Incidence Of Proteinuria Research Articles

ЭФФЕКТИВНОСТЬ ТЕРАПИИ ИНГИБИТОРАМИ АНГИОТЕНЗИН- ПРЕВРАЩАЮЩЕГО ФЕРМЕНТА В ПРОФИЛАКТИКЕ РАЗВИТИЯ ПРОТЕИНУРИИ У МАЛЬЧИКОВ С Х-СЦЕПЛЕННЫМ СИНДРОМОМ АЛЬПОРТА: ДАННЫЕ ОДНОЦЕНТРОВОГО КОГОРТНОГО НЕРАНДОМИЗИРОВАННОГО ИССЛЕДОВАНИЯ

Patients with a hemizygous mutation in the COL4A5 gene have a high risk of developing renal failure at a young age. Proteinuria reflects the progression of glomerulopathy in Alport syndrome (AS). In order to improve renal survival in AS patients with proteinuria are prescribed with angiotensin system inhibitors. There is a limited, insufficient number of studies demonstrating the effectiveness of angiotensin-converting enzyme inhibitors (ACEI) in children with AS; the therapeutic effect initiated prior to the development of proteinuria has not been studied as yet. The purpose of the research was to determine the effectiveness of ACEI therapy in the form of enalapril in the prevention of proteinuria in boys with X-linked AS (XLAS). Materials and methods used: boys aged 2 to 15 y/o with genetically confirmed XLAS were included in a single-center prospective cohort study. Enalapril was prescribed at doses of 1 to 3 mg/m2/day. Urinary protein excretion (Pr) and estimated glomerular filtration rate (eGFR) were studied at the time of inclusion and with a frequency of one time per six months for the three-year period or longer. The primary endpoint was the time of onset of proteinuria. Results: 72 boys in total, incl. 29 without proteinuria, who received enalapril therapy (Group 1, age 6.2±1.9 y/o, Pr 67±20 mg/m2/day, eGFR 118±15.2 ml /min/1.73 m2) and 43 children without therapy (Group 2, age 6.8±1.9 y/o, Pr 87±23 mg/m2/day, eGFR 119±17.3 ml/min/1.73 m2). The incidence of proteinuria (0.45 in G1 vs. 0.98 in G2, p<0.001), incl. up to the age of 10 y/o (0.42 vs 0.91, respectively, p<0.001) was statistically significantly lower in G1. Proteinuria developed later in the treatment group (10.2±2.9 vs. 4.9±1.4 years, p=0.300). Non-missense mutations in the COL4A5 gene, episodes of macrohematuria in records and lack of therapy were the risk factors for proteinuria; the lack of enalapril therapy was a predictor for proteinuria. The risk of proteinuria during therapy was reduced by 50% (RR=0.46 (95% CI 0.31; 0.68); ARR=0.53; NNT=1.9). Conclusion: initiation of enalapril therapy at the pre-proteinuria stage of nephropathy in boys with XLAS reduces the risk of proteinuria preventing its occurrence in every 50$ of cases when receiving treatment. Early initiation of therapy may be effective in preventing the progression of kidney disease in boys with XLAS.

Diet Quality and Kidney Outcomes in Adolescent and Adult American Indians: the Strong Heart Family Study.

The burden of kidney disease is exceedingly high among American Indians (AIs). We sought to examine the relationship of diet quality, a modifiable risk factor, and kidney outcomes in AI adolescents and adults, hypothesizing that healthier diets are associated with lower odds of incident albuminuria and eGFR decline. This is an analysis from the Strong Heart Family Study, a longitudinal study of cardiovascular disease and its risk factors among AIs from Arizona, North and South Dakota, and Oklahoma (n = 1720, mean age 39 + / - 16years, 16% adolescents at baseline). Participants completed two exams (baseline: 2001-2003; follow-up: 2007-2009). The primary exposure was diet quality, expressed as the Alternative Healthy Eating Index 2010 (AHEI), on a 110-point scale (assessed using a 119-item Block food frequency questionnaire). The primary outcomes were as follows: 1) incident albuminuria (albumin to creatinine ratio 30mg/g or greater); and 2) eGFR decline of 30% or greater. Generalized estimating equations were used to examine the association of AHEI (in quartiles) with outcomes. Ten percent of participants (6% of adolescents) had incident albuminuria and 2% of participants (2% of adolescents) had eGFR decline. For those with normal fasting glucose levels, the odds ratio (OR) for incident albuminuria comparing extreme quartiles of diet quality (least healthy [reference] versus healthiest quartiles) was 0.48 (95% CI 0.28, 0.81) after adjustment for demographics and comorbidities. For American Indians with normal fasting glucose, higher diet quality decreases the odds of developing albuminuria. These findings inform future efforts to prevent CKD in American Indian adolescents and young adults.

Patient-Specific Pharmacokinetics and Dasatinib Nephrotoxicity.

Dasatinib has been associated with nephrotoxicity. We sought to examine the incidence of proteinuria on dasatinib and determine potential risk factors that may increase dasatinib-associated glomerular injury. We examined glomerular injury through urine albumin-creatinine ratio (UACR) in 82 patients with chronic myelogenous leukemia who were on tyrosine-kinase inhibitor therapy for at least 90 days. t tests were used to compare mean differences in UACR, while regression analysis was used to assess the effects of drug parameters on proteinuria development while on dasatinib. We assayed plasma dasatinib pharmacokinetics using tandem mass spectroscopy and further described a case study of a patient who experienced nephrotic-range proteinuria while on dasatinib. Participants treated with dasatinib ( n =32) had significantly higher UACR levels (median 28.0 mg/g; interquartile range, 11.5-119.5) than participants treated with other tyrosine-kinase inhibitors ( n =50; median 15.0 mg/g; interquartile range, 8.0-35.0; P < 0.001). In total, 10% of dasatinib users exhibited severely increased albuminuria (UACR >300 mg/g) versus zero in other tyrosine-kinase inhibitors. Average steady-state concentrations of dasatinib were positively correlated with UACR ( ρ =0.54, P = 0.03) and duration of treatment ( P = 0.003). There were no associations with elevated BP or other confounding factors. In the case study, kidney biopsy revealed global glomerular damage with diffuse foot process effacement that recovered on termination of dasatinib treatment. Exposure to dasatinib was associated with a significant chance of developing proteinuria compared with other similar tyrosine-kinase inhibitors. Dasatinib plasma concentration significantly correlated with higher risk of developing proteinuria while receiving dasatinib. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_09_08_CJN0000000000000219.mp3.

14-LB: Abdominal Obesity Indices Predict Incident Renal Events in a 10-Year Cohort with Type 2 Diabetes Mellitus

Background: Obesity, especially abdominal obesity, has been associated with diabetes. However, few studies focused on the association between obesity indices and diabetic nephropathy, let alone the longitudinal studies. Waist circumference (WC), visceral adiposity index (VAI), Chinese visceral adiposity index (CVAI) and lipid accumulation product (LAP) are described as abdominal obesity indices. The present study aimed to explore the associations between these indices and incident renal events in a 10-year cohort with type 2 diabetes mellitus (T2DM). Methods: A total of 2709 participants with T2DM from the Beijing Community Diabetes Study were included. Prespecified renal outcomes included incident or worsening nephropathy (progression to macroalbuminuria, doubling of the serum creatinine, initiation of renal-replacement therapy, or renal death) and incident albuminuria. Multivariable Cox regression were applied to analyze the associations between these indices and renal events. Results: Multivariable analyses indicated that each 1-SD increase in WC, VAI, CVAI and LAP was associated with a higher risk of renal events, with adjusted hazard ratios (HRs) being 1.236 [95% CI (confidence interval): 1.079-1.417], 1.135 (1.026-1.257), 1.295 (1.132-1.483), and 1.144 (1.036-1.263), respectively. Moreover, participants in the highest quartile of abdominal obesity indices were at higher risk of renal events compared to those in the lowest quartile (all P for trend&amp;lt;0.05). However, only CVAI was always significantly positively associated with incident renal events in all subgroups, including gender (male vs. female), age (&amp;lt; 60 years vs. ≥60 years) and ACEI (angiotensin-converting enzyme inhibitor) or ARB (angiotensin II receptor blocker) treatment (no vs. yes). Conclusion: Abdominal obesity indices could predict renal events in a 10-year cohort with T2DM, and CVAI may be more universal to predict renal events than WC, VAI and LAP in certain population. Disclosure C. Ma: None. M. Yuan: None. Funding Capital's Funds for Health Improvement and Research (2022-1-1101, 2016-1-2057)

#3610 EPIDEMIOLOGY AND CLINICAL CORRELATES OF POST-AKI PROTEINURIA IN CHINESE HOSPITALIZED ADULTS

Abstract Background and Aims Acute kidney injury (AKI) has been associated with increased risks of new-onset and worsening proteinuria. However, the epidemiologic data of post-AKI proteinuria was still lacking. This study aimed to determine the incidence, risk factors and clinical correlations of post-AKI proteinuria among hospitalized patients. Method This study conducted a multicenter cohort from Chinese Renal disease Data System (CRDS), including patients aged 18–100 years with hospital-acquired AKI (HA-AKI) hospitalized at 19 medical centers throughout China. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) creatine criteria. The results of both quantitative and qualitative urinary protein tests were used to determine post-AKI proteinuria. The primary outcome was the incidence of post-AKI proteinuria. Secondary outcomes included AKI recovery and kidney disease progression. Cox proportional hazard model with stepwise regression was used to determine the risk factors for post-AKI proteinuria. The associations of post-AKI proteinuria with kidney disease progression were analyzed by logistic regression models. Results Of 6,206 HA-AKI patients without proteinuria at baseline, 2,102 (33.9%) had new-onset proteinuria, whereas, of 5,137 HA-AKI with baseline proteinuria, 894 (17.4%) had worsening proteinuria after AKI (Table 1). Higher AKI stage and preexisting CKD diagnosis were risk factors for new-onset proteinuria and worsening proteinuria, whereas treatment with RAS inhibitors was associated with an 11% lower risk of incident proteinuria. About 60% and 75% of patients with post-AKI new-onset and worsening proteinuria, respectively, recovered within 3 months. Worsening proteinuria was associated with a lower incidence of AKI recovery and a higher risk of kidney disease progression (Table 2). Conclusion Post-AKI proteinuria is common and usually transient among hospitalized patients. The risk profiles for new-onset and worsening post-AKI proteinuria differed markedly. Worsening proteinuria after AKI was associated with adverse kidney outcomes, which emphasized the need for close monitoring of proteinuria after AKI.

Epidemiology and outcomes of post-AKI proteinuria.

Acute kidney injury (AKI) has been associated with increased risks of new-onset and worsening proteinuria. However, epidemiologic data for post-AKI proteinuria was still lacking. This study aimed to determine the incidence, risk factors and clinical correlations of post-AKI proteinuria among hospitalized patients. This study was conducted in a multicenter cohort including patients aged 18-100 years with hospital-acquired AKI (HA-AKI) hospitalized at 19 medical centers throughout China. The primary outcome was the incidence of post-AKI proteinuria. Secondary outcomes included AKI recovery and kidney disease progression. The results of both quantitative and qualitative urinary protein tests were used to define post-AKI proteinuria. Cox proportional hazard model with stepwise regression was used to determine the risk factors for post-AKI proteinuria. Of 6206 HA-AKI patients without proteinuria at baseline, 2102 (33.9%) had new-onset proteinuria, whereas of 5137 HA-AKI with baseline proteinuria, 894 (17.4%) had worsening proteinuria after AKI. Higher AKI stage and preexisting CKD diagnosis were risk factors for new-onset proteinuria and worsening proteinuria, whereas treatment with renin-angiotensin system inhibitors was associated with an 11% lower risk of incident proteinuria. About 60% and 75% of patients with post-AKI new-onset and worsening proteinuria, respectively, recovered within 3 months. Worsening proteinuria was associated with a lower incidence of AKI recovery and a higher risk of kidney disease progression. Post-AKI proteinuria is common and usually transient among hospitalized patients. The risk profiles for new-onset and worsening post-AKI proteinuria differed markedly. Worsening proteinuria after AKI was associated with adverse kidney outcomes, which emphasized the need for close monitoring of proteinuria after AKI.

A Dose-Dependent Association between Alcohol Consumption and Incidence of Proteinuria and Low Glomerular Filtration Rate: A Systematic Review and Meta-Analysis of Cohort Studies.

Previous cohort studies have reported conflicting associations between alcohol consumption and chronic kidney disease, characterized by proteinuria and low glomerular filtration rate (GFR). This systematic review, which included 14,634,940 participants from 11 cohort studies, assessed a dose-dependent association of alcohol consumption and incidence of proteinuria and low estimated GFR (eGFR) of <60 mL/min/1.73 m2. Compared with non-drinkers, the incidence of proteinuria was lower in drinkers with alcohol consumption of ≤12.0 g/day (relative risk 0.87 [95% confidence interval 0.83, 0.92]), but higher in drinkers with alcohol consumption of 36.1-60.0 g/day (1.09 [1.03, 1.15]), suggesting a J-shaped association between alcohol consumption and the incidence of proteinuria. Incidence of low eGFR was lower in drinkers with alcohol consumption of ≤12.0 and 12.1-36.0 than in non-drinkers (≤12.0, 12.1-36.0, and 36.1-60.0 g/day: 0.93 [0.90, 0.95], 0.82 [0.78, 0.86], and 0.89 [0.77, 1.03], respectively), suggesting that drinkers were at lower risk of low eGFR. In conclusion, compared with non-drinkers, mild drinkers were at lower risk of proteinuria and low eGFR, whereas heavy drinkers had a higher risk of proteinuria but a lower risk of low eGFR. The clinical impact of high alcohol consumption should be assessed in well-designed studies.

Triglycerides and Renal Outcomes According to Albuminuria and in Consideration of Other Metabolic Syndrome Components in Diabetic US Veterans

Introduction: Hypertriglyceridemia, a component of the metabolic syndrome, is a known independent predictor of albuminuria and chronic kidney disease (CKD) in the general population. Previous studies have shown that the relationship of triglycerides (TGs) with outcomes changes across stages of CKD. Our objective was to examine the association of TG independent of other metabolic syndrome components with renal outcomes in diabetic patients with or without CKD. Methods: This retrospective cohort study included diabetic US veteran patients with valid data on TGs, estimated glomerular filtration rate (eGFR), and albuminuria (urinary albumin/creatinine ratio) between fiscal years 2004 and 2006. Using Cox models adjusted for clinical characteristics and laboratory markers, we evaluated the relationship of TG with incident albuminuria (stratified by eGFR category) and based on eGFR (stratified by baseline albuminuria categories). To evaluate the relationship of TG with time to end-stage renal disease (ESRD), we stratified models by baseline CKD stage (eGFR category) and baseline albuminuria stage ascertained at time of TG measurement. Results: In a cohort of 138,675 diabetic veterans, the mean ± SD age was 65 ± 11 years old and included 3% females and 14% African Americans. The cohort also included 28% of patients with non-dialysis-dependent CKD (eGFR <60 mL/min/1.73 m²), as well as 28% of patients with albuminuria (≥30 mg/g). The median (IQR) of serum TG was 148 (100, 222) mg/dL. We observed a slight positive linear association between TG and incident CKD after adjustment for Case-Mix and Laboratory variables among non-albuminuric and microalbuminuric patients. The relationship of high TG trended towards a higher risk of ESRD in CKD 3A non-albuminuric patients and in CKD 3A and 4/5 patients with microalbuminuria. Conclusion: In a large cohort, we have shown that elevated TGs are associated with all kidney outcomes tested independently of other metabolic syndrome components in diabetic patients with normal eGFR and normal albumin excretion rate, but the association is weaker in some groups of diabetic patients with preexisting renal complications.

Assessment of the adverse effects of sirolimus versus everolimus in pediatric heart transplant recipients

Literature is limited comparing adverse effects (AEs) of the proliferation signal inhibitors (PSIs) sirolimus (SRL) and everolimus (EVL) in pediatric heart transplant (HTx) recipients. Single-center, observational cohort analysis assessing first use of SRL or EVL in pediatric HTx recipients <21 years of age with up to 2 years follow-up between 2009 and 2020. Eighty-seven patients were included, with 52 (59.8%) receiving EVL and 35 (40.2%) receiving SRL. Tacrolimus with PSI was the most common regimen. Intergroup comparison revealed lower baseline estimated glomerular filtration rate (eGFR) and greater increase in eGFR from baseline to 6 months and latest follow-up in SRL cohort compared to EVL cohort. There was greater increase in HDL cholesterol in SRL cohort compared to EVL cohort. Intragroup analysis revealed eGFR and HDL cholesterol increased significantly within SRL cohort, triglycerides and glycosylated hemoglobin increased in EVL cohort, and LDL cholesterol and total cholesterol increased in both cohorts (all p < .05). There were no differences in hematological indices or rates of aphthous ulcers, effusions, or infections between cohorts. Incidence of proteinuria was not significantly different among those screened within cohorts. Of those included in our analysis, one patient in SRL cohort (2.9%) and two in EVL cohort (3.8%) had PSI withdrawn due to AE. Low-dose PSIs in calcineurin inhibitor minimization regimens appear well-tolerated with low withdrawal rate secondary to AE in pediatric HTx recipients. While incidence of most AE was similar between PSI, our results suggest EVL may be associated with less favorable metabolic impact than SRL in this population.

Risk Factors for Early Onset of Proteinuria in Patients Receiving Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma

Introduction: Proteinuria is one of the adverse events of atezolizumab plus bevacizumab combination therapy (Atezo + Bev) and can cause interruption in the use of Bev. However, the risk factors for proteinuria in patients with hepatocellular carcinoma (HCC) who are receiving Atezo + Bev have not yet been investigated. The aim of this study was to identify the risk factors for early onset of proteinuria in Atezo + Bev for patients with unresectable HCC. Methods: Sixty-four patients with Child-Pugh scores of 5–7, an Eastern Cooperative Oncology Group performance status of 0 or 1, and low level of proteinuria (1+ or less on a dipstick test and urine protein-to-creatinine ratio (UPCR) less than 2.0 g/g Cr) at the initiation of therapy were analyzed. The level of proteinuria was evaluated based on the Common Terminology Criteria for Adverse Events version 5.0. We adopted the UPCR for the quantitative test instead of a 24-h urine collection. The incidence of proteinuria and changes in liver function were retrospectively investigated. Results: The cumulative incidence of proteinuria over a 24-week period was 34.4%. Multivariate analysis showed that a low estimated glomerular filtration rate (hazard ratio [HR], 3.807; 95% confidence interval [CI], 1.579–9.180; p = 0.003), treatment for hypertension (HR, 6.224; 95% CI, 1.614–24.010; p = 0.008), and high systolic blood pressure (SBP) (HR, 2.649; 95% CI, 1.133–6.194; p = 0.025) were risk factors for proteinuria. Serum albumin levels and albumin-bilirubin scores in patients with proteinuria worsened. In addition, a mean SBP ≥135 mm Hg during treatment was the only risk factor for the development of severe proteinuria (UPCR >2 g/g Cr). Conclusion: Our study found that controlling blood pressure is extremely important for the management of proteinuria in patients with HCC who are receiving Atezo + Bev.

Gender-Specific Renal Function and Urinary Syndrome in Patients with Liver Cirrhosis of Alcoholic Etiology: Observational Study

Background. Gender has now been proven to have a significant impact on the development, course and outcome of a large number of diseases, including alcoholic liver disease. Alcohol consumption is one of the leading risk factors for various diseases. Alcohol-related diseases cause 10% of all deaths worldwide among young and middle-aged people. The occurrence of renal dysfunction in cirrhosis of the liver is an integral part of the natural course of the disease. At the moment, the diagnosis of gender-specific renal dysfunction that occurs against the background of liver cirrhosis is essential for the development of effective treatment strategies and the improvement of survival.Objectives. The study is aimed at identifying the features of the gender-specific renal function and urinary syndrome in patients with liver cirrhosis of alcoholic etiology and assessing the comprehensive prognostic significance of the indicators of common urine analysis in the diagnosis of renal dysfunction.Methods. An observational study was carried out using data from medical records of 158 patients with alcoholic liver cirrhosis (95 men and 63 women), aged 36 to 72 years, who were inpatients between February 2016 and March 2020. Physical examination and laboratory diagnostic data were taken into account. Binary predictors of renal dysfunction progression in patients with alcoholic liver cirrhosis were determined based on the analysis of descriptive statistics. Statistical data processing was performed using computer program Statistica 10 (StatSoft, Inc., USA) and standard Microsoft Excel software package (Microsoft Office 2016). Non-parametric statistical methods were used to describe the results. Quantitative results were analyzed using the Mann-Whitney test; comparison of two samples by a qualitatively defined feature was performed by means of the Fisher angular transformation method. Differences were considered significant at p ˂ 0.05. A multilayer neural network function from the Statistica 10 Neural Networks software was used to construct a classification scheme for renal dysfunction (yes/no). Neural network performance was assessed using descriptive and inductive statistics, calculating sensitivity, specificity, performing ROC analysis and constructing cumulative gains charts.Results. A renal function test revealed a significant decrease in glomerular filtration rate (p = 0.029) and a significant increase in urinary albumin/creatinine ratio (p &lt; 0.0001) in women with alcoholic liver cirrhosis as compared with men. Women are also reported to have a high incidence of proteinuria, leukocyturia and bacteriuria. According to ROC-analysis, the urinalysis indicators have a high prognostic significance in identifying renal dysfunction in men and women with alcoholic liver cirrhosis (AUROC = 0.902 and sensitivity 81.82%, AUROC = 0.881 and sensitivity 75.00%, respectively).Conclusion. Renal dysfunction develops earlier and occurs twice as often in women with alcoholic cirrhosis than in men of the same age. The application of a neural network mechanism to predict renal dysfunction in men and women with alcoholic liver cirrhosis according to the indicators of urinalysis provides a high prognostic ability.

The Role of Vitamin D in Kidney Transplantation Outcomes: A Systematic Review.

The aim of this systematic review is to assess the impact of vitamin D on the outcomes of kidney transplantation and investigate whether its deficiency is associated with a negative impact. Methods: We conducted a systematic literature search in PubMed, Scopus and Cochrane databases, as well as gray literature. Ultimately, 16 articles with an average of 255.75 patients were included in this review. These articles compared the long-term outcomes of vitamin D deficiency and/or vitamin D supplementation therapy on kidney transplant recipients by assessing various parameters. Results: Most of the included studies showed a negative effect of vitamin D deficiency on kidney transplantation by being associated with a worse graft function, higher incidence of acute rejection episodes, higher incidence of proteinuria and lower overall graft and patient survival rate. Conclusions: We suggest that patients awaiting kidney transplantation have a careful evaluation in order to assess their vitamin D status and the optimal supplementation therapy. Regular follow-up of vitamin D levels post-transplant is also suggested. Prospective studies will be needed to establish the positive effects of vitamin D supplementation therapy on kidney transplant outcomes.

Relationship between Ideal Cardiovascular Health and Incident Proteinuria: A 5 Year Retrospective Cohort Study.

The objective of this study was to examine whether a higher number of ideal cardiovascular health (CVH) metrics are beneficial for lowering the risk of proteinuria. This is a retrospective cohort study with an average follow-up of 5 years. Participants between 21 and 75 years old and without a history of cardiovascular disease and proteinuria were enrolled. CVH metrics, including smoking, diet, physical activity, blood pressure, body mass index (BMI), cholesterol, and fasting glucose, were assessed by questionnaires, physical examination, and blood analysis. Proteinuria was assessed by dipstick measurement. During the follow-up period, 169,366 participants were enrolled, and 1481 subjects developed proteinuria. A higher number of ideal CVH metrics was related to a lower risk of proteinuria after adjustment. Among the components of CVH metrics, ideal blood pressure (HR = 0.33, 95% CI = 0.25–0.43), fasting glucose (HR = 0.17, 95% CI = 0.12–0.22), and BMI (HR = 0.20, 95% CI = 0.15–0.27) had beneficial effects on proteinuria. Despite no significant benefit of diet score, the corresponding lower sodium intake showed a lower risk of proteinuria (HR = 0.58, 95% CI = 0.43–0.79). Incident proteinuria was inversely related to the number of ideal CVH metrics. CVH metrics may be a predictor of proteinuria, and achieving a higher number of ideal scores should be recommended as a proteinuria prevention strategy.

Meta-Analysis of Efficacy and Safety of Karelizumab Combined with Apatinib in the Treatment of Advanced Gastric Cancer.

Objective To systematically evaluate the clinical efficacy and safety of karelizumab combined with apatinib in the treatment of advanced gastric cancer. Methods The published databases were searched by computer, Chinese: China Biomedical Literature Database (CBM), Wanfang Journal Database, China national knowledge infrastructure (CNKI), and China Science and Technology Journal Database (VIP); English: Embase, Cochrane library, and PubMed. The search time is from the establishment of the database to May 2022, and clinical randomized controlled trials (RCT) with advanced gastric cancer as the research object and karelizumab combined with apatinib as the research variables are collected. According to the bias risk evaluation standard of Cochrane System Evaluator's Manual, the literatures meeting the inclusion standard were evaluated for bias risk, and the meta-analysis was conducted by Review Manager 5.3. Results. A total of 20 articles with 1150 patients were included in this study. All the included 20 articles reported objective remission rate (ORR), and the heterogeneity among 20 studies was low (P > 0.05, I2 = 0%). The ORR of gastric cancer patients in the observation group was significantly higher than that in the blank group [odds ratio (OR) = 1.97, 95% CI [1.53, 2.62], P < 0.01). All the included 20 articles reported disease control rate (DCR), and the heterogeneity among 20 studies was low (P = 0.87, I2 = 0%). The ORR of gastric cancer patients in the observation group was significantly higher than that in the blank group (OR = 3.09, 95% CI [2.29, 4.16], P < 0.01). Three articles in the included literature reported the median OS, and the heterogeneity among the three studies was low (P = 0.70, I2 = 0%). The median OS of gastric cancer patients in the observation group was significantly higher than that in the blank group (MD = 3.97, 95% CI [3.61, 4.39], P < 0.01). There are three reports on median progression-free survival (PFS) in the included literature, and there is high homogeneity among the three studies (P < 0.00001, I2 = 86%). There is no statistical difference between the median PFS of gastric cancer patients in the observation group and the blank group (MD = 1.21, 95% CI [−1.20, 3.70], P = 0.29). The incidence of hypertension in the observation group was significantly higher than that in the blank group [OR = 6.19, 95% CI (1.91, 20.20), P = 0.003]. The incidence of proteinuria in the observation group was significantly higher than that in the blank group [OR = 3.97, 95% CI (1.08, 14.59), P = 0.03]. There was no significant difference in the incidence of other adverse reactions such as hand-foot syndrome, diarrhea, and myelosuppression between the observation group and the blank group. The levels of IFN-γ and TNF-α in the observation group were significantly higher than those in the blank group (P < 0.0001). The levels of IL-10, IL-4, and tumor markers in the observation group were significantly lower than those in the blank group (P < 0.05). Egger's test showed that there was no publication bias in the 20 included studies (P > 0.05). Conclusion Karelizumab combined with apatinib is effective in the treatment of advanced gastric cancer, with low incidence of adverse reactions and high safety. However, a large number of multicenter, large sample size, and high-level RCT are needed for clinical verification.

Different clinical features of children and adults in regional outbreak of Delta COVID-19

BackgroundThis study compared clinical features of the Delta variant of coronavirus disease 2019 (COVID-19) in children and adults.MethodsClinical data included 80 children and 132 adults with the Delta variant of COVID-19, hospitalized in the Affiliated Hospital of Putian College between September and October 2021. The data was analyzed retrospectively.ResultsThe proportion of mild patients in the children group (50%) was higher than that in the adults group (17.9%). Cough (25%, 20/80) and diarrhea (1.3%, 1/80) symptoms in children group were significantly less frequent. Compared with adults, there was no significant difference in the viral load of SARS-CoV-2 in samples collected by nasopharyngeal swabs. In children, lymphocyte count was higher [1.98 (0.25–4.25) vs 1.20 (0.29–4.27) ×109/L], whereas the interleukin-6 level was lower [5.87 (1.50–61.40) vs 15.15 (1.79–166.30) pg/mL] than that in adults group. Additionally, the incidence of liver injury in children group was lower than that in adults group. There was no significant difference in the incidence of proteinuria (22/75 vs 45/112) between the two groups, but the serum creatinine level in children was lower [42.0 (28.0–73.0) vs 57.0 (32.0–94.0) µmol/L].ConclusionCompared with adults, children with the Delta variant of COVID-19 have differences in symptoms, clinical classification, inflammatory indices, and liver/kidney function injury. Children’s illness is relatively mild. Clinicians should pay attention to their differences and use drugs accurately.

U-Shaped Relationship Between Proteinuria and High-Density Lipoprotein Cholesterol: Results of Cross-Sectional and Six Years Cohort Studies (KITCHEN-10).

BackgroundAlthough a very high level of high-density lipoprotein cholesterol (HDL-C) may be a potential cardiovascular disease risk factor, the detail and underlying mechanism remain unclear. Therefore, we examined the associations of serum HDL-C with the incidence of proteinuria, a predictor for cardiovascular disease, in a community-based study.MethodsWe investigated clinical parameters, including serum HDL-C and proteinuria, among 1,191,409 people aged 40 - 74 years who underwent a health checkup in a cross-sectional study. In the cohort study, the incidence of proteinuria after 6 years was investigated in 451,987 participants without proteinuria at baseline, who were simultaneously enrolled in the cross-sectional study.ResultsThe prevalence of proteinuria showed a U-shaped relationship with 10 HDL-C categories, with a minimum of 60 - 89 mg/dL in the cross-sectional study. Logistic regression analysis showed similar U-shaped relationships between odds ratios for proteinuria and HDL-C categories, with a minimum of 70 - 79 mg/dL. The associations between very high HDL-C (≥ 90 mg/dL) and proteinuria were strengthened after adjustment for body mass index (BMI). In the cohort study, a crude L-shaped relationship was observed between the incidence of proteinuria and baseline HDL-C, which turned into U-shaped relationship after adjustment for baseline BMI and HDL-C after 6 years.ConclusionsLow and very high levels of HDL-C may be associated with the incidence of proteinuria, and BMI may be a potent contributing factor to the underlying mechanism.

Folate intake and incident chronic kidney disease: a 30-year follow-up study from young adulthood to midlife

The relation of long-term dietary folate intake with incident chronic kidney disease (CKD) remains uncertain. We aimed to investigate the association between dietary folate intake and incident CKD in a 30-y follow-up study from young adulthood to midlife. A total of 4038 American adults aged 18-30 y and without reduced estimated glomerular filtration rate (eGFR) were enrolled in 1985-1986 and monitored until 2015-2016 in the CARDIA (Coronary Artery Risk Development in Young Adults) study. Diet was assessed by a validated dietary history questionnaire at baseline, in 1992-1993, and in 2005-2006. The primary outcome was incident CKD, defined as an eGFR <60 mL · min-1 · 1.73 m-2 or a urinary albumin to creatinine ratio (ACR) ≥30 mg/g. The secondary outcomes included 1) incident decreased eGFR, defined as an eGFR <60 mL · min-1 · 1.73 m-2, and 2) incident albuminuria, defined as an ACR ≥30 mg/g. During the follow-up, 642 (15.9%) participants developed CKD. Overall, there was a significant L-shaped relation of dietary folate with incident CKD after adjustment for potential confounders. Compared with the lowest quintile of total folate intake, the multivariable-adjusted HRs (95% CIs) in quintiles 2-5 for incident CKD were 0.69 (0.56, 0.85), 0.35 (0.27, 0.45), 0.34 (0.26, 0.45), and 0.39 (0.30, 0.51), respectively. Similar results were found for the secondary outcomes. Moreover, the L-shaped association was confirmed in a subset of the cohort (n = 1462) with serum folate measured at baseline, in 1992, and in 2000. Higher folate intake in young adulthood was longitudinally associated with a lower incidence of CKD later in life. Additional studies are warranted to establish the causal inference.

Clusters of clinical and immunologic features in patients with bullous systemic lupus erythematosus: experience from a single-center cohort study in China

BackgroundBullous systemic lupus erythematosus (BSLE) is a rare subtype of systemic lupus erythematosus (SLE) that is clinically characterized by subepidermal tense vesicles or bullae. We aimed to investigate the clinical and laboratory features of patients with BSLE.MethodsWe retrospectively reviewed all patients who fulfilled the diagnostic criteria for BSLE in our institution from 2015 to 2021. Cutaneous lesions, systemic manifestations, treatment options, and outcomes were evaluated. For each case of BSLE, four controls were randomly selected from patients with single SLE. Major clinical and laboratory characteristics were compared between the two groups.ResultsAmong 4221 patients with SLE, 12 developed BSLE. Vesiculobullous lesions were the first sign in five of the BSLE patients (5/12, 41.7%) and appeared after SLE diagnosis in the remaining seven patients (7/12, 58.3%), with a median duration from SLE onset of 36 months (4–115 months). The most common BSLE-affected sites were the head and neck (10/12, 83.3%), extremities (9/12, 75.0%), trunk (7/12, 58.3%), and mucosae (6/12, 50.0%). All patients with BSLE had extra-cutaneous involvement. The SLE disease activity index score exceeded 5 in 10/12 (83.3%) patients, which indicated high disease activity. Patients in the BSLE group had significantly higher incidences of proteinuria (83.3% vs. 47.9%, P = 0.027), hematuria (75% vs. 31.3%, P = 0.006), hemolytic anemia (33.3% vs. 0%, P = 0.000), and leukopenia (66.7% vs. 25.0%, P = 0.006) than those in the control group. The use of systemic corticosteroids, immunosuppressants, dapsone, and skin care was effective in controlling disease.ConclusionsVesiculobullous lesions may be the first manifestation and indicate a high disease activity in patients with BSLE. Early diagnosis using clinical, histopathological, and immunological evaluations can lead to appropriate treatment of this progressive disease and improve prognosis.

Clinical significance of low pre-transplant donor specific antibodies (DSA) in living donor kidney recipients with negative complement-dependent cytotoxicity crossmatches (CDCXM), and negative flow cytometry crossmatches (FLXM) – A single-center experience

BackgroundIt is controversial whether all donor-specific antibodies (DSA) detected by the solid-phase single antigen bead (SAB) assay negatively affect kidney transplantation outcomes. The study aimed to evaluate the possible clinical significance of low pre-transplant DSA in living donor kidney recipients. We analyzed a group of patients with HLA-A, B, and -DR DSA reactivities below a virtual crossmatch (VXM) value of 5000 MFI but with all VXM DSA reactivities at HLA-DQ, -DP, and -Cw, which were not typed routinely for donors prior to transplantation. We also investigated the incidence of persistent and de novo DSAs in available posttransplant SAB assays. MethodsFrom the historical cohort of living donor recipients transplanted between 2014 and 2018 at our center (n = 82), 55 patients met the inclusion criteria, namely: these patients were > 18 years old with non-HLA identical sibling donors, who were not desensitized, who had available pre-transplant SAB results, and who had negative both complement-dependent cytotoxicity crossmatch (CDCXM) and flow cytometry crossmatch (FLXM) results. An additional donor HLA typing, performed for all 55 recipients, identified donor additional HLA-DQ, -DP, and -Cw DSA reactivities. These patients were then divided by SAB reactivity into three groups: 1) those with DSA-positive reactivities; 2) those with non-donor-specific anti-HLA reactivities (NDSA); and, 3) those who were anti-HLA-negative. All these recipients were followed for three years and checked for their de novo or persistent DSA. ResultsIn the studied cohort, DSA-positive, NDSA reactive, and anti-HLA negative recipients constituted 33%, 36%, and 31% of 55 patients, respectively. Non-routinely considered pre-transplant HLA-DQ, -DP, and -Cw DSA-positive reactivities were shown in as many as 78% of DSA-positive cases (group 1) with the lowest MFI value of 319 to DP4 and the highest MFI of 5767 to DQ2. Of the pre-transplant HLA-A, B, and -DR DSA reactivities, only -DR52 DSA reactivity reached the highest MFI value of 2191. These detected DSAs did not reduce the mean estimated glomerular filtration rate (eGFR) values and did not increase the incidence of proteinuria in recipients. While the 3-year graft survival was lower in the DSA-positive group (94.4%) with one recipient who lost kidney transplant, the difference was not significantly different (p = 0.7) from the NDSA (100%) and negative (100%) groups. In terms of the incidence of de novo acute antibody-mediated rejection (AMR) at three years after transplantation, no case has been reported in the cohort. This may suggest that low DSA-positive recipients do not experience higher rejection rate. However, DSA-positive recipients had a tendency for a higher frequency of C4d deposits in peritubular capillaries (PTC) and de novo DSA. ConclusionOur 3-year follow-up of patients with low pre-transplant DSA found no association with a deterioration in graft function and worse graft survival. Furthermore, we did not observe an increase in AMR in our patients with low DSA. A larger cohort and a longer follow-up period may be needed to evaluate the tendency of low DSA-positive recipients towards the higher incidence of C4d deposits in PTC and/or de novo DSA.

Association Between Serum Carnosinase Concentration and Activity and Renal Function Impairment in a Type-2 Diabetes Cohort.

Introduction: Genetic studies have identified associations of carnosinase 1 (CN1) polymorphisms with diabetic kidney disease (DKD). However, CN1 levels and activities have not been assessed as diagnostic or prognostic markers of DKD in cohorts of patients with type 2 diabetes (T2D). Methods: We established high-throughput, automated CN1 activity and concentration assays using robotic systems. Using these methods, we determined baseline serum CN1 levels and activity in a T2D cohort with 970 patients with no or only mild renal impairment. The patients were followed for a mean of 1.2 years. Baseline serum CN1 concentration and activity were assessed as predictors of renal function impairment and incident albuminuria during follow up. Results: CN1 concentration was significantly associated with age, gender and estimated glomerular filtration rate (eGFR) at baseline. CN1 activity was significantly associated with glycated hemoglobin A1c (HbA1c) and eGFR. Serum CN1 at baseline was associated with eGFR decline and predicted renal function impairment and incident albuminuria during the follow-up. Discussion: Baseline serum CN1 levels were associated with presence and progression of renal function decline in a cohort of T2D patients. Confirmation in larger cohorts with longer follow-up observation periods will be required to fully establish CN1 as a biomarker of DKD.