Objective To investigate the clinical practice of chronic kidney disease-mineral and bone disorder (CKD-MBD) in maintenance hemodialysis patients in Shanghai, and to better understand the changes of clinical practice for CKD-MBD. Methods Sixty-four hospitals with qualified dialysis center in Shanghai were selected for questionnaire survey as of March 2019. The survey questionnaire included the number of hemodialysis and peritoneal dialysis patients, the implementation of CKD-MBD guidelines, the learning of CKD-MBD guidelines, the detection and distribution of CKD-MBD biochemical indicators, the treatment of hyperphosphatemia, the treatment of secondary heperparathyroidism (SHPT) and renal bone disease, and the concentration of calcium ion in dialysate. The results were compared with previous survey data in 2011. Results There were sixty-three hospitals included in this study, with 10 168 maintenance hemodialysis patients and 4 610 maintenance peritoneal dialysis patients in Shanghai. 84.1%(53/63) hospitals implemented the guidelines smoothly, which increased by 28.5% compared with the rate (55.6%) of 2011. The successful implementation rates for guidelines in secondary and tertiary hospitals were 83.3%(25/30) and 84.8%(28/33), which increased by 44.0% and 11.7% respectively (39.3% of secondary hospitals and 73.1% of tertiary hospitals in 2011). All hospitals carried out the detection for serum calcium and phosphorus. The rate for parathyroid hormone (PTH), total alkaline phosphatase (AKP), bone specific alkaline phosphatase (BAP), 25-hydroxy vitamin D[25(OH)D], and other bone metabolism-related biomarkers were 98.4%(62/63), 90.5%(57/63), 19.0%(12/63), 90.5%(57/63) and 42.9%(27/63), respectively; coronary artery CT, lumbar lateral X-ray plain, echocardiography, bone mineral density, and vascular ultrasound were carried out in 68.3%(43/63), 74.6%(47/63), 100.0%(63/63), 68.3%(43/63)and 69.8%(44/63), respectively. Compared with 2011, the proportion of detection for PTH, AKP, BAP, 25(OH)D, coronary artery CT, lumbar lateral film and echocardiography increased by 2.1%, 1.6%, 0.5%, 47.9%, 14.6%, 20.9% and 1.9%, respectively. The proportion of patients with serum phosphorus ranging in 0.80-1.45 mmol/L(KDIGO guideline), serum phosphorus ranging in 0.80-1.78 mmol/L(KDOQI guideline), calcium ranging in 2.10-2.54 mmol/L, and PTH ranging in 150-600 ng/L were 37.0%(3 323/8 969), 50.7%(4 571/9 018), 60.2%(5 568/9 244) and 33.2%(3 018/9 087). Compared with 2011(39.6%, 53.5% and 34.1%), the proportion of patients with ideal serum phosphorus (0.80-1.78 mmol/L) and calcium (2.10-2.54 mmol/L) levels increased by 11.1% and 6.7% respectively, and the proportion with PTH 150-300 ng/L decreased by 0.9%. The proportion of hospitals for using non-calcium phosphate binders (lanthanum carbonate from 1.9% to 87.3% and sevelamer carbonate from 14.8% to 63.5%) and surgical treatment (from 38.9% to 68.3%) for SHPT dramatically increased. Conclusions Through the availability of medicine increases, and nephrologists gain deeper understanding in management and treatment of CKD-MBD, the detection rate for CKD-MBD indicators and the eligible rate have significantly improved compared with those in 2011. However, the comprehensive management of CKD-MBD in Shanghai still faces great challenges. It is still necessary to further improve eligible rate for serum phosphorus and iPTH, so as to provide more evidences and management strategies for integrated management of end-stage renal disease and prevention of abnormal calcium and phosphorus metabolism in patients.

Objective To investigate the association between ambulatory arterial stiffness index (AASI) and renal poor prognosis in patients with chronic kidney disease (CKD). Methods A prospective study was conducted to enroll 117 non-dialysis patients with CKD who volunteered for receiving ambulatory blood pressure monitoring test from December 2017 to December 2018 in the Department of Nephropathy of the First Medical Center of Chinese PLA General Hospital. According to the AASI tertiles, patients were divided into low AASI group (≤0.414, n=38), medium AASI group (0.414-0.517, n=40), and high AASI group (≥0.517, n=39). The differences of clinical baseline information among the three groups were compared. The follow-up time was until August 2020. Kaplan-Meier curve and Cox proportional hazard regression model were used to explore the effect of AASI on renal poor prognosis. Results The median age of 117 patients was 61(49, 65) years old. There were 80 males (68.4%) and patients with hypertension accounted for 77.8%(91 cases). After a median follow-up of 27 months, 34 cases had composite endpoint events [renal replacement therapy (dialysis or kidney transplantation), 40% estimated glomerular filtration rate (eGFR) decline, and death], of which 10 patients were on dialysis, 19 patients had 40% eGFR decline, and 5 patients died. There were significant differences in age, hemoglobin, body mass index, eGFR, 24 h systolic blood pressure (SBP), daytime SBP, nighttime SBP, morning SBP, 24 h mean arterial pressure and 24 h pulse pressure among the three groups (all P<0.05). Kaplan-Meier survival analysis indicated that higher AASI was associated with lower cumulative survival rate in patients (Log-rank test χ²=13.111, P=0.001). Univariate Cox regression analysis showed that high AASI was an influencing factor for renal endpoint events (P<0.05), and after adjusting for age, gender, mean arterial pressure, eGFR, 24 h urine protein, diabetes and body mass index, high AASI was an independent influencing factor for renal poor prognosis in classification and continuous variable analysis models (HR=2.88, 95%CI 1.00-8.26, P=0.050; HR=1.50, 95%CI 1.02-2.21, P=0.039). Conclusion High AASI is an independent influencing factor for renal poor prognosis in CKD patients.

Objective To investigate the predictive value of abnormal heart rate circadian rhythm for all-cause mortality in stage 5 chronic kidney disease (CKD 5) patients. Methods The retrospective study was performed in CKD 5 patients enrolled from the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) and the Affiliated BenQ Hospital of Nanjing Medical University from February, 2011 to December, 2019. A total of 159 healthy volunteers were enrolled as the healthy control group during the same period. The circadian rhythm of heart rate was monitored by 24-hour Holter. Related indices (including 24-hour, daytime and nighttime mean heart rate, night/day heart rate ratio, 24-hour maximum heart rate, 24-hour minimum heart rate and difference between maximum and minimum of 24-hour heart rate) were calculated. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Cox regression model was used to analyze the risk factors of all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve and Log-rank test were used to compare the differences of cumulative mortality between high ratio group (night/day heart rate ratio>0.91) and low ratio group (night/day heart rate ratio≤0.91). The nonlinear relationship between night/day heart rate ratio and all-cause mortality was analyzed by restricted cubic spline plot. Time-dependent receiver operating characteristic (ROC) curve was used to analyze the predictive value of night/day heart rate ratio for all-cause mortality in CKD 5 patients. Results A total of 159 healthy volunteers and 221 CKD 5 patients were included in this study. There were 123 males (55.66%) and the age was (52.72±13.13) years old in CKD 5 patients. The total median follow-up time was 50.0 months. Compared with controls, 24-hour, nighttime mean heart rate, 24-hour minimum heart rate in CKD 5 patients were increased (all P<0.05), furthermore, the night/day heart rate ratio was higher [(0.91±0.09) vs (0.81±0.08), P<0.001], showing "non-dipping heart rate". However, the 24-hour maximum heart rate and the difference between maximum and minimum of 24-hour heart rate in CKD 5 patients were lower than controls (both P<0.05). Multivariate Cox regression analysis showed that the increased night/day heart rate ratio (per 0.1 increase, HR=1.557, 95%CI 1.073-2.258, P=0.020) was an independent influencing factor for all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve analysis showed that the cumulative mortality of the high ratio group was significantly increased than that of the low ratio group (Log-rank test χ²=7.232, P=0.007). From the restricted cubic spline plot, there was a linear effect between night/day heart rate ratio and all-cause mortality (P=0.141), and when night/day heart rate ratio was above 0.91, the risk of all-cause mortality was significantly increased in CKD 5 patients. According to time-dependent ROC curve, the accuracy of night/day heart rate ratio in predicting all-cause mortality was 70.90% even when the survival time was up to 70.0 months. Conclusions The circadian rhythm of heart rate in CKD 5 patients displays "non-dipping" state. High night/day heart rate ratio is an independent influencing factor for all-cause mortality in CKD 5 patients.

Objective To investigate the relationship between monocyte/high-density lipoprotein ratio (MHR) and clinical parameters and the prognosis of patients with chronic kidney disease (CKD). Methods Clinical data were collected of CKD patients who were diagnosed and followed up regularly in Henan Provincial People's Hospital from January 1, 2017 to June 30, 2020. According to the median baseline MHR of the selected patients, they were divided into two groups: low-level MHR group (MHR≤0.347 8) and high-level MHR group (MHR>0.347 8). The patients were regularly followed up for 3-42 months, the renal adverse prognostic events were defined as serum creatinine doubled, estimated glomerular filtration rate (eGFR) reduced to at least 50% of the original, new entry into end-stage renal disease (ESRD), starting renal replacement therapy, death due to renal or cardiovascular events. The Kaplan-Meier method was used to compare the differences in survival rates between the two groups, and Cox regression analysis method was used to explore the influencing factors of renal adverse prognosis in CKD patients. Stratified analysis was used to find special factors that might affect the relationship between MHR and renal adverse prognosis in CKD patients. Results A total of 405 patients were included in this study. Their age was (49.77±14.82) years old. Body mass index was (25.18±4.22) kg/m². Women accounted for 30.62%(124/405). The proportion of patients with smoking, drinking, hypertension and diabetes was 39.51%(160/405), 35.06%(142/405), 73.33%(297/405) and 38.27%(155/405), respectively. Compared with the low-level MHR group (n=202), the high-level MHR group (n=203) had more people in late CKD, males, and hypertension (all P<0.01), and body mass index, white blood cells, monocytes, serum creatinine, serum uric acid, serum urea nitrogen, retinol binding protein, cystatin C, blood phosphorus were higher (all P<0.05), while hemoglobin, high density lipoprotein and eGFR were lower (all P<0.05). Spearman rank correlation results show that MHR level was positively correlated with white blood cells, serum creatinine, serum uric acid, serum urea nitrogen, retinol-binding protein, cystatin C, serum phosphorus (all P<0.01), and negatively correlated with hemoglobin and eGFR (both P<0.01). The median follow-up time was 8(4, 16) months. To the end of the follow-up, 113 patients (27.90%) had renal adverse prognostic events. Kaplan-Meier survival analysis results showed that the renal cumulative survival rate of the high-level MHR group was lower than that of the low-level MHR group (χ²=8.277, P=0.004). Multivariate Cox regression analysis showed that high MHR level was an independent influencing factor for poor renal prognosis in CKD patients (HR=1.628, 95%CI 1.050-2.523, P=0.029). Stratified analysis showed that, without hypertension, MHR had a more significant effect on the prognosis of the kidneys (HR=3.414, 95%CI 1.091-10.686, P for interaction=0.001). Conclusions The level of MHR is related to the severity and poor renal prognosis of CKD, and the high MHR level is an independent predictor for poor renal prognosis in CKD patients.

Objective To investigate the predictive value of peritoneal protein clearance (Pcl) for cardiovascular events and cardiovascular mortality in peritoneal dialysis (PD) patients. Methods Eligible PD patients were prospectively enrolled from January 2014 to April 2015 in the PD Center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University. All patients were followed up until death, withdrawing from PD, transferring to other centers, or the end of study period (October 1, 2018). The patients were divided into high Pcl group and low Pcl group by the median Pcl, and the differences of related indicators between the two groups were compared. A multiple linear regression model was used to analyze the influencing factors of Pcl. The Kaplan-Meier method and Log-rank test were used to compare the cumulative survival rates of patients between the two groups. A multivariate Cox regression model was used to estimate the risk of cardiovascular events and cardiovascular mortality in relation to Pcl in PD patients. Results A total of 271 patients were enrolled, with 135 males (49.8%), age of (56.92±0.84) years old and a median PD duration of 38.77(19.00, 63.10) months. There were 70 patients (25.8%) comorbiding with diabetes and 81 patients (29.9%) with cardiovascular diseases (CVD). The median Pcl of this cohort was 67.93(52.31, 88.36) ml/d. Compared with the low Pcl group (Pcl<67.93 ml/d), the high Pcl group (Pcl≥67.93 ml/d) had older age, and greater proportion of CVD, body mass index (BMI), pulse pressure, brain natriuretic peptide, mass transfer area coefficient of creatinine (MTACcr), and lower serum albumin (all P<0.05). There was no significant difference in gender, dialysis duration, proportion of diabetes, proportion of angiotensin converting enzyme inhibitor and angiotensin receptor blocker, proportion of continuous ambulatory PD, high sensitivity C reactive protein, fluid removal including 24 h urine volume and 24 h ultrafiltration, and residual renal function between the two groups (all P>0.05). Multiple linear regression analysis showed that serum albumin (β=-0.388, P<0.001), BMI (β=0.189, P<0.001), and MTACcr (β=0.247, P<0.001) were independently related to lg(Pcl). During the study period, 55 patients experienced one or more cardiovascular events and 39 patients had cardiovascular mortality. According to Kaplan-Meier analysis, cardiovascular mortality in the high Pcl group was higher than that of low Pcl group (Log-rank χ²=6.902, P=0.009). Multivariate Cox regression analysis showed that, high lg(Pcl) was an independent influencing factor of cardiovascular events in PD patients (HR=7.654，95%CI 1.676-34.945, P=0.009). Conclusions Serum albumin, BMI and MTACcr are independently associated with Pcl, and Pcl is an independent predictor of cardiovascular events in PD patients.

Objective To evaluate the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) on lipid homeostasis and cellular injury of podocytes, and to clarify its mechanism. Methods Twelve-week old C57BL/6 wild-type mice (n=10) and PCSK9 knockout (PCSK9 KO) mice (n=10) were selected as the animal models. The renal tissues were taken after perfusion through heart. Mouse podocytes were transfected with PCSK9 siRNA to downregulate PCSK9 expression. BODIPY 493/503 staining was performed for evaluating lipid accumulation, and standard transmission electron microscopy (TEM) was used to observe the foot process of podocytes, the shape of mitochondria and lipid droplet in podocytes. TUNEL staining was carried out to evaluate cell apoptosis in glomerulus. The parameters about mitochondria function (key enzymes such as PGC-1α, CPT-1 and Acox-1) and apoptosis were quantified through qPCR and western blotting. Results The lipid accumulation in glomerulus of PCSK9 KO mice were more serious than controls. The expression of PGC-1α protein and PGC-1α, CPT-1 and Acox-1 mRNA in PCSK9 KO mouse kidney tissues were decreased than controls (all P<0.05), and mitochondria swelling and cristae disappearance in podocytes of PCSK9 KO mice were observed. In PCSK9 KO group, the foot process of podocytes partially fused and disappeared, and the apoptosis index increased compared with the control group (P<0.05). In vitro, compared with the control group, the lipid accumulation was more significant, transcription level of key enzymes related to mitochondrial function was decreased, mitochondrial structure was damaged and the apoptosis index was increased in cultured podocyte PCSK9 siRNA group (all P<0.05). Conclusions PCSK9 is involved in the lipid homeostasis of podocytes. The decrease of PCSK9 results in the increase of intracellular lipid accumulation, accompanied by the mitochondrial structure damage and disfunction of podocytes, and leads to cell apoptosis.