Treatment of Patients with IgA Nephropathy: Evaluation of the Safety and Efficacy of Mycophenolate Mofetil.

INTRODUCTION AND AIM: Immunoglobulin A nephropathy (IgAN), characterized by aberrant IgA immune complex deposition, is the most prevalent primary glomerular disease and the main cause of end-stage renal disease, causing a significant physical and psychological burden on people worldwide. Conventional therapeutic approaches, such as renin-angiotensin-aldosterone system inhibitors and corticosteroids, may not achieve sufficient effectiveness and may produce major side events in the past. The previous data in Asian populations indicated that mycophenolate mofetil (MMF) might significantly advance the development of a new therapy strategy for IgAN. The effectiveness and safety of MMF in patients with IgAN will be investigated in this study. METHODS: A literature search was conducted on June 30th, 2023, by searching the following databases: PubMed and the Cochrane Library according to predefined criteria. To investigate the renoprotective benefits and safety of MMF, statistical analyses were performed using Cochrane's Review Manager Version 5.3. RESULTS: The meta-analysis included nine randomized controlled studies that fulfilled the inclusion criterion. In the Asian population, the results revealed a substantial difference in remission rates between the MMF group and the control group (OR: 2.53, 95% CI: 1.02, 6.30, P = 0.05). MMF can increase the rate of decrease in proteinuria in IgAN patients when compared with controls in Asians (OR: 7.34, 95% CI: 2.69, 20.08, P = 0.0001), and MMF can reduce the urinary protein in patients with IgAN in Asians (WMD: -0.61, 95% CI: -1.15, -0.08, P = 0.02). Interestingly, these studies on Asians were conducted in China. However, the differences in remission rate, rate of decrease in proteinuria, and urinary protein reduction between the MMF group and control group were not found in overall populations and in the Caucasian population. The differences in complete remission rate, partial remission rate, serum creatinine (SCr) doubling rate, rate of 50% increase in SCr, and rate of need for renal replacement treatment between the MMF group and control group were not found in Asians, Caucasians, and overall populations. The difference in the rate of side effects between the MMF group and the control group was not found. CONCLUSION: MMF protects renal function and is a safe medication for treating Chinese IgAN patients. MMF might significantly advance the development of a new therapy strategy for IgAN in the Chinese population

Role and Mechanism of Growth Differentiation Factor 15 in Chronic Kidney Disease.

GDF-15 is an essential member of the transforming growth factor-beta superfamily. Its functions mainly involve in tissue injury, inflammation, fibrosis, regulation of appetite and weight, development of tumor, and cardiovascular disease. GDF-15 is involved in various signaling pathways, such as MAPK pathway, PI3K/AKT pathway, STAT3 pathway, RET pathway, and SMAD pathway. In addition, several factors such as p53, ROS, and TNF-α participate the regulation of GDF-15. However, the specific mechanism of these factors regulating GDF-15 is still unclear and more research is needed to explore them. GDF-15 mainly improves the function of kidneys in CKD and plays an important role in the prediction of CKD progression and cardiovascular complications. In addition, the role of GDF-15 in the kidney may be related to the SMAD and MAPK pathways. However, the specific mechanism of these pathways remains unclear. Accordingly, more research on the specific mechanism of GDF-15 affecting kidney disease is needed in the future. In conclusion, GDF-15 may be a therapeutic target for kidney disease.

Thymoquinone: An Effective Natural Compound for Kidney Protection.

Kidney disease is a common health problem worldwide. Acute or chronic injuries may interfere with kidney functions, eventually resulting in irreversible kidney damage. A number of recent studies have shown that the plant-derived natural products have an extensive potential for renal protection. Thymoquinone (TQ) is an essential compound derived from Nigella Sativa (NS), which is widely applied in the Middle East as a folk medicine. Previous experiments have demonstrated that TQ has a variety of potential pharmacological effects, including anti-oxidant, antibacterial, antitumor, immunomodulatory, and neuroprotective activities. In particular, the prominent renal protective efficacy of TQ has been demonstrated in both in vivo and in vitro experiments. TQ can prevent acute kidney injuries from various xenobiotics through anti-oxidation, anti-inflammatory, and anti-apoptosis effects. In addition, TQ exhibited significant pharmacological effects on renal cell carcinoma, renal fibrosis, and urinary calculi. The essential mechanisms involve scavenging ROS and increasing anti-oxidant activity, decreasing inflammatory mediators, inducing apoptosis, and inhibiting migration and invasion. The purpose of this review is to conclude the pharmacological effects and the potential mechanisms of TQ in renal protection, shedding new light on the exploration of medicinal phyto-protective agents targeting kidneys.

Ketonuria as an Indicator of Improvement of Renal Function in Patients with Type 2 Diabetes Receiving SGLT2 Inhibitor Treatment.

We investigated the potential association between ketonuria during treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors and its renoprotective effect in patients with type 2 diabetes. We included 192 patients who had received SGLT2 inhibitors for more than 6 months. After propensity score matching, 52 patients each were allocated into groups with or without ketonuria, respectively. The estimated glomerular filtration rate exhibited a significant improvement only in subjects with ketonuria (without ketonuria: mean difference, -0.02 mL/min/1.73 m2 [95% confidence interval (CI), -3.87 to 3.83 mL/min/1.73 m2] vs. with ketonuria: mean difference, 6.81 mL/min/1.73 m2 [95% CI, 3.16 to 10.46 mL/min/1.73 m2]; P<0.001). Improvement in estimated glomerular filtration rate at 6 months was associated with female sex and lower baseline body weight, blood pressure, and triglyceride levels in patients with ketonuria. In conclusion, the presence of ketonuria was associated with the renoprotective effect of SGLT2 inhibitors, and female sex and the absence of metabolic syndrome components may serve as additional indicators of these medications' substantial renoprotective effects in individuals with ketonuria.

Therapeutic potential of nicorandil beyond anti-anginal drug: A review on current and future perspectives.

Nicorandil (NIC) is a well-known anti-anginal agent, which has been recommended as one of the second-line treatments for chronic stable angina as justified by the European guidelines. It shows an efficacy equivalent to that of classic anti-anginal agents. NIC has also been used clinically in various cardiovascular diseases such as variant or unstable angina and reperfusion-induced damage following coronary angioplasty or thrombolysis. Different mechanisms have been involved in the protective effects of nicorandil in various diseases, including opening of adenosine triphosphate-sensitive potassium (KATP) channel and donation of nitric oxide (NO). In recent years, NIC has been found to show numerous pharmacological activities such as neuroprotective, nephroprotective, hepatoprotective, cardioprotective, and testicular protective effects, among other beneficial effects on the body. The present review dwells on the pharmacological potentials of NIC beyond its anti-anginal action.

Safety and Efficacy of Para-Aminohippurate Coinfusion for Renal Protection During Peptide Receptor Radiotherapy in Patients with Neuroendocrine Tumors.

Para-aminohippurate, also known as p-aminohippuric acid (PAH), is used clinically to measure effective renal plasma flow. Preclinically, it was shown to reduce 177Lu-DOTATOC uptake in the kidneys while improving bioavailability compared with amino acid (AA) coinfusion. We report the safety and efficacy of PAH coinfusion during peptide receptor radiotherapy in patients with neuroendocrine tumors. Methods: Twelve patients with metastatic or unresectable gastroenteropancreatic neuroendocrine tumors received 177Lu-DOTATOC in 33 treatment cycles. Either 8 g of PAH or a mixture of 25 g of arginine and 25 g of lysine were coinfused. Safety was assessed by monitoring laboratory data, including hematologic and renal data, as well as electrolytes obtained before and 24 h after treatment. For radiation dosimetry, whole-body scans were performed at 1, 24, and 48 h and a SPECT/CT scan was performed at 48 h, along with blood sampling at 5 min and 0.5, 2, 4, 24, and 48 h after administration. Absorbed dose estimations for the kidneys and bone marrow were performed according to the MIRD concept. Results: In 15 treatment cycles, PAH was coinfused. No changes in mean creatinine level, glomerular filtration rate, and serum electrolytes were observed before or 24 h after treatment when using PAH protection (P ≥ 0.20), whereas serum chloride and serum phosphate increased significantly under AA (both P < 0.01). Kidney-absorbed dose coefficients were 0.60 ± 0.14 Gy/GBq with PAH and 0.53 ± 0.16 Gy/GBq with AA. Based on extrapolated cumulative kidney-absorbed doses for 4 cycles, 1 patient with PAH protection and 1 patient with AA protection in our patient group would exceed the 23-Gy conservative threshold. The bone marrow-absorbed dose coefficient was 0.012 ± 0.004 Gy/GBq with PAH and 0.012 ± 0.003 Gy/GBq with AA. Conclusion: PAH is a promising alternative to AA for renal protection during peptide receptor radiotherapy. Further research is required to systematically investigate the safety profile and radiation dosimetry at varying PAH plasma concentrations.

Astaxanthin treatment reduces kidney damage and facilitates antioxidant recovery in lithium-intoxicated rats.

OBJECTIVE: This study aimed to evaluate the protective effects of astaxanthin against lithium-induced nephrotoxicity, focusing on histopathological changes, oxidative stress modulation, and alteration in the expression of key proteins related to apoptosis and inflammation. METHODS: In this study, 56 male rats were utilized and divided into experimental groups subjected to lithium-induced nephrotoxicity, with and without astaxanthin treatment, over 14 and 28 days. The parameters assessed included oxidative stress markers (MDA, GSH, SOD), protein expression levels of BCL-2, BAX, TNF- α, PI3K, NF-κ B-p65, IL-1ß, and comprehensive histopathological examinations to evaluate the integrity of renal tissue. RESULTS: Lithium exposure led to significant renal damage, as evidenced by histological distortions in renal architecture, increased oxidative stress indicated by elevated MDA levels, and dysregulated expressions of apoptotic and inflammatory proteins. Notably, histopathological analysis revealed glomerular and tubular degeneration in lithium-treated groups. Astaxanthin treatment effectively mitigated these effects, demonstrating its efficacy in reducing lipid peroxidation, rebalancing apoptotic proteins, suppressing pro-inflammatory cytokines, and preserving renal histological structure. The concurrent use of lithium and astaxanthin showed a considerable amelioration of lithium-induced damage, suggesting astaxanthin's role in attenuating the nephrotoxic effects of lithium, both at a molecular and structural level. CONCLUSION: Astaxanthin demonstrates significant renoprotective effects against lithium-induced nephrotoxicity, suggesting its utility as an effective adjunctive therapy. Through its potent antioxidative, anti-inflammatory, and anti-apoptotic actions, astaxanthin effectively reduces renal damage associated with lithium treatment, underscoring its potential for enhancing renal health in patients receiving lithium therapy.

The effect of the concurrent use of Dexmedetomidine (DEX) during the perioperative period on the renal function of patients following craniocerebral interventional surgery.

BACKGROUND: Craniocerebral interventional surgery is a common and essential treatment for cerebrovascular diseases. Despite continuous progress in interventional diagnosis and treatment technology, there is no effective method to alleviate contrast-induced kidney injuries. In this retrospective cohort study, we investigated the effect of the concurrent use of Dexmedetomidine (DEX) during the perioperative period on the renal function of patients following craniocerebral interventional surgery. METHODS: We identified 228 cases of patients underwent craniocerebral interventional surgery from January 2018 to March 2022. Patients who used DEX during general anesthesia were in the DEX group (DEX group) or that did not use dexmedetomidine as the control group (CON group). The markers of kidney injury were recorded before and within 48 h after surgery. RESULTS: Compared with CON group, the urea nitrogen (BUN) of the DEX group decreased significantly on the first day and the second day after surgery (p < 0.05). The serum cystatin-C and the blood urea nitrogen/creatinine ratio (BUN/Cr) was significantly lower than that in CON group on the second day (p < 0.05). The urine output in the DEX group increased significantly, and the mean arterial pressure (MAP) was higher than the CON group (p < 0.01). There was no difference in postoperative complications, ICU stay time and hospitalization time between the two groups. CONCLUSION: The combined use of dexmedetomidine in general anesthesia for craniocerebral interventional surgery can reduce BUN levels within 48 h after surgery, significantly increase intraoperative urine volume, maintain intraoperative circulation stability.

Transforming Diabetes Care: The Molecular Pathways through Which GLP1-RAs Impact the Kidneys in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a substantial complication of type 2 diabetes (T2D), presenting challenges in chronic kidney disease (CKD) management. In addition to traditional and recent therapies, including angiotensin, converting enzyme (ACE) inhibitors, angiotensin receptor blockers, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists, the evolution of antihyperglycemic treatments has introduced a promising agent, glucagon-like peptide-1 receptor agonist (GLP-1RA) for the management of DKD. GLP-1RAs enhance insulin release and reduce glucagon release, offering a novel approach to DKD management. This review analyzes the molecular pathways through which GLP1-RAs confer renal protection in T2D and DKD, which are complex and multifaceted. They include modulation of renal hemodynamics, antioxidative and anti-inflammatory actions, metabolic regulation, and direct cellular effects. These mechanisms highlight GLP1-RA's potential as a therapeutic option for glycemic control and direct or indirect renal function protection in diabetic patients, emphasizing the potentiality of GLP-1RAs for dual therapy, with cardiovascular and renal protection as a holistic approach. Clinical evidence supports GLP-1RAs in reducing albuminuria and enhancing kidney outcomes, highlighting their value in a comprehensive DKD management strategy.

Hesperitin-Copper(II) Complex Regulates the NLRP3 Pathway and Attenuates Hyperuricemia and Renal Inflammation.

BACKGROUND: Hyperuricaemia (HUA) is a disorder of purine metabolism in the body. We previously synthesized a hesperitin (Hsp)-Cu(II) complex and found that the complex possessed strong uric acid (UA)-reducing activity in vitro. In this study we further explored the complex's UA-lowering and nephroprotective effects in vivo. METHODS: A mouse with HUA was used to investigate the complex's hypouricemic and nephroprotective effects via biochemical analysis, RT-PCR, and Western blot. RESULTS: Hsp-Cu(II) complex markedly decreased the serum UA level and restored kidney tissue damage to normal in HUA mice. Meanwhile, the complex inhibited liver adenosine deaminase (ADA) and xanthine oxidase (XO) activities to reduce UA synthesis and modulated the protein expression of urate transporters to promote UA excretion. Hsp-Cu(II) treatment significantly suppressed oxidative stress and inflammatory in the kidney, reduced the contents of cytokines and inhibited the activation of the nucleotide-binding oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory pathway. CONCLUSIONS: Hsp-Cu(II) complex reduced serum UA and protected kidneys from renal inflammatory damage and oxidative stress by modulating the NLRP3 pathway. Hsp-Cu(II) complex may be a promising dietary supplement or nutraceutical for the therapy of hyperuricemia.

Dexmedetomidine mitigates acute kidney injury after coronary artery bypass grafting: a prospective clinical trial.

INTRODUCTION AND OBJECTIVES: To evaluate the impact of dexmedetomidine impact on cardiac surgery-associated acute kidney injury (CSA-AKI), kidney function, and metabolic and oxidative stress in patients undergoing coronary artery bypass grafting with heart-lung machine support. METHODS: A randomized double-masked trial with 238 participants (50-75 years) undergoing coronary artery bypass grafting was conducted from January 2021 to December 2022. The participants were divided into Dex (n=119) and NS (n = 119) groups. Dex was administered at 0.5 mcg/kg over 10minutes, then 0.4 mcg/kg/h until the end of surgery; the NS group received equivalent saline. Blood and urine were sampled at various time points pre- and postsurgery. The primary outcome measure was the incidence of CSA-AKI, defined as the occurrence of AKI within 96hours after surgery. RESULTS: The incidence of CSA-AKI was significantly lower in the Dex group than in the NS group (18.26% vs 32.46%; P=.014). Substantial increases were found in estimated glomerular filtration rate value at T4-T6 (P<.05) and urine volume 24hours after surgery (P<.01). Marked decreases were found in serum creatinine level, blood glucose level at T1-T2 (P<.01), blood urea nitrogen level at T3-T6 (P<.01), free fatty acid level at T2-T3 (P<.01), and lactate level at T3-T4 (P<.01). CONCLUSIONS: Dex reduces CSA-AKI, potentially by regulating metabolic disorders and reducing oxidative stress.

Renal Rehabilitation: Present and Future Perspectives.

Chronic kidney disease (CKD) is a global health problem. In patients with CKD, exercise endurance is decreased, especially as renal dysfunction advances. This is due to the combined effects of protein-energy wasting, uremic acidosis, and inflammatory cachexia, which lead to sarcopenia and are aggravated by a sedentary lifestyle, resulting in a progressive downward spiral of deconditioning. Renal rehabilitation (RR) is a coordinated, multifaceted intervention designed to optimize a patient's physical, psychological, and social functioning, as well as to stabilize, slow, or even reverse the progression of renal deterioration, improving exercise tolerance and preventing the onset and worsening of heart failure, thereby reducing morbidity and mortality. This review focused on the history and benefits of RR in patients with CKD. Based on current evidence, RR is an effective, feasible, and safe secondary prevention strategy in CKD. RR is a promising model for a new field of rehabilitation. Therefore, efforts to increase RR implementation rates are urgently needed.

Protective Effects of Bombyx batryticatus Protein-Rich Extract Against Cisplatin-Induced Nephrotoxicity in HEK293 Cells and a Mouse Model.

Cisplatin, a potent and prominent chemotherapeutic drug, has considerable side effects, including nephrotoxicity, which limits its therapeutic application and efficacy. Therefore, the development of agents that protect normal cells while preserving cisplatin's chemotherapeutic properties is of utmost importance. This study aimed to explore the protective effects of Bombyx batryticatus protein-rich extract (BBPE) against cisplatin-induced nephrotoxicity in a cisplatin-treated mouse model and human embryonic kidney (HEK293) cells. Apoptosis was assessed in HEK293 cells to determine the cytoprotective effects of BBPE and its effects on the generation of cisplatin-induced reactive oxygen species (ROS) and mitochondrial transmembrane potential (MTP) collapse. Although cisplatin induced nephrotoxicity in HEK293 cells, pretreatment with BBPE showed significant protective effects against cisplatin-induced nephrotoxicity by regulating the expression levels of pro- and antiapoptotic proteins. The cytoprotective effects of BBPE were mediated by decreased ROS production and MTP loss in cisplatin-treated HEK293 cells. The in vitro results were confirmed in the cisplatin-treated mouse model. Pretreatment with BBPE protected against cisplatin-induced nephrotoxicity by restoring malondialdehyde, superoxide dismutase, and catalase levels in kidney tissue and blood urea nitrogen and creatinine serum levels. Furthermore, histopathological assessment and terminal dUTP nick end-labeling staining showed that BBPE mitigated cisplatin-induced nephrotoxicity in kidney tissues. Overall, BBPE may act as a potent agent for alleviating cisplatin-induced nephrotoxicity, thereby increasing the safety of cisplatin-based chemotherapy.

Dimeric N-Acetyldopamine Derivatives Featuring a Seco-Benzene System from the Insects Aspongopus chinensis and Periostracum cicadae.

Aspongamide F (1), a novel N-acetyldopamine (NADA) dimer possessing a 6/6/6 ring system, and (±)-aspongamides G (2) and H (3), rare NADA derivatives with fragmented benzene rings, were isolated from Aspongopus chinensis. (±)-Cicadamides C (4) and D (5), the first 1,4-Benzodioxane NADA dimers featuring a seco-benzene system, and (±)-cicadamides E (6) and F (7), the NADA dimers derivatives, were isolated from Periostracum cicadae. The structures of all compounds were elucidated by spectroscopic analyses and computational methods. A plausible biosynthetic pathway for compounds 1-5 was proposed. The biological assay revealed that (+)-4 and (-)-4 exhibit renal protection in a dose-dependent manner.

Novel spirooxindole alkaloid derivatives from the medicinal insect Blaps japanensis and their biological evaluation.

Blapspirooxindoles A-C (1-3), three novel spirooxindole alkaloids with a unique spiro[chromane-4,3'-indoline]-2,2'-dione motif, blapcumaranons A and B (4 and 5), two new 2-cumaranon derivatives, blapoxindoles A-J (6-15), ten new oxindole alkaloid derivatives, along with one known compound (16), were isolated from the whole bodies of Blaps japanensis. Their structures including absolute configurations were determined by using spectroscopic, X-ray crystallographic, and computational methods. Compounds 1-11 and 13 exist as racemic mixtures in nature, and their (-)- and (+)-antipodes were separated by chiral HPLC. Biological evaluations of these compounds were determined with multiple assays including anti-tumor, anti-inflammatory, and renal protection activities in vitro. Several compounds displayed effective activity in one or more assays.

Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease.

Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, emerging as novel hypoglycemic agents, have demonstrated significant cardiorenal protective effects in patients with DKD. Initially, it was believed that the efficacy of SGLT-2 inhibitors declined as the estimated glomerular filtration rate (eGFR) decreased, which led to their preferential use in DKD patients at G1-G3 stages. However, recent findings from the DAPA-CKD and EMPA-KIDNEY studies have revealed equally beneficial cardiorenal effects of SGLT-2 inhibitors in individuals at stage G4 DKD, although the underlying mechanism behind this phenomenon remains unclear. In this comprehensive analysis, we provide a systematic review of the mechanisms and functioning of SGLT-2 inhibitors, potential renal protection mechanisms, and the therapeutic efficacy and safety of SGLT-2 inhibitors in kidney diseases, with a particular focus on stage G4 DKD. Gaining a deeper understanding of the renal protective effect of SGLT-2 inhibitors and their underlying mechanisms is highly significance for the successful utilization of these inhibitors in the treatment of diverse kidney disorders.

New Insights into the Nephroprotective Potential of Lercanidipine.

Kidneys are responsible for many crucial biological processes in the human body, including maintaining the water-electrolyte balance, pH, and blood pressure (BP), along with the elimination of toxins. Despite this, chronic kidney disease (CKD), which affects more and more people, is a disease that develops insidiously without causing any symptoms at first. The main purpose of this article is to summarize the existing literature on lercanidipine, with a particular focus on its nephroprotective properties. Lercanidipine is a third-generation dihydropyridine (DHP) blocker of calcium channels, and as such it possesses unique qualities such as high lipophilicity and high vascular selectivity. Furthermore, it acts by reversibly inhibiting L-type and T-type calcium channels responsible for exerting positive renal effects. It has been shown to reduce tissue inflammation and tubulointerstitial fibrosis, contributing to a decrease in proteinuria. Moreover, it exhibited antioxidative effects and increased expression of molecules responsible for repairing damaged tissues. It also decreased cell proliferation, preventing thickening of the vascular lumen. This article summarizes studies simultaneously comparing the effect of lercanidipine with other antihypertensive drugs. There is still a lack of studies on the medications used in patients with CKD, and an even greater lack of studies on those used in patients with concomitant hypertension. Therefore, further studies on lercanidipine and its potential in hypertensive patients with coexisting CKD are required.

Renal Protection and Safety of Sodium-glucose Cotransporter-2 Inhibitors in Chronic Kidney Disease.

INTRODUCTION: Chronic kidney disease (CKD) has a clinical characteristic of progressive loss of kidney function and becomes a serious health and social concern. SGLT2i (sodium-glucose cotransporter 2 inhibitors), a class of anti-diabetic medications, are shown to reduce cardiovascular and renal events. This systematic review and meta-analysis aimed to assess whether SGLT2i could become a new treatment strategy for CKD for its renal protection and safety. METHODS: Based on predetermined criteria, a bibliographical search was performed on May 31, 2022, by searching the following databases: ISI Web of Science, Embase, PubMed, and the Cochrane Library. Statistical analysis was conducted to assess renal protection and safety of SGLT2i by using Cochrane Review Manager Version 5.3. RESULTS: Thirty randomised controlled trials fulfilled the inclusion criteria and were eligible for this meta-analysis. Our study found that the SGLT2i can sustainably reduce the urine albumin/creatinine ratio (UACR) at different time points and prevent the progression to macroalbuminuria. Before 24 weeks, SGLT2i can decrease the estimated glomerular filtration rate (eGFR) compared to the control group. Interestingly, after 24 weeks, SGLT2i can continuously maintain the increase in eGFR when compared with the control group. Furthermore, SGLT2i can reduce the event rates of incident or worsening nephropathy, a decline in estimated eGFR of ≥ 50%, doubling of serum creatinine level, acute renal failure and renal failure. Interestingly, the renoprotective effects of SGLT2i are independent of its glycemic effects. SGLT2i can reduce the morbidity rate of any related adverse events, any related severe adverse events and SGLT2i have not increased the event rates of urinary tract infection, bone fractures, amputation, and acute pancreatitis when compared with the control group. CONCLUSION: SGLT2i can protect renal function and are safe drug for CKD. SGLT2i are promising therapeutic agents for CKD patients.

Clerodendranthus spicatus inhibits epithelial-mesenchymal transition of renal tubular cells through the NF-κB/Snail signalling pathway in hyperuricaemia nephropathy.

CONTEXT: Clerodendranthus spicatus Thunb. (Labiatae) (CS), a perennial traditional Chinese medicinal herb that can reduce serum uric acid (sUA) levels and ameliorate renal function is widely used to treat hyperuricaemic nephropathy (HN). OBJECTIVE: To investigate the molecular mechanism of action of CS in HN treatment using in vivo and in vitro experiments. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into control, HN, CS and positive control allopurinol groups. The HN group was intraperitoneally injected with 750 mg/kg oxonic acid potassium (OA), whereas the CS group was injected with OA along with a gavage of CS (low dose 3.125 g/kg, high dose 6.25 g/kg) for five weeks. For in vitro studies, uric acid-treated HK2 cells were used to verify the therapeutic mechanism of CS in HN. RESULTS: HN rats exhibit pathological phenotypes of elevated sUA levels and renal injury. CS significantly improved these symptoms and sUA (p < 0.05) and blood urea nitrogen (p < 0.01) levels, and dramatically improved renal tubular injury in HN rats. The IC50 value of UA (uric acid) in HK2 cells was 826.32 ± 3.55 µg/mL; however, 120 ng/mL CS had no significant cytotoxicity on HK2 cells. In vivo and in vitro studies showed that CS inhibited NF-κB phosphorylation and inhibited α-smooth muscle actin (α-SMA) and vimentin expression while increasing E-cadherin expression, suggesting that CS inhibited the fibrotic process in renal cells, thus protecting renal function. DISCUSSION AND CONCLUSIONS: These findings provide a fundamental understanding of the application of CS in HN treatment to better guide clinical interventions.