Chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor for neurotrophic keratopathy

Neurotrophic keratopathy is a persistent defect of the corneal epithelium,with or without stromal ulceration,due to corneal nerve deficiency caused by a variety of etiologies.The treatment options for neurotrophic keratopathy are limited.In this study,an ophthalmic solution was constructed from a chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor(CTH-mNGF).Its effectiveness was evaluated in corneal denervation(CD)mice and patients with neurotrophic keratopathy.In the preclinical setting,CTH-mNGF was assessed in a murine corneal denervation model.CTH-mNGF was transparent,thermosensitive,and ensured sustained release of mNGF for over 20 hours on the ocular surface,maintaining the local mNGF concentration around 1300 pg/mL in vivo.Corneal denervation mice treated with CTH-mNGF for 10 days showed a significant increase in corneal nerve area and total corneal nerve length compared with non-treated and CTH treated mice.A subsequent clinical trial of CTH-mNGF was conducted in patients with stage 2 or 3 neurotrophic keratopathy.Patients received topical CTH-mNGF twice daily for 8 weeks.Fluorescein sodium images,Schirmer’s test,intraocular pressure,Cochet-Bonnet corneal perception test,and best corrected visual acuity were evaluated.In total,six patients(total of seven eyes)diagnosed with neurotrophic keratopathy were enrolled.After 8 weeks of CTH-mNGF treatment,all participants showed a decreased area of corneal epithelial defect,as stained by fluorescence.Overall,six out of seven eyes had fluorescence staining scores<5.Moreover,best corrected visual acuity,intraocular pressure,Schirmer’s test and Cochet-Bonnet corneal perception test results showed no significant improvement.An increase in corneal nerve density was observed by in vivo confocal microscopy after 8 weeks of CTH-mNGF treatment in three out of seven eyes.This study demonstrates that CTH-mNGF is transparent,thermosensitive,and has sustained-release properties.Its effectiveness in healing corneal epithelial defects in all eyes with neurotrophic keratopathy suggests CTH-mNGF has promising application prospects in the treatment of neurotrophic keratopathy,being convenient and cost effective.

Functional gastrointestinal disorders,mental health,genetic susceptibility,and incident chronic kidney disease

Background:Whether functional gastrointestinal disorders(FGIDs)are associated with the long-term risk of chronic kidney disease(CKD)remains unclear.We aimed to investigate the prospective association of FGIDs with CKD and examine whether mental health mediated the association.Methods:About 416,258 participants without a prior CKD diagnosis enrolled in the UK Biobank between 2006 and 2010 were included.Participants with FGIDs(including irritable bowel syndrome[IBS],dyspepsia,and other functional intestinal disorders[FIDs;mainly composed of constipation])were the exposure group,and non-FGID participants were the non-exposure group.The primary outcome was incident CKD,ascertained from hospital admission and death registry records.A Cox proportional hazard regression model was used to investigate the association between FGIDs and CKD,and the mediation analysis was performed to investigate the mediation proportions of mental health.Results:At baseline,33,156(8.0%)participants were diagnosed with FGIDs,including 21,060(5.1%),8262(2.0%),and 6437(1.6%)cases of IBS,dyspepsia,and other FIDs,respectively.During a mean follow-up period of 12.1 years,11,001(2.6%)participants developed CKD.FGIDs were significantly associated with a higher risk of incident CKD compared to the absence of FGIDs(hazard ratio[HR],1.36;95%confidence interval[CI],1.28-1.44).Similar results were observed for IBS(HR,1.27;95%CI,1.17-1.38),dyspepsia(HR,1.30;95%CI,1.17-1.44),and other FIDs(HR,1.60;95%CI,1.43-1.79).Mediation analyses suggested that the mental health score significantly mediated 9.05%of the association of FGIDs with incident CKD and 5.63-13.97%of the associations of FGID subtypes with CKD.Specifically,the positive associations of FGIDs and FGID subtypes with CKD were more pronounced in participants with a high genetic risk of CKD.Conclusion:Participants with FGIDs had a higher risk of incident CKD,which was partly explained by mental health scores and was more pronounced in those with high genetic susceptibility to CKD.

Distribution of Traditional Chinese Medicine syndromes in diabetic kidney disease chronic kidney disease 1-5: a correlation study

OBJECTIVE: To analyze the distribution of Traditional Chinese medicine(TCM) syndromes in patients with diabetic kidney disease(DKD) and its related factors.METHODS: We enrolled 435 patients with DKD, who were not undergoing dialysis, admitted to the Department of Nephrology, First Medical Center, Chinese PLA General Hospital from April 2020 to August 2021.Analysis of their TCM syndromes and related factors was carried out.RESULTS: The 435 patients included 109, 117, 86, and 123 chronic kidney disease(CKD) 1-2, CKD3, CKD4, and CKD5 cases, respectively. With the progression of CKD1-5, the proportion of Yin deficiency and dry heat syndrome,and that of Qi and Yin deficiency syndrome showed a downward trend, whereas the proportion of spleen-kidney Yang deficiency, blood deficiency, blood stasis, water stagnation, and phlegm turbidity syndromes showed an upward trend;the differences were statistically significant(P < 0.05). Multivariate logistic regression analysis showed that Yin deficiency and dry heat syndrome was positively correlated with hemoglobin [odds ratio(OR) =1.022, P = 0.005], albumin(OR = 1.058, P = 0.006), and estimated glomerular filtration rate(eGFR)(OR = 1.020,P < 0.001) but negatively correlated with male sex(OR =0.277, P = 0.004). Qi and Yin deficiency syndrome was positively correlated with albumin(OR = 1.056, P < 0.001)and eGFR(OR = 1.008, P = 0.022) but negatively correlated with age(OR = 0.977, P = 0.023). Liver-kidney Yin deficiency syndrome was positively correlated with age(OR = 1.028, P = 0.021) and glycosylated hemoglobin(OR = 1.223, P = 0.007) but negatively correlated with total cholesterol(OR = 0.792, P = 0.006).Spleen-kidney Yang deficiency syndrome was negatively correlated with hemoglobin(OR = 0.977, P < 0.001),albumin(OR = 0.891, P < 0.001), and eGFR(OR = 0.978,P < 0.001) but positively correlated with high density lipoprotein(OR = 3.376, P = 0.001). CONCLUSION: With CKD1-5 progression, TCM syndromes changed from Yin deficiency and dry heat syndrome to syndrome of deficiency of both Qi and Yin, liver-kidney Yin, and spleen-kidney Yang deficiency syndromes. TCM syndromes were correlated with laboratory test results.

Blood pressure targets in patients with chronic kidney disease:Comments and controversies

According to the Global Burden of Disease Study 2017,there are 132 million patients with chronic kidney disease(CKD)in China,^([1])and the prevalence of hypertension in Chinese patients with CKD(67.3%)is significantly higher than that in the general population(23.2%).^([2,3])CKD is both a cause and a consequence of hypertension,and these two conditions form a vicious cycle that leads to the high prevalence rate of hypertension in patients with CKD.Uncontrolled hypertension accelerates the deterioration of renal function,which significantly increases the risk of developing end-stage renal disease(ESRD),as well as cardiovascular and cerebrovascular diseases,leading to poor patient outcomes.

J-shaped association between dietary thiamine intake and the risk of cognitive decline in cognitively healthy,older Chinese individuals

Background The prospective association of dietary thiamine intake with the risk of cognitive decline among the general older adults remains uncertain.Aims To investigate the association between dietary thiamine intake and cognitive decline in cognitively healthy,older Chinese individuals.Methods The study included a total of 3106 participants capable of completing repeated cognitive function tests.Dietary nutrient intake information was collected through 3-day dietary recalls and using a 3-day food-weighed method to assess cooking oil and condiment consumption.Cognitive decline was defined as the 5-year decline rate in global or composite cognitive scores based on a subset of items from the Telephone Interview for Cognitive Status-modified.Results The median follow-up duration was 5.9 years.There was a J-shaped relationship between dietary thiamine intake and the 5-year decline rate in global and composite cognitive scores,with an inflection point of 0.68 mg/day(95%confidence interval(Cl):0.56 to 0.80)and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.Before the inflection point,thiamine intake was not significantly associated with cognitive decline.Beyond the inflection point,each unit increase in thiamine intake(mg/day)was associated with a significant decrease of 4.24(95%Cl:2.22 to 6.27)points in the global score and 0.49(95%Cl:0.23 to 0.76)standard units in the composite score within 5 years.A stronger positive association between thiamine intake and cognitive decline was observed in those with hypertension,obesity and those who were non-smokers(all p<0.05).Conclusions This study revealed a J-shaped association between dietary thiamine intake and cognitive decline in cognitively healthy,older Chinese individuals,with an inflection point at 0.68 mg/day and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.

Noninvasive identificational diagnosis of diabetic nephropathy and non-diabetic renal disease based on clinical characteristics of Traditional Chinese Medicine symptom pattern and conventional medicine

OBJECTIVE:To study the clinical characteristics relating to differential diagnosis of diabetic nephropathy(DN) and non-diabetic renal disease(NDRD).METHODS:The subjects were patients with type 2 diabetes mellitus(T2DM) complicated with chronic kidney disease(CKD).Western medical history data and Traditional Chinese Medicine(TCM) symptom pattern were collected,and logistic regression was used to analyze.RESULTS:Blood deficiency pattern [odds ratio(OR) = 2.269,P = 0.017] and Qi stagnation pattern(OR = 1.999,P = 0.041) are independently related to DN.CONCLUSIONS:TCM factors blood deficiency pattern and Qi stagnation pattern are relating to differential diagnosis of DN and NDRD.

Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine

Objective:To investigate the factors related to renal impairment in patients with diabetic kidney disease(DKD)from the perspective of integrated Chinese and Western medicine.Methods:Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included.According to Kidney Disease Improving Global Outcomes(KDIGO)staging guidelines,patients were divided into a chronic kidney disease(CKD)1-3 group and a CKD 4-5 group.Clinical data were collected,and logistic regression was used to analyze the factors related to different CKD stages in DKD patients.Results:Demographically,male was a factor related to increased CKD staging in patients with DKD(OR=3.100,P=0.002).In clinical characteristics,course of diabetes>60 months(OR=3.562,P=0.010),anemia(OR=4.176,P<0.001),hyperuricemia(OR=3.352,P<0.001),massive albuminuria(OR=4.058,P=0.002),atherosclerosis(OR=2.153,P=0.007)and blood deficiency syndrome(OR=1.945,P=0.020)were factors related to increased CKD staging in patients with DKD.Conclusion:Male,course of diabetes>60 months,anemia,hyperuricemia,massive proteinuria,atherosclerosis,and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD.(Registration No.NCT03865914).

Clinical features of acute kidney injury in patients with nephrotic syndrome and minimal change disease:a retrospective,cross-sectional study

Background:Minimal change nephropathy(MCD)is a common pathological type of nephrotic syndrome and is often associated with acute kidney injury(AKI).This study aimed to investigate the clinical characteristics and related factors of AKI in patients with MCD and nephrotic syndrome.Methods:Patients from Chinese People’s Liberation Army General Hospital who were diagnosed with pathological renal MCD with clinical manifestations of nephrotic syndrome were included from January 1,2013 to December 31,2017.Patients diagnosed with membranous nephropathy(MN)by renal biopsy from January 1,2013 to December 31,2017 are included as a control population.We retrospectively analyzed the clinical and pathological characteristics of patients as well as the percentages and clinical characteristics of AKI in different age groups.We assessed the correlation of pathological characteristics with serum creatinine using multivariate linear regression analysis.Results:A total of 367 patients with MCD were included in the analysis,with a sex ratio of 1.46:1(male:female)and an age range of 6 to 77 years.Among all the patients,109 developed AKI(29.7%),and of these patients,85 were male(78.0%).In the 586 patients with MN,27(4.6%)patients developed AKI.The percentage of AKI in MCD patients was significantly higher than that in MN patients(χ^(2)=41.063,P<0.001).The percentage of AKI increased with age in the MCD patients.The percentage of AKI in patients aged 50 years or older was 52.9%(46/87),which was significantly higher than that[22.5%(63/280)]in patients under 50 years(χ^(2)=6.347,P=0.013).We observed statistically significant differences in age(43[27,59]years vs.28[20,44]years,Z=5.487,P<0.001),male(78.0%vs.51.4%,χ^(2)=22.470,P<0.001),serum albumin(19.9±6.1 g/L vs.21.5±5.7 g/L,t=2.376,P=0.018),serum creatinine(129.5[105.7,171.1]μmol/L vs.69.7[57.7,81.9]μmol/L,Z=14.190,P<0.001),serum urea(10.1[6.2,15.8]mmol/L vs.4.7[3.6,6.4]mmol/L,Z=10.545,P<0.001),IgE(266.0[86.7,963.0]IU/ml vs.142.0[35.3,516.5]IU/ml,Z=2.742,P=0.007),history of diabetes(6.4%vs.1.2%,P=0.009),and history of hypertension(23.9%vs.5.1%,χ^(2)=28.238,P<0.001)between the AKI group and the non-AKI group.According to multivariate linear regression analysis,among the renal pathological features analyzed,renal tubular epithelial cell damage(β=178.010,95%CI:147.888-208.132,P<0.001)and renal interstitial edema(β=28.833,95%CI:11.966-45.700,P=0.001)correlated with serum creatinine values.Conclusions:The percentage of AKI in MCD patients is significantly higher than that in MN patients.Patients over 50 years old are more likely to develop AKI.Renal tubular epithelial cell injury and renal interstitial edema may be the main pathological lesions that are associated with elevated serum creatinine in patients with MCD.

Efficacy and Safety of Niaoduqing Particles for Delaying Moderate-to-severe Renal Dysfunction： A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study

Background： Chronic kidney disease （CKD） with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD.Methods： The present study was a prospective, randomized, double-blind, placebo-controlled, naulticentcr clinical trial. Frorn May 2013 to December 2013,300 CKD patients with an estimated glomerular filtration rate （eGFR） between 20 and 45 ml ＂rain ~＂ 1.73 m 2, aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1：1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine （Scr） and eGFR after completion of treatment. The primary endpoints were analyzed using Student＇s t-test or Wilcoxon＇s rank-sum test. The present study reported results based on an intention-to-treat （ITT） analysis. Results： A total of 292 participants underwent the ITT analysis. At 24 weeks, the median （interquartile range） change in Scr was 1.1 （-13.0-24.1） and 11.7 （-2.6-42.9） p, mol/L for the test and control groups, respectively （Z = 2.642, P = 0.008）, and the median change in eGFR was -0.2 （-4.3-2.7） and -2.2 （-5.7-0.8） ml.min-1·1.73 m-2, respectively （Z = -2.408, P = 0.016）. There were no significant differences in adverse events between the groups. Conclusions： Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction.

Integrated Chinese and Western medicine in the treatment of a patient with podocyte infolding glomerulopathy:A case report

BACKGROUND Podocyte infolding glomerulopathy(PIG)is a newly described and rare glomerular disease.To date,only approximately 40 cases have been reported globally.CASE SUMMARY A 26-year-old female patient presented to our hospital with a complaint of intermittent edema of both lower limbs over the past 2 years.The patient was diagnosed with PIG.She was prescribed corticosteroid therapy in other hospitals during the initial stage,to which she had responded poorly and had developed femoral head necrosis.Therefore,we administered immunosuppressants,reninangiotensin system inhibitors,combined with traditional Chinese medicine.The patient was followed for 1 year,during which her clinical condition improved.CONCLUSION Integrated Chinese and Western medicine may be effective for PIG treatment,which requires active intervention to improve prognosis.

Research advances in the function and anti-aging effects of nicotinamide mononucleotide

Aging and age-related ailments have emerged as critical challenges and great burdens within the global contemporary society.Addressing these concerns is an imperative task,with the aims of postponing the aging process and finding effective treatments for age-related degenerative diseases.Recent investigations have highlighted the significant roles of nicotinamide adenine dinucleotide(NAD+)in the realm of anti-aging.It has been empirically evidenced that supplementation with nicotinamide mononucleotide(NMN)can elevate NAD+levels in the body,thereby ameliorating certain age-related degenerative diseases.The principal anti-aging mechanisms of NMN essentially lie in its impact on cellular energy metabolism,inhibition of cell apoptosis,modulation of immune function,and preservation of genomic stability,which collectively contribute to the deferral of the aging process.This paper critically reviews and evaluates existing research on the anti-aging mechanisms of NMN,elucidates the inherent limitations of current research,and proposes novel avenues for anti-aging investigations.

Composition analysis of Compound Shenhua Tablet,a seven-herb Chinese medicine for IgA nephropathy:evaluation of analyte-capacity of the assays

Compound Shenhua Tablet,a medicine comprising seven herbs,is employed in treating IgA nephropathy.This study aimed to meticulously analyze its chemical composition.Based on a list of candidate compounds,identified through extensive literature review pertinent to the tablet’s herbal components,the composition analysis entailed the systematic identification,characterization,and quantification of the constituents.The analyte-capacity of LC/ESI-MS-based and GC/EI-MS-based assays was evaluated.The identified and characterized constituents were quantified to determine their content levels and were ranked based on the constituents’daily doses.A total of 283 constituents,classified into 12 distinct categories,were identified and characterized in the Compound Shenhua Tablet.These constituents exhibited content levels of 1−10982μg·g^(−1),with daily doses of 0.01−395μmol·d^(−1).The predominant constituents,with daily doses of≥10μmol·d^(−1),include nine organic acids(citric acid,quinic acid,chlorogenic acid,cryptochlorogenic acid,gallic acid,neochlorogenic acid,isochlorogenic acid C,isochlorogenic acid B,and linoleic acid),five iridoids(specnuezhenide,nuezhenoside G13,nuezhenidic acid,secoxyloganin,and secologanoside),two monoterpene glycosides(paeoniflorin and albiflorin),a sesquiterpenoid(curzerenone),a triterpenoid(oleanolic acid),and a phenylethanoid(salidroside).Additionally,there were 83,126,and 55 constituents detected in the medicine with daily doses of 1–10,0.1–1,and 0.01–0.1μmol·d^(−1),respectively.The combination of the LC/ESI-MS-based and GC/EI-MS-based assays demonstrated a complementary relationship in their analyte-capacity for detecting the constituents present in the medicine.This comprehensive composition analysis establishes a solid foundation for further pharmacological research on Compound Shenhua Tablet and facilitates the quality evaluation of this complex herbal medicine.

Analysis of chronic kidney disease staging with different estimated glomerular filtration rate equations in Chinese centenarians

Background: Accurate estimation of the glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Currently, there is no research on the differences in several estimated GFR equations for staging CKD in a large sample of centenarians. Thus, this study aimed to investigate the differences in CKD staging with the most commonly used equations and to analyze sources of discrepancy. Methods: A total of 966 centenarians were enrolled in this study from June 2014 to December 2016 in Hainan province, China. The GFR with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study 1 (BIS1) equations were estimated. Agreement between these equations was investigated with the k statistic and Bland-Altman plots. Sources of discrepancy were investigated by partial correlation analysis. Results: The k values of the MDRD and CKD-EPI equations, MDRD and BIS1 equations, and CKD-EPI and BIS1 equations were 0.610, 0.253, and 0.381, respectively. Serum creatinine (Scr) explained 10.96%, 41.60% and 17.06% of the variability in these three comparisons, respectively. Serum uric acid (SUA) explained 3.65% and 5.43% of the variability in the first 2 comparisons, respectively. Gender was associated with significant differences in these 3 comparisons (P<0.001). Conclusions: The strengths of agreement between the MDRD and CKD-EPI equations were substantial, but those between the MDRD and BIS 1 equations and the CKD-EPI and BIS 1 equations were fair. The difference in CKD staging of the first 2 comparisons strongly depended on Scr, SUA and gender, and that of CKD-EPI and BIS1 equations strongly depended on Scr and gender. The incidence at various stages of CKD staging was quite different. Thus, a new equation that is more suitable for the elderly needs to be built in the future.

A non-invasive diagnostic model of immunoglobulin A nephropathy and serological markers for evaluating disease severity

Background: Immunoglobulin A nephropathy (IgAN) is the most common pathological type of glomerular disease. Kidney biopsy, the gold standard for IgAN diagnosis, has not been routinely applied in hospitals worldwide due to its invasion nature. Thus, we aim to establish a non-invasive diagnostic model and determine markers to evaluate disease severity by analyzing the serological parameters and pathological stages of patients with IgAN. Methods: A total of 272 biopsy-diagnosed IgAN inpatients and 518 non-IgA nephropathy inpatients from the Department of Nephrology of Chinese People's Liberation Army General Hospital were recruited for this study. Routine blood examination, blood coagulation testing, immunoglobulin-complement testing, and clinical biochemistry testing were conducted and pathological stages were analyzed according to Lee grading system. The serological parameters and pathological stages were analyzed. The receiver operating characteristic (ROC) analysis was performed to estimate the diagnostic value of the clinical factors. Logistic regression was used to establish the diagnostic model. Results: There were 15 significantly different serological parameters between the IgAN and non-IgAN groups (all P< 0.05). The ROC analysis was performed to measure the diagnostic value for IgAN of these parameters and the results showed that the area under the ROC curve (AUC) of total protein (TP), total cholesterol (TC), fibrinogen (FIB), D-dimer (D2), immunoglobulin A (IgA), and immunoglobulin G (IgG) were more than 0.70. The AUC of the "TC + FIB + D2 + IgA + age" combination was 0.86, with a sensitivity of 85.98% and a specificity of 73.85%. Pathological grades of Ⅰ,Ⅱ,Ⅲ,Ⅳ, and Ⅴ accounted for 2.21 %, 17.65%, 62.50%, 11.76%, and 5.88%, respectively, with grade Ⅲ being the most prevalent. The levels of urea nitrogen (UN)(13.57土 5.95 vs. 6.06 土 3.63, 5.92 + 2.97, 5.41 ± 1.73, and 8.41 ±3.72μmol/L, respectively) and creatinine (Cr)(292.19± 162.21 vs. 80.42±24.75, 103.79±72.72, 96.41 ±33.79, and 163.04±47.51 μmol/L, respectively) were significantly higher in grade V than in the other grades, and the levels of TP (64.45±7.56, 67.16±6.94, 63.22±8.56, and 61.41 ± 10.86 vs. 37.47 ± 5.6 mg/d, respectively), direct bilirubin (DB)(2.34± 1.23, 2.58± 1.40, 1.91 ±0.97, and 1.81±1.44 vs. 0.74±0.57μmol/L, respectively), and IgA (310.35± 103.78, 318.48± 107.54, 292.58±81.85, and 323.29± 181.67 vs. 227.17±68.12g/L, respectively) were significantly increased in grades II-V compared with grade I (all P<0.05). Conclusions: The established diagnostic model that combined multiple factors (TC, FIB, D2, IgA, and age) might be used for IgAN non-invasive diagnosis. TP, DB, IgA, Cr, and UN have the potential to be used to evaluate IgAN disease severity.

Single-cell RNA sequencing data suggest a role for angiotensin-converting enzyme 2 in kidney impairment in patients infected with 2019-novel coronavirus

The World Health Organization has recently declared the 2019-novel coronavirus(2019-nCoV)a global public health emergency.Huang et al[1]reported acute kidney injury(AKI)in 7%of the 41 patients infected with 2019-nCoV,this value was even higher(up to 31%)among intensive-care patients.Furthermore,Li et al[2]reported that plasma creatinine levels increased in 11 of 59 patients with 2019-nCoV infection,suggesting that kidney function was probably impaired when the disease progressed.Guan et al[3]reported that plasma creatinine level increased in 4.3%of severely diseased patients.2019-nCoV is a highly contagious pathogen that predominantly causes pneumonic symptoms.Although respiratory failure has been associated with the highest mortality,the lung was not the only organ involved.Hoffmann et al[4]reported that 2019-nCoV and severe acute respiratory syndrome-associated coronavirus(SARS-CoV)share a common receptor angiotensin-converting enzyme 2(ACE2)that is required to enter target cells,and cellular protease transmembrane protease serine 2(TMPRSS2)can cleave and activate the spike protein of 2019-nCoV for membrane fusion.We investigated whether ACE2 and TMPRSS2 were expressed in kidney cells using precisiontechnology single-cell RNA sequencing.

Embryonic Stem Cells-loaded Gelatin Microcryogels Slow Progression of Chronic Kidney Disease

Background： Chronic kidney disease （CKD） has become a public health problem.New interventions to slow or prevent disease progression are urgently needed.In this setting, cell therapies associated with regenerative effects are attracting increasing interest.We evaluated the effect of embryonic stem cells （ESCs） on the progression of CKD.Methods： Adult male Sprague-Dawley rats were subjected to 5/6 nephrectomy.We used pedicled greater omentum flaps packing ESC-loaded gelatin microcryogets （GMs） on the 5/6 nephrectomized kidney.The viability of ESCs within the GMs was detected using in vio two-photon fluorescence confocal imaging.Rats were sacrificed after 12 weeks.Renal injury was evaluated using serum creatinine, urea nitrogen, 24 h protein, renal pathology, and tubular injury score results.Structural damage was evaluated by periodic acid-Schiff and Masson trichrome staining.Results： In vitro, ESCs could be automatically loaded into the GMs.Uniform cell distribution, good cell attachment, and viability were achieved from day 1 to 7 in vitro.After 12 weeks, in the pedicled greater omentum flaps packing ESC-loaded GMs on 5/6 nephrectomized rats group, the plasma urea nitrogen levels were 26% lower than in the right nephrectomy group, glomerulosclerosis index was 62% lower and tubular injury index was 40% lower than in the 5/6 nephrectomized rats group without GMs.Conclusions： In a rat model of established CKD, we demonstrated that the pedicled greater omentum flaps packing ESC-loaded GMs on the 5/6 nephrectomized kidney have a long-lasting therapeutic rescue function, as shown by the decreased progression of CKD and reduced glomerular injury.

Diagnostic Value of Sensitive Biomarkers for Early Kidney Damage in Diabetic Patients with Normoalbuminuria

To the Editor:Diabetic kidney disease (DKD)is the most common cause of end-stage renal disease (ESRD);however,the onset of DKD is difficult to detect.[1]When persistent microalbuminuria becomes detectable,DKD has already progressed to the third disease stage,and finding biomarkers that are more sensitive than microalbuminuria is therefore necessary to indicate kidney damage at an earlier stage of DKD.[2]Both glomerular and tubulointerstitial damages have been repeatedly demonstrated to be important factors in the pathophysiology of DKD.[3] Therefore,we investigated the expression levels of six markers closely related to the glomerulus and renal tubule.

Safety,Effectiveness,and Manipulability of Peritoneal Dialysis Machines Made in China:A Randomized,Crossover, Multicenter Clinical Study

Background: Automated peritoneal dialysis (APD) can cater to individual needs, provide treatment while asleep, take into account the adequacy of dialysis, and improve the quality of life. Currently, independent research and development of APD machines made in China are more conducive to patients. A randomized, multicenter, crossover study was conducted by comparing an APD machine made in China with an imported machine. The safety, effectiveness, and manipulability of the two machines were compared. Methods: Two hundred and sixty patients who underwent peritoneal dialysis (PD) on a regular basis in 18 centers between August 2015 and February 2016 were included. The inclusion criteria include age ≥18 years and PD ≥30 days. The exclusion criteria were as follows: hemodialysis; exit site or tunnel infection; and peritonitis ≤30 days. The patients were randomly divided into Group A, who were first treated with a FM machine made in China, then changed to an imported machine; and Group B, who were treated using the reverse sequence. APD treatment was performed with 10 L/10 h and 5 cycles of exchange. After 72 h, the daily peritoneal Kt/V, the accuracy of the injection rate, accuracy of the injection temperature, safety, and manipulability of the machine were assessed. Noninferiority test was conducted between the two groups. Results: The daily peritoneal Kt/V in the APD machine made in China and the imported APD machine were 0.17 (0.14, 0.25) and 0.16 (0.13, 0.23), respectively. There was no significant difference between the groups (Z = 0.15, P = 0.703). The lower limit of the daily Kt/V difference between the two groups was 0.0069, which was greater than the noninferiority value of -0.07 in this study. The accuracy of the injection rate and injection temperature was 89.7% and 91.5%, respectively, in the domestic APD machine, which were both slightly better than the accuracy rates of 84.0% and 86.8% in the imported APD machine (89.7% vs. 84.0%, P = 0.2466; 91.5% vs. 86.8%, P = 0.0954). Therefore, the APD machine made in China was not inferior to the imported APD machine. The fuselage of the imported APD machine was space?saving, while the APD machine made in China was superior with respect to body mobility, man?machine dialog operation, alarm control, and patient information recognition. Conclusions: The FM machine made in China was not inferior to the imported APD machine. In addition, the FM machine made in China had better operability.

Efficacy and safety of Shenyankangfu Tablet,a Chinese patent medicine,for primary glomerulonephritis:A multicenter randomized controlled trial

Background:Shenyankangfu Tablet(SYKFT)is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.Objective:This trial compared the efficacy and safety of SYKFT,for the control of proteinuria in primary glomerulonephritis patients,against the standard drug,losartan potassium.Design,setting,participants and intervention:This was a multicenter,double-blind,randomized,controlled clinical trial.Primary glomerulonephritis patients,aged 18-70 years,with blood pressure≤140/90 mmHg,estimated glomerular filtration rate(eGFR)>45 mL/min per 1.73 ㎡,and 24-hour proteinuria level of 0.5-3.0 g,were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups:SYKFT,losartan potassium 50 mg or 100 mg,SYKFT plus losartan potassium 50 mg or 100 mg.Main outcome measu res:The primary outcome was change in the 24-hour proteinuria level,after 48 weeks of treatment.Results:A total of 735 participants were enrolled.The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78%±2.56%(P=0.006)more than that in the losartan 50 mg group,which was 0.51%±2.54%(P=1.000)less than that in the losartan 100 mg group.Compared with the losartan potassium 50 mg group,the SYKFT plus losartan potassium 50 mg group had a 13.39%±2.49%(P<0.001)greater reduction in urine protein level.Compared with the losartan potassium 100 mg group,the SYKFT plus losartan potassium 100 mg group had a 9.77%±2.52%(P=0.001)greater reduction in urine protein.With a superiority threshold of 15%,neither was statistically significant.eGFR,serum creatinine and serum albumin from the baseline did not change statistically significant.The average change in TCM syndrome score between the patients who took SYKFT(-3.00[-6.00,-2.00])and who did not take SYKFT(-2.00[-5.00,0])was statistically significant(P=0.003).No obvious adverse reactions were observed in any group.Conclusion:SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients,with no change in the rate of decrease in the eGFR.SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.Trial registration number:NCT02063100 on ClinicalTrials.gov.

Comparative risk of acute kidney injury among cancer patients treated with immune checkpoint inhibitors

With the development and introduction of immune checkpoint inhibitors(ICIs)in cancer patients,immune-related side effects have increasingly attracted attention.However,the risks of immune-related renal toxicity are poorly characterized.In this study,we performed a network meta-analysis(NMA)of ICI-related randomized clinical trials(RCTs)to elucidate the comparative risk of acute kidney injury(AKI)in cancer patients receiving different ICIs.We also sought to identify other factors potentially affecting the risk of AKI.PubMed and EMBASE were searched for peer-reviewed trial reports published between January 2000 and May 2021.Eligible studies were RCTs studying ICIs in cancer patients and reporting AKI data.We performed a frequentist NMA to evaluate the risk ratios for grade 1-5 and grade 3-5 AKI between the treatment groups.We also assessed the absolute incidence of AKI in the ICI-containing arm using traditional direct meta-analysis.Once significant heterogeneity was detected in a traditional direct meta-analysis,multivariable meta-regression analysis was applied to identify factors that significantly affected the absolute incidence of AKI.A total of 85 RCTs were included in this study.In the NMA for the risk of grade 1-5 and 3-5 AKI,ipilimumab showed a significantly higher risk than avelumab and durvalumab,whereas 1 mg/kg nivolumab plus 3 mg/kg ipilimumab(N1I3)showed a significantly higher risk than other groups.In terms of treatment ranking,durvalumab±low-dose tremelimumab and avelumab were consistently among the top three safest treatments for grade 1-5 or 3-5 AKI,whereas N1I3,ipilimumab and tremelimumab were consistently among the top three treatments with the highest risk for grade 1-5 or 3-5 AKI.Compared with other cancers,renal cell carcinoma and urothelial carcinoma showed a significantly higher risk of AKI.The incidence of AKI was significantly higher with ICI+chemotherapy than with ICI monotherapy.In this NMA involving largescale up-to-date ICI trials,we demonstrated the comparative safety of existing ICI drugs for grade 1-5 and grade 3-5 AKI.Based on data from the ICI arms of these trials,we also revealed several potential risk factors for immune-related AKI,including tumor type and treatment paradigm.