The purpose of the present study was to determine the role of inositol 1,4,5-trisphosphate receptor 3 (IP₃R3) in renal cyst development in autosomal dominant polycystic kidney disease (ADPKD). 2-aminoethoxy-diphenyl borate (2-APB) and shRNA were used to suppress the expression of IP₃R3. The effect of IP₃R3 on cyst growth was investigated in Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney specific Pkd1 knockout (PKD) mouse model. The underlying mechanism of IP₃R3 in promoting renal cyst development was investigated by Western blot and immunofluorescence staining. The results showed that the expression level of IP₃R3 was significantly increased in the kidneys of PKD mice. Inhibiting IP₃R3 by 2-APB or shRNA significantly retarded cyst expansion in MDCK cyst model and embryonic kidney cyst model. Western blot and immunofluorescence staining results showed that hyperactivated cAMP-PKA signaling pathway in the growth process of ADPKD cyst promoted the expression of IP₃R3, which was accompanied by a subcellular redistribution process in which IP₃R3 was translocated from endoplasmic reticulum to intercellular junction. The abnormal expression and subcellular localization of IP₃R3 further promoted cyst epithelial cell proliferation by activating MAPK and mTOR signaling pathways and accelerating cell cycle. These results suggest that the expression and subcellular distribution of IP₃R3 are involved in promoting renal cyst development, which implies IP₃R3 as a potential therapeutic target of ADPKD.
Animals ; Dogs ; Mice ; Cysts/genetics* ; Inositol 1,4,5-Trisphosphate Receptors/pharmacology* ; Kidney/metabolism* ; Polycystic Kidney Diseases/metabolism* ; Polycystic Kidney, Autosomal Dominant/drug therapy* ; Madin Darby Canine Kidney Cells

OBJECTIVE: To observe the variability of hemoglobin (HB) level in patients with renal anemia, and to analyze its relationship with effect of repeated blood transfusion therapeutic in patients. METHODS: A retrospective cohort study and propensity score matching method were used, 60 patients with renal anemia who had effective treatment with repeated blood transfusion in Changzhou No.2 People's Hospital from May 2018 to May 2021 were retrospectively analyzed and set as the effective group; 153 patients with renal anemia who had ineffective treatment with repeated blood transfusion in the hospital in the same period were collected and set as the ineffective group, the propensity score matching method was used, the patients who were effective and ineffective in repeated blood transfusion were matched 1∶1 for analysis; the medical records and laboratory indexes of the two groups were checked; the Hb level of patients within 6 months (1/month) were recorded, the residual standard deviation (Res-SD) of Hb of patients was calculated according to the Hb level and evaluated the variability of Hb level; the relationship between HB variability level and therapeutic effect of repeated blood transfusion in patients with renal anemia was analyzed. RESULTS: After propensity score matching, there was no statistical significant difference between the two groups in terms of baseline data such as age, sex, dialysis age and BMI (P>0.05). The levels of serum albumin and transferrin of patients in the ineffective group were significantly lower than those of patients in the effective group (P<0.05); at 1 and 2 months of the observation period, there was no statistical significant difference in Hb levels of patients in both groups (P>0.05); the Hb level of patients in the ineffective group was significantly lower than that of patients in the effective group at 3, 5 and 6 months, and significantly higher than that of patients in the effective group at 4 months (P<0.05); the Res-SD of male patients and female patients in the ineffective group were respectively significantly higher than that of male patients and female patients in the effective group (P<0.05). Logistic regression analysis results showed that high variability of Hb level (Res-SD) was a risk factor for the ineffective treatment of repeated blood transfusion in patients with renal anemia (OR>1, P<0.05); the decision curve results showed that, when the high-risk threshold was 0.0-1.0, Res-SD predicted the net benefit rates of male and female patients with renal anemia were greater than 0, which was clinically significant, the smaller the high-risk threshold in the above range, the greater the net benefit rate. CONCLUSION The therapeutic effect of repeated blood transfusion in patients with renal anemia may be related to the variability of Hb level.
Humans ; Male ; Female ; Retrospective Studies ; Hemoglobins/therapeutic use* ; Anemia/therapy* ; Chronic Disease ; Blood Transfusion ; Kidney Diseases

OBJECTIVE: To observe the therapeutic effect of governor vessel moxibustion combined with wenyang yiqi qiwei decoction on erectile dysfunction (ED) with spleen-kidney deficiency and to explore the possible mechanism. METHODS: A total of 130 ED patients with spleen-kidney deficiency were randomized into an observation group (65 cases, 2 cases dropped off) and a control group (65 cases, 3 cases dropped off). The control group was given wenyang yiqi qiwei decoction orally, one dose daily. On the basis of the treatment in the control group, governor vessel moxibustion was applied from Dazhui (GV 14) to Yaoshu (GV 2) in the observation group, 110 min a time, once a day. The treatment of 4 weeks was required in both groups. Before and after treatment, 5-question international index of erectile function (IIEF-5) score, erection quality scale (EQS) score, erectile hardness assessment (EHS) score, TCM syndrome score, serum testosterone (T) level and vascular endothelial function indexes (prostaglandin I2 [PGI2], endothelin-1 [ET-1] and nitric oxide [NO] levels) were observed respectively, and the clinical efficacy was evaluated in both groups. RESULTS: After treatment, the scores of IIEF-5, EQS, EHS and serum levels of T, PGI2, NO were increased compared before treatment (P<0.01), the TCM syndrome scores and serum ET-1 levels were decreased compared before treatment (P<0.01) in the two groups; the scores of IIEF-5, EQS, EHS and serum levels of T, PGI2, NO in the observation group were higher than those in the control group (P<0.01, P<0.05), the TCM syndrome score and serum ET-1 level were lower than those in the control group (P<0.01, P<0.05). The total effective rate was 88.9% (56/63) in the observation group, which was superior to 74.2% (46/62) in the control group (P<0.05). CONCLUSION Governor vessel moxibustion combined with wenyang yiqi qiwei decoction can improve the erectile function and increase the erection hardness and quality in ED patients with spleen-kidney deficiency, its mechanism may relate to improving serum T level and vascular endothelial function.
Humans ; Male ; Administration, Oral ; Drugs, Chinese Herbal/therapeutic use* ; Erectile Dysfunction/therapy* ; Kidney/pathology* ; Kidney Diseases/complications* ; Moxibustion ; Spleen/pathology* ; Splenic Diseases/complications* ; Testosterone/blood* ; Combined Modality Therapy

Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus (DM). Qianjin Wenwu decoction (QWD), a well-known traditional Korean medicine, has been used for the treatment of DKD, with satisfactory therapeutic effects. This study was designed to investigate the active components and mechanisms of action of QWD in the treatment of DKD. The results demonstrated that a total of 13 active components in five types were found in QWD, including flavonoids, flavonoid glycosides, phenylpropionic acids, saponins, coumarins, and lignins. Two key proteins, TGF-β1 and TIMP-1, were identified as the target proteins through molecular docking. Furthermore, QWD significantly suppressed Scr and BUN levels which increased after unilateral ureteral obstruction (UUO). Hematoxylin & eosin (H&E) and Masson staining results demonstrated that QWD significantly alleviated renal interstitial fibrosis in UUO mice. We also found that QWD promoted ECM degradation by regulating MMP-9/TIMP-1 homeostasis to improve renal tubulointerstitial fibrosis and interfere with the expression and activity of TGF- β1 in DKD treatment. These findings explain the underlying mechanism of QWD for the treatment of DKD, and also provide methodological reference for investigating the mechanism of traditional medicine in the treatment of DKD.
Rats ; Mice ; Animals ; Ureteral Obstruction/metabolism* ; Kidney/metabolism* ; Tissue Inhibitor of Metalloproteinase-1/metabolism* ; Molecular Docking Simulation ; Rats, Sprague-Dawley ; Kidney Diseases/drug therapy* ; Extracellular Matrix/metabolism* ; Flavonoids/metabolism* ; Fibrosis

Extracellular vesicles (EVs) are lipid bilayer-enclosed structures containing diverse bioactive cargoes that play a major role in intercellular communication in both physiological and pathological conditions. Currently, the field of EV-based therapy has been rapidly growing, and two main therapeutic uses of EVs can be surmised: (i) exploiting stem cell-derived EVs as therapeutic agents; and (ii) employing EVs as natural therapeutic vectors for drug delivery. This review will discuss the recent advances in EV-based therapy in the treatment of renal disease.
Cell Communication ; Drug Delivery Systems ; Extracellular Vesicles ; Humans ; Kidney Diseases/therapy*

OBJECTIVE: To investigate the protective effects of Schisandra chinensis oil (SCEO) against aristolochic acid I (AA I)-induced nephrotoxicity in vivo and in vitro and elucidate the underlying mechanism. METHODS: C57BL/6 mice were randomly divided into 5 groups according to a random number table, including control group, AA I group, and AA I +SCEO (0.25, 0.5 and 1 g/kg) groups (n=5 per group). Pretreatment with SCEO was done for 2 days by oral administration, while the control and AA I groups were treated with sodium carboxymethyl cellulose. Mice of all groups except for the control group were injected intraperitoneally with AA I (5 mg/kg) from day 3 until day 7. Histopathological examination and apoptosis of kidney tissue were observed by hematoxylin and eosin and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatinine (SCr), as well as renal malondialdehyde (MDA), glutathione, r-glutamyl cysteingl+glycine (GSH), and superoxide dismutase (SOD) were analyzed using enzyme-linked immunosorbent assay (ELISA). Expressions of hepatic cytochrome P450 1A1 (CYP1A1), CYP1A2, and nad(p)hquinonedehydrogenase1 (NQO1) were analyzed using ELISA, quantitative real-time polymerase chain reaction (qPCR) and Western blot, respectively. In vitro, SCEO (40 µ g/mL) was added 12 h before treatment with AA I (40 µ mol/mL for 48 h) in human renal proximal tubule cell line (HK-2), then apoptosis and reactive oxygen species (ROS) were analyzed by flow cytometry. RESULTS: SCEO 0.5 and 1 g/kg ameliorated histopathological changes and TUNEL⁺ staining in the kidney tissues of mice with AA I-induced nephrotoxicity, and reduced serum levels of ALT, AST, BUN and SCr (P<0.01 or P<0.05). SCEO 0.5 and 1 g/kg alleviated the ROS generation in kidney, containing MDA, GSH and SOD (P<0.01 or P<0.05). SCEO 1 g/kg increased the expressions of CYP1A1 and CYP1A2 and decreased NQO1 level in the liver tissues (P<0.01 or P<0.05). Besides, in vitro studies also demonstrated that SCEO 40 µ g/mL inhibited apoptosis and ROS generation (P<0.05 or P<0.01). CONCLUSIONS SCEO can alleviate AA I-induced kidney damage both in vivo and in vitro. The protective mechanism may be closely related to the regulation of metabolic enzymes, thereby inhibiting apoptosis and ROS production.
Animals ; Apoptosis ; Aristolochic Acids/toxicity* ; Cytochrome P-450 CYP1A1/metabolism* ; Cytochrome P-450 CYP1A2/metabolism* ; Glutathione/metabolism* ; Kidney/drug effects* ; Kidney Diseases/drug therapy* ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Plant Oils/therapeutic use* ; Protective Agents/therapeutic use* ; Reactive Oxygen Species/metabolism* ; Schisandra ; Superoxide Dismutase/metabolism*

Objective: To explore the expulsion effect of sodium dimercaptopropanesulfonate (DMPS) on mercury in different organs of mercury poisoning and the therapeutic effect of glutathione (GSH) combined with antioxidant therapy on mercury poisoning. Methods: In February 2019, 50 SPF male SD rats were randomly divided into 5 groups, 10 rats in each group: A (saline negative control group) , B (HgCL2 positive control group) , treatment group (C: intramuscular injection of DMPS 15 mg/kg treatment, D: intramuscular injection of DMPS30 mg/kg treatment, E: intramuscular injection of DMPS 15 mg/kg and intraperitoneal injection of GSH200 mg/kg treatment) . Rats in group B, C, D and E were subcutaneously injected with mercury chloride solution (1 mg/kg) to establish a rat model of subacute mercury poisoning kidney injury. Rats in group A were subcutaneously injected with normal saline. After the establishment of the model, rats in the treatment group were injected with DMPS and GSH. Rats in group A and group B were injected with normal saline. At 21 d (treatment 7 d) and 28 d (treatment 14 d) after exposure, urine and blood samples of 5 rats in each group were collected. Blood biochemistry, urine mercury, urine microalbumin and mercury content in renal cortex, cerebral cortex and cerebellum were detected. Results: After exposure to mercury, the contents of mercury in renal cortex, cerebrum and cerebellum of rats in group B, C, D and E increased, and urine microalbumin increased. Pathology showed renal tubular injury and renal interstitial inflammation. Compared with group B, urinary mercury and renal cortex mercury in group C, D and E decreased rapidly after DMPS treatment, and there was no significant decrease in mercury levels in cerebellum and cerebral cortex of rats, accompanied by transient increase in urinary albumin after DMPS treatment (P<0.05) ; the renal interstitial inflammation in group E was improved after GSH treatment. There was a positive correlation between urinary mercury and the contents of mercury in renal cortex, cerebral cortex and cerebellum (r=0.61, 0.47, 0.48, P<0.05) . Conclusion: DMPS mercury expulsion treatment can significantly reduce the level of metal mercury in the kidney, and there is no significant change in the level of metal mercury in the cortex and cerebellum.
Animals ; Brain/drug effects* ; Glutathione ; Inflammation ; Kidney/drug effects* ; Kidney Diseases/chemically induced* ; Male ; Mercuric Chloride/therapeutic use* ; Mercury/urine* ; Mercury Poisoning/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Saline Solution/therapeutic use* ; Unithiol/therapeutic use*

OBJECTIVE: To study the efficacy and safety of continuous renal replacement therapy (CRRT) in the treatment of neonates with inherited metabolic diseases and hyperammonemia. METHODS: A retrospective analysis was performed on the medical records of neonates with inherited metabolic diseases and hyperammonemia who were hospitalized and underwent CRRT in the Department of Neonatology, Hunan Children's Hospital, from September 2016 to March 2020, including general conditions, clinical indices, laboratory markers, and adverse reactions. RESULTS: A total of 11 neonates were enrolled, with 7 boys (64%) and 4 girls (36%). The neonates had a mean gestational age of (38.9±0.8) weeks, a mean body weight of (3 091±266) g on admission, and an age of (5.7±2.0) days at the time of CRRT. The main clinical manifestations were vomiting (100%), convulsions (100%), and coma (55%), and the main primary disease was urea cycle disorder (55%). The mean duration of CRRT was (44±14) hours, the medium duration of coma before CRRT was 2 hours, and the total duration of coma was 10 hours. The patients had a mean hospital stay of (18±10) days and a survival rate of 73%, and 2 survivors had epilepsy. After treatment, all patients had significant reductions in blood ammonia, lactic acid, and K CONCLUSIONS CRRT is safe and effective in the treatment of neonates with inherited metabolic diseases and hyperammonemia.
Acute Kidney Injury ; Child ; Continuous Renal Replacement Therapy ; Female ; Humans ; Hyperammonemia/therapy* ; Infant ; Infant, Newborn ; Length of Stay ; Male ; Metabolic Diseases/therapy* ; Retrospective Studies

Blood Pressure ; Cardiovascular Diseases ; Cardiovascular System ; Humans ; Kidney Failure, Chronic/therapy* ; Renal Dialysis

Colchicine plays an important role in the treatment of gout and some other diseases. Besides gastrointestinal symptoms, myopathy has been reported as a rare side effect of colchicine in some patients. We report a case of myopathy in a patient with chronic kidney disease caused by high-dose colchicine, and then review literature on colchicine-induced myopathy, so as to provide some experience for the clinical diagnosis, treatment and medication safety. A 51-year-old male patient with 10 years of gout and 5 years of chronic kidney disease history and irregular treatment was admitted to the hospital with complaint of recurrent left wrist arthralgia and emerging lower extremities myalgia after intake of 40-50 mg colchicine in total within 20 days. Laboratory examinations showed significantly increased creatine kinase (CK) and then colchicine-induced myopathy was diagnosed preliminarily. After withdrawl of colchicine and implementation of hydration, alkalization and intramuscular injection of compound betamethasone, the symptoms of arthralgia and myalgia were relieved within 3 days and CK decreased to normal range gradually. According to literature reports, colchicine related myopathy was mostly characterized by proximal myasthenia and myalgia, accompanied by elevated CK level, which usually occurred days to weeks after initial administration of colchicine at the usual dosage in patients with renal impairment or a change in the underlying disease state in those receiving long-term therapy, and the features might remit within three to four weeks after the drug was discontinued. Electromyography of proximal muscles showed myopathy marked by abnormal spontaneous activity and muscle pathology waa marked by accumulation of lysosomes and autophagic vacuoles. Chronic kidney disease, liver cirrhosis, higher colchicine dose and concomitant cytochrome P450 3A4 (CYP3A4) inhibitors were associated with increased risk of myo-pathy. Based on the similar efficacy and lower adverse reaction rate compared with larger dosage, small dose of colchicine was recommended by many important current guidelines and recommendations in the treatment of gout. In consideration of potential risks, colchicine should be used with caution in patients with kidney or liver impairment, and in those taking CYP3A4 or P-glycoprotein inhibitors. For those patients, the drug dose should be adjusted and the latent adverse reactions should be monitored carefully.
Colchicine/adverse effects* ; Gout/drug therapy* ; Humans ; Kidney ; Male ; Middle Aged ; Muscular Diseases/chemically induced* ; Renal Insufficiency, Chronic/complications*