Is nighttime masked uncontrolled hypertension (MUCH) in patients with chronic kidney disease (CKD) not receiving dialysis associated with worse cardiovascular and kidney outcomes?In this cohort study of 675 patients with hypertension and nondialysis CKD, approximately one-third of patients had nighttime MUCH, consisting of 13.0% day-night MUCH and 22.8% isolated nighttime MUCH. Day-night MUCH was associated with left ventricular hypertrophy, and isolated nighttime MUCH was associated with kidney function deterioration.In this study, ambulatory blood pressure monitoring was necessary among patients with CKD to promote the management of nighttime hypertension and to benefit cardiovascular and kidney outcomes, even in patients with controlled office hypertension. This cohort study investigates the prevalence of nighttime masked uncontrolled hypertension and its associations with cardiovascular and kidney outcomes in patients with chronic kidney disease (CKD) who were not receiving dialysis. Nighttime hypertension is prevalent and associated with adverse outcomes in patients with chronic kidney disease (CKD), but nighttime hypertension, a subtype of masked uncontrolled hypertension (MUCH), is often undetected among patients with controlled office blood pressure. Little attention has been paid to patients with CKD and nighttime MUCH.To investigate the prevalence of nighttime MUCH and its associations with cardiovascular and kidney outcomes in patients with CKD who were not receiving dialysis.This retrospective cohort study included patients with nondialysis CKD and hypertension, enrolled in Shanghai, China, from July 2012 through November 2020 and followed up for a median of 39 months.Participants were classified as having controlled hypertension, sustained hypertension, and MUCH, which was further divided into isolated nighttime MUCH and day-night MUCH, assessed by office and ambulatory blood pressure monitoring.Left ventricular hypertrophy (LVH) was determined by echocardiography. The composite kidney outcome consisted of end-stage kidney diseases (ESKD) and a reduction of estimated glomerular filtration rate (eGFR) by 50% or more. Logistic and Cox regression assessed the associations of hypertension subtypes with LVH and kidney outcomes.2) included 125 (19.3%) with controlled hypertension, 244 (37.6%) with MUCH, and 280 (43.1%) sustained hypertension. Among patients with MUCH, 2 (0.8%) had isolated daytime MUCH, 154 (63.1%) had isolated nighttime MUCH, and 88 (36.1%) had day-night MUCH. During a median (IQR) follow-up of 39 (19-64) months, 130 composite kidney events, including 97 ESKD events, occurred. Compared with controlled hypertension, MUCH and sustained hypertension were associated with LVH  and the composite kidney outcome  after adjustment for age, sex, proteinuria, eGFR, and other baseline risk factors. Multivariate-adjusted associations were also significant between day-night MUCH and LVH  and between isolated nighttime MUCH and the composite kidney outcome .The 675 patients (425 [63.0%] men; mean [SD] age, 50.8 [15.9] years; mean [SD] eGFR, 61.6 [29.4] mL/min/1.73 mIn this cohort study, nighttime MUCH was common and associated with LVH and poor kidney outcomes among patients with hypertension and nondialysis CKD. These findings suggest that ambulatory blood pressure monitoring was inadequately used in patients with CKD and hypertension, calling for more widespread use, even in patients with controlled office hypertension. Additionally, the association between nighttime MUCH and cardiovascular and kidney outcomes among patients with CKD is unknown. Therefore, we conducted a retrospective analysis in Chinese patients with CKD not receiving dialysis.Masked uncontrolled hypertension (MUCH) has usually been defined as uncontrolled 24-hour or daytime hypertension in the presence of a controlled office BP.STROBE) reporting guideline.From July 1, 2012, through November 31, 2020, patients with CKD and hypertension were enrolled in the Nephrology Department of Ruijin Hospital, which is affiliated with the Shanghai Jiao Tong University School of Medicine. The study protocol was approved and an exemption of informed consent granted because of the retrospective nature of the study by the Ethics Committee of the Ruijin Hospital. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology  2012 clinical practice guideline21; with an estimated GFR (eGFR) of at least 20 mL/min/1.73 m2 at baseline; and a diagnosis of hypertension based on an office systolic BP measurement of at least 140 mm Hg and diastolic BP measurement of at least 90 mm Hg or the use of antihypertensive drugs. Patients were excluded for having acute kidney injury; receiving kidney transplantation; being pregnancy; having atrial fibrillation; having inadequate ABPM readings; and having invalid follow-up data . A total of 1122 patients fulfilled the inclusion criteria, and 125 patients were excluded because of acute kidney injury (n = 68), kidney transplantation (n = 14), pregnancy (n = 1), atrial fibrillation (n = 21), and inadequate ABPM readings (n = 21). Among the remaining 997 patients with nondialysis CKD, 322 with a follow-up of less than 3 months without any kidney events were further excluded to avoid any possible confounding associated with the short follow-up. Therefore, 675 patients were included in the present analyses  of 60 mL/min/1.73 manalyses . Compareanalyses .am to 10 pm and every 30 minutes from 10 pm to 6 am. Daytime and nighttime were defined accordingly. If at least 1 systolic and diastolic BP measurement was obtained every hour, with at least 20 readings during the day and 7 readings during the night, the ABPM was considered adequate. The BP dipping ratio was calculated as the percentage of the difference between daytime and nighttime average BPs to the daytime average BP.Office BP was measured with an automated sphygmomanometer (Omron HBP-1300) after patients had 5 minutes of rest in a sitting position. Three consecutive readings with an interval of 1 minute were obtained and averaged for analyses. The 24-hour ABPM was performed with the 90217A monitors (Spacelabs Inc). The monitors recorded BP every 15 to 20 minutes from 6 22 was calculated as 0.8 × 1.04 × ([LVEDD + IVST + PWT]3 – LVEDD3] + 0.6. The LVM index (LVMI) was the ratio of LVM to body surface area. Left ventricular hypertrophy (LVH) was defined as an LVMI greater than 115 g/m2 in men and greater than 95 g/m2 in women.23Echocardiography was performed by experienced cardiologists. End-diastolic interventricular septal wall thickness (IVST), left ventricular diameter (LVEDD), and posterior wall thickness (PWT) were assessed from M-mode tracings. Left ventricular mass (LVM)24 We evaluated a composite kidney end point consisting of ESKD  and a reduction of eGFR by 50% or greater, whichever occurred first. The occurrence of events was confirmed through medical records during follow-up visits.Serum creatinine was analyzed by automated enzymatic methods. The eGFR was estimated using the CKD–Epidemiology Collaboration (CKD-EPI) formula and graded to CKD stages 1, 2, 3, and 4 according to KDIGO.6 respectively. Controlled out-of-office hypertension was defined as controlled daytime and nighttime hypertension. White coat hypertension was uncontrolled office hypertension with controlled out-of-office hypertension. MUCH was controlled office hypertension with uncontrolled out-of-office hypertension. According to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines,5 we defined stage 1 MUCH as a daytime systolic BP of 135 to 144 mm Hg and diastolic BP of 85 to 89 mm Hg or nighttime systolic BP of 120 to 139 mm Hg and diastolic BP of 70 to 84 mm Hg. Stage 2 MUCH was defined as a daytime systolic BP of 135 mm Hg or greater and diastolic BP of 85 mm Hg or greater or nighttime systolic BP of 140 mm Hg or greater and diastolic BP of 85 mm Hg or greater. MUCH was further subdivided into isolated daytime MUCH, isolated nighttime MUCH, and day-night MUCH  and 95% CIs of LVH. Univariate and multivariate Cox regression analyses were performed to estimate the associations of hypertension subtypes with kidney outcomes. In multivariate analyses, age, sex, and body mass index were included as covariables in model 1 and diabetes, use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, eGFR, hemoglobin level, and proteinuria were included in model 2. All P values were 2-sided and were considered significant if P < .05. Graphs were generated with Prism version 9 (GraphPad Software).Statistical analyses were performed using SPSS statistical software version 25 (IBM Corp). Data were tested for normal distribution using the Shapiro-Wilk test. Descriptive statistics are mean and SD for continuous variables, median and IQR for nonparametric variables, and frequency and percentage for categorical variables. Comparisons among groups were performed using nonparametric tests or analysis of variance with Bonferroni method for post hoc multiple comparisons for continuous variables and χ2. Among all patients, 141 (20.9%), 169 (25.0%), 256 (37.9%), and 109 (16.1%) had CKD stages 1, 2, 3, and 4, respectively. The median (IQR) of 24-hour urinary protein excretion was 1786 (574-3938) mg.Of the 675 patients with nondialysis CKD and hypertension , 425 , 154 patients (63.1%), and 88 patients (36.1%), respectively . The 2 pP = .02) and sustained hypertension  were associated with higher odds of LVH in fully adjusted analyses. In the further fully adjusted grade analysis, stage 2 MUCH was associated with LVH with an OR of 4.03  (eTable 6 in the LVH was detected in 6 patients with controlled hypertension (5.2%), 39 patients with MUCH (16.5%), and 72 patients with sustained hypertension (26.7%); it was detected among 24 patients with isolated nighttime MUCH (15.9%) and 15 with day-night MUCH (17.9%). P = .03). The odds for isolated nighttime MUCH was not significant  after fully multivariable adjustment  follow-up of 39 (19-64 months) month, 130 (19.3%) composite kidney events and 97 (14.4%) ESKD events occurred. Event numbers and hazard ratios (HRs) with 95% CIs by hypertension subtype are reported in P = .001) and sustained hypertension  were significantly associated with increased risk of the composite kidney outcome and ESKD. The significance persisted after partial and full adjustment for covariates, except for the association of ESKD with MUCH after full multivariable adjustment . Furthermore, both stages 1 and 2 MUCH had a significantly higher risk of composite kidney outcomes compared with controlled hypertension , daytime BP measurement  and nighttime BP measurement  recommended by the 2017 ACC/AHA hypertension guidelines, a total of 74 (11.0%), 107 (15.9%), and 440 (65.2%) had controlled hypertension, MUCH, and sustained hypertension, respectively. Among the 107 patients with MUCH, isolated daytime, isolated nighttime, and day-night MUCH accounted for 10 (9.3%), 53 (49.6%), and 44 (41.1%), respectively. Compared with controlled hypertension, MUCH was not associated with a statistically significant higher odds of LVH   participants in the CKD subgroup had masked asleep hypertension.35 In the current study, both stage 1 and 2 MUCH were associated with LVH and an increased risk of kidney function deterioration. Furthermore, when using lower BP thresholds recommended by the 2017 ACC/AHA hypertension guidelines, MUCH remained significant in the association with kidney function deterioration. A cross-sectional and observational cohort that enrolled 1492 patients with CKD and an eGFR of 20 to 70 mL/min/1.73 m2 reported that MUCH was associated with lower eGFR and greater LVMI only in the presence of elevated nighttime BP,16 suggesting that nighttime hypertension played an important role in target organ damage in patients with MUCH. In this study, we verified that nighttime MUCH, irrespective of the combination with daytime MUCH, was associated with LVH. Furthermore, we reported, to our knowledge for the first time, that nighttime MUCH increased the risk of progression of kidney diseases and ESKD in patients with CKD. Most previous studies evaluating the prognostic value of MUCH relied on daytime BP measurements or the 24-hour BP measurement.41 Only a few emphasized nighttime BP.41 In 738 White patients with treated hypertension, nighttime MUCH was associated with increased risk of cardiovascular events, but isolated nighttime MUCH did not attain statistical significance after adjustment.32 A report from the Chronic Renal Insufficiency Cohort Study demonstrated that MUCH, defined as achieved office BP and elevated 24-hour BP, was associated with high risk of cardiovascular disease and progression of kidney disease in patients with CKD, and nighttime BP predicted the progression of kidney disease.39MUCH was associated with kidney dysfunction, the extent of proteinuria, and higher LVMI in earlier cohorts.We observed that more than one-third patients with CKD had MUCH, with 99.5% with nighttime MUCH, suggesting the poor management status of nighttime hypertension in our clinical practice. It is important to note that patients with nighttime MUCH, irrespective of the subtype (day-night or isolated nighttime), were at high risk of target organ damage and kidney disease progression, reinforcing the importance of controlling nighttime BP and both subtypes of nighttime MUCH to prevent poor kidney outcomes in patients with CKD. Our findings support the value of 24-hour ABPM in the management of hypertension, especially in patients with CKD. However, clinical use of ABPM has been limited in the past by variable factors, including economic and human cost. Meanwhile, management of nighttime MUCH still lacks clinical experience reports or evidence-based medical research. For example, antihypertensive regimens might be different for the 2 types of MUCH, with varying dosing times of drugs and choice of long or short half-life drugs. Future clinical trials are needed to explore effective interventions on nighttime MUCH and to assess the effect of lowering BP on clinical outcomes among patients with CKD.43 with a similar baseline eGFR. Our conclusions may not be directly generalized to other populations. Third, ABPM was performed once at baseline. Considering the moderate reproducibility of ABPM,44 it is better to define MUCH based on repeated ABPM. Fourth, residual confounding or some unmeasured variables,45 such as interventions over follow-up, physical activities, diet, smoking, and sleep disorders, might in part explain the associations between MUCH and outcomes. Fifth, there might be a chance of false-positive results because of multiple comparisons in the analyses of logistic and Cox regressions. The small sample size in subgroups may affect the significance of differences. Prospective cohort studies with larger scale and including other ethnic populations may be required.This study has limitations, including its retrospective observational design. Second, the patients were recruited from a single Chinese nephrology ward in a tertiary hospital, among whom nearly 60% had glomerulonephritis. The incidence rate of ESKD was higher than that in other studies,The present study found that MUCH, especially nighttime MUCH, was common among patients with CKD and was associated with LVH and poor kidney outcomes. These findings may suggest the importance and irreplaceability of ABPM in the management of nighttime hypertension in patients with CKD.


Shrunken pore syndrome (SPS) represents selective impairment of kidney filtration of low-molecular-weight molecules between 1 and 30 kDa and has been related to outcomes including morbidity, mortality, and cardiovascular events. However, the prevalence and kidney outcomes of SPS have not been investigated in patients with IgA nephropathy (IgAN) and membranous nephropathy (MN).  We retrospectively collected information of 536 patients including 414 with IgAN and 122 with MN. SPS was mainly defined by cystatin C-based eGFR < 70% of creatinine-based eGFR using the CAPA-LM equation pairs, while CKD-EPI equations were also employed in sensitivity analyses. Prevalence rate of SPS and its association with end-stage renal disease (ESRD) or severe eGFR decline (≥50% eGFR reduction or doubling of baseline creatinine) were investigated.  44% (8%) patients were identified as possessing SPS using the CAPA-LM definition. ESRD happened in 24 patients during the average follow-up period of 27.7 months. Despite dramatic increase of incidence rate of ESRD for SPS, significant hazard ratio (HR) only existed in IgAN patients after multivariable adjustment , but lost significance in sensitivity analyses. 36 patients were determined as having experienced severe eGFR decline after excluding transient creatinine fluctuation. SPS was associated with severe eGFR decline by Kaplan-Meier survival analyses in the overall population as well as the IgAN, MN, male, and female subpopulations, which remained significant in multivariable adjustments in all groups except IgAN. However, only in female patients the association between SPS and eGFR decline remained significant in all the sensitivity analyses.  SPS was independently associated with eGFR decline in female patients with IgAN and MN. The kidneys are important organs governing fluid homeostasis and substance excretion. Reduced kidney function has become prevalent and is devastating as it greatly increases morbidity, mortality, and cardiovascular complications . CurrentHowever, the role of kidney is far beyond the filtration of small molecules. A substantial proportion of low-molecular-weight molecules within 1~30 kDa are cleared by kidneys in normal physiology, but this function has long been overlooked among academic society . CystatiSo far, SPS has been identified in diverse populations from pregnant women  to patieThis is a retrospective cohort study based on subjects with biopsy-proven IgAN or MN admitted to Tongji Hospital between December 2011 and September 2019. The study was approved by the medical ethical review board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and was conducted according to the Declaration of Helsinki. Informed consent was waived due to its retrospective design and observational nature.1741 patients with IgAN and 650 patients with MN were screened, and those were included with simultaneous measurements of cystatin C and creatinine at baseline when corticosteroids were not used. Patients who were pregnant, less than 18 years old, undergoing renal replacement therapy, with AKI, uncontrolled malignant neoplasm, thyroid diseases, end-stage renal disease (ESRD), syphilis, adrenal cortical insufficiency, concomitant ANCA vasculitis, or SLE were excluded. The final sample enrolled 536 patients.We collected information on kidney pathology from biopsy records and demographic, behavioral, and laboratory information together with data on comorbidities and medications from electronic medical records. All laboratory results were produced from a centralized laboratory of Tongji Hospital using standard methods periodically recalibrated against the reference material. Mean arterial pressure was calculated by adding 1/3 of systolic blood pressure to 2/3 times diastolic blood pressure.The Caucasian Asian Pediatric Adult (CAPA) equation:(ii) The revised Lund-Malmö (LMrev) equation:μmol/L, X is calculated asμmol/L, X is calculated asμmol/L, X is calculated asμmol/L, X is calculated asThe CAPA-LM equation pair was the default method for assessing SPS unless stated otherwise, by using the definition of eGFRcys < 70% of eGFRcr at baseline as previously reported , 21. CorThe cystatin C-based CKD-EPI (CKD-EPIcys) equation:For females with cystatin C ≤ 0.8 mg/L,(2) For females with cystatin C > 0.8 mg/L,(3) For males with cystatin C ≤ 0.8 mg/L,(4) For males with cystatin C > 0.8 mg/L,(ii) The creatinine-based CKD-EPI (CKD-EPIcr) equation:For females with creatinine ≤ 0.7 mg/dL,(2) For females with creatinine > 0.7 mg/dL,(3) For males with creatinine ≤ 0.9 mg/dL,(4) For males with creatinine > 0.9 mg/dL,However, in sensitivity analyses, positive results were confirmed by examining the more relaxed CKD-EPI definition for diagnosis of SPS. Detailed equations are listed as follows:2 or the initiation of renal replacement therapy. Severe eGFR decline was defined as stable serum creatinine doubling or ≥50% eGFRcr decline compared with baseline [Medical records were screened, and all the outpatient and in-hospital creatinine results were exported from the clinical examination database till February 18th, 2022. ESRD referred to eGFR ≤ 15 mL/min/1.73 mbaseline . For cont-test or Mann–Whitney test was used according to data distribution to compare continuous variables. A chi-square test was conducted to compare nominal variables. Ordinal variables were compared using the Mann–Whitney test.Categorical variables were represented as number (percentage). Continuous variables were either represented as the mean ± standard deviation when normally distributed or as median  otherwise. An independent Kidney survival was analyzed using Kaplan-Meier plots followed by a log-rank test. Hazard ratios (HRs) and 95% confidence interval (95% CI) were calculated using Cox regression. Variables significantly associated with outcomes were adjusted in a stepwise manner: Model 1 was adjusted for basic demographics and anthropometrics—age, sex, and MAP ; Model 2 was further adjusted for follow-up treatments—ACEi/ARB, glucocorticoids, and immunosuppressants; Model 3 was further adjusted for kidney pathology—presence of glomerulosclerosis, crescents, and pathology diagnosis; Model 4 was further adjusted for laboratory results—baseline eGFR, bicarbonate, blood urea nitrogen, uric acid, total cholesterol, serum potassium, natrium, chloride, calcium, phosphate, hemoglobin, albumin, fibrinogen, and lgUALB . To minimize the possibility of overfitting, SPS was fitted using Enter method in block 1 followed by covariables fitted in block 2 using Forward LR (likelihood ratio) method. Urine albumin concentration was log transformed in Cox regression to approximate normal distribution.Missing values were omitted in baseline description and group comparison where total number of patients with complete records is shown. However, in Cox regression, an imputed dataset where missing values were replaced by median values of the overall population was used . If the P values < 0.05 were considered statistically significant. Patients' preselection procedure for determining outcomes, as well as data sorting and preprocessing was performed using Microsoft EXCEL . All statistical calculations were performed using SPSS 26.0.0.0 . Plots were drawn using R version 4.1.1  with R packages survival and survminer loaded.Double-sided n = 414, 77%) and the MN subpopulation . The IgAN subpopulation comprised more female patients, were younger, and had higher creatinine and blood pressure, more pronounced kidney pathology with respect to glomerulosclerosis and crescent formation, and severer hematuria, whereas the MN patients had more prevalent glucocorticoids and immunosuppressant usage in the follow-up period, thicker basement membrane, higher blood cholesterol and fibrinogen, lower blood albumin, and more abundant urine albumin secretion.We performed the patient selection procedure as shown in 2 compared to the LMrev equation (median eGFR: 95 mL/min/1.73 m2 by CKD-EPIcr vs. 84 mL/min/1.73 m2 by LMrev), whereas the two cystatin C-based equations performed similarly . These unparallel differences caused the assessment of prevalence to be much high once the CKD-EPI formulae were used to determine SPS .We observed 44 patients (8%) possessing SPS in our overall population. Although the prevalence did not differ significantly between the IgAN (7%) and MN (12%) patients, the eGFRcys/eGFRcr ratio was significantly higher among IgAN patients compared with the MN population. Also, prevalence of SPS was significantly higher in male patients than in female patients (12% in men vs. 5% in women). Moreover, it is worth noting that the CKD-EPIcr equation overestimated GFR by around 5~10 mL/min/1.73 mP = 0.088). As expected, serum cystatin C level was higher and both eGFRcys and eGFRcys/eGFRcr ratio were lower among all groups.When comparing patients with and without SPS, we found those with SPS had significantly higher serum fibrinogen and lower albumin in the overall population. In subgroup analyses, creatinine level was higher and glomerulosclerosis was more common in SPS patients than in non-SPS ones among the IgAN subgroup; in MN subpopulation, a tendency of more urine albumin concentration in SPS patients than non-SPS ones was noted with a marginal significance  and was the mildest in male patients (2.2-fold). This was paralleled with the survival analyses , follow-up treatments , kidney pathology , and laboratory results  as listed in Automatic algorithm selected a total of 44 patients fulfilling the requirements for doubling of serum creatinine or loss of more than 50% eGFR. After carefully screening each patients' creatinine lists and medical records, we excluded 8 patients with transient eGFR decline and postponed the occurrence of severe eGFR decline by 39.9 months for one patient (the former was transient but the latter was a permanent loss) and finally determined 36 patients who had experienced severe eGFR decline in our follow-up.The pattern of influence of SPS on occurrence of severe eGFR decline was somewhat similar to that seen in ESRD, with the fold increasement which was much higher in women than in men (6.6-fold vs. 3-fold). Of note, the fold increasement was the highest in MN patients (7.6 folds), which corresponds to the highest hazard ratio in Cox regression before adjustment. In IgAN patients, the presence of SPS brought about a 3.5-fold increasement of incidence of severe eGFR decline. Survival plots  with possibly milder situation due to the looser standard. Consequently, hazard ratio decreased in all settings and significant result only maintained in female patients after full adjustment with respect to the relationship between SPS and severe eGFR decline. Furthermore, we also tested the correlation between the eGFRcys/eGFRcr ratio calculated by both the CKD-EPI and the CAPA-LM methods and relevant outcomes. Still, only in female patients a higher eGFRcys/eGFRcr ratio was protective for eGFR decline after adjustments .In this study, we investigated the prevalence of SPS in biopsy-proven IgAN and MN patients and assessed its association with kidney outcomes. SPS greatly increased the incidence rates of ESRD and severe eGFR decline. However, only in female patients the association between SPS and severe eGFR decline was statistically significant after multivariable adjustment and sensitivity analyses. Thus, our study suggests SPS as a potential risk factor for disease progression in female patients with kidney diseases.The association of cystatin C with cardiovascular or renal outcomes have been discovered for a long time, and the predictive value of cystatin C for adverse clinical outcomes is not only superior to creatinine –27 but aPrevious researches unveiled the existence of SPS in diverse populations with varying prevalence rate from 0.2% to 36%, and the occurrence of SPS is irrelevant to conventional GFR measured by small molecules, reflecting the role of SPS as a formerly unrecognized type of renal dysfunction . The selThere is no consensus regarding the cut-off value for defining SPS. Both 60% and 70% eGFRcys/eGFRcr ratio have been used in previous studies , 15, 17.The major difference between the CKD-EPI and CAPA-LM standards lay in the higher eGFRcr computed by the CKD-EPIcr than the LMrev equation. This resulted in lower eGFRcys/eGFRcr ratio by the CKD-EPI equations compared to the CAPA-LM equations, which led to greater proportion of patients classified as SPS. In other words, the CAPA-LM definition represents a stricter criterion for SPS classification that identifies patients with more advanced pathophysiological changes. This judgment could be verified by the fact that all the 44 afflicted patients by SPSCAPA-LM were also included in the 95 patients with SPSCKD-EPI. The hazard ratios were generally greater, and statistical significances were more pronounced by SPSCAPA-LM compared to that of SPSCKD-EPI, which were also present in other studies involving both definitions , 17, 18.Although incidence rates of both ESRD and severe eGFR decline were dramatically elevated under SPS, we could only demonstrate significant effect concerning eGFR decline after multivariable adjustment in female patients. Due to limited follow-up duration of around one and a half year by median, ESRD happened in only 24 patients of our sample. Thus, insufficient sample size might account for our inability to get a significant result. However, since doubling of creatinine or more than 50% eGFR decline have been established as reliable surrogate markers for final ESRD , 23, we Sex difference was observed in our study, as the prevalence of SPS was lower but the HR was significant in women compared to men. Sex-related difference has been reported in some researches: a lower eGFRcys/eGFRcr ratio was shown to be hazardous in the development of first-ever myocardial infarction  and aortEven if cystatin C has many advantages in clinics, special caution must be paid to non-renal influences of cystatin C, which might deviate the true level of eGFRcys/eGFRcr ratio and cause false classification of SPS. One of the most prevalent nonrenal influences in patients with kidney diseases is the use of glucocorticoids, which is frequently prescribed in immunologic kidney diseases and causes abnormal elevation of cystatin C –42. AnotOur study has both limitations and strengths. The major limitation is the retrospective observational design, which prohibited us to test causal relationships. Second, limited sample size not only restricted the statistical power to gain significant results but also diminished the reliability of our conclusion. However, as we employed a group of sensitivity analyses, we are convinced to the validity of our results. Further, mGFR is not measured in our study. Using eGFRcr to approximate mGFR suffered from the risk of non-renal influences of creatinine, for example, sarcopenia. Though lack of parameters such as body mass index prevented us to rule out the risk, we believe it is not very likely due to our SPS group had higher creatinine value at baseline compared to the non-SPS patients. The primary strength of our study relates to the clearly defined pathologic changes diagnosed by biopsy, which have not been studied before and the homogenous pathologic background reduces possible confounding factors. Second, we adjusted various potential factors in multivariable models encompassing basic demographics, anthropometric measurements, important medication, and laboratory parameters. Third, sensitivity analyses listed above made our results more convincing.In conclusion, we investigated the incidence rates and clinical consequences of SPS in patients with IgAN or MN and found significant association between SPS and eGFR decline in female patients. Further studies are needed to verify the link between SPS and renal outcomes in larger prospective cohorts concerning diverse populations.


In the initial diagnostics of arterial hypertension (AH) laboratory medicine is a cornerstone, along with a blood pressure (BP) measurement and an electrocardiogram. It mainly refers to routine blood and urine tests for diagnosis and monitoring primary hypertension and its associated conditions such as asymptomatic hypertension-mediated organ damage, chronic kidney disease and hypertensive disorders of pregnancy. In addition, long term non-fatal and fatal risks for cardiovascular (CV) events in hypertension are assessed based on clinical and laboratory data. Furthermore, laboratory medicine is involved in the management of hypertension, especially in monitoring the disease progression. However, antihypertensive drugs may interfere with laboratory test results. Diuretics, especially thiazides, can affect blood and urine sodium concentrations, or angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can affect the blood biomarkers of the renin-angiotensin-aldosterone system (RAAS). It’s dysfunction plays a critical role in primary aldosteronism (PA), the most common endocrine disorder in secondary hypertension, which accounts for only small proportion of AH in relative terms but substantial proportion of hypertensives in absolute terms, affecting younger population and carrying a higher risk of CV mortality and morbidity. When screening for PA, aldosterone-to-renin ratio still contributes massively to the increased incidence of the disease, despite certain limits. In conclusion, laboratory medicine is involved in the screening, diagnosis, monitoring and prognosis of hypertension. It is of great importance to understand the preanalytical and analytical factors influencing final laboratory result. In accordance with recent data published by the World Health Organization (WHO) about 41 million people around the world die from noncommunicable diseases (NCD) . In addition, an online survey was conducted with the aim to check symposium participants’ familiarity with the blood pressure (BP) measurement and methodology.Hypertension is defined as a systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mmHg. The optimal arterial pressure value within the classification is defined as < 120/80 mmHg, a normal range is between 120 and 129 mmHg for systolic and/or 80 to 84 mmHg for diastolic pressure, whereas a high normal value is between 130 and 139 and/or 85 to 89 mmHg. Grade I of AH is a systolic pressure of 140-159 mmHg and/or a diastolic pressure of 90-99 mmHg; grade II includes a systolic pressure of 160-179 mmHg and/or diastolic pressure of 100-109 mmHg; grade III refers to a value > 180 mmHg for systolic and/or > 100 mmHg for diastolic pressure. Isolated systolic hypertension applies to people with systolic pressure > 140 mmHg and diastolic pressure < 90 mmHg (The use of mercury-based blood pressure monitors (sphygmomanometers) is abandoned today within the European Union, and it is recommended that office arterial pressure measurement should be performed using automated oscillometric devices, which are validated and calibrated at least once a year. In addition to the BP measuring device, it is worth addressing the importance of the BP methodology. A patient’s body position and relaxation in accordance with environmental conditions can contribute to the accuracy of the BP measurement  (PH), which accounts for 85% of cases; and SH, which is present in up to 15% of patients. The most common causes of SH are chronic kidney disease (CKD) and endocrine disorders. Namely, AH can be a presentation of 15 different endocrine disorders, of which primary aldosteronism (PA) is the most common  examination. It is recommended to assess the overall CV risk as well. Patients with hypertension and documented CVD, diabetes type 1 or 2, or CKD are considered to have a very high 10-year CV risk  or high risk  . The survey was based on the current guidelines for BP measurement in office (OBP) and out-of-office  were familiar with the influence of the upper arm position on the BP.To the first question referring to the BP measuring devices, 69% (71/103) of the participants answered correctly that hybrid semi-automatic and automatic oscillometric devices are recommended for BP measurement. Apart from the measuring devices, the patient’s sitting position and body condition can also affect the BP values. Therefore, it is mandatory that the patient sits relaxed without talking for 3 to 5 minutes, before the test. According to the answers to the question about optimal body condition, the vast majority of participants  were familiar with the need to relax before BP measurement. In addition, a seated position with the back leaning against the chair’s back and with the legs uncrossed is preferred during the test. When asked about the position of the person’s legs, 94% (97/103) of participants responded correctly. In addition to rest, calm state and sitting position, there are other methodological factors that can influence BP values such as the position of the arm chosen for the test. The upper arm for BP measurement should be at heart level while the forearm is resting on tableAccording to the guidelines, patients should avoid food consumption, exposure to cold, exercise, and abstain from cigarettes, caffeine and alcoholic beverages at least 30 minutes before the measurement. More than half of the participants  were aware of the need to abstain from coffee and cigarettes for the required period of time.At home BP monitoring (HBPM) in the form of a diary is recommended as the best method for long-term monitoring of treated hypertension, and for detecting white-coat hypertension and masked hypertension. About 81% (83/103) of participants answered correctly that HBPM has the advantage over OBP measurement.Blood pressure should be measured in the morning (before taking medication) and in the evening  twice at 1-minute intervals over a 7 day period. When asked about measurement intervals, half of participants  knew about the HBPM protocol.The device used for HBPM must be calibrated and the patient must be educated about self-measurement. When following these rules, there is no difference between the HBPM and OBP methods. Next question in the survey was whether there is a difference between the HBPM and OBM methods and 68% (70 /103) of participants chose the correct answer.In general, values of BP measured by the patient at home are lower than those measured in the office. Therefore, the cut-off value indicating AH at HBPM is ≥ 135/85 mmHg, whereas in the office it is set at > 140/90 mmHg. According to the responses, only 18% (19/103) of the participants recognized differences in the cut-off values between the two types of BP measurements.The survey results show an acceptable knowledge of the BP measurement among the participants, but there is also room for improvement.In primary hypertension, the laboratory plays an important role in risk stratification for adverse CV and peripheral vascular events, in assessing asymptomatic hypertension-mediated organ damage (HMOD), and in determining the therapeutic approach for a patient  and the European Society of Cardiology (ESC), the following data must be collected in every patient diagnosed at AH: detailed clinical history, physical examination, initial laboratory tests, and other diagnostic procedures (12-lead ECG)  (4).2), dyslipidemia , and/or diabetes with or without complications. The latter two, together with hypertension, form a metabolic triad that multiplies the risk of a fatal CV event. Patients with these conditions are already in a very high or high risk category, so calculating the 10-year risk does not change their predicted risk  for patients aged 40-69 years or the Systematic Coronary Risk Estimation 2-Older Person (SCORE2-OP) for patients aged 70 years or older  and the number of adults , there are about 1,350,000 hypertensive patients in Croatia. In 2005, 102 patients in Croatia underwent dialysis because of hypertensive kidney disease which is one end-stage renal disease per 13,000 hypertensive patients . Despite the low incidence of end-stage renal disease in hypertensive patients, a significant number of renal failures occur because of the high prevalence of hypertension  and/or renal impairment  accompanied by albuminuria (> 30 mg/day) for more than three months  and albuminuria (categories 1 to 3), and is used to predict the progression of the disease itself , but also hypertension and atherosclerosis. The role and impact of AH should be reviewed from the perspective of traditional common risk factors for other cardiovascular events in patients with CKD. Arterial hypertension leads to changes in the endothelium of the renal blood vessels and increased permeability leading to the accumulation of macromolecules from the circulation that increases intraluminal pressure. To compensate for the increased intraluminal pressure, hypertrophy of the media occurs in a process called hypertensive nephrosclerosis  increase the risk of developing CKD and cardiovascular changes, and the range of blood pressure values that can be considered ideal for patients with CKD is very narrow  is important in hypertensive patients and in patients with signs and/or symptoms of fluid overload. Smoking cessation is also of paramount importance and it is necessary to assist the patient in this process. These measures are immediately followed by tight control of BP. Poorly controlled BP progressively damages the kidneys and increases the risk of CV mortality. With this in mind, treatment should be intensive, with target values of < 125/75 mmHg for patients with diabetes and/or proteinuria and < 130/80 mmHg for patients without proteinuria. Achieving optimal BP in patients with CKD is often very challenging and involves non-pharmacological measures and pharmacological treatment but also on-going education and support from healthcare professionals , elevated serum creatinine and elevated liver transaminases (twice the upper reference limit). Pregnant women with preeclampsia may experience a new-onset generalized seizures, a condition known as eclampsia. A variant of preeclampsia with severe features is known as HELLP syndrome, an acronym for in vivo haemolysis, elevated liver enzymes and low platelet count. Typical symptoms include abdominal pain, nausea and vomiting, accompanied by headache and visual changes   that includes sample dilution. The aqueous portion of the sample is diluted to a greater ratio, so the result of sodium is falsely decreased. The solution to this problem is a direct ISE method because it does not dilute the samples and it is usually used on a blood gas analyser  , the cardiovascular system (CCBs), the kidneys (diuretics), and the central nervous system  (via immune modulation, positive antinuclear antibodies and smooth muscle actin antibodies, which can remain positive for up to six months after the last dose administration (Most of these drugs are not selective and can cause adverse side effects and affect laboratory findings. For example, ACE inhibitors decrease serum ACE activity, a test used in sarcoidosis diagnosis. Diuretics can cause hyponatremia, hypokalemia, as well as hyperuricemia and could potentially lead to gout development (Current ESC/ESH guidelines for the management of newly diagnosed arterial hypertension, recommend dual drug therapy with either an ACE inhibitor or ARB, and a thiazide diuretic or CCB (Because these medications are widely used and multi-drug therapy is common, it is necessary to be familiar with the pharmacokinetics, pharmacodynamics, and side effects of antihypertensive medications to correctly interpret laboratory results.As aforementioned earlier, SH is hypertension with known and potentially treatable causes affecting approximately 10-20% of patients (Secondary hypertension should be screened in individuals with hypertension onset before puberty or before 30 years of age, in stable hypertensive patients with acute rise in blood pressure and in individuals with malignant hypertension. It is recommended that an accurate measurement of BP is performed along with a review of the patient’s diet and/or medication regimen before screening for SH (Primary aldosteronism is a group of diseases that involve dysfunction of RAAS with an autonomous production of aldosterone, resulting in renin suppression, hypertension, cardiovascular damage and occasionally hypokalemia (In the postanalytical phase, an appropriate cut-off value of ARR is essential for accurate screening of PA. However, it should be emphasised that the ARR result of an individual may be strongly influenced by confounding preanalytical factors and the used methodology (


Subdural hematomas (SDH) account for an estimated 5 to 25% of intracranial hemorrhages. Acute SDH occur secondary to rupture of the bridging veins leading to blood collecting within the dural space. Risk factors associated with SDH expansion are well documented, however, there are no established guidelines regarding blood pressure goals in the management of acute SDH. This study aims to retrospectively evaluate if uncontrolled blood pressure within the first 24 h of hospitalization in patients with acute SDH is linked to hematoma expansion as determined by serial CT imaging.A single center, retrospective study looked at 1,083 patients with acute SDH, predominantly above age 65. Of these, 469 patients met the inclusion criteria. Blood pressure was measured during the first 24 h of admission along with PT, INR, platelets, blood alcohol level, anticoagulation use and antiplatelet use. Follow-up CT performed within the first 24 h was compared to the initial CT to determine the presence of hematoma expansion. Mean systolic blood pressure (SBP), peak SBP, discharge disposition, length of stay and in hospital mortality were evaluated.We found that patients with mean SBP <140 in the first 24 h of admission had a lower rate of hematoma expansion than those with SBP > 140. Patients with peak SBP > 200 had an increased frequency of hematoma expansion with the largest effect seen in patients with SBP > 220. Other risk factors did not contribute to hematoma expansion.These results suggest that blood pressure is an important factor to consider when treating patients with SDH with medical management. Blood pressure management should be considered in addition to serial neurological exams, repeat radiological imaging, seizure prophylaxis and reversal of anticoagulation. Subdural hematomas (SDH) are a common subtype of intracranial hemorrhage occurring in an estimated 5 to 25% of patients after head trauma . Known rSDH that do not meet criteria for early surgical intervention are managed conservatively with close monitoring, often in the ICU, with serial neurological exams, repeat radiological imaging, seizure prophylaxis and reversal of anticoagulation . Blood pThis is a single-center, retrospective observational study. Institutional review board (IRB) approval was obtained from the Naples Community Hospital (NCH) IRB. No written consent was required as this was a retrospective study. Electronic medical record data were collected for clinical purposes and no additional tests or interviews were necessary. All data were de-identified and stored in HIPAA-secured environments. With the help of the IT department, a list of the patients over the age of 18 who were admitted to NCH Healthcare System through the emergency department between 01/01/2015 and 12/31/2021 was created using the SDH ICD diagnosis codes S06.5X9A , S06.5X0A , I62.00  and I62.03 . This resulted in a list of 1,083, predominantly above age 65, patients. Manual chart review was then conducted on each patient. Patients were excluded if they did not receive an initial head CT in the emergency department with follow up head CT no later than 24 h after admission, or if SDH was not clearly visualized on initial CT. Patients were also excluded with chronic SDH without an acute component, chronic subdural hygromas, post-operative SDH, concurrent large intraparenchymal or subarachnoid hemorrhage, or those who underwent neurosurgical intervention prior to repeat head CT.Additional background data collected included age at time of admission, sex, race, ethnicity, admission date and time, discharge date and time and discharge disposition. Patient charts were then manually reviewed to collect initial CT head date and time, repeat CT head date and time, hemoglobin, hematocrit, platelets, blood urea nitrogen (BUN), creatinine, prothrombin time (PT), INR, PTT, blood alcohol level and use of anticoagulation or antiplatelet agents.The primary author was responsible for data oversight and maintaining the integrity of the data. Quality control was performed throughout data collection and statistical analysis. The data that support the findings of this study are available upon reasonable request from the corresponding author.All SBP measurements over the first 24 h, starting from patient arrival at the ED, were collected. Mean SBP was calculated for each patient and patients were divided into three groups: mean SBP <140, 140–159, and >160 mmHg. The peak SBP value was also recorded for each patient, and they were divided into six groups: < 140, 140–159, 160–179, 180–199, 200–219, and >220 mmHg.Hematoma expansion was defined as >2 mm increase in size, positive leakage sign, defined as >10 percent Hounsfield unit increase in density of subdural hematoma on CT scan , new midThe primary endpoint was hematoma expansion in relation to both mean and peak SBP.Secondary endpoints include hospital length of stay, disposition and in hospital mortality in relation to mean SBP, peak SBP and hematoma expansion.Patients were divided into their respective groups based on mean and peak SBP values. Chi-square analysis was then performed on each group to evaluate its relationship with frequency of hematoma expansion.Logistic regression was performed with hematoma expansion as the dependent variable and mean SBP and peak SBP as the predictive factors. Age, sex, anticoagulation, antiplatelet therapies, active alcohol use, thrombocytopenia, prolonged PTT, and prolonged INR were added as factors in addition to both the mean SBP analysis and the peak SBP. There were too few cases of thrombocytopenia to test for an interaction effect of thrombocytopenia and mean or peak SBP.The secondary endpoint of length of stay was evaluated using one-way ANOVA. The secondary endpoint of discharge disposition was evaluated using chi-square analysis. Patients discharged to inpatient psychiatric facility or transferred to long term care facility were excluded due to insufficient numbers for analysis. There were not enough data points to determine statistical differences when evaluating the secondary endpoint of in-hospital mortality.Of the initial 1,083, 614 patients were excluded leaving a total of 469 patients included in the study, of which, 108 patients (23%) met criteria for hematoma expansion. The criteria for hematoma expansion can be seen in The baseline characteristics including age, sex, race, ethnicity, admission labs and time between CT scans are reported in In this study, 388 (83%) patients were older than 65 years of age which is consistent with the aging population at our hospital system. There was a distribution of 253 (53.9%) men and 216 (46.1%) women. There were 82 (17.5%) patients on anticoagulation, 153 (32.6%) patients using antiplatelet medication and 11 (2.3%) patients with thrombocytopenia, as defined as platelets >50,000, at time of diagnosis of SDH. A positive blood alcohol level was found in 52 (11.1%) patients at time of admission. We observed 29 (6.2%) patients with prolonged PTT and 80 (17.1%) patients with prolonged INR. The complete data for risk factors for hematoma expansion can be seen in 2(1) = 10.788, p-value < 0.01] and as compared to the SBP mean group of 160 mmHg or more . There was not a significant difference between the 140–159.99 mmHg mean SBP group and the mean SBP group of 160 mmHg or more. The distribution of cases can be seen in The proportion of those with hematoma expansion was significantly less for the SBP Mean group of <140mmHg when compared to the SBP mean group of 140–159 mmHg . Mean SBP group of 160 mmHg or more was 3.324 times more likely to have hematoma expansion than mean SBP group <140 mmHg. There was no significant difference between mean SBP group 140–159.99 mmHg when compared to mean SBP group of 160 mmHg or more. The following variables were not significant when added as a factor in addition to mean SBP: age, sex, anticoagulation, antiplatelet therapies, active alcohol use, thrombocytopenia, prolonged PTT and prolonged INR; each with p-values > 0.05. The p-value was 0.059 for aspirin when antiplatelet therapies was included with the mean SBP group as independent variables. The p-value for the significance of thrombocytopenia within the regression model was 0.051. There were too few cases of thrombocytopenia to test for an interaction effect of thrombocytopenia and mean SBP group on hematoma expansion.Logistic regression was performed with hematoma expansion as the dependent variable and mean SBP as the predictive factor. The proportion of those with hematoma expansion was significantly less for the mean SBP group <140 mmHg when compared to the mean SBP group of 160 mmHg or more . The proportion of those with hematoma expansion was significantly greater for the peak SBP group >220 mmHg when compared to each of the other five groups, each at the 5% level of significance. The only other pairwise comparison that showed a significant difference in the proportion of hematoma expansion was between the peak SBP group <140 mmHg and peak SBP group 200–219 mmHg, . The distribution of cases can be seen in Overall, there was a significant difference in the proportion of those with hematoma expansion between groups . A single reading of SBP > 220 mmHg was associated with an increased frequency of hematoma expansion.Logistic regression was performed with hematoma expansion as the dependent variable and peak SBP as the predictive factor. The following figure gives the significance for each Peak SBP group as well as the odds ratio for each group in comparison to the reference group (SBP > 220 mmHg). As detailed in p-values > 0.05. The p-value for the main effect significance of thrombocytopenia within the regression model was 0.034, but there were too few cases of thrombocytopenia to test for an interaction effect of thrombocytopenia and peak SBP group on hematoma expansion.The following variables were not significant when added as a factor in addition to peak SBP: age, sex, anticoagulation, antiplatelet therapies, active alcohol use, thrombocytopenia, prolonged PTT, and prolonged INR; each with F = 1.234, p-value > 0.05]. One-way ANOVA revealed a significantly longer mean length of stay in those with hematoma expansion, .There was no significant difference in mean length of stay between mean SBP groups, using one-way ANOVA . Overall, the proportion of those with hematoma expansion differs significantly between discharge dispositions . Pairwise comparisons revealed significant differences in the proportion of those with hematoma expansion between home and hospice  and between home and transfer to skilled nursing facility (SNF) . This is detailed below in There were no significant differences between mean SBP group and discharge disposition [χThere were insufficient numbers to determine any statistical differences in relationship to mean SBP and hematoma expansion.This study showed that patients with mean SBP <140 mmHg in the first 24 h of admission had a lower rate of hematoma expansion than those with SBP > 140 mmHg. Patients with peak SBP > 200 mmHg had an increased frequency of hematoma expansion with the largest effect seen in patients with SBP > 220 mmHg. This effect was seen in patients with even a single peak SBP reading > 200. Other risk factors did not contribute to hematoma expansion when logistic regression was performed. To date, only one study has shown a positive association between SBP and change in SDH volume as calculated by the ABC/2 method . There aRisk factors that have been associated with SDH expansion in the literature include age, gender, alcohol use, anticoagulation, antiplatelet medications, thrombocytopenia, prolonged PTT, and prolonged INR –6. In a The reason uncontrolled SBP was correlated with an increased risk of hematoma expansion is unclear, as acute SDH primarily occur secondary to rupture of the bridging veins leading to blood collecting within the dural space . HoweverOne limitation of this study is the retrospective design. As a result of this some of the data is incomplete such as alcohol level and laboratory studies on admission. We were also unable to calculate a modified rankin score on discharge. It was not possible to examine all desired variables such as the effect size may have on SDH and relationship of SDH to trauma. This was performed at a single center and as a result may have a lack of diversity. There was not a standardized protocol for repeat radiological imaging and there was variability in the timing of the repeat scans. There is the potential for interrater variability when reading the CT scans despite criteria for hematoma expansion being designed to attempt to minimize radiologist bias. There was also variability in the number of blood pressure measurements that were taken in that not all patients had blood pressure measurements every hour. Some patients had significantly more blood pressure measurements throughout their stay than others. Only acute SDH were included in the study but the relationship in time to an inciting event was not able to be evaluated. Although data was collected over a 5-year span there is no long term follow up data on the patients. Despite the large sample size there were not enough patients within certain subgroups such as the thrombocytopenia group to perform complete statistical analysis.The current study provides a foundation on which to design a prospective or randomized control trial. Future designs should examine risk factors such as age, gender, alcohol use, anticoagulation, antiplatelet therapies, thrombocytopenia, prolonged PTT and prolonged INR in relationship to SDH and hematoma expansion. The effect of size of hematoma and incidence of traumatic events should be examined. Efforts should be made to objectively quantify hematoma expansion using a formula such as the ABC/2 formula. Long term follow up of acute SDH will determine whether people with uncontrolled SBP had higher progression to chronic SDH and higher morbidity and mortality.These results suggest that blood pressure is an important, potentially modifiable, factor which should be addressed when treating patients with SDH with medical management. A goal of mean SBP < 140 mmHg in the first 24 h of management may decrease the risk of hematoma expansion and elevated blood pressure, particularly those greater than a systolic of 200 mmHg, should be avoided. Blood pressure management has the potential to reduce morbidity, mortality, and healthcare burden. A randomized, controlled trial with longitudinal follow-up is needed to determine optimal blood pressure goals to decrease the risk of hematoma expansion.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by NCH Institutional Review Board. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.KP designed and conceptualized study, major role in the acquisition of data, data collection and processing, interpreted and analyzed the data, and drafted and revised the article. DL designed and conceptualized study, interpreted and analyzed the data, and revised the article. EV-G revised the article. AA major role in the acquisition of data and drafted and revised the article. JB designed and conceptualized study, interpreted and analyzed the data, and drafted and revised the article. CR designed and conceptualized study and revised the article. All authors contributed to the article and approved the submitted version.This work was performed as part of employment under NCH Healthcare System. The authors KP, DL, EV-G, AA, JB, and CR are all employed within this system.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The blood pressure (BP) lowering response to renal denervation (RDN) remains variable with about one-third of patients not responding to ultrasound or radiofrequency RDN. Identification of predictors of the BP response to RDN is needed to optimize patient selection for this therapy. This is a post-hoc analysis of the RADIANCE-HTN SOLO study. BP response to RDN was measured by the change in daytime ambulatory systolic blood pressure (dASBP) at 2 months post procedure. Univariate regression was used initially to assess potential predictors of outcome followed by multivariate regression analysis. In the univariate analysis, predictors of response to RDN were higher baseline daytime ambulatory diastolic blood pressure (dADBP), the use of antihypertensive medications at screening, and presence of orthostatic hypertension (OHTN) whilst the presence of untreated accessory arteries was a negative predictor of response. Multivariate analysis determined that dADBP and use of antihypertensive medications were predictors of response to RDN with a trend for OHTN to predict response. Obese females also appeared to be better responders to RDN in an interaction model. RDN is more effective in patients with elevated baseline dADBP and those with OHTN, suggesting increased peripheral vascular resistance secondary to heightened sympathetic tone. These assessments are easy to perform in clinical setting and may help in phenotyping patients who will respond better to RDN. Novel antihypertensive therapies using second-generation renal denervation (RDN) catheter systems causing modification of renal sympathetic nerve signaling have shown encouraging results in randomized controlled trials –4. The mGiven that RDN is invasive to perform compared to drug therapy, the lack of markers of procedural success is a significant issue at the present time , 7. WhilPrevious studies have analyzed the clinical, anatomical, and procedural predictors of BP response to RDN –10. ImpoThis is a post-hoc analysis of the RADIANCE-HTN SOLO study data. To summarize, RADIANCE-HTN SOLO was a multicenter, international, double-blind, randomized, sham-controlled trial done at 21 centers in the USA and 18 centers in Europe [Male or female patients aged 18–75 years with combined systolic–diastolic hypertension (office BP ≥ 140/≥90 mmHg) on 0–2 antihypertensive medications were enrolled in the study. Patients were eligible for randomization if they had daytime ambulatory BP (ABP) ≥ 135/≥85 mmHg and <170/<105 mmHg after a 4-week discontinuation of their antihypertensive medications and had suitable renal artery anatomy on CT- or MR-angiography.Eligible patients were randomized in a 1:1 ratio to either the sham procedure  or ultrasound RDN with the Paradise catheter System  after renal angiography under conscious sedation. Patients, outcome assessors, and study personnel were blinded to the randomization. Patients were not started on any antihypertensive medications for 2 months post procedure unless specified BP escape criteria were met.Patients were assessed at 2 months post procedure for evaluation of the primary efficacy endpoint which was change in daytime ambulatory systolic BP (dASBP) from baseline in the intention-to-treat population. Major adverse events and safety outcomes were also collected. The study is registered with ClinicalTrials.gov, number NCT02649426.® MIT ELITE Plus or M10-IT device . All efforts were made to standardize office BP recordings for each patient including measurement from the same arm at same time of day using the same device by the same person. Caffeine, exercise, and smoking were avoided for at least 30 min prior to the measurement and patients sat quietly in a chair for at least 5 min before recordings.Office BP was recorded using the OmronAn appropriately sized cuff was used to ensure the bladder within the BP cuff encircled at least 80% of the arm. BP was measured in both arms and the arm with the higher reading was used for office BP recording. For study defined BP measurements, three sitting BP and heart rate (HR) measurements were recorded, 1–2 min apart. The average of the 2nd and the 3rd measurements have been used for analysis. Standing BP and HR were recorded after 1 min to check the presence of OHTN, defined as office standing minus office seated systolic blood pressure (SBP) ≥ 20 mmHg and/or office standing minus office sitting diastolic blood pressure (DBP) ≥ 10 mmHg at baseline. The presence of any symptoms was not required for the diagnosis of OHTN.® WatchBP machine  at baseline and 2-month follow-up visits. The ambulatory blood pressure (ABP) was recorded on patient’s non-dominant arm for 25 h. BP was recorded every 20 min during daytime (07:00–22:00 h) and every 30 min overnight (22:00–07:00 h). 24-H ABP recordings with a minimum of 21 measurements during the daytime period were considered valid. In the case of a non-valid measurement, a new ABP recording was performed. All ABP recordings were sent to a core laboratory  with treatment assignments masked.The 24-h ambulatory BP (24-H ABP) recordings were made using the MicrolifeAll analyses were conducted on the per-protocol population (RDN = 64 and Sham = 58). As previously described, the per-protocol population excluded patients who did not meet baseline daytime ambulatory SBP or DBP or renal artery anatomical inclusion criteria, patients in the RDN group who did not receive bilateral RDN, patients who were treated with antihypertensive medications before the 2-month 24-H ABP, and patients who did not complete the 2-month 24-H ABP assessment .Univariate regression was used to assess potential predictors of outcome defined as change in dASBP at 2 months. In addition, we evaluated whether predictors of outcome differed between responders (defined as reduction in dASBP ≥ 5 mmHg) and super responders (defined as reduction in dASBP ≥ 15 mmHg) at 2 months following treatment.p value less than 0.20 from the univariate analysis. Backward selection with a stay criterion of 0.20 was used to select predictors. In the multivariate regression analysis, we checked that the variance inflation factor was less than 5 for all input variables.Multivariate regression analysis was conducted for the RDN arm including variables with Multiple interaction analyses were conducted looking at the impact of these variables: treatment (RDN vs. Sham), sex , abdominal obesity (yes vs. no), and age (<55 vs. ≥ 55) on change in dASBP. The least square means were used to compare the effect size of different combinations.Treatment effects  were assessed comparing patients with and without orthostatic hypertension (OHTN) using analysis of covariance, adjusting for baseline values.Abdominal obesity was defined as abdominal circumference >102 cm in males and >88 cm in females measured at the level of umbilicus. Pulse Pressure was defined as the difference between office SBP and DBP or between 24-H ambulatory SBP and DBP.t-tests for continuous variables and Fisher’s exact test, for categorical variables. Continuous variables are expressed as mean ± standard deviation unless otherwise specified and between-group differences are expressed as mean and corresponding two-sided 95% confidence intervals. All analyses were performed using statistical analysis system (SAS) software version 9.4 . A p value lower than 0.05 (two-sided) was considered significant. Reported p values are based on nominal values not adjusted for multiple comparisons.Comparisons between groups were made using two-sample The distribution of the patient population in the RADIANCE-HTN SOLO trial was evenly matched between the RDN and Sham groups and has been previously reported . The basAll the variables assessed in the univariate model for the RDN group are listed in Table In responders to RDN (defined as reduction in dASBP ≥ 5 mmHg), the age and the presence of OHTN were positive predictors of response and the presence of any untreated accessories was a negative predictor of response. In the Sham group, there were no predictors of response identified Table .Table 2CIn super responders to RDN (defined as reduction in dASBP ≥ 15 mmHg), BMI, abdominal obesity, antihypertensive medications at screening, the presence of OHTN, baseline 24-H ambulatory heart rate (AHR), and the presence of side branches proximal to ablation, were significant predictors for BP-lowering effect of RDN. Whereas the presence of any untreated accessories was a negative predictor of response. There were no significant variables identified in the sham group  and medicated patients (N = 53) were similar at 150 ± 7.6/95 ± 4.4 mmHg and 151 ± 7.3/93 ± 4.4 mmHg, respectively. The presence of OHTN was also associated with a greater response to RDN albeit non-significant (p = 0.077).Results of the multivariate analysis are shown in Table A variety of interaction models were analyzed  was associated with a larger reduction in dASBP and dADBP 2 months after RDN Table . Figure Previous studies have identified baseline SBP, younger age, higher eGFR, higher HR, use of central sympatholytic agents or aldosterone antagonists, indices of baseline sympathetic overdrive, and various biological markers as markers of response to catheter-based RF RDN , 16–22.In addition to being limited to populations treated with RF energy to achieve renal sympathectomy, these studies mostly included patients taking antihypertensive medications. Given that dynamic patterns of adherence and non-adherence to antihypertensive drugs in trials are now established, it might be expected that this would have confounding effects on clinical outcomes . The RADIn this post-hoc analysis of the RADIANCE-HTN SOLO trial, we found that the predictors of a larger response to RDN were mainly linked to heightened sympathetic nervous system (SNS) activity in addition to anatomical predictors. Indeed, the positive predictors of BP response to endovascular ultrasound RDN were use of antihypertensive medications at screening, higher baseline dADBP, abdominal obesity, female sex, and OHTN. Patients receiving antihypertensive medications at screening may have demonstrated an enhanced response to RDN due to medication-induced priming of the SNS at the time of screening even though baseline BPs were similar between the groups . PatientFinally, muscle sympathetic nerve activity (MSNA) is an established surrogate marker for SNS activity. In males and females more than 40 years of age, MSNA correlates significantly with mean arterial pressure, which has a major contribution from diastolic pressure compared to systolic pressure . It is aIn the three-way interaction model, females with abdominal obesity showed striking reduction in BP following RDN. Abdominal obesity is also a known feature of the metabolic syndrome characterized by higher baseline SNS activity . MoreoveThe presence of systolic and/or diastolic OHTN was a positive predictor of dASBP and dADBP lowering following RDN in the univariate analysis although this did not reach significance in the multivariate analysis. Interestingly, the OHTN phenotype was also associated with younger age, female sex, higher BMI, and eGFR, but the sample size may have been too small to achieve statistical significance in most factors , study design, and patient population studied.This is the first evaluation of clinical, anatomical, and procedural predictors of response specific to endovascular ultrasound RDN.The study design offers a unique opportunity to evaluate predictors in absence of BP-lowering drugs in the study cohort.The study has identified novel predictors  that show bigger BP response with RDN and should be evaluated in future studies.Supplemental Materials


Self-care behavior plays a pivotal role in the management of chronic kidney disease. Improved self-care behavior in patients with chronic kidney disease is a key factor in health management and treatment adherence. This study aimed to evaluate the participants’ general and medical condition-related characteristics, physiological indices and the level of health literacy affecting self-care behavior in patients with chronic kidney disease in South Korea. The data of 278 participants were analyzed using t-test, analysis of variance, correlation coefficient, and linear multiple regression analysis. There were significant differences in self-care behavior scores depending on participants’ age and cohabitation status, employment, and smoking status as well as having dialysis due to end-stage kidney disease; number of comorbidities; levels of serum hemoglobin, calcium, and creatinine; and estimated glomerular filtration rate. The results of regression analysis revealed that not currently working, non-smoker, end-stage kidney disease, and positive response to the “actively managing my health” scale of the Health Literacy Questionnaire significantly affected self-care behavior in patients with chronic kidney disease, and the explanatory power of the model was 32.7%. Therefore, it is necessary to identify each patient’s barriers or needs according to individual characteristics, such as age, cohabitation and employment status, and daily life circumstances, including smoking habits, comorbidities, social support, and level of health literacy to develop efficient support strategies for promoting adequate self-care behavior with CKD. The burden of chronic kidney disease (CKD) has been rising, and this trend is projected to continue due to an increase in the number of cases of diabetes and hypertension as well as an aging population in Korea. The prevalence of CKD in the US is estimated to be approximately 13% . The numCKD is an irreversible disease and the primary treatment goal is delaying the kidney function deterioration. Integrated management involving various strategies such as monitoring of blood pressure and blood glucose, dietary restrictions, and medication adherence as well as treatment of causative diseases can improve the prognosis of patients with CKD , 6. The Diet is one of the main management methods for alleviating uremia, metabolic abnormalities and deterioration of renal function, and personalized diet prescriptions are provided to help the patients in maintaining proper nutritional status according to their symptoms. It is necessary to include information on forming routines foe healthy diet habits during patient education sessions, and healthcare providers must pay attention to and continuously encourage the patients with low levels of understanding of their disease .2 can successfully reduce the occurrence of proteinuria [Physical activity is also associated with improved cardiovascular function in patients with CKD, whereas smoking , 6 and ateinuria . As suchteinuria .According to previous studies, self-care behaviors and disease awareness in patients with CKD are closely related , 10, 11.Hence, this study aimed to identify the medical condition-related characteristics, physiological indicators, and health literacy levels of patients with CKD that affect their self-care behavior and to provide evidence that can help these patients enhance their health status.This cross-sectional descriptive study examined the relationship between characteristics, physiological indices, health literacy, and self-care behavior in patients with CKD.The participants of this study were adults aged 18 years or older who were diagnosed with CKD stages 1–5, understood the purpose of this study, agreed to participate in surveys, and gave permission to access their electronic medical records. The minimum number of participants required for this study was calculated to be 245 individuals, with an effect size of .15, significance level of ⍺ = .05, power (1-β) = .95, and 26 predictors  for linear multiple regression analysis using the G*Power 3.1.6 program. Data were collected from 285 participants. After excluding the data of seven participants who submitted incomplete questionnaires, the data of 278 were finally analyzed.We investigated the general characteristics  and medical condition-related characteristics  using surveys and the respective electronic medical records. Comorbidity was measured using the Davies Comorbidity Index (DCI) . The DCIThe Health Literacy Questionnaire (HLQ) is a self-reported measurement tool with 44 questions under the following 9 scales : (1) feeThe Chronic Kidney Disease Self-Care (CKDSC) scale was developed to measure self-care behavior in CKD patients . The CKDData collection was conducted after obtaining approval from the Institutional Review Board (no. 1041078-202006-HR-162-01) at Chung-Ang University. The purpose and procedure of this study were explained to the participants and written consent was obtained. They were assured that there would be no disadvantages if they did not participate in this study, and that only voluntary participation was allowed. The patient medical registration numbers for checking the respective electronic medical records were written on separate papers. Immediately after completing the questionnaires and collecting data from the electronic medical records, the papers with the patient medical registration numbers were shredded. No personally identifiable information was collected.The data collection period was from July 25, 2020 to December 2, 2020. The participants were recruited after obtaining permission from the concerned department head at a university affiliated hospital located in D City, South Korea. Recruitment notices were posted in front of the dialysis room and nephrology outpatient clinic at the hospital. Data collection was conducted in the dialysis room and waiting room of the outpatient clinic by two nurses who were research assistants.3. The correlation between health literacy and self-care behavior of the participants was determined using calculated Pearson’s correlation coefficients. A linear multiple regression analysis was performed to identify factors affecting self-care behavior.Data analysis was performed using SPSS Statistics for Windows, version 26.0 . The general and medical condition-related characteristics of the participants were analyzed using descriptive statistics. The differences in self-care behavior and health literacy according to the participants’ characteristics were analyzed using t-test and one-way analysis of variance. A post-hoc test was performed with an equivalence test followed by Scheffé test or Dunnett TThe study sample included 152 men (54.7%). The mean age was 57.04 years, and 222 (79.9%) participants were cohabitating, 106 (38.2%) participants were unemployed, and 28 (10.1%) were smokers. In terms of medical condition-related characteristics, 184 (66.2%) patients were on dialysis because of end-stage kidney disease, 69 (24.8%) had CKD for <1 year, and 107 (38.5%) had CKD for ≥5 years. The most common cause of CKD was diabetes mellitus, followed by kidney disease and hypertension. In addition, 134 (48.2%) patients were taking less than four prescribed medications, and 207 (74.4%) participants had one or two comorbidities. The serum test results showed that 130 patients (47.3%) had normal hemoglobin levels, 151 (54.7%) had normal calcium levels, 122 (44.2%) had normal phosphate levels, 211 (76.7%) had normal total protein levels, 60 (32.3%) had normal blood urea nitrogen levels, 59 (21.4%) had normal creatinine levels, 47 (17.0%) had normal glomerular filtration rate levels, and 133 (89.9%) had normal Kt/V ratios .The overall mean CKDSC score was 3.53±0.61. The mean scores for each scale were as follows: 4.59±0.54 for medication adherence, 4.06±1.04 for smoking behavior, 3.31±1.29 for blood pressure monitoring, 2.86±0.97 for diet control, and 2.81±1.18 for exercise. The HLQ scores are shown in p < .001), those who were cohabiting , those currently unemployed , and non-smokers . The mean CKDSC scores for the medical condition-related characteristics were significantly high for patients with end-stage kidney disease; those with a DCI score ≥2 compared to those with a DCI score of 0; and those with abnormal levels of hemoglobin, calcium, creatinine, and eGFR , and the correlation coefficient with the score on the scale 8 (“ability to find good information”) (r = .16) was the lowest  . The variables of current unemployed status (B = .16), non-smoker status (B = .32), end-stage kidney disease (B = .31), and the “actively managing my health” scale (B = .41) significantly affected the CKDSC score, and their explanatory power was 32.7%. The variable “age 65 years or older” (B = .14), although not significantly affected by CKDSC, was near the significant level ( = .059) .The mean CKDSC score in this study was 3.53 points, which is similar to that reported by Wang et al.  in theirThe results of our analysis of self-care behavior scores according to medical condition revealed that the self-care behavior score was high for those with low hemoglobin level, high creatinine level, low eGFR, and many comorbidities with regard to the physiological indices. The self-care behavior score was higher in patients with end-stage kidney disease who were on dialysis when compared to other patients with CKD. These results are consistent with the results of Wang et al. , who repRobatSarpooshi et al. , who invWe found that scale 3 of the HLQ  positively affected CKDSC. As “actively managing my health” refers to the act of recognizing the importance of one’s own health and making health-related decisions with a sense of responsibility , this miThe results of this study showed that health literacy, except for the scale 3 of the HLQ , had no significant effect on self-care behavior in patients with CKD. Although health literacy is an important element for practicing self-care in patients with CKD , it can Finally, this study has a few limitations. As self-care behavior and health literacy in patients with CKD patients were measured using a self-report questionnaire, the participants’ recall bias might have affected the results of this study. We recruited patients with CKD at a single hospital, which may limit the generalizability of results. The study had slightly higher proportion (66.2%) of participants who were on dialysis; therefore, care should be taken when interpreting the results. Considering that various factors are included in the self-care behavior of patients with CKD, including dietary restrictions and disease management, this study is important because to our knowledge, this is the first study to analyze the effects of health literacy on self-care behavior in Korean patients with CKD using a tool that encompassed a multidimensional concept of health literacy including access to healthcare, interactions with experts, and social support systems instead of using a tool that measured only functional health literacy, such as reading and writing abilities in patients with CKD.This study analyzed factors affecting self-care in patients with CKD using a questionnaire survey and medical record analysis. The results indicate the importance of having a responsible attitude toward actively managing one’s health. Specialized interventions are needed to help patients with CKD who have a job, are living alone, and have a low frequency of contact with nurses or healthcare providers. Further multi-site studies on the relationship between health literacy and self-care according to CKD stage are needed to acquire basic data that can help improve self-care behavior in patients with CKD. In addition, to enhance self-care behavior in patients with CKD, future studies can investigate the effects of the use of Korean healthcare systems on applying health information related to CKD.S1 Dataset(XLSX)Click here for additional data file.


In conclusion, fasting serum A-FABP value has positive association with PAD in T2DM patients.The adipocyte fatty-acid binding protein (A-FABP) is predominantly expressed in macrophages and adipocytes and is an essential mediator of inflammation and atherosclerosis pathogenesis. Atherosclerosis is an aggravating factor for peripheral arterial disease (PAD). Our study intended to study the association between PAD and serum A-FABP levels in type-2 diabetes mellitus (T2DM) patients. One hundred and twenty T2DM subjects were enrolled in the study. Fasting blood samples were collected to determine biochemical data and A-FABP levels. By the automatic oscillometric method, the ankle–brachial index (ABI) was measured. Low ABI was defined as any value < 0.9. Twenty participants with T2DM (16.7%) were included in the low ABI group. Low ABI T2DM participants had an increased mean body mass index, body fat mass, systolic blood pressure, C-reactive protein, urine albumin–creatinine ratio, and A-FABP levels compared to those in the normal ABI group. After variables significantly associated with PAD were adjusted by multivariate logistic regression analyses, circulating A-FABP levels (odds ratio [OR]: 1.138; 95 percent confidence interval [CI]: 1.023–1.266;  Type-2 diabetes mellitus (T2DM) is associated with various complications. Cardiovascular disease (CVD) causes more than 60% of the life-years lost from DM and is the main cause of disability and mortality among populations with T2DM ,2. In DMThe adipocyte fatty-acid binding protein , a 15-kDa member of the intracellular fatty-acid binding protein mainly expressed in adipose cells or macrophages, is associated with arterial stiffness, dysmetabolic syndrome, and CVD ,14. In aThe PAD prevalence of DM patients varies from 20% to 30% depending on the research population . Cross-sn = 5), or warfarin (n = 3), or acute infection (n = 2) during blood sampling, and refusal to offer informed consent (n = 10). Finally, 120 patients with T2DM were invited to this study. The Research Ethics Committee of Hualien Tzu Chi Hospital approved this study (IRB103-136-B). Every participant provided written informed consent before entering this study. In the morning, after the participants had sat for ten minutes, the blood pressure (BP) was determined by standard mercury sphygmomanometers. Systolic BP (SBP) and diastolic BP (DBP) were obtained every 5 min, 3 times, and averaged for further analyses. Hypertension was defined as BP values ≥ 140/90 mmHg, or using any antihypertensive medication over the past two weeks.From November 2014 to March 2015, 140 patients with T2DM were enrolled at a medical center in Hualien, Taiwan. Twenty participants were excluded due to the use of protease-activated receptor-1 antagonists (2). Body fat mass was measured by bioimpedance analysis  in accordance with the standard tetrapolar whole-body (hand-foot) technique [The height and body weight of each patient were recorded to the 0.50 cm and 0.50 kg, respectively. We calculated the body mass index (BMI) as a ratio of weight and height squared . Serum fasting glucose, glycated hemoglobin (HbA1c), total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), blood urea nitrogen (BUN), creatinine, and C-reactive protein (CRP) levels were measured using a Siemens Advia 1800 autoanalyzer  [An overnight-fasting 10 mL blood sample from each participant was collected and immediately centrifuged (3000× Germany) ,22,23. IGermany) ,22. The Germany) .We measured ABI values with an automatic machine  which recorded both the arm and ankle BP simultaneously with the oscillometric method . The occt-test. Non-normally distributed variables were reported by the median (interquartile range) and examined via the Mann–Whitney U test . We used the χ2 test for categorical variables analysis. Variables significantly associated with PAD among T2DM populations were tested for multivariate logistical regression analysis . The association between A-FABP concentrations and clinical variables was evaluated using the nonparametric Spearman’s rank correlation coefficient. The area under the receiver operating characteristic (ROC) curve was analyzed to identify the A-FABP level that predicts PAD in T2DM patients. We used SPSS Statistics 19.0 software for data analyses. A p-value of 0.05 or lower was considered significant. The Kolmogorov–Smirnov test was used to determine whether the data are normally distributed. Continuous variables with normal distribution were shown as the mean ± standard deviation and were compared by using Student’s p = 0.037), body fat mass (p = 0.019), SBP (p = 0.002), CRP (p < 0.001), UACR (p = 0.001), and A-FABP (p < 0.001) values than those within the normal ABI group. Medications used by the study participants included statins , fibrates , metformin , sulfonylurea , dipeptidyl peptidase-4 inhibitor , and insulin . No statistically significant differences existed between the patients with low and normal ABI values regarding sex, comorbid conditions with hypertension, the use of anti-hyperlipidemic medications, or the anti-diabetic medications usage, such as statins, fibrates, metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitors, and insulin.The demographic, clinical, and biochemical information of the 120 enrolled patients with T2DM is shown in p = 0.017), SBP , and CRP level  were risk factors for PAD in T2DM subjects  in the multivariate logistic regression analysis. The analysis showed that elevated circulating A-FABP level . Second, serum A-FABP was found to be positively correlated with BMI , body fat mass , SBP , TG , CRP , and UACR  but negatively associated with HDL-C , and eGFR . Our cross-sectional study of 120 patients with T2DM showed that serum A-FABP concentrations, together with SBP and CRP, were independent predictors of PAD diagnosed based on ABI values.Systemic atherosclerosis events are the most important factor determining PAD prevalence and are increasing in number. It is estimated that 200 million patients are affected by PAD around the world . PAD canStudies have identified many established risk factors for PAD development, including smoking, DM, hypertension, obesity, dyslipidemia, aging, and chronic kidney disease ,29,30, aPAD reflects systemic atherosclerosis, a complicated process involving oxidative stress, endothelial dysfunction, vascular smooth muscle cell activation, changes in matrix metabolism, platelet activation, and lipid disturbances . The ABIOur research has limitations. First, this research was conducted as a single-center, cross-sectional study without the control group, and various lifestyle habits that may affect PAD occurrence, such as smoking and alcohol consumption, were not recorded ,49. ThisOur present study showed, for the first time, that the fasting serum A-FABP level is positively associated with PAD. Moreover, in T2DM populations, fasting serum A-FABP levels are regarded as a consistent and significant predictor associated with PAD determined by ABI.