Helicobacter pylori Infection is Associated with Occurrence of Proteinuria in Type 2 Diabetes Patients:A Systemic Review and Meta-Analysis

Background:Type 2diabetes (T2DM)patients are susceptible to Helicobacterpylori (HP),and it has been reported that the occurrence of proteinuria is associated with HP infection in T2DM patients;however,this view remains controversial.This meta-analysis aimed to explore the association between HP infection and the occurrence of proteinuria in T2DM patients.In addition,we hope to provide some recommendations to readers in clinical or related fields. Methods:Our meta-analysis was conducted with the methodology of the Cochrane Collaboration.Search strategies were formulated by relevant professionals.Case-control studies that compared the occurrence ofproteinuria in T2DM patients with and without HP infection were involved in our meta-analysis.Relevant English or Chinese studies were searched on online databases before 2018,including PubMed,the Cochrane library,Medline,Google Scholar,the China National Infrastructure,and Wanfang database.The search strategies were "diabetic proteinuria,diabetic microalbuminuria,diabetic albumainuria,diabetic kidney disease,diabetic renal dysfunction,diabetic renal disease,diabetic nephropathy,diabetic complications,and diabetic mellitus,combined with HP."The quality of these involved articles was separately assessed by two investigators using the Newcastle-Ottawa Scale (NOS).Odds ratios (ORs)and associated 95% confidence intervals (CIs)were extracted and pooled using fixed-effects models. Results:Seven studies involving 1029participants were included.The quality of these seven articles was all above five stars as assessed by NOS,and there was no significant publication bias in our meta-analysis.We found that T2DM patients with HP infection had a 2.00 times higher risk of the occurrence of proteinuria than patients without HP infection (OR:2.00,95%CI:1.48-2.69). Conclusions:Our analysis showed that HP infection was associated with the occurrence of proteinuria in T2DM patients.HP radical surgery might be a therapeutic option for protecting kidney function in patients with T2DM.

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.

Machine learning in nephrology: scratching the surface

Machine learning shows enormous potential in facilitating decision-making regarding kidney diseases.With the development of data preservation and processing,as well as the advancement of machine learning algorithms,machine learning is expected to make remarkable breakthroughs in nephrology.Machine learning models have yielded many preliminaries to moderate and several excellent achievements in the fields,including analysis of renal pathological images,diagnosis and prognosis of chronic kidney diseases and acute kidney injury,as well as management of dialysis treatments.However,it is just scratching the surface of the field;at the same time,machine learning andits applications in renal diseases are facing a number of challenges.In this review,we discuss the application status,challenges and future prospects of machine learning in nephrology to help people further understand and improve the capacity for prediction,detection,and care quality in kidney diseases.

Critical hubs of renal ischemia-reperfusion injury:endoplasmic reticulum-mitochondria tethering complexes

Mitochondrial injury and endoplasmic reticulum(ER)stress are considered to be the key mechanisms of renal ischemia-reperfusion(I/R)injury.Mitochondria are membrane-bound organelles that form close physical contact with a specific domain of the ER,known as mitochondrial-associated membranes.The close physical contact between them is mainly restrained by ER-mitochondria tethering complexes,which can play an important role in mitochondrial damage,ER stress,lipid homeostasis,and cell death.Several ER-mitochondria tethering complex components are involved in the process of renal I/R injury.A better understanding of the physical and functional interaction between ER and mitochondria is helpful to further clarify the mechanism of renal I/R injury and provide potential therapeutic targets.In this review,we aim to describe the structure of the tethering complex and elucidate its pivotal role in renal I/R injury by summarizing its role in many important mechanisms,such as mitophagy,mitochondrial fission,mitochondrial fusion,apoptosis and necrosis,ER stress,mitochondrial substance transport,and lipid metabolism.

Potential Value of Datura stramonium Agglutinin-recognized Glycopatterns in Urinary Protein on Differential Diagnosis of Diabetic Nephropathy and Nondiabetic Renal Disease

Background： Diabetic nephropathy （DN） is the most common and serious microvascular complication of diabetes. To date, the gold standard for identifying DN and nondiabetic renal disease （NDRD） is a renal biopsy; however, there is currently no reliable diagnostic marker to identify DN and NDRD in a noninvasive manner. This study aimed to investigate the different glycopatterns in urine specimens of DN patients and NDRD patients for a differential diagnosis. Methods： In total, 19 DN patients and 18 NDRD patients who underwent renal biopsies between March 2015 and March 2016 at the Chinese People＇s Liberation Army General Hospital were enrolled in this study. A lectin microarray was used to investigate the glycopatterns in the urinary protein of the 37 patients. Ratio analysis and one-way analysis of variance were used to screen altered glycopatterns. Then, the altered glycopatterns between the DN and NDRD groups were verified by a urinary protein microarray among another 32 patients （15 with DN and 17 with NDRD）, and receiver operating characteristic （ROC） curve analysis was used to determine the diagnostic value of the altered glycopatterns in differentiating DN and NDRD. Finally, lectin blotting was used to evaluate the altered glycosylation in protein level. Results： The result of lectin microarrays revealed that the relative abundance of the （13-1,4）-linked N-acetyI-D-glucosamine （GlcNAc） recognized by lectin Datura stramonium agglutinin （DSA） was significantly higher in urinary protein in DN patients than that in NDRD patients （fold change 〉1.50, P 〈 0.001）. Subsequently, the results of urinary protein microarrays were consistent with lectin microarrays （P 〈 0.05）. Furthermore, the ROC curve showed that glycopatterns could effectively distinguish DN from NDRD patients （area under the ROC curve = 0.94, P 〈 0.001）. DSA lectin blotting showed that glycoproteins, with a molecular weight of approximately 50,000, demonstrated a difference in urine samples between DN patients and NDRD patients. Conclusions： The relative abundance of （13-1,4）-linked GIcNAc recognized by/ectin DSA and urinary glycoprotein with a molecular weight of approximately 50,000 are significantly different between DN and NDRD patients, indicating that the glycopatterns could be used as potential biomarkers for a differential diagnosis.

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.