|Year : 2017 | Volume
| Issue : 2 | Page : 253-260
|Update on pathogenesis, management, and treatment of hypertension in autosomal dominant polycystic kidney disease
Imed Helal1, Fadel Al-Rowaie2, Ezzedine Abderrahim1, Adel Kheder1
1 Department of Medicine A (M8), Charles Nicolle Hospital; Laboratory of Kidney Pathology (LR00SP01), Charles Nicolle Hospital; Faculty of Medicine, University of Tunis El Manar, Tunis, Tunisia
2 Department of Nephrology, King Fahad Medical City, Riyadh, Saudi Arabia
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|Date of Web Publication||23-Mar-2017|
| Abstract|| |
Hypertension is a common early finding in autosomal dominant polycystic kidney disease (ADPKD). Improvements in screening and diagnosis of ADPKD have allowed earlier diagnosis, later onset of end-stage renal disease, and better survival. However, the main and most effective therapy remains control of hypertension. Hypertension is the most important modifiable risk factor in ADPKD. Therefore, early management of hypertension reduces the incidence of cardiovascular events in ADPKD patients. Stimulation of the renin–angiotensin–aldosterone system (RAAS) plays a central role in the pathogenesis of hypertension in ADPKD. Therapies that block the RAAS have improved patient management, blood pressure control, and ADPKD patient survival. This review highlights the current understanding of the epidemiology, potential pathogenetic mechanisms and proposes a strategy for the treatment and management of hypertension in ADPKD.
|How to cite this article:|
Helal I, Al-Rowaie F, Abderrahim E, Kheder A. Update on pathogenesis, management, and treatment of hypertension in autosomal dominant polycystic kidney disease. Saudi J Kidney Dis Transpl 2017;28:253-60
|How to cite this URL:|
Helal I, Al-Rowaie F, Abderrahim E, Kheder A. Update on pathogenesis, management, and treatment of hypertension in autosomal dominant polycystic kidney disease. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2018 Jun 18];28:253-60. Available from: http://www.sjkdt.org/text.asp?2017/28/2/253/202774
| Introduction|| |
Autosomal dominant polycystic kidney disease (ADPKD) is the most common, life-threatening single-gene disease in adults. It affects over 15 million people worldwide and is responsible for 5%–10% of end-stage renal disease (ESRD).,
Patients with ADPKD have an increased incidence of hypertension, left ventricular hypertrophy (LVH), and cardiovascular abnormalities., The reported relative mortality rate in patients with ADPKD is 1.6-fold [95% confidence interval (CI) 1.3–2.0] and 3.2-fold higher (95% CI 2–4.8) in comparison to the general population. Hypertension represents the most important modifiable risk factor of ADPKD Therefore, early and effective treatment of hypertension is very important to slow down kidney progression and decrease morbidity and mortality of ADPKD patients.
Recently, exciting molecular pathogenesis breakthrough and new treatments halting disease progression have been discovered. In this review, we highlight the current understanding of the epidemiology, potential pathogenetic mechanisms, and therapeutic strategies and propose an approach to the treatment and management of hypertension in ADPKD.
| Epidemiology of Hypertension in ADPKD|| |
Hypertension occurs early in the natural history of ADPKD, and in 50%–70%, it actually appears even before kidney function decline., However, the development of hypertension and its complications begins even earlier in the course of natural history of this disease. The median age at diagnosis of hypertension in ADPKD is 32 years for male and 34 years for female and occurs at an earlier age in comparison with general population. Young ADPKD patients have also significantly higher ambulatory blood pressure (BP) and left ventricular mass index than control population. Furthermore, hypertension occurs in 30% of children with ADPKD.,,,
Hypertension occurs earlier and more frequently in PKD1 than in PKD2, and with ADPKD patients whose parents have hypertension, whether they have ADPKD or not. Hypertension is more frequent and more severe in men than women. BP monitoring allows earlier diagnosis of hypertension and identifies nondipping circadian BP rhythm. Currently, ambulatory BP monitoring represents the best tool for the diagnosis and follow-up of patients with hypertension according to the new clinical guidelines, and we have to apply this recommendation to our ADPKD patients.
Patients with essential hypertension are less frequently affected by end-organ damage than hypertensive ADPKD patients. Other cardiovascular abnormalities such as LVH, early diastolic dysfunction, carotid intimal wall thickening, and impaired coronary flow velocity reserve have also been demonstrated in ADPKD., Therefore, a cardiovascular risk assessment must be systematic in ADPKD patients. However, lower incidence of LVH using cardiac magnetic resonance has recently been reported in HALT-PKD study. This low prevalence has been attributed to the high usage of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs).
Current published data confirm that patients with ADPKD in the United Sates,, Denmark, and Great Britain have a better prognosis than in the past. There has been an earlier diagnosis, better control of BP, more use of renin–angiotensin–aldosterone system (RAAS) inhibitors, better preservation of kidney function, later onset of ESRD, and better survival.,,, Early and effective treatment of hypertension is very important in patients with ADPKD to slow down renal failure progression and prevent the occurrence of cardiovascular events. This improved prognosis no doubt involves other factors in addition to the better control of BP.
| Pathogenesis of Hypertension in ADPKD|| |
Hypertension is common in most chronic kidney diseases (CKD). However, the pathogenesis is somewhat different in ADPKD. The pathogenesis of hypertension in ADPKD involves several interactive factors. Activation of the RAAS of the vascular dysfunction related to ciliopathy and other factors have all been found to be involved in the development of hypertension in ADPKD [Figure 1].
|Figure 1: Potential pathogenetic mechanisms of hypertension in ADPKD.|
ADPKD: Autosomal dominant polycystic kidney disease, RAAS: Renin–angiotensin–aldosterone system.
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Activation of the RAAS
The pathogenesis of hypertension in ADPKD patients is dominated by activation of RAAS. CRISP (the consortium for radiologic imaging studies of polycystic kidney disease) trial and other previous studies demonstrated that the decline of kidney function in ADPKD patients is directly related to progressive enlargement of multiple cysts.,,, It is believed that distortion of the renal parenchyma leads to structural damage, tubular dysfunction, and renal vascular ischemia and results in activation of the RAAS.
There are several explanations for the involvement of RAAS in the development of hypertension in ADPKD patients. Plasma renin activity and plasma aldosterone concentrations are higher the in supine and upright positions in patients with ADPKD compared with patients with essential hypertension matched for age, sex, kidney function, sodium intake, and degree of hypertension. All components of the RAAS have been identified in kidneys from patients with ADPKD. In addition, higher renin activity has been demonstrated in the cyst fluid.
The roles of vascular abnormalities in the pathogenesis of hypertension have been investigated. There is growing evidence confirming that GFR decline occurs after extensive vascular remodeling.,,,, Recently, several studies have demonstrated an altered intimamedia thickness of carotid arteries, impaired endothelial-dependent vascular relaxation and vascular ultrasound thickness in ADPKD 36,38-42 patients.
Recent studies have demonstrated that some proteins such as polycystin-1 and polycystin-2 are expressed in vascular smooth muscle cells., and play an important role in maintaining the integrity of dense plaques of the arterial wall. Histological study of specimens of cerebral aneurysms in ADPKD patients demonstrated an altered expression of polycystins in arterial smooth muscle cells. Furthermore, cardiovascular abnormalities were related to functional alteration of polycystins.,,, Evidence for endothelial dysfunction has been reported in both animal models and human studies of ADPKD.
Cilia are a local regulator of blood vessel. The alteration of cilia in ADPKD may be responsible for defective autoregulation of BP in ADPKD.,,,,,,
Other pathogenic factors are involved in ADPKD hypertension. Intrarenal ischemia/ hypoxia is increased which may affect renal tubular sodium handling and increases the activity of the sympathetic nervous system.
The chronic intrarenal ischemia and capsular stretch caused by cyst growth activate the renal sympathetic nervous system, potentially contributing to hypertension. Adrenaline and noradrenaline are significantly increased in ADPKD patients even when the kidney function is normal. Other factors that may contribute to the development of hypertension in ADPKD include insulin resistance.
| Treatment of Hypertension in ADPKD|| |
Currently, there is no effective treatment to slow down the progression of ADPKD but are some promising drugs under study. Hypertension is the most important modifiable risk factor in ADPKD. Early management of hypertension reduces the progression of kidney disease and onset of cardiovascular events.
An unresolved issue in ADPKD is the optimal BP for patients with hypertension. In patients with CKD, the goal is a BP of less than 130/80 mm Hg, based on NICE guidelines for hypertension published in 2011. However, other clinical practice guidelines differ on this recommendation. The 2013 ESH/ ESC guidelines for the management of arterial hypertension propose a target systolic BP (SBP) <140 mm Hg for patients with CKD and <130 mm Hg when overt proteinuria is present. The 2014 Evidence-based Guideline for the Management of High Blood Pressure in Adults (JNC 8) states that for patients with CKD, it is recommended that pharmacologic treatment is needed to lower BP at SBP <140 mm Hg or diastolic BP (DBP) <90 mm Hg and treat to goal SBP <140 mm Hg and goal DBP <90 mm Hg. Both clinical practice guidelines acknowledge that there is a lack of high-quality evidence. Until more evidence is available, in patients with ADPKD, we recommend adopting BP target of less than 130/80 mm Hg and should be pursued as soon as microalbuminuria or LVH is present.
Diet and lifestyle changes should be the first-line treatments for hypertensive ADPKD patients. Dietary salt restriction <6 g/day, avoidance of caffeine intake, smoking cessation, and maintenance of adequate fluid intake (3 L/day) should be recommended to all ADPKD patients. High water intake has been shown to decrease cyst growth in animal models and human studies by suppressing cAMP pathway.,
In addition to lifestyle changes, pharmacologic therapy is often necessary to control hypertension in ADPKD. Unfortunately, we do not have enough studies that examined the effect of hypertension control on kidney disease progression and occurrence of cardiovascular events. The HALT-PKD trial is a prospective randomized study to test whether dual blockade of the RAAS using ACEI and ARB combination therapy delay normal progression of kidney disease compared to ACEI monotherapy. The results have been published recently and showed that in the early stages of ADPKD, the dual inhibition of RAAS by a combination of ACEI and ARB did not significantly decrease the rate of total kidney volume growth. Rigorous BP control was associated with a slower rate of total kidney volume growth in comparison with standard BP control, a greater decline in the left ventricular mass index, and greater reduction in urinary albumin excretion. However, no effect on kidney function was observed. In later stages of ADPKD, monotherapy blockade of RAAS with an ACEI was associated with BP control in ADPKD patients with Stage 3 CKD. The addition of an ARB did not affect the kidney function progression.
Based on the current understanding of the pathogenesis of hypertension and results of clinical trials in ADPKD,,,,,,, we suggest that the optimal treatment of this disease is RAAS inhibitors with ACEI or ARBs. These agents remain the most recommended drugs to treat hypertension in patients with ADPKD although clinical studies have not convincingly demonstrated evident benefit.
We suggest the following treatment algorithm [Figure 2], an ACEI or ARB should be the initial antihypertensive agent. Careful monitoring is indicated in ADPKD patients at advanced stage of CKD after institution of a RAAS inhibitor or following an episode of volume depletion. Patients who develop a significant decline in renal function may be more safely treated with another agent such as a beta-blocker or calcium channel blocker; we prefer to use a beta blocker as a second agent given the potentially detrimental effects of calcium blockers on cyst formation.
|Figure 2: Treatment algorithm of hypertension in ADPKD.|
ADPKD: Autosomal dominant polycystic kidney disease, ACEI: Angiotensin-converting enzyme inhibitor, ARB: Angiotensin receptor blockers, CCB: Calcium channel blockers, BB: â-Blockers, BP: Blood pressure.
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Beta blockers and calcium channel blockers also reduce BP in ADPKD patients and are effective in those with concomitant cardiac disease, and as second line in those with uncontrolled hypertension under ACEI or ARBs. There is a sodium retention in ADPKD patients related to higher level of aldosterone than in patients with essential hypertension. Diuretics, used in conjunction with inhibitors of the RAAS, may be effective in reducing BP in ADPKD patients, particularly those with established CKD where the capacity to excrete sodium is reduced, and BP is maintained through intravascular volume expansion. In hypertensive ADPKD patients with normal kidney function, thiazide diuretics are the first choice. In those with impaired kidney function, long-acting loop diuretics must be the first choice. Diuretics should be considered as second- or third-line treatment in hypertensive ADPKD.
To the best of our knowledge, alpha blockers and direct vasodilators have not been tested and compared with RAAS inhibitors in ADPKD population.
| Conclusions|| |
Hypertension occurs early in ADPKD patients, even before impairment of renal function. Hypertension is associated with a faster progression to ESRD and represents the most important potentially treatable factor in ADPKD. Cardiovascular disease represents the first cause of death in ADPKD. Various animal and human studies confirm the important of RAAS in the genesis of hypertension in ADPKD. More prospective randomized studies are needed to determine the most appropriate agents for the treatment of hypertension in these patients.
Conflict of interest:
| References|| |
Iglesias CG, Torres VE, Offord KP, Holley KE, Beard CM, Kurland LT. Epidemiology of adult polycystic kidney disease, Olmsted County, Minnesota: 1935-1980. Am J Kidney Dis 1983;2:630-9.
U. S. Renal Data System: USRDS 2014 Annual Data Report; Chapter 1: Incidence, prevalence, patient characteristics, and treatment modalities, P103, 2014.
Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet 2007;369:1287-301.
Fick GM, Johnson AM, Hammond WS, Gabow PA. Causes of death in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1995;5:2048-56.
Helal I, Reed B, Mettler P, et al. Prevalence of cardiovascular events in patients with autosomal dominant polycystic kidney disease. Am J Nephrol 2012;36:362-70.
Florijn KW, Noteboom WM, van Saase JL, Chang PC, Breuning MH, Vandenbroucke JP. A century of mortality in five large families with polycystic kidney disease. Am J Kidney Dis 1995;25:370-4.
Bell PE, Hossack KF, Gabow PA, Durr JA, Johnson AM, Schrier RW. Hypertension in autosomal dominant polycystic kidney disease. Kidney Int 1988;34:683-90.
Chapman AB, Johnson A, Gabow PA, Schrier RW. The renin-angiotensin-aldosterone system and autosomal dominant polycystic kidney disease. N Engl J Med 1990;323:1091-6.
Schrier RW, Johnson AM, McFann K, Chapman AB. The role of parental hypertension in the frequency and age of diagnosis of hypertension in offspring with autosomal-dominant polycystic kidney disease. Kidney Int 2003;64:1792-9.
Kelleher CL, McFann KK, Johnson AM, Schrier RW. Characteristics of hypertension in young adults with autosomal dominant polycystic kidney disease compared with the general U.S. population. Am J Hypertens 2004;17(11 Pt 1):1029-34.
Zeier M, Geberth S, Schmidt KG, Mandelbaum A, Ritz E. Elevated blood pressure profile and left ventricular mass in children and young adults with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1993;3: 1451-7.
Sedman A, Bell P, Manco-Johnson M, et al. Autosomal dominant polycystic kidney disease in childhood: A longitudinal study. Kidney Int 1987;31:1000-5.
Fick GM, Duley IT, Johnson AM, Strain JD, Manco-Johnson ML, Gabow PA. The spectrum of autosomal dominant polycystic kidney disease in children. J Am Soc Nephrol 1994;4: 1654-60.
Ivy DD, Shaffer EM, Johnson AM, Kimberling WJ, Dobin A, Gabow PA. Cardiovascular abnormalities in children with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1995;5:2032-6.
Shamshirsaz AA, Reza Bekheirnia M, Kamgar M, et al. Autosomal-dominant polycystic kidney disease in infancy and childhood: Progression and outcome. Kidney Int 2005;68:2218-24.
Handa SP. Cardiovascular manifestations of autosomal dominant polycystic kidney disease in young adults. Clin Invest Med 2006;29:339-46.
Ritchie LD, Campbell NC, Murchie P. New NICE guidelines for hypertension. BMJ 2011;343:d5644.
Chapman AB, Johnson AM, Rainguet S, Hossack K, Gabow P, Schrier RW. Left ventricular hypertrophy in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1997;8:1292-7.
Oflaz H, Alisir S, Buyukaydin B, et al. Biventricular diastolic dysfunction in patients with autosomal-dominant polycystic kidney disease. Kidney Int 2005;68:2244-9.
Schrier RW. Renal volume, renin–angiotensin–aldosterone system, hypertension, and left ventricular hypertrophy in patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2009;20:1888-93.
Perrone RD, Abebe KZ, Schrier RW, et al. Cardiac magnetic resonance assessment of left ventricular mass in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 2011;6:2508-15.
Schrier RW, McFann KK, Johnson AM. Epidemiological study of kidney survival in autosomal dominant polycystic kidney disease. Kidney Int 2003;63:678-85.
Helal I, McFann K, Reed B, Yan XD, Schrier RW. Changing referral characteristics of patients with autosomal dominant polycystic kidney disease. Am J Med 2013;126(9): 832.e7-e11.
Orskov B, Rømming Sørensen V, Feldt-Rasmussen B, Strandgaard S. Improved prognosis in patients with autosomal dominant polycystic kidney disease in Denmark. Clin J Am Soc Nephrol 2010;5:2034-9.
Patch C, Charlton J, Roderick PJ, Gulliford MC. Use of antihypertensive medications and mortality of patients with autosomal dominant polycystic kidney disease: A population-based study. Am J Kidney Dis 2011;57:856-62.
Tkachenko O, Helal I, Shchekochikhin D, Schrier RW. Renin-Angiotensin-aldosterone system in autosomal dominant polycystic kidney disease. Curr Hypertens Rev 2013;9: 12-20.
Chapman AB, Guay-Woodford LM, Grantham JJ, et al. Renal structure in early autosomal-dominant polycystic kidney disease (ADPKD): The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) cohort. Kidney Int 2003;64:1035-45.
Lee YR, Lee KB. Reliability of magnetic resonance imaging for measuring the volumetric indices in autosomal-dominant polycystic kidney disease: Correlation with hypertension and renal function. Nephron Clin Pract 2006;103:c173-80.
Grantham JJ, Cook LT, Torres VE, et al. Determinants of renal volume in autosomal-dominant polycystic kidney disease. Kidney Int 2008;73:108-16.
Grantham JJ, Torres VE, Chapman AB, et al. Volume progression in polycystic kidney disease. N Engl J Med 2006;354:2122-30.
Loghman-Adham M, Soto CE, Inagami T, Cassis L. The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease. Am J Physiol Renal Physiol 2004;287:F775-88.
Zeier M, Ritz E, Geberth S, Gonzalo A. Genesis and significance of hypertension in autosomal dominant polycystic kidney disease. Nephron 1994;68:155-8.
Azurmendi PJ, Fraga AR, Galan FM, et al. Early renal and vascular changes in ADPKD patients with low-grade albumin excretion and normal renal function. Nephrol Dial Transplant 2009;24:2458-63.
Itty CT, Farshid A, Talaulikar G. Spontaneous coronary artery dissection in a woman with polycystic kidney disease. Am J Kidney Dis 2009;53:518-21.
Rong S, Jin X, Ye C, Chen J, Mei C. Carotid vascular remodelling in patients with autosomal dominant polycystic kidney disease. Nephrology (Carlton) 2009;14:113-7.
Sawicki M, Walecka A, Rozanski J, Safranow K, Ciechanowski K. Doppler sonography measurements of renal vascular resistance in autosomal-dominant polycystic kidney disease. Med Sci Monit 2009;15:MT101-4.
Turkmen K, Oflaz H, Uslu B, et al. Coronary flow velocity reserve and carotid intima media thickness in patients with autosomal dominant polycystic kidney disease: From impaired tubules to impaired carotid and coronary arteries. Clin J Am Soc Nephrol 2008;3:986-91.
Ecder T, Schrier RW. Cardiovascular abnormalities in autosomal-dominant polycystic kidney disease. Nat Rev Nephrol 2009;5:221-8.
Reed BY, Masoumi A, Elhassan E, et al. Angiogenic growth factors correlate with disease severity in young patients with autosomal dominant polycystic kidney disease. Kidney Int 2011;79:128-34.
Kocaman O, Oflaz H, Yekeler E, et al. Endothelial dysfunction and increased carotid intima-media thickness in patients with autosomal dominant polycystic kidney disease. Am J Kidney Dis 2004;43:854-60.
Persu A, Stoenoiu MS, Messiaen T, et al. Modifier effect of ENOS in autosomal dominant polycystic kidney disease. Hum Mol Genet 2002;11:229-41.
Wang D, Iversen J, Strandgaard S. Endothelium-dependent relaxation of small resistance vessels is impaired in patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2000;11:1371-6.
Griffin MD, Torres VE, Grande JP, Kumar R. Vascular expression of polycystin. J Am Soc Nephrol 1997;8:616-26.
Torres VE, Cai Y, Chen X, et al. Vascular expression of polycystin-2. J Am Soc Nephrol 2001;12:1-9.
Qian Q, Li M, Cai Y, et al. Analysis of the polycystins in aortic vascular smooth muscle cells. J Am Soc Nephrol 2003;14:2280-7.
Boulter C, Mulroy S, Webb S, Fleming S, Brindle K, Sandford R. Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene. Proc Natl Acad Sci U S A 2001;98:12174-9.
Kim K, Drummond I, Ibraghimov-Beskrovnaya O, Klinger K, Arnaout MA. Polycystin 1 is required for the structural integrity of blood vessels. Proc Natl Acad Sci U S A 2000; 97:1731-6.
Muto S, Aiba A, Saito Y, et al. Pioglitazone improves the phenotype and molecular defects of a targeted Pkd1 mutant. Hum Mol Genet 2002;11:1731-42.
Wu G, Markowitz GS, Li L, et al. Cardiac defects and renal failure in mice with targeted mutations in Pkd2. Nat Genet 2000;24:75-8.
Klawitter J, Reed-Gitomer BY, McFann K, et al. Endothelial dysfunction and oxidative stress in polycystic kidney disease. Am J Physiol Renal Physiol 2014;307:F1198-206.
AbouAlaiwi WA, Takahashi M, Mell BR, et al. Ciliary polycystin-2 is a mechanosensitive calcium channel involved in nitric oxide signaling cascades. Circ Res 2009;104:860-9.
Nauli SM, Kawanabe Y, Kaminski JJ, Pearce WJ, Ingber DE, Zhou J. Endothelial cilia are fluid shear sensors that regulate calcium signaling and nitric oxide production through polycystin-1. Circulation 2008;117:1161-71.
Hierck BP, Van der Heiden K, Alkemade FE, et al. Primary cilia sensitize endothelial cells for fluid shear stress. Dev Dyn 2008;237:725-35.
Poelmann RE, Van der Heiden K, Gittenberger-de Groot A, Hierck BP. Deciphering the endothelial shear stress sensor. Circulation 2008;117:1124-6.
Van der Heiden K, Groenendijk BC, Hierck BP, et al. Monocilia on chicken embryonic endocardium in low shear stress areas. Dev Dyn 2006;235:19-28.
Van der Heiden K, Hierck BP, Krams R, et al. Endothelial primary cilia in areas of disturbed flow are at the base of atherosclerosis. Atherosclerosis 2008;196:542-50.
Greisen G. Autoregulation of cerebral blood flow in newborn babies. Early Hum Dev 2005;81:423-8.
Eckardt KU, Mollmann M, Neumann R, et al. Erythropoietin in polycystic kidneys. J Clin Invest 1989;84:1160-6.
Cerasola G, Vecchi M, Mulè G, et al. Sympathetic activity and blood pressure pattern in autosomal dominant polycystic kidney disease hypertensives. Am J Nephrol 1998;18:391-8.
Lumiaho A, Pihlajamäki J, Hartikainen J, et al. Insulin resistance is related to left ventricular hypertrophy in patients with polycystic kidney disease type 1. Am J Kidney Dis 2003;41: 1219-24.
Torres VE, Chapman AB, Devuyst O, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 2012;367:2407-18.
Torres VE, Bankir L, Grantham JJ. A case for water in the treatment of polycystic kidney disease. Clin J Am Soc Nephrol 2009;4:1140-50.
Barash I, Ponda MP, Goldfarb DS, Skolnik EY. A pilot clinical study to evaluate changes in urine osmolality and urine cAMP in response to acute and chronic water loading in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 2010;5:693-7.
Chapman AB, Torres VE, Perrone RD, et al. The HALT polycystic kidney disease trials: Design and implementation. Clin J Am Soc Nephrol 2010;5:102-9.
Schrier RW, Abebe KZ, Perrone RD, et al. Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med 2014;371:2255-66.
Torres VE, Abebe KZ, Chapman AB, et al. Angiotensin blockade in late autosomal dominant polycystic kidney disease. N Engl J Med 2014;371:2267-76.
Keith DS, Torres VE, Johnson CM, Holley KE. Effect of sodium chloride, enalapril, and losartan on the development of polycystic kidney disease in Han:SPRD rats. Am J Kidney Dis 1994;24:491-8.
Schrier R, McFann K, Johnson A, et al. Cardiac and renal effects of standard versus rigorous blood pressure control in autosomal-dominant polycystic kidney disease: Results of a seven-year prospective randomized study. J Am Soc Nephrol 2002;13:1733-9.
Ecder T, Chapman AB, Brosnahan GM, Edelstein CL, Johnson AM, Schrier RW. Effect of antihypertensive therapy on renal function and urinary albumin excretion in hypertensive patients with autosomal dominant polycystic kidney disease. Am J Kidney Dis 2000;35:427-32.
Nutahara K, Higashihara E, Horie S, et al. Calcium channel blocker versus angiotensin II receptor blocker in autosomal dominant polycystic kidney disease. Nephron Clin Pract 2005;99:c18-23.
van Dijk MA, Breuning MH, Duiser R, van Es LA, Westendorp RG. No effect of enalapril on progression in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 2003;18:2314-20.
Zeltner R, Poliak R, Stiasny B, Schmieder RE, Schulze BD. Renal and cardiac effects of antihypertensive treatment with ramipril vs metoprolol in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 2008;23:573-9.
Ecder T, Edelstein CL, Fick-Brosnahan GM, et al. Progress in blood pressure control in autosomal dominant polycystic kidney disease. Am J Kidney Dis 2000;36:266-71.
Department of Medicine A (M8), Charles Nicolle Hospital, Tunis
[Figure 1], [Figure 2]
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