Protective effect of GLP-1 analog liraglutide on podocytes in mice with diabetic nephropathy.

Protection of podocytes is one of the important means to delay the progression of diabetic nephropathy (DN), and glucagon-like peptide-1 (GLP-1) has been shown to have a protective effect on the kidney in DN models, but whether it has a protective effect on podocytes and the potential mechanisms of action remain largely unknown. In the present study, we established a type 2 diabetes mellitus (T2DM) mouse model by high-fat diet feeding combined with streptozotocin (STZ) induction and administered the intervention for 14 weeks. We found that liraglutide significantly ameliorated podocyte injury in DN mice. Mechanistically, we detected glucagon-like peptide-1 receptor (GLP-1R) protein expression levels in kidney tissues by immunohistochemical staining, immunofluorescence staining, and western blotting and found that podocytes could express GLP-1R and liraglutide treatment could restore GLP-1R expression in the kidney tissues of DN mice. Furthermore, we found that NLRP3-induced inflammation and pyroptosis were positively correlated with podocyte injury in DN mice, and liraglutide inhibited the expression of NLRP3-induced inflammation and pyroptosis-related proteins. Our results suggest that liraglutide protects DN mouse podocytes by regulating GLP-1R in renal tissues and by regulating NLRP3-induced inflammation and pyroptosis.

Association between preoperative C-reactive protein to albumin ratio and late arteriovenous fistula dysfunction in hemodialysis patients: a cohort study.

Arteriovenous fistula (AVF) dysfunction is a critical complication in hemodialysis (HD) patients, with inflammation potentially contributing to its development. This retrospective cohort study aimed to investigate the association between preoperative C-reactive protein to albumin ratio (CAR) and AVF dysfunction in Chinese HD patients. A total of 726 adults with end-stage renal disease who underwent new AVF placement between 2011 and 2019 were included. Multivariable Cox regression and Fine and Gray competing risk models were employed to assess the relationship between CAR and AVF dysfunction, considering death and renal transplantation as competing risks. Among 726 HD patients, 29.2% experienced AVF dysfunction during a median follow-up of 36 months. Adjusted analyses revealed that higher CAR levels were associated with an increased risk of AVF dysfunction, with a 27% higher risk per one-unit increase in CAR. Furthermore, patients with CAR values ≥ 0.153 exhibited a 75% elevated risk compared to those with CAR values < 0.035 (P = 0.004). The relationship between CAR and AVF dysfunction varied by the site of internal jugular vein catheter placement (P for trend = 0.011). Notably, the Fine and Gray analysis confirmed the association between CAR and AVF dysfunction, with a 31% increased risk per one-unit increase in CAR. The highest CAR tertile remained an independent predictor of AVF dysfunction (HR = 1.77, 95% CI 1.21-2.58, P = 0.003). These findings highlight the potential of CAR as a prognostic marker for AVF dysfunction in Chinese HD patients. Clinicians should consider CAR levels and catheter placement site when assessing the risk of AVF dysfunction in this population.

Association between Preoperative Monocyte-to-Lymphocyte Ratio and Late Arteriovenous Fistula Dysfunction in Hemodialysis Patients: A Cohort Study.

BACKGROUND: Inflammation appears to be at the biological core of arteriovenous fistula (AVF) dysfunction, and the occurrence of AVF dysfunction is related to high death and disability in hemodialysis (HD) patients. Despite several studies on the correlations between AVF dysfunction and inflammatory indicators, how AVF dysfunction is related to the monocyte-to-lymphocyte ratio (MLR) is much unclear. We hypothesize that preoperative MLR is associated with AVF dysfunction in Chinese HD patients. METHODS: In this single-center retrospective cohort study, totally 769 adult HD patients with a new AVF created between 2011 and 2019 were included. Association of preoperative MLR with AVF dysfunction (thrombosis or decrease of normal vessel diameter by >50%, requiring either surgical revision or percutaneous transluminal angioplasty) was assessed by multivariable Cox proportional hazard regression. RESULTS: The patients were aged 55.8 ± 12.2 years and were mostly males (55%). During the average 32-month follow-up (maximum 119 months), 223 (29.0%) patients had permanent vascular access dysfunction. In adjusted multivariable Cox proportional hazard regression analyses, the risk of AVF dysfunction was 4.32 times higher with 1 unit increase in MLR (hazard ratio [HR]: 5.32; 95% confidence interval [CI]: 3.1-9.11). Compared with patients with MLR <0.28, HRs associated with an MLR of 0.28-0.41 and ≥0.41 are 1.54 (95% CI: 1.02-2.32) and 3.17 (2.18-4.62), respectively. CONCLUSIONS: A higher preoperative MLR is independently connected with a severer risk of AVF dysfunction in HD patients. Its clinical value should be determined in the future.

Corrigendum to "The Cumulative Rate of SARS-CoV-2 Infection in Chinese Hemodialysis Patients" [Kidney Int. Rep. 2020 1416-1421].

[This corrects the article DOI: 10.1016/j.ekir.2020.07.010.][This corrects the article DOI: 10.1016/j.ekir.2021.07.022.].

Erratum: The Cumulative Rate of SARS-CoV-2 Infection in Chinese Hemodialysis Patients.

[This corrects the article DOI: 10.1016/j.ekir.2021.07.021.][This corrects the article DOI: 10.1016/j.ekir.2020.07.010.].

The Cumulative Rate of SARS-CoV-2 Infection in Chinese Hemodialysis Patients.

BACKGROUND: There is a paucity of information regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients undergoing maintenance hemodialysis. We aimed to estimate the cumulative attack rate of SARS-CoV-2 in hemodialysis patients in China using a serological test. METHODS: We enrolled all hemodialysis patients from 8 hemodialysis facilities in Honghu and Jingzhou of Hubei province and Guangzhou and Foshan of Guangdong province in China. We screened these patients for SARS-CoV-2 infection by both a reverse-transcriptase polymerase chain reaction (RT-PCR) test for viral RNA and a serological test for IgG and IgM antibodies. Data on demographics and clinical characteristics were collected via case report forms. We also enrolled the health care workers from the participating hospitals and compared the seropositive rate between hemodialysis patients and health care workers in the same region. RESULTS: Among 1542 hemodialysis patients, 5 (0.32%) and 51 (3.3%) were tested positive by the RT-PCR test and the serological test, respectively. The seropositive rate in Hubei (3.6%) was higher than that in Guangdong (2.8%), although the difference was not statistically significant (P = 0.5). Most of the seropositive patients were asymptomatic. Independent risk factors for SARS-CoV-2 infection were being older than 65 years, having manifestation of lung infection in imaging examinations, and having a lower level of serum albumin. In comparison, the seropositive rate in 3205 health care workers was 1.2%，which was significantly lower than that observed in the hemodialysis patients (P < .001). CONCLUSION: The cumulative rate of SARS-CoV-2 infection in hemodialysis patients in China was high at 3.3%. Serological test detected 10 times more cases of SARS-CoV-2 infection than the RT-PCR test and should be the preferred tool for estimating the prevalence of coronavirus disease 2019 (COVID-19).

Author Correction: Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in China.

Detection of asymptomatic or subclinical novel human coronavirus SARS-CoV-2 infection is critical for understanding the overall prevalence and infection potential of COVID-19. To estimate the cumulative prevalence of SARS-CoV-2 infection in China, we evaluated the host serologic response, measured by the levels of immunoglobulins M and G in 17,368 individuals, in the city of Wuhan, the epicenter of the COVID-19 pandemic in China, and geographic regions in the country, during the period from 9 March 2020 to 10 April 2020. In our cohorts, the seropositivity in Wuhan varied between 3.2% and 3.8% in different subcohorts. Seroposivity progressively decreased in other cities as the distance to the epicenter increased. Patients who visited a hospital for maintenance hemodialysis and healthcare workers also had a higher seroprevalence of 3.3% (51 of 1,542, 2.5-4.3%, 95% confidence interval (CI)) and 1.8% (81 of 4,384, 1.5-2.3%, 95% CI), respectively. More studies are needed to determine whether these results are generalizable to other populations and geographic locations, as well as to determine at what rate seroprevalence is increasing with the progress of the COVID-19 pandemic. Serologic surveillance has the potential to provide a more faithful cumulative viral attack rate for the first season of this novel SARS-CoV-2 infection.

Randomized controlled trials for comparison of laparoscopic versus conventional open catheter placement in peritoneal dialysis patients: a meta-analysis.

BACKGROUND: The application of laparoscopic catheterization technology in peritoneal dialysis (PD) patients has recently increased. However, the advantages and disadvantages of laparoscopic versus conventional open PD catheter placement are still controversial. The aim of this meta-analysis is to assess the complications of catheterization in PD patients and to provide a reference for choosing a PD-catheter placement technique in the clinic. METHODS: We searched numerous databases, including Embase, PubMed, CNKI and the Cochrane Library, for published randomized controlled trials (RCTs). RESULTS: Eight relevant studies (n = 646) were included in the meta-analysis. The pooled results showed a lower incidence of catheter migration (OR: 0.42, 95% CI: 0.19 to 0.90, P: 0.03) and catheter removal (OR: 0.41, 95% CI: 0.21 to 0.79, P: 0.008) but a higher incidence of bleeding (OR: 3.25, 95% CI: 1.18 to 8.97, P: 0.02) with a laparoscopic approach than with a conventional approach. There was no significant difference in the incidence of omentum adhesion (OR: 0.32, 95% CI: 0.05 to 2.10, P: 0.24), hernia (OR: 0.38, 95% CI: 0.09 to 1.68, P: 0.20), leakage (OR: 0.69, 95% CI: 0.38 to 1.26, P: 0.23), intestinal obstruction (OR: 0.96, 95% CI: 0.48 to 1.91, P: 0.90) or perforation (OR: 0.95, 95% CI: 0.06 to 15.42, P: 0.97). The statistical analysis showed no significant difference in early (OR: 0.44, 95% CI: 0.15 to 1.33, P: 0.15), late (OR: 0.89, 95% CI: 0.41 to 1.90, P: 0.76) or total (OR: 0.68, 95% CI: 0.42 to 1.12, P: 0.13) peritonitis infections between the 2 groups, and there are no no significant difference in early (OR: 0.39, 95% CI: 0.06 to 2.36, P: 0.30), late (OR: 1.35, 95% CI: 0.78 to 2.33, P: 0.16) or total (OR: 1.20, 95% CI: 0.71 to 2.02, P: 0.17) tunnel or exit-site infections between the 2 groups. CONCLUSION: Laparoscopic catheterization and conventional open catheter placement in PD patients have unique advantages, but laparoscopic PD catheterization may be superior to conventional open catheter placement. However, this conclusion needs to be confirmed with further large-sample-size, multi-centre, high-quality RCTs.

Efficacy and safety of nicotinamide on phosphorus metabolism in hemodialysis patients: A systematic review and meta-analysis.

BACKGROUND: Recent evidence has shown that nicotinamide treatment may have an impact on phosphorus metabolism in hemodialysis patients. Nevertheless, the treatment remains controversial. This study aimed to precisely estimate the efficacy and safety of nicotinamide on phosphorus, calcium and iPTH in hemodialysis patients. METHODS: We searched numerous information sources regarding randomized controlled trials (RCTs) of nicotinamide treatment in hemodialysis patients, including PubMed, EMBASE, and the Cochrane Library. RESULTS: Nine relevant studies (n = 428) were included in the meta-analysis. Meta-analysis showed that levels of serum phosphorus (SMD -1.06; 95% CI, -1.27 to -0.85, P < .001), parathyroid hormone (SMD -1.09; 95% CI, -1.49 to -0.70, P < .001), and calcium-phosphorus (SMD -0.65; 95% CI, -0.97 to -0.34, P < .001) in the nicotinamide group were significantly lower than those of the control group. There was no significant difference in the levels of serum calcium (SMD 0.08; 95% CI, -0.15 to 0.30, P = .51) between the groups. The meta-analysis showed that the nicotinamide group had a significantly higher risk of adverse events (OR 3.99; 95% CI, 1.94-8.23, P < .001) than did the control group, especially for thrombocytopenia (OR 49.00; 95% CI, 2.68-897.36, P = .009). However, no serious adverse reactions were observed. There was no significant difference in the incidence of withdrawal (OR 3.51; 95% CI, 0.49-25.00, P = .21) between the groups. CONCLUSION: Evidence to date clearly indicates that nicotinamide is safe and effective for improving phosphorus metabolism in hemodialysis patients. However, nicotinamide probably causes thrombocytopenia. Further large-sample size, high-quality RCTs are needed.

Efficacy and safety of tacrolimus combined with glucocorticoid treatment for IgA nephropathy: a meta-analysis.

Objective As a classical immunosuppressant, tacrolimus (TAC) has been widely used in organ transplantation therapy, but the general benefits of TAC for the treatment of IgA nephropathy (IgAN) remain uncertain. We conducted a meta-analysis to examine the effects of TAC combined with glucocorticoid on IgAN. Methods We searched the information databases PubMed/Medline, Embase, Science Citation Index, Chinese Biomedical Literature and the Chinese databases VIP, CNKI and Wan Fang for randomized controlled trials of TAC combined with glucocorticoid as a therapy for IgAN. Results Ten relevant studies involving 472 patients were included in a meta-analysis. Overall, the TAC group showed a significant decrease in proteinuria compared with the control group (MD: -0.18 g/d, 95% CI: -0.32 to -0.04). No increased risk of adverse events was observed (OR: 0.93, 95% CI: 0.65 to 1.33). In general, the TAC group showed good tolerance. Conclusion Evidence to date clearly indicates that TAC combined with glucocorticoid is quite effective in reducing proteinuria and albuminuria in patients with IgAN. Moreover, we found that patients receiving TAC therapy did not show an increased risk of side effects compared with control group patients. TAC combined with glucocorticoid is a promising medication and merits further research.

Sustained low-efficiency daily diafiltration for diabetic nephropathy patients with acute kidney injury.

OBJECTIVE: To investigate the efficacy, safety and cost of treating patients with acute kidney injury (AKI) and diabetic nephropathy (DN) with continuous renal replacement therapy (CRRT) or sustained low-efficiency daily diafiltration with hemofiltration (SLEDD-f). SUBJECTS AND METHODS: Medical records of patients with AKI/DN from January 2006 to December 2012 were reviewed. Fifty-five patients who received CRRT and 52 who received SLEDD-f were included in the study. CRRT and SLEDD-f were performed for 20-72 h per session and 8-10 h per session, respectively. Mortality and renal function recovery rates were evaluated 30 days after the initiation of renal replacement therapy (RRT) and APACHE-II and SOFA scores, anticoagulant dose, inflammatory indices and cost were calculated at baseline and at the end of RRT. RESULTS: Of the 55 patients treated with CRRT, 49 (89.1%) had a 30-day survival rate and 30 (54.5%) had a 30-day renal recovery rate. Of the 52 patients with SLEDD-f, these rates were 92.3% (n = 48) and 61.5% (n = 32), respectively. The dosage of low-molecular-weight heparin in the CRRT and SLEDD-f groups was 15,230 ± 1,460 and 6,320 ± 490 U/day, respectively. The cost of hemopurification and the total cost for patients treated with CRRT was CNY 28,628 ± 5,576 (USD 4,210 ± 820) and CNY 38,828 ± 6,324 (USD 5,710 ± 930), respectively. These were higher than those for patients treated with SLEDD-f at CNY 13,260 ± 1,564 (USD 1,950 ± 230) and CNY 19,720 ± 2,652 (USD 2,900 ± 390), respectively. CONCLUSIONS: SLEDD-f offered a similar chance of renal recovery and also had further advantages such as a lower heparin dosage, a shorter therapy time and lower hospitalization costs for patients than CRRT. Studies with larger, randomized sample sizes are needed to confirm these findings.

Diagnostic value of phospholipase A2 receptor in idiopathic membranous nephropathy: a systematic review and meta-analysis.

BACKGROUND: Detection of M-type phospholipase A2 receptor (PLA2R) can be used in serologic diagnosis of idiopathic membranous nephropathy (IMN), but there are limited data about the sensitivity and specificity of its diagnostic values. METHODS AND RESULTS: Meta-analysis of diagnostic test studies assessing the values of PLA2R in diagnosis of IMN. MEDLINE, EMBASE, and CENTRAL databases and congress abstracts were searched for studies reporting the value of PLA2R to predict IMN. The quality of the studies was evaluated using the guidelines of the updated Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The results are summarized as sensitivity, specificity, and diagnostic odds ratio (OR). Data from 10 studies involving 1,550 participants were analyzed. Across all settings, the diagnostic OR for serum anti-PLA2R level to predict IMN at different stages was 247.41, with sensitivity of 0.69 and specificity of 0.99. The estimated sensitivity and specificity of serum anti-PLA2R level for diagnosis of IMN in the active stage were 74.0 and 95.0%, respectively, with diagnostic OR of 54.22. The estimated sensitivity and specificity of biopsy anti-PLA2R for diagnosis of IMN at different stages was 73.0 and 83.0%, respectively, with diagnostic OR of 13.75. CONCLUSIONS: This meta-analysis shows that serum anti-PLA2R level is of diagnostic value for IMN in the active stage. Future large-cohort prospective studies are required to reveal the diagnostic value of circulating anti-PLA2R antibodies versus PLA2R antigens in kidney biopsy for IMN at different stages.

Nephrin phosphorylation regulates podocyte adhesion through the PINCH-1-ILK-α-parvin complex.

Nephrin, a structural molecule, is also a signaling molecule after phosphorylation. Inhibition of nephrin phosphorylation is correlated with podocyte injury. The PINCH-1-ILK-α-parvin (PIP) complex plays a crucial role in cell adhesion and cytoskeleton formation. We hypothesized that nephrin phosphorylation influenced cytoskeleton and cell adhesion in podocytes by regulating the PIP complex. The nephrin phosphorylation, PIP complex formation, and F-actin in Wistar rats intraperitoneally injected with puromycin aminonucleoside were gradually decreased but increased with time, coinciding with the recovery from glomerular/podocyte injury and proteinuria. In cultured podocytes, PIP complex knockdown resulted in cytoskeleton reorganization and decreased cell adhesion and spreading. Nephrin and its phosphorylation were unaffected after PIP complex knockdown. Furthermore, inhibition of nephrin phosphorylation suppressed PIP complex expression, disorganized podocyte cytoskeleton, and decreased cell adhesion and spreading. These findings indicate that alterations in nephrin phosphorylation disorganize podocyte cytoskeleton and decrease cell adhesion through a PIP complex-dependent mechanism.

High glucose induces autophagy in podocytes.

Autophagy is a cellular pathway involved in protein and organelle degradation. It is relevant to many types of cellular homeostasis and human diseases. High level of glucose is known to inflict podocyte injury, but little is reported about the relationship between high concentrations of glucose and autophagy in these cells. The present study demonstrates that high glucose promotes autophagy in podocytes. Rapamycin further enhances this effect, but 3-methyadenine inhibits it. The proautophagic effect of high glucose manifested in the form of enhanced podocyte expression of LC3-2 and beclin-1; interestingly, antioxidants such as NAC were found to inhibit high glucose-induced autophagy. High glucose induced the generation of ROS by podocytes in a time-dependent manner. High glucose also enhanced podocyte expression of MnSOD and catalase. These findings indicate that high glucose-induced autophagy is mediated through podocyte ROS generation.

Effects of residual renal function on left ventricle and analysis of related factors in patients with hemodialysis.

BACKGROUND: Left ventricular hypertrophy (LVH) and systolic dysfunction would predict the mortality of patients undergoing maintenance hemodialysis. The cause of LVH is usually related to the increase of total peripheral vascular resistance and overloading volume. The presence of residual diuresis enables greater control of the volume. This study evaluated the effects of residual renal function (RRF) on the left ventricle and analyzed the related factors involved in hemodialysis patients. METHODS: A total of 59 hemodialysis patients were classified into two groups. The patients in the RRF (RRF+) group had a urine volume greater than 200 mL/24 h, and the patients in the non-RRF (RRF-) group had a urine volume less than 200 mL/24 h. B-type natriuretic peptide (BNP), blood total homocysteine (tHcy), and blood biochemical indexes were determined for the patients in both groups. Echocardiography and Doppler tests were performed to determine the cardiac indexes. RESULTS: LVH and systolic dysfunction in the RRF+ group were less severe than those in the RRF- group. The concentration of tHcy and BNP in patients with RRF was decreased in comparison with those without RRF. The concentration of tHcy and BNP was positively correlated with the residual diuresis. CONCLUSIONS: There were distinct ventricular geometric patterns and different functional performances between RRF+ and RRF- groups. The presence of residual diuresis had a beneficial effect on the left ventricular function in hemodialysis patients.