Peripheral Neuropathy Associated with Higher Mortality in Population with Chronic Kidney Disease: National Health and Nutrition Examination Surveys.

Introduction: Peripheral neuropathy (PN), one of the commonest neurological complications of chronic kidney disease (CKD), was associated with physical limitation. Studies showed that a decrease in physical capability in patients with CKD is related with an increased risk of mortality. The objective of our research was to directly explore the relationship between PN and risk of mortality in patients with CKD. Method: 1,836 participants with CKD and 6,036 participants without CKD, which were classified by PN based on monofilament examination in National Health and Nutrition Examination Survey (NHANES), were collected from the 1999 to 2004 National Health and Nutrition Examination Surveys. Multivariable Cox proportional hazard models were conducted to assess the relationships of PN and deaths in patients with CKD and non-CKD. Results: During 14 years of a median follow-up from 1999 to 2015 and 2004 to 2015, 1,072 (58.4%) and 1,389 (23.0%) deaths were recorded in participants with CKD and without CKD, respectively. PN was related with increased all-cause mortality even after adjusting possible confounding factors in population with CKD (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.17-1.53) and without CKD (HR 1.27, 95% CI 1.12-1.43). And the adjusted HRs (95% CI) for cardiovascular mortality of the people with CKD and without CKD who suffered from PN were 1.42 (1.07, 1.90) and 1.23 (0.91, 1.67), respectively, versus those without PN. Conclusion: PN was related with a higher risk of all-cause and cardiovascular death in people with CKD, which clinically suggests that the adverse prognostic impact of PN in the CKD population deserves attention and is an important target for intervention.

Development of a new prognostic index PNPI for prognosis prediction of CKD patients with pneumonia at hospital admission.

Background: The aim of this study was to investigate the relationship between pneumonia and chronic kidney disease (CKD), to elucidate potential risk factors, and to develop a new predictive model for the poor prognosis of pneumonia in CKD patients. Method: We conducted a retrospective observational study of CKD patients admitted to Tongji Hospital between June 2012 and June 2022. Demographic information, comorbidities or laboratory tests were collected. Applying univariate and multivariate logistic regression analyses, independent risk factors associated with a poor prognosis (i.e., respiratory failure, shock, combined other organ failure, and/or death during hospitalization) for pneumonia in CKD patients were discovered, with nomogram model subsequently developed. Predictive model was compared with other commonly used pneumonia severity scores. Result: Of 3,193 CKD patients with pneumonia, 1,013 (31.7%) met the primary endpoint during hospitalization. Risk factors predicting poor prognosis of pneumonia in CKD patients were selected on the result of multivariate logistic regression models, including chronic cardiac disease; CKD stage; elevated neutrophil to lymphocyte ratio (NLR) and D-dimer; decreased platelets, PTA, and chloride iron; and significant symptom presence and GGO presentation on CT. The nomogram model outperformed other pneumonia severity indices with AUC of 0.82 (95% CI: 0.80, 0.84) in training set and 0.83 (95% CI: 0.80, 0.86) in testing set. In addition, calibration curve and decision curve analysis (DCA) proved its efficiency and adaptability. Conclusion: We designed a clinical prediction model PNPI (pneumonia in nephropathy patients prognostic index) to assess the risk of poor prognosis in CKD patients with pneumonia, which may be generalized after more external validation.

Clinical characteristics and risk factor analysis of Pneumocystis jirovecii pneumonia in patients with CKD: a machine learning-based approach.

Patients with chronic kidney disease (CKD) who are being treated with immunosuppressive medications are at risk for developing Pneumocystis jirovecii pneumonia (PCP). We attempted to characterize the clinical aspects of PCP in CKD patients in order to alert high-risk patients with bad prognosis. A retrospective study of CKD patients was conducted from June 2018 to June 2022. Based on PCP diagnostic criteria, these patients were divided into PCP and non-PCP groups. Using univariate and multivariate logistic regression analysis, risk indicators were evaluated, and nomogram and decision tree were developed. Of the CKD patients screened for Pneumocystis carinii nucleic acid, 1512 were included. Two-hundred forty four (16.14%) were diagnosed with PCP. Of the PCP, 88.5% was receiving glucocorticoid (GC) therapy, of which 66.3% received more than 0.5 mg/kg GC. Multivariate analysis showed that membranous nephropathy (OR 2.35, 95% CI 1.45-3.80), immunosuppressive therapy (OR 1.94, 95% CI 1.06-3.69), and ground glass opacity of CT scanning (OR 1.71, 95% CI 1.10-2.65) were associated with increased risk of Pneumocystis carinii infection. The AUC of nomogram based on logistics regression was 0.78 (0.75-0.81). The mortality in patients with PCP was 32.40%. Univariate analysis and decision tree showed that pulmonary insufficiency (PO2: OR 0.98, 95% CI 0.96-1.00), elevated APTT (OR 1.07, 95% CI 1.04-1.11), and reduced hemoglobin (OR 0.97, 95% CI 0.96-0.98) were associated with poor prognosis. PCP is not rare in CKD patients, particularly in those treated with immunosuppressive therapy. Considering the high mortality of the cases, further studies on the prevention and management of these patients are needed.

Identification of Hub Genes and Immune-Related Pathways for Membranous Nephropathy by Bioinformatics Analysis.

OBJECTIVE: We aim to explore the detailed molecular mechanisms of membrane nephropathy (MN) related genes by bioinformatics analysis. METHODS: Two microarray datasets (GSE108109 and GSE104948) with glomerular gene expression data from 65 MN patients and 9 healthy donors were obtained from the Gene Expression Omnibus (GEO) database. After processing the raw data, DEGs screening was conducted using the LIMMA (linear model for microarray data) package and Gene set enrichment analysis (GSEA) was performed with GSEA software (v. 3.0), followed by gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The protein-protein interaction (PPI) network analysis was carried out to determine the hub genes, by applying the maximal clique centrality (MCC) method, which was visualized by Cytoscape. Finally, utilizing the Nephroseq v5 online platform, we analyzed subgroups associated with hub genes. The findings were further validated by immunohistochemistry (IHC) staining in renal tissues from MN or control patients. RESULTS: A sum of 370 DEGs (188 up-regulated genes, 182 down-regulated genes) and 20 hub genes were ascertained. GO and KEGG enrichment analysis demonstrated that DEGs of MN were preponderantly associated with cell damage and complement cascade-related immune responses. Combined with literature data and hub gene-related MN subset analysis, CTSS, ITGB2, and HCK may play important roles in the pathological process of MN. CONCLUSION: This study identified novel hub genes in MN using bioinformatics. We found that some hub genes such as CTSS, ITGB2, and HCK might contribute to MN immunopathological process, providing new insights for further study of the molecular mechanisms underlying glomerular injury of MN.

Sugar-sweetened beverage consumption and mortality of chronic kidney disease: results from the US National Health and Nutrition Examination Survey, 1999-2014.

Background: The relationship between intake of sugar-sweetened beverages (SSBs) and the risk of death in patients with chronic kidney disease (CKD) is unclear. We evaluated the association between SSB intake and subsequent overall mortality in CKD patients. Methods: We included data from 3996 CKD patients who participated in the 1999-2014 National Health and Nutrition Examination Survey (NHANES). SSB intake was assessed by a 24-h dietary recall, grouped as none, >0 to <1 serving/day, 1 to <2 servings/day and ≥2 servings/day. After adjusting for demographic variables, lifestyle, diet and comorbidities, Cox proportional risk regressions were applied to analyze the associations between the daily intake of SSBs as well as added sugar from beverages and all-cause mortality. Results: In the whole research population, the median age at baseline was 67 years, 22% were Black and 54% were female. A total of 42% had stage 3 CKD. During an average follow-up period of 8.3 years, a sum of 1137 (28%) deaths from all causes was recorded. The confounder-adjusted risk of mortality was associated with an increase of 1 serving/day of SSBs, with all-cause mortality of 1.18 [95% confidence interval (95% CI)1.08-1.28], and intakes of increased 20-g added sugar/1000 kcal of total energy per day were associated with all-cause mortality of 1.14 (1.05-1.24). Equivalently substituting 1 serving/day of SSBs with unsweetened coffee [HR (95% CI) 0.82 (0.74-0.91)], unsweetened tea [HR (95% CI) 0.86 (0.76-0.98)], plain water [HR (95% CI) 0.79 (0.71-0.88)], or non- or low-fat milk [HR (95% CI) 0.75 (0.60-0.93)] were related to a 14-25% reduced risk of all-cause mortality. Conclusion: Findings suggest that in the CKD population, increased SSB intake was associated with a higher risk of mortality and indicated a stratified association with dose. Plain water and unsweetened coffee/tea might be possible alternatives for SSBs to avert untimely deaths.

Early Menopause May Associate With a Higher Risk of CKD and All-Cause Mortality in Postmenopausal Women: An Analysis of NHANES, 1999-2014.

Background: Chronic kidney disease (CKD) in women is often accompanied by hormone disorders such as sex hormones, and most women with CKD are in the post-menopausal age group. Due to the close relationship between menopause and sex hormones, we aimed to explore the association between early menopause and CKD in post-menopausal women, and the influence of early menopause on longevity in the CKD population. Methods: Information regarding 4,945 post-menopausal women was extracted from the database of the National Health and Nutrition Examination Survey (NHANES) 1999-2014, and then divided into 4 groups according to the type of menopause (natural or surgical) and early menopause (menopause at age <45) or not. The association between early menopause and CKD prevalence was examined using multivariable logistic regression, while we used multivariable Cox proportional hazards models to investigate the possible relationship between early menopause and all-cause mortality in CKD and non-CKD populations. The differences in the levels of sex hormones between women with and without CKD were also explored. Results: Compared with women with natural menopause at age ≥45, women experiencing early natural menopause had a higher risk of CKD [OR = 1.26 (1.01-1.56)]. Similarly, as compared to women with surgical menopause at age ≥ 45, women in the early surgical menopause group were more likely to have CKD [OR = 1.38 (1.05-1.81)]. In addition, early surgical menopause was associated with higher mortality in the non-CKD group [HR = 1.62 (1.06-2.49)], but not in the CKD group. Women with CKD had a higher level of luteinizing hormone and follicle-stimulating hormone, combined with a lower level of testosterone and estradiol than the non-CKD women. Conclusion: Both early natural and surgical menopause were associated with a higher risk of CKD. Early surgical menopause was a hazard factor for survival in the non-CKD group, but not in the CKD group. Further research is required to understand the mechanisms.

Dietary Omega-3 Fatty Acid Intake and Mortality in CKD Population: A 1999-2014 NHANES Analysis.

INTRODUCTION: High risk of early death, especially contributed to cardiovascular disease, exists in patients who have chronic kidney disease (CKD). And the burden of cardiovascular disease is able to be lightened by an increase in omega-3 polyunsaturated fatty acid (omega-3 PUFA). A diet high in omega-3 PUFA in the general population is protective, although it is inconclusive about its beneficial role in the CKD population. METHODS: From the 1999 to 2014 National Health and Nutrition Examination Surveys (NHANES), we can collect 2,990 participants who suffered from CKD, who were classified into 4 groups: <0.86, 0.87-1.30, 1.31-1.92, and 1.93-9.65 g/day based on NHANES 24-h dietary recall questionnaire dietary omega-3 PUFA. Moreover, their mortality details were available to be obtained by linking NHANES to the National Death Index. The associations between dietary omega-3 PUFA and mortality were evaluated by constructing multivariable Cox proportional hazards models. RESULTS: Over 8 years of a median follow-up, 864 deaths were recorded. The adjusted hazard ratios (95% confidence interval) for all-cause mortality of the diseased people with CKD in the 2nd (0.87-1.30 g/day), 3rd (0.87-1.30 g/day), and 4th (1.93-9.65 g/day) quartiles of dietary omega-3 PUFA were 0.94 (0.72, 1.23), 0.74 (0.54, 1.02), and 0.67 (0.48, 0.93), respectively, versus those with the lowest quartile of dietary omega-3 PUFA intake (<0.86 g/day) (p for trend = 0.011). CONCLUSION: There may be a inverse relation of dietary omega-3 PUFA intake and all-cause mortality in patients with CKD. Therefore, an increase of dietary omega-3 PUFA may be encouraged to be used clinically in patients with CKD.

Effect of Marital Status on Depression and Mortality among Patients with Chronic Kidney Disease from National Health and Nutrition Examination Survey 2005-2014.

BACKGROUND: The relationship between marital status and CKD is rarely studied. We aimed to explore the effect of marital status on the depression and mortality of patients with CKD. METHODS: The data sources came from the NHANES database during 2005-2014 and 3,865 participants were included in this study. We used logistic regression models to examine the relationship between marital status and depression of CKD patients. The Cox proportional hazard models were used to evaluate the association between marital status and mortality of CKD patients. RESULTS: In terms of depression in CKD patients, unmarried patients had a worse situation than married patients. Meanwhile, after adjusting the covariables, unmarried patients had increased risk of depression (OR = 1.26, 95% CI: 1.01-1.57) compared with married CKD patients, especially in males (OR = 1.45, 95% CI: 1.02-2.06) and patients with more than college education level (OR = 12.4, 95% CI: 3.75-41.02). There was a significant relationship between marital status and mortality of general CKD patients (HR = 1.36, 95% CI: 1.17-1.58). Moreover, marriage showed a protective effect against death among male patients, patients with school graduate or less and more than college educational level, patients with high income, and patients in different estimated glomerular filtration rate groups. CONCLUSIONS: The use of large numbers of participants has revealed the effect of marital status on CKD patients. Unmarried ones had a higher risk of depression than married ones among CKD patients. Meanwhile, the risk of death was higher in unmarried ones than married ones among CKD patients in this study.

Recovery of new-onset kidney disease in COVID-19 patients discharged from hospital.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has emerged as a major global health threat with a great number of deaths worldwide. Despite abundant data on that many COVID-19 patients also displayed kidney disease, there is limited information available about the recovery of kidney disease after discharge. METHODS: Retrospective and prospective cohort study to patients with new-onset kidney disease during the COVID-19 hospitalization, admitted between January 28 to February 26, 2020. The median follow-up was 4 months after discharge. The follow-up patients were divided into the recovery group and non-recovery group. Descriptive statistics and between-groups comparison were used. RESULTS: In total, 143 discharged patients with new-onset kidney disease during the COVID-19 hospitalization were included. Patients had a median age was 64 (IQR, 51-70) years, and 59.4% of patients were men. During 4-months median follow-up, 91% (130 of 143) patients recovered from kidney disease, and 9% (13 of 143) patients haven't recovered. The median age of patients in the non-recovery group was 72 years, which was significantly higher than the median age of 62 years in the recovery group. Discharge serum creatinine was significantly higher in the non-recovery group than in the recovery group. CONCLUSIONS: Most of the new-onset kidney diseases during hospitalization of COVID-19 patients recovered 4 months after discharge. We recommend that COVID-19 patients with new-onset kidney disease be followed after discharge to assess kidney recovery, especially elderly patients or patients with high discharge creatinine.

LRG1 Mitigates Renal Interstitial Fibrosis through Alleviating Capillary Rarefaction and Inhibiting Inflammatory and Pro-Fibrotic Cytokines.

INTRODUCTION: Increasing evidence has demonstrated that loss of peritubular capillaries plays a critical role in renal interstitial fibrosis. Leucine-rich α2-glycoprotein-1 (LRG1) has been observed promoting angiogenesis in the ocular disease mouse model and myocardial infarction model. We aimed to explore the role of LRG1 in renal interstitial fibrosis. METHODS: We analyzed the expression of LRG1 in the plasma and kidney of CKD patients by ELISA and immunohistochemistry. Relationships between the expression of LRG1 in plasma and kidney and renal fibrosis and inflammation were analyzed. Tube formation assay was used to detect the angiogenesis in the human umbilical vein endothelial cell lines (HUVECs). And real-time PCR was used to detect the mRNA expression of LRG1, inflammatory factors, renal tubular injury indicators, pro-fibrotic cytokines, and CD31. We examined the effects of genetic ablation of LRG1 on renal fibrosis induced by unilateral ureteral obstruction (UUO) mice model at day 7. RESULTS: We demonstrated that the expression of LRG1 in renal tissues and plasma samples was upregulated in CKD patients. And the expression of LRG1 was elevated in human renal tubular epithelial cell line (HK-2) cells in response to the stimulation of TNF-α in vitro, and in kidney after UUO in vivo. The deficiency of the LRG1 gene aggravated renal fibrosis, inflammatory cells infiltration, and capillary rarefaction after UUO. In vitro, LRG1 promoted the tube formation of HUVEC cells. LRG1 inhibits fibronectin secretion induced by TGF-ß1 in HK-2 and overexpression of LRG1 in HK-2 cells decreased fibronectin secretion. CONCLUSION: LRG1 may prevent renal fibrosis by inhibiting the secretion of inflammatory and pro-fibrotic cytokines and promoting angiogenesis.

Characteristics and Prognostic Value of Tertiary Lymphoid Organs in Membranous Nephropathy: A Retrospective Study.

BACKGROUND: Tertiary lymphoid organs play an essential role in the inflammation of the kidney. The clinical association between TLOs and membranous nephropathy (MN) is not clear yet. METHODS: Consecutive patients with the histologically confirmed membranous nephropathy in Tongji Hospital from July 19, 2012, to September 26, 2019, were included in this study. TLOs in renal biopsy tissues were detected by periodic acid-Schiff-stained and immunohistochemistry. Logistic regression was performed to evaluate the correlations of TLOs and clinical features of patients with MN. Kaplan-Meier analysis was utilized to examine the relationship between TLOs and remission of proteinuria. RESULTS: A total of 442 patients with MN were included in this study, of which the average age was 46.4 years old, and 58.8% were male. Moreover, 33% of patients with MN had TLOs in this study. The median value of proteinuria among patients with MN with TLOs was 4.9 g/24 h, which was much greater than no-TLOs ones (3.2 g/24 h, p < 0.001). Moreover, the patients with TLOs had higher serum creatinine and lower serum albumin. The severity of clinical features among the patients with MN aggravated with the increase in the grade of TLOs. In addition, the patients who had TLOs were more likely to be positive of anti-phospholipase A2 receptor autoantibodies. Meanwhile, the patients without TLOs showed significantly higher complete remission and total remission of proteinuria. CONCLUSION: In this study, we demonstrated that TLOs were common among patients with MN. Moreover, the patients with MN with TLOs showed a worse clinical manifestation and an outcome compared with the patients without TLOs.

Leisure-Time Physical Activity and Mortality in CKD: A 1999-2012 NHANES Analysis.

BACKGROUND: For patients with CKD, evidence on the optimal dose of physical activity and possible harm with excessive exercise is limited. This study aimed to analyze the dose-response association between leisure-time physical activity (LTPA) and mortality in those with CKD and explore the optimal dose or possible harm associated with increased levels of LTPA. METHODS: 4,604 participants with CKD from the 1999 to 2012 National Health and Nutrition Examination Surveys with linked mortality data obtained through 2015 were classified into 6 groups: 0, 1-149, 150-299, 300-599, 600-899, and ≥900 min/week based on the total duration of the self-reported LTPA. Multivariable-adjusted Cox proportional hazards models were used to examine dose-response associations between LTPA and mortality. RESULTS: During the median follow-up of 114 months, 1,449 (31%) all-cause deaths were recorded. Compared to the inactive group (0 min/week), we observed a 22% lower risk of all-cause mortality (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.63-0.97) among participants who performed 1-149 min per week for LTPA. The corresponding HRs and 95% CIs for all-cause mortality for 150-299 and 300-599 min/week of LTPA were 0.79 (0.64-0.97) and 0.74 (0.56-0.98). The benefit appeared to reach a threshold of a 43% (HR, 0.57; 95% CI, 0.36-0.91) lower risk of all-cause mortality among individuals performing 600-899 min/week for LTPA. Importantly, for ≥900 min/week of LTPA, the continued benefits were observed (HR, 0.62; 95% CI, 0.44-0.87). CONCLUSION: LTPA was associated with lower mortality in those with CKD. The optimal dose was observed at the LTPA level of approximately 600-899 min/week, and there were still benefits rather than the excess risk with LTPA levels as high as ≥900 min/week. Therefore, clinicians should encourage inactive CKD patients to perform LTPA and do not need to discourage CKD patients who already adhere to long-term physical activity.

Plasma chemokine CXC motif-ligand 16 as a predictor of renal prognosis in immunoglobulin A nephropathy.

BACKGROUND: There are few non-invasive biomarkers that have been identified to improve the risk stratification of patients with IgA nephropathy (IgAN). CXCL16 has been shown to play a key role as a chemoattractant, adhesion, and fibrosis factor in inflammatory disease. This study evaluated the potential for CXCL16 plasma as a potential biomarker in patients with IgAN. METHODS: Plasma CXCL16 was measured in 230 patients with renal biopsied IgAN enrolled from 2012 to 2014. The patients were followed for 41.3 months, with a 50% reduction in estimated glomerular filtration rate or end-stage renal disease as endpoints. RESULTS: The plasma CXCL16 levels in IgAN patients were strongly correlated with the uric acid, estimated glomerular filtration rate and tubular atrophy/interstitial fibrosis score in multivariate analysis. Furthermore, counts of CD4+ T cells, CD8+ T cells, and CD20+ B cells in renal biopsies of IgAN patients were significantly correlated with the plasma CXCL16 levels, but not CD68+ macrophage. Lastly, we concluded that patients with higher levels of plasma CXCL16 had an increased risk of poor renal outcome compared to those with lower levels. There was no association between the polymorphisms and clinical parameters of CXCL16, including the levels and prognosis of plasma CXCL16. CONCLUSIONS: Plasma CXCL16 levels were associated with clinical parameters; pathological damage; CD4+ T cell, CD8+ T cell, and CD20+ B cell infiltration in renal tissue; and renal outcome in IgAN patients. Plasma CXCL16 might be a potential prognosis predictor in Chinese IgAN patients.

Plasma fractalkine levels are associated with renal inflammation and outcomes in immunoglobulin A nephropathy.

BACKGROUND: A recognized noninvasive biomarker to improve risk stratification of immunoglobulin A nephropathy (IgAN) patients is scarce. Fractalkine has been shown to play a key role in glomerular disease as chemoattractant, adhesion and even fibrosis factor. The current study assessed the possibility of plasma fractalkine as a novel biomarker in IgAN patients. METHODS: Plasma fractalkine was measured in 229 patients with renal biopsy consistent IgAN from 2012 to 2014, and clinical, pathological and prognostic relationships were analyzed. RESULTS: The plasma fractalkine levels in IgAN patients were significantly correlated with the creatinine level and 24-h urine protein by both univariate and multivariate analysis. Mesangial hypercellularity was still significantly correlated with the plasma fractalkine levels even after adjustment for other potential predictor variables by multivariate analysis. In addition, the counts of CD20+ B cells or CD68+ macrophage in renal biopsies of IgAN patients were significantly correlated with the plasma fractalkine levels, but not CD4+ and CD8+ T cells. Finally, we concluded that patients with higher plasma fractalkine levels had higher risk of poor renal outcome compared with those with lower plasma fractalkine levels. No association was observed between the CX3CR1 polymorphisms and clinical parameters including plasma fractalkine levels and prognosis. Recombinant fractalkine induced mesangial cells extracellular matrix synthesis and promoted the migration of microphage cells RAW264.7. CONCLUSIONS: Plasma fractalkine levels were associated with creatinine level, 24-h urine protein, mesangial hypercellularity pathological damage, the CD68+ macrophage and CD20+ B cell infiltration in renal tissue and renal outcome in IgAN patients. Plasma fractalkine might be a potential prognosis novel predictor in Chinese patients with IgAN.

Proton-pump inhibitors use, and risk of acute kidney injury: a meta-analysis of observational studies.

BACKGROUND: Recent studies have suggested a potential increased risk of acute kidney injury (AKI) among proton-pump inhibitor (PPI) users. However, the present results are conflicting. Thus, we performed a meta-analysis to investigate the association between PPI therapy and the risk of AKI. METHODS: EMBASE, PubMed, Web of Science, and Cochrane Library databases (up to September 23, 2016) were systematically searched for any studies assessing the relationship between PPI use and risk of AKI. Studies that reported relevant risk ratios (RRs), odds ratios, or hazard ratios were included. We calculated the pooled RRs with 95% confidence intervals (CI) using a random-effects model of the meta-analysis. Subgroup analysis was conducted to explore the source of heterogeneity. RESULTS: Seven observational studies (five cohort studies and two case-control studies) were identified and included, and a total of 513,696 cases of PPI use among 2,404,236 participants were included in the meta-analysis. The pooled adjusted RR of AKI in patients with PPIs use was 1.61 (95% CI: 1.16-2.22; I2=98.1%). Furthermore, higher risks of AKI were found in the subgroups of cohort studies, participant's average age <60 years, participants with and without baseline PPI excluded, sample size <300,000, and number of adjustments ≥11. Subgroup analyses revealed that participants with or without baseline PPI excluded might be a source of heterogeneity. CONCLUSION: PPI use could be a risk factor for AKI and should be administered carefully. Nevertheless, some confounding factors might impact the outcomes. More well-designed prospective studies are needed to clarify the association.

Soluble Urokinase Receptor Levels Are Correlated with Focal Segmental Glomerulosclerosis Lesions in IgA Nephropathy: A Cohort Study from China.

BACKGROUND: Soluble urokinase receptor (suPAR) may be involved in the pathological mechanisms of focal segmental glomerulosclerosis (FSGS) changes. However, it remains unclear whether suPAR is correlated with the FSGS-like lesions in IgA nephropathy (IgAN). METHODS: We measured the plasma suPAR levels in 138 patients with IgAN, and then their clinical and pathological relationships were analyzed. RESULTS: We found that the plasma suPAR levels were significantly correlated with age and renal function by both univariate and multivariate analysis in our IgAN patient cohort. Female had higher plasma suPAR levels and no significant correlation was observed between plasma suPAR levels and 24-h urine protein and highly sensitive C-reaction protein with multivariate analysis. In our cohort, sixty of these IgAN patients could be diagnosed with a type of FSGS lesions. The plasma suPAR levels were higher in the IgAN patients with FSGS lesions than in the IgAN patients without FSGS lesions by univariate (P < 0.0001) and multivariate (P < 0.001) analysis adjusting for other predictor variables, which might be helpful to differentiate the pathological changes with and without FSGS lesions. And the optimal cutoff value was 1806 pg/ml in this study. The plasma suPAR concentrations were also associated with the degree of tubular atrophy/interstitial fibrosis in both univariate and multivariate analysis. In multivariate analysis, the plasma suPAR levels were correlated with the percentage of crescents, not global sclerosis and arterial lesions. CONCLUSIONS: Our study suggested that the plasma suPAR levels were associated with age, gender, renal function, the degree of tubular atrophy/interstitial fibrosis and the percentage of crescent formation. The plasma suPAR might be a potential predictor for the presence of FSGS pathological lesions in Chinese patients with IgAN.