Patients with C3 glomerulopathy (C3G) often have a history of infection, which implies that infection may lead to abnormal activation of the complement alternative pathway (CAP) and induce the development of C3G. However, patients with postinfectious glomerulonephritis (PIGN) often have a low serum C3 concentration and positive glomerular C3 staining, consistent with the activation of the CAP. PIGN, especially if it involves simultaneous IgA deposition, is often difficult to differentiate from C3G. In this study, we report the consequences of Mycoplasma pneumoniae (MP) infection in a 66-year-old male Chinese patient, who developed persistent hypocomplementemia, gross hematuria, and rapidly progressive glomerulonephritis. The findings of the histologic examination of an initial renal biopsy were consistent with a diagnosis of IgA-dominant postinfectious glomerulonephritis. The sample was negative for Gd-IgA1 staining. After treatment with antibiotics, glucocorticoids, and mycophenolate mofetil, the patient’s serum creatinine decreased from a peak of 387 µmol/L to 195 µmol/L prior to discharge, and there was a partial response in his urinary protein concentration. After 2 months, his serum C3 concentration had returned to normal. However, owing to reinfection with MP the patient’s serum creatinine rapidly increased again to 475.07 µmol/L, and this was accompanied by a decrease in serum C3 concentration (> 8 months) and positivity for C3 nephritis factor. Examination of both renal biopsies showed stronger immunostaining for C3 than for IgA in the glomeruli. Thus, MP infection can cause sustained activation of the CAP, leading to C3G. For patients with MP infection, if there is an ongoing decrease in complement C3 levels and a progressive increase in serum creatinine, it is crucial to be vigilant for possible C3G and to consider the use of immunosuppressive therapy in conjunction with anti-infective treatment to prevent the ongoing activation of the CAP.

BackgroundFor IgA nephropathy (IgAN), tubular atrophy/interstitial fibrosis is the most important prognostic pathological indicator in the mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and presence of crescents (MEST-C) score. The identification of non-invasive biomarkers for tubular atrophy/interstitial fibrosis would aid clinical monitoring of IgAN progression and improve patient prognosis.MethodsThe study included 188 patients with primary IgAN in separate confirmation and validation cohorts. The associations of miR-92a-3p, miR-425-5p, and miR-185-5p with renal histopathological lesions and prognosis were explored using Spearman correlation analysis and Kaplan-Meier survival curves. Bioinformatics analysis and dual luciferase experiments were used to identify hub genes for miR-185-5p. The fibrotic phenotypes of tubular epithelial cells were evaluated in vivo and in HK-2 cells.ResultsmiRNA sequencing and cohort validation revealed that the expression levels of miR-92a-3p, miR-425-5p, and miR-185-5p in urine were significantly increased among patients with IgAN; these levels could predict the extent of tubular atrophy/interstitial fibrosis in such patients. The combination of the three biomarkers resulted in an area under the receiver operating characteristic curve of 0.742. The renal prognosis was significantly worse in the miR-185-5p high expression group than in the low expression group (P=0.003). Renal tissue in situ hybridization, bioinformatics analysis, and dual luciferase experiments confirmed that miR-185-5p affects prognosis in patients with IgAN mainly by influencing expression of the target gene tight junction protein 1 (TJP1) in renal tubular epithelial cells. In vitro experiment revealed that an miR-185-5p mimic could reduce TJP1 expression in HK-2 cells, while increasing the levels of α-smooth muscle actin, fibronectin, collagen I, and collagen III; these changes promoted the transformation of renal tubular epithelial cells to a fibrotic phenotype. An miR-185-5p inhibitor can reverse the fibrotic phenotype in renal tubular epithelial cells. In a unilateral ureteral obstruction model, the inhibition of miR-185-5p expression alleviated tubular atrophy/interstitial fibrosis.ConclusionUrinary miR-185-5p, a non-invasive biomarker of tubular atrophy/interstitial fibrosis in IgAN, may promote the transformation of renal tubular epithelial cells to a fibrotic phenotype via TJP1.

OBJECTIVE: To study the clinical characteristics relating to differential diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD).METHODS: The subjects were patients with type 2 diabetes mellitus (T2DM) complicated with chronic kidney disease (CKD). Western medical history data and Traditional Chinese Medicine (TCM) symptom pattern were collected, and logistic regression was used to analyze.RESULTS: Blood deficiency pattern [odds ratio (OR) = 2.269, P = 0.017] and Qi stagnation pattern (OR = 1.999, P = 0.041) are independently related to DN.CONCLUSIONS: TCM factors blood deficiency pattern and Qi stagnation pattern are relating to differential diagnosis of DN and NDRD.

Objective To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. Methods Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. Results Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. Conclusions Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914)

OBJECTIVES:Ischemia-reperfusion injury (IRI) is a major cause of chronic renal fibrosis. Currently, numerous therapies have shown a minimal effect on the blockade of fibrosis progression. Here, the therapeutic potential of peptide-based TGF-β1 inhibitor P144 in IRI-induced renal fibrosis and the underlying mechanism were analyzed.MATERIALS AND METHODS:The unilateral ischemia-reperfusion injury with the contralateral nephrectomy model was established, and the P144 was administered intravenously 1d/14d after the onset of IRI. The histopathology and immunofluorescence staining were used to detect renal fibrosis and macrophage infiltration. The in vivo fluorescence imaging was used to measure the bio-distribution of P144. The transwell assays were used to observe the migration of macrophages. RT-qPCR and western blot were used to analyze TGF-β1 signaling.RESULTS:P144 ameliorated the accumulation of extracellular matrix in the kidney and improved the renal function in the unilateral ischemia-reperfusion injury plus contralateral nephrectomy model. Mechanistically, P144 downregulated the TGF-β1-Smad3 signaling at both the transcriptional and translational levels and further reduced the TGF-β1-dependent infiltration of macrophages to the injured kidney. Additionally, P144 blocked the polarization of macrophages to an M2-like phenotype induced by TGF-β1 in vitro, but showed no effect on their proliferation.CONCLUSIONS:Our study showed that the TGF-β1 peptide-based inhibitor P144 decreased renal fibrosis through the blockade of the TGF-β1-Smad3 signaling pathway and the modulation of macrophage polarization, suggesting its potential therapeutic use in IRI-induced renal fibrosis.

Background: Renal replacement therapy (RRT) was often needed by some severe burn patients with acute kidney injury (AKI). The primary aim of this study was to review incidence rate and mortality of RRT in severe burn patients. Second aims were to review RRT complications and renal outcome. Methods: We searched multiple databases for studies published between 1 January 1960 and 31 December 2019. Studies about adult populations with burn injury, providing epidemiologic data on prevalence or mortality of RRT, were included. Results: A total of selected 57 studies, including 27,437 patients were enrolled in our analysis. The prevalence rates of RRT were 8.34% (95% CI 7.18–9.5%) in all burn patients and 37.05% (95% CI 29.85–44.24%) in AKI patients. The mortality of all burn patients with RRT was 65.52% (95% CI 58.41–72.64%). The prevalence rates of RRT in sample size≥100 group were 6.86% (95% CI 5.70–8.03%), which was lower than that of <100 group (17.61%, 95% CI 13.39–21.82%). With the increase of TBSA, the prevalence of RRT may have the increasing trend. The prevalence rates of RRT in Asian group was 12.75% (95% CI 9.50–16.00%), which was higher than that of European (10.45%, 95% CI 7.30–13.61%) and North America group (5.61%, 95% CI 4.27–6.95%). The prevalence rates of RRT in 2010–2019 group was 12.22% (95% CI 10.09–14.35%), which was higher than that of 2009–2000 group (5.17%, 95% CI 2.88–7.46%). The prevalence rates of RRT in 1989 and before group was the lowest, which was 1.56% (95% CI 0–3.68%). However, there was no significant correlation between the year of publication and the mortality of burn patients with RRT. Dialysis-requiring AKI in burn patients could increases the risk of chronic kidney disease progression and end-stage renal disease. About 35% of RRT patients need to maintain haemodialysis temporarily, even if they survive and leave hospital. Conclusions: The prevalence rate of RRT is about 6–8%; approximately, one-third of burn patients with AKI need RRT. The prevalence rate of RRT increased over time, but the mortality did not change. The prevalence rates of RRT in Asian group was higher than that of European and North America group.

BACKGROUND Use of anticoagulant as lock solutions is an important method to maintain the function of haemodialysis (HD) central venous catheters (CVCs), and the common anticoagulants heparin and citrate are not suitable for some patients. Argatroban can inhibit thrombin directly, has a definite anticoagulant effect, and is expected to be a new anticoagulant for CVC lock solutions. METHODS A total of 60 HD patients with non-tunnelled or tunnelled CVCs will be randomly assigned to two groups: an argatroban group and a control group. The participants will be given argatroban 0.5 mg/mL or unfractionated heparin (UFH) 1,000 U/mL locked post-dialysis instilled into the CVC lumens and followed up for 2 weeks. Data on demographic and general clinical information, laboratory examination, adverse events, adverse reactions and serious adverse events in the two groups will be collected. The differences in coagulation indexes at 30 min following catheter lock will be compared. The thrombosis rate, infection rate and percentage of catheter-days in the two groups will be observed. The primary outcomes include: efficacy assessments of combined outcome events: (I) rates of cumulative catheter survival in the 2-week HD session (the standard of catheter survival was catheter mean blood flow ≥250 mL/min); (II) rates of cumulative survival free of catheter thrombosis in the 2-week HD session. The second outcomes include: catheter dysfunction, the variation value (seconds) in activated partial thromboplastin time (aPTT) at 30 min following catheter locking and aPTT before next dialysis, catheter-associated bleeding, and catheterassociated infections. DISCUSSION At present, there is no clinical study of argatroban as a CVC lock solution. This study will explore the efficacy and safety of the argatroban as locking solution in the prevention of the dysfunction of HD CVCs to provide evidence for further research. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR1800017105. Registered 12 July, 2018 (prospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=29054).

Despite available prevention and treatment measures, such as hydration, diuresis, magnesium supplementation, and amifostine, renal toxicity is still one of the major dose-limiting side effects of cisplatin. The aim of this review is to discuss the issue of cisplatin-induced nephrotoxicity in the elderly. Compared with young patients, the incidences of cisplatin-induced nephrotoxicity and acute kidney injury (AKI) in elderly patients are significantly increased, and survival time may be decreased. Following cisplatin treatment of elderly patients, tubulointerstitial injuries will be significantly aggravated based on their original age, both for acute injuries due to cell necrosis and exfoliation and chronic injuries due to interstitial fibrosis, tubular atrophy, and dilatation. The high incidence of cisplatin-induced nephrotoxicity in elderly patients may be associated with renal hypoperfusion; increased comorbidities, such as chronic kidney disease (CKD), cardiovascular disease, and diabetes mellitus; increased use of combined drugs [especially non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitor and angiotensin receptor blockers (ACEI/ARB), and antibiotics]; decreased clearance of cisplatin; and high plasma ultrafilterable cisplatin. Considering hemodynamic stability and water balance, short duration and low volume hydration may be more suitable for treating elderly people. With the increasing popularity of low-dose daily/weekly regimens, we do not recommend routine diuretic treatment for elderly patients. We recommend using a less nephrotoxic platinum if large doses of cisplatin (100mg/m(2)) are needed.

Despite available prevention and treatment measures, such as hydration, diuresis, magnesium supplementation, and amifostine, renal toxicity is still one of the major dose-limiting side effects of cisplatin. The aim of this review is to discuss the issue of cisplatin-induced nephrotoxicity in the elderly. Compared with young patients, the incidences of cisplatin-induced nephrotoxicity and acute kidney injury (AKI) in elderly patients are significantly increased, and survival time may be decreased. Following cisplatin treatment of elderly patients, tubulointerstitial injuries will be significantly aggravated based on their original age, both for acute injuries due to cell necrosis and exfoliation and chronic injuries due to interstitial fibrosis, tubular atrophy, and dilatation. The high incidence of cisplatin-induced nephrotoxicity in elderly patients may be associated with renal hypoperfusion; increased comorbidities, such as chronic kidney disease (CKD), cardiovascular disease, and diabetes mellitus; increased use of combined drugs [especially non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitor and angiotensin receptor blockers (ACEI/ARB), and antibiotics]; decreased clearance of cisplatin; and high plasma ultrafilterable cisplatin. Considering hemodynamic stability and water balance, short duration and low volume hydration may be more suitable for treating elderly people. With the increasing popularity of low-dose daily/weekly regimens, we do not recommend routine diuretic treatment for elderly patients. We recommend using a less nephrotoxic platinum if large doses of cisplatin (100mg/m2) are needed.

Background: To improve the prognosis of burn patients with renal replacement therapy (RRT), we performed this systematic review and meta-analysis. Methods: We searched multiple databases for studies published before February 2020. Studies about adult populations with burn injury, providing epidemiologic data on prevalence or mortality of RRT, were included. Results: A total of selected 58 studies, including 38,787 patients were enrolled in our analysis. The prevalence rates of RRT were 5.14% (95%CI 4.54%-5.74%) in all burn patients and 35.8% (95%CI 29.54%-42.07%) in acute kidney injury (AKI) patients. The prevalence of RRT among burn patients in the intensive care unit (ICU) was 10.92% (95%CI 8.71%-13.14%). The mortality of all burn patients with RRT was 65.52% (95%CI 58.41%-72.64%). The mortality of patients with RRT in ICU was 62.7% (95%CI 53.7%-71.7%). The mortality rate of RRT patients was 30.33% (95%CI 22.06%-38.59%) of the total. There was no significant correlation (r=-0.224, P=0.159) between the year of publication and the mortality of burn patients with RRT. Neither cohort studies nor RCT studies of subgroup analyses show that RRT could reduce the risk of death in burn patients with AKI. Bleeding (10.92%) and secondary infection (9.61%) were the most common RRT-related adverse reactions. Compared with heparin, regional citrate anticoagulation has advantages in superior filter life spans and fewer bleeding episodes. Dialysis-requiring AKI in burn patients could increases the risk of chronic kidney disease progression and end-stage renal disease. About 35% of RRT patients need to maintain hemodialysis temporarily, even if they survive and leave hospital. Conclusions: The prevalence of RRT is not low; approximately, one-third of burn patients with AKI need RRT. The mortality of burn patients with RRT is very high and accounts for 1/3 of the total deaths. There is no evidence that RRT can improve the prognosis of burn patients with AKI. Regional citrate anticoagulation has some advantages in reducing bleeding and extending filter life spans, which may be more suitable for severe burn patients with CRRT.

The mechanisms of traumatic injury-induced acute kidney injury (AKI) are very complicated. Among these mechanisms, sepsis-related AKI is the most harmful and the most difficult to treat. The medical community gave a high priority on this disease, dedicated to raise the level of awareness and treatment through its pathogenesis, early diagnosis ideas and biomarkers, and standardization of treatment. There has been some consensus on the classification of sepsis, AKI, and treatments of antiinfection, fluid resuscitation, renal replacement therapy. A series articles and guidelines have also been published and the survival status of patients have been improved, but many basic and clinical issues are still controversial and need to be answered by further trails. This article focuses on the progress of pathogenesis, diagnosis and treatment about sepsis-related AKI, and tries to raise the understanding level of early diagnosis and standardized treatment of it. DOI: 10.11855/j.issn.0577-7402.2019.07.05

To investigate the role of toll like receptors (TLRs) 2 and 4 in rhabdomyolysis (RM)-related acute kidney injury (AKI). Wild-type (WT) mice and TLR2 knockout (TLR2-/-) or TLR4 knockout (TLR4-/-) mice were injected with either saline (sham) or glycerin (to induce RM-related AKI). Samples were collected for detection of 0 h 24 h (Cr) creatinine, urea nitrogen (BUN), creatine kinase (CK), and PAS staining of renal tissues. Serum Cr and BUN level was significantly increased in TLR2-/- and TLR4-/-AKI groups more than those in the control group and the WT mice in AKI group. TLR4-/-AKI group Cr, BUN level, and the pathological damage was lightest. The expression levels of signal transduction proteins in TLR2-/- and TLR4-/-AKI group were higher than in the control group, but was lower than that in the wild AKI group, with the TLR4-/-AKI group having the lowest levels. The expression level of inflammatory factor mRNA in TLR2-/- and TLR4-/-AKI groups was higher than that in control group, but was lower than that in wild AKI group, with TLR4-/-AKI group displaying lowest levels. Knockout of TLRs 2 and 4 decreased kidney inflammation and improved RM-related AKI.

Background: Renal toxicity limits the clinical use of platinum-based therapy in the elderly. In order to clarify the impact of aging on the risk of platinum-related nephrotoxicity, the following meta-analysis was performed. Methods: We searched multiple databases for studies published before January 2017. The inclusion criteria were case-control, cohort studies published in any language. Results: The risk of platinum-induced nephrotoxicity in the older group was 1.43 times (risk rate) higher than in the non-older group. Platinum-induced nephrotoxicity in older patients was mainly I/II. There was no significant difference in the incidence of grade III/IV renal toxicity between groups. The risk for elderly patients in Asia was significantly higher than in Europe and North America. Carboplatin had a lower risk of renal toxicity and only half of the amount of moderate and severe nephrotoxicity than cisplatin. In the age stratification analysis, the RR values were 1.43, 1.51 and 1.35 respectively for the elderly group (55, 60, 70 years old), and all had significant differences. The risk of platinum-related nephrotoxicity in elderly patients was significantly increased in the high comorbidity rate group. Moreover, the RR values of the normal renal function group were significantly higher than that of the 'no mention or renal insufficiency' subgroup. Conclusions: Aging increased the risk of platinum-induced nephrotoxicity by 43%, partly due to more co-morbidities in elderly patients, and mild renal toxicity was dominant. The risk of renal toxicity of the elderly patients in Asian countries was much higher than that of in European countries and North America.

Recent studies have indicated that urinary sediment miRNAs not only are able to serve as non-invasive diagnostic biomarkers for IgA nephropathy (IgAN) but may also be closely related to several clinical and pathological indicators. However, the lack of a suitable internal reference miRNA has hampered research into urinary sediment miRNAs. To date, U6 has been used as a reference gene in urinary sediment miRNA studies mostly based on the results from studies using tissue samples and cell lines. In a total of 330 IgAN patients, 164 disease control patients and 130 normal control patients, there was no significant difference in U6 levels. We also compared the U6 levels in different types of primary glomerular disease groups (IgA nephropathy, membranous nephropathy, minimal change nephrosis and focal segmental glomerular sclerosis). The results confirmed that there was no significant difference in the expression of U6 in different primary glomerular disease groups. Moreover, treatment had no significant effect on the expression levels of U6 in IgA nephropathy. Therefore, U6 is an excellent housekeeping gene for urinary sediment miRNA studies of IgA nephropathy.

血管钙化是慢性肾脏病患者常见的并发症之一,是导致其心血管事件发生和猝死的重要原因.在慢性肾脏病病因中,高血压肾病已成为第三位,而高血压可以导致动脉血管硬化,引起心血管事件发生,有研究表明动脉血管硬化是机体异位钙化的最常见部位[1,2].因此,研究高血压肾病患者中血管钙化具有重要意义.血管钙化是由多因素参与的主动调节过程,调节机制比较复杂,主要调节机制为钙化激活和钙化抑制,分别由相应的因子参与.胎球蛋白A就是钙化抑制因子之一,对异位钙化具有抑制作用.高血压肾病患者的血管钙化是否与血清胎球蛋白A水平有关,目前尚缺乏相应的临床证据.本实验通过对高血压肾病患者血清胎球蛋白A水平及相关项目的检测,探讨它与血管钙化的关系.

Objective To investigate the incidence of restless legs syndrome (RLS) in hemodialysis patients and to analyze the related risk factors. Methods There were 220 cases of hemodialysis as hemodialysis group and 40 cases of chronic nephrosis as control group. The severity of RLS was measured by International Restless Legs Syndrome Study Group Rating Scale (IRLS). Beck Depression Inventory (BDI) was used to evaluate the status of depression, Epworth Sleepiness Scale (ESS) was used to evaluate excessive daytime sleepiness (EDS), and Insomnia Severity Index (ISI) was used to evaluate the status of insomnia. Univariate and multivariate forward Logistic regression analysis was used to analyze the related risk factors for RLS in hemodialysis patients. Results In hemodialysis group duration ( Z =-9.837, P = 0.000), serum ferritin ( t = 2.847, P = 0.005), incidence rate of RLS ( χ 2 = 10.918, P = 0.001), the proportion of using hypnotic drugs ( χ 2 = 7.669, P = 0.006), IRLS ( t = 2.322, P = 0.020) and ISI ( Z = 4.117, P = 0.001) were significantly higher than control group. Univariate and multivariate forward Logistic regression analysis showed diabetes ( OR = 3.387, 95% CI: 1.538-7.461; P = 0.002), BDI > 9 score ( OR = 2.643, 95% CI: 1.457-4.795; P = 0.001) and ISI > 7 score ( OR = 3.542, 95%CI: 1.939-6.468; P = 0.000) were independent risk factors for RLS in hemodialysis patients. Conclusions Hemodialysis patients have a high incidence of RLS and insomnia. RLS is closely related with insomnia. Depression plays an important role therein. DOI: 10.3969/j.issn.1672-6731.2018.01.009

Objective To compare the effect of one-step and two-step approach in establishing 5/6 nephrectomy model of renal failure.Methods One-step and two-step approach were used to establish the model of 5/6 nephrectomy, and the mortality rate and the levels of creatinine and urea nitrogen were recorded in the two groups at the end of week 4, week 8 and week 12 after the operation.Results The mortality rate was 17.65% in the one-step group at the end of the 4th week, compared with 29.41% in the two-step group at the same time after the operation. The renal failure models were successfully established in the two groups, and there was no significant difference in the levels of creatinine and urea nitrogen between the two groups at the end of the 8th week.Conclusion One-step and two-step approach can successfully establish 5/6 nephrectomy model of renal failure, and the one-step approach may produce lower mortality.