Indices Of Renal Function Research Articles

Evaluation of the Safety and Efficacy of Bivalirudin Anticoagulation in Patients with Heparin-Induced Thrombocytopenia According to Renal Function and Body Mass Index

Background: Heparin-induced thrombocytopenia (HIT) is a life-threatening complication in which antibodies to platelet factor 4 complexed to heparin lead to platelet overactivation resulting in a hypercoagulable state. Treatment begins with stopping all sources of heparin and initiating rapid-acting non-heparin anticoagulation. Bivalirudin is a direct thrombin inhibitor (DTI) used off-label for the prevention and treatment of HIT. It is primarily enzymatically cleared; however, dose reductions are required in renal impairment. Despite its widespread off-label use in HIT, there is a paucity of data for dosing bivalirudin in patients with renal dysfunction and obesity. Here we report the results of a medication use evaluation (MUE) investigating the safety and efficacy of dosing bivalirudin based on renal function and body mass index (BMI). Methods: We conducted a retrospective MUE including patients 18-89 years of age receiving bivalirudin with ≥3 DTI levels between June 2019 and December 2021. Patients receiving bivalirudin for percutaneous coronary intervention were excluded. Creatinine clearance was measured with the Cockcroft-Gault equation. The primary outcome was time to therapeutic anticoagulation (TTA) defined as the time in hours (hr) between bivalirudin initiation and the first of two consecutive therapeutic DTI levels. Secondary outcomes included average initial therapeutic dose, time in therapeutic range (TTR) calculated as the percentage of therapeutic DTI levels, incidence of clinically significant bleeding, and average number of dose changes before reaching therapeutic goal. Results: Thirty-eight patients (21 females, 55%) with a mean (SD) age of 60.3 (13.5) years were included, 12 of which had a history of or confirmed HIT by serotonin release assay. The remaining patients had suspected HIT or coagulation abnormalities precluding the use of heparin. One patient was classified as an outlier and excluded due to requiring an abnormal number of dose adjustments. Among this population, 17 (45%) had normal renal function (CrCl >60 mL/min), 11 (29%) had mild renal impairment (CrCl 30-60 mL/min), 1 (3%) had moderate renal impairment (CrCl <30 mL/min), 4 (10%) were on intermittent hemodialysis (IHD), and 5 (13%) were on continuous renal replacement therapy (CRRT). Stratified by BMI, 2 (5%) were underweight (BMI <18.5 kg/m2), 3 (8%) were healthy (BMI 18.5-24.9 kg/m2), 17 (45%) were overweight (BMI 25.0-29.9 kg/m2), and 16 (42%) were obese (BMI ≥30 kg/m2). There was no statistically significant difference in TTA based on renal function or BMI. However, clinically, patients on IHD or CRRT trended toward having a shorter TTA compared to patients with normal, mildly impaired, and moderately impaired renal function (28.2 ± 9.0 or 28.9 ± 16.3 hr vs. 40.0 ± 27.6, 36.7 ± 31.6, and 42.9 hr, respectively). Obese and overweight patients trended toward a shorter TTA compared to healthy and underweight patients (31.4 ± 28.9 and 32.8 ± 17.4 hr vs. 62.3 ± 35.6 and 54.8 ± 5.0 hr, respectively). The difference in TTA may be affected by lab turnaround time (TAT). To adjust for lab TAT, the average number of dose adjustments was assessed. There was no difference in the number of dose adjustments based on renal function. In contrast, overweight and obese patients trended toward requiring fewer dose changes compared to underweight and healthy patients. This trend aligned with overweight and obese patients achieving a statistically significantly higher TTR compared to underweight and healthy patients (55.5 vs. 34.4%, p = 0.02). Based on bivalirudin's standard renal dose adjustments, patients with a CrCl >60 mL/min had a statistically significantly larger average initial therapeutic dose compared to those with a CrCl ≤60 mL/min (0.114 vs. 0.069 mg/kg/hr, p < 0.001). However, this difference was not observed based on BMI. Incidences of clinically significant bleeding were not observed to have affected TTA, TTR, average initial therapeutic dose, or number of dose changes before reaching therapeutic anticoagulation. Conclusion: While our data are consistent with bivalirudin requiring renal dose adjustments, it was observed that underweight and healthy BMI patients required more dose adjustments and took longer to achieve therapeutic anticoagulation. More studies are needed to determine if these patients would benefit from a higher initial dosing strategy. This study was limited due to the sample size. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prevalence of cardiovascular diseases in kidney transplant recipients and its relationship with asymmetric dimethylarginine, fibroblast growth factor-23 and multiple inflammatory markers.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase, a marker of endothelial damage and progression of atherosclerosis. Research confirms the association of ADMA with an increased risk of cardiac complications and an increased risk of death, graft loss among kidney transplant recipients (KTRs). The aim of our study was to establish the significance of ADMA and FGF-23 as biomarkers of cardiovascular risk as well as predictors of graft failure and progression of chronic transplant kidney disease in comparison to CKD subjects. In addition, an analysis of the relationship between ADMA, FGF23 and cardiovascular diseases in CKD subjects and KTRs was performed. The study group included 132 KTRs. The control group consisted of age- and sex-adjusted 40 individuals with clinically stable CKD. ADMA, FGF-23, hs-CRP and IL-6 were measured by the enzyme-linked immunoassay method (ELISA). Parameters of body mass composition such as fat mass, FTI, lean tissue mass, LTI, body water and overhydration were assessed by multi-frequency bioimpedance analysis (BIA). Cardiovascular diseases (CVDs) were present in 31.8% of KTRs. Independent variables related to nutritional status (SGA, s-albumin), according to multivariate regression, may have an impact on the prevalence of CVD in the kidney transplant recipients' group. Our study findings suggested a correlation between ADMA and serum albumin (r=-0.41, p<0.05), oxLDL (r=-0.42, p<0.05) and overhydration (OH%, r=0.28, p<0.05). Moreover, administration of statins and/or angiotensin-converting-enzyme inhibitors was significantly related to a reduction of ADMA in KTRs. We have also identified a significant positive correlation between FGF-23 levels and inflammatory markers (hs-CRP, IL-6) and negative with overall index of renal function (eGFR-CKD EPI, eGFR-MDRD). Nutritional status, inflammation and endothelial dysfunction markers (ADMA, FGF-23) are considerably altered even in stable kidney transplant recipients.

Association of metabolic dysfunction-associated fatty liver disease, type 2 diabetes mellitus, and metabolic goal achievement with risk of chronic kidney disease.

Although type 2 diabetes mellitus (T2DM) plays a significant role in the association between metabolic dysfunction-associated fatty liver disease (MAFLD) and chronic kidney disease (CKD), how T2DM development and glycemic deterioration affect CKD and its renal function indicators, estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), remains unknown. We aimed to assess the association between MAFLD, along with T2DM, and risk of CKD, and then evaluate the effect of metabolic goal achievement in MAFLD on the risk of CKD. In this cross-sectional study, 5,594 participants were included. Multivariate logistic regression and linear regression were used to examine the association between MAFLD with its T2DM status and metabolic goal achievement and risk of CKD, as well as eGFR and UACR. The MAFLD group had a higher prevalence of CKD (16.2 vs. 7.6%, P < 0.001) than the non-MAFLD group. MAFLD was independently associated with an increased risk of CKD (odds ratio [OR]: 1.35, 95% CI: 1.09-1.67) and increased eGFR and UACR. Among the three MAFLD subtypes, only the T2DM subtype exhibited significant associations with increased risk of CKD (OR: 2.85, 95% CI: 2.24-3.63), as well as increased eGFR and UACR. Glycemic deterioration in MAFLD was dose-dependently associated with an increased risk of CKD (P-trend < 0.001). Achieved metabolic goals in MAFLD decreased the risk of CKD, eGFR, and UACR; MAFLD with 2 or 3 achieved metabolic goals was not significantly associated with the risk of CKD (OR: 0.81, 95% CI: 0.59-1.12) and albuminuria. MAFLD was independently associated with an increased risk of CKD, as well as increased eGFR and UACR. This association is strongly driven by T2DM status. Glycemic deterioration in MAFLD was dose-dependently associated with an increased risk of CKD. Achieved metabolic goals in MAFLD decreased the risk of CKD by reducing the risk of albuminuria.

Effects of different low-dose of insulin glargine on antioxidation of organs in burned rats with delayed resuscitation

To study the antioxidant protective effects of different low-dose of insulin glargine on organs of burned rats with delayed resuscitation. Forty male Sprague-Dawley (SD) rats were randomly divided into sham group, delayed resuscitation control group, and insulin glargine 0.5, 1.0, and 2.0 U groups, with 8 rats in each group. The rats were immersed in hot water (95.0±0.5) centigrade for 15 s to establish the third-degree scald model with 30% total body surface area. The rats in the sham group were immersed in a 37 centigrade water bath for 15 s. Insulin glargine (0.5, 1.0, 2.0 U×kg-1×d-1) was injected subcutaneously in corresponding insulin glargine group 2 hours after injury, and the same amount of normal saline was injected intraperitoneally in the delayed resuscitation control group. Intraperitoneal injection of normal saline 40 mL/kg simulated delayed resuscitation 6 hours after injury in all groups. Abdominal aortic blood samples, heart and kidney tissue were collected immediately after simulating burn in the sham group, and 24 hours after burn in other four groups. The blood glucose, myocardial enzymes [lactate dehydrogenase (LDH), creatine kinase (CK), α-hydroxybutyrate dehydrogenase (α-HBDH), and aspartate aminotransferase (AST)] and renal function indexes [blood urea nitrogen (BUN) and serum creatinine (SCr)] were measured by spectrophotometry, and the isoenzyme MB of creatine kinase (CK-MB) level was determined by immunosuppression method to evaluate the effects of different low-dose insulin glargine intervention on blood glucose, cardiac and renal functions in scalded rats with delayed resuscitation. The oxidative and antioxidant indices [xanthine oxidase (XOD), myeloperoxidase (MPO), copper-zinc superoxide dismutase (CuZn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC)] from the heart and kidney tissues of rats were detected by spectrophotometry to analyze the antioxidant effects of different low-dose insulin glargine interventions. Compared with the sham group, the blood glucose of the rats in the delayed resuscitation control group was significantly increased, the heart and kidney functions were significantly reduced, the oxidation capacity was enhanced, and the antioxidant indicators were significantly reduced. After the intervention of insulin glargine, with the increase of insulin glargine dose, the blood glucose, myocardial enzyme and renal function indicators of rats showed a gradual downward trend, the oxidation indicators continued to decrease, and the antioxidant indicators showed a gradual upward trend. When the dose was 2.0 U×kg-1×d-1, the blood glucose, LDH, CK, CK-MB, α-HBDH, AST, BUN, SCr, XOD and MPO were significantly lower than those in the delayed resuscitation control group [blood glucose (mmol/L): 5.91±0.25 vs. 11.76±0.36, LDH (U/L): 3 332.12±51.61 vs. 5 008.94±490.12, CK (kU/L): 0.49±0.03 vs. 0.85±0.04, CK-MB (U/L): 125.40±12.19 vs. 267.52±11.63, α-HBDH (U/L): 122.99±5.37 vs. 240.85±13.99, AST (U/L): 11.95±1.81 vs. 17.87±1.57, BUN (mmol/L): 4.72±0.15 vs. 7.16±0.34, SCr (μmol/L): 87.11±6.51 vs. 137.50±11.36, XOD (U/g): 166.29±3.27 vs. 204.90±4.82 in heart tissue, 63.51±1.46 vs. 79.69±1.75 in kidney tissue, MPO (U/g): 1.05±0.02 vs. 1.55±0.06 in heart tissue, 1.04±0.04 vs. 1.87±0.01 in kidney tissue, all P < 0.05], and CuZn-SOD, CAT, GSH-Px and T-AOC were significantly higher than those in the delayed resuscitation control group [CuZn-SOD (kU/g): 82.95±2.69 vs. 56.52±2.26 in heart tissue, 94.50±2.73 vs. 62.02±1.66 in kidney tissue, CAT (U/g): 36.07±2.01 vs. 15.15±2.22 in heart tissue, 184.49±4.53 vs. 156.02±3.96 in kidney tissue, GSH-Px (kU/g): 231.93±8.03 vs. 179.48±3.15 in heart tissue, 239.63±7.30 vs. 172.20±2.09 in kidney tissue, T-AOC (kU/g): 4.85±0.23 vs. 2.71±0.11 in heart tissue, 5.51±0.08 vs. 3.50±0.07 in kidney tissue, all P < 0.05]. Different low-dose of insulin glargine (≤ 2.0 U×kg-1×d-1) could exert antioxidant protection on the heart and kidney of rats with delayed resuscitation after burns, with a dose-dependent manner.

Intervention effects of erythropoietin derived peptide (HBSP) on renal injury induced by acute skeletal muscle strain in rats

Objective: To investigate the protective effects of erythropoietin derived peptide, also known as spiral B surface peptide (HBSP), on kidney and aggregated proteins (Agrin) levels in acute skeletal muscle strain rats. Methods: Forty SPF grade SD male rats were randomly divided into control group, injury group, HBSP group and EPO group, with 10 rats in each group. Acute skeletal muscle strain animal models were established except the control group. After successful modeling, the rats in HBSP group and EPO group were intraperitoneally injected with 60 μg/kg HBSP and 5 000 U/kg recombinant human erythropoietin (rhEPO), and the rats in the control group and the injured group were intraperitoneally injected with 0.9% normal saline. Renal function was monitored with relevant kits; Hematoxylin-eosin staining was used to observe the pathological morphology of kidney tissue and skeletal muscle strain tissue. The apoptosis rate of renal tissue cells was detected by in situ terminal transferase labeling (TUNEL). Western blot and quantitative polymerase chain reaction (Q-PCR) were used to determine the expressions of Agrin and muscular-specific kinase (MuSK) in the injured skeletal muscle of rats in each group. Results: Compared with the control group, the renal function indexes serum creatinine (Cr), urea nitrogen (BUN) and 24 h urinary protein (UP24) levels of rats in injured group were increased (P＜ 0.05), but the levels of BUN, Cr and UP24 of rats in HBSP group were decreased (P＜0.05). Compared with HBSP group, there were no significant differences in the above indexes in EPO group (P＞0.05). In the control group, the muscle fiber structure was intact, the shape and structure of the fiber bundles were normal, and there was no infiltration of red blood cells and inflammatory cells in the interstitium, and no fibrohyperplasia. In the injured group, the muscle tissue showed sparse and irregular arrangement, and the interstitial widened with a large number of inflammatory cells and red blood cell infiltration. Erythrocytes and inflammatory cells were reduced in HBSP group and EPO group, and the transverse and longitudinal lines of muscle were clear. The glomerular structure of the rats in the fibrohyperplasia control group was intact and no lesions were observed. In the injured group, glomerular hypertrophy and significant matrix hyperplasia were observed, as well as the expansion of renal cysts with vacuolar and significant inflammatory infiltration were observed, and the inflammatory infiltration was reduced in the HBSP and EPO groups. Glomerular hypertrophy and hyperplasia were alleviated. The apoptosis rates of kidney cells in control group, injured group, HBSP group and EPO group were (4.05±0.51) %, (26.30±2.05) %, (14.28±1.62) % and (16.03±1.77) %, respectively, and there were significant differences among these groups (P＜0.05). Compared with control group, the levels of Agrin and MuSK in skeletal muscle pulled tissue were significantly decreased (P＜0.05), and those of HBSP group and EPO group were significantly increased compared with injured group (P＜0.05), but there was no significant difference between HBSP group and EPO group (P＞0.05). Conclusion: Erythropoietin derived peptide (HBSP) has obvious intervention effects on renal function injury in rats with acute skeletal muscle strain, and its mechanisms may be related to reducing the apoptosis rate of renal tissue cells and activating Agrin and MuSK expression.

Effect of Copper on the Function of Isolated Porcine Kidneys Stored Using Simple Hypothermia.

Renal ischemia in the peri-transplant period causes a number of changes that adversely affect the initiation of normal vital functions in grafts after transplantation. To minimise the extent of ischemic damage, organs are stored in preservation fluid. The components of the fluid are supposed to ensure stabilisation of the cell cytoskeleton, protect against oxygen free radicals, reduce cell swelling, and ensure endothelial cell integrity. The aim of this study was to analyse the protective effect of Cu2+, as a component of Biolasol preservative fluid, in the prevention of nephron damage occurring during the graft storage period. Analyses of the effectiveness of copper in the presence of prolactin added to Biolasol fluid were also carried out. Forty isolated pig slaughter kidneys were used in the study, avoiding the use of laboratory animals. The kidneys were stored using simple hypothermia. After 2 h and 48 h of graft storage, selected biochemical indicators of renal function were determined in the collected perfusates. The addition of Cu2+ at a dose of 1 µg/L to the composition of Biolasol fluid was found to affect the generation of ischemic damage in the isolated pig kidney. The intensity of the occurrence of these processes is exacerbated by the presence of prolactin at a dose of 0.1 µg/L.

Optimal stage of initiating continuous renal replacement therapy in the treatment of neonatal acute kidney injury.

To explore the optimal stage of initiating continuous renal replacement therapy (CRRT) in the treatment of neonatal acute kidney injury (AKI), a total of 25 AKI neonates treated with CRRT were hospitalized at the Department of Neonatology of Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University (Shanghai, China) from November 2016 to June 2021. According to the renal function, the AKI neonates prior to CRRT were divided into two groups as follows: AKI stage 0-1 and AKI stage 2-3. The changes noted in specific indicators including renal function, electrolyte concentration, and acid-base balance index were analyzed at 0, 12, 24 and 48 h, and at the end of the CRRT treatment. Among the 25 neonates with AKI, serum potassium, urea nitrogen and creatinine levels were significantly decreased following 12 h of CRRT treatment and reached the normal range following 24 h of CRRT treatment with a significant increase in the volume of urine. The serum creatinine levels of the neonates in the AKI stage 0-1 group were significantly decreased following 24 h of CRRT treatment and urine output was significantly increased. At 24 h and following CRRT treatment, the levels of serum creatinine of AKI stage 2-3 neonates were higher than those of AKI stage 0-1 neonates (F=3.013, 5.005; P<0.05), and at all time-points, the urine output of AKI stage 0-1 was higher than that of AKI stage 2-3 (F=13.785, 4.008, 0.965; P<0.05). A total of four cases of thrombocytopenia, two cases of obstruction, and two cases of hypotension were noted in the course of CRRT treatment (the occurrence rate was 8/25). Therefore, it was concluded that CRRT could be an effective measure for the treatment of AKI neonates. Thus, ideally CRRT treatment of AKI neonates should be initiated in cases characterized as AKI stages 0-1.

Differential Bias for Creatinine- and Cystatin C- Derived Estimated Glomerular Filtration Rate in Critical COVID-19.

COVID-19 is a systemic disease, frequently affecting kidney function. Dexamethasone is standard treatment in severe COVID-19 cases, and is considered to increase plasma levels of cystatin C. However, this has not been studied in COVID-19. Glomerular filtration rate (GFR) is a clinically important indicator of renal function, but often estimated using equations (eGFR) based on filtered metabolites. This study focuses on sources of bias for eGFRs (mL/min) using a creatinine-based equation (eGFRLMR) and a cystatin C-based equation (eGFRCAPA) in intensive-care-treated patients with COVID-19. This study was performed on 351 patients aged 18 years old or above with severe COVID-19 infections, admitted to the intensive care unit (ICU) in Uppsala University Hospital, a tertiary care hospital in Uppsala, Sweden, between 14 March 2020 and 10 March 2021. Dexamethasone treatment (6 mg for up to 10 days) was introduced 22 June 2020 (n = 232). Values are presented as medians (IQR). eGFRCAPA in dexamethasone-treated patients was 69 (37), and 74 (46) in patients not given dexamethasone (p = 0.01). eGFRLMR was not affected by dexamethasone. eGFRLMR in females was 94 (20), and 75 (38) in males (p = 0.00001). Age and maximal CRP correlated negatively to eGFRCAPA and eGFRLMR, whereas both eGFR equations correlated positively to BMI. In ICU patients with COVID-19, dexamethasone treatment was associated with reduced eGFRCAPA. This finding may be explained by corticosteroid-induced increases in plasma cystatin C. This observation is important from a clinical perspective since adequate interpretation of laboratory results is crucial.

Associations between serum polychlorinated biphenyls, halogen flame retardants, and renal function indexes in residents of an e-waste recycling area

E-waste handling activities release large quantities of polychlorinated biphenyls (PCBs) and halogen flame retardants (HFRs) into the surrounding area, creating a high exposure risk for local residents. However, the possibility of PCBs and HFRs exposure contributing to renal injury has not been extensively studied. To fill this knowledge gap, we conducted an epidemiological analysis of adolescents and adults recruited from an e-waste recycling area and a control area. Some PCBs and HFRs compounds were statistically significantly associated with the levels of β2-microglobulin (β2-MG), blood urea nitrogen (BUN), serum creatinine (SCr), and uric acid, with thyroid hormone-related genes found to partly mediate these associations. The interactions of PCBs and HFRs with metals also influenced renal function indexes. Exposure to high concentrations of PCBs and HFRs resulted in higher levels of β2-MG and lower levels of BUN and SCr in the exposed group. As indicated by the elevated β2-MG levels, high exposure to PCBs and HFRs may increase the risk of early renal injury for adolescents. These findings help to clarify the impacts of PCBs and HFRs on renal function and highlight the need to protect the health of residents in regions impacted by e-waste handling activities.

Cannabidiol-enriched cannabis extraction product in Parkinson's disease: A randomized, double-blind, and placebo-controlled trial in Buriram Hospital.

The objective of this study was to assess cannabidiol-enriched cannabis extraction product (CBDEP) efficacy in patients with Parkinson's disease (PD). Forty patients with PD were randomly assigned to the sublingual CBDEP (n = 20) or placebo (n = 20) group. All patients were prescribed a low initial dose with gradual titration within 2 weeks based on individual response - including side effects - followed by 6 weeks of stable dosing. The primary outcome was the Unified Parkinson's Disease Rating Scale (UPDRS) score. The secondary outcomes were as follows: Quality of life (QOL) evaluated by the EQ-5D-5L, timed up and go (TUG) test, 5 times sit to stand (FTSTS) test, gait velocity, hospital anxiety and depression scale (HADS), renal and liver function indices, and adverse events. All outcomes were measured at baseline and at 8 weeks. The generalized estimating equation adjusted for baseline scores was used to compare the values at baseline and at 8 weeks, and between the groups. Four patients were lost to follow-up (CBDEP group, n = 1; placebo group, n = 3) and 36 were included in the analysis (CBDEP group, n = 19; placebo group, n = 17). The CBDEP group received mean cannabidiol and tetrahydrocannabinol dosages of 15.59 ± 5.04 mg/day and 0.61 ± 0.19 mg/day, respectively. No significant differences were found between the groups in terms of the UPDRS, TUG test, FTSTS test, gait velocity, HADS-anxiety, and HADS-depression. The placebo group had significantly improved EQ-5D-5L scores for QOL (P = 0.004). The CBDEP group showed significantly improved blood urea nitrogen (BUN), serum albumin, serum globulin levels, and albumin/globulin ratio (P = 0.037, P < 0.001, P = 0.011, and P = 0.002, respectively) compared with the placebo group. Neither group had serious side effects. No evidence was found that CBDEP can reduce disease severity or improve functional performance, anxiety, or depression in PD. However, CBDEP is safe and can improve the levels of BUN, serum albumin, serum globulin, and albumin/globulin ratio in patients with PD. Thai Clinical Trials Registry (registration number: TCTR 20210303005).

Long-term low-dose microcystin-LR exposure induces renal injury in mice by activating PI3K/AKT signaling pathway

To investigate the toxic effect of long-term low-dose exposure to microcystin-LR (MC-LR) on kidney and its underlying molecular mechanism. Forty male C57BL/6 mice were randomized into 4 groups for exposure to 0, 1, 60, and 120 μg/L MC-LR (mixed in drinking water) for 12 months, and the body and kidney weight changes and renal pathologies of the mice were observed. The renal function indexes, the mRNA expression levels of IL-6, TNF-α and IL-10, and relative expression levels of PI3K/AKT pathway proteins in the kidney of the mice were detected. These parameters were also detected in HEK293 cells treated with MC- LR, LY294002, or both. The overall trend of body weight changes was consistent among the 4 groups of mice, and their kidney mass and kidney index underwent no significant changes. In mice exposed to 60 and 120 μg/L MC-LR, obvious renal structural damage and significant elevation of the BUN and SCr levels were observed (P < 0.05) with up-regulated levels of IL-6 and TNF-α mRNA and increased protein expressions of p-PI3K/PI3K and p-AKT/AKT in the renal tissues (P < 0.05). IL-10 mRNA expression was significantly decreased in all the exposure groups (P < 0.05). The levels of BUN and Cr increased significantly in MC-LR-treated HEK293 cells and decreased in cells treated with both MC-LR and LY294002 (P < 0.05). The mRNA expression levels of IL-6 and TNF-α increased and the level of IL-10 mRNA decreased obviously in MC-LR-treated cells, and the opposite changes were observed in the cells with the combined treatment (P < 0.05). The proteins levels of p-PI3K/PI3K and p-AKT/AKT were significantly up-regulated in MC-LR group and down-regulated in the combined treatment group (P < 0.05). MC- LR can activate inflammatory response and induce renal structural and functional damages in mice by activating the PI3K/AKT signaling pathway.

Reduction in risk of contrast-induced nephropathy in patients with chronic kidney disease and diabetes mellitus by enhanced external counterpulsation.

To evaluate the efficacy of enhanced external counterpulsation (EECP) in the prevention of contrast-induced nephropathy (CIN) in patients with combined chronic kidney disease (CKD) and diabetes mellitus (DM) by comparing the changes in renal function-related indicators in patients before and after coronary angiography (CAG) or percutaneous coronary intervention (PCI). There were 230 subjects consecutively included in the study. Of these, 30 cases with DM underwent rehydration therapy, and 200 cases underwent EECP therapy in addition to rehydration therapy, comprising 53 patients with DM and 147 patients without. All the patients were tested to measure the renal function indicators before and after CAG/PCI. The postoperative results of blood urea nitrogen (BUN), serum creatinine (Scr), estimated glomerular filtration rate (eGFR), B2 microglobulin, and high-sensitivity C-reactive protein in the three groups showed a statistically significant difference (P < 0.05). After EECP therapy, patients with DM showed a significant decrease in BUN (9.1 ± 4.2 vs. 7.2 ± 3.0, t = 3.899, P < 0.001) and a significant increase in eGFR (41.5 ± 12.7 vs. 44.0 ± 15.6, t = -2.031, P = 0.047), while the patients without DM showed a more significant difference (P < 0.001). Patients with DM showed a lower percentage of elevated Scr (66.7% vs. 43.4%, P = 0.042), a higher percentage of elevated eGFR (30.0% vs. 52.8%, P = 0.044), and a lower incidence of CIN (16.7% vs. 3.8%, P = 0.042) after EECP therapy. Treatment with EECP can reduce Scr in patients with combined CKD and DM post CAG/PCI, increase eGFR, and decrease the incidence of CIN.

Comparison of Febuxostat and Allopurinol in the Treatment of Patients with Chronic Kidney Disease Stage 3∼5 with Hyperuricemia

Objective To compare the efficacy of febuxostat and allopurinol in the treatment of chronic kidney disease (CKD) at stages 3∼5 with hyperuricemia. Methods A total of 100 patients with stage 3 to 5 CKD with hyperuricemia in our hospital from July 2018 to December 2019 were selected and divided into the control group (n = 50) and the experimental group (n = 50) according to the random number expression method, the control group on the basis of conventional treatment with allopurinol treatment, the experimental group based on conventional treatment using the febuxostat be treatment. The clinical efficacy, incidence of adverse reactions, and renal function indexes, blood urea nitrogen (BUN), serum creatinine (Scr), serum sodium (Na), serum potassium (K), and serum uric acid (UA) before and after treatment were compared between the two groups. Results The total effective rate of the experimental group and the control group was 82.00% and 78.00%, respectively, with little difference (P > 0.05); compared with before treatment, BUN, Scr, and UA of the two groups were decreased (P < 0.05); and the degree of decline in the experimental group was significantly greater than that in the control group (P < 0.05); the incidence of adverse reactions in the control group was 22.00%, which was significantly higher than that in the experimental group (10.00%) (P < 0.05). Conclusion Compared with allopurinol, febuxostat can improve renal function, reduce UA levels, and reduce the occurrence of complications, with high safety, which is worthy of further clinical promotion.

Prevalence and risk factors of diabetic retinopathy among Chinese adults with type 2 diabetes in a suburb of Shanghai, China.

BackgroundTo investigate the prevalence and risk factors of diabetic retinopathy (DR) in a Chinese population with type 2 diabetes mellitus (T2DM) in a suburb (Qingpu) of Shanghai, China.MethodsA population-based cross-sectional study. A total of 7462 residents with T2DM in Qingpu were enrolled according to the resident health archives from January 2020 to December 2020. Blood and urine samples of the subjects were collected. Disc- and macula-centred retinal images were taken to assess DR. SPSS was used to analyse and investigate the prevalence and risk factors of DR.ResultsThe fundus images of 6380 (85.5%) subjects were of sufficiently good quality for grading. The average (range) age of 6380 subjects was 63.46±7.77 (28–92) years. Six hundred forty-four subjects were diagnosed with DR. The prevalence of DR was 10.1% (95% CI 9.4%-10.8%), with mild, moderate, and severe non-proliferative retinopathy and proliferative retinopathy being 2.1%, 6.3%, 1.3% and 0.4%, respectively. The prevalence of bilateral DR was 6.5%. Higher T2DM duration (OR, 1.057), fasting plasma glucose (OR, 1.063), glycated hemoglobinA1c (OR, 1.269), urea nitrogen (OR, 1.059), and urinary albumin (OR, 1.001) were associated with the higher DR prevalence.ConclusionThe prevalence of DR among Chinese adults with T2DM in Qingpu was 10.1%, in which non-proliferative DR was more common. Higher fasting plasma glucose and glycated hemoglobinA1c are well-known risk factors of DR, consistent with the findings in our study. Our study didn’t find the risk between lipid indicators and DR. However, several renal function indicators, like higher urea nitrogen and urinary albumin, were risk factors for DR in this study. Appropriate diagnosis and intervention should be taken in time to prevent and control DR development.

Therapeutic effect and mechanism of combination therapy with ursolic acid and insulin on diabetic nephropathy in a type I diabetic rat model.

This work aims to investigate the therapeutic effect of ursolic acid (UA) plus insulin (In) on diabetic nephropathy (DN) in streptozotocin (STZ)-induced T1DM rats. The experimental groups and operational details are as follows: A total of thirty-two SD rats were divided into four groups: the DN model group (DN, n = 8), DN + In treatment group (DN + In, n = 8), DN + In + UA administration group (DN + In + UA, n = 8), and negative control group (control, n = 8). After 8 weeks, changes in renal function indices and pathological damage were assessed. Additionally, oxidative stress-, apoptosis-, and fibrosis-related proteins in kidney tissue were measured. Compared with the control group, the vehicle group showed higher levels of creatine, blood urea nitrogen, urinary protein, apoptosis, and lipid peroxidation; lower superoxide dismutase levels; more severe levels of pathological kidney damage and renal fibrosis; and a deepened degree of EMT and EndMT. Better outcomes were achieved with the combined treatment than with insulin-only treatment. The improvement of TGF-β1, phosphorylated p38 MAPK, FGFR1, SIRT3 and DPP-4 expression levels in renal tissues after combination therapy was greater than that after insulin-only treatment. This study shows that the combination of insulin and UA significantly improved the pathological changes in the renal tissue of T1DM rats, and the underlying mechanism may be related to improving apoptosis and oxidative stress by regulating p38 MAPK, SIRT3, DPP-4 and FGFR1 levels, thereby blocking TGF-β signaling pathway activation and inhibiting EMT and EndMT processes.

Analysis of the Effectiveness of the Nurse-Led "Outpatient-Ward-Home" Management Model in Chronic Kidney Patients.

Objective To investigate the application and effect of the nurse-led “outpatient-ward-home” management model in the care of patients with chronic kidney disease (CKD). Methods 120 patients with CKD admitted to our hospital between April 2020 and April 2021 were selected as trial subjects. All patients were divided into experimental and control groups according to the random number table method, with 60 cases in each group. The patients in the experimental group implemented the nurse-led “outpatient-ward-home” management model; the patients in the control group were given routine care and telephone follow-up. The self-rating anxiety scale (SAS), self-rating depression scale (SDS), Pittsburgh Sleep Quality Index (PSQI) score, self-management scores, nutritional status, renal function indicators, and chronic renal failure quality of life scale (QLICD-CRF2.0) were compared between the two groups before and 6 months after the intervention. Results Before the intervention, there were no statistically significant differences between the control and experimental groups in SAS, SDS, PSQI scores, self-management scores, QLICD-CRF2.0 scores, body mass index (BMI), prealbumin (PAb), albumin (ALB), serum creatinine (Scr), blood urea nitrogen (BUN), and glomerular filtration rate (GFR) levels (P > 0.05). After 6 months of intervention, SAS, SDS, PSQI scores, Scr, BUN, and GFR levels were lower in the experimental group than in the control group; self-management scores, QLICD-CRF2.0 scores, BMI, PAb, and ALB levels were higher in the experimental group than in the control group (P < 0.05). Conclusion The nurse-led “outpatient-ward-family” intervention model can improve the negative emotions and sleep disorders of CKD patients, enhance patients' self-management ability, and to a certain extent, slow down the disease process and improve the quality of life.

PROGNOSTIC SIGNIFICANCE OF CLINICAL AND LABORATORY FINDINGS IN THE NEW CORONAVIRUS INFECTION COVID-19

The new coronavirus infection COVID-19 is characterized by high mortality. The aim of the study was to establish the role of gender, age, concomitant diseases, shifts in laboratory findings in predicting fatal outcome in COVID-19 patients. The study was conducted on the basis of emergency medical care hospital (Cheboksary). 182 case histories of COVID-19 patients who underwent inpatient treatment were analyzed, 82 of whom died. The frequency of outcomes in different clinical conditions and laboratory shifts were analyzed, the relative risk (RR) of lethal outcome and its confidence interval were calculated. Mortality is naturally associated with the number of points on the NEWS 2 scale, the extent of pulmonary tissue involvement, no connection with gender was found. The prognostic value of acute kidney injury (RR – 2.57), chronic kidney disease (RR – 1.47), arterial hypertension (RR – 3.04), coronary heart disease (RR – 2.60), chronic nonspecific lung diseases (RR – 1.53), elderly and senile age (RR – 2.84, HR – 4.90), obesity of II-III degrees (RR – 1.97), body weight deficit (RR – 1.82) is shown. The ROC analysis method determined the levels of C-reactive protein in the blood (&gt; 25 mg/l, RR – 3.2), an increase in procalcitonin (RR – 3.80), D-dimer (&gt; 562.8 ng/ml, RR – 3.15), leukocytes (&gt; 9.52×109/l, RR – 2.22), lymphocytes (&lt; 1.15×109/l, RR – 2.04), interleukin-6 (&gt; 13.2 pg/ml, RR – 3.38), fibrinogen (&gt; 6.4 g/l, RR – 1.57), creatinine (&gt; 91.8 mmol/l, RR – 1.95), lactate dehydrogenase (&gt; 558 mmol/l, RR – 2.28), glomerular filtration rate (GFR &lt; 63.8 ml/min / 1.73 m2, RR – 2.55), going beyond which significantly increases the risk of fatal outcome. Hence, along with the known factors in the high-risk group, it is necessary to take into account a specific body mass index, age group, renal function indicators and a number of inflammatory changes in the blood.

Comparison of the Effects of Laparoscopic Surgery and Traditional Open Surgery on Stone Clearance, Laboratory Indexes and Life Quality in Patients with Renal Calculi.

Objective A case-control study was conducted to determine the effectiveness of laparoscopic surgery and traditional open surgery on stone clearance, laboratory indexes, and life quality in patients with renal calculi. Methods During March 2017 to March 2022, 272 patients with complex renal calculi (CRC) cured in our hospital were assigned into control group (n = 136) and research group (n = 136) arbitrarily. The former accepted traditional open surgery, while the latter accepted laparoscopic surgery. The operation time, intraoperative blood loss, hospital stay, and time of getting out of bed were compared. The degree of postoperative incision pain was assessed by visual analogue scale (VAS). The life quality was assessed by the Comprehensive Assessment Questionnaire-74 (GQOL-74). The indexes of renal function and urine metabolism were measured. Then, the postoperative stone clearance rate and complications were calculated. Results Operation time, blood loss intraoperatively, time out of bed, and hospitalization were all remarkably reduced in the research group, and the difference was statistically significant (P < 0.05). The complete stone clearance rates in study and control cohorts were 75.73% and 63.24%, respectively. The VAS scores were lessened after the operation. Compared with the two groups, the VAS scores of the research group were remarkably lower at 1 to 2 weeks and 1 and 3 months after the operation, and the difference was statistically significant (P < 0.05). One week after operation, the levels of β 2-microglobulin (β 2-MG), N-acetyl-β-glucosaminidase (NAG), and renal injury molecule-1 (kidney injury molecule-1, Kim-1) in the research group were remarkably lower. The levels of urinary β 2-MG, NAG, and KIM-1 in the research group were remarkably lower, and the difference was statistically significant (P < 0.05). One week after operation, the levels of urinary oxalic acid, uric acid, and urinary calcium lessened averagely. The levels of urinary oxalic acid, uric acid, and urinary calcium in the research group were lower, and the difference was statistically significant (P < 0.05). The quality-of-life scores were compared. One week after the operation, the scores of physical function, psychological function, social function, and material function were all augmented, and the difference was statistically significant (P < 0.05). The incidence of complications was 9.56% and 2.21%, respectively. The incidence of complications in the research group was lower, and the difference was statistically significant (P < 0.05). Conclusion Laparoscopic surgery is successful when treating CRC, which is superior to invasive surgery in postoperative complications, stone clearance rate, improvement of postoperative renal function, and life quality. It is one of the ideal treatment methods for CRC. However, the role of open surgery when treating CRC cannot be ignored. This needs to be further confirmed by large samples of randomized controlled trials.

Increased CD8+ T cells in patients with Henoch–Schonlein purpura nephritis exhibit suppressive immune activity

BackgroundAbout 40% to 50% of children with Henoch-Schonlein purpura often suffer from nephritis, which can cause irreversible renal damage. Significantly increased peripheral T lymphocytes and reduced B lymphocytes have been widely reported as hallmarks of Henoch-Schonlein purpura nephritis (HSPN) differing from Henoch-Schonlein purpura without nephritis (HSP). While the role of peripheral immune cells, especially CD8+ T cells, in the development of nephritis of Henoch-Schonlein purpura is not clear. ObjectivesTo explore the changes of peripheral CD8+ T cells and the association of CD8+ T cell markers with indicators of renal function in HSP and HSPN patients. Patients and MethodsA total of 27 HSP and 16 HSPN patients were included in this study. The serum urea, serum creatinine, 24-hour urinary protein and peripheral white blood cell counts were collected from hospital registry systems. The T cell surface markers (CD28, CD107a and CD69) and cytokine (TNFα and IFNγ) secretion capacity were measured by flow cytometry. ResultsCompared with HSP patients, The number of CD8+ T cells in HSPN patients increased significantly (p=0.0003) and demonstrated with decreased CD69 expression (p<0.0001) and decreased cytokine secretion. The expression level of CD69 in CD3+, CD4+ and CD8+ T cells all significantly correlated negatively with serum creatinine and 24-hour urinary protein in HSP and HSPN children. ConclusionsThe inhibition of CD8+ T cell activity was significantly related to the decline of renal function in HSP and HSPN patients. It is possible to monitor renal function by detecting the expression of CD69 on CD8+ T cells in HSP and HSPN patients.

Albuminuria as a marker of systemic congestion in patients with heart failure.

Albuminuria is common in patients with heart failure and associated with worse outcomes. The underlying pathophysiological mechanism of albuminuria in heart failure is still incompletely understood. The association of clinical characteristics and biomarker profile with albuminuria in patients with heart failure with both reduced and preserved ejection fractions were evaluated. Two thousand three hundred and fifteen patients included in the index cohort of BIOSTAT-CHF were evaluated and findings were validated in the independent BIOSTAT-CHF validation cohort (1431 patients). Micro-albuminuria and macro-albuminuria were defined as urinary albumincreatinine ratio (UACR) 30 mg/gCr and 300 mg/gCr in spot urines, respectively. The prevalence of micro- and macro-albuminuria was 35.4 and 10.0, respectively. Patients with albuminuria had more severe heart failure, as indicated by inclusion during admission, higher New York Heart Association functional class, more clinical signs and symptoms of congestion, and higher concentrations of biomarkers related to congestion, such as biologically active adrenomedullin, cancer antigen 125, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (all P 0.001). The presence of albuminuria was associated with increased risk of mortality and heart failure (re)hospitalization in both cohorts. The strongest independent association with log UACR was found for log NT-proBNP (standardized regression coefficient 0.438, 95 confidence interval 0.350.53, P 0.001). Hierarchical clustering analysis demonstrated that UACR clusters with markers of congestion and less with indices of renal function. The validation cohort yielded similar findings. In patients with new-onset or worsening heart failure, albuminuria is consistently associated with clinical, echocardiographic, and circulating biomarkers of congestion.