Diabetes mellitus: association of cystatin C- versus creatinine-based estimated glomerular filtration rate with mortality and cardiovascular events.

BACKGROUND: To explore the association between the differences between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff), and the risk of mortality and cardiovascular (CV) events in individuals with diabetes. METHODS: Three prospective cohorts analyzed data from adults with diabetes from the Incident, Development, and Prognosis of Diabetic Kidney Disease (INDEED) study (2016-17 to 2020) in China, the National Health Nutrition Examination Survey (NHANES, 1999-2004 to 2019) in the USA and UK Biobank (UKB, 2006-10 to 2022) in the UK. Baseline eGFRdiff was calculated using both absolute difference between cystatin C- and creatinine-based calculations (eGFRabdiff), and the ratio between them (eGFRrediff). Cox proportional hazards regression models were used to investigate the association between eGFRdiff and outcomes including all-cause mortality and incident CV events. RESULTS: A total of 8129 individuals from INDEED (aged 60.7 ± 10.0 years), 1634 from NHANES (aged 62.5 ± 14.4 years) and 29 358 from UKB (aged 59.4 ± 7.3 years) were included. At baseline, 43.6%, 32.4% and 42.1% of participants in INDEED, NHANES and UKB, respectively, had an eGFRabdiff value ≥15 mL/min/1.73 m2. During a median follow-up of 3.8 years for INDEED, 15.2 years for NHANES and 13.5 years for UKB, a total of 430, 936 and 6143 deaths and a total of 481, 183 and 5583 CV events occurred, respectively. Each 1-standard deviation higher baseline eGFRabdiff was independently associated with a lower risk of all-cause mortality and CV events, with hazard ratios of 0.77 and 0.82 in INDEED, 0.70 and 0.68 in NHANES, and 0.66 and 0.78 in UKB. Similar results were observed for eGFRrediff. CONCLUSIONS: eGFRdiff represents a marker of adverse events for diabetes among general population. Monitoring both eGFRcys and eGFRcr yields additional prognostic information and has clinical utility in identifying high-risk individuals for mortality and CV events.

A 71-year-old male with a life-threatening recurrence of hemolytic anemia, thrombocytopenia, and acute kidney injury after pembrolizumab therapy: a case report.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, their use has been restricted in patients with preexisting autoimmune diseases due to concerns about increased risk of immune-related adverse events (irAEs). CASE PRESENTATION: We present a case of a patient with stage IV lung adenocarcinoma and a history of complement-mediated autoimmune hemolytic anemia in remission. After receiving a single dose of pembrolizumab, the patient experienced life-threatening recurrent hemolytic anemia, de novo thrombocytopenia, diarrhea, myocarditis, and acute kidney injury. Laboratory tests confirmed the diagnosis of Evan's syndrome, with positive PAIgG and direct antiglobulin test. Treatment with intravenous methylprednisolone at a dose of 2 mg/kg resulted in a favorable response, with resolution of symptoms and rapid recovery of kidney function. The probable cause of pre-renal hypoperfusion (evidenced by a BUN-to-creatinine ratio of 48.1) leading to acute tubular injury was attributed to pembrolizumab-induced diarrhea. CONCLUSIONS: This case illustrates a life-threatening recurrence of complement-mediated autoimmune hemolytic anemia induced by ICIs. Clinicians should carefully consider the expected efficacy and potential toxicity before initiating ICIs therapy in patients with preexisting autoimmune diseases. Additionally, the occurrence of acute kidney injury during ICIs therapy adds complexity and requires careful differential diagnosis.

Association of left ventricular hypertrophy and functional impairment with cardiovascular outcomes and mortality among patients with chronic kidney disease, results from the C-STRIDE study.

AIM: Left ventricular hypertrophy and impaired systolic and diastolic function are commonly seen in patients with chronic kidney disease (CKD), but relationships between the disorders and cardiovascular outcomes are not well established among the patients. METHODS: Totally, 2020 patients with CKD Stages 1-4 were used in the analysis. Left ventricular hypertrophy was defined by left ventricular mass index >49.2 g/m2.7 in men and > 46.7 g/m2.7 in women. Incident heart failure, non-heart failure cardiovascular events, and all-cause mortality were recorded longitudinally. Cox proportional hazards regression model was used to evaluate the association between the echo parameters and the outcomes, with death treated as the competing risk event for the cardiovascular events. RESULTS: After a median follow-up of 4.5 years, 53 heart failure, 76 non-heart failure cardiovascular events and 82 deaths occurred. No overall association was found between left ventricular hypertrophy and subsequent heart failure, but the relationship was significant among patients with no diabetes with the multivariable adjusted hazard ratio of 3.66 (95% confidence interval: 1.42-9.46). Ejection fraction<55% was associated with both heart failure and non-heart failure cardiovascular events with hazard ratios of 3.16 (1.28-7.77) and 2.76 (1.08-7.04), respectively. E/A ratio ≤ 0.75 was associated with non-heart failure cardiovascular events [hazard ratio = 2.03 (1.09-3.80)], compared with E/A ratio of 0.76-1.49. CONCLUSION: Associations of reduced left ventricular ejection fraction with both heart failure and non-heart failure cardiovascular events and of impaired left ventricular diastolic function with non-heart failure cardiovascular events were validated in a Chinese cohort of CKD.

Estimation of Prevalence of Kidney Disease Treated With Dialysis in China: A Study of Insurance Claims Data.

RATIONALE & OBJECTIVE: The national prevalence of dialysis in China has not been well studied. We aimed to estimate the prevalence of kidney disease treated with dialysis and predict the trend using claims data in order to provide evidence for developing prevention strategies. STUDY DESIGN: Cross-sectional study of insurance claims. SETTING & PARTICIPANTS: Medical claims data from January 1, 2013, to December 31, 2017, were extracted from a large claims database by using a 2-stage sampling design to obtain a national sample covered by the urban basic medical insurance, the most predominant insurance program in China. EXPOSURE: Patients receiving maintenance dialysis, including hemodialysis (HD) and peritoneal dialysis (PD), were identified according to medical billing data and International Classification of Diseases, Tenth Revision (ICD-10) codes. OUTCOMES: The age- and sex-standardized population prevalence of kidney disease treated with dialysis was estimated by year and treatment modality. ANALYTICAL APPROACH: Crude and age- and sex-standardized prevalence of kidney disease treated with dialysis were calculated stratified by year and treatment modality. The gray Verhulst model was used to predict dialysis prevalence from 2018 to 2025. RESULTS: The age-and sex-standardized prevalence of dialysis patients increased from 255.11 per million population (pmp) in 2013 to 419.39 pmp in 2017. The age- and sex-standardized prevalence of HD and PD in 2017 were 384.41 pmp and 34.98 pmp, respectively, and the total number of dialysis patients in China was estimated to be 581,273. The prevalence of dialysis was predicted to rise above 2017 levels, with a predicted prevalence of 534.60 pmp in 2020 and 629.67 pmp in 2025, corresponding to 744,817 and 874,373 patients, respectively. LIMITATIONS: Claims data have potential errors in classification of patients, and population selection bias may have limited inferences to the entire Chinese population. CONCLUSIONS: The prevalence of kidney disease treated with dialysis has risen between 2013 and 2017 in China and is predicted to increase further through 2025. These findings highlight the importance of prevention and control strategies to reduce the escalating burden of kidney failure.

The Prevalence of Diabetic Microvascular Complications in China and the USA.

PURPOSE OF REVIEW: Diabetes can lead to development of devastating microvascular complications, such as nephropathy, retinopathy, and peripheral sensory and autonomic neuropathy. While China and the USA both face the threat of this major public health challenge, the literature is limited in describing similarities and differences in the prevalence, and risk factors for the development, of diabetic microvascular complications between these two countries. RECENT FINDINGS: The current review discusses the following: (1) the most recent evidence on prevalence of diabetic microvascular complications in China and the USA (including downtrends of diabetes retinopathy and neuropathy in the USA); (2) differences in patient risk factors of these complications; (3) challenges and current knowledge gaps (such as lacking national epidemiological data of diabetic complications in China); and (4) potential future clinical and research opportunities (including needs in diabetes evaluation and management in remote areas and standardization of methods in evaluating diabetic complications across countries). Diabetic microvascular complications remain to be health threats in both China and the USA. Further investigations are needed for comprehensive understanding and effect prevention and management of these complications.

Executive summary for China Kidney Disease Network (CK-NET) 2016 Annual Data Report.

Chronic kidney disease (CKD) has been recognized as a public health problem globally. The spectrum of CKD in China has been evolving toward that of developed countries, which will have enormous impacts on the health care system. However, there has been no well-established national surveillance system for kidney diseases. Furthermore, China still faces several challenges of kidney care, including limited capacity and efficiency, suboptimal awareness, and huge heterogeneity in diagnosis and treatment. The China Kidney Disease Network has published 2 reports regarding the burden of CKD and end-stage kidney disease in China and intends to become a comprehensive surveillance system for kidney diseases based on multisource data. With the expansion of research group and data sources, the content of the China Kidney Disease Network 2016 Annual Data Report was further enriched. Section I addresses the epidemiologic characteristics of patients with CKD based on a national inpatient database, Hospital Quality Monitoring System, covering more than 52% of China's tertiary hospitals in China in 2016. Section II focuses on the burden of patients receiving dialysis, mainly based on the nationwide claims database, China Health Insurance Research Association database, which collects data from approximately 2% of the insured population from the municipalities/provincial capital cities and approximately 5% from the prefecture-level cities. An independent chapter regarding dialysis in 3 provincial dialysis quality control centers has been added. The China Kidney Disease Network 2016 Annual Data Report symbolizes a successful team effort in the era of big data, with support from the specialists and partners of the collaborative network, which is of substantial value for understanding the burden of kidney diseases in China and developing prevention and control strategies.

Executive summary for the 2015 Annual Data Report of the China Kidney Disease Network (CK-NET).

Chronic kidney disease (CKD) has received increased attention as a leading public health problem worldwide. Globally surveillance systems for kidney disease are still lacking, especially in developing countries like China, which constitutes an obstacle to develop effective preventive strategies. China Kidney Disease Network (CK-NET) was initiated in 2014 and further developed in accordance with the national strategy of prompting Big Data application in China. One major output of CK-NET is to generate an Annual Data Report (ADR) providing resourceful information regarding kidney disease in China. Entering the second cycle of ADR, we have expanded the scope and depth of our research based on the previous ADR. There are 2 sections in the current ADR, generated from data from 2015 from various sources. Section I is based on a dataset of national hospitalized patients and describes the characteristics regarding hospitalized patients with CKD. Section II focuses on patients receiving renal replacement therapy based on 2 nationwide claims databases. There is also a chapter that focuses on patients on the waiting list for renal transplantation based on the China Organ Transplant Response System. Certain findings, including the effect of metabolic disease on the spectrum of CKD, the underdiagnoses of CKD and acute kidney injury among hospitalized patients, and the less-optimal treatment of complications among dialysis patients, will inspire the following research as well as changes in health policy. By integrating and mining national patient-level administrative or claim databases, we are able to provide a comprehensive description of the burden of CKD and end stage kidney disease in China, which could be used by multiple stakeholders with interests in kidney disease.

Hemophagocytic lymphohistiocytosis followed by an episode of peritoneal dialysis associated peritonitis: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is characterized by excessive activation of the immune system due to infection, autoimmune diseases, or malignancy. As an aggressive and life-threatening clinical syndrome, HLH secondary to peritoneal dialysis associated peritonitis (PDAP) has never been reported. CASE PRESENTATION: A 34-year-old female peritoneal dialysis (PD) patient was hospitalized for fever, progressively multi-organ damage (including cytopenias, abnormalities of coagulation and liver enzyme) after an episode of organism-specific peritonitis. She was refractory to the broad-spectrum antimicrobial agent. Further tests found hemophagocytosis on the bone marrow examination, and extremely high level of sIL2-R and impaired activity of NK cell. The diagnosis of HLH was eventually established. After HLH-specific therapy, this patient recovered and discharged. CONCLUSIONS: The present case suggests that clinicians should to be aware of HLH in those patients apparently suspected with refractory or relapsing peritonitis, especially those accompanied with persist fever, hyperferritinemia, and cytopenias. HLH-specific therapy and supportive care should be applied without delay.

Clinical significance of C4d deposition in renal tissues from patients with primary Sjögren's syndrome-a preliminary study.

BACKGROUND: To evaluate renal expression of C4d, a complement component in the classical/mannose binding lectin (MBL) pathway, in patients with primary Sjögren's syndrome (pSS)-associated renal impairments. METHODS: We retrospectively reviewed the clinical and pathological data from 39 patients with pSS presenting with renal impairments. C4d was examined in paraffin-embedded biopsy tissues using immunohistochemistry. Glomerular C4d positive was defined when > 75% glomeruli were globally stained. Tubulointerstitial C4d (TI-C4d) were scored semi-quantitatively as 0 (absent), 1 (spotty or weak), 2 (patchy) and 3 (diffuse). A TI-C4d score ≥ 2 was considered TI-C4d positive and included in the TI-C4d+ group and vice versa. Peritubular capillary (PTC) C4d was scored as 0 (absent), 1 (0~10%, minimal), 2 (10%~ 50%, focal), and 3 (> 50%, diffuse). RESULTS: Glomerular C4d deposition was observed in all 8 patients with pSS-related membranous nephropathy (MN) without obvious C1q deposition. Two of 5 patients with mesangial proliferative glomerulonephritis and 1 of 2 patients with IgA nephropathy had mild mesangial C4d deposition. Sixteen patients (6 glomerular dominant and 10 tubulointerstitial dominant) presented TI-C4d score ≥ 2. Patients in the TI-C4d+ group exhibited a higher serum creatinine level at the time of renal biopsy (TI-C4d+ 132.5 [89.7, 165.5] vs. TI-C4d- 83.0 [70.7, 102.0] µmol/L, P = 0.008). PTC C4d was observed in 12 patients, with each of minimal, focal and diffuse staining being noted in 4 patients. CONCLUSIONS: The MBL pathway of complement activation was potentially involved in pSS-related MN. Tubulointerstitial C4d might be a pathological marker of severe renal injury in patients with pSS-related renal impairments.

Serum uromodulin and progression of kidney disease in patients with chronic kidney disease.

BACKGROUND: Uromodulin is specifically synthesized and secreted by kidney tubular epithelial cells. Studies on the association of serum uromodulin and outcomes of chronic kidney disease (CKD) are lacking. This study aimed to evaluate whether serum uromodulin was associated with outcomes of patients with CKD. METHODS: We measured serum uromodulin concentrations by ELISA in 2652 CKD patients from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) and investigated the association of serum uromodulin with outcomes of CKD patients, including end-stage kidney disease (ESKD) receiving kidney replacement therapy, cardiovascular events and mortality by Cox proportional hazards regression model. RESULTS: A total of 2652 CKD patients were enrolled in this study, with an age of 48.7 ± 13.8 years and the baseline eGFR of 49.6 ± 29.4 mL/min/1.73 m2, of whom 58.4% were male. The median level of urinary albumin/creatinine ratio and serum uromodulin was 473.7 mg/g (IQR 134.1-1046.6 mg/g) and 77.2 ng/mL (IQR 48.3-125.9 ng/mL), respectively. Altogether, 404 ESKD, 189 cardiovascular events, and 69 deaths occurred during the median follow-up of 53.6 (IQR 44.0-64.0) months. Lower levels of serum uromodulin were independently associated with higher risk of incident ESKD after adjusting for traditional cardiovascular risk factors, with the hazard ratios (HRs) of 3.23 (95% confidence intervals [CIs] 2.15-4.85) for the middle tertile and 7.47 (95% CI 5.06-11.03) for the bottom tertile, compared with top tertile and 0.31 (95% CI 0.25-0.38) per every standard deviation increase. After further adjustment for the baseline eGFR, the association was greatly attenuated, but still significant, with HRs of 1.92 (95% CI 1.26-2.90) for the bottom tertile compared with top tertile and 0.69 (95% CI 0.55-0.86) per every standard deviation increase. CONCLUSIONS: Serum uromodulin is independently associated with an increased risk of incident ESKD in CKD patients.

Minimal change disease associated with anti-PD1 immunotherapy: a case report.

BACKGROUND: Oncologic immunotherapy is a form of therapy intended to reactivate the immune response to tumor cells using agents that modulate immune checkpoints, such as programmed cell death protein 1 and its ligand (PD-1/PD-L), and cytotoxic T-lymphocyte-associated antigen 4. Along with activation of the immune system to tumors, immune-mediated kidney side effects have been reported, most of which are cases of interstitial nephritis. Glomerular disease, however, appears rare. CASE PRESENTATION: Herein, we describe a patient with nephrotic syndrome related to treatment with an anti-PD1 antibody for Hodgkin lymphoma. Following the third dose of anti-PD1 antibody, the patient developed massive proteinuria and nephrotic syndrome. Kidney biopsy showed diffuse podocyte foot process effacement upon electron microscopy, which was consistent with minimal change disease. Corticosteroid treatment yielded full and rapid remission of nephrotic syndrome in 1 month. CONCLUSION: The present case suggests an association between anti-PD1 therapeutic immune activation and the development of nephrotic syndrome. Given the increasing prevalence of oncologic immunotherapy, patients should be routinely monitored for kidney side effects associated with these agents.

Rapidly progressive glomerulonephritis due to anti-glomerular basement membrane disease accompanied by IgA nephropathy: a case report.

Anti-glomerular basement membrane (anti-GBM) disease is characterized by autoantibodies against antigenic site on type IV collagen of the GBM. The coexistence of anti-GBM disease and other immune complex mediated glomerulonephritis is common. Herein, we describe a patient presented with rapidly progressive glomerulonephritis, who was diagnosed as IgA-mediated nephropathy and was found to have abundant serum anti-glomerular basement membrane IgG antibodies. The patient's renal function improved considerably with intensive immunosuppressive therapy.

The Difference Between Cystatin C- and Creatinine-Based Estimated Glomerular Filtration Rate and Risk of Diabetic Microvascular Complications Among Adults With Diabetes: A Population-Based Cohort Study.

OBJECTIVE: The impact of the difference between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff) on diabetic microvascular complications (DMCs) remains unknown. We investigated the associations of eGFRdiff with overall DMCs and subtypes, including diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN). RESEARCH DESIGN AND METHODS: This prospective cohort study included 25,825 participants with diabetes free of DMCs at baseline (2006 to 2010) from the UK Biobank. eGFRdiff was calculated using both absolute difference (eGFRabdiff) and the ratio (eGFRrediff) between cystatin C- and creatinine-based calculations. Incidence of DMCs was ascertained using electronic health records. Cox proportional hazards regression models were used to evaluate the associations of eGFRdiff with overall DMCs and subtypes. RESULTS: During a median follow-up of 13.6 years, DMCs developed in 5,753 participants, including 2,752 cases of DR, 3,203 of DKD, and 1,149 of DN. Each SD decrease of eGFRabdiff was associated with a 28% higher risk of overall DMCs, 14% higher risk of DR, 56% higher risk of DKD, and 29% higher risk of DN. For each 10% decrease in eGFRrediff, the corresponding hazard ratios (95% CIs) were 1.16 (1.14, 1.18) for overall DMCs, 1.08 (1.05, 1.11) for DR, 1.29 (1.26, 1.33) for DKD, and 1.17 (1.12, 1.22) for DN. The magnitude of associations was not materially altered in any of the sensitivity analyses. CONCLUSIONS: Large eGFRdiff was independently associated with risk of DMCs and its subtypes. Our findings suggested monitoring eGFRdiff in the diabetes population has potential benefit for identification of high-risk patients.

Identifying subtypes of Type 2 diabetes mellitus based on real-world electronic medical record data in China.

AIMS: To replicate the European subtypes of type 2 diabetes mellitus (T2DM) in Chinese diabetes population, and investigate the risk of complications in different subtypes. METHODS: A diabetes cohort using real-world patient data was constructed and clustering was employed to subgroup the T2DM patients. Kaplan-Meier analysis and the Cox model were used to analyze the association between diabetes subtypes and the risk of complications. RESULTS: A total of 2,652 T2DM patients with complete clustering data were extracted. Among them, 466 (17.57 %) were classified as severe insulin-deficient diabetes (SIDD), 502 (18.93 %) as severe insulin-resistant diabetes (SIRD), 672 (25.34 %) as mild obesity-related diabetes (MOD), and 1,012 (38.16 %) as mild age-related diabetes (MARD). The risk of chronic kidney disease (CKD) and diabetic retinopathy (DR) were different in the four subtypes. Compared with MARD, SIRD had a higher risk of CKD (HR 2.01 [1.03, 3.91]), and SIDD had a higher risk of DR (HR 2.17 [1.12, 4.20]). The risk of stroke and coronary events had no difference. CONCLUSIONS: The European T2DM subtypes can be replicated in Chinese diabetes population. The risk of CKD and DR varied among different subtypes, indicating that proper interventions can be taken to prevent specific complications in different subtypes.

The effect of different levels of systolic blood pressure control on new-onset chronic kidney disease in hypertension multimorbidity.

To explore the effect of different levels of systolic blood pressure (SBP) control on new-onset chronic kidney disease in hypertension multimorbidity. The hypertensive patients with multimorbidity information were enrolled from the Kailuan Study. The isolated hypertension patients undergoing physical examination during the same period were selected in a 1:1 ratio as control. Finally, 12,897 participants were divided into six groups: Group SBP < 110 mmHg, Group 110 ≤ SBP < 120 mmHg, Group 120 ≤ SBP < 130 mmHg, Group 130 ≤ SBP < 140 mmHg, Group 140 ≤ SBP < 160 mmHg and Group SBP ≥ 160 mmHg. The outcomes were new-onset CKD, new onset proteinuria, decline in eGFR and high or very high risk of CKD. Cox proportional hazards regression was used to examine the hazard ratios (HRs) of the outcomes among SBP levels. When 110 ≤ SBP < 120 mmHg, the incidence density of new-onset CKD, new onset proteinuria and decline in eGFR were 59.54, 20.23 and 29.96 per 1000 person-years, respectively. Compared to this group, the HR (95% CI) values for the risk of new-onset CKD from Group SBP < 110 mmHg to Group SBP ≥ 160 mmHg were 1.03 (0.81-1.32), 1.04 (0.91-1.19), 1.09 (0.95-1.16), 1.16 (1.02-1.21) and 1.18 (1.04-1.24), respectively. For patients over 65 years old, the risks of outcomes were increased when SBP < 120 mmHg. The lowest HR of high or very high risk of CKD for participants with or without multimorbidity occurred when 120 ≤ SBP < 130 mmHg. The HR of new-onset CKD in hypertension multimorbidity was lowest at 110-120 mmHg. The optimal SBP level was between 120 and 130 mmHg for individuals with high or very high risk of CKD. For patients over 65 years old, the low limit of target BP is advised to be not lower than 120 mmHg.

The Relationship between Vascular Aging Phenotypes and Renal Damage among Individuals with Type 2 Diabetes.

OBJECTIVE: The aim of this study was to investigate the relationship between vascular aging (VA) phenotypes and renal damage in type 2 diabetic population. METHODS: In this cross-sectional study, we included 8,141 individuals with type 2 diabetes who participated in the Kailuan Study during 2010-2018 and completed the brachial-ankle pulse wave velocity (baPWV) assessment for arterial stiffness, an indicator for VA. The age- and sex-specific 10th and 90th percentiles of baPWV based on a reference cohort were used as cutoffs to define supernormal VA (SUPERNOVA, baPWV<10th percentiles), normal VA (NVA, baPWV 10th to 90th percentiles), and early VA (EVA, baPWV>90th percentiles). The estimated glomerular filtration rate (eGFR) and proteinuria levels were used to assess renal damage, including isolated proteinuria, isolated kidney function decline (eGFR<60 mL/min/1.73 m2), and proteinuria combined with kidney function decline. Multivariable logistic regression analysis was used to analyze the relationship between VA phenotypes and diabetic kidney damage. RESULTS: The prevalences of isolated proteinuria, isolated kidney function decline, and proteinuria combined with kidney function decline were 17.0%, 12.2%, and 5.4%, respectively. Compared with NVA, SUPERNOVA was associated with 34% lower odds (95% confidence interval [CI]: 0.46-0.96) of isolated proteinuria after adjusting for age, sex, and other potential confounders. EVA was associated with higher odds of all three types of kidney damage; the adjusted odds ratio (95% CI) was 1.42 (1.20-1.67) for proteinuria, 1.24 (1.01-1.51) for kidney function decline, and 1.56 (1.18-2.06) for proteinuria combined with kidney function decline. CONCLUSIONS: VA phenotypes are associated with renal damage, especially isolated proteinuria. SUPERNOVA was associated with lower odds of isolated proteinuria and EVA was associated with higher odds of proteinuria and kidney function decline.

ESKD Risk Prediction Model in a Multicenter Chronic Kidney Disease Cohort in China: A Derivation, Validation, and Comparison Study.

BACKGROUND AND OBJECTIVES: In light of the growing burden of chronic kidney disease (CKD), it is of particular importance to create disease prediction models that can assist healthcare providers in identifying cases of CKD individual risk and integrate risk-based care for disease progress management. The objective of this study was to develop and validate a new pragmatic end-stage kidney disease (ESKD) risk prediction utilizing the Cox proportional hazards model (Cox) and machine learning (ML). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE), a multicenter CKD cohort in China, was employed as the model's training and testing datasets, with a split ratio of 7:3. A cohort from Peking University First Hospital (PKUFH cohort) served as the external validation dataset. The participants' laboratory tests in those cohorts were conducted at PKUFH. We included individuals with CKD stages 1~4 at baseline. The incidence of kidney replacement therapy (KRT) was defined as the outcome. We constructed the Peking University-CKD (PKU-CKD) risk prediction model employing the Cox and ML methods, which include extreme gradient boosting (XGBoost) and survival support vector machine (SSVM). These models discriminate metrics by applying Harrell's concordance index (Harrell's C-index) and Uno's concordance (Uno's C). The calibration performance was measured by the Brier score and plots. RESULTS: Of the 3216 C-STRIDE and 342 PKUFH participants, 411 (12.8%) and 25 (7.3%) experienced KRT with mean follow-up periods of 4.45 and 3.37 years, respectively. The features included in the PKU-CKD model were age, gender, estimated glomerular filtration rate (eGFR), urinary albumin-creatinine ratio (UACR), albumin, hemoglobin, medical history of type 2 diabetes mellitus (T2DM), and hypertension. In the test dataset, the values of the Cox model for Harrell's C-index, Uno's C-index, and Brier score were 0.834, 0.833, and 0.065, respectively. The XGBoost algorithm values for these metrics were 0.826, 0.825, and 0.066, respectively. The SSVM model yielded values of 0.748, 0.747, and 0.070, respectively, for the above parameters. The comparative analysis revealed no significant difference between XGBoost and Cox, in terms of Harrell's C, Uno's C, and the Brier score (p = 0.186, 0.213, and 0.41, respectively) in the test dataset. The SSVM model was significantly inferior to the previous two models (p < 0.001), in terms of discrimination and calibration. The validation dataset showed that XGBoost was superior to Cox, regarding Harrell's C, Uno's C, and the Brier score (p = 0.003, 0.027, and 0.032, respectively), while Cox and SSVM were almost identical concerning these three parameters (p = 0.102, 0.092, and 0.048, respectively). CONCLUSIONS: We developed and validated a new ESKD risk prediction model for patients with CKD, employing commonly measured indicators in clinical practice, and its overall performance was satisfactory. The conventional Cox regression and certain ML models exhibited equal accuracy in predicting the course of CKD.

Red Blood Cell Distribution Width Is Associated With Adverse Kidney Outcomes in Patients With Chronic Kidney Disease.

Background: Chronic kidney disease (CKD) is a global public health issue. Red blood cell distribution width (RDW) is a recently recognized potential inflammatory marker, which mirrors the variability in erythrocyte volume. Studies indicate that elevated RDW is associated with increased risk of mortality in CKD patients, while evidence regarding the impact of RDW on kidney outcome is limited. Methods: Altogether 523 patients with CKD stage 1-4 from a single center were enrolled. We identified the cutoff point for RDW level using maximally selected log-rank statistics. The time-averaged estimated glomerular filtration rate (eGFR) slope was determined using linear mixed effects models. Rapid CKD progression was defined by an eGFR decline >5 ml/min/1.73 m2/year. The composite endpoints were defined as doubling of serum creatinine, a 30% decline in initial eGFR or incidence of eGFR < 15 ml/min/1.73 m2, whichever occurred first. Multivariable logistic regression or Cox proportional hazards regression was performed, as appropriate. Results: During a median follow-up of 26 [interquartile range (IQR): 12, 36] months, 65 (12.43%) patients suffered a rapid CKD progression and 172 (32.89%) composite kidney events occurred at a rate of 32.3/100 patient-years in the high RDW group, compared with 14.7/100 patient-years of the remainder. The annual eGFR change was clearly steeper in high RDW group {-3.48 [95% confidence interval (CI): -4.84, -2.12] ml/min/1.73 m2/year vs. -1.86 [95% CI: -2.27, -1.45] ml/min/1.73 m2/year among those with RDW of >14.5% and ≤14.5%, respectively, P for between-group difference <0.05}. So was the risk of rapid renal function loss (odds ratio = 6.79, 95% CI: 3.08-14.97) and composite kidney outcomes (hazards ratio = 1.51, 95% CI: 1.02-2.23). The significant association remained consistent in the sensitivity analysis. Conclusion: Increased RDW value is independently associated with accelerated CKD deterioration. Findings of this study suggest RDW be a potential indicator for risk of CKD progression.

Catalytic performance and periodate activation mechanism of anaerobic sewage sludge-derived biochar.

Periodate (PI)-based advanced oxidation processes are a newly discovered approach for effective pollutant elimination. In this study, we demonstrated that biochar obtained from pyrolysis of anaerobic sewage sludge without any pretreatment can be used for PI activation. The biochar obtained at 800 °C (SBC-800) exhibited the best PI activation capacity using acid organic II (AO7) as substrate. The PI activation was strongly dependent on pH and exhibited the highest AO7 removal rate at pH 3.0. Meanwhile, the anti-interference capacity with common wastewater components and reusability of the SBC-800/PI system were confirmed. Combined with the results of chemical quenching, reactive oxygen species (ROS) trapping, X-ray photoelectric spectroscopy (XPS), electrochemical and density function theory (DFT)-based calculations, singlet oxygen production and electron transfer mediated by the SBC-800-PI complex were the dominant AO7 oxidation mechanisms. This study provides easily prepared catalysts for PI activation and paves the way for solid waste recycling and reuse.