Hematological and renoprotective effects of folic acid and lentil extract in diclofenac sodium exposed rats

Excessive intake of non-steroidal anti-inflammatory drugs such as, diclofenac sodium (DS) may lead to toxicity in the rats. In this work, we aimed to examine the protective impact of lentil extract (LE) and folic acid (FA) on the hematological markers, the kidney tissue oxidative stress and the renal function against diclofenac sodium (DS) in male albino rats. The rats (120-150 g) were divided into four equal groups randomly, the first group kept as the untreated control. The second group was administrated with DS (11.6 mg/kg b.wt. orally once/day). The third group was received DS+FA (11.6 mg/kg b.wt.+76.9 microgram/kg b.wt.) orally once/day. The fourth group was treated with DS+LE (11.6 mg/kg b.wt.+500 mg/kg b.wt.) orally once/day. After four weeks, the results revealed that DS produced a significant decrease in the values of red blood cells (RBCs), hemoglobin concentration (Hb), hematocrit (HCT) and white blood cells (WBCs). On the other hand, there was a significant increase in the platelets count. Also, DS induced a renal deterioration; this was evidenced by the significant increase in the serum levels of urea, creatinine, uric acid, Na, Ca, Mg as well as the nitric oxide (NO) level in the kidney tissue. Also, there were a significant reduction in the serum levels of potassium (K) and reduced glutathione (GSH) in the kidney homogenates. Moreover, the findings in the rats treated by DS+LE or DS+FA showed a potential protection on the hematological markers, oxidative stress in the kidney tissue and the renal function disturbed by DS. LE and FA could play a potent role for the prevention the adverse hematological, the kidney tissue oxidative stress and the renal dysfunction caused by DS via their anti-oxidative and bioactive phytochemicals.

Prediction of chronic kidney disease after orthotopic liver transplantation: development and validation of a nomogram model

Background We aimed to develop and validate a nomogram model for predicting CKD after orthotopic liver transplantation (OLT). Methods The retrospective data of 399 patients who underwent transplantation and were followed in our centre were collected. They were randomly assigned to the training set (n = 293) and validation set (n = 106). Multivariable Cox regression analysis was performed in the training set to identify predictors of CKD. According to the Cox regression analysis results, a nomogram model was developed and validated. The renal function of recipients was monitored, and the long-term survival prognosis was assessed. Results The incidence of CKD at 5 years after OLT was 25.6%. Cox regression analysis identified several predictors of post-OLT CKD, including recipient age at surgery (HR 1.036, 95% CI 1.006-1.068; p = 0.018), female sex (HR 2.867, 95% CI 1.709-4.810; p < 0.001), preoperative hypertension (HR 1.670, 95% CI 0.962-2.898; p = 0.068), preoperative eGFR (HR 0.996, 95% CI 0.991-1.001; p = 0.143), uric acid at 3 months (HR 1.002, 95% CI 1.001-1.004; p = 0.028), haemoglobin at 3 months (HR 0.970, 95% CI 0.956-0.983; p < 0.001), and average concentration of cyclosporine A at 3 months (HR 1.002, 95% CI 1.001-1.003; p < 0.001). According to these parameters, a nomogram model for predicting CKD after OLT was constructed and validated. The C-indices were 0.75 and 0.80 in the training and validation sets. The calibration curve of the nomogram showed that the CKD probabilities predicted by the nomogram agreed with the observed probabilities at 1, 3, and 5 years after OLT (p > 0.05). Renal function declined slowly year by year, and there were significant differences between patients divided by these predictors. Kaplan-Meier survival analysis showed that the survival prognosis of recipients decreased significantly with the progression of renal function. Conclusions With excellent predictive abilities, the nomogram may be a simple and reliable tool to identify patients at high risk for CKD and poor long-term prognosis after OLT.

Effect of Huaiqihuang Granules Combined with Comprehensive Nursing on Children with Primary Nephrotic Syndrome

Background. To observe the effect of Huaiqihuang granules combined with comprehensive nursing intervention on children with primary nephrotic syndrome (PNS) and its effect on renal function index. Methods. A total of 104 patients were included, and the patients were randomly divided into two groups, with 52 cases in each group. The control group was treated with glucocorticoid, and the study group was treated with Huaiqihuang granules. The clinical efficacy of the two groups was observed. The levels of TG, TC, EGFR, 24 h UTP, BUN, Scr, IgA, IgG, IgM, IFN-γ and TNF-α were compared between two groups before and after treatment. The incidence of adverse reactions and recurrence rate after treatment were compared between the two groups. Results. The effective rate of the study group (94.23%) was significantly higher than that of the control group (78.85%). Before treatment, there was no significant difference in TG and TC levels between the two groups. After treatment, the levels of TG and TC in both groups were decreased, and the decrease was more obvious in the study group. Compared with before treatment, the levels of 24 h UTP, BUN, Scr, IFN-γ, and TNF-α in both groups were significantly decreased after treatment, while EGFR, IgA, IgG, and IgM levels were significantly increased. Compared with the control group, the changes of each index in the study group were more obvious after treatment. After treatment, the incidence of adverse reactions and recurrence rate in the study group were significantly lower than those in the control group. Conclusions. Huaiqihuang granules combined with comprehensive nursing treatment in children with PNS can reduce the occurrence of recent recurrence and adverse reactions and improve the cellular immune function and renal function.

Meta-analysis of the efficacy and safety of finerenone in diabetic kidney disease

Background: The Phase III clinical trial of the non-steroidal mineralocorticoid receptor antagonist finerenone (BAY 94-8862) has been completed, aiming to investigate renal and cardiovascular (CV) outcomes in type 2 diabetes (T2D) with chronic kidney disease (CKD). However, the efficacy and safety of finerenone in renal function remain controversial. The purpose of this study was to explore the efficacy and safety of finerenone in treating the patients with diabetic kidney disease (DKD). Methods: Databases of PubMed, Cochrane Library, Embase, and Web of Science were searched for randomized controlled trials (RCTs) on patients with DKD receiving finerenone treatment from inception to September 2021. Data including patient characteristics and interested outcomes were extracted, and the dichotomous data and continuous variables were evaluated using risk ratio (RR) with 95% confidence intervals (CIs) and mean differences (MD) with 95% CIs, respectively. Results: A total of 4 RCTs involving 13945 patients were included in this meta-analysis. Analysis results demonstrated that patients receiving finerenone showed a significant decrease in changing urinary albumin-to-creatinine ratio (UACR) from baseline (MD: ﹣0.30; 95%CI [﹣0.33, ﹣0.27] P=0.46, I2=0%) (P＜0.05). The number of patients with ≥40% reduction in estimated glomerular filtration rate (eGFR) from baseline in the finerenone group was significantly smaller than that in the placebo group (RR: 0.85; 95%CI [0.78, 0.93] P=0.60, I2=0%) (P＜0.05). No difference was found in adverse events between the finerenone and placebo groups (RR: 1.00; 95%CI [0.98, 1.01] P = 0.94, I2=0%) (P=0.65). The incidence of hyperkalemia was higher in the finerenone group than that in the placebo group (RR: 2.03; 95%CI [1.83, 2.26] P = 0.95, I2=0%) (P＜0.05). Conclusion: Finerenone contributes to the reduction of UACR and can ameliorate the deterioration of renal function in patients with T2D and CKD. The higher risk of hyperkalemia was found in the finerenone group compared with placebo, however, there was no difference in the risk of overall adverse events.

Novel Renal Autologous Cell Therapy for Type 2 Diabetes Mellitus Chronic Diabetic Kidney Disease: Clinical Trial Design

<b><i>Background:</i></b> Cell therapies explore unmet clinical needs of patients with chronic kidney disease with the potential to alter the pathway toward end-stage kidney disease. We describe the design and baseline patient characteristics of a phase II multicenter clinical trial utilizing the novel renal autologous cell therapy (REACT), by direct kidney parenchymal injection via the percutaneous approach in adults with type 2 diabetic kidney disease (T2DKD), to delay or potentially avoid renal replacement therapy. <b><i>Design:</i></b> The study conducted a prospective, multicenter, randomized control, open-label, phase II clinical trial between an active treatment group (ATG) receiving REACT from the beginning of the trial and a contemporaneous deferred treatment group (DTG) receiving standard of care for 12 months before crossing over to receive REACT. <b><i>Objectives:</i></b> The objective of this study was to establish the safety and efficacy of 2 REACT injections with computed tomography guidance, into the renal cortex of patients with T2DKD administered 6 months apart, and to compare the longitudinal change in renal function between the ATG and the DTG. <b><i>Setting:</i></b> This was a multicenter study conducted in major US hospitals. <b><i>Patients:</i></b> We enrolled eighty-three adult patients with T2DKD, who have estimated glomerular filtration rates (eGFRs) between 20 and 50 mL/min/1.73 m². <b><i>Methods:</i></b> All patients undergo an image-guided percutaneous kidney biopsy to obtain epithelial phenotype selective renal cells isolated from the kidney tissue that is then expanded ex vivo over 4–6 weeks, resulting in the REACT biologic product. Patients are randomized 1:1 into the ATG or the DTG. Primary efficacy endpoints for both study groups include eGFR measurements at baseline and at 3-month intervals, through 24 months after the last REACT injection. Safety analyses include biopsy-related complications, REACT injection, and cellular-related adverse events. The study utilizes Good Clinical and Manufacturing Practices and a Data and Safety Monitoring Board. The sample size confers a statistical power of 80% to detect an eGFR change in the ATG compared to the DTG at 24 months with an α = 0.05. <b><i>Limitations:</i></b> Blinding cannot occur due to the intent to treat procedure, biopsy in both groups, and open trial design. <b><i>Conclusion:</i></b> This multicenter phase II randomized clinical trial is designed to determine the efficacy and safety of REACT in improving or stabilizing renal function among patients with T2DKD stages 3a–4.

The Dynamics and Plasticity of Epigenetics in Diabetic Kidney Disease: Therapeutic Applications Vis-à-Vis

Chronic kidney disease (CKD) refers to the phenomenon of progressive decline in the glomerular filtration rate accompanied by adverse consequences, including fluid retention, electrolyte imbalance, and an increased cardiovascular risk compared to those with normal renal function. The triggers for the irreversible renal function deterioration are multifactorial, and diabetes mellitus serves as a major contributor to the development of CKD, namely diabetic kidney disease (DKD). Recently, epigenetic dysregulation emerged as a pivotal player steering the progression of DKD, partly resulting from hyperglycemia-associated metabolic disturbances, rising oxidative stress, and/or uncontrolled inflammation. In this review, we describe the major epigenetic molecular mechanisms, followed by summarizing current understandings of the epigenetic alterations pertaining to DKD. We highlight the epigenetic regulatory processes involved in several crucial renal cell types: Mesangial cells, podocytes, tubular epithelia, and glomerular endothelial cells. Finally, we highlight epigenetic biomarkers and related therapeutic candidates that hold promising potential for the early detection of DKD and the amelioration of its progression.

Dehydration Status Aggravates Early Renal Impairment in Children: A Longitudinal Study

Dehydration is common in children for physiological and behavioral reasons. The objective of this study was to assess changes in hydration status and renal impairment across school weekdays. We conducted a longitudinal study of three repeated measures of urinalysis within one week in November 2019 in a child cohort in Beijing, China. We measured urine specific gravity (USG) to determine the dehydration status, and the concentration of β2-microglobulin (β2-MG) and microalbumin (MA) to assess renal function impairment among 1885 children with a mean age of 7.7 years old. The prevalence of dehydration was 61.9%, which was significantly higher in boys (64.3%). Using chi-square tests and linear mixed-effects regression models, we documented the trends of the renal indicators’ change over time among different hydration statuses. Compared to Mondays, there were apparent increases of β2-MG concentrations on Wednesdays (β = 0.029, p < 0.001) and Fridays (β = 0.035, p < 0.001) in the dehydrated group, but not in the euhydrated group. As for the MA concentrations, only the decrease on Fridays (β = −1.822, p = 0.01) was significant in the euhydrated group. An increased trend of elevated β2-MG concentration was shown in both the euhydrated group (Z = −3.33, p < 0.001) and the dehydrated group (Z = −8.82, p < 0.001). By contrast, there was a decreased trend of elevated MA concentrations in the euhydrated group (Z = 3.59, p < 0.001) but not in the dehydrated group. A new indicator ratio, β2-MG/MA, validated the consistent trends of renal function impairment in children with dehydration. Renal impairment trends worsened as a function of school days during the week and the dehydration status aggravated renal impairment during childhood across school weekdays, especially tubular abnormalities in children.

Diacerein Versus Chondroitin Sulfate in Treatment of Adult Kashin-Beck Disease: An Intervention Trial in Heilongjiang Province, China

Background: Kashin-Beck disease (KBD) is a special type of osteoarthritis and has disabled and stunted the growth of hundreds of people in China. It also can affect patients' ability to work and live. So, how to conduct effective treatment for adult KBD patients has become a major public health problem in current KBD endemic areas. In this trial, therapeutic effects of diacerein and chondroitin sulfate on adult KBD was to evaluate and compare so that we can screen out more suitable drug. Methods: 308 KBD patients were divided into two groups and received chondroitin sulphate (Group A) and diacerein (Group B) for 24 weeks, respectively. Data were collected at 0 week (baseline), 12 weeks (primary end point) and 24 weeks (secondary end point) to calculate the proportion of patients with effective therapeutic effect and overall improvement rate (primary efficacy parameters), WOMAC pain and stiffness scores (secondary efficacy parameters). Blood sample was collected to measure liver and renal function indexes. All indexes and parameters were analysed with SPSS software and intent-to-treat (ITT) analysis was applied. Results: Two primary efficacy parameters in group B at primary end point were significantly higher than those in group A (P=0.021, P=0.007), but no statistical differences were seen in these two primary efficacy parameters between two groups at secondary end point or between primary and secondary end points in same group (all P>0.05). In both groups, with the prolongation of treatment time, WOMAC pain and stiffness scores decreased significantly (all P<0.001), but no significant differences were seen between primary and secondary end points (all P>0.05). In addition, in both groups, the occurrences of total adverse events were relatively low and no side effect on liver function was seen. Diacerein also had no side effect on renal function. Conclusion: For treatment of adult KBD, both diacerein and chondroitin sulfate were effective, and diacerein might work stronger than chondroitin sulfate. Taking into account both efficacy and safety, the optimal intervention time of diacerein was 12 weeks. Trial registration: The trial was registered complementally on 31/10/2020, and the registration number in the Chinese Clinical Trial Registry is ChiCTR2000039600 (http://www.chictr.org.cn).