BACKGROUND AND OBJECTIVE

Gastrointestinal (GI) manifestations among COVID-19 patients are common; however, their relation with patient outcomes remains unclear. The study, therefore, aims to determine the association of GI manifestation with in-hospital mortality among end-stage renal disease patients (ESRD).

This is a retrospective cohort design. All 501 ESRD patients with COVID-19 and admitted to the National Kidney and Transplant Institute from June 2020 to 2021 were included. GI manifestation was defined as the presence of any of the following signs and symptoms on admission: dysgeusia, anorexia, abdominal pain, nausea, vomiting, diarrhea, and jaundice. The outcome of interest was in-hospital mortality, defined as death due to any cause during hospital stay. Stata17 was used for data analysis.

The overall prevalence of GI manifestation was 58.08% (95% CI: 53.63-62.45). The most common symptoms were abdominal pain (27.15%), loss of appetite (24.35%), and nausea (19.76%). Patients with GI manifestation had a higher proportion of stroke, lower median systolic blood pressure, and a lower proportion of abnormal oxygen saturation and diastolic blood pressure than those without GI manifestation. Across all clinical outcomes, only hospital stay significantly differ between those with and without GI manifestation. In-hospital mortality was 31.14% (95% CI: 27.10-35.39%) and showed no significant association with GI manifestation (OR= 0.94, p=0.749).

GI manifestation was common among ESRD patients with moderate-to-severe COVID-19. The inhospital mortality rate is also high; however, GI manifestation was not associated with this outcome. Meanwhile, GI manifestation leads to longer hospital stay.

OBJECTIVE: To observe the clinical efficacy of heat-sensitive moxibustion combined with western medication for preconception intervention in prethrombotic state of recurrent spontaneous abortion (RSA) with kidney deficiency and blood stasis. METHODS: A total of 100 RSA patients of prethrombotic state with kidney deficiency and blood stasis were randomized into a combination group (50 cases, 5 cases were eliminated) and a medication group (50 cases, 5 cases were eliminated). In the medication group, the aspirin enteric-coated tablet was given orally at a dose of 75 mg a time, once daily. On the basis of the treatment in the medication group, in the combination group, heat-sensitive moxibustion was applied at the heat-sensitive points selected among the areas of Guanyuan (CV4), Shenque (CV8), and bilateral Sanyinjiao (SP6), Zusanli (ST36), Qihai (CV6), Taixi (KI3), Zigong (EX-CA1), Luanchao (Extra), Xuehai (SP10), and Yinlingquan (SP9), about 40 min a time, once every two days. Both groups were treated for 3 menstrual cycles continuously. Pregnancy success rate of 12 weeks was recorded in the two groups in follow-up of 3 months after treatment completion, during which conception was tried under the guidance of doctor. The TCM symptom score was observed and the coagulation-fibrinolysis indexes (activated partial thromboplastin time [APTT], prothrombin time [PT], platelet count [PLT], D-dimer [D-D], fibrinogen [FIB], protein S [PS], protein C [PC] and antithrombin Ⅲ [AT-Ⅲ]) were detected before and after treatment in the two groups. RESULTS: The pregnancy success rate of 12 weeks was 80.0% (32/40) in the combination group, which was higher than 54.3% (19/35) in the medication group (P<0.05). After treatment, the TCM symptom scores were decreased compared with those before treatment in the two groups (P<0.05), and the TCM symptom score in the combination group was lower than that in the medication group (P<0.05). Compared before treatment, the APTT and PT was prolonged (P<0.05), the levels of PLT, FIB and D-D were reduced (P<0.05), the activity of AT-Ⅲ, PS and PC was increased (P<0.05) after treatment in the two groups. After treatment, in the combination group, the APTT was longer (P<0.05), the levels of PLT, FIB and D-D were lower (P<0.05), the activity of AT-Ⅲ, PS and PC was higher (P<0.05) than those in the medication group. CONCLUSION Heat-sensitive moxibustion combined with western medication can effectively improve the prethrombotic state and TCM clinical symptoms in RSA patients with kidney deficiency and blood stasis, enhance pregnancy success rate, its mechanism may be related to ameliorating hypercoagulability.
Humans ; Female ; Moxibustion ; Adult ; Pregnancy ; Abortion, Habitual/blood* ; Young Adult ; Combined Modality Therapy ; Kidney/drug effects* ; Acupuncture Points ; Aspirin/administration & dosage*

OBJECTIVE: To observe the clinical effect and safety of Jiuci renmai therapy (moxibustion and acupuncture on the conception vessel) combined with bladder function training in treatment of post-stroke neurogenic bladder (PSNB). METHODS: Sixty patients with PSNB were randomly divided into an observation group and a control group, 30 cases in each group. On the basis of conventional treatment with western medication, bladder function training was delivered in the control group, once a day for 4 weeks. In the observation group, Jiuci renmai therapy was supplemented besides the regimen as the control group. The main acupoints were Guanyuan (CV4), Zhongji (CV3), Qihai (CV6) and Qugu (CV2); and the supplementary acupoints were Henggu (KI11), Zhongwan (CV12), Xiawan (CV10) and Shuifen (CV9). Warm needling and moxibustion were operated, once every other day, for 4 weeks. Separately, before treatment and in 2 and 4 weeks of treatment, the urodynamic parameters were detected in the two groups, including maximal urine flow rate (Qmax), maximal detrusor pressure (PdetQmax), residual urine volume (RUV), maximal bladder capacity in the filling phase (MCC), and maximal intravesical pressure in the voiding phase (Pvesmax); the voiding parameters (the average daily number of micturition, urinary leakage episodes, and single voiding volume) were recorded; neurogenic bladder symptom score (NBSS), lower urinary tract symptom score (LUTS) and the score of quality of life scale for incontinence of urine (I-QoL) were evaluated, as well as the clinical effect and safety in the two groups. RESULTS: In 2 and 4 weeks of treatment, Qmax, PdetQmax, MCC, Pvesmax, and average daily single voiding volume were increased compared with the levels before treatment in each group (P<0.05), and the above indexes in the observation group were higher than those of the control group (P<0.05). RUV, the average daily number of micturition, urinary leakage episode, NBSS and LUTS scores of the two groups were reduced in comparison with those before treatment (P<0.05 ), and these indexes in the observation group were lower than those of the control group (P<0.05). In 4 weeks of treatment, the average urinary leakage episode was reduced largely in comparison with the control group (P<0.05); and the improvement in RUV for the patients with retention of urine in the observation group was superior to the control group (P<0.05). In 4 weeks of treatment, the score of each dimension in I-QoL and the total score were elevated compared with those before treatment in the two groups (P<0.05), and the scores in the observation were higher when compared with the control group (P<0.05). The total effective rate in the observation group was 90.0% (27/30) which was higher than 70.0% (21/30) of the control group (P<0.05). The incidence of adverse reactions was 3.3% (1/30) in the observation group, which was not significantly different from that in the control group [10.0% (3/30), P>0.05]. CONCLUSION The combination of Jiuci renmai therapy and bladder function training can effectively alleviate clinical symptoms, recover bladder voiding function, and improve the quality of life in the patients with PSNB, presenting the favorable safety profile in treatment.
Humans ; Female ; Male ; Middle Aged ; Urinary Bladder, Neurogenic/etiology* ; Urinary Bladder/physiopathology* ; Adult ; Aged ; Stroke/complications* ; Acupuncture Therapy ; Acupuncture Points ; Treatment Outcome ; Combined Modality Therapy ; Moxibustion

OBJECTIVE: To compare the clinical efficacy of herbal cake-separated moxibustion at Baliao acupoints combined with western medication versus western medication alone in treating erectile dysfunction (ED) with kidney deficiency and blood stasis. METHODS: A total of 108 ED patients were randomly divided into a combination group (54 cases, 2 cases dropped out) and a western medication group (54 cases, 1 case was eliminated, 2 cases dropped out). The western medication group received oral tadalafil tablets 5 mg a time, once daily. The combination group received additional herbal cake-separated moxibustion at Baliao acupoints (Shangliao [BL31], Ciliao [BL32], Zhongliao [BL33], Xialiao [BL34]) twice weekly (administered on Tuesdays and Fridays). Both groups were treated for 4 weeks. The 5-question international index of erectile function (IIEF-5) score, erectile hardness assessment (EHS) score, TCM syndrome score, serum sex hormone levels (follicle-stimulating hormone [FSH], luteinizing hormone [LH], prolactin [PRL], testosterone [T]), penile hemodynamic parameters [peak systolic velocity (PSV) of penile cavernosal artery, end-diastolic velocity (EDV), resistance index (RI)] were compared before and after treatment between the two groups, and the safety and clinical efficacy were evaluated. RESULTS: After treatment, the IIEF-5 scores, EHS scores, serum T levels, PSV and RI of penile cavernosal artery were increased compared with those before treatment in the two groups (P<0.05). Except for RI, the combination group exhibited significantly higher improvements in the above indexes than those in the western medication group (P<0.05). After treatment, the TCM syndrome scores, the serum FSH, LH levels, and EDV in the two groups and the serum PRL level in the combination group were decreased compared with those before treatment (P<0.05), while the above indexes in the combination group were lower than those in the western medication group (P<0.05). The total effective rate of the combination group was 88.5% (46/52), which was superior to 72.5% (37/51) in the western medication group (P<0.05). No significant adverse reactions occurred in either group. CONCLUSION Herbal cake-separated moxibustion at Baliao acupoints combined with western medicine can regulate sex hormone levels, improve penile blood supply, enhance erectile function and hardness, and is superior to western medication alone, with no observed adverse reactions.
Humans ; Male ; Moxibustion ; Erectile Dysfunction/drug therapy* ; Middle Aged ; Adult ; Acupuncture Points ; Drugs, Chinese Herbal/administration & dosage* ; Kidney/physiopathology* ; Aged ; Follicle Stimulating Hormone/blood* ; Luteinizing Hormone/blood* ; Treatment Outcome

OBJECTIVE: To observe the effects of acupuncture on podocyte autophagy and long non-coding RNA SOX2 overlapping transcript (LncRNA SOX2OT)/mammalian target of rapamycin C1 (mTORC1)/Unc-51-like kinase 1 (ULK1) pathway in rats with diabetic kidney disease (DKD), and to explore the mechanism by which acupuncture reduces urinary protein. METHODS: A total of 40 SPF-grade male Sprague-Dawley rats were randomly divided into a control group (n=10) and a modeling group (n=30). The DKD model was established by feeding a high-fat, high-sugar diet combined with intraperitoneal injection of streptozotocin (STZ) in the modeling group. Twenty rats with successful DKD model were randomly divided into a model group (n=10) and an acupuncture group (n=10). The acupuncture group received "spleen and stomach-regulating" acupuncture at bilateral "Zusanli" (ST36), "Fenglong" (ST40), "Yinlingquan" (SP9), and "Zhongwan" (CV12), 30 min per session, once daily, five times per week, for four weeks. The general condition, fasting blood glucose (FBG), 2-hour postprandial glucose (2hPG), serum creatinine (SCr), blood urea nitrogen (BUN), 24-hour urinary protein quantification, and urine albumin-to-creatinine ratio (UACR) were compared before and after the intervention. After intervention, urinary podocyte injury marker SPON2 was measured by ELISA. Podocyte autophagosomes and glomerular basement membrane ultrastructure in renal tissue were observed via transmission electron microscopy. Podocyte apoptosis was assessed by TUNEL staining. The protein expression of microtubule-associated protein 1 light chain 3Ⅱ (LC3-Ⅱ), mTORC1, ULK1, Beclin-1, and p62 in renal tissue was detected by Western blot. LncRNA SOX2OT expression in renal tissue was measured by real-time PCR. RESULTS: After the intervention, compared with the control group, the model group exhibited increased food and water intake, increased urine output, weight loss, and loose stools; compared with the model group, the food and water intake, urine volume, and loose stools were improved in the acupuncture group. Compared with the control group, FBG, 2hPG, SCr, BUN, 24-hour urinary protein quantification, UACR, and urinary SPON2 were all higher in the model group (P<0.01); compared with the model group, the FBG, 2hPG, SCr, BUN, 24-hour urinary protein quantification, UACR, and urinary SPON2 were all lower in the acupuncture group (P<0.01). Compared with the control group, the model group showed reduced podocyte autophagosomes and thickened glomerular basement membrane; compared with the model group, the acupuncture group had increased podocyte autophagosomes and less thickened basement membrane. Compared with the control group, the podocyte apoptosis index (AI) was higher in the model group (P<0.01); compared with the model group, the AI was lower in the acupuncture group (P<0.01). Compared with the control group, the expression of ULK1, Beclin-1, and LC3-Ⅱ proteins was lower, and the expression of mTORC1 and p62 proteins was higher in the model group (P<0.01). Compared with the model group, the expression of ULK1, Beclin-1, and LC3-Ⅱ proteins was higher, and the expression of mTORC1 and p62 proteins was lower in the acupuncture group (P<0.01). Compared with the control group, the LncRNA SOX2OT expression was lower in the model group (P<0.01). Compared with the model group, LncRNA SOX2OT expression was higher in the acupuncture group (P<0.01). CONCLUSION The "spleen and stomach-regulating" acupuncture method could improve renal function in DKD rats, reduce blood glucose and urinary protein excretion, alleviate podocyte injury, and enhance podocyte autophagy. The mechanism may be related to modulation of the renal LncRNA SOX2OT/mTORC1/ULK1 pathway.
Animals ; Podocytes/cytology* ; Diabetic Nephropathies/physiopathology* ; Rats, Sprague-Dawley ; Male ; Rats ; Mechanistic Target of Rapamycin Complex 1/genetics* ; Autophagy ; Acupuncture Therapy ; Autophagy-Related Protein-1 Homolog/genetics* ; RNA, Long Noncoding/metabolism* ; Humans ; Signal Transduction

OBJECTIVE: To observe the effect of governor vessel moxibustion on improving cardiopulmonary fitness in patients with stable chronic obstructive pulmonary disease (COPD) of qi deficiency of lung and kidney. METHODS: A total of 40 patients with stable COPD of qi deficiency of lung and kidney were randomized into an observation group (20 cases) and a control group (20 cases). The routine basic treatment and nursing were adopted in the control group. In the observation group, on the basis of the treatment in the control group, governor vessel moxibustion was applied at the area from Dazhui (GV14) to Yaoshu (GV2) of the governor vessel, 1 hour a time, once a week. Both groups were treated for 8 weeks consecutively. The maximal oxygen uptake (VO₂max), 6-minute walking test (6MWT) and Borg score, pulmonary function indexes (forced expiratory volume in 1 second [FEV₁], forced vital capacity [FVC] and ratio of FEV₁ and FVC [FEV₁/FVC]), chronic obstructive pulmonary disease assessment test (CAT) score, and TCM syndrome score were observed in the two groups before and after treatment respectively. RESULTS: After treatment, the VO₂max, 6MWT, FEV₁, FVC and FEV₁/FVC were increased compared with those before treatment in the two groups (P<0.001, P<0.05), the above indexes in the observation group were higher than those in the control group (P<0.05, P<0.01). After treatment, the Borg, CAT and TCM syndrome scores were decreased compared with those before treatment in the two groups (P<0.05, P<0.001), the above indexes in the observation group were lower than those in the control group (P<0.05). CONCLUSION Governor vessel moxibustion can effectively improve the cardiopulmonary fitness, clinical symptoms and the quality of life in patients with stable COPD of qi deficiency of lung and kidney.
Humans ; Moxibustion ; Pulmonary Disease, Chronic Obstructive/physiopathology* ; Male ; Female ; Middle Aged ; Aged ; Qi ; Lung/physiopathology* ; Kidney/physiopathology* ; Acupuncture Points

Acute kidney injury (AKI) is a common clinically critical syndrome in hospitalized patients with high morbidity and mortality. At present, the mechanism of AKI has not been fully elucidated, and no therapeutic drugs exist. As known, glycolytic product lactate is a key metabolite in physiological and pathological processes. The kidney is an important gluconeogenic organ, where lactate is the primary substrate of renal gluconeogenesis in physiological conditions. During AKI, altered glycolysis and gluconeogenesis in kidneys significantly disturb the lactate metabolic balance, which exert impacts on the severity and prognosis of AKI. Additionally, lactate-derived posttranslational modification, namely lactylation, is novel to AKI as it could regulate gene transcription of metabolic enzymes involved in glycolysis or Warburg effect. Protein lactylation widely exists in human tissues and may severely affect non-histone functions. Moreover, the strategies of intervening lactate metabolic pathways are expected to bring a new dawn for the treatment of AKI. This review focused on renal lactate metabolism, especially in proximal renal tubules after AKI, and updated recent advances of lactylation modification, which may help to explore potential therapeutic targets against AKI.
Humans ; Acute Kidney Injury/metabolism* ; Lactic Acid/metabolism* ; Animals ; Glycolysis/physiology* ; Gluconeogenesis/physiology* ; Kidney/metabolism*

BACKGROUND: Spatiotemporal disparities exist in the disease burden of non-communicable diseases (NCDs) attributable to kidney dysfunction, which has been poorly assessed. The present study aimed to evaluate the spatiotemporal trends of the global burden of NCDs attributable to kidney dysfunction and to predict future trends. METHODS: Data on NCDs attributable to kidney dysfunction, quantified using deaths and disability-adjusted life-years (DALYs), were extracted from the Global Burden of Diseases Injuries, and Risk Factors (GBD) Study in 2019. Estimated annual percentage change (EAPC) of age-standardized rate (ASR) was calculated with linear regression to assess the changing trend. Pearson's correlation analysis was used to determine the association between ASR and sociodemographic index (SDI) for 21 GBD regions. A Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2040. RESULTS: Between 1990 and 2019, the absolute number of deaths and DALYs from NCDs attributable to kidney dysfunction increased globally. The death cases increased from 1,571,720 (95% uncertainty interval [UI]: 1,344,420-1,805,598) in 1990 to 3,161,552 (95% UI: 2,723,363-3,623,814) in 2019 for both sexes combined. Both the ASR of death and DALYs increased in Andean Latin America, the Caribbean, Central Latin America, Southeast Asia, Oceania, and Southern Sub-Saharan Africa. In contrast, the age-standardized metrics decreased in the high-income Asia Pacific region. The relationship between SDI and ASR of death and DALYs was negatively correlated. The BAPC model indicated that there would be approximately 5,806,780 death cases and 119,013,659 DALY cases in 2040 that could be attributed to kidney dysfunction. Age-standardized death of cardiovascular diseases (CVDs) and CKD attributable to kidney dysfunction were predicted to decrease and increase from 2020 to 2040, respectively. CONCLUSION NCDs attributable to kidney dysfunction remain a major public health concern worldwide. Efforts are required to attenuate the death and disability burden, particularly in low and low-to-middle SDI regions.
Humans ; Noncommunicable Diseases/epidemiology* ; Global Burden of Disease ; Disability-Adjusted Life Years ; Male ; Female ; Risk Factors ; Middle Aged ; Kidney Diseases/epidemiology* ; Bayes Theorem ; Adult ; Aged ; Global Health ; Quality-Adjusted Life Years

BACKGROUND: Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq). METHODS: Eight-week-old male C57BL/6J mice were randomly allocated into three groups: control group ( n = 5), adenine and high-phosphate (HP) diet group ( n = 20), and the optimized adenine-containing diet group ( n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 ( Acer1 ), alkaline ceramidase 2 ( Acer2 ), prosaposin-like 1 ( Psapl1 ), adenosine A1 receptor ( Adora1 ), and sphingosine-1-phosphate receptor 5 ( S1pr5 ) were successfully validated in mouse femurs by qRT-PCR. CONCLUSIONS Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.
Animals ; Mice ; Chronic Kidney Disease-Mineral and Bone Disorder/genetics* ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Sphingolipids/metabolism* ; Transcriptome/genetics* ; Signal Transduction/genetics* ; X-Ray Microtomography ; Adenine

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged