**6. References**


ACE inhibitors showed several adverse effects in HDD-CKD patients. High-dose ACE inhibitors suppressed erythropoiesis and induced resistance to erythropoietin therapy in HDD-CKD patients. Occasionally, ACE inhibitors may cause anaphylactoid reactions with AN69 dialysis membrane in HDD-CKD patients by elevation of bradykinin level (Kammerl *et al.*, 2000). Hyperkalemia, which is a frequent concern in HDD-CKD patients independently of medication use, is the primary danger from RAAS blocking medications. Several clinical trials of ACE inhibitors, ARBs, and renin inhibitor in HDD-CKD patients tracked potassium levels. Increased hyperkalemia by these RAAS blockers in HDD-CKD patients was not observed in these trials. These results suggested that the risk of

From previous studies, it is suggested that RAAS blockade has a beneficial effect in controlling BP and preventing CVD in DD-CKD patients. However, the choice of the RAAS inhibitor as well as its use in the treatment of DD-CKD patients have to be carefully determined considering the possible adverse effects and potential interactions with other drugs being used in the treatment of DD-CKD patients. Further studies with an adequate sample size and a thorough design are still needed to determine the effect of RAAS blockade

Some parts of this manuscript were reported in Cardiovascular & Hematological Agents in Medical Chemistry (submitted), Hypertension Research (2011), 34, 308-313 and Clinical

Agarwal, R., Nissenson, A.R., Batlle, D., Coyne, D.W., Trout, J.R., Warnock, D.G., 2003.

Agarwal, R., Sinha, A.D., 2009. Cardiovascular protection with antihypertensive drugs in dialysis patients: systematic review and meta-analysis. Hypertension 53, 860-866. Austin, E.W., Parrish, J.M., Kinder, D.H., Bull, R.J., 1996. Lipid peroxidation and formation

Blankestijn, P.J., Ligtenberg, G., 2004. Volume-independent mechanisms of hypertension in

Collins, A.J., Roberts, T.L., St Peter, W.L., Chen, S.C., Ebben, J., Constantini, E., 2002. United

hemodialysis patients: clinical implications. Semin Dial 17, 265-269.

Prevalence, treatment, and control of hypertension in chronic hemodialysis patients

of 8-hydroxydeoxyguanosine from acute doses of halogenated acetic acids.

States Renal Data System assessment of the impact of the National Kidney Foundation-Dialysis Outcomes Quality Initiative guidelines. Am J Kidney Dis 39,

**3.4 Adverse effects of RAAS blockers in DD-CKD patients** 

hyperkalemia by RAAS blocking is small.

**5. Conflict of interest statement** 

Experimental Nephrology(2011), 15, 398-404.

Fundam Appl Toxicol 31, 77-82.

in the United States. Am J Med 115, 291-297.

**4. Conclusion** 

on DD-CKD patients.

None declared

**6. References** 

784-795.


renin-angiotensin system: further mechanisms of angiotensin II-induced inflammation. J Am Soc Nephrol 18, 1093-1102.

The Renin-Angiotensin-Aldosterone System in Dialysis Patients 123

Morishita, Y., Hanawa, S., Miki, T., Sugase, T., Sugaya, Y., Chinda, J., Iimura, O.,

Nussberger, J., Wuerzner, G., Jensen, C., Brunner, H.R., 2002. Angiotensin II suppression in

Prescott, G., Silversides, D.W., Reudelhuber, T.L., 2002. Tissue activity of circulating

Racki, S., Zaputovic, L., Mavric, Z., Vujicic, B., Dvornik, S., 2006. C-reactive protein is a strong predictor of mortality in hemodialysis patients. Ren Fail 28, 427-433. Sadoshima, J., Izumo, S., 1993. Molecular characterization of angiotensin II--induced

Saracho, R., Martin-Malo, A., Martinez, I., Aljama, P., Montenegro, J., 1998. Evaluation of the Losartan in Hemodialysis (ELHE) Study. Kidney Int Suppl 68, S125-129. Schaefer, R.M., Schaefer, L., Horl, W.H., 1994. Anaphylactoid reactions during hemodialysis.

Shibasaki, Y., Masaki, H., Nishiue, T., Nishikawa, M., Matsubara, H., Iwasaka, T., 2002.

ventricular hypertrophy in end-stage renal disease. Nephron 90, 256-261. Siragy, H.M., 2000. AT(1) and AT(2) receptors in the kidney: role in disease and treatment.

Suzuki, H., Kanno, Y., Sugahara, S., Ikeda, N., Shoda, J., Takenaka, T., Inoue, T., Araki, R.,

Suzuki, H., Kanno, Y., Sugahara, S., Okada, H., Nakamoto, H., 2004. Effects of an

Takahashi, A., Takase, H., Toriyama, T., Sugiura, T., Kurita, Y., Ueda, R., Dohi, Y., 2006.

Takemitsu, T., Ichihara, A., Kaneshiro, Y., Sakoda, M., Kurauchi-Mito, A., Narita, T.,

Tarng, D.C., Huang, T.P., Wei, Y.H., Liu, T.Y., Chen, H.W., Wen Chen, T., Yang, W.C., 2000.

Vaidyanathan, S., Bigler, H., Yeh, C., Bizot, M.N., Dieterich, H.A., Howard, D., Dole, W.P.,

chronic hemodialysis patients. Am J Kidney Dis 36, 934-944.

hypertension. Hypertens Res 34, 308-313.

patients. Clin Exp Nephrol 15, 398-404.

prorenin. Am J Hypertens 15, 280-285.

role of the AT1 receptor subtype. Circ Res 73, 413-423.

enalapril. Hypertension 39, E1-8.

Clin Nephrol 42 Suppl 1, S44-47.

CAPD. Am J Kidney Dis 43, 1056-1064.

human artery. Am J Nephrol 30, 361-370.

Am J Kidney Dis 36, S4-9.

Transplant 21, 2507-2512.

Dis 52, 501-506.

disease in hemodialysis-dependent chronic kidney disease patients with

Tsunematsu, S., Ishibashi, K., Kusano, E., 2011b. The association of plasma prorenin level with an oxidative stress marker, 8-OHdG, in nondiabetic hemodialysis

humans by the orally active renin inhibitor Aliskiren (SPP100): comparison with

hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical

Angiotensin II type 1 receptor antagonist, losartan, causes regression of left

2008. Effect of angiotensin receptor blockers on cardiovascular events in patients undergoing hemodialysis: an open-label randomized controlled trial. Am J Kidney

angiotensin II receptor blocker, valsartan, on residual renal function in patients on

Candesartan, an angiotensin II type-1 receptor blocker, reduces cardiovascular events in patients on chronic haemodialysis--a randomized study. Nephrol Dial

Kinouchi, K., Yamashita, N., Itoh, H., 2009. Association of (pro)renin receptor mRNA expression with angiotensin-converting enzyme mRNA expression in

8-hydroxy-2'-deoxyguanosine of leukocyte DNA as a marker of oxidative stress in

2007. Pharmacokinetics of the oral direct renin inhibitor aliskiren alone and in combination with irbesartan in renal impairment. Clin Pharmacokinet 46, 661-675.


Kammerl, M.C., Schaefer, R.M., Schweda, F., Schreiber, M., Riegger, G.A., Kramer, B.K.,

Kanno, Y., Kaneko, K., Kaneko, M., Kotaki, S., Mimura, T., Takane, H., Suzuki, H., 2004.

Kimura, G., Takahashi, N., Kawano, Y., Inenaga, T., Inoue, T., Nakamura, S., Matsuoka, H.,

Kohagura, K., Higashiuesato, Y., Ishiki, T., Yoshi, S., Ohya, Y., Iseki, K., Takishita, S., 2006.

Krop, M., Danser, A.H., 2008. Circulating versus tissue renin-angiotensin system: on the

Kupfahl, C., Pink, D., Friedrich, K., Zurbrugg, H.R., Neuss, M., Warnecke, C., Fielitz, J., Graf,

Landomesser, U., Drexler, H., 2003. oxidative stress, the renin-angiotensin system, and

Lenz, T., Sealey, J.E., Maack, T., James, G.D., Heinrikson, R.L., Marion, D., Laragh, J.H., 1991.

Leung, P.S., Wong, T.P., Lam, S.Y., Chan, H.C., Wong, P.Y., 2000. Testicular hormonal

London, G.M., Pannier, B., Guerin, A.P., Marchais, S.J., Safar, M.E., Cuche, J.L., 1994. Cardiac

Macdougall, I.C., 1999. The role of ACE inhibitors and angiotensin II receptor blockers in the

Matsumoto, N., Ishimitsu, T., Okamura, A., Seta, H., Takahashi, M., Matsuoka, H., 2006.

Methot, D., Silversides, D.W., Reudelhuber, T.L., 1999. In vivo enzymatic assay reveals catalytic activity of the human renin precursor in tissues. Circ Res 84, 1067-1072. Mimran, A., Shaldon, S., Barjon, P., Mion, C., 1978. The effect of an angiotensin antagonist

Morishita, Y., Hanawa, S., Chinda, J., Iimura, O., Tsunematsu, S., Kusano, E., 2011a. Effects

response to epoetin. Nephrol Dial Transplant 14, 1836-1841.

determinants and impact on survival. Hypertens Res 29, 597-604.

mRNA expression in the human heart. Cardiovasc Res 46, 463-475.

origin of (pro)renin. Curr Hypertens Rep 10, 112-118.

atherosclerosis. european heart journal 5, A3-A7.

monkeys. Am J Physiol 260, R804-810.

blockade. Circulation 90, 2786-2796.

hypertensive patients. Clin Nephrol 9, 63-67.

Hypertens Res 29, 253-260.

1324.

inflammation. J Am Soc Nephrol 18, 1093-1102.

follow-up. Am J Kidney Dis 25, 589-592.

Nephrol 53, 486-488.

renin-angiotensin system: further mechanisms of angiotensin II-induced

2000. Extracorporal therapy with AN69 membranes in combination with ACE inhibition causing severe anaphylactoid reactions: still a current problem? Clin

Angiotensin receptor antagonist regresses left ventricular hypertrophy associated with diabetic nephropathy in dialysis patients. J Cardiovasc Pharmacol 43, 380-386.

Omae, T., 1995. Plasma renin activity in hemodialyzed patients during long-term

Plasma aldosterone in hypertensive patients on chronic hemodialysis: distribution,

K., Fleck, E., Regitz-Zagrosek, V., 2000. Angiotensin II directly increases transforming growth factor beta1 and osteopontin and indirectly affects collagen

Half-life, hemodynamic, renal, and hormonal effects of prorenin in cynomolgus

regulation of the renin-angiotensin system in the rat epididymis. Life Sci 66, 1317-

hypertrophy, aortic compliance, peripheral resistance, and wave reflection in endstage renal disease. Comparative effects of ACE inhibition and calcium channel

Effects of imidapril on left ventricular mass in chronic hemodialysis patients.

(saralasin) on arterial pressure and plasma aldosterone in hemodialysis-resistant

of aliskiren on blood pressure and the predictive biomarkers for cardiovascular

disease in hemodialysis-dependent chronic kidney disease patients with hypertension. Hypertens Res 34, 308-313.


van Ampting, J.M., Penne, E.L., Beek, F.J., Koomans, H.A., Boer, W.H., Beutler, J.J., 2003. Prevalence of atherosclerotic renal artery stenosis in patients starting dialysis. Nephrol Dial Transplant 18, 1147-1151.

**8** 

*Turkey*

**Diagnosis and Treatment** 

Ozlem Tiryaki\* and Celalettin Usalan

 **of Primary Aldosteronism** 

*Gaziantep University School of Medicine, Department of Nephrology* 

Primary aldosteronism (PAL) is a clinical disorder characterized by excessive production and release of aldosterone from the cortical zona glomerulosa of the adrenal gland. The high level of circulating aldosterone increases sodium reabsorption with potassium loss in the distal tubule, leading to mild hypernatremia, hypertension (HTN), severe hypokalemia, and alkalosis. 1,2 Primary aldosteronism, as originally described by Conn in the 1950s.3,4 (PAL)is characterized by an increased secretion of aldosterone that seems to be autonomous of the renin–angiotensin system, as the secretion of renin is suppressed. PAL represents the most common form of secondary hypertension.5,6 In recent years, the large- scale hypertension trials, It is now widely recognized that PAL is much more common than previously thought, being present in up to 5–13% of unselected hypertensive patients7 and in resistant HTN (BP above goal with three or more antihypertensive medications) with a reported prevalence of 20% to 23% in this group of patients.5,8 As older age and obesity are 2 of the strongest risk factors for uncontrolled hypertension, the incidence of resistant hypertension will likely increase as the population becomes more elderly and heavier. The prognosis of resistant hypertension is unknown, but cardiovascular risk is undoubtedly increased as patients often have a history of long-standing, severe hypertension complicated by multiple other cardiovascular risk factors such as obesity, sleep apnea, diabetes, and chronic kidney disease.5 In ALLHAT, older age, higher baseline systolic blood pressure, LVH, and obesity all predicted treatment resistance as defined by needing 2 or more antihypertensive medications. Overall, the strongest predictor of treatment resistance was having CKD as defined by a serum creatinine of ≥1.5 mg/dL. Other predictors of the need for multiple medications included having diabetes mellitus and living in the southeastern United States. African-American participants had more treatment resistance, as did women, such that black women had the lowest control rate (59%) and non-black men the highest (70%).8 Furthermore, experimental and clinical studies showed that excess aldosterone has detrimental effects on the heart, brain and kidneys that are partly hypertensionindependent.9 Patients diagnosed with PAL, compared with patients with essential hypertension seems to increase the left ventricular wall thickness.10 In addition, aldosterone excess appears to independently increase the risk of cardiac fibrosis.11 Likewise, mineralocorticoid receptor blockage has been showed to diminish the effects of aldosterone

**1. Introduction** 

 \*

Corresponding Author

