Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis.

OBJECTIVES: Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant. DESIGN: Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722). SETTING: One hundred-fifty-three ICUs in 13 countries. PATIENTS: Altogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p < 0.001). The median time to RRT initiation among patients allocated to the standard strategy was longest in Europe compared with North America and ANZ (p < 0.001; p < 0.001). Continuous RRT was the initial RRT modality in 60.8% of patients in North America and 56.8% of patients in Europe, compared with 96.4% of patients in ANZ (p < 0.001). After adjustment for predefined baseline characteristics, compared with North American and European patients, those in ANZ were more likely to survive to ICU (p < 0.001) and hospital discharge (p < 0.001) and to 90 days (for ANZ vs. Europe: risk difference [RD], -11.3%; 95% CI, -17.7% to -4.8%; p < 0.001 and for ANZ vs. North America: RD, -10.3%; 95% CI, -17.5% to -3.1%; p = 0.007). CONCLUSIONS: Among STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions.

Clinical Manifestations and Risk Factors Associated with 14 Deaths following Swarm Wasp Stings in a Chinese Tertiary Grade A General Hospital: A Retrospective Database Analysis Study.

INTRODUCTION: The objective was to evaluate the poisoning severity score (PSS) as an early prognostic predictor in patients with wasp stings and identify associated clinical characteristics and risk factors for mortality. METHODS: A total of 363 patients with wasp stings at Suining Central Hospital between January 2016 and December 2018 were enrolled. Within the first 24 h of admission, the poisoning severity score (PSS) and the Chinese expert consensus on standardized diagnosis and treatment of wasp stings (CECC) were utilized for severity classification, and their correlation was examined. Patients were then divided into survival and death groups based on discharge status. Logistic regression analysis was employed to analyze factors influencing patients' outcomes. RESULTS: The mortality of wasp sting patients was 3.9%. The PSS and CECC were found to correlate for severity classification. Additionally, female gender, age, number of stings, and PSS were identified as independent risk factors for mortality in wasp sting patients. Combining these four factors yielded an AUC of 0.962 for predicting death. CONCLUSIONS: PSS aids in early severity classification of wasp stings. Female gender, age, number of stings, and PSS were independent mortality risk factors in these patients.

Effect of kidney disease on all-cause and cardiovascular mortality in patients undergoing coronary angiography.

Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is associated with increased mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular disease (CVD). Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined. The aim of our study was to investigate the relationship between acute and CKD and mortality in patients undergoing CAG. The cohort study included 49,194 patients in the multicenter cohort from January 2007 to December 2018. Cox regression analyses and Fine-Gray proportional subdistribution risk regression analysis are used to examine the association between kidney disease and all-cause and cardiovascular mortality. In the present study, 13,989 (28.4%) patients had kidney disease. During follow-up, 6144 patients died, of which 4508 (73.4%) were due to CVD. AKI without CKD (HR: 1.54, 95% CI: 1.36-1.74), CKD without AKI (HR: 2.02, 95% CI: 1.88-2.17), AKI with CKD (HR: 3.26, 95% CI: 2.90-3.66), and end-stage kidney disease (ESKD; HR: 5.63, 95% CI: 4.40-7.20) were significantly associated with all-cause mortality. Adjusted HR (95% CIs) for cardiovascular mortality was significantly elevated among patients with AKI without CKD (1.78 [1.54-2.06]), CKD without AKI (2.28 [2.09-2.49]), AKI with CKD (3.99 [3.47-4.59]), and ESKD (6.46 [4.93-8.46]). In conclusion, this study shows that acute or CKD is present in up to one-third of patients undergoing CAG and is associated with a substantially increased mortality. These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD.Impact StatementWhat is already known on this subject? Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is linked to a 22.2% increase in mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular events. Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined.What do the results of this study add? This study shows that kidney disease is present in up to one-third of patients undergoing CAG and is associated with a substantially increased mortality. AKI and CKD are independent predicators for mortality in patients undergoing CAG.What are the implications of these findings for clinical practice and/or further research? These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD.

Characterization of Risk Prediction Models for Acute Kidney Injury: A Systematic Review and Meta-analysis.

Importance: Despite the expansion of published prediction models for acute kidney injury (AKI), there is little evidence of uptake of these models beyond their local derivation nor data on their association with patient outcomes. Objective: To systematically review published AKI prediction models across all clinical subsettings. Data Sources: MEDLINE via PubMed (January 1946 to April 2021) and Embase (January 1947 to April 2021) were searched using medical subject headings and text words related to AKI and prediction models. Study Selection: All studies that developed a prediction model for AKI, defined as a statistical model with at least 2 predictive variables to estimate future occurrence of AKI, were eligible for inclusion. There was no limitation on study populations or methodological designs. Data Extraction and Synthesis: Two authors independently searched the literature, screened the studies, and extracted and analyzed the data following the Preferred Reporting Items for Systematic Review and Meta-analyses guideline. The data were pooled using a random-effects model, with subgroups defined by 4 clinical settings. Between-study heterogeneity was explored using multiple methods, and funnel plot analysis was used to identify publication bias. Main Outcomes and Measures: C statistic was used to measure the discrimination of prediction models. Results: Of the 6955 studies initially identified through literature searching, 150 studies, with 14.4 million participants, met the inclusion criteria. The study characteristics differed widely in design, population, AKI definition, and model performance assessments. The overall pooled C statistic was 0.80 (95% CI, 0.79-0.81), with pooled C statistics in different clinical subsettings ranging from 0.78 (95% CI, 0.75-0.80) to 0.82 (95% CI, 0.78-0.86). Between-study heterogeneity was high overall and in the different clinical settings (eg, contrast medium-associated AKI: I2 = 99.9%; P < .001), and multiple methods did not identify any clear sources. A high proportion of models had a high risk of bias (126 [84.4%]) according to the Prediction Model Risk Of Bias Assessment Tool. Conclusions and Relevance: In this study, the discrimination of the published AKI prediction models was good, reflected by high C statistics; however, the wide variation in the clinical settings, populations, and predictive variables likely drives the highly heterogenous findings that limit clinical utility. Standardized procedures for development and validation of prediction models are urgently needed.

Renal Insufficiency Increases the Combined Risk of Left Ventricular Hypertrophy and Dysfunction in Patients at High Risk of Cardiovascular Diseases.

BACKGROUND: The identification of asymptomatic structural and functional cardiac abnormalities can help us to recognize early and intervene in patients at pre-heart failure (HF). However, few studies have adequately evaluated the associations of renal function and left ventricular (LV) structure and function in patients at high risk of cardiovascular diseases (CVD). METHODS: Patients undergoing coronary angiography and/or percutaneous coronary interventions were enrolled from the Cardiorenal ImprovemeNt II (CIN-II) cohort study, and their echocardiography and renal function were assessed at admission. Patients were divided into five groups according to their estimated glomerular filtration rate (eGFR). Our outcomes were LV hypertrophy and LV systolic and diastolic dysfunction. Multivariable logistic regression analyses were conducted to investigate the associations of eGFR with LV hypertrophy and LV systolic and diastolic dysfunction. RESULTS: A total of 5610 patients (mean age: 61.6 ± 10.6 years; 27.3% female) were included in the final analysis. The prevalence of LV hypertrophy assessed by echocardiography was 29.0%, 34.8%, 51.9%, 66.7%, and 74.3% for the eGFR categories >90, 61-90, 31-60, 16-30, and ≤15 mL/min per 1.73 m2 or for patients needing dialysis, respectively. Multivariate logistic regression analysis showed that subjects with eGFR levels of ≤15 mL/min per 1.73 m2 or needing dialysis (OR: 4.66, 95% CI: 2.96-7.54), as well as those with eGFR levels of 16-30 (OR: 3.87, 95% CI: 2.43-6.24), 31-60 (OR: 2.00, 95% CI: 1.64-2.45), and 61-90 (OR: 1.23, 95% CI: 1.07-1.42), were significantly associated with LV hypertrophy. This reduction in renal function was also significantly associated with LV systolic and diastolic dysfunction (all P for trend <0.001). In addition, a per one unit decrease in eGFR was associated with a 2% heightened combined risk of LV hypertrophy and systolic and diastolic dysfunction. CONCLUSIONS: Among patients at high risk of CVD, poor renal function was strongly associated with cardiac structural and functional abnormalities. In addition, the presence or absence of CAD did not change the associations. The results may have implications for the pathophysiology behind cardiorenal syndrome.

Podocyte Infolding Glomerulopathy: A Case Series Report and Literature Review.

BACKGROUND: Podocyte infolding glomerulopathy (PIG) is a peculiar and very rare manifestation in renal pathology. Its underlying pathogenesis mechanism and clinical characteristics remain unclear due to sparse reports. OBJECTIVE: To further elucidate the clinical profile of PIG by carefully reporting our four cases and a comprehensive review of cases in the literature. METHODS: This study retrospectively reviewed four cases of PIG from 2010 to 2022 in our centre. Clinical and pathological profiles were reported. PIG cases in the literature were searched in the MEDLINE database and analysed together with our cases. RESULTS: Four cases of PIG identified from our centre and 40 cases from the current literature were reported. The pooled analysis of these 44 cases indicated 79.5% (35/44) were females, 93.2% (41/44) were East Asians, and 63.6% (28/44) were reported in Japan. The average age was 42.0 ± 12.5 years old. The average amount of proteinuria at the time of renal biopsy was 3.06 ± 3.2 g/day. The most reported comorbidities were connective tissue diseases, mainly systemic lupus erythematosus, and 20.5% (9/44) of the cases did not have any contaminant disease. Most of the cases (81.8%, 36/44) had been treated with immunosuppressants, of which a combination of corticosteroids and one other type of immunosuppressant was most commonly reported. In addition, 45.4% (20/44) and 34.1% (15/44) of the cases had achieved complete response and partial response, respectively, after treatment. Whole exosome sequencing indicated mutations in the INF2 gene. CONCLUSIONS: PIG is a rare condition and seen in relatively younger populations, often associated with connective tissue diseases clinically and one or two other glomerulopathies histologically. The outcomes following immunosuppressive treatment are relatively good. Mutations in INF2 might be involved in the development of PIG; however, the implications of these results need to be investigated.

Artificial intelligence for the prediction of acute kidney injury during the perioperative period: systematic review and Meta-analysis of diagnostic test accuracy.

BACKGROUND: Acute kidney injury (AKI) is independently associated with morbidity and mortality in a wide range of surgical settings. Nowadays, with the increasing use of electronic health records (EHR), advances in patient information retrieval, and cost reduction in clinical informatics, artificial intelligence is increasingly being used to improve early recognition and management for perioperative AKI. However, there is no quantitative synthesis of the performance of these methods. We conducted this systematic review and meta-analysis to estimate the sensitivity and specificity of artificial intelligence for the prediction of acute kidney injury during the perioperative period. METHODS: Pubmed, Embase, and Cochrane Library were searched to 2nd October 2021. Studies presenting diagnostic performance of artificial intelligence in the early detection of perioperative acute kidney injury were included. True positives, false positives, true negatives and false negatives were pooled to collate specificity and sensitivity with 95% CIs and results were portrayed in forest plots. The risk of bias of eligible studies was assessed using the PROBAST tool. RESULTS: Nineteen studies involving 304,076 patients were included. Quantitative random-effects meta-analysis using the Rutter and Gatsonis hierarchical summary receiver operating characteristics (HSROC) model revealed pooled sensitivity, specificity, and diagnostic odds ratio of 0.77 (95% CI: 0.73 to 0.81),0.75 (95% CI: 0.71 to 0.80), and 10.7 (95% CI 8.5 to 13.5), respectively. Threshold effect was found to be the only source of heterogeneity, and there was no evidence of publication bias. CONCLUSIONS: Our review demonstrates the promising performance of artificial intelligence for early prediction of perioperative AKI. The limitations of lacking external validation performance and being conducted only at a single center should be overcome. TRIAL REGISTRATION: This study was not registered with PROSPERO.

Impact of renal-replacement therapy strategies on outcomes for patients with chronic kidney disease: a secondary analysis of the STARRT-AKI trial.

PURPOSE: To assess whether pre-existing chronic kidney disease (CKD) modified the relationship between the strategy for renal-replacement theraphy (RRT) initiation and clinical outcomes in the STARRT-AKI trial. METHODS: This was a secondary analysis of a multi-national randomized trial. We included patients who had documented pre-existing estimated glomerular filtration rate (eGFR) data prior to hospitalization, and we defined CKD as an eGFR ≤ 59 mL/min/1.73 m2. The primary outcome was all-cause mortality at 90 days. Secondary outcomes included RRT dependence and RRT-free days at 90 days. We used logistic and linear regression and interaction testing to explore the effect of RRT initiation strategy on outcomes by CKD status. RESULTS: We studied 1121 patients who had pre-hospital measures of kidney function. Of these, 432 patients (38.5%) had CKD. The median (IQR) baseline serum creatinine was 130 (114-160) and 76 (64-90) µmol/L for those with and without CKD, respectively. Patients with CKD were older and more likely to have cardiovascular comorbidities and diabetes mellitus. Patients with CKD had higher 90-day mortality (47% vs. 40%, p < 0.001) compared to those without CKD, though this was not significant after covariate adjustment (adjusted odds ratio [aOR], 1.05; 95% CI, 0.79-1.41). Patients with CKD were more likely to remain RRT dependent at 90 days (14% vs. 8%; aOR, 1.89; 95% CI, 1.05-3.43). CKD status did not modify the effect of RRT initiation strategy on 90-day mortality. Among patients with CKD, allocation to the accelerated strategy conferred more than threefold greater odds of RRT dependence at 90 days (aOR 3.18; 95% CI, 1.41-7.91) compared with the standard strategy, whereas RRT initiation strategy had no effect on this outcome among those without CKD (aOR 0.71; 95% CI, 0.34-1.47, p value for interaction, 0.009). CONCLUSION: In this secondary analysis of the STARRT-AKI trial, an accelerated strategy of RRT initiation conferred a higher risk of 90-day RRT dependence among patients with pre-existing CKD; however, no effect was observed in the absence of CKD.

Cardiorenal Syndrome in COVID-19 Patients: A Systematic Review.

Aims: To perform a systematic review assessing the clinical manifestations and outcomes of cardiorenal syndrome or the presence of both cardiac and renal complications in the 2019 coronavirus disease (COVID-19) patients. Methods: All relevant studies about cardiorenal syndrome or both cardiac and renal complications in COVID-19 patients were retrieved on PUBMED, MEDLINE, and EMBASE from December 1, 2019 to February 20, 2022. Results: Our search identified 15 studies including 637 patients with a diagnosis of cardiorenal syndrome or evidence of both cardiac and renal complications followingSARS-CoV-2 infection. They were male predominant (66.2%, 422/637), with a mean age of 58 years old. Cardiac complications included myocardial injury (13 studies), heart failure (7 studies), arrhythmias (5 studies), or myocarditis and cardiomyopathy (2 studies). Renal complications manifested as acute kidney injury with or without oliguria. Patients with cardiorenal injury were often associated with significantly elevated levels of inflammatory markers (CRP, PCT, IL-6). Patients with a diagnosis of cardiorenal syndrome or evidence of both cardiac and renal complications had more severe disease and poorer prognosis (9 studies). Conclusion: The presence of either cardiorenal syndrome or concurrent cardiac and renal complications had a significant impact on the severity of the disease and the mortality rate among patients with COVID-19 infection. Therefore, careful assessment and management of potential cardiac and renal complications in patients with COVID-19 infection are important to improve their outcomes.

A Novel Risk Prediction Model for Severe Acute Kidney Injury in Intensive Care Unit Patients Receiving Fluid Resuscitation.

Background: To develop a risk prediction model for the occurrence of severe acute kidney injury (AKI) in intensive care unit (ICU) patients receiving fluid resuscitation. Methods: We conducted a secondary analysis of the Crystalloid vs. Hydroxyethyl Starch Trial (CHEST) trial, a blinded randomized controlled trial that enrolled ICU patients who received intravenous fluid resuscitation. The primary outcome was the first event in a composite outcome of doubling of serum creatinine and/or treatment with renal replacement treatment (RRT) within 28 days of randomization. The final model developed using multivariable logistic regression with backwards elimination was validated internally and then translated into a predictive equation. Results: Six thousand seven hundred twenty-seven ICU participants were studied, among whom 745 developed the study outcome. The final model having six variables, including admission diagnosis of sepsis, illness severity score, mechanical ventilation, tachycardia, baseline estimated glomerular filtration rate and emergency admission. The model had good discrimination (c-statistic = 0.72, 95% confidence interval 0.697-0.736) and calibration (Hosmer-Lemeshow test, χ2 = 14.4, p = 0.07) for the composite outcome, with a c-statistic after internal bootstrapping validation of 0.72, which revealed a low degree of over-fitting. The positive predictive value and negative predictive value were 58.8 and 89.1%, respectively. The decision curve analysis indicates a net benefit in prediction of severe AKI using the model across a range of threshold probabilities between 5 and 35%. Conclusions: Our model, using readily available clinical variables to identify ICU patients at high risk of severe AKI achieved good predictive performance in a clinically relevant population.

Thrombomodulin activation driven by LXR agonist attenuates renal injury in diabetic nephropathy.

Objective: Inflammation and thrombosis are recognized as interrelated biological processes. Both thrombomodulin (TM) and factor XIII-A (FXIII-A) are involved in inflammation and coagulation process. However, their role in the pathogenesis of diabetic nephropathy (DN) remains unclear. In vitro study, the liver X receptor (LXR) agonist T0901317 can up-regulate the expression of TM in glomerular endothelial cells. Now we evaluated the interaction between TM activation and FXIII-A and their effects against renal injury. Methods: We first evaluated the serum levels of FXIII-A and TM and the expression of TM, LXR-α and FXIII-A in renal tissues of patients with biopsy-proven DN. We then analyzed the expression of TM, LXR-α and FXIII-A in renal tissues of db/db DN mice after upregulating TM expression via T0901317 or downregulating its expression via transfection of TM shRNA-loaded adenovirus. We also investigated the serum levels of Tumor necrosis factor (TNF)-α, Interleukin (IL)-6, creatinine, and urinary microalbumin level in db/db mice. Results: Our study showed that elevations in serum levels of FXIII-A positively correlated to the serum levels of TM and were also associated with end-stage kidney disease in patients with DN. The number of TM+ cells in the renal tissues of patients with DN negatively correlated with the number of FXIII-A+ cells and positively correlated with the number of LXR-α+ cells and estimated glomerular filtration rate (eGFR), whereas the number of FXIII-A+ cells negatively correlated with the eGFR. Conclusion: Thrombomodulin activation with T0901317 downregulated FXIII-A expression in the kidney tissue and alleviated renal injury in db/db mice.

Effect of Angiotensin-Neprilysin Versus Renin-Angiotensin System Inhibition on Renal Outcomes: A Systematic Review and Meta-Analysis.

Aims: We aim to perform a systematic review and meta-analysis examining randomized controlled trials assessing the efficacy and safety of sacubitril/valsartan in patients on renal outcomes, in comparison with the renin-angiotensin-aldosterone system inhibitor (RAASi). Methods: Eligible studies were retrieved on MEDLINE, EMBASE, and Cochrane until September 2021. The primary outcome was the incidence of renal impairment, which was defined as the composite of increases in serum creatinine by >0.3 mg/dl and/or a reduction in eGFR ≥25%, development of ESRD, or renal death. We pooled relative risks (RRs) with 95% confidence intervals (CIs) or the mean difference with 95% CIs for the variables. Results: Our search yielded 10 randomized controlled trials with a total of 18,362 patients. Compared with RAASi treatment, patients treated with sacubitril/valsartan had lower incidence of composite renal impairment (10 studies, 18,362 patients, RR 0.84; 95% CI 0.72-0.96, p = 0.01; I 2  = 22%), ESRD development (3 studies, 13,609 patients, RR 0.53; 95% CI 0.30-0.96, p = 0.03; I 2 = 0%), drug discontinuation due to renal events (4 studies, 9,995 patients, RR 0.58; 95% CI 0.40-0.83, p = 0.003; I 2  = 47%), severe hyperkalemia (6 studies, 16,653 patients, RR 0.80; 95% CI 0.68-0.93, p = 0.01; I 2  = 25%) and a slower eGFR decline (4 studies, 13,608 patients, WMD 0.56; 95% CI 0.36-0.76, p < 0.00001; I 2  = 65%). Subgroup analysis demonstrated that sacubitril/valsartan was associated with a lower incidence of renal impairment in patients with heart failure and preserved ejection fraction (HFpEF), but not in those with heart failure and reduced ejection fraction (HFrEF). The superior renal function preservation of sacubitril/valsartan treatment was not associated with different baseline eGFR levels and follow-up duration. There was a smaller increase in the change in the urine albumin-to-creatinine ratio (UACR) (3 studies, 9,114 patients, SMD 0.06; 95% CI 0.02-0.10, p = 0.003; I 2  = 14%) with sacubitril/valsartan treatment. However, patients with heart failure appeared to have increased microalbuminuria, not patients without HF (p = 0.80 for interaction). Conclusion: Sacubitril/valsartan was associated with a lower incidence of composite renal impairment especially in patients with HFpEF, but higher microalbuminuria in patients with heart failure (both HFrEF and HFpEF) compared with RAASi. The lower incidence of severe hyperkalemia and drug discontinuation due to renal events in patients with sacubitril/valsartan treatment demonstrated its superior safety compared with RAASi.

HLA-DQB1 and HLA-DRB1 expression is associated with disease severity in IgAN.

BACKGROUND: Several genome-wide association studies have found that HLA class II histocompatibility antigen, DQ beta1 (HLA-DQB1) and HLA class II histocompatibility antigen, DR beta1 (HLA-DRB1) were associated with immunoglobulin A nephropathy (IgAN). However, few studies have explored the association between HLA-DQB1 and HLA-DRB1 expression and IgAN. This is the first study to investigate the relationship between HLA-DQB1 and HLA-DRB1 expression and clinical pathological characteristics. METHODS: A total of 113 patients with biopsy-proven IgAN and 71 healthy control patients participated in this study. HLA-DQB1 and HLA-DRB1 expression in peripheral blood lymphocytes was measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and flow cytometry. Serum galactose-deficient IgA1 (Gd-IgA1) level was measured by an enzyme-linked immunosorbent assay kit. The clinical and histopathological data of patients with IgAN were collected at the time of renal biopsy. Pearson's or Spearman's correlation coefficients were used to analyze the correlation between the expression of HLA-DQB1 and HLA-DRB1 mRNA and protein and the clinical pathological features of IgAN. RESULTS: HLA-DQB1 and HLA-DRB1 messenger ribonucleic acid expression was decreased in IgAN patients compared to healthy control patients (P<0.01). HLA-DQB1 and HLA-DRB1 protein expression was significantly lower in IgAN patients than healthy control patients (P<0.05). HLA-DQB1 and HLA-DRB1 protein expression was positively correlated with 24-h urinary protein excretion (P<0.05). HLA-DRB1 protein expression was negatively correlated with renal function as measured by an estimated glomerular filtration rate (P<0.05). HLA-DRB1 protein expression was higher in patients with crescentic IgAN than patients without crescent formation (P<0.05). CONCLUSIONS: Our study found the expression of HLA-DQB1, HLA-DRB1 were associated with the disease severity of IgAN and abnormal HLA-DQB1 and HLA-DRB1 expression may aggravate the progression of IgAN. We intend to gather further follow-up data to explore the effects of HLA-DQB1 and HLA-DRB1 expression on the prognosis of IgAN.

Effect of high cut-off dialysis for acute kidney injury secondary to cast nephropathy in patients with multiple myeloma: a systematic review and meta-analysis.

BACKGROUND: Acute kidney injury (AKI) caused by cast nephropathy is associated with increased morbidity and mortality among patients with multiple myeloma (MM). High cut-off haemodialysis (HCO-HD) has proven to be effective in the removal of serum light chains but the effect on clinical outcomes, especially renal recovery, remains uncertain. METHODS: A systematic review and meta-analysis were performed examining all randomized controlled trials (RCTs) and observational studies (OBSs) assessing the effect of HCO-HD on clinical outcomes of patients with MM complicated by cast nephropathy-induced severe AKI. The primary outcome was all-cause mortality at the end of the study. The secondary outcomes included all-cause mortality at 12 months, HD independence and serum kappa and lambda light chain reduction. Pooled analysis was performed using random effects models. RESULTS: We identified five studies, comprising two RCTs and three retrospective cohort studies, including 276 patients with a mean follow-up of 18.7 months. The majority of the studies were of suboptimal quality and underpowered. Compared with patients treated with conventional HD, HCO-HD was not associated with a survival benefit at 12 months {five studies, 276 patients, relative risk [RR] 1.02 [95% confidence interval (CI) 0.76-1.35], I 2 = 33.9%} or at the end of the studies at an average of 34 months [five studies, 276 patients, RR 1.32 (95% CI 0.71-2.45), I 2 = 62.0%]. There was no difference in HD independence at 90 days [two trials, 78 patients, RR 2.23 (95% CI 1.09-4.55)], 6 months [two studies, 188 patients, RR 1.19 (95% CI 0.68-2.06)] or 12 months [two studies, 188 patients, RR 1.14 (95% CI 0.58-2.26)]. Patients receiving HCO dialysis, however, had a greater reduction in serum kappa [two studies, 188 patients, weighted mean difference (WMD) 46.7 (95% CI 38.6-54.7), I 2 = 52.0%] and lambda [two studies, 188 patients, WMD 50.3 (95% CI 21.4-79.3), I 2 = 95.1%] light chain levels. CONCLUSION: Current evidence from RCTs and OBSs suggests HCO dialysis is able to reduce serum free light chains but makes no significant improvement in all-cause mortality and renal outcomes compared with conventional HD for patients with myeloma cast nephropathy. However, there is a trend towards better renal outcomes with the use of HCO dialysis. The lack of long-term data and the small sample sizes of the included studies limit this analysis. Therefore further large-scale RCTs with longer follow-up are needed to assess the effect of HCO dialysis on clinical outcomes in patients with myeloma cast nephropathy.

The association between variants in PLA2R and HLA-DQA1 and renal outcomes in patients with primary membranous nephropathy in Western China.

BACKGROUND: Both Genome-wide associations and our previous study have shown that single nucleotide polymorphisms (SNPs) of M-type phospholipase A2 receptor (PLA2R) and human leukocyte antigen complex class II HLA-DQα-chain 1 (HLA-DQA1) gene were identified to be associated with primary membranous nephropathy (PMN). However, whether these SNPs affect clinical manifestation and renal outcome for PMN patients is poorly defined. Here, we evaluated whether there is an association between these SNPs and clinical manifestations and renal outcomes of PMN in a western Chinese cohort. METHODS: Seven SNPs within PLA2R and one SNP in HLA-DQA1 were selected in our study. Clinical data from 314 patients with PMN were collected and the relationship between the genotype and phenotype was evaluated. A total of 186 patients had follow-up data. We assessed the treatment responses and renal outcomes between patients with these gene polymorphisms after a median follow-up of 18.6 months. RESULTS: Eight SNPs were not associated with clinical manifestations of PMN patients (Pc < 0.05). rs3828323 T allele was marginally significantly associated with hypertension (P = 0.008, Pc = 0.064, OR = 1.821). After treatment for PMN, the SR group (including CR and PR) had lower serum creatinine level (68.4 ± 18.8 µmol/L vs. 122.8 ± 126.6 µmol/L, P < 0.001), urea (5.5 ± 1.9 mmol/L vs. 8.0 ± 4.0 mmol/L, P < 0.001), uric acid (358.5 ± 95.1 µmol/L vs. 392.8 ± 118.1 µmol/L, P = 0.037) and urinary protein (0.23 (0.76,1.05) g/d vs. 3.01 (2.06,7.95) g/d, P < 0.001), higher eGFR (100.0 ± 20.1 ml/min/1.73m2 vs. 77.1 ± 35.3 ml/min/1.73m2, P < 0.001) and albumin (41.1 ± 5.1 g/L vs.30.4 ± 8.2 g/L, P < 0.001). We also identified that PMN patients with CT/TT genotype for rs3828323 achieved higher cumulative survival rate than patients with CC genotype. CONCLUSIONS: Rs3828323 may influence hypertension and renal outcome in patients with PMN. Further research is needed to explore the mechanism for this genotype-disease phenotype association.

Roxadustat in treating anemia in dialysis patients (ROAD): protocol and rationale of a multicenter prospective observational cohort study.

BACKGROUND: Roxadustat has been shown effective in treating patients with anemia due to chronic kidney disease. However, its long-term effect on clinical outcomes and socioeconomic burden and safety remains unclear. METHODS/DESIGN: This is a multicenter, prospective, longitudinal observational cohort study assessing if Roxadustat improves prognosis in dialysis patients. Primary outcomes will be major adverse cardiovascular events (MACE), defined as composites of cardiovascular death, myocardial infarction, cerebral infarction, hospitalization because of heart failure; all-cause mortality, and annual economic costs in two years. The data will be collected via Research electronic data capture (REDCap) based database as well as software-based dialysis registry of Sichuan province. The primary outcomes for the ROAD study participants will be compared with those in the dialysis registry cohort. Data at baseline and study follow up will also be compared to assess the association between Roxadustat and long-term clinical outcomes. DISCUSSION: The main objective of this study is to the assess long-term association of Roxadustat on MACE, all-cause mortality, socio-economic burden, safety in dialysis patients, which will provide guidance for designing further large randomized controlled trials to investigate this clinic question. STUDY REGISTRATION: The study has been registered in Chinese Clinical Trials Registry (ROAD, ROxadustat in treating Anemia in Dialysis patients, registration number ChiCTR1900025765) and provincial observational cohort database (Renal disEAse observational CoHort database, REACH, ChiCTR1900024926), registered 07 September 2019, http://www.chictr.org.cn .

Acute interstitial nephritis and nephrogenic diabetes insipidus following treatment with sulfamethoxazole-trimethoprim and temozolomide.

We report a case of acute interstitial nephritis with associated nephrogenic diabetes insipidus in a patient treated with temozolomide and sulfamethoxazole-trimethoprim for glioblastoma multiforme. Kidney biopsy demonstrated focal tubulointerstitial change with tubular dilatation, epithelial change and interstitial inflammation. The patient's kidney function improved with cessation of sulfamethoxazole-trimethoprim and treatment with hydrochlorothiazide for nephrogenic diabetes insipidus. Recommencement of temozolomide did not result in further deterioration in kidney function. In this case report, we discuss the novel association between sulfamethoxazole-trimethoprim-induced acute interstitial nephritis and nephrogenic diabetes insipidus, and suggest possible mechanisms involved.

Social Determinants of Health and COVID-19 Among Patients in New York City.

Background: Covid-19 testing and disease outcomes according to demographic and neighborhood characteristics must be understood. Methods: Using aggregate administrative data from a multi-site academic healthcare system in New York from March 1 - May 14, 2020, we examined patient demographic and neighborhood characteristics according to Covid-19 testing and disease outcomes. Results: Among the 23,918 patients, higher proportions of those over 65 years old, male sex, Hispanic ethnicity, Medicare, or Medicaid insurance had positive tests, were hospitalized, or died than those with younger age, non-Hispanic ethnicity, or private insurance. Patients living in census tracts with more non-White individuals, Hispanic individuals, individuals in poverty, or housing crowding had higher proportions of Covid-19 positive tests, hospitalizations, and deaths than counterparts. Discussion: Variation exists in Covid-19 testing and disease outcomes according to patient and neighborhood characteristics. There is a need to monitor Covid-19 testing access and disease outcomes and resolve racist policies and practices.