| Background and ObjectiveUnder normal physiological status, human blood pressure presents periodical rhythmchanges in the form of a “long-handle dipper” with “Double peaks and single valley”, andthe mean blood pressure at night is10%lower than that in the daytime, which is defined asdipper blood pressure. It is a blood pressure change mode naturally emerging in the courseof human evolution and adapting to the physiological activity characteristics and energyconsumption of the body day and night, which is crucial to ensure the balance betweenblood perfusion and functional requirements of vitals such as the heart, brain and kidney.For abnormal circadian rhythm, it is called non-dipper blood pressure if the mean nocturnalblood pressure is lower less than10%and anti-dipper blood pressure in case it is higherthan that in the daytime. Abnormal blood pressure rhythm may be accompanied byhypertension or independently exist. The incidence of non-dipper blood pressure rhythm inthe population with normal blood pressure is25%[1-2]. And that of abnormal blood pressurein patients with primary hypertension is40.6%-61.8%[3-4]. It is demonstrated that abnormalblood pressure rhythm is an independent risk and predictive factor for cardiovascular andcerebrovascular events[5]. The kidney is the core organ for the blood pressure adjustment.The mutually causal relationship between kidney diseases and hypertension is thepathological basis of the cardiarenal syndrome, but the relationship between kidneydiseases and blood pressure rhythm and the influence on renal and cardiac outcomes havenot yet been highlighted. It is reported that the incidence rate of non-dipper blood pressurein CKD patients is63.9%—81.4%[6-10], and patients undergoing a hemodialysis (82%)represent non-dipper rhythms[11]; and the morbility and mortality of cardiovascular eventsin hemodialysis patientsfor non-dipper blood pressure is3.5and9times of those in patientswith dipper blood pressure respectively[12]. IgAN is the leading cause of chronic renalfailure, which is mainly occurred in young adults with hypertension as their commonclinical manifestation. We explore the relationship between abnormal blood pressure rhythm and clinical and pathological manifestations to reveal the clinical significance andinfluencing factors of abnormal blood pressure rhythms in CKD patients, which willpresent an important clinical value in preparation of comprehensive preventions to delaythe progression of chronic kidney diseases and reduce the morbility and mortality ofcardiovascular events.Methods:From January2011to October2012,427cases of primary IgANs were diagnosedthrough renal biopsy in Nephrology Department of Daping Hospital (patient age:18-69years). A24h dynamic blood pressure monitoring was performed for all the patients, andtheir blood pressure and rhythms were evaluated in accordance with JNC7[13]hypertensiondiagnosis standard and the diagnosis standard of blood pressure circadian rhythm[14]. First,a research was conducted on the total incidence of abnormal blood pressure rhythm in allthe patients and the distribution characteristics of abnormal blood pressure rhythm inpatients with different sex, age group and medication. After exclusion of the patientscombined with diabetes mellitus, acute interstitial renal damage and administration ofglucocorticoids and antihypertensive drugs (86cases), a collection was conducted in341patients, including clinical data, renal pathology diagnosis information and blood andmorning urine on the day of blood pressure monitoring as well as24h urine specimen. Atotal of50indexes are included, including9items of clinical data (sex, age, height, bodyweight, BMI, course of disease, medical history, previous medications and smokinghistory),23laboratory indexes (hepatorenal function, blood lipid, blood glucose, urinebiochemistry, urine protein/creatinine and urinary NAG enzyme) and18renal histologicalindexes (Oxford IgAN classification and scoring[15]and immunopathogenesis indexes). Themeasurement data are expressed as mean±SD, and the classified variables are expressed asa rate. The comparison of measurement data between both groups was conducted by t test,the counting of data was performed by X2test, and the classification data were analyzed byRidit method. The study adopted the univariate and multivariate logistic regression analysisto investigate the influencing factors of blood pressure circadian rhythms in IgAN patientsby using the type of blood pressure circadian rhythm as the dependent variable, accompanied by analysis on discontinuous independent variable after assignment. All thedata were processed by using SPSS18.0and Ridit statistical software.Results:I. Distribution characteristics of blood pressure rhythm in427IgAN patients1. Incidence of abnormal blood pressure rhythm:68.0%(290/427) for non-dipper andanti-dipper blood pressure in IgAN patients;73.2%(120/164) for non-dipper blood pressurein patients with IgAN combined with hypertension, and68.8%(181/263) for non-dipperblood pressure in IgAN patients with normal blood pressure levels.2. Sex and age distribution of abnormal blood pressure rhythm: male,237cases,73.0%for non-dipper blood pressure; female,190cases,67.4%for non-dipper bloodpressure, and the incidence difference between both groups is not statistically significant(P=0.205). The age groups include18-45,46-65and>65years, with the percentage of67.6%(192/284),71.0%(98/138) and73.3%(11/15) respectively for non-dipper bloodpressure; and the incidence of non-dipper blood pressure for each age group was notsignificantly different (P>0.05).3. Non-dipper blood pressure distribution in Phase CKD1-4patients:65.6%(147/224)for Phase CKD1,71.8%(94/131) for Phase CKD2,79.4%(27/34) for Phase CKD3a,85.0%(17/20) for Phase CKD3b and88.9%(16/18) for Phase CKD4; and the differenceof comparison among groups is statistically significant (P<0.05).4. Blood pressure rhythm distribution in patients who have taken medicine:antihypertensive drugs: non-dipper blood pressure incidence58.6%(17/29). Glucocorticoids:non-dipper blood pressure incidence77.8%(14/18).II. Influencing factors of abnormal blood pressure circadian rhythms in341IgANpatients1. Clinical data comparison between IgAN patients with dipper and non-dipper bloodpressureNo matter whether the blood pressure levels of the patients are normal or not, there areno significant differences between both groups in age, sex, BMI, smoking history and bloodpressure level (24hSBP,24hDBP)(P>0.05). For patients with non-dipper blood pressure,the Cystatin C,urine protein/creatinine, blood uric acid, natriuresis level at night and urinary chloride excretion level at night are all significantly higher than those of the groupwith dipper blood pressure (P<0.05), and the difference between other laboratory detectionindexes has no statistical significance.2. Comparison of renal histopathological indexes between IgAN patients with dipperand non-dipper blood pressure(1) Histological damage indices: no matter whether the blood pressure levels arenormal or not, for the group with non-dipper blood pressure, the parameters below aresignificantly higher than those of the group with dipper blood pressure (P<0.05): the MESTscores, glomerular sclerosis>25%, glomerular collapse/ischemic change, renal tubularatrophy and interstitial fibrosis>25%, renal interstitial inflammatory infiltration>25%andrenal tubular lesions (including arcuate artery sclerosis, interlobular artery sclerosis andarteriole hyalinosis); and the difference between other renal histopathological indices hasno statistical significance.(2)Immunopathogenesis indices: the deposition strength of complement C3is“negative～＋＋＋＋”, and the incidence of non-dipper blood pressure is negative68.3%(69/101),“＋”67.9%(72/106),“＋＋”76.0%(76/100),“＋＋＋”93.5%(29/31) and “＋＋＋＋”100%(3/3) respectively; and the difference among groups is statistically different(P<0.05).3. Univariate analysis on abnormal blood pressure rhythm in IgAN patientsThe univariate analysis results of50indexes indicate, the following are related toabnormal blood pressure rhythm of IgAN: Cystatin C, Urinary P/C, blood uric acid, NUNa,NUCl, MEST scoring, Glomerular sclerosis>25%, glomerular collapse/ischemic change,TIF>25%, interstitial inflammatory infiltration>25%, arcuate artery sclerosis, interlobularartery sclerosis, arteriole hyalinosis, and the deposition strength of IgA and complement C3higher than “＋＋”.4. Multivariate logistic regression analysis on abnormal blood pressure rhythm inIgAN patientsFifteen variables with statistical significance in the univariate analysis were includedin the logistic regression analysis. The results showed that the influencing factors forabnormal blood pressure rhythm included Cystatin C(OR=3.121，95％Cl=1.794～6.469),Urinary P/C(OR=2.013，95％Cl=1.888～4.560), uric acid(OR=2.005，95％Cl=1.371～ 4.638), NUNa(OR=3.264，95％Cl=2.392～7.400)、 MEST score (OR=2.127，95％Cl=1.337～4.654), TIF>25％(OR=7.936，95％Cl=3.829～12.802), hyaline degeneration ofsmall arteries (OR=2.208，95％Cl1.418～5.739).III. Analysis of influencing factors on abnormal blood pressure rhythm in126IgANpatients combined with hypertension1. Clinical data of patients with dipper and non-dipper blood pressure in both groupsFor patients in the group with non-dipper blood pressure, the CHOL, Scr, Cystatin C,Urinary P/Cr, UA, NUNa and NUCl values are significantly higher than those of the groupwith dipper blood pressure, and the eGFR value of the group with non-dipper bloodpressure is significantly lower than that of the group with dipper blood pressure (P<0.05).The difference between other clinical and laboratory examination indexes has no statisticalsignificance.2. Comparison of renal histopathological indexes between patients with dipper andnon-dipper blood pressureFor patients in the group with non-dipper blood pressure, the MEST scores, segmentalglomerulosclerosis/capsular synechia, glomerular sclerosis>25%, glomerular collapse/ischemic change, renal tubular atrophy and interstitial fibrosis>25%, interstitialinflammatory infiltration>25%, renal tubular lesions (interlobular artery sclerosis andarteriole hyalinosis), and IgA and C3deposition strength>＋＋are significantly higherthan those of the group with dipper blood pressure (P<0.05); and the difference betweenother renal histopathological indexes has no statistical significance.3. Univariate analysis on abnormal blood pressure circadian rhythm in126IgANpatients combined with hypertentionThe analysis results of50single factors show, the CHOL, Scr, eGFR, Cystatin C,Urinary P/C, blood uric acid, NUNa, NUCl, MEST scores, segmental glomerulosclerosis/capsular synechia, glomerular sclerosis>25%, glomerular collapse/ischemic change,TIF>25%, interstitial inflammatory infiltration>25%, renal tubular lesions (interlobularartery sclerosis and arteriole hyalinosis), and complement C3deposition strength>＋＋are relevant to the non-dipper blood pressure rhythm of IgAN patients combined withhypertension.4. Multivariate logistic regression analysis on abnormal blood pressure circadian rhythm in126IgAN patients combined with hypertensionSeventeen variables with statistical significance in the univariate analysis wereincluded in the logistic regression analysis. The results showed that the influencing factorsfor IgAN patients combined with hypertension included eGFR (OR=1.237，95％Cl=1.003～1.655), uric acid (OR=1.574，95％Cl=1.109～2.922), MEST score (OR=3.010，95％Cl=1.345～6.005), TIF>25％(OR=3.549，95％Cl=1.529～6.428) and hyalinedegeneration of small arteries (OR=1.207，95％Cl=1.066～3.017).IV. Analysis of influencing factors on abnormal blood pressure rhythm in215IgANpatients with normal blood pressure1. Comparison of clinical data between dipper and non-dipper IgAN patientsThere are no significant differences between both groups in age, sex, BMI, smokinghistory and blood pressure level (24h SBP,24h DBP)(P>0.05). For patients withnon-dipper blood pressure, the urine protein/creatinine, blood uric acid, NUNa and NUClvalues are significantly higher than those of the group with dipper blood pressure (P<0.05),and the difference between other laboratory detection indexes has no statisticalsignificance.2. Comparison of renal histopathological indexes between dipper and non-dipper IgANpatientsFor the group with non-dipper blood pressure, the values of MEST scores, glomerularcollapse/ischemic change, renal tubular atrophy and interstitial fibrosis>25%, interstitialinflammatory infiltration>25%, and renal tubular lesions (including arcuate artery sclerosis,interlobular artery sclerosis and arteriole hyalinosis) are higher than those of the group withdipper blood pressure respectively (P<0.05); and the difference between other renalhistopathological indexes has no statistical significance.3. Univariate analysis on abnormal blood pressure rhythm in IgAN patients withnormal blood pressureThe univariate analysis on50items of clinical data and renal histopathological indexesindicates, the values of urine protein/creatinine, blood uric acid, NUNa, NUCl, MESTscores, glomerular collapse/ischemic change, TIF>25%, interstitial inflammatoryinfiltration>25%, and renal tubular lesions (arcuate artery and interlobular artery sclerosisand arteriole hyalinosis) may be relevant to the abnormal blood pressure non-dipper blood pressure circadian rhythm of IgAN patients with normal blood pressure.4. Multivariate logistic regression analysis on abnormal blood pressure rhythm inIgAN patients with normal blood pressureEleven variables with statistical significance in the univariate analysis were includedin the logistic regression analysis. The results showed that the influencing factors for IgANpatients with normal blood pressure included Urinary P/C (OR＝2.827，95％Cl＝1.722～5.382)，uric acid (OR＝1.995，95％Cl＝1.002～3.999)、NUNa(OR＝3.147，95％Cl＝2.020～6.296), MEST score (OR＝2.283，95％Cl＝1.299～4.641), TIF>25％(OR＝5.931，95％Cl＝1.718～10.476), hyaline degeneration of small arteries (OR＝4.044，95％Cl＝2.448～8.926). Conclusions:1. For IgAN patients, no matter whether their blood pressure levels are normal or not,the incidence of abnormal blood pressure rhythm is70.5%; it is73.2%for IgAN combinedwith hypertension, and68.8%for those with normal blood pressure which is1.8-3times ofthat of patients with primary hypertension and the general population, indicating abnormalblood pressure rhythm is an important problem for CKD patients. Taking corticosteroidsmay have a certain effect on blood pressure rhythm of IgAN patients;58.8%of the IgANpatients receiving antihypertensive drugs still present abnormal blood pressure rhythm,indicating the therapy of antihypertensive drugs cannot completely solve the problem ofabnormal blood pressure rhythm in CKD patients and this may be an adverse factoraffecting the renal and cardiac outcomes.2. The analysis on correlation between blood pressure rhythm and clinical pathologicalparameters of341IgAN patients shows, no matter what the blood pressure level is,non-dipper blood pressure rhythms are directly related to the severity of renal damage andthe clinical pathological parameters affecting the outcomes of the IgAN patients, includingCysC, urine protein/creatinine ratio, MEST scores, and renal interstitium and renal tubularlesions, indicating non-dipper blood pressure rhythms have a warning significance forIgAN progression and renal and cardiac outcomes. Furthermore, our study stilldemonstrated, no matter what the blood pressure level is, the abnormal blood pressurerhythm of IgAN patients is directly related to natriuresis at night and blood uric acid level,indicating the abnormal ion transport function caused by renal tubular interstitial lesions inIgAN patients may be an important factor to lead to abnormal blood pressure rhythm.3. The subgroup analysis conducted by this study in IgAN patients with normal blood pressure reveals, the incidence of non-dipper blood pressure is unexpectedly up to68.8%,and the non-dipper blood pressure rhythm is directly related to increased urine proteinexcretion, MEST scores, renal tubular interstitial lesions and arteriole hyalinosis. Thisindicates, even the IgAN patients have no hypertension combined, abnormal blood pressurerhythm is an important factor affecting the IgAN progress. Furthermore, we also found, theincidence of arteriole hyalinosis reaches up to40.5%in the IgAN patients with normalblood pressure, and is directly related to abnormal blood pressure rhythm, indicating theabnormal blood pressure rhythm may be independent of the blood pressure level and has amutually causal relationship with IgAN renal tubular lesions and thus to promote the IgANprogress and the occurrence of cardiovascular system damage. The above results show, theevaluation on blood pressure rhythm of CKD patients with normal blood pressure cannot beignored in clinical practice, especially for the patients with normal blood pressure butcombined with hyperuricemia and abnormal natriuresis at night, more should be done toscreen blood pressure rhythm and the abnormal blood pressure rhythm should be regardedas an important target for improvement of CKD renal and cardiac outcomes. In addition,reducing blood uric acid level and promoting natriuresis may be regarded as the measuresfor treatment of abnormal IgAN blood pressure rhythm not combined with hypertension.4. The subgroup analysis conducted by this study in IgAN patients combined withhypertension reveals, in addition to renal histopathological indexes and blood uric acidlevel, the abnormal blood pressure rhythm is also directly related to eGFR, indicating thesuperimposed effect of abnormal blood pressure rhythm is an important influencing factorto lead to poor IgAN rental and cardiac outcomes. Therefore, for treatment of IgAN patientscombined with hypertension, it is necessary to control the blood pressure level to reach thestandard, and it is also crucial to correct the abnormal blood pressure rhythm andhyperuricemia and thus to improve the renal and cardiac outcomes.Limitations and deficiencies1. This study is to explore the clinical significance and influencing factors of abnormalblood pressure rhythm in IgAN patients through a cross-sectional study, but lacking directevidence of abnormal blood pressure rhythm affecting the renal outcomes andcardiovascular event risks of IgAN patients. More should be done in the future to longitudinally track the risk and severity of renal function damage and cardiovascularcomplications in IgAN patients with abnormal blood pressure rhythm.2. Due to limited cases, the relationship between the anti-dipper and deep-dipper bloodpressure rhythms and IgAN were insufficiently studied. A further analysis should be doneby using an enlarged sample size.3. This study failed to conduct a comprehensive collection for demographic data (suchas occupation, work environment and life style, etc.) which may affect blood pressurecircadian rhythms, Accurate course ofIgAN disease course and occurrence time ofabnormal blood pressure rhythm, which had a certain effect on the exploration of bloodpressure rhythm influencing factors. |
PDF Full Text Request