Prognostic performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal procalcitonin.

INTRODUCTION: It is important to predict adverse outcomes in febrile children with hematology/oncology diseases. Procalcitonin (PCT) is a promising biomarker for the prediction of infection severity, but further studies have revealed its performance in excluding adverse outcomes of infection. IL-6 and IL-10 were reported to have a close association with those infection outcomes. The aim of the study was to investigate the performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal PCT. METHODS: This was a retrospective study conducted in a tertiary children's hospital in China over the past ten years. Inflammatory biomarkers, including IL-6, IL-10, PCT and C-reactive protein (CRP), were detected at the onset of infection. Separate analyses were conducted in patients with neutropenia and without neutropenia. RESULTS: In total, 5987 febrile cases were enrolled. For patients with neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with bloodstream infection (BSI), gram-negative bacteremia (GNB) and severe sepsis (SS), but only IL-6 and IL-10 were predictive of GNB and SS. For patients without neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with BSI, GNB and SS, but no biomarkers were predictive of adverse outcomes. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis in patients with neutropenia. CONCLUSIONS: IL-6 and IL-10 could be predictors for GNB and SS in febrile patients with neutropenia and had some association with unfavorable outcomes in febrile patients without neutropenia. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis.

The predictive utility of cytokines, procalcitonin and C-reactive protein among febrile pediatric hematology and oncology patients with severe sepsis or septic shock.

Severe sepsis and septic shock are life-threatening for pediatric hematology and oncology patient receiving chemotherapy. Th1/Th2 cytokines, C-reactive protein (CRP), and procalcitonin (PCT) are all thought to be associated with disease severity. The aim of this study was to prospectively verify the utility of Th1/Th2 cytokines and compare them with PCT and CRP in the prediction of adverse outcomes. Data on patients were collected from January 1, 2011, to December 31, 2020. Blood samples were taken for Th1/Th2 cytokine, CRP, and PCT measurements at the initial onset of infection. Severe infection (SI) was defined as severe sepsis or septic shock. Th1/Th2 cytokine levels were determined by using flow cytometric bead array technology. In total, 7,735 febrile episodes were included in this study. For SI prediction, the AUCs of IL-6, IL-10 and TNF-α were 0.814, 0.805 and 0.624, respectively, while IL-6 and IL-10 had high sensitivity and specificity. IL-6 > 220.85 pg/ml and IL-10 > 29.95 pg/ml had high odds ratio (OR) values of approximately 3.5 in the logistic regression. Within the subgroup analysis, for bloodstream infection (BSI) prediction, the AUCs of IL-10 and TNF-α were 0.757 and 0.694, respectively. For multiorgan dysfunction syndrome (MODS) prediction, the AUC of CRP was 0.606. The AUC of PCT for mortality prediction was 0.620. In conclusion, IL-6 and IL-10 provide good predictive value for the diagnosis of SI. For children with SI, IL-10 and TNF-α are associated with BSI, while CRP and PCT are associated with MODS and death, respectively.

A Prediction Model for Acute Kidney Injury in Adult Patients With Minimal Change Disease.

Background: Early prediction of acute kidney injury (AKI) can allow for timely interventions, but there are still few methods that are easy and convenient to apply in predicting AKI, specially targeted at patients with minimal change disease (MCD). Motivated by this, we aimed to develop a predicting model for AKI in patients with MCD within the KDIGO criteria. Methods: Data on 401 hospitalized adult patients, whose biopsy was diagnosed as MCD from 12/31/2010 to 15/7/2021, were retrospectively collected. Among these data, patients underwent biopsy earlier formed the training set (n = 283), while the remaining patients formed the validation set (n = 118). Independent risk factors associated with AKI were analyzed. From this, the prediction model was developed and nomogram was plotted. Results: AKI was found in 55 of 283 patients (19%) and 15 of 118 patients (13%) in the training and validation cohorts, respectively. According to the results from lasso regression and logistic regression, it was found that four factors, including mean arterial pressure, serum albumin, uric acid, and lymphocyte counts, were independent of the onset of AKI. Incorporating these factors, the nomogram achieved a reasonably good concordance index of 0.84 (95%CI 0.77-0.90) and 0.75 (95%CI 0.62-0.87) in predicting AKI in the training and validation cohorts, respectively. Decision curve analysis suggested clinical benefit of the prediction models. Conclusions: Our predictive nomogram provides a feasible approach to identify high risk MCD patients who might develop AKI, which might facilitate the timely treatment.

GLA missense and promoter variants co-segregating in a Chinese family with Fabry disease.

BACKGROUND: Fabry disease (FD) is an X-linked recessive inheritance lysosomal storage disorder due to mutations in the GLA gene leading to deficiency of lysosomal α-galactosidase A (α-Gal A) and has a wide range of clinical presentations. Over 900 GLA gene mutations are currently known and of those most are thought not to be clinically significant, some with doubtful clinical significance, posing diagnostic and prognostic difficulties for the clinician. METHODS: Whole-exome sequencing (WES) was performed to detect the mutation in family members with Fabry disease. The function of g.1170C>T mutation was confirmed by dual luciferase system. RESULTS: A total of 1,375 variants were found in a Chinese family with FD. A missense variants c.1025C>T (p.Arg342Gln) which have been previously reported in association with FD and g.1170C>T single-nucleotide polymorphism (SNP) in the GLA gene were found in five patients. The g.1170C>T SNP affects transcription of GLA gene, presumably the transcription start site. Female patients only have hypohidrosis and neuropathic pain, while male patients have severe symptoms with simultaneous renal impairment. CONCLUSIONS: Two simultaneous variants in cis of the GLA gene, c.1025C>T (p.Arg342Gln) and g.1170C>T, were verified in Chinese individuals, and the corresponding clinical symptoms were described. The disease severity in male patients is worse than in female patients. These results may be helpful for genetic counseling, diagnosis and prognosis of patients with FD.

Clinical features of acute kidney injury in patients with nephrotic syndrome and minimal change disease: a retrospective, cross-sectional study.

BACKGROUND: Minimal change nephropathy (MCD) is a common pathological type of nephrotic syndrome and is often associated with acute kidney injury (AKI). This study aimed to investigate the clinical characteristics and related factors of AKI in patients with MCD and nephrotic syndrome. METHODS: Patients from Chinese People's Liberation Army General Hospital who were diagnosed with pathological renal MCD with clinical manifestations of nephrotic syndrome were included from January 1, 2013 to December 31, 2017. Patients diagnosed with membranous nephropathy (MN) by renal biopsy from January 1, 2013 to December 31, 2017 are included as a control population. We retrospectively analyzed the clinical and pathological characteristics of patients as well as the percentages and clinical characteristics of AKI in different age groups. We assessed the correlation of pathological characteristics with serum creatinine using multivariate linear regression analysis. RESULTS: A total of 367 patients with MCD were included in the analysis, with a sex ratio of 1.46: 1 (male: female) and an age range of 6 to 77 years. Among all the patients, 109 developed AKI (29.7%), and of these patients, 85 were male (78.0%). In the 586 patients with MN, 27 (4.6%) patients developed AKI. The percentage of AKI in MCD patients was significantly higher than that in MN patients (χ2 = 41.063, P < 0.001). The percentage of AKI increased with age in the MCD patients. The percentage of AKI in patients aged 50 years or older was 52.9% (46/87), which was significantly higher than that [22.5% (63/280)] in patients under 50 years (χ2 = 6.347, P = 0.013). We observed statistically significant differences in age (43 [27, 59] years vs. 28 [20, 44] years, Z = 5.487, P < 0.001), male (78.0% vs. 51.4%, χ2 = 22.470, P < 0.001), serum albumin (19.9 ±â€Š6.1 g/L vs. 21.5 ±â€Š5.7 g/L, t = 2.376, P = 0.018), serum creatinine (129.5 [105.7, 171.1] µmol/L vs. 69.7 [57.7, 81.9] µmol/L, Z = 14.190, P < 0.001), serum urea (10.1 [6.2, 15.8] mmol/L vs. 4.7 [3.6, 6.4] mmol/L, Z = 10.545, P < 0.001), IgE (266.0 [86.7, 963.0] IU/ml vs. 142.0 [35.3, 516.5] IU/ml, Z = 2.742, P = 0.007), history of diabetes (6.4% vs. 1.2%, P = 0.009), and history of hypertension (23.9% vs. 5.1%, χ2 = 28.238, P < 0.001) between the AKI group and the non-AKI group. According to multivariate linear regression analysis, among the renal pathological features analyzed, renal tubular epithelial cell damage (ß = 178.010, 95% CI: 147.888-208.132, P < 0.001) and renal interstitial edema (ß = 28.833, 95% CI: 11.966-45.700, P = 0.001) correlated with serum creatinine values. CONCLUSIONS: The percentage of AKI in MCD patients is significantly higher than that in MN patients. Patients over 50 years old are more likely to develop AKI. Renal tubular epithelial cell injury and renal interstitial edema may be the main pathological lesions that are associated with elevated serum creatinine in patients with MCD.

Predictive Capabilities of Three Widely Used Pathology Classification Systems and a Simplified Classification (Beijing Classification) in Primary IgA Nephropathy.

BACKGROUND/AIMS: Several pathological classification systems were commonly used in clinical practice to predict the prognosis of IgA nephropathy (IgAN). However, how prognostic value differs between these systems is unclear. The aim of this study was to compare the Lee grade, the Oxford classification, and the Haas classification and to find a simplified classification. METHODS: We retrospectively analyzed IgAN cases diagnosed between January 2002 and December 2007. The endpoints were progression to end-stage renal disease (ESRD) or a ≥50% decline in estimated glomerular filtration rate (eGFR). The predictive capabilities were evaluated by comparing the ability of discrimination (continuous net reclassification) and calibration (Akaike information criterion [AIC]). RESULTS: A total of 412 IgAN patients were included in the study. The average follow-up period was 80.62 ± 23.63 months. A total of 44 (10.68%) patients progressed to ESRD, and 70 (16.99%) patients showed a ≥50% decline in eGFR. All multivariate Cox regression models had limited power for high AIC values. The prognostic values of the Lee grade and the Oxford classification were higher than those of models containing only established baseline clinical indicators for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.50, 95% CI 0.21-0.74; Oxford classification 0.48, 95% CI 0.28-0.71). The prognostic value of the Haas classification was lower than that of the other pathological classification systems for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.53, 95% CI 0.23-0.92; Oxford classification 0.59, 95% CI 0.10-0.74). The prognostic value of hierarchical classification (Beijing classification) using M and T lesion was similar to the Oxford classification. CONCLUSIONS: Both the Lee grade and the Oxford classification showed incremental prognostic values beyond established baseline clinical indicators. The Haas classification was slightly inferior to the Lee grade and the Oxford classification. The hierarchical classification (Beijing classification) using less pathological parameters does not lose predictive efficiency.

Aging promotes progression of IgA nephropathy: a systematic review and meta-analysis.

BACKGROUND: There has been considerable interest in whether old age is associated with IgA nephropathy (IgAN) progression, which is still controversial. METHODS: We searched multiple databases for studies published from 1980 to 2012. The inclusion criteria were case-control, cohort studies published in any language. The included studies needed to have an older group. IgAN was proven by biopsy. RESULTS: We included 9 studies with a total of 6,543 patients. The meta-analyses of other risk factors between the older group (>50 years old) and the non-older group (15-50 years old) found significant differences in the presence of hypertension, proteinuria, serum cholesterol levels and baseline renal function. In the overall analysis, compared to the non-older group, older age significantly increased the incidence of developing end-stage renal disease [ESRD; relative risk (RR) random model 1.95; 95% CI: 1.27-3.01]. In the subgroup analyses, we found the age limit and traditional risk factors of IgAN may be the sources of heterogeneity between studies. Moreover, the RR (2.56) of the Asian countries was much higher than the RR (1.11) of the European countries. CONCLUSIONS: This comprehensive review revealed that old age is a real risk factor for IgAN progression to ESRD. The incidence of ESRD in the older IgAN patients was 1.95 times higher than that in the non-older IgAN patients. Moreover, the risk of IgAN progression to ESRD of the older patients in Asia was higher than that of the older patients in Europe.

Identifying parameters to distinguish non-diabetic renal diseases from diabetic nephropathy in patients with type 2 diabetes mellitus: a meta-analysis.

BACKGROUND: Renal injuries in patients with diabetes include diabetic nephropathy (DN) and non-diabetic renal diseases (NDRD). The value of a clinical diagnosis of DN and NDRD remains inconclusive. We conducted a meta-analysis of the literature to identify predictive factors of NDRD and to compare the clinical characteristics of DN and NDRD for differential diagnosis. METHODS: We searched PubMed (1990 to January 2012), Embase (1990 to February 2009), and CNKI (1990 to January 2012) to identify studies that enrolled patients with DN and NDRD. Then, the quality of the studies was assessed, and data were extracted. The results were summarized as odds ratios (ORs) for dichotomous outcomes and weighted mean differences (WMDs) for continuous outcomes. RESULTS: Twenty-six relevant studies with 2,322 patients were included. The meta-analysis showed that the absence of diabetic retinopathy (DR) predicts NDRD (OR, 0.15; 95% confidence interval [CI], 0.09-0.26, p<0.00001). A shorter duration of diabetes mellitus (DM) also predicted NDRD (weighted mean difference, -34.67; 95% CI, -45.23--24.11, p<0.00001). The levels of glycosylated hemoglobin (HbA1C%), blood pressure (BP), and total cholesterol were lower in patients with NDRD, whereas triglycerides and body mass index were higher. Other clinical parameters, including age, 24-h urinary protein excretion, serum creatinine, creatinine clearance, blood urea nitrogen, and glomerular filtration rate were not different between patients with NDRD and DN. CONCLUSIONS: We identified that the absence of DR, shorter duration of DM, lower HbA1C, and lower BP may help to distinguish NDRD from DN in patients with diabetes. This could assist clinicians in making a safe and sound diagnosis and lead to more effective treatments.

Change of expression of renal alpha1-adrenergic receptor and angiotensin II receptor subtypes with aging in rats.

BACKGROUND AND AIMS: It has been considered that the functional decline of renal vasoconstriction during senescence is associated with an alteration in renal alpha1-adrenergic receptor (alpha1-AR) expression. While alterations in renal angiotensin II receptor (ATR) expression was considered to have an effect on renal structure and function, until now little information has been available concerning alpha1-AR and ATR expression variations over the entire aging continuum. The present study was undertaken to examine the expression levels of alpha1-AR and ATR subtypes in renal tissue during the spectrum running from young adulthood, to middle age, to the presenium, and to the senium. METHODS: Semiquantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western Blot were used to quantify the messenger RNA (mRNA) and protein levels of alpha1-AR and ATR subtypes in renal tissue in 3-month-old (young adult), 12-month-old (middle age), 18-month-old (presenium) and 24-month-old (senium) Wistar rats. RESULTS: alpha1A-AR expression decreased gradually with aging: it was decreased during middle age, the presenium and the senium, compared, respectively, with young adult values (p<0.01), and there was a significant decline both in the presenium with respect to middle age and in the senium with respect to the presenium. alpha1B-AR and alpha1D-AR expression were unmodified during senescence. AT1R expression was unaffected by aging during young adulthood and middle age, but exhibited a remarkable downregulation in the presenium and senium periods (p<0.01). AT2R expression was markedly increased in the senium (p<0.01). CONCLUSIONS: These results suggest that there are considerable variations in the expression levels of renal alpha1-AR and ATR subtypes during aging. alpha1A-AR expression downregulation may account for the reduced reactivity of renal alpha1-AR to vasoconstrictors and to renal function decline in the senium. Both the downregulation of AT1R and the upregulation of AT2R may be influential in maintaining normal physiological renal function during aging.

[Effect of aging on pulmonary ICAM-1 and MCP-1 expressions in rats with lipopolysaccharide- induced acute lung injury].

OBJECTIVE: To investigate the effect of aging on the expressions of monocyte chemoattractant protein 1 (MCP-1) and intercellular adhesion molecule 1 (ICAM-1) in the lung tissue of rats with lipopolysaccharide (LPS)-induced acute lung injury (ALI). METHODS: Both young (3 months old) and aged (27 months old) female Wistar rats were randomly divided into two groups (n=8), namely the normal control and LPS-induced ALI groups. Immunohistochemistry for of ED-1 was used to detect the infiltrating inflammatory cells. Western blot and Northern blot analyses were employed for evaluating the expressions of MCP-1 and ICAM-1 at the protein and mRNA levels. RESULTS: Virtually no ED-1-positive cells were found in the lung tissue of the control rats in the young and aged groups. After LPS-induced ALI, ED-1-positive cells in the lung tissues increased significantly in both young and aged groups (P<0.05), and the increment was more obviously in the aged group (P<0.05). In the two normal control groups, the aged rats showed significantly higher expressions of MCP-1 and ICAM-1 than the young rats (P<0.05); LPS significantly up-regulated their expression in the young and aged groups (P<0.05), but the latter showed greater increments (P<0.05). The aged rats with ALI also showed significantly greater MCP-1 and ICAM-1 increments than those of the young rats (P<0.05). CONCLUSIONS: Aging may upregulate lung MCP-1 and ICAM-1 expressions and enhance LPS-induced increments of MCP-1 and ICAM-1 expressions to exacerbate the pulmonary inflammation in rats.