Risk factors of different mortality periods in older patients with end-stage renal disease undergoing urgent-start peritoneal dialysis: a retrospective observational study.

BACKGROUND: The first six months of therapy represents a high-risk period for peritoneal dialysis (PD) failure. The risk of death in the first six months is higher for older patients treated with urgent-start PD (USPD). However, there are still gaps in research on mortality and risk factors for death in this particular group of patients. We aimed to investigate mortality rates and risk factors for death in older patients with end-stage renal disease (ESRD) receiving USPD within and after six months of therapy. METHODS: We retrospectively studied the clinical information of older adults aged ≥ 65 years with ESRD who received USPD between 2013 and 2019 in five Chinese hospitals. Patients were followed up to June 30, 2020. The mortality and risk factors for death in the first six months of USPD treatment and beyond were analyzed. RESULTS: Of the 379 elderly patients in the study, 130 died over the study period. During the follow-up period, the highest number (45, 34.6%) of deaths occurred within the first six months. Cardiovascular disease was the most common cause of death. The baseline New York Heart Association (NYHA) class III-IV cardiac function [hazard ratio (HR) = 2.457, 95% confidence interval (CI): 1.200-5.030, p = 0.014] and higher white blood cell (WBC) count (HR = 1.082, 95% CI: 1.021-1.147, p = 0.008) increased the mortality risk within six months of USPD. The baseline NYHA class III-IV cardiac function (HR = 1.945, 95% CI: 1.149-3.294, p = 0.013), lower WBC count (HR = 0.917, 95% CI: 0.845-0.996, p = 0.040), lower potassium levels (HR = 0.584, 95% CI: 0.429-0.796, p = 0.001), and higher calcium levels (HR = 2.160, 95% CI: 1.025-4.554, p = 0.043) increased the mortality risk after six months of USPD. CONCLUSION: Different risk factors correlated with mortality in older adults with ESRD within and after six months of undergoing USPD, including baseline NYHA class III-IV cardiac function, WBC count, potassium, and calcium levels.

[Clinical Outcome and Risk Factors of Treatment Failure of Peritoneal Dialysis Associated Peritonitis Caused by Klebsiella Pneumoniae:A Multicenter Study].

Objective To investigate the treatment outcomes,prognosis,and risk factors of treatment failure of peritoneal dialysis associated peritonitis (PDAP) caused by Klebsiella pneumoniae,and thus provide clinical evidence for the prevention and treatment of this disease. Methods The clinical data of PDAP patients at four peritoneal dialysis centers from January 1,2014 to December 31,2019 were collected retrospectively.The treatment outcomes and prognosis were compared between the patients with PDAP caused by Klebsiella.pneumoniae and that caused by Escherichia coli.Kaplan-Meier method was employed to establish the survival curve of technical failure,and multivariate Logistic regression to analyze the risk factors of the treatment failure of PADP caused by Klebsiella pneumoniae. Results In the 4 peritoneal dialysis centers,1034 cases of PDAP occurred in 586 patients from 2014 to 2019,including 21 cases caused by Klebsiella pneumoniae and 98 cases caused by Escherichia coli.The incidence of Klebsiella pneumoniae caused PDAP was 0.0048 times per patient per year on average,ranging from 0.0024 to 0.0124 times per patient per year during 2014-2019.According to the Kaplan-Meier survival curve,the technical failure rate of Klebsiella pneumoniae caused PDAP was higher than that of Escherichia coli caused PDAP (P=0.022).The multivariate Logistic regression model showed that long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP (OR=1.082,95%CI=1.011-1.158,P=0.023).Klebsiella pneumoniae was highly sensitive to amikacin,meropenem,imipenem,piperacillin,and cefotetan,and it was highly resistant to ampicillin (81.82%),cefazolin (53.33%),tetracycline (50.00%),cefotaxime (43.75%),and chloramphenicol (42.86%). Conclusion The PDAP caused by Klebsiella pneumoniae had worse prognosis than that caused by Escherichia coli,and long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP.

Influence of Early-Onset Peritonitis on Mortality and Clinical Outcomes in ESRD Patients with Diabetes Mellitus on Peritoneal Dialysis: A Retrospective Multicenter Study.

INTRODUCTION: The impact of early-onset peritonitis (EOP) on patients with diabetes undergoing peritoneal dialysis (PD) has not been adequately addressed. We therefore sought to investigate the effects of EOP on the therapeutic response to management and long-term prognostic outcomes in patients with diabetes undergoing PD. METHODS: For this retrospective cohort study, we analyzed the data for patients with end-stage renal disease, who were also suffering from diabetes mellitus and had undergone PD between January 1, 2013, and December 31, 2018. EOP was defined as the first episode of peritoneal dialysis-related peritonitis (PDAP) occurring within 12 months of PD initiation. All patients were divided into an EOP group and a later-onset peritonitis (LOP) group. Clinical data, treatment results, and outcomes were compared between groups. RESULTS: Ultimately, 202 patients were enrolled for the analysis. Compared to the EOP group, the LOP group had more Streptococcus (p = 0.033) and Pseudomonas (p = 0.048). Patients with diabetes in the EOP group were less likely to have PDAP-related death (OR 0.13, CI: 0.02-0.82, p = 0.030). Patients with diabetes in the EOP group were more likely to have multiple episodes of PDAP and had higher rates of technical failure and poorer patient survival than those in the LOP group, as indicated by Kaplan-Meier analysis (p = 0.019, p = 0.004, and p < 0.001). In the multivariate Cox proportional hazards model, EOP was a significant predictor for multiple PDAP (HR 4.20, CI: 1.48-11.96, p = 0.007), technical failure (HR 6.37, CI: 2.21-18.38, p = 0.001), and poorer patient survival (HR 3.09, CI: 1.45-6.58, p = 0.003). CONCLUSIONS: The occurrence of EOP is significantly associated with lower rates of PDAP-related death and poorer clinical outcomes in patients with diabetes undergoing PD.

Risk factors for hypocalcemia in dialysis patients with refractory secondary hyperparathyroidism after parathyroidectomy: a meta-analysis.

OBJECTIVE: Hypocalcemia after parathyroidectomy (PTX) results in tetany, diarrhea, cardiac arrhythmia, and even sudden death. However, a meta-analysis or systematic evaluation of risk factors with the occurrence and development of hypocalcemia in patients with secondary hyperparathyroidism (SHPT) after PTX has never been performed. METHODS: A thorough search of electronic databases, including PubMed, Web of Science, the Cochrane Library, and EMBASE, was performed to retrieve relevant studies from database inception to June 2021. Quality of the included studies was assessed by two independent reviewers using the Newcastle-Ottawa Scale. Review Manager 5.3 and Stata 16.0 were used for meta-analysis. The random-effects model was adopted to calculate the 95% CIs (I2> 50% or p < 0.05) of the combined effect size and the corresponding homogeneous data. Otherwise, a fixed-effects model was used. RESULTS: Thirteen studies including 2990 participants who met the inclusion criteria were enrolled in the present meta-analysis. The overall quality of the enrolled studies had a score of >7 points. Risk factors significantly related to hypocalcemia in patients with SHPT after PTX were preoperative serum calcium (OR 0.19, 95%CI 0.11-0.31), preoperative alkaline phosphatase (ALP) (OR 1.01, 95% CI 1.01-1.02), and preoperative intact parathyroid hormone (iPTH) (OR 1.38, 95%CI 1.20-1.58). Meanwhile, age (OR 0.97, 95%CI 0.87-1.10) was not significantly correlated with hypocalcemia after PTX. CONCLUSIONS: Based on the current evidence, preoperative serum calcium, preoperative ALP, and preoperative iPTH were significant predictors of hypocalcemia in patients with SHPT after PTX. More attention should be given to patients with these risk factors for the prevention of postoperative hypocalcemia.

Feasibility of a break-in period of less than 24 hours for urgent start peritoneal dialysis: a multicenter study.

PURPOSE: Urgent start peritoneal dialysis (USPD) is an effective therapeutic method for end-stage renal disease (ESRD). However, whether it is safe to initiate peritoneal dialysis (PD) within 24 h unclear. We examined the short-term outcomes of a break-in period (BI) of 24 h for patients undergoing USPD. METHODS: This real-world, multicenter, retrospective cohort study evaluated USPD patients from five centers from January 2013 to August 2020. Patients were divided into BI ≤ 24 h or BI > 24 h groups. The Primary outcomes included incidence of mechanical and infectious complications. The secondary outcome was technique failure. Moreover, we presented a subgroup analysis for patients who did not receive temporary hemodialysis (HD). RESULTS: A total of 871 USPD patients were included: 470 in the BI ≤ 24 h and 401 in the BI > 24 h groups. Mechanical and infectious complications did not differ between the two groups across the follow-up timepoints (2 weeks, 1 month, 3 months, and 6 months) (p > 0.05). Multiple logistic regression analysis revealed that BI ≤ 24 h was not an independent risk factor for mechanical complications, catheter migration, or infectious complications (p > 0.05). A BI ≤ 24 h was not an independent significant risk factor for technique failure by multivariate Cox regression analysis (p > 0.05). The subgroup analysis of patients who did not receive temporary HD returned the same results. CONCLUSION: Initiating PD within 24 h of catheter insertion was not associated with increased mechanical complications, infectious complications, or technique failures.

[Clinical Characteristics and Treatment Outcome of Pseudomonas Peritoneal Dialysis-associated Peritonitis].

Objective To explore the clinical characteristics and treatment of Pseudomonas peritoneal dialysis-associated peritonitis(PsP). Methods The data of patients receiving peritoneal dialysis in four tertiary hospitals in Jilin province from 2015 to 2019 were retrospectively analyzed.According to the etiological classification,the patients with peritoneal dialysis-associated peritonitis(PDAP)were classified into PsP group and non-PsP group.The incidence of PsP was calculated,and the clinical characteristics and treatment outcomes of the two groups were compared.Kaplan-Meier method was used to draw the survival curve,and Cox regression was performed to analyze the risk factors affecting the technical failure of PsP.The treatment options of Pseudomonas aeruginosa-caused PDAP and the drug sensitivity of PsP were summarized. Results A total of 1530 peritoneal dialysis patients with complete data were included in this study,among which 439 patients had 664 times of PDAP.The incidence of PsP was 0.007 episodes/patient-year.PsP group had higher proportion of refractory peritonitis(41.38% vs.19.69%,P=0.005),lower cure rate(55.17% vs.80.79%, P=0.001),and higher extubation rate(24.14% vs.7.09%,P=0.003)than non-PsP group.The technical survival rate of PsP group was lower than that of non-PsP group(P<0.001).Multivariate Cox regression analysis showed that Pseudomonas aeruginosa was an independent risk factor for technical failure in patients with PsP(HR=9.020,95%CI=1.141-71.279,P=0.037).Pseudomonas was highly sensitive to amikacin,meropenem,and piperacillin-tazobactam while highly resistant to compound sulfamethoxazole,cefazolin,and ampicillin. Conclusion The treatment outcome of PsP is worse than that of non-PsP,and Pseudomonas aeruginosa is an independent risk factor for technical failure of PsP.

Serum elabela and apelin levels during different stages of chronic kidney disease.

PURPOSE: The association of serum elabela (ELA) and apelin with the progression of chronic kidney disease (CKD) is unknown. We determined if serum ELA and apelin levels were associated with CKD stage. METHODS: This observational study involved 60 CKD patients and 20 healthy, age-, race-, and gender-matched controls. The participants were grouped according to renal function as follows: normal control group, CKD1 group (stage-1 CKD, 20 patients), CKD3 group (stage-3 CKD, 20 patients), and CKD5 group (stage-5 CKD, 20 patients) in accordance with the Kidney Disease Outcomes - Quality Initiative criteria. We recorded the demographic, clinical, and biochemical data of all participants. Serum ELA and apelin levels were measured using commercially available enzyme-linked immunosorbent assays. RESULTS: Serum ELA levels gradually and significantly declined with decreases in the estimated glomerular filtration rate (eGFR). Serum ELA showed significant negative correlations with serum creatinine (r = -0.529, p < .001), blood urea nitrogen (r = -0.575, p < .001), systolic blood pressure (r = -0.455, p < .001), and diastolic blood pressure (r = -0.450, p < .001), and significant positive correlations with hemoglobin (r = 0.523, p < .001) and eGFR (r = 0.728, p < .001). Multiple regression analysis showed that eGFR independently influenced serum ELA levels. No significant association was found between serum apelin levels and CKD progression. CONCLUSION: In CKD patients, serum ELA levels decreased with decreasing eGFR. This finding may provide a new target for the prediction, diagnosis, and staging of CKD.

Protective or deleterious role of Wnt/beta-catenin signaling in diabetic nephropathy: An unresolved issue.

In recent years, the Wnt/ß-catenin signaling has gained tremendous attention due to its ability to modulate a number of diseases including diabetic nephropathy. Studies have shown that there is decrease in the secretion of Wnt proteins including Wnt4, 5a and Wnt 6 during high glucose concentration or diabetic conditions, which leads to decreased translocation of ß-catenin to nucleus. The down-regulation of Wnt/ß-catenin signaling leads to detrimental effects on kidney including increased apoptosis of mesangial cells and increased deposition of fibrous tissue in mesangium. The pharmacological modulators such as spironolactone, NO donor and antioxidant are shown to produce beneficial effects in diabetic nephropathy by up regulating the expression of Wnt proteins and activation of diabetes-induced suppressed Wnt/ß-catenin signaling. On the other hand, it is documented that diabetes leads to overactivation of Wnt1/ß-catenin signaling, which promotes podocyte injury, induce epithelial-mesenchymal transition of podocytes along with renal injury and fibrosis. Accordingly, different interventions aimed to suppress overactivated Wnt/ß-catenin signaling are reported to improve the condition and symptoms associated with diabetic nephropathy. The present review discusses the dual role of Wnt/beta-catenin signaling in the pathogenesis of diabetic nephropathy.

A simplified percutaneous technique for inserting Tenckhoff catheters for peritoneal dialysis.

AIM: Successful catheter implantation is highly essential for delivering effective peritoneal dialysis (PD). The aim of the present study was to describe a newly developed, minimally invasive percutaneous technique for providing safe, timely, and effective peritoneal catheter insertion and assess the long-term outcome. MATERIALS AND METHODS: 100 PD catheters were placed in 100 consecutive patients by a nephrologist using the modified percutaneous technique with a special trocar, from August 1, 2010 to December 31, 2011. The patients were followed up until October 31, 2015. Demographic and clinical features of study subjects, duration of hospital stay, follow-up time, complications, and catheter survival were assessed in all patients. RESULTS: The patient study group included 47 men and 53 women, with a mean age of 55.3 ± 13.7 years. The mean hospitalization time was 17.1 ± 8.6 days, and the mean duration of follow-up was 44.7 ± 15.1 months. 71 patients were still on continuous ambulatory peritoneal dialysis at the time of study completion. Peritonitis was the most common complication observed, with an incidence of 28%. None of the patients experienced surgical complications such as bleeding or incisional hernia. The mean catheter survival time was 57.0 ± 1.5 months. CONCLUSION: Peritoneal catheter placement using our modified percutaneous technique is simple, safe, minimally invasive, and efficient. It carried less morbidity with respect to bowel perforation, catheter-related infection, and exit-site leak.
.

Diagnostic Value of Urinary miR-152-5p in Patients with IgA Nephropathy with Elevated Proteinuria Levels.

BACKGROUND: The current study aims to observe the correlation between the expression of miR-152-5p in urine samples and the condition of IgA nephropathy (IgAN). METHODS: From January 2017 to October 2017, 40 patients with IgAN, 10 patients with mild glomerular lesions, 10 patients with membranous proliferative glomerulonephritis type I, 10 patients with focal segmental glomeruloscle-rosis, 10 patients with Henoch-Schonlein purpura nephritis, and 10 patients with lupus nephritis. Meanwhile, 25 healthy controls were also included in the physical examination center of our hospital. The expression level of miR-152-5p was detected by RT-qPCR. The correlation between the expression level of miR-152-5p and patholog-ical Haas grading and urinary protein was analyzed. RESULTS: The expression level of miR-152-5p in IgA nephropathy patients was higher than that in other types of glomerulonephritis and healthy control group (p < 0.0001). Meanwhile, the level of miR-152-5p in IgAN patients with high score (p < 0.01) was significantly increased. Furthermore, the level of miR-152-5p was positively corre-lated with the level of urinary protein and the degree of renal pathological damage (r2 = 0.89, p < 0.01). CONCLUSIONS: The expression of urinary miR-152-5p is positively correlated with IgA nephropathy, which provides a new way for early diagnosis and treatment of IgA nephropathy with elevated proteinuria.

FFNT25 ameliorates unilateral ureteral obstruction-induced renal fibrosis.

Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) patients who progress to end-stage renal disease (ESRD). With the increasing incidence of CKD, it is of importance to develop effective therapies that blunt development of renal fibrosis. FFNT25 is a newly developed molecular compound that could be used to prevent fibrosis. In this study, we administered FFNT25 to rats following unilateral ureteral obstruction (UUO) to investigate its anti-fibrosis mechanism. Thirty-two Sprague-Dawley rats were randomly divided into four groups: (1) control (normal rats), (2) sham-operated, (3) UUO-operated + vehicle, and (4) UUO-operated + FFNT25. Two weeks after UUO, the rats were gavaged with either FFNT25 (20.6 mg/kg/day) or vehicle for two weeks. Serum, urine, and kidney samples were collected at the end of the study. FFNT25 reduced levels of renal fibrosis and decreased mRNA and protein levels of extracellular matrix (ECM) markers α-smooth muscle actin (α-SMA) and plasminogen activator inhibitor-1 (PAI-1) following UUO compared to vehicle treatment (n = 8, p<.05). The current results indicate that FFNT25 can affect both the production and degradation of collagen fibers to reduce fibrosis.

Long Noncoding RNA Small Nucleolar RNA Host Gene 1 (SNHG1) Promotes Renal Cell Carcinoma Progression and Metastasis by Negatively Regulating miR-137.

BACKGROUND Data on the expression of RCC tissues from the GEO database and patient survival data from TCGA were used to explore the prognostic significance of long noncoding RNA SNHG1. SNHG1 has been reported to participate in the development of several cancers, but, the underlying mechanism of SNHG1 in renal cell carcinoma (RCC) has not been reported. The purpose of our study was to investigate the potential function of SNHG1 in RCC. MATERIAL AND METHODS The expression of SNHG1 in 40 cases of RCC and adjacent normal tissues and 5 cell lines was detected by qRT-PCR. Cell proliferation, Transwell assay, and Western blotting assay were carried out to investigate the biological function of SNHG1. A rescue experiment was performed to verify that miR-137 can partly impede the effect of SNHG1 on renal cancer cells. RESULTS SNHG1 was identified to be overexpressed in RCC tissues and RCC cell lines. High levels of SNHG1 were correlated with poor prognosis of RCC patients. Knockdown of SNHG1 suppressed the proliferation, invasion, and EMT capacity in RCC. Moreover, miR-137 abrogated the effect of SNHG1 on RCC. CONCLUSIONS SNHG1 is significantly upregulated in RCC and renal cancer cell lines. Overexpression of SNHG1 participates in RCC tumorigenesis by regulating miR-137.

Efficacy and safety of mycophenolate mofetil in patients with IgA nephropathy: an update meta-analysis.

BACKGROUND: The application of mycophenolate mofetil (MMF) in treating patients with immunoglobulin A nephropathy (IgAN) remains uncertain. This update meta-analysis was performed to re-evaluate the therapeutic potential of MMF in IgAN. METHODS: Articles were obtained by searching the electronic databases without language restriction. Randomized controlled trials studying the role of MMF in treating IgAN were collected. The quality of included studies was critically evaluated. Data analyses were performed by using RevMan 5.3 software. RESULTS: A total of 297 articles were screened and eight articles were finally included. Among the eight randomized controlled trials, five and three were high quality and low quality, respectively. Both fixed-effect and random-effect model were used. Pooled results by combining all the eight studies suggested that IgAN patients in MMF group had a higher remission rate than that in control group. Compared to placebo or corticosteroid monotherapy, MMF monotherapy exerted a higher remission rate and side effect rate in both main analysis and subgroup analysis by human race. Compared to corticosteroid plus other immunosuppressive agent therapy, corticosteroid plus MMF therapy had a higher remission rate, lower serum creatinine doubling rate, progression to end-stage renal disease rate and side effects rate. Subgroup analysis by therapeutic regimen further confirmed these results between corticosteroid plus MMF therapy and corticosteroid plus cyclophosphamide therapy. Funnel-plot displayed a symmetrical figure, indicating no publication bias existed. CONCLUSIONS: MMF has the potential in treatment of IgAN, especially for Asians. The evidence currently available shows that MMF monotherapy has a more efficacy but higher side effects when compared to placebo or corticosteroid monotherapy in treatment of Asians with IgAN. While MMF combined with corticosteroid regimen has a more efficacy and lower side effects when compared with corticosteroid plus cyclophosphamide regimen.

Interaction of thrombospondin1 and CD36 contributes to obesity-associated podocytopathy.

Obesity is associated with podocyte injury and the development of proteinuria. Elevated plasma free fatty acid is one of the characteristics of obesity and has been linked to podocyte dysfunction. However, the mechanisms remain unclear. In the current study, we examined the effect of saturated free fatty acid (FFA) on human podocyte apoptosis and function in vitro. The mechanism and its in vivo relevance were also determined. We found that FFA treatment induced human podocyte apoptosis and dysfunction, which was associated with increased expression of a matricellular protein-thrombospondin1 (TSP1). FFA stimulated TSP1 expression in podocytes at the transcriptional levels through activation of MAPK pathway. Addition of purified TSP1 to cell culture media induced podocyte apoptosis and dysfunction. Tis effect is though a TGF-ß independent mechanism. Moreover, peptide treatment to block TSP1 binding to its receptor-CD36 attenuated FFA induced podocyte apoptosis, suggesting that TSP1/CD36 interaction mediates FFA-induced podocyte apoptosis. Importantly, using a diet-induced obese mouse model, in vivo data demonstrated that obesity-associated podocyte apoptosis and dysfunction were attenuated in TSP1 deficient mice as well as in CD36 deficient mice. Taken together, these studies provide novel evidence that the interaction of TSP1 with its receptor CD36 contributes to obesity--associated podocytopathy.

Novel curcumin analog C66 prevents diabetic nephropathy via JNK pathway with the involvement of p300/CBP-mediated histone acetylation.

Glomerulosclerosis and interstitial fibrosis represent the key events in development of diabetic nephropathy (DN), with connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1) and fibronectin 1 (FN-1) playing important roles in these pathogenic processes. To investigate whether the plant metabolite curcumin, which exerts epigenetic modulatory properties when applied as a pharmacological agent, may prevent DN via inhibition of the JNK pathway and epigenetic histone acetylation, diabetic and age-matched non-diabetic control mice were administered a 3-month course of curcumin analogue (C66), c-Jun N-terminal kinase inhibitor (JNKi, sp600125), or vehicle alone. At treatment end, half of the mice were sacrificed for analysis and the other half were maintained without treatment for an additional 3 months. Renal JNK phosphorylation was found to be significantly increased in the vehicle-treated diabetic mice, but not the C66- and JNKi-treated diabetic mice, at both the 3-month and 6-month time points. C66 and JNKi treatment also significantly prevented diabetes-induced renal fibrosis and dysfunction. Diabetes-related increases in histone acetylation, histone acetyl transferases' (HATs) activity, and the p300/CBP HAT expression were also significantly attenuated by C66 or JNKi treatment. Chromatin immunoprecipitation assays showed that C66 and JNKi treatments decreased H3-lysine9/14-acetylation (H3K9/14Ac) level and p300/CBP occupancy at the CTGF, PAI-1 and FN-1 gene promoters. Thus, C66 may significantly and persistently prevent renal injury and dysfunction in diabetic mice via down-regulation of diabetes-related JNK activation and consequent suppression of the diabetes-related increases in HAT activity, p300/CBP expression, and histone acetylation.

A porcine model of relief of unilateral ureteral obstruction: study on self-repairing capability over multiple time points.

It is still controversial whether renal tubular interstitial fibrosis (TIF) is a reversible process. Although previous studies examining TIF have been carried out in rodents, their kidney size and physiological character differ with humans, and the difference among diverse individuals before and after damage was obvious. Thus an experimental animal model to simulate human kidney disease was urged to be established. In order to clarify whether TIF is reversible, and the exact time points that the kidney has the capacity to be repaired, a porcine relief of unilateral ureteral obstruction (R-UUO) model was developed. Kidney damage and reparation were observed dynamically in vivo over various time points. Pigs were randomized divided into three groups (n = 6): UUO 5 days group, UUO 7 days, and UUO 10 days group. Each porcine in that groups underwent UUO and subsequent R-UUO for three time points. Renal function, histological structure, and protein expressions of α-smooth muscle actin (α-SMA), vimentin and E-cadherin were evaluated at different time points. Following R-UUO after 5 and 7 days of UUO, compared to UUO, serum creatinine levels were significantly decreased. Renal pathological tissue damage was repaired. The expressions of α-SMA and vimentin were decreased and E-cadherin expression was increased (P < 0.05). However, during R-UUO 14, 28, and 56 days after 10 days of UUO, serum creatinine was not decreased significantly. The expressions of α-SMA and vimentin consistently remained at high levels. Renal damage was unable to be restored and resulted in chronic lesions. Kidney damage induced by UUO can be reversed in early stages. However, longer time of UUO with significant levels of TIF showed limited reversibility. The porcine R-UUO model provides an ideal animal model for the investigation of kidney injury and repair as well as for the evaluation of the effect of drug treatment.

Zinc is essential for the transcription function of Nrf2 in human renal tubule cells in vitro and mouse kidney in vivo under the diabetic condition.

Increasing evidence from human and laboratory studies showed the effect of zinc (Zn) on diabetic complications. Nuclear factor-erythroid 2-related factor 2 (Nrf2) plays important role in the prevention of oxidative damage. This study was to define whether Zn statues (deficiency or supplement) affect the Nrf2 expression and function, and also affect the damage severity of human renal tubular (HK11) cells exposed to high glucose (HG) with palmitate (Pal) and kidney of diabetic mice induced by multiple low-dose streptozotocins. For Zn deficiency diabetic mice were treated with Zn chelator PTEN at 5 mg/kg bw daily for 4 months. Results showed that HG/Pal significantly increased the expression of pro-fibrotic mediators, connective tissue growth factor and PAI-1, in HK11 cells, which was exacerbated by TPEN that depleted intracellular free Zn and decreased Nrf2 expression and transcription. Zn supplement prevented the effects of TPEN and also increased Akt and GSK-3ß phosphorylation with a decrease in Nrf2 nuclear exporter, Fyn. All these effects of Zn were abolished by Akt inhibitor. Therefore, Zn up-regulates Nrf2 function via activating Akt-mediated inhibition of Fyn function. Treatment of diabetic mice with TPEN decreased renal Zn level and Nrf2 expression and transcription, with an exacerbation of renal oxidative damage, inflammation and fibrosis. These results suggest the essentiality of Zn for Nrf2 expression and transcription function.

Increasing cGMP-dependent protein kinase activity attenuates unilateral ureteral obstruction-induced renal fibrosis.

Our previous studies support the protective effect of cGMP and cGMP-dependent protein kinase I (PKG-I) pathway on the development of renal fibrosis. Therefore, in the present studies, we determined whether pharmacologically or genetically increased PKG activity attenuates renal fibrosis in a unilateral ureteral obstruction (UUO) model and also examined the mechanisms involved. To increase PKG activity, we used the phosphodiesterase 5 inhibitor sildenafil and PKG transgenic mice. UUO model was induced in wild-type or PKG-I transgenic mice by ligating the left lateral ureteral and the renal fibrosis was observed after 14 days of ligation. Sildenafil was administered into wild-type UUO mice for 14 days. In vitro, macrophage and proximal tubular cell function was also analyzed. We found that sildenafil treatment or PKG transgenic mice had significantly reduced UUO-induced renal fibrosis, which was associated with reduced TGF-ß signaling and reduced macrophage infiltration into kidney interstitial. In vitro data further demonstrated that both macrophages and proximal tubular cells were important sources of UUO-induced renal TGF-ß levels. The interaction between macrophages and tubular cells contributes to TGF-ß-induced renal fibrosis. Taken together, these data suggest that increasing PKG activity ameliorates renal fibrosis in part through regulation of macrophage and tubular cell function, leading to reduced TGF-ß-induced fibrosis.

A nomogram prediction model for hungry bone syndrome in dialysis patients with secondary hyperparathyroidism after total parathyroidectomy.

OBJECTIVE: Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD). Hungry bone syndrome (HBS) after parathyroidectomy (PTX) is a serious complication, which can lead to diarrhea, convulsion, arrhythmia and even death. This study was aimed to determine the risk factors for HBS after PTX in dialysis patients with SHPT and construct a nomogram prediction model to predict the incidence of postoperative complications. METHODS: Clinical data were collected from 80 maintenance hemodialysis (MHD) patients with SHPT who received total PTX in the Second Hospital of Jilin University from January 2018 to September 2021. In line with the inclusion and exclusion criteria, totally 75 patients were finally enrolled for analysis. Patients were divided into two groups for retrospective analysis according to the severity of postoperative HBS, including HBS group and non-HBS (N-HBS) group. Univariate and multivariate logistic regression analyses were conducted to determine the risk factors for postoperative HBS. Afterwards, the receiver operating characteristic (ROC) curves were plotted based on the statistical analysis results, aiming to compare the prediction effects of different predicting factors. Finally, the nomogram was established to evaluate the occurrence probability of postoperative complications predicted by the risk factors. RESULTS: Among the 75 patients, 32 had HBS (HBS group), while 43 did not have HBS (N-HBS group). Univariate analysis results indicated that, the preoperative intact parathyroid hormone (iPTH) and serum alkaline phosphatase (ALP) levels in HBS group were significantly higher than those in N-HBS group, while preoperative hemoglobin and preoperative albumin (Alb) levels were significantly lower than those in N-HBS group. As discovered by multivariate logistic regression analysis, preoperative iPTH (OR = 1.111, P = 0.029) and ALP (OR = 1.010, P < 0.001) were the independent risk factors for postoperative HBS. ROC curve analysis suggested that the area under the curve (AUC) values of these two indicators were 0.873 and 0.926, respectively (P < 0.0001). Subsequently, the nomogram model for predicting HBS was constructed. The model verification results indicated that the predicted values were basically consistent with the measured values, with the C-index of 0.943 (95% CI 0.892-0.994). Besides, the calibration curve was consistent with the ideal curve, demonstrating the favorable accuracy and discrimination of the model. CONCLUSIONS: Preoperative iPTH and preoperative ALP are the risk factors for postoperative HBS, which can be used to guide the early clinical intervention.

Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation.

This study was to investigate whether sulforaphane (SFN) can prevent diabetic cardiomyopathy. Type 1 diabetes was induced in FVB mice by multiple intraperitoneal injections with low-dose streptozotocin. Hyperglycemic and age-matched control mice were treated with or without SFN at 0.5mg/kg daily in five days of each week for 3 months and then kept until 6 months. At 3 and 6 months of diabetes, blood pressure and cardiac function were assessed. Cardiac fibrosis, inflammation, and oxidative damage were assessed by Western blot, real-time qPCR, and histopathological examination. SFN significantly prevented diabetes-induced high blood pressure and cardiac dysfunction at both 3 and 6 months, and also prevented diabetes-induced cardiac hypertrophy (increased the ratio of heart weight to tibia length and the expression of atrial natriuretic peptide mRNA and protein) and fibrosis (increased the accumulation of collagen and expression of connective tissue growth factor and tissue growth factor-ß). SFN also almost completely prevented diabetes-induced cardiac oxidative damage (increased accumulation of 3-nitrotyrosine and 4-hydroxynonenal) and inflammation (increased tumor necrotic factor-α and plasminogen activator inhibitor 1 expression). SFN up-regulated NFE2-related factor 2 (Nrf2) expression and transcription activity that was reflected by increased Nrf2 nuclear accumulation and phosphorylation as well as the mRNA and protein expression of Nrf2 downstream antioxidants. Furthermore, in cultured H9c2 cardiac cells silencing Nrf2 gene with its siRNA abolished the SFN's prevention of high glucose-induced fibrotic response. These results suggest that diabetes-induced cardiomyopathy can be prevented by SFN, which was associated with the up-regulated Nrf2 expression and transcription function.