Ambulatory Blood Pressure Monitoring Guide To Alleviate Renal Damage In Children With Primary Nephrotic Syndrome

Backgrounds Primary nephrotic syndrome (PNS) was the most common of the renal disease with a long and complex course of treatment. There were a series of factors that promote its continuous development. PNS renal hypertension promoted to decrease the renal function and to enter into the end-stage renal disease (ESRD). Adult studies had shown that the progress of renal disease and systolic blood pressure (SBP), mean arterial blood pressure (MAP) showed significant positive correlation. GFR decline in chronic kidney disease was closely correlated with blood pressure, especially systolic blood pressure. Effectively controlling of blood pressure to protect the kidney function of patients was an important method.PNS hypertension mechanisms were not yet entirely clear, might be involved in a variety of factors. Mechanisms of hypertension increasing kidney injury might include hemodynamic factors, non-hemodynamic factors. These might be related to upgrade level of sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS). The existing relationship between hypertension and kidney disease research information was mainly for adults with hypertension and chronic renal damage in the study about typeⅡdiabetes with chronic renal damage and high blood pressure. The effects of hypertension on renal damage in Children might be similar to the adults. But there were differences certainly. However, there was lack of similar studies in children now. It needed researches urgently about hypertension and renal damages in children with chronic renal disease, especially PNS.Ambulatory blood pressure monitoring (ABPM) avoiding human error could be a good response to blood pressure levels and blood pressure regularity. ABPM was more correlative to target organ damage than casual blood pressure (CBP). ABPM could also assess the control level of blood pressure exactly.Angiotensin-converting enzyme inhibitors (ACEI) showed the protective effect on the kidney through controlling blood pressure and urinary protein excretion rate. Monopril (Fosinopril) is a kind of ACEI having dual channel clear mode:liver and kidney. Kidney damaged children will increase discharge of Monopril compensatory by the liver to remain the overall clearance of drug relatively stable avoiding drug accumulation. ABPM could give efficacy proof of application of ACEI and other antihypertensive drugs for children with PNS.Objective To investigate the changes of ABPM value in children with PNS and its clinical significance. To research elevated RAAS activity in children with PNS and its relationship with ABPM and its pathogenesis role in PNS. To research elevated SNS activity in PNS children and its relationship with ABPM and its pathogenesis role in PNS. To explore the relationship between the elevated RAAS activity and the elevated SNS activity. Using ABPM evaluates the efficacy of Monopril and guide to create a new drug approach.Methods Using ambulatory blood pressure instrument to record ambulatory blood pressure monitoring data in children with PNS and using ordinary mercury sphygmomanometer to survey casual blood pressure. Utilizingγ-radiation immune counter to detect plasma renin (PRA), angiotensinⅡ(AngⅡ) and aldosterone (ALD). To analyze the correlation between PRA, AngⅡand ALD level change and ABPM data. Utilizing high-performance liquid chromatography with electrochemical luminescence detection to measure 24-hour urine SNS levels. To analyze the correlation in SNS level changes, ABPM data and renal damages. To compare changes in ABPM among different medication methods after 2 weeks treatment. To analyze the significance of different medication methods in improving ABPM data. The Monopril point using group was selecting Monopril using point according ABPM levels and Non-dipper, and use Monopril 3 hours before ABP elevated intensively or sleeping. The Monopril routine using group according conventional medication used Monopril at 8am.Results1.101 cases (88.6%) of all kinds of ambulatory hypertension in total 114 cases of PNS showed the high incidence. Moreover, systolic blood pressure increased significantly. In addition, both light and severity masked hypertension possess 45 cases (39.5% of the total PNS cases), in which included severe masked hypertension 18 cases (15.8% of the total). It also indicated the high incidence of non-dipper blood pressure at 70.2% of the total PNS cases. Increasing of ABP mean and load in children with PNS decreased creatinine clearance rate and elevated 24-hour urine protein, urineβ2-microglobulin and urinary NAG. Children of non-dipper blood pressure with PNS significantly reduced creatinine clearance and increased 24-hour urine protein, urinary (32-MG and urinary NAG.3. RAAS levels were significantly increased in PNS children. AngⅡlevels were closely correlated with ABP mean and ABP load. RAAS levels were closely negative correlated with Ccr. RAAS levels were closely negative correlated with urinary (32-MG and urinary NAG.4. Urinary SNS levels were significantly increased in children with PNS and were closely positive related with non-dipper blood pressure. Urinary NA levels were closely positive correlated with SBP. Urinary A levels were closely positive correlated with DBP. Urinary DA levels were closely positive correlated with blood pressure load. SNS levels were closely positive correlated with urinaryβ2-MG.5. RAAS levels were closely positive correlated with urine SNS levels in PNS children.6. In 7 cases of Monopril time point medication Group included five cases of Non-dipper and 2 cases of Dipper. On one hand,5 cases of Non-dipper blood pressure mainly according evaluated stage of blood pressure and Non-dipper factors selected medication time 3 hours before sleep time. On the other hand, Monopril medication time also selected 3 hours before bed time in two cases of Dipper according to evaluated stage of blood pressure. ABP mean of the two groups of application Monopril after 2 weeks improved significantly than the unused Monopril. The ABPM data of the group selecting Monopril using point according ABPM levels and Non-dipper changed better in ABP levels than conventional medication at 8am.Conclusion1. ABPM helped to find the large proportion of MHT and showed a high rate of ambulatory hypertension in children with PNS. Moreover, ABPM found that children with high incidence of non-dipper blood pressure showing 24-hour ambulatory blood pressure rhythm abnormalities in children with PNS. In addition, high levels of ambulatory hypertension and decline of circadian rhythm of blood pressure prompted renal damage. Classification of severe MHT helped to pay more attention to the target organ damage.2. RAAS activity increased in children with PNS which lifted the blood pressure mainly through AngⅡand caused kidney damage.3. SNS activity increased in children with PNS which elevated children's blood pressure levels and declined the rhythm of ambulatory blood pressure which both causing renal damage. SNS activity and RAAS levels promoted each other.4. Monopril time point medication applied more effectively to reduce the mean blood pressure, to decrease blood load and to improve the circadian rhythm that illustrated that it was an ideal blood pressure Medication approach. The hospital without ABPM can choose using Monopril 3 hours before going to bed at night. Objective To study ABPM value changes and correlations of renal damage in children with primary nephrotic syndrome.Methods 24-hour ambulatory blood pressure monitoring was done through ABPM instrument in children with primary nephrotic syndrome. ABPM was compared with CBP. To analyze the relationship in ABPM, CBP and renal damages.Results1. Nephrotic syndrome children have higher positive rate in blood pressure test by ABPM than CBP. All kinds of ambulatory hypertension arrived 101 cases (88.6%). There was a large proportion of high blood pressure mean, blood pressure load in which demonstrated SBP levels much higher than DBP and also illustrated SBP load greater than DBP load. Blood pressure mean and blood load had no significant differences between initial and relapse cases (P>0.05). Blood pressure mean and blood load had no significant differences between different course(≤8w and>8w) of disease(P>0.05).2. Children with PNS showed high incidence of MHT which possessed 45 cases (39.5% of the total PNS) including severe MHT 18 cases (15.8% of the total PNS).3. There was a high incidence of non-dipper blood pressure at 70.2%, Moreover, the blood pressure mean and blood pressure mean load increased higher in sleeping time than awaking time. However, the incidence of non-dipper blood pressure was not correlated with genders and blood pressure levels.4. Ccr was negatively correlated with 24h systolic blood pressure levels and SBP load, and positive correlated with night SBP decreasing rates. Meanwhile,24 hours urinary protein positive correlated with SBP, DBP increasing index and negatively correlated with decreasing rate of SBP and DBP at night. Urinary (32-MG and urinary NAG were negatively related to DBP decreasing rate at night. Urine protein and Ccr were no significant correlated with renal pathological pattern.Conclusion1. ABPM had high sensitivity to find high incidence of hypertension in children with PNS, which accurately find the lifted degree of blood pressure mean and blood pressure load which illustrated SBP increasing more significantly than DBP.2. It indicated the high incidence of MHT. That was conducive to provide early diagnosis and treatment of hypertension, classification of severe MHT benefited to establish the probability of target organ damage. 3. Night time blood pressure in children with PNS was significantly increased, and incidence of non-dipper blood pressure was high, which marked the 24-hour ambulatory blood pressure rhythm of children with PNS reduced or disappeared.4. The increase of ABP mean and load in children with PNS caused glomerular filtration rate reducing and renal injury.5. Non-dipper blood pressure in children with PNS lead to glomerular filtration rate reduce and renal damage. Objective To study the RAAS levels changes in children with PNS. To explore the relationships in RAAS elevated levels, ABPM and renal damage in children with PNS.Methods Applying Immuneγ-radiation counter measured RAAS(PRA, AngⅡand ALD) blood levels in children with PNS through decubitus anticoagulated blood. Correlation analysis in RAAS levels, ABP, renal damages and renal pathology.Results1. Blood PRA, AngⅡand ALD in children with PNS were significantly higher.2. Angll levels were closely positive correlation to ABPM(SBP, DBP) mean increased ratio. AngⅡlevels were closely positive correlation to ABP load(SBP, DBP).3. RAAS levels were closely negative correlation to Ccr. RAAS levels were closely positive correlation toβ2-MG and NAG. Conclusion1. RAAS levels were elevated in children with PNS.2. RAAS activity in children with PNS prompted blood pressure primarily by AngⅡ. Angll might be one of the factors to lift BP mean and loads.3. Elevated levels RAAS in children with PNS decreased renal function and increased renal damage. Increased Levels of blood PRA, AngⅡ, ALD might cause renal damage directly or indirectly. Objective To study the SNS levels changes in children with PNS. To explore the relationships in SNS elevated levels, ABPM and renal damage in children with PNS.Methods Utilizing high-performance liquid chromatography with electrochemical luminescence detection to measure 24-hour urine SNS (NA, A and DA)levels in children. To analyze the correlation in SNS level changes, ABPM data, renal damages and renal pathology.Results1.24-hour urinary NA, A and DA were significantly higher in children with PNS. The SNS levels were closely positive correlation to ABPM.2. NA, A and DA levels in Non-dipper group increased significantly.3. The overall effects of NA, A and DA were closely positive correlation to ABP mean and ABP load. They were also closely positive correlation to renal damages.4. NA elevated levels were closely positive correlation to urine β2-MG.5. AngⅡelevated levels were closely correlated to 24-hour urine NA, A and DA.Conclusion1. PNS children 24-hour urinary NA, A and DA levels were increased.2. Non-dipper patients had increased levels of NA, A and DA. That showed that the Non-dipper patients sympathetic nerve excitability were higher.3. NA, A and DA were the factors to promote ABP mean and ABP load increased.4. NA elevated level might be one of the factors of renal damages.5. RAAS elevated levels of AngⅡmay be directly increase the levels of SNS system. Objective Using ABPM evaluated the efficacy of Monopril in children with PNS and guided to create a new drug approach.Methods To compare changes in ABPM among different medication methods after 2 weeks treatment. To analyze the significance of different medication methods in improving ABPM figures. The Monopril point using group was selecting Monopril using point according ABPM levels and Non-dipper, and use Monopril 3 hours before ABP elevated intensively point or sleeping point. The Monopril routine using group according conventional medication used Monopril at 8am.Results1.7 cases of Monopril time point medication group included five cases of Non-dipper and 2 cases of Dipper. On one hand,5 cases of Non-dipper blood pressure mainly according to evaluated stage of blood pressure and Non-dipper factors selected medication time 3 hours before sleep time. On the other hand, Monopril medication time also selected 3 hours before went to bed in two cases of Dipper according to evaluated stage of blood pressure. 2. After 2 weeks application in two Monopril groups in children, the ABP mean and load decreased, meanwhile 24-hour ambulatory blood pressure rhythm improved.3. ABP mean and load decreased significantly in Monopril time point using group than in the conventional group and the Group without using Monopril.4. Night time decreasing rate increased significantly in Monopril time point using group than in the conventional group and the Group without using Monopril.Conclusion1. Monopril had the patency effect on high blood pressure control to reduce the ABP mean and load, and to lift the night time decreasing rate.2. ABP mean and load decreased significantly in Monopril time point using group than in the conventional group, which might be more powerful control in ABP extremely raised period. Monopril time point using is an ideal antihypertensive drug application method.3. Monopril time point medication method had high opportunity using pills before or in night which more significantly declined nocturnal blood pressure and reversed the non-dipper blood pressure, and improved 24-hour ambulatory blood pressure rhythm, which ensured controlling blood pressure more rationally.4. Monopril time point medication applied more effectively to reduce the mean blood pressure, to decrease blood load and to improve the circadian rhythm that illustrated an ideal blood pressure medicine method. The hospital without ABPM can choose using Monopril 3 hours before going to bed at night.