptin resistance. Galician medical journal. 2012;19(1):155-7. (in Ukrainian).
  25. Pertseva ТА, Rokutova MK. Obesity and metabolic syndrome: relation to renal dysfunction. Urology. 2010;1:52-8. (in Russian). 
  26. Kryachkova AA, Savelyeva SA, Gallyamov MG, Shestakova MV, Kutiryna IM. The role of obesity in renal injury in patients with metabolic syndrome. Nefrologiia i dializ. 2010;12(1):34-8. (in Russian).
  27. Kutyrina IМ, Krуachkova АА, Savielieva SА. The role of hyperinsulinemia and insulin resistance in development of chronic kidney disease in patients with metabolic syndrome. Terapevticheskij arkhiv. 2012;84(6):32-6. (in Russian).
  28. Pertseva TO, Rokutova MK. Influence of insulin resistance on renal function in patients with abdominal obesity. Medicni perspektivi. 2015;20(2):30-6. (in Ukrainian).
  29. Pertseva TO, Rokutova MK, Tadgieva EI. The influence of cardiovascular risk factors on glomerular filtration rate in young patients with abdominal obesity. Urology. 2012;16(3(62)):38-44. (in Ukrainian).
  30. Saginova EA, Gallyamov MG, Severova MM, et al. The role of leptin, adiponectin and insulin-resistance markers in development of early stages of chronic kidney disease and atherosclerosis of carotid arteries in obese patients. Terapevticheskij arkhiv. 2011;83(6):47-53. (in Russian).
  31. Fedorova EU, Kutyrina IM. Mechanisms of progression of kidney injury in obesity. Nefrologiia i dializ. 2006;8(2):102-11. (in Russian).
  32. Petunina NА, Al`tshuler NE, Rakova NH, Trukhina LV. Hormones of the adipose tissue and functional activity of the thyroid. Obesity and metabolism. 2010;7(4):8-11. (in Russian).
  33. Zakharova SМ, Savielieva LV, Fadeeva MI. Obesity and hypothyroidism. Obesity and metabolism. 2013;2(35):54-8. (in Russian).
  34. Baig M, Azhar A, Zaidi P, Kamal S, Karira K. Serum leptin level in hypothyroid males. J Coll Physicians Surg Pak. 2005;15(12):757-60. doi: 12.2005/JCPSP.757760. 
  35. Nyrnes A, Jorde R, Sundsfjord J. Serum TSH is positively associated with BMI. Int J Obes (Lond). 2006 Jan;30(1):100-5. doi: 10.1038/sj.ijo.0803112. 
  36. Papafragkaki DK, Tolis G. Obesity and renal disease: A possible role of leptin. Hormones (Athens). 2005 Apr-Jun;4(2):90-5. PMID: 16613810.
  37. Korpachev VV, Kushnar’ova NM. Features of fatty-acid spectrum of triglycerides in patients with insulin resistance and metabolic syndrome. Lik Sprava. 2009 Oct-Dec;(7-8):50-5.
  38. Mitchenko OI, Logvinenko AO, Romanov VYu. Diurnal profile of blood pressure and structural-functional state of myocardium in patients with metabolic syndrome and thyroid dysfunction, treatment optimization. Ukrainian cardiology journal. 2010;4:70-7. (in Ukrainian). 
  39. Pan’kiv VІ. Practical thyroidology. Donetsk.: Publisher Zaslavskyi OYu; 2011. 224 p. (in Ukrainian).
  40. Mitchenko ОІ, Lutaj МІ. Dyslipidemia: diagnosis, prevention and treatment. Kyi’v: Chetverta hvylja; 2007. 56 p. (in Ukrainian). 
  41. Mitchenko ОІ, Lohvinenko АО, Romanov VYu. The optimisation of lipid and carbohydrate exchange correction in patients with metabolic syndrome and thyroid dysfunction. Ukrainian cardiology journal. 2010;1:73-80. (in Ukrainian).
  42. Kolina IB. Hyperlipidemia in chronic kidney disease: peculiarities and approaches to treatment. Lechashchii vrach. 2012;1:63-70. (in Russian).
  43. Loboda OM, Dudar IO. Dislipidemia in patients with chronic kidney disease. Ukrainian journal of nephrology and dialysis. 2014;2:50-61. (in Ukrainian).
  44. Calabia J, Torguet P, Garcia I. et al. The relationship between renal resistive index, arterial stiffness, and atherosclerotic burden: the link between macrocirculation and microcirculation. J Clin Hypertens (Greenwich). 2014 Mar;16(3):186-91. doi: 10.1111/jch.12248. Epub 2014 Feb 19. 

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