Impact of atorvastatin reload on the prevention of contrast-induced nephropathy in patients on chronic statin therapy: A prospective randomized trial.

BACKGROUND: This trial aimed to assess the efficacy of Atorvastatin reloading on the prevention of Contrast-induced nephropathy (CIN) in patients pre-treated with this statin and undergoing coronary catheterization. METHODS: This was a prospective randomized controlled study including patients on chronic atorvastatin therapy. We randomly assigned the population to the Atorvastatin Reloading group (AR group), by reloading patients with 80 mg of atorvastatin one day before and three days after the coronary procedure, and the Non-Reloading group (NR group), including patients who received their usual dose without a reloading dose. The primary endpoints were the incidence of cystatin (Cys)-based CIN and Creatinine (Scr)-based CIN. The secondary endpoints consisted of the changes in renal biomarkers (Δ biomarkers) defined as the difference between the follow-up level and the baseline level. RESULTS: Our population was assigned to the AR group (n = 56 patients) and NR group (n = 54 patients). The baseline characteristics of the 2 groups were similar. Serum creatinine (SCr)-based CIN occurred in 11.1% in the NR group, and in 8.9% in the AR group without any significant difference. Cys-based CIN occurred in 37% in the NR group and 26.8% in the AR group without any significant difference. The subgroup analysis showed that high dose reloading had significantly reduced the CYC-based CIN risk in patients with type 2 diabetes (43.5% vs 18.8%, RR = 0.43. CI 95% [0.18-0.99])). The comparison of "Δ Cystatin" and Δ eGFR between the AR and NR groups didn't show any significant difference. However, cystatin C had significantly increased between baseline and at 24 hours in the NR group (0.96 vs 1.05, p = 0.001), but not in the AR group (0.94 vs 1.03, p = 0.206). CONCLUSIONS: Our study did not find a benefit of systematic atorvastatin reloading in patients on chronic atorvastatin therapy in preventing CIN. However, it suggested that this strategy could reduce the risk of CyC-based CIN in diabetic type 2 patients.

Myo-Inositol Attenuates Renal Interstitial Fibrosis in Obstructive Nephropathy by Inhibiting PI3K/AKT Activation.

Emerging evidence suggests that myo-inositol (MI) has a critical role in reducing renal inflammatory processes and improving podocyte function and preventing diabetes-related renal damage. We aimed to explore the function and underlying workings of MI in renal interstitial fibrosis (RIF). Based on a mouse model, we explored the effect of MI in unilateral ureteral obstruction (UUO) and in transforming growth factor-ß1 (TGF-ß1)-treated HK-2 cells. Pathological changes of the kidney tissues were examined following staining of the tissues with hematoxylin, eosin, and Masson's trichrome. The mRNA quantities of fibrosis markers, fibronectin, α-smooth muscle actin (α-SMA), and collagen I, were analyzed by means of real-time polymerase chain reaction, whereas those of protein levels were assessed with Western blotting. We also determined the expression of collagen I by immunofluorescence, and the levels of phosphorylated phosphotidylinositol-3-kinase and protein kinase B (PI3K/AKT) by Western blot. In vivo, histopathological examination in the UUO mice revealed renal tubular epithelial cell necrosis, inflammatory cell infiltration, and RIF. UUO mice showed higher expression levels of collagen I, fibronectin, α-SMA, pPI3K, and pAKT compared with sham-operated mice. However, MI treatment diminished the pathological alterations of RIF in UUO mice and downregulated the expression of fibrosis markers and phosphorylated PI3K/AKT. In vitro, TGF-ß1 positively influenced the propagation and differentiation of HK-2 cells and upregulated the levels of α-SMA, fibronectin, collagen I, pPI3K, and pAKT, but these became significantly reversed by MI treatment. In conclusion, MI ameliorates RIF, possibly by negatively regulating TGF-ß1-induced epithelial transdifferentiation and PI3K/AKT activation.

Tartary buckwheat flavonoids alleviates high-fat diet induced kidney fibrosis in mice by inhibiting MAPK and TGF-ß1/Smad signaling pathway.

Tartary buckwheat flavonoids (TBF) are active components extracted from Tartary buckwheat, which have abundant biological effects. According to this study, we investigated the effect of TBF on high-fat diet (HFD)-induced kidney fibrosis and its related mechanisms. In vivo, we established an HFD-induced kidney fibrosis model in mice and administered TBF. The results showed that TBF was able to alleviate kidney injury and inflammatory response. Subsequently, the mRNA levels between the HFD group and the TBF + HFD group were detected using RNA-seq assay. According to the gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) results, the differential genes were enriched in lipid metabolism and mitogen-activated protein kinases(MAPK) signaling pathways. We examined the protein expression of lipid metabolism-related pathways and the level of lipid metabolism. The results showed that TBF significantly activated the adenosine monophosphate activated protein kinase/acetyl-CoA carboxylase (AMPK/ACC) pathway and effectively reduced kidney total cholesterol (TC), triglyceride (TG) and low-density lipoproteinc cholesterol (LDL-C) levels and increased high-density lipoprotein cholesterol (HDL-C) levels in mice. TBF also inhibited transforming growth factor-ß1/Smad (TGF-ß1/Smad) and MAPK signaling pathways, thus slowing down the kidney fibrosis process. In vitro, using palmitic acid (PA) to stimulate TCMK-1 cells, the in vivo results similarly demonstrated that TBF could alleviate kidney fibrosis in HFD mice by inhibiting TGF1/Smad signaling pathway and MAPK signaling pathway.

Mechanism of dioscin ameliorating renal fibrosis through NF­κB signaling pathway­mediated inflammatory response.

Dioscin (DIS) is a natural compound derived from Chinese herbal medicine. In recent years, multiple studies have reported that DIS has immunoregulation, anti­fibrosis, anti­inflammation, anti­viral and anti­tumor effects. However, the mechanism by which DIS ameliorates renal fibrosis and inflammation remains to be elucidated. The aim of the present study was to investigate the role of DIS in renal fibrosis and inflammation and to explore its underlying mechanism. It used network pharmacology to predict the targets of DIS for the treatment of renal interstitial fibrosis. The present study was performed using unilateral ureteral obstruction mice and HK­2 cells in vivo and in vitro. The mice were treated with different doses of DIS. Kidney tissues were collected for histopathology staining, western blotting, immunohistochemistry staining and reverse transcription­quantitative (RT­q) PCR. TGF­ß1 (2 ng/ml) was used to induce renal fibrosis in the cells. Then, cells were respectively treated with DIS (3.125, 6.25, 12.5 µM) and Bay11­7082 (an inhibitor of NF­κB p65 nuclear transcription, 1 µM) for another 24 h. The expressions of inflammatory factors and NF­κB pathway proteins were detected by immunofluorescence, ELISA, western blotting and RT­qPCR. DIS alleviated renal injury in the UUO mice. Mechanistically, DIS not only decreased the expressions of inflammatory factors including IL­1ß, NOD­like receptor thermal protein domain associated protein 3, monocyte chemotactic protein 1, IL­6, TNF­α and IL­18 but also reduced the level of phosphorylation of NF­κB p65 in vivo and in vitro, which was similar to the impact of Bay11­7082. DIS ameliorated renal fibrosis by inhibiting the NF­κB signaling pathway­mediated inflammatory response, which may be a therapeutic pathway for delaying chronic kidney disease.

Potassium and the kidney: a reciprocal relationship with clinical relevance.

By controlling urinary potassium excretion, the kidneys play a key role in maintaining whole-body potassium homeostasis. Conversely, low urinary potassium excretion (as a proxy for insufficient dietary intake) is increasingly recognized as a risk factor for the progression of kidney disease. Thus, there is a reciprocal relationship between potassium and the kidney: the kidney regulates potassium balance but potassium also affects kidney function. This review explores this relationship by discussing new insights into kidney potassium handling derived from recently characterized tubulopathies and studies on sexual dimorphism. These insights reveal a central but non-exclusive role for the distal convoluted tubule in sensing potassium and subsequently modifying the activity of the sodium-chloride cotransporter. This is another example of reciprocity: activation of the sodium-chloride cotransporter not only reduces distal sodium delivery and therefore potassium secretion but also increases salt sensitivity. This mechanism helps explain the well-known relationship between dietary potassium and blood pressure. Remarkably, in children, blood pressure is related to dietary potassium but not sodium intake. To explore how potassium deficiency can cause kidney injury, we review the mechanisms of hypokalemic nephropathy and discuss if these mechanisms may explain the association between low dietary potassium intake and adverse kidney outcomes. We discuss if potassium should be repleted in patients with kidney disease and what role dietary potassium plays in the risk of hyperkalemia. Supported by data and physiology, we reach the conclusion that we should view potassium not only as a potentially dangerous cation but also as a companion in the battle against kidney disease.

Inflammatory Burden and Immunomodulative Therapeutics of Cardiovascular Diseases.

Phenotyping cardiovascular illness and recognising heterogeneities within are pivotal in the contemporary era. Besides traditional risk factors, accumulated evidence suggested that a high inflammatory burden has emerged as a key characteristic modulating both the pathogenesis and progression of cardiovascular diseases, inclusive of atherosclerosis and myocardial infarction. To mechanistically elucidate the correlation, signalling pathways downstream to Toll-like receptors, nucleotide oligomerisation domain-like receptors, interleukins, tumour necrosis factor, and corresponding cytokines were raised as central mechanisms exerting the effect of inflammation. Other remarkable adjuvant factors include oxidative stress and secondary ferroptosis. These molecular discoveries have propelled pharmaceutical advancements. Statin was suggested to confer cardiovascular benefits not only by lowering cholesterol levels but also by attenuating inflammation. Colchicine was repurposed as an immunomodulator co-administered with coronary intervention. Novel interleukin-1ß and -6 antagonists exhibited promising cardiac benefits in the recent trials as well. Moreover, manipulation of gut microbiota and associated metabolites was addressed to antagonise inflammation-related cardiovascular pathophysiology. The gut-cardio-renal axis was therein established to explain the mutual interrelationship. As for future perspectives, artificial intelligence in conjunction with machine learning could better elucidate the sequencing of the microbiome and data mining. Comprehensively understanding the interplay between the gut microbiome and its cardiovascular impact will help identify future therapeutic targets, affording holistic care for patients with cardiovascular diseases.

Mesenchymal Stem Cell-Derived Extracellular Vesicles to the Rescue of Renal Injury.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are rising in global prevalence and cause significant morbidity for patients. Current treatments are limited to slowing instead of stabilising or reversing disease progression. In this review, we describe mesenchymal stem cells (MSCs) and their constituents, extracellular vesicles (EVs) as being a novel therapeutic for CKD. MSC-derived EVs (MSC-EVs) are membrane-enclosed particles, including exosomes, which carry genetic information that mimics the phenotype of their cell of origin. MSC-EVs deliver their cargo of mRNA, miRNA, cytokines, and growth factors to target cells as a form of paracrine communication. This genetically reprograms pathophysiological pathways, which are upregulated in renal failure. Since the method of exosome preparation significantly affects the quality and function of MSC-exosomes, this review compares the methodologies for isolating exosomes from MSCs and their role in tissue regeneration. More specifically, it summarises the therapeutic efficacy of MSC-EVs in 60 preclinical animal models of AKI and CKD and the cargo of biomolecules they deliver. MSC-EVs promote tubular proliferation and angiogenesis, and inhibit apoptosis, oxidative stress, inflammation, the epithelial-to-mesenchymal transition, and fibrosis, to alleviate AKI and CKD. By reprogramming these pathophysiological pathways, MSC-EVs can slow or even reverse the progression of AKI to CKD, and therefore offer potential to transform clinical practice.

Long-term administration of low-dose selenium nanoparticles with different sizes aggravated atherosclerotic lesions and exhibited toxicity in apolipoprotein E-deficient mice.

Exploration of long-term in vivo effects of nanomaterials, particularly those with potential biomedical applications, is quite important for better understanding and evaluating their biosafety. Selenium nanoparticles (SeNPs) has been considered as a good candidate in biomedical applications due to its high bioavailability, considerable biological activity, and low toxicity. However, its long-term biological effects and biosafety remain unknown. Our previous study demonstrated that 8-week supplementation with SeNPs (50 µg Se/kg/day) was safe and had an anti-atherosclerotic activity in apolipoprotein E-deficient (ApoE-/-) mice, a well-known animal model of atherosclerosis. As a chronic disease, atherosclerosis needs long-term drug therapy. The aim of this study is to investigate the long-term effects of SeNPs with different sizes on atherosclerotic lesions and their biosafety in ApoE-/- mice fed with a high fat diet. Unexpectedly, the results showed that 24-week administration of SeNPs even at a low dose (50 µg Se/kg/day) aggravated atherosclerotic lesions. Furthermore, SeNPs exacerbated oxidative stress by inhibiting the activities of antioxidant enzymes and the expression of antioxidant selenoenzymes. SeNPs also exacerbated hyperlipidaemia by inducing hepatic lipid metabolic disorder. In the meanwhile, SeNPs aggravated organ injury, especially liver and kidney injury. The above adverse effects of SeNPs were size dependent: SeNPs with the size of 40.4 nm showed the highest adverse effects among the SeNPs with three sizes (23.1 nm, 40.4 nm, and 86.8 nm). In conclusion, the present work shows that long-term administration of low-dose SeNPs aggravated atherosclerotic lesions by enhancing oxidative stress and hyperlipidaemia in ApoE-/- mice, indicative of cardiovascular toxicity. Moreover, long-term administration of SeNPs led to injury to liver and kidney. These results offer novel insights for better understanding the biosafety of SeNPs and other biomedical nanomaterials.

Curcumin modulates gut microbiota and improves renal function in rats with uric acid nephropathy.

It is well known that the progression of hyperuricemia disease often contributes to renal dysfunction. However, there have been few studies on uric acid nephropathy (UAN), especially its relationship with gut microbiota. UAN is usually accompanied by disordered intestinal flora, and damaged gut barrier, which are closely related to tubulointerstitial fibrosis, and systemic inflammation. In previous studies, it has been confirmed that curcumin could alleviate tubulointerstitial fibrosis, and improve renal function through its antioxidant, anti-apoptotic, and anti-inflammatory efficacies. However, the effects curcumin exerts on intestinal flora in uric acid nephropathy are still unknown. Therefore, we used next-generation sequencing technology to investigate the effects of curcumin on gut microbiota in a rat model of UAN induced by adenine and potassium oxonate, and rats were randomly divided into control, model or curcumin treatment groups. The results demonstrated that, compared to the model group, the treatment group showed decreased serum uric acid (156.80 ± 11.90 µmol/L vs. 325.60 ± 18.65 µmol/L, p < 0.001), serum creatinine (66.20 ± 11.88 µmol/L vs. 182.20 ± 8.87 µmol/L, p < 0.001) and BUN level (13.33 ± 3.16 mmol/L vs. 36.04 ± 6.60 mmol/L, p < 0.001). The treatment group also displayed attenuated renal pathological lesions and metabolic endotoxemia (25.60 ± 5.90 ng/mL vs. 38.40 ± 4.98 ng/mL, p < 0.01), and improved tightly linked proteins expression. Besides, curcumin altered the gut microbiota structure in UAN rats. More specifically, curcumin treatment protected against the overgrowth of opportunistic pathogens in UAN, including Escherichia-Shigella and Bacteroides, and increased the relative abundance of bacteria producing short-chain fatty acids (SCFAs), such as Lactobacillus and Ruminococcaceae. These results suggest that curcumin could modulate gut microbiota, fortify the intestinal barrier, attenuate metabolic endotoxemia, and consequently protect the renal function in UAN rats.

Anti-tumor NAMPT inhibitor, KPT-9274, mediates gender-dependent murine anemia and nephrotoxicity by regulating SIRT3-mediated SOD deacetylation.

KPT-9274 is a phase 1 first-in-class dual PAK4/NAMPT inhibitor for solid tumor and non-Hodgkin's lymphoma. It demonstrates pre-clinical efficacy toward a broad spectrum of acute myeloid leukemia (AML) subtypes by inhibiting NAMPT-dependent NAD+ production. NAMPT is the rate-limiting enzyme in the salvage metabolic pathway leading to NAD+ generation. Tumor cells which are deficient in de novo pathway enzyme NAPRT1 are addicted to NAMPT. In clinical trials, treatment with NAMPT inhibitors resulted in dose-limiting toxicities. In order to dissect the mechanism of toxicity, mice were treated with KPT-9274 and resulting toxicities were characterized histopathologically and biochemically. KPT-9274 treatment caused gender-dependent stomach and kidney injuries and anemia. Female mice treated with KPT-9274 had EPO deficiency and associated impaired erythropoiesis. KPT-9274 treatment suppressed SIRT3 expression and concomitantly upregulated acetyl-manganese superoxide dismutase (MnSOD) in IMCD3 cells, providing a mechanistic basis for observed kidney toxicity. Importantly, niacin supplementation mitigated KPT-9274-caused kidney injury and EPO deficiency without affecting its efficacy. Altogether, our study delineated the mechanism of KPT-9274-mediated toxicity and sheds light onto developing strategies to improve the tolerability of this important anti-AML inhibitor.

Kidney Allograft Fibrosis: Diagnostic and Therapeutic Strategies.

Interstitial fibrosis with tubule atrophy (IF/TA) is the response to virtually any sustained kidney injury and correlates inversely with kidney function and allograft survival. IF/TA is driven by various pathways that include hypoxia, renin-angiotensin-aldosterone system, transforming growth factor-ß signaling, cellular rejection, inflammation, and others. In this review, we will focus on key pathways in the progress of renal fibrosis, diagnosis and therapy of allograft fibrosis. This review discusses the role and origin of myofibroblasts as matrix producing cells and therapeutic targets in renal fibrosis with a particular focus on renal allografts. We summarize current trends to use multiomic approaches to identify new biomarkers for IF/TA detection and to predict allograft survival. Furthermore, we review current imaging strategies that might help to identify and follow-up IF/TA complementary or as alternative to invasive biopsies. We further discuss current clinical trials and therapeutic strategies to treat kidney fibrosis.

Nephrotoxicity of Herbal Products in Europe-A Review of an Underestimated Problem.

Currently in Europe, despite the many advances in production technology of synthetic drugs, the interest in natural herbal medicines continues to increase. One of the reasons for their popular use is the assumption that natural equals safe. However, herbal medicines contain pharmacologically active ingredients, some of which have been associated with adverse effects. Kidneys are particularly susceptible to injury induced by toxins, including poisonous constituents from medicinal plants. The most recognized herb-induced kidney injury is aristolochic acid nephropathy connected with misuse of certain Traditional Chinese herbal medicines. Data concerning nephrotoxicity of plant species of European origin are scarce. Here, we critically review significant data of the nephrotoxicity of several plants used in European phytotherapy, including Artemisia herba-alba, Glycyrrhiza glabra, Euphorbia paralias, and Aloe). Causative mechanisms and factors predisposing to intoxications from the use of herbs are discussed. The basic intention of this review is to improve pharmacovigilance of herbal medicine, especially in patients with chronic kidney diseases.

Hempseed (Cannabis sativa) offers effective alternative over statins in ameliorating hypercholesterolemia associated nephropathy.

A direct link between hypercholesterolemia (HC) and renal pathologies has been established. Statins, the drugs of choice for HC management, have been associated with various side effects and toxicities, including nephropathy and other renal insults. Thus, natural dietary products based-alternative strategies for HC and associated pathologies are being considered. OBJECTIVES: Based on the unique nutritional composition and numerous health benefits of Hempseeds (Cannabis sativa), currently the potential anti-inflammatory and redox modulatory effects of hempseeds lipid extract (HEMP) against HC associated renal damage were evaluated and compared with statins (Simvastatin) in HFD induced experimental model of HC in rats. DESIGN & METHODS: The hempseed lipid fractions (HEMP) were prepared and their ameliorating effects on HFD induced lipid profiles, renal function markers (RFT), histopathological/morphological changes, renal oxidative stress, and inflammation markers were studied and compared with statins (HFD + STATINS). Further, HEMP-mediated modulation of lipid metabolism mediators (APO-B/E) was studied. RESULTS: Not only, HEMP administration improved the lipid profiles and morphological signs of HC, but it also was safe compared to Simvastatin in terms of hepatic and renal function markers. Further, changes in renal histoarchitecture, biochemical markers of oxidative stress, and expression profiles of lipid metabolism and inflammatory pathways (Cox-1/2, PGDS, PGES) revealed that HEMP positively modulating the redox homeostasis activated the resolution pathways against HC associated renal insults. CONCLUSION: The outcomes of the current study indicated HEMP's ameliorative and therapeutic potential against hypercholesterolemia-associated nephropathies and other systemic effects.

Omega-3 Fatty Acids Upregulate SIRT1/3, Activate PGC-1α via Deacetylation, and Induce Nrf1 Production in 5/6 Nephrectomy Rat Model.

Mitochondrial dysfunction contributes to the pathogenesis of kidney injury related with cardiovascular disease. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) protects renal tubular cells by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2). AMP-activated protein kinase (pAMPK)-mediated phosphorylation and sirtuin 1/3 (SIRT1/3)-mediated deacetylation are required for PGC-1α activation. In the present study, we aimed to investigate whether omega-3 fatty acids (FAs) regulate the expression of mediators of mitochondrial biogenesis in 5/6 nephrectomy (Nx) rats. Male Sprague-Dawley rats were assigned to the following groups: sham control, Nx, and Nx treated with omega-3 FA. The expression of PGC-1α, phosphorylated PGC-1α (pPGC-1α), acetylated PGC-1α, and factors related to mitochondrial biogenesis was examined through Western blot analysis. Compared to the control group, the expression of PGC-1α, pAMPK, SIRT1/3, Nrf1, mTOR, and Nrf2 was significantly downregulated, and that of Keap 1, acetylated PGC-1α, and FoxO1/3, was significantly upregulated in the Nx group. These changes in protein expression were rescued in the omega-3 FA group. However, the expression of pPGC-1α was similar among the three groups. Omega-3 FAs may involve mitochondrial biogenesis by upregulating Nrf1 and Nrf2. This protective mechanism might be attributed to the increased expression and deacetylation of PGC-1α, which was triggered by SIRT1/3.

Curcumin analogue C66 attenuates obesity-induced renal injury by inhibiting chronic inflammation.

Obesity has been recognized as a major risk factor for the development of chronic kidney disease, which is accompanied by increased renal inflammation, fibrosis, and apoptosis. C66 is a curcumin derivative that exerts anti-inflammatory effects by inhibiting the JNK pathway and prevents diabetic nephropathy. The present study investigates the possible protective effect of C66 on high-fat diet (HFD)-induced obesity-related glomerulopathy. Mice were fed with HFD for 8 weeks while some were treated with C66 every 2 days for 11 weeks. The HFD-fed mice developed renal dysfunction, as well as elevated triglyceride and cholesterol. Kidneys of the HFD-fed mice showed marked glomerular injuries, apoptosis, and inflammation with markedly increased cytokine production. Interestingly, treating HFD-fed mice with C66 remarkably reversed these pathological changes via inhibiting inflammation and NF-κB/JNK activation. In cultured mesangial cells, Palmitic Acid was able to activate the pro-fibrotic mechanisms, apoptosis, inflammatory response, and NF-κB and JNK signaling pathways, all of which could be attenuated by C66 treatment. In all, we demonstrated that curcumin analogue C66 attenuates obesity-induced renal injury by inhibiting chronic inflammation and apoptosis via targeting NF-κB and JNK. Our data suggest that C66 can be potentially used to prevent obesity-associated renal diseases warranting future investigations.

Hypouricaemic and nephroprotective effects of Poria cocos in hyperuricemic mice by up-regulating ATP-binding cassette super-family G member 2.

CONTEXT: Poria coco F.A.Wolf (Polyporaceae) dispels dampness and promotes diuresis implying hypouricaemic action. OBJECTIVE: To examine hypouricaemic action of Poria coco. MATERIALS AND METHODS: Ethanol extract (PCE) was prepared by extracting the sclerotium of P. cocos with ethanol, and the water extract (PCW) was produced by bathing the remains with water. PCE and PCW (50, 100 and 200 mg/kg, respectively) were orally administered to hyperuricemic Kunming mice (n = 8) to examine its hypouricaemic effect. Also, molecular docking was performed. RESULTS: P. cocos showed excellent hypouricaemic action, decreasing the serum uric acid of hyperuricaemia (HUA) control (526 ± 112 µmol/L) to 178 ± 53, 153 ± 57 and 151 ± 62 µmol/L (p < 0.01) by PCE and 69 ± 23, 63 ± 15 and 62 ± 20 µmol/L (p < 0.01) by PCW, respectively. According to SCrs, BUNs and H&E staining, PCE and PCW partially attenuated renal dysfunction caused by HUA. They presented no negative effects on ALT, AST and ALP activities. They elevated ABCG2 (ATP-binding cassette super-family G member 2) mRNA and protein expression in comparison to HUA control. In molecular docking, compound 267, 277, 13824, 15730 and 5759 were predicted as the top bioactives of P. cocos against HUA, which even presented better scores than the positive compound, oestrone 3-sulfate. DISCUSSION AND CONCLUSIONS: This paper demonstrated the hypouricaemic and nephroprotective effects of P. cocos in hyperuricemic mice by up-regulating ABCG2. These results may be useful for the development of a hypouricaemic agent.

Efficacy of Huanglian root decoction on kidney injury in rat's model of metabolic syndrome.

OBJECTIVE: To evaluate the efficacy of Huanglian root decoction (, HLD) on kidney injury in rat's model of metabolic syndrome (MetS), and investigate the possible mechanism. METHODS: A fructose-induced MetS rat model and human renal tubular epithelial cell-line model were used to compare the efficacy of HLD with that of berberine and tauroursodeoxycholic acid (TUDCA). Blood pressure, biochemical parameters, histopathological changes and the expression levels of oxidative stress markers were evaluated in the animal model at the end of an 8-week treatment regimen. Oxidative stress markers and molecules of the signal pathway of endoplasmic reticulum (ER) stress were evaluated in the human cell-line model. RESULTS: Levels of fasting insulin, systolic blood pressure and diastolic blood pressure were significantly decreased in rats in the Huanglian group compared to those in the MetS group (P < 0.05). Rats treated with HLD and TUDCA exhibited a significant reduction in blood levels of malondialdehyde compared to those in rats in the MetS group (P < 0.05). Significant increases in glutathione peroxidase in human tubular epithelial cells was found in the Huanglian group compared to that in the MetS group (14.02 vs 18.31, P < 0.05). The mRNA expression of protein kinase RNA-like endoplasmic reticulum kinase and eukaryotic translation initiation factor 2 α decreased significantly in Huanglian groups compared with that in the MetS group. CONCLUSION: HLD has therapeutic efficacy on kidney injury in the MetS rat's model, and is non-inferior to berberine and TUDCA.

Antiphospholipid antibody syndrome-associated renal thrombotic microangiopathy improved not with rivaroxaban but with warfarin in a systemic lupus erythematosus patient without lupus nephritis.

A 34-year-old Japanese woman with systemic lupus erythematosus (SLE) was admitted to our hospital for exacerbation of renal dysfunction, hemolytic anemia and thrombocytopenia. Twenty-two years before admission, she was diagnosed with SLE. Eight years before, lupus anticoagulant (LAC) positivity was detected without any thrombotic findings. Fourteen months before, renal function started to worsen. Three months before, unprovoked left leg swelling appeared. She was diagnosed with deep vein thrombosis (DVT) by ultrasonography. Blood examination revealed mild anemia, thrombocytopenia, and renal dysfunction. Rivaroxaban was started after which the left leg swelling subsided. When she was referred to our hospital, LAC was positive, but hypocomplementemia nor elevation of serum anti-double-stranded DNA antibodies was detected. Renal biopsy showed acute and chronic thrombotic microangiopathy (TMA) without concurrent lupus nephritis. Brain magnetic resonance imaging showed new small multiple cerebral infarcts. Antiphospholipid antibody syndrome (APS), causing renal TMA, new cerebral infarction, and DVT was diagnosed. Rivaroxaban was changed to warfarin. Two months after admission, renal impairment improved, and the complete disappearance of DVT and brain infarcts was confirmed. This case suggests that warfarin may be more effective than direct oral anticoagulants in the treatment of APS-associated renal TMA.

Whey protein supplementation and its potentially adverse effects on health: a systematic review.

Whey protein comprises soluble whey proteins and its benefits are well described in the literature. However, there are not many studies investigating the potential adverse effect of a diet with indiscriminate use of this supplement. The aim of this study was to perform a systematic review of papers that addressed this theme. A search was conducted in Medline, LILACS, TOXNET, Web of science, and Scopus electronic databases. In the end, 11 documents comprised this review. The majority of the papers associated the damaging effect with the chronic and abusive use of whey protein, with the kidneys and liver being the main organs affected. The other studies related whey protein to aggravation of aggression, presence of acne, and modification of the microbiota. Therefore, excessive consumption over a long period of protein supplementation may have some adverse effects on the body, which is aggravated when associated with sedentary lifestyle. PROSPERO registration no.: CRD42020140466. Novelty: A systematic review of experimental and randomized studies about the use of whey proteins supplements and its impact on physical health. Analysis revealed that chronic and without professional guidance use of whey protein supplementation may cause some adverse effects specially on kidney and liver function. Presented data support a need for future studies co-relating the use of different types of whey protein with and without exercise to better see the impact on human physical health.