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of cases the diagnosis is performed before any renal function impairment appears&#46; It seems that the increase in kidney size<span class="elsevierStyleSup">5-7 </span>and the activity in the renin-angiotensin-aldosterone system<span class="elsevierStyleSup">8-10 </span>are primarily responsible for the development of hypertension in these patients&#46; Studies in patients with ADPKD and normal renal function have shown the presence of target organ damage &#40;increased left ventricular mass&#41;<span class="elsevierStyleSup">11&#44;12 </span>before developing AHT&#46; This damage appears to be related more to the increase in systolic blood pressure &#40;SBP&#41; determined by ambulatory blood pressure monitoring &#40;ABPM&#41; than to the blood pressure &#40;BP&#41; measured at the clinic&#46;<span class="elsevierStyleSup">12 </span></p><p class="elsevierStylePara">Twenty-four hour ABPM adds additional information to the BP measurements in the clinic &#40;BPc&#41; as it reports on the circadian rhythm and the variability of the BP&#46; Furthermore&#44; it identifies patients with masked hypertension &#40;normal clinic BP and high ambulatory BP&#41; and isolated clinic hypertension &#40;high BP readings in the clinic and normal ambulatory BP&#41;&#46; A non-physiological BP profile &#40;non&#173;dipper nocturnal pattern&#41;&#44; a greater BP variability &#40;average of standard deviations over 24 hours greater than 18 mmHg for SBP or greater than 15mmHg for DBP&#41; and the presence of masked or isolated clinic hypertension have been related to greater cardiovascular risk&#46;<span class="elsevierStyleSup">13-17 </span></p><p class="elsevierStylePara">Therefore&#44; although hypertension is a key factor in cardiovascular morbidity and mortality in patients with polycystic disease&#44; little is known about the pre-hypertensive stage&#46; In addition&#44; it is not known whether the increase in kidney size could be associated with a change in the BP profile and its variability&#46; We therefore decided to evaluate the following points in patients with normotensive ADPKD <span class="elsevierStyleItalic">a priori </span>and with eGF by MDRD &#62;60 mL&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#58;</p><p class="elsevierStylePara">1&#46;&#160;&#160;&#160; Whether there are differences between the BPc and the ABPM readings&#46;</p><p class="elsevierStylePara">2&#46;&#160;&#160;&#160; The relationship between maximum kidney diameter and SBP&#44; DBP and mean BP &#40;MBP&#41; over 24 hours&#44; day and night&#44; and pulse pressure &#40;PP&#41; obtained by 24-hour ABPM&#46;</p><p class="elsevierStylePara">3&#46;&#160;&#160;&#160; If there is a relationship between maximum kidney diameter and the variability of BP or the circadian BP pattern&#46;</p><p class="elsevierStylePara">&#160;</p><ul> </ul><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHODS </span></p><p class="elsevierStylePara">We performed a transversal&#44; observational study that included 37 patients with ADPKD from those who visited outpatient clinics&#44; who were between the ages of 18 and 50 years&#44; with eGF by MDRD &#62;60 mL&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2 </span>and who were normotensive &#40;patients with home BP &#60;135&#47;85 mmHg and not receiving treatment for hypertension&#41;&#46;</p><p class="elsevierStylePara">The following information was collected from these 37 patients&#58;</p><p class="elsevierStylePara">1&#46; Three readings of SBP and DBP with the OMRON 705 IT blood pressure monitor &#40;Tokyo&#44; Japan&#41;&#44; following the standard for BPc readings of the European Society of Hypertension &#40;ESH&#41;&#44;<span class="elsevierStyleSup">18 </span>using the average of three readings as the clinical BP value&#46;</p><p class="elsevierStylePara">2&#46; ABPM data &#40;via the Dyasis Integra device&#41; &#40;Rueil-Malmaison&#44; France&#41;&#46;</p><p class="elsevierStylePara">- SBP&#44; DBP and MBP &#40;DBP &#43; 1&#47;3 pulse pressure &#40;PP&#41; &#40;PP &#61; SBP &#8211; DBP&#41; during the day&#44; night and over 24 hours&#46; Heart rate and 24-hour PP&#46;</p><p class="elsevierStylePara">- Percentage of nocturnal BP decrease with respect to the daytime SBP&#44; DBP and MBP and quality of sleep on the ABPM date&#46;</p><p class="elsevierStylePara">- Load index &#40;percentage of BP measurements above the established target BP&#41; for SBP and DBP during the day&#44; night and over 24 hours&#46;</p><p class="elsevierStylePara">- Typical or standard deviation of the average SBP and DBP during the day&#44; night and over 24 hours&#46; Maximum daytime&#44; nightime and 24-hour SBP and DBP&#46;</p><p class="elsevierStylePara">3&#46; Anthropometric data&#58; weight&#44; height&#44; body surface area and body mass index&#46;</p><p class="elsevierStylePara">4&#46; Mean maximum diameter of both kidneys &#40;in millimetres&#41; by renal ultrasound performed by ultrasound specialists who are expert in renovesical ultrasound&#44; using a single measure&#46;</p><p class="elsevierStylePara">According to the ABPM readings and following the recommendation in the 2007 ESH Guidelines&#44;<span class="elsevierStyleSup">18 </span>patients are consider normotensive if they present a SBP &#60;130 mmHg and a DBP &#60;80 mmHG by ABPM over 24 hours&#46;</p><p class="elsevierStylePara">The percentage of decrease in nocturnal MBP versus daytime MBP allows us to classify patients according to their BP profile&#58;</p><p class="elsevierStylePara">1&#46; Non-dipper pattern&#58; nocturnal MBP decrease versus daytime MBP less than 10&#37;&#46;</p><p class="elsevierStylePara">2&#46; Dipper pattern&#58; nocturnal MBP decrease versus daytime MBP between 10 and 20&#37;&#46;</p><p class="elsevierStylePara">3&#46; Riser pattern&#58; nocturnal MBP higher than daytime MBP&#46;</p><p class="elsevierStylePara">4&#46; Extreme dipper pattern&#58; nocturnal MBP decrease versus daytime MBP greater than 20&#37;&#46; The circadian profile was not assessed if the patient reported suffering from a bad night&#8217;s sleep&#46;</p><p class="elsevierStylePara">Considering the BP readings obtained from the ABPM and the BPc&#44; we can classify the patients into four groups&#58;</p><p class="elsevierStylePara">1&#46; White coat AHT&#58; patients with high BPc &#40;&#40;&#62;140&#47;90 mmHg&#41; and BP by ABPM over 24 hours &#60;130&#47;80 mmHg&#46;</p><p class="elsevierStylePara">2&#46; Masked AHT&#58; patients with normal BPc &#40;&#60;140&#47;90 mmHg&#41; and high BP by ABPM over 24 hours &#40;&#40;&#62;130&#47;80 mmHg&#41;&#46;</p><p class="elsevierStylePara">3&#46; True AHT&#58; patients with high BPc and BP by ABPM over 24 hours&#46;</p><p class="elsevierStylePara">4&#46; True normotensives&#58; patients with normal BPc and BP by ABPM over 24 hours&#46;</p><p class="elsevierStylePara">The statistical analysis was carried out with the SPSS software&#46; The results are expressed as the mean &#177; standard deviation &#40;SD&#41; for the continuously distributed variables and as frequencies for the categorical variables&#46;</p><p class="elsevierStylePara">Given the small sample size&#44; the normal distribution of variables was studied using the Kolmogorov-Smirnov and Shapiro-Wilks tests&#46; After verifying the normality of the variables&#44; the Student&#8217;s t-test was used to compare samples with two categories and ANOVA was used for those with three or more categories&#46; For the non-parametric variables&#44; the Mann-Whitney and Kruskall-Wallis tests were used depending on whether they had two or more categories&#46;</p><p class="elsevierStylePara">To study the association between the mean maximum kidney diameter and the various data provided by the ABPM&#44; the linear Pearson correlation coefficient was used&#46; The distribution of categorical variables was analysed by means of the chi-squared test&#46; A p less than 0&#46;05 was considered statistically significant&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Blood pressure classification according to BP values obtained in the clinic and by ambulatory blood pressure monitoring </span></p><p class="elsevierStylePara">The 37 patients included were classified into four groups according to the BP obtained in the clinic and through 24-hour ABPM&#46; Of these&#44; 13 were true normotensives &#40;35&#46;1&#37;&#41;&#44; 9 were true hypertensives &#40;24&#46;3&#37;&#41;&#44; 4 patients had white coat hypertension &#40;10&#46;8&#37;&#41; and the remaining 11 &#40;29&#46;7&#37;&#41; had masked hypertension &#40;Table 1&#41;&#46;</p><p class="elsevierStylePara">Taking into account the average BP by ABPM over 24 hours and hypertension being diagnosed for a SBP &#62;130 mmHg or a DBP &#62;80 mmHg&#44; 20 of the 37 patients &#40;54&#37;&#41; initially selected as normotensives according to the home BP readings were diagnosed with AHT&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Relationship between kidney size and blood pressure characteristics </span></p><p class="elsevierStylePara">There is currently no standard of normality in relation to maximum kidney diameter in the general population but it is known that the maximum kidney diameter is correlated with height&#44;<span class="elsevierStyleSup">19 </span>which was coherent with our population &#40;r &#61; 0&#46;572&#44; p &#61; 0&#46;016&#41;&#46; The mean maximum diameter was measured for both kidneys of each individual and was adjusted for height&#46;</p><p class="elsevierStylePara">We had set out to only assess normotensive patients with ADPKD but because we had a significant percentage of hypertensive patients&#44; we decided to study whether there was any relationship among the total available population &#40;37 patients&#41; between the various parameters obtained by the ABPM and the mean kidney diameter adjusted for height&#46; This analysis revealed a statistically significant negative correlation between a greater kidney size and a lower PP &#40;r &#61; -0&#46;325&#44; p &#61; 0&#46;05&#41; &#40;Figure 1&#41;&#46;</p><p class="elsevierStylePara">Subsequently and because this was the main objective of the paper&#44; the results in the subset of 17 normotensive patients by ABPM over 24 hours were analysed&#46; Table 2 and Table 3 contain the demographic characteristics&#44; kidney size and BP obtained in the clinic and by ABPM&#46; When analysing the data from the group of the 17 normotensive patients&#44; positive correlations were identified between average maximum kidney size adjusted for height and all parameters of ABPM with the exception of PP&#44; without reaching statistical significance&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Kidney size&#44; circadian profile and blood pressure variability </span></p><p class="elsevierStylePara">Clinically&#44; the parameter used for assessing the BP pattern was the decrease in daytime to nightime MBP&#46; In the group of 17 normotensive patients&#44; there were no statistically significant differences in the maximum renal diameter adjusted for height between patients with a non-dipper pattern &#40;n &#61; 6&#41;&#44; dipper pattern &#40;n &#61; 8&#41; and extremely dipper pattern &#40;n &#61; 3&#41; &#40;p &#61; 0&#46;662&#41; &#40;Figure 2&#41;&#46; None of the 17 patients reported a riser pattern&#46;</p><p class="elsevierStylePara">Of the 17 normotensive patients&#44; we decided to study those who had a physiological BP profile&#44; maintaining 11 assessable patients with a dipper BP pattern&#46;</p><p class="elsevierStylePara">In the group of 11 patients with dipper BP patterns according to the decrease in MBP&#44; positive correlations were found&#44; although not significant&#44; between kidney size and all parameters &#40;SBP&#44; DBP&#44; systolic and diastolic load index&#44; SD of SBP and DBP&#41; for daytime&#44; nightime and 24-hour BP readings by ABPM&#44; where diastolic load index over 24 hours showed the greatest positive correlation &#40;p &#61; 0&#46;07&#41;&#46; The nocturnal decrease in BP for this group had a negative correlation&#44; although not statistically significant&#44; with the increase in kidney size&#46;</p><p class="elsevierStylePara">Since&#44; strictly speaking&#44; a dipper pattern should present a nocturnal decrease in both SBP and DBP greater than 10&#37;&#44; we investigated in the 17 normotensive patients whether the absence of a noctural decrease in SBP and&#47;or DBP was associated with a greater maximum renal diameter adjusted for height&#46; No significant differences were found in kidney size among patients with or without a dipper BP pattern&#46;</p><p class="elsevierStylePara">Applying this criterion of a nocturnal SBP and DBP decrease of &#62;10&#37; versus daytime to define the dipper pattern&#44; only 6 of the 17 patients had a dipper pattern&#44; all with a proper night&#8217;s rest on the date of the ABPM&#46; In these six patients&#44; a trend was once again observed towards a positive correlation that approached statistical significance for the 24-hour mean DBP&#44; the diastolic load index for day and night&#44; with the 24-hour diastolic load index achieving statistical significance &#40;r &#61; 0&#46;875&#44; p &#61; 0&#46;023&#41; &#40;Table 4&#41;&#46;</p><p class="elsevierStylePara">In the group of 11 patients without a dipper pattern of SBP and DBP&#44; a positive and statistically significant correlation was observed &#40;r &#61; 0&#46;623&#44; p &#61; 0&#46;04&#41; between the maximum kidney diameter adjusted for height and the standard deviation of DBP at night&#44; which once again is a parameter that reflects the BP variability&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION </span></p><p class="elsevierStylePara">The ABPM study of this group of patients who reported correct home BP readings allowed us to diagnose some 54&#46;1&#37; of them as hypertensive&#46; The patients were not trained to carry out a proper home blood pressure monitoring &#40;HBPM&#41;&#44; which would have helped diagnose hypertension in some of the patients who reported being normotensive at home&#46;</p><p class="elsevierStylePara">An important aspect of this study is that 11 of the 37 patients selected &#40;29&#46;7&#37;&#41; would not have been diagnosed with hypertension using only the clinical measurements&#44; since they had masked AHT&#46; Some studies have shown that patients with masked hypertension have more important subclinical organ damage than subjects with white coat hypertension or with grade I AHT&#44; which causes this condition to carry a greater cardiovascular risk&#46;<span class="elsevierStyleSup">15-17 </span>Population studies have also shown a significant increase in mortality in this subset of the population&#44; which might become comparable to the established AHT&#46;<span class="elsevierStyleSup">18 </span>The prevalence of masked AHT&#44; according to the literature&#44; varies between 6 and 26&#37;&#46; In the population studied&#44; the prevalence of masked hypertension is very important and&#44; if not detected and corrected&#44; it can increase cardiovascular risk and the likelihood of developing target organs damages&#46;</p><p class="elsevierStylePara">The existence of a statistically significant negative correlation between a greater maximum kidney diameter and a lower PP in the initial group of patients indirectly suggests an alteration of the DBP&#46; The population studied was young&#44; with an average age of approximately 38 years&#46; As with our group&#44; the general hypertensive young population is much more likely to have high DBP than SBP&#44; which leads to a decrease in PP&#46;</p><p class="elsevierStylePara">In the group of normotensive patients&#44; no relationship was detected between kidney size and the alteration of the circadian BP cycle&#44; although only a few patients were analysed&#46; However&#44; there remains a discernible trend towards a poorer BP profile associated with a poorer DBP to greater kidney diameter&#46; This trend persists even in the group of normotensive patients with proper nocturnal decrease in MBP&#46; The relationship between a greater diastolic load index over 24 hours to greater renal diameter in patients with dipper pattern of SBP and DBP is statistically significant&#46; The load index &#40;percentage of the BP readings by the ABPM that exceed the preset target BP&#41; is one of the measures used for evaluating BP variability and it has been shown that an increased load index is related to greater target organ damage &#40;left ventricular hypertrophy&#41;&#46;<span class="elsevierStyleSup">20 </span>The trend towards increased diastolic load index as kidney size increases could ultimately be related to greater target organ involvement&#44; which has been shown in some studies with this type of population&#46;<span class="elsevierStyleSup">12 </span></p><p class="elsevierStylePara">Given the importance of the results obtained in this study&#44; it is necessary to expand the sample size to confirm the findings and to evaluate the possible relationship that these findings may have to subclinical involvement of target organs&#46;</p><p class="elsevierStylePara">In conclusion&#44; the single reading of BPc in patients with ADPKD and normal renal function leaves many hypertensive patients undiagnosed given the high prevalence of masked AHT&#46; ABPM-assisted examination helps to identify these patients early on&#46;</p><p class="elsevierStylePara">The analysis of the overall group of 37 patients&#44; as well as the separate analysis of the group of normotensive patients&#44; show a statistically significant relationship between greater renal size and a worse performance of DBP&#44; as revealed by a lower PP in the former group and a greater variability in DBP in the latter group&#46; This data shows a worse DBP profile as compared to SBP&#46; These findings indicate that a relationship might exist along the entire evolution of the disease between renal growth and DBP alteration&#46;</p><p class="elsevierStylePara"><a href="grande&#47;10418&#95;108&#95;9205&#95;en&#95;10418&#95;t1&#46;jpg" class="elsevierStyleCrossRefs"><img src="10418_108_9205_en_10418_t1.jpg" alt="Classification of BP according to measurements taken in the clinic and by ABPM "></img></a></p><p class="elsevierStylePara">Table 1&#46; Classification of BP according to measurements taken in the clinic and by ABPM </p><p class="elsevierStylePara"><a href="grande&#47;10418&#95;108&#95;9206&#95;en&#95;10418&#95;t2&#46;jpg" class="elsevierStyleCrossRefs"><img src="10418_108_9206_en_10418_t2.jpg" alt="Demographic and clinical characteristics of the normotensive population confirmed by 24-hour ABPM &#40;n &#61; 17&#41; "></img></a></p><p class="elsevierStylePara">Table 2&#46; Demographic and clinical characteristics of the normotensive population confirmed by 24-hour ABPM &#40;n &#61; 17&#41; </p><p class="elsevierStylePara"><a href="grande&#47;10418&#95;108&#95;9207&#95;en&#95;10418&#95;t3&#46;jpg" class="elsevierStyleCrossRefs"><img src="10418_108_9207_en_10418_t3.jpg" alt="BP readings by ABPM of the normotensive population &#40;n &#61; 17&#41; "></img></a></p><p class="elsevierStylePara">Table 3&#46; BP readings by ABPM of the normotensive population &#40;n &#61; 17&#41; </p><p class="elsevierStylePara"><a href="grande&#47;10418&#95;108&#95;9208&#95;en&#95;10418&#95;t4&#46;jpg" class="elsevierStyleCrossRefs"><img src="10418_108_9208_en_10418_t4.jpg" alt="Study of the relationship between average renal diameter adjusted for height and the variability of BP in the group of normotensives with a dipper pattern of SBP and DBP &#40;n &#61; 6&#41; "></img></a></p><p class="elsevierStylePara">Table 4&#46; Study of the relationship between average renal diameter adjusted for height and the variability of BP in the group of normotensives with a dipper pattern of SBP and DBP &#40;n &#61; 6&#41; </p><p class="elsevierStylePara"><a href="grande&#47;10418&#95;108&#95;9209&#95;en&#95;10418&#95;f1&#46;jpg" class="elsevierStyleCrossRefs"><img src="10418_108_9209_en_10418_f1.jpg" alt="Linear regression line between height adjusted average renal diameter and pressure differential in the overall population &#40;n &#61; 37&#41;&#46; "></img></a></p><p class="elsevierStylePara">Figure 1&#46; Linear regression line between height adjusted average renal diameter and pressure differential in the overall population &#40;n &#61; 37&#41;&#46; </p><p class="elsevierStylePara"><a href="grande&#47;10418&#95;108&#95;9210&#95;en&#95;10418&#95;f2&#46;jpg" class="elsevierStyleCrossRefs"><img src="10418_108_9210_en_10418_f2.jpg" alt="Height adjusted average renal diameter as a function of the circadian BP profile in the normotensive group &#40;n &#61; 17&#41;&#46;"></img></a></p><p class="elsevierStylePara">Figure 2&#46; Height adjusted average renal diameter as a function of the circadian BP profile in the normotensive group &#40;n &#61; 17&#41;&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Antecedentes&#58; </span>El aumento del tama&#241;o renal desempe&#241;a un papel importante en el desarrollo de la hipertensi&#243;n arterial &#40;HTA&#41; en pacientes con poliquistosis renal autos&#243;mica dominante &#40;PQRAD&#41; con funci&#243;n renal normal&#46; <span class="elsevierStyleBold">Material y m&#233;todos&#58; </span>Se han practicado a 37 pacientes con PQRAD&#44; filtrado glomerular estimado &#40;FGe&#41; por MDRD &#62;60 ml&#47;min&#47;1&#44;73 m&#178; y&#160;supuestamente normotensos&#44; una monitorizaci&#243;n de la presi&#243;n arterial &#40;MAPA&#41; y una ecograf&#237;a renovesical para investigar la posible relaci&#243;n entre el aumento del tama&#241;o renal y un perfil patol&#243;gico de presi&#243;n arterial &#40;PA&#41; en estadios de prehipertensi&#243;n&#46; <span class="elsevierStyleBold">Resultados&#58; </span>13 pacientes resultaron ser normotensos&#44; 11 presentaron HTA enmascarada&#44; 4 tuvieron HTA de bata blanca y 9&#44; HTA verdadera&#46;<span class="elsevierStyleBold"> </span>Se ha observado en los pacientes normotensos con patr&#243;n reductor de la PA una correlaci&#243;n positiva y estad&#237;sticamente significativa entre el tama&#241;o renal y la variabilidad de la presi&#243;n arterial diast&#243;lica &#40;PAD&#41;&#46; <span class="elsevierStyleBold">Conclusiones&#58; </span>La MAPA permite realizar un diagn&#243;stico precoz de la HTA e identificar a pacientes con hipertensi&#243;n enmascarada&#46; Este trabajo sugiere que en pacientes normotensos con PQRAD existe una posible relaci&#243;n entre el tama&#241;o renal y un perfil de PA con mayor riesgo cardiovascular&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Background&#58;</span> Enlargement of renal size plays an important role in the development of hypertension in patients with autosomic dominant polycystic kidney disease &#40;ADPKD&#41; and normal renal function&#46; <span class="elsevierStyleBold">Methods&#58;</span> A 24h blood pressure monitoring &#40;ABPM&#41; and a renal ecography have been performed in 37 patients with ADPKD and estimated glomerular filtration rate &#62;60 ml&#47;min&#47;1&#44;73m<span class="elsevierStyleSup">2</span> &#160;to study the relationship between renal size and an altered blood pressure profile in prehypertension stages&#46; <span class="elsevierStyleBold">Results&#58;</span> 13 patients had normal blood pressure&#44; 11 were diagnosed of masked hypertension&#44; 4 had white coat hypertension and 9 had&#160; hypertension&#46; We have found in the normotensive group with a dipper blood pressure profile a positive and statistically significant relationship between renal size and diastolic blood pressure variability&#46; <span class="elsevierStyleBold">Conclusions&#58;</span> ABPM helps to make an early diagnosis of hypertension and to identify those patients with masked hypertension&#46; This study suggests a relationship between renal size and a blood pressure profile linked to a major cardiovasular risk in normotensive patients with ADPKD&#46;</p>"
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Relationship between kidney size and blood pressure profile in patients with autosomal dominant polycystic kidney disease without renal failure
Relación entre el tamaño renal y el perfil de presión arterial en pacientes con poliquistosis renal autosómica dominante sin insuficiencia renal
L.. Sans Atxera, A.. Roca-Cusachsb, R.. Torrac, F.. Caleroc, P.. Ariasd, J.. Ballarinc, P.. Fernández-Llamac
a Servicio de Nefrología, Hospital del Mar. Barcelona,
b Servicio de Medicina Interna, Unidad de Hipertensión. Hospital de la Santa Creu i Sant Pau. Universitat Autònoma de Barcelona,
c Servicio de Nefrología, Fundació Puigvert. Departament de Medicina (Universitat Autònoma de Barcelona). REDinREN. Instituto de Investigación Carlos III,
d Departamento de Enfermería, Fundació Puigvert. Barcelona,
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION </span></p><p class="elsevierStylePara">Autosomal dominant polycystic kidney disease &#40;ADPKD&#41; is a genetic disease characterised by the presence of bilateral renal cysts that progressively increase in number and size&#46;<span class="elsevierStyleSup">1 </span>It is the most common genetic disease affecting the kidneys and leads to terminal kidney failure as patients get into their 40s and 50s&#46;<span class="elsevierStyleSup">2&#44;3 </span></p><p class="elsevierStylePara">The leading cause of death in patients with polycystic kidney disease is cardiovascular disease&#44; being arterial hypertension &#40;AHT&#41; its main determinant&#46;<span class="elsevierStyleSup">4 </span>Both hypertension and the increase in renal size secondary to the growth of cysts<span class="elsevierStyleSup">1 </span>is correlated with a progressive deterioration of renal funcion in ADPKD&#46; The onset of hypertension in these patients is common and in approximately 60&#37; of cases the diagnosis is performed before any renal function impairment appears&#46; It seems that the increase in kidney size<span class="elsevierStyleSup">5-7 </span>and the activity in the renin-angiotensin-aldosterone system<span class="elsevierStyleSup">8-10 </span>are primarily responsible for the development of hypertension in these patients&#46; Studies in patients with ADPKD and normal renal function have shown the presence of target organ damage &#40;increased left ventricular mass&#41;<span class="elsevierStyleSup">11&#44;12 </span>before developing AHT&#46; This damage appears to be related more to the increase in systolic blood pressure &#40;SBP&#41; determined by ambulatory blood pressure monitoring &#40;ABPM&#41; than to the blood pressure &#40;BP&#41; measured at the clinic&#46;<span class="elsevierStyleSup">12 </span></p><p class="elsevierStylePara">Twenty-four hour ABPM adds additional information to the BP measurements in the clinic &#40;BPc&#41; as it reports on the circadian rhythm and the variability of the BP&#46; Furthermore&#44; it identifies patients with masked hypertension &#40;normal clinic BP and high ambulatory BP&#41; and isolated clinic hypertension &#40;high BP readings in the clinic and normal ambulatory BP&#41;&#46; A non-physiological BP profile &#40;non&#173;dipper nocturnal pattern&#41;&#44; a greater BP variability &#40;average of standard deviations over 24 hours greater than 18 mmHg for SBP or greater than 15mmHg for DBP&#41; and the presence of masked or isolated clinic hypertension have been related to greater cardiovascular risk&#46;<span class="elsevierStyleSup">13-17 </span></p><p class="elsevierStylePara">Therefore&#44; although hypertension is a key factor in cardiovascular morbidity and mortality in patients with polycystic disease&#44; little is known about the pre-hypertensive stage&#46; In addition&#44; it is not known whether the increase in kidney size could be associated with a change in the BP profile and its variability&#46; We therefore decided to evaluate the following points in patients with normotensive ADPKD <span class="elsevierStyleItalic">a priori </span>and with eGF by MDRD &#62;60 mL&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#58;</p><p class="elsevierStylePara">1&#46;&#160;&#160;&#160; Whether there are differences between the BPc and the ABPM readings&#46;</p><p class="elsevierStylePara">2&#46;&#160;&#160;&#160; The relationship between maximum kidney diameter and SBP&#44; DBP and mean BP &#40;MBP&#41; over 24 hours&#44; day and night&#44; and pulse pressure &#40;PP&#41; obtained by 24-hour ABPM&#46;</p><p class="elsevierStylePara">3&#46;&#160;&#160;&#160; If there is a relationship between maximum kidney diameter and the variability of BP or the circadian BP pattern&#46;</p><p class="elsevierStylePara">&#160;</p><ul> </ul><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHODS </span></p><p class="elsevierStylePara">We performed a transversal&#44; observational study that included 37 patients with ADPKD from those who visited outpatient clinics&#44; who were between the ages of 18 and 50 years&#44; with eGF by MDRD &#62;60 mL&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2 </span>and who were normotensive &#40;patients with home BP &#60;135&#47;85 mmHg and not receiving treatment for hypertension&#41;&#46;</p><p class="elsevierStylePara">The following information was collected from these 37 patients&#58;</p><p class="elsevierStylePara">1&#46; Three readings of SBP and DBP with the OMRON 705 IT blood pressure monitor &#40;Tokyo&#44; Japan&#41;&#44; following the standard for BPc readings of the European Society of Hypertension &#40;ESH&#41;&#44;<span class="elsevierStyleSup">18 </span>using the average of three readings as the clinical BP value&#46;</p><p class="elsevierStylePara">2&#46; ABPM data &#40;via the Dyasis Integra device&#41; &#40;Rueil-Malmaison&#44; France&#41;&#46;</p><p class="elsevierStylePara">- SBP&#44; DBP and MBP &#40;DBP &#43; 1&#47;3 pulse pressure &#40;PP&#41; &#40;PP &#61; SBP &#8211; DBP&#41; during the day&#44; night and over 24 hours&#46; Heart rate and 24-hour PP&#46;</p><p class="elsevierStylePara">- Percentage of nocturnal BP decrease with respect to the daytime SBP&#44; DBP and MBP and quality of sleep on the ABPM date&#46;</p><p class="elsevierStylePara">- Load index &#40;percentage of BP measurements above the established target BP&#41; for SBP and DBP during the day&#44; night and over 24 hours&#46;</p><p class="elsevierStylePara">- Typical or standard deviation of the average SBP and DBP during the day&#44; night and over 24 hours&#46; Maximum daytime&#44; nightime and 24-hour SBP and DBP&#46;</p><p class="elsevierStylePara">3&#46; Anthropometric data&#58; weight&#44; height&#44; body surface area and body mass index&#46;</p><p class="elsevierStylePara">4&#46; Mean maximum diameter of both kidneys &#40;in millimetres&#41; by renal ultrasound performed by ultrasound specialists who are expert in renovesical ultrasound&#44; using a single measure&#46;</p><p class="elsevierStylePara">According to the ABPM readings and following the recommendation in the 2007 ESH Guidelines&#44;<span class="elsevierStyleSup">18 </span>patients are consider normotensive if they present a SBP &#60;130 mmHg and a DBP &#60;80 mmHG by ABPM over 24 hours&#46;</p><p class="elsevierStylePara">The percentage of decrease in nocturnal MBP versus daytime MBP allows us to classify patients according to their BP profile&#58;</p><p class="elsevierStylePara">1&#46; Non-dipper pattern&#58; nocturnal MBP decrease versus daytime MBP less than 10&#37;&#46;</p><p class="elsevierStylePara">2&#46; Dipper pattern&#58; nocturnal MBP decrease versus daytime MBP between 10 and 20&#37;&#46;</p><p class="elsevierStylePara">3&#46; Riser pattern&#58; nocturnal MBP higher than daytime MBP&#46;</p><p class="elsevierStylePara">4&#46; Extreme dipper pattern&#58; nocturnal MBP decrease versus daytime MBP greater than 20&#37;&#46; The circadian profile was not assessed if the patient reported suffering from a bad night&#8217;s sleep&#46;</p><p class="elsevierStylePara">Considering the BP readings obtained from the ABPM and the BPc&#44; we can classify the patients into four groups&#58;</p><p class="elsevierStylePara">1&#46; White coat AHT&#58; patients with high BPc &#40;&#40;&#62;140&#47;90 mmHg&#41; and BP by ABPM over 24 hours &#60;130&#47;80 mmHg&#46;</p><p class="elsevierStylePara">2&#46; Masked AHT&#58; patients with normal BPc &#40;&#60;140&#47;90 mmHg&#41; and high BP by ABPM over 24 hours &#40;&#40;&#62;130&#47;80 mmHg&#41;&#46;</p><p class="elsevierStylePara">3&#46; True AHT&#58; patients with high BPc and BP by ABPM over 24 hours&#46;</p><p class="elsevierStylePara">4&#46; True normotensives&#58; patients with normal BPc and BP by ABPM over 24 hours&#46;</p><p class="elsevierStylePara">The statistical analysis was carried out with the SPSS software&#46; The results are expressed as the mean &#177; standard deviation &#40;SD&#41; for the continuously distributed variables and as frequencies for the categorical variables&#46;</p><p class="elsevierStylePara">Given the small sample size&#44; the normal distribution of variables was studied using the Kolmogorov-Smirnov and Shapiro-Wilks tests&#46; After verifying the normality of the variables&#44; the Student&#8217;s t-test was used to compare samples with two categories and ANOVA was used for those with three or more categories&#46; For the non-parametric variables&#44; the Mann-Whitney and Kruskall-Wallis tests were used depending on whether they had two or more categories&#46;</p><p class="elsevierStylePara">To study the association between the mean maximum kidney diameter and the various data provided by the ABPM&#44; the linear Pearson correlation coefficient was used&#46; The distribution of categorical variables was analysed by means of the chi-squared test&#46; A p less than 0&#46;05 was considered statistically significant&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Blood pressure classification according to BP values obtained in the clinic and by ambulatory blood pressure monitoring </span></p><p class="elsevierStylePara">The 37 patients included were classified into four groups according to the BP obtained in the clinic and through 24-hour ABPM&#46; Of these&#44; 13 were true normotensives &#40;35&#46;1&#37;&#41;&#44; 9 were true hypertensives &#40;24&#46;3&#37;&#41;&#44; 4 patients had white coat hypertension &#40;10&#46;8&#37;&#41; and the remaining 11 &#40;29&#46;7&#37;&#41; had masked hypertension &#40;Table 1&#41;&#46;</p><p class="elsevierStylePara">Taking into account the average BP by ABPM over 24 hours and hypertension being diagnosed for a SBP &#62;130 mmHg or a DBP &#62;80 mmHg&#44; 20 of the 37 patients &#40;54&#37;&#41; initially selected as normotensives according to the home BP readings were diagnosed with AHT&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Relationship between kidney size and blood pressure characteristics </span></p><p class="elsevierStylePara">There is currently no standard of normality in relation to maximum kidney diameter in the general population but it is known that the maximum kidney diameter is correlated with height&#44;<span class="elsevierStyleSup">19 </span>which was coherent with our population &#40;r &#61; 0&#46;572&#44; p &#61; 0&#46;016&#41;&#46; The mean maximum diameter was measured for both kidneys of each individual and was adjusted for height&#46;</p><p class="elsevierStylePara">We had set out to only assess normotensive patients with ADPKD but because we had a significant percentage of hypertensive patients&#44; we decided to study whether there was any relationship among the total available population &#40;37 patients&#41; between the various parameters obtained by the ABPM and the mean kidney diameter adjusted for height&#46; This analysis revealed a statistically significant negative correlation between a greater kidney size and a lower PP &#40;r &#61; -0&#46;325&#44; p &#61; 0&#46;05&#41; &#40;Figure 1&#41;&#46;</p><p class="elsevierStylePara">Subsequently and because this was the main objective of the paper&#44; the results in the subset of 17 normotensive patients by ABPM over 24 hours were analysed&#46; Table 2 and Table 3 contain the demographic characteristics&#44; kidney size and BP obtained in the clinic and by ABPM&#46; When analysing the data from the group of the 17 normotensive patients&#44; positive correlations were identified between average maximum kidney size adjusted for height and all parameters of ABPM with the exception of PP&#44; without reaching statistical significance&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Kidney size&#44; circadian profile and blood pressure variability </span></p><p class="elsevierStylePara">Clinically&#44; the parameter used for assessing the BP pattern was the decrease in daytime to nightime MBP&#46; In the group of 17 normotensive patients&#44; there were no statistically significant differences in the maximum renal diameter adjusted for height between patients with a non-dipper pattern &#40;n &#61; 6&#41;&#44; dipper pattern &#40;n &#61; 8&#41; and extremely dipper pattern &#40;n &#61; 3&#41; &#40;p &#61; 0&#46;662&#41; &#40;Figure 2&#41;&#46; None of the 17 patients reported a riser pattern&#46;</p><p class="elsevierStylePara">Of the 17 normotensive patients&#44; we decided to study those who had a physiological BP profile&#44; maintaining 11 assessable patients with a dipper BP pattern&#46;</p><p class="elsevierStylePara">In the group of 11 patients with dipper BP patterns according to the decrease in MBP&#44; positive correlations were found&#44; although not significant&#44; between kidney size and all parameters &#40;SBP&#44; DBP&#44; systolic and diastolic load index&#44; SD of SBP and DBP&#41; for daytime&#44; nightime and 24-hour BP readings by ABPM&#44; where diastolic load index over 24 hours showed the greatest positive correlation &#40;p &#61; 0&#46;07&#41;&#46; The nocturnal decrease in BP for this group had a negative correlation&#44; although not statistically significant&#44; with the increase in kidney size&#46;</p><p class="elsevierStylePara">Since&#44; strictly speaking&#44; a dipper pattern should present a nocturnal decrease in both SBP and DBP greater than 10&#37;&#44; we investigated in the 17 normotensive patients whether the absence of a noctural decrease in SBP and&#47;or DBP was associated with a greater maximum renal diameter adjusted for height&#46; No significant differences were found in kidney size among patients with or without a dipper BP pattern&#46;</p><p class="elsevierStylePara">Applying this criterion of a nocturnal SBP and DBP decrease of &#62;10&#37; versus daytime to define the dipper pattern&#44; only 6 of the 17 patients had a dipper pattern&#44; all with a proper night&#8217;s rest on the date of the ABPM&#46; In these six patients&#44; a trend was once again observed towards a positive correlation that approached statistical significance for the 24-hour mean DBP&#44; the diastolic load index for day and night&#44; with the 24-hour diastolic load index achieving statistical significance &#40;r &#61; 0&#46;875&#44; p &#61; 0&#46;023&#41; &#40;Table 4&#41;&#46;</p><p class="elsevierStylePara">In the group of 11 patients without a dipper pattern of SBP and DBP&#44; a positive and statistically significant correlation was observed &#40;r &#61; 0&#46;623&#44; p &#61; 0&#46;04&#41; between the maximum kidney diameter adjusted for height and the standard deviation of DBP at night&#44; which once again is a parameter that reflects the BP variability&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION </span></p><p class="elsevierStylePara">The ABPM study of this group of patients who reported correct home BP readings allowed us to diagnose some 54&#46;1&#37; of them as hypertensive&#46; The patients were not trained to carry out a proper home blood pressure monitoring &#40;HBPM&#41;&#44; which would have helped diagnose hypertension in some of the patients who reported being normotensive at home&#46;</p><p class="elsevierStylePara">An important aspect of this study is that 11 of the 37 patients selected &#40;29&#46;7&#37;&#41; would not have been diagnosed with hypertension using only the clinical measurements&#44; since they had masked AHT&#46; Some studies have shown that patients with masked hypertension have more important subclinical organ damage than subjects with white coat hypertension or with grade I AHT&#44; which causes this condition to carry a greater cardiovascular risk&#46;<span class="elsevierStyleSup">15-17 </span>Population studies have also shown a significant increase in mortality in this subset of the population&#44; which might become comparable to the established AHT&#46;<span class="elsevierStyleSup">18 </span>The prevalence of masked AHT&#44; according to the literature&#44; varies between 6 and 26&#37;&#46; In the population studied&#44; the prevalence of masked hypertension is very important and&#44; if not detected and corrected&#44; it can increase cardiovascular risk and the likelihood of developing target organs damages&#46;</p><p class="elsevierStylePara">The existence of a statistically significant negative correlation between a greater maximum kidney diameter and a lower PP in the initial group of patients indirectly suggests an alteration of the DBP&#46; The population studied was young&#44; with an average age of approximately 38 years&#46; As with our group&#44; the general hypertensive young population is much more likely to have high DBP than SBP&#44; which leads to a decrease in PP&#46;</p><p class="elsevierStylePara">In the group of normotensive patients&#44; no relationship was detected between kidney size and the alteration of the circadian BP cycle&#44; although only a few patients were analysed&#46; However&#44; there remains a discernible trend towards a poorer BP profile associated with a poorer DBP to greater kidney diameter&#46; This trend persists even in the group of normotensive patients with proper nocturnal decrease in MBP&#46; The relationship between a greater diastolic load index over 24 hours to greater renal diameter in patients with dipper pattern of SBP and DBP is statistically significant&#46; The load index &#40;percentage of the BP readings by the ABPM that exceed the preset target BP&#41; is one of the measures used for evaluating BP variability and it has been shown that an increased load index is related to greater target organ damage &#40;left ventricular hypertrophy&#41;&#46;<span class="elsevierStyleSup">20 </span>The trend towards increased diastolic load index as kidney size increases could ultimately be related to greater target organ involvement&#44; which has been shown in some studies with this type of population&#46;<span class="elsevierStyleSup">12 </span></p><p class="elsevierStylePara">Given the importance of the results obtained in this study&#44; it is necessary to expand the sample size to confirm the findings and to evaluate the possible relationship that these findings may have to subclinical involvement of target organs&#46;</p><p class="elsevierStylePara">In conclusion&#44; the single reading of BPc in patients with ADPKD and normal renal function leaves many hypertensive patients undiagnosed given the high prevalence of masked AHT&#46; ABPM-assisted examination helps to identify these patients early on&#46;</p><p class="elsevierStylePara">The analysis of the overall group of 37 patients&#44; as well as the separate analysis of the group of normotensive patients&#44; show a statistically significant relationship between greater renal size and a worse performance of DBP&#44; as revealed by a lower PP in the former group and a greater variability in DBP in the latter group&#46; This data shows a worse DBP profile as compared to SBP&#46; These findings indicate that a relationship might exist along the entire evolution of the disease between renal growth and DBP alteration&#46;</p><p class="elsevierStylePara"><a href="grande&#47;10418&#95;108&#95;9205&#95;en&#95;10418&#95;t1&#46;jpg" class="elsevierStyleCrossRefs"><img src="10418_108_9205_en_10418_t1.jpg" alt="Classification of BP according to measurements taken in the clinic and by ABPM "></img></a></p><p class="elsevierStylePara">Table 1&#46; Classification of BP according to measurements taken in the clinic and by ABPM </p><p class="elsevierStylePara"><a href="grande&#47;10418&#95;108&#95;9206&#95;en&#95;10418&#95;t2&#46;jpg" class="elsevierStyleCrossRefs"><img src="10418_108_9206_en_10418_t2.jpg" alt="Demographic and clinical characteristics of the normotensive population confirmed by 24-hour ABPM &#40;n &#61; 17&#41; "></img></a></p><p class="elsevierStylePara">Table 2&#46; Demographic and clinical characteristics of the normotensive population confirmed by 24-hour ABPM &#40;n &#61; 17&#41; </p><p class="elsevierStylePara"><a href="grande&#47;10418&#95;108&#95;9207&#95;en&#95;10418&#95;t3&#46;jpg" class="elsevierStyleCrossRefs"><img src="10418_108_9207_en_10418_t3.jpg" alt="BP readings by ABPM of the normotensive population &#40;n &#61; 17&#41; "></img></a></p><p class="elsevierStylePara">Table 3&#46; BP readings by ABPM of the normotensive population &#40;n &#61; 17&#41; </p><p class="elsevierStylePara"><a href="grande&#47;10418&#95;108&#95;9208&#95;en&#95;10418&#95;t4&#46;jpg" class="elsevierStyleCrossRefs"><img src="10418_108_9208_en_10418_t4.jpg" alt="Study of the relationship between average renal diameter adjusted for height and the variability of BP in the group of normotensives with a dipper pattern of SBP and DBP &#40;n &#61; 6&#41; "></img></a></p><p class="elsevierStylePara">Table 4&#46; Study of the relationship between average renal diameter adjusted for height and the variability of BP in the group of normotensives with a dipper pattern of SBP and DBP &#40;n &#61; 6&#41; </p><p class="elsevierStylePara"><a href="grande&#47;10418&#95;108&#95;9209&#95;en&#95;10418&#95;f1&#46;jpg" class="elsevierStyleCrossRefs"><img src="10418_108_9209_en_10418_f1.jpg" alt="Linear regression line between height adjusted average renal diameter and pressure differential in the overall population &#40;n &#61; 37&#41;&#46; "></img></a></p><p class="elsevierStylePara">Figure 1&#46; Linear regression line between height adjusted average renal diameter and pressure differential in the overall population &#40;n &#61; 37&#41;&#46; </p><p class="elsevierStylePara"><a href="grande&#47;10418&#95;108&#95;9210&#95;en&#95;10418&#95;f2&#46;jpg" class="elsevierStyleCrossRefs"><img src="10418_108_9210_en_10418_f2.jpg" alt="Height adjusted average renal diameter as a function of the circadian BP profile in the normotensive group &#40;n &#61; 17&#41;&#46;"></img></a></p><p class="elsevierStylePara">Figure 2&#46; Height adjusted average renal diameter as a function of the circadian BP profile in the normotensive group &#40;n &#61; 17&#41;&#46;</p>"
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            1 => "Tama&#241;o renal"
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            1 => "Renal size"
            2 => "Ambulatory monitoring of blood pressure"
            3 => "Blood pressure profile"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Antecedentes&#58; </span>El aumento del tama&#241;o renal desempe&#241;a un papel importante en el desarrollo de la hipertensi&#243;n arterial &#40;HTA&#41; en pacientes con poliquistosis renal autos&#243;mica dominante &#40;PQRAD&#41; con funci&#243;n renal normal&#46; <span class="elsevierStyleBold">Material y m&#233;todos&#58; </span>Se han practicado a 37 pacientes con PQRAD&#44; filtrado glomerular estimado &#40;FGe&#41; por MDRD &#62;60 ml&#47;min&#47;1&#44;73 m&#178; y&#160;supuestamente normotensos&#44; una monitorizaci&#243;n de la presi&#243;n arterial &#40;MAPA&#41; y una ecograf&#237;a renovesical para investigar la posible relaci&#243;n entre el aumento del tama&#241;o renal y un perfil patol&#243;gico de presi&#243;n arterial &#40;PA&#41; en estadios de prehipertensi&#243;n&#46; <span class="elsevierStyleBold">Resultados&#58; </span>13 pacientes resultaron ser normotensos&#44; 11 presentaron HTA enmascarada&#44; 4 tuvieron HTA de bata blanca y 9&#44; HTA verdadera&#46;<span class="elsevierStyleBold"> </span>Se ha observado en los pacientes normotensos con patr&#243;n reductor de la PA una correlaci&#243;n positiva y estad&#237;sticamente significativa entre el tama&#241;o renal y la variabilidad de la presi&#243;n arterial diast&#243;lica &#40;PAD&#41;&#46; <span class="elsevierStyleBold">Conclusiones&#58; </span>La MAPA permite realizar un diagn&#243;stico precoz de la HTA e identificar a pacientes con hipertensi&#243;n enmascarada&#46; Este trabajo sugiere que en pacientes normotensos con PQRAD existe una posible relaci&#243;n entre el tama&#241;o renal y un perfil de PA con mayor riesgo cardiovascular&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Background&#58;</span> Enlargement of renal size plays an important role in the development of hypertension in patients with autosomic dominant polycystic kidney disease &#40;ADPKD&#41; and normal renal function&#46; <span class="elsevierStyleBold">Methods&#58;</span> A 24h blood pressure monitoring &#40;ABPM&#41; and a renal ecography have been performed in 37 patients with ADPKD and estimated glomerular filtration rate &#62;60 ml&#47;min&#47;1&#44;73m<span class="elsevierStyleSup">2</span> &#160;to study the relationship between renal size and an altered blood pressure profile in prehypertension stages&#46; <span class="elsevierStyleBold">Results&#58;</span> 13 patients had normal blood pressure&#44; 11 were diagnosed of masked hypertension&#44; 4 had white coat hypertension and 9 had&#160; hypertension&#46; We have found in the normotensive group with a dipper blood pressure profile a positive and statistically significant relationship between renal size and diastolic blood pressure variability&#46; <span class="elsevierStyleBold">Conclusions&#58;</span> ABPM helps to make an early diagnosis of hypertension and to identify those patients with masked hypertension&#46; This study suggests a relationship between renal size and a blood pressure profile linked to a major cardiovasular risk in normotensive patients with ADPKD&#46;</p>"
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ISSN: 20132514
Original language: English
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Idiomas
Nefrología (English Edition)