Acute kidney injury among hospitalized children with cancer.

BACKGROUND: Few studies to date have analyzed the epidemiology of acute kidney injury (AKI) in children with cancer in developing countries. The aim of this study was to assess the incidence, risk profile and outcomes of AKI in Chinese children hospitalized with cancer. METHODS: This multi-center study analyzed Chinese children hospitalized with cancer in 2013-2015. Electronic hospital and laboratory databases were screened to select pediatric patients with malignancy who had at least two Scr results within any 7-day window during their first 30 days of hospitalization. AKI events were identified and staged according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The incidence of and risk factors for AKI were analyzed, as were mortality rate, incidence of kidney recovery, and length of hospital stay. RESULTS: Of the 9828 children with cancer, 1657 (16.9%) experienced AKI events, including 549 (5.6%) community-acquired (CA-AKI) and 1108 (11.3%) hospital-acquired AKI (HA-AKI) events. The three types of cancer with the highest incidence of AKI were urinary system cancer (25.8%), hepatic cancer (19.4%), and retroperitoneal malignancies (19.1%). The risk factor profiles of CA-AKI and HA-AKI events differed, with many HA-AKI events due to treatment with nephrotoxic agents. In-hospital death rates were 5.4% (90 of 1657) in children with and 0.9% (74 of 8171) in children without AKI events. AKI events were also associated with longer hospitalization and higher daily costs. CONCLUSIONS: AKI events are common among Chinese children hospitalized for cancer and are associated with adverse in-hospital outcomes.

New Criterion to Evaluate Acute-on-Chronic Kidney Injury Based on the Creatinine Reference Change.

BACKGROUND: The lack of consensus criteria of acute on chronic kidney injury (ACKI) affects the judgment for its clinical prognosis. METHODS: In this study, we analyzed the data from 711,615 hospitalized adults who had at least 2 serum creatinine (SCr) tests within 30 days. We estimated the reference change value (RCV) of SCr given initial SCr level in adults without known risks of acute kidney injury other than chronic kidney disease (CKD). We proposed a criterion for ACKI based on the RCV of SCr (cROCK), which defined ACKI as a ≥25% increase in SCr in 7 days. We validated cROCK by its association with the risks of in-hospital mortality, death after discharge, and CKD progression in a large cohort of patients with CKD stage 3. RESULTS: In 21,661 patients with CKD stage 3, a total of 3,145 (14.5%), 1,512 (7.0%), and 221 (1.0%) ACKI events were detected by both cROCK and Kidney Disease Improving Global Outcomes (KDIGO), cROCK only, and KDIGO only, respectively. cROCK detected 40% more ACKI events than KDIGO. Compared with patients without ACKI by both definitions, those with cROCK- but not KDIGO-defined ACKI had a significantly increased risk of in-hospital mortality (hazard ratio [HR] 5.53; 95% CI 3.75-8.16), death after discharge (HR 1.51; 95% CI 1.21-1.83), and CKD progression (OR 5.65; 95% CI 3.05-10.48). CONCLUSIONS: RCV-based criterion (cROCK) for ACKI is clinically valid in that it has a substantially improved sensitivity in identifying patients with high risk of adverse outcomes.

Epidemiology and outcomes of acute kidney injury in hospitalized cancer patients in China.

Acute kidney injury (AKI) is a common complication in cancer patients, but the data are lacking in Asian countries. We aimed to assed the epidemiology, correlated risk factors and outcomes of AKI in cancer patients from China. We conducted a nationwide cohort study of cancer patients who were admitted to 25 general and children hospitals across China from January 1, 2013 to December 31, 2015. We obtained patient-level data from the electronic hospitalization information system and laboratory databases of all inpatients who had at least two serum creatinine tests within any 7-day window during their first 30 days of hospitalization. AKI was defined and staged according to Kidney Disease Improving Global Outcomes criteria. Incidence rate and risk factor profiles for AKI were examined. Outcomes of interest included in-hospital mortality, length of stay and daily costs. A total of 136,756 adult cancer patients were assessed in our study. The overall incidence of AKI was 7.5%, of which 1.6% were community acquired and 5.9% hospital acquired. The top three cancer types with high incidence of AKI were bladder cancer, leukemia, and lymphoma. Risk factors for community-acquired and hospital-acquired AKI were similar, including age, increased baseline serum creatinine, shock and urinary tract obstruction. In-hospital death occurred in 12.0% with AKI vs. 0.9% cancer patients without AKI. After adjustment for confounders, the severe AKI was associated with higher risk of in-hospital death, prolonged length of stay and higher daily costs. Clinicians should increase their awareness of AKI in hospitalized cancer patients.

Epidemiology of acute kidney injury in hospitalized pregnant women in China.

BACKGROUND: Epidemiologic data of acute kidney injury (AKI) during pregnancy is lacking in China. This study aims to determine the effect of pregnancy on the risk of AKI among hospitalized women of childbearing age, and to describe the incidence, risk factors and outcomes of AKI in hospitalized pregnant women in China. METHODS: We previously conducted a nationwide, multi-centered cohort of hospitalized patients from 25 hospitals in China during 1/1/2013 to 31/12/2015. Women of childbearing age (14-50 year) who had at least two serum creatinine tests within any 7-day window were selected as analysis set. Patient-level data were obtained from the electronic hospitalization information system and laboratory databases. AKI events were identified according to the creatinine criteria of Kidney Disease Improving Global Outcomes. RESULTS: Among 110,873 women of childbearing age, pregnant women (n = 10,920) had a 51% higher risk of AKI than non-pregnant women (n = 99,953). Community acquired and hospital acquired AKI occurred in 3.6% (n = 393) and 3.7% (n = 402) of the pregnant women, respectively, giving rise to an overall AKI incidence of 7.3%. While, hospital coding would have identified less than 5% of AKI episodes. The top three risk factors of AKI during pregnancy, ranked in order of decreasing population attributable fractions were pregnancy-induced hypertension syndrome (21.1%), acute fatty liver (13.5%), and chronic kidney disease (6.2%). CONCLUSION: AKI in pregnancy is associated with increased maternal mortality rate, longer length of stay and higher daily cost. AKI is a common and severe complication during pregnancy in China.

LncRNA NONRATT021972 siRNA attenuates P2X7 receptor expression and inflammatory cytokine production induced by combined high glucose and free fatty acids in PC12 cells.

Diabetic neuropathy (DNP) is a frequent chronic complication of diabetes mellitus with potentially life-threatening outcomes. High glucose and elevated free fatty acids (FFAs) have been recently recognized as major causes of nervous system damage in diabetes. Our previous study has indicated extracellular stimuli, such as high glucose and/or FFA stress, may activate the p38 mitogen-activated protein kinase (MAPK) signaling pathway and induce a p38 MAPK-dependent sensitization of the P2X7 receptor and release of inflammatory factors in PC12 cells, while the mechanisms underlying remain to be elucidated. Long noncoding RNAs (lncRNAs) play important roles in diverse biological processes, including activation of a series of pathway signalings. Here, we showed combined high D-glucose and FFAs (HGHF) induced an increment of lncRNA-NONRATT021972 (NONCODE ID, nc021972) in PC12 cells. Nc021972 small interference RNA (siRNA) alleviated HGHF-induced activation of p38 MAPK, expression of the P2X7 receptor, and [Ca(2+)]i increment upon P2X7 receptor activation. Further experiments showed that there existed a crosstalk between nc021972 and the p38 MAPK signaling pathway. Inhibition of p38 MAPK signaling decreased nc021972-induced expression of the P2X7 receptor and [Ca(2+)]i increment upon P2X7 receptor activation. Also, nc021972 siRNA inhibited HGHF-induced PC12 release of TNF-α and IL-6 and rescued decreased cell viability mediated by the P2X7 receptor. Therefore, inhibition of nc021972 may serve as a novel therapeutic strategy for diabetes complicated with nervous inflammatory diseases.

The profiles of biopsy-proven renal tubulointerstitial lesions in patients with glomerular disease.

BACKGROUND: Renal tubules and interstitium are vulnerable to injury and play a central role in the progression of various chronic kidney diseases (CKDs). However, high quality epidemiologic study on the profiles of biopsy-proven tubulointerstitial lesions (TILs) is extremely limited. METHODS: We conducted a retrospective renal biopsy series including 62,569 native biopsies at 1,211 hospitals across China from 2015 to 2017. The TILs, including the shedding of tube epithelial, renal tubular atrophy, renal interstitial fibrosis, edema and inflammatory infiltration, were identified from the pathological report. We analyzed the severity and chronicity of TILs stratified by gender, age groups, biopsy indications, and concurrent glomerular diseases. We also examined the correlation between TIL and glomerulosclerosis. RESULTS: Of 56,880 patients with biopsy-proven glomerular disease, 79.5% had TILs. Renal interstitial inflammatory infiltration was the most common type of TIL (77.7%), followed by renal tubular atrophy (56.0%) and renal interstitial fibrosis (32.8%). Severe and chronic TILs were more common in adults than in children. The three glomerular diseases with the highest proportion of moderate-to-severe and chronic TIL were diabetic nephropathy, immunoglobulin A (IgA) nephropathy and focal segmental glomerulosclerosis. The severity of TILs was moderately correlated with glomerulosclerosis score (r=0.51). Moderate-to-severe and chronic TIL were more common in southern China. After adjusting for age, sex, hospital level, region, biopsy indication and type of concurrent glomerular diseases, adults with renal arteriole injury had a six-fold higher risk of moderate-to-severe TIL [odds ratio (OR), 7.12; 95% confidence interval (CI), 6.42 to 7.91] and a three-fold higher risk of chronic TIL (OR, 4.58; 95% CI, 4.37 to 4.79). CONCLUSIONS: TILs were common in patients with biopsy-proven glomerular disease. The type and severity of TILs varied with age, region and concurrent glomerular diseases. Renal arteriole injury and glomerulosclerosis was associated with a significantly increased risk of TIL.

Proton pump inhibitors and the risk of hospital-acquired acute kidney injury in children.

BACKGROUND: To evaluate the association between use of proton pump inhibitor (PPI) and the risk of hospital-acquired acute kidney injury (HA-AKI) in hospitalized children. METHODS: We conducted a multicenter retrospective cohort study in hospitalized children aged 1 month to 18 years from 25 tertiary hospitals across China from 2013 to 2015. Patient-level data were obtained from the electronic hospitalization databases. AKI was defined and staged using the serum creatinine (SCr) data according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS: Among 42,232 children analyzed, 11,496 (27.2%) used PPI, 1,760 (4.2%) used histamine 2 receptor antagonist (H2RA), and 3,514 (8.3%) had HA-AKI during hospitalization. Over 85% of PPIs were prescribed for prophylaxis of gastro-duodenal lesions in children. The use of PPI was associated with a significantly increased risk of HA-AKI compared with both non-users [odds ratio (OR), 1.37; 95% confidence interval (CI), 1.23-1.53)] and H2RA users (OR, 1.24; 95% CI, 1.01-1.52). The associations were consistent across children of different age range, gender, subtypes of PPIs and methods of administration. A larger effect was observed in children with chronic kidney disease (OR, 3.37; 95% CI, 2.46-4.62) and those needed intensive care (OR, 1.54; 95% CI, 1.33-1.78). The risk of HA-AKI was increased even within the recommended dosage range of PPI. CONCLUSIONS: PPIs were widely used and associated with an increased risk of HA-AKI in hospitalized children in China.

The modern spectrum of biopsy-proven renal disease in Chinese diabetic patients-a retrospective descriptive study.

BACKGROUND: Renal biopsies performed in diabetic patients are increasing and becoming more complex. Comprehensive data on modern spectrum of biopsy-proven renal disease in Chinese diabetic patients are lacking. METHODS: In a nationwide renal biopsy survey including 71,151 native biopsies from 2004 to 2014, diabetic patients were identified according to the clinical diagnosis from referral records. The clinical data were extracted from referral records and pathological reports. RESULTS: A total of 1,604 diabetic patients, including 61 patients with T1DM, were analyzed in this study. The median age is 51.39 ± 11.37 years. Male patients accounted for 58% of the population. We found that only 44.7% of diabetic patients had the isolated pathological diagnosis of diabetic nephropathy (DN), while 49.1% had non-diabetic renal disease (NDRD) alone, and 6.2% had NDRD superimposed on DN. Nephrotic syndrome (n = 824, 51.4%) was the most common clinical indication for renal biopsy. Among 887 patients with NDRD, membranous nephropathy (n = 357) was the leading diagnosis, followed by IgA nephropathy (n = 179). Hypertensive renal disease (n = 32), tubulointerstitial nephropathy (n = 27) and acute tubular necrosis (n = 16) accounted for 3.5%, 2.9%, 1.7% of the NDRD cases respectively. Nearly a half (49.2%) of patients with T1DM had NDRD. DISCUSSION: Over 55% diabetic patients with kidney disease were diagnosed as non-diabetic renal disease, among which MN and IgAN were the most common two pathological types.