Comparative accuracy of biomarkers for the prediction of hospital-acquired acute kidney injury: a systematic review and meta-analysis.

BACKGROUND: Several biomarkers have been proposed to predict the occurrence of acute kidney injury (AKI); however, their efficacy varies between different trials. The aim of this study was to compare the predictive performance of different candidate biomarkers for AKI. METHODS: In this systematic review, we searched PubMed, Medline, Embase, and the Cochrane Library for papers published up to August 15, 2022. We selected all studies of adults (> 18 years) that reported the predictive performance of damage biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP)), inflammatory biomarker (interleukin-18 (IL-18)), and stress biomarker (tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein-7 (TIMP-2 × IGFBP-7)) for the occurrence of AKI. We performed pairwise meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CIs) individually. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence. RESULTS: We identified 242 published relevant studies from 1,803 screened abstracts, of which 110 studies with 38,725 patients were included in this meta-analysis. Urinary NGAL/creatinine (diagnostic odds ratio [DOR] 16.2, 95% CI 10.1-25.9), urinary NGAL (DOR 13.8, 95% CI 10.2-18.8), and serum NGAL (DOR 12.6, 95% CI 9.3-17.3) had the best diagnostic accuracy for the risk of AKI. In subgroup analyses, urinary NGAL, urinary NGAL/creatinine, and serum NGAL had better diagnostic accuracy for AKI than urinary IL-18 in non-critically ill patients. However, all of the biomarkers had similar diagnostic accuracy in critically ill patients. In the setting of medical and non-sepsis patients, urinary NGAL had better predictive performance than urinary IL-18, urinary L-FABP, and urinary TIMP-2 × IGFBP-7: 0.3. In the surgical patients, urinary NGAL/creatinine and urinary KIM-1 had the best diagnostic accuracy. The HSROC values of urinary NGAL/creatinine, urinary NGAL, and serum NGAL were 91.4%, 85.2%, and 84.7%, respectively. CONCLUSIONS: Biomarkers containing NGAL had the best predictive accuracy for the occurrence of AKI, regardless of whether or not the values were adjusted by urinary creatinine, and especially in medically treated patients. However, the predictive performance of urinary NGAL was limited in surgical patients, and urinary NGAL/creatinine seemed to be the most accurate biomarkers in these patients. All of the biomarkers had similar predictive performance in critically ill patients. Trial registration CRD42020207883 , October 06, 2020.

Nomenclature and diagnostic criteria for acute kidney injury - 2020 consensus of the Taiwan AKI-task force.

Acute kidney injury (AKI) is a common syndrome that has a significant impact on prognosis in various clinical settings. To evaluate whether new evidence supports changing the current definition/classification/staging systems for AKI suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline, the Taiwan AKI-TASK Force, composed of 64 experts in various disciplines, systematically reviewed the literature and proposed recommendations about the current nomenclature and diagnostic criteria for AKI. The Taiwan Acute Kidney Injury (TW-AKI) Consensus 2020 was established following the principles of evidence-based medicine to investigate topics covered in AKI guidelines. The Taiwan AKI-TASK Force determined that patients with AKI have a higher risk of developing chronic kidney disease, end-stage renal disease, and death. After a comprehensive review, the TASK Force recommended using novel biomarkers, imaging examinations, renal biopsy, and body fluid assessment in the diagnosis of AKI. Clinical issues with regards to the definitions of baseline serum creatinine (sCr) level and renal recovery, as well as the use of biomarkers to predict renal recovery are also discussed in this consensus. Although the present classification systems using sCr and urine output for the diagnosis of AKI are not perfect, there is not enough evidence to change the current criteria in clinical practice. Future research should investigate and clarify the roles of the aforementioned tools in clinical practice for AKI.

Incidence, characteristics and outcomes among inpatient, outpatient and emergency department with reported high critical serum potassium values.

OBJECTIVES: Severe hyperkalemia can cause life-threatening arrhythmia, cardiac arrest, or death. This study aimed to investigate the incidence and the associated factors relevant to critical hyperkalemia (≥6 mmol/L) among inpatients, outpatients, and emergency department. Their clinical outcomes were also analyzed. METHODS: All patients whose high serum potassium values had been reported as critical laboratory values in 2016 were enrolled. Their demographic data, comorbidities, clinical symptoms, biochemical data, and outcomes were reviewed and collected. The Charlson comorbidity score (CCS) and glomerular filtration rate (GFR) were computed to assess the comorbidity burden and renal function. Patients were divided into groups according to different settings, potassium and GFR levels, and their survival. RESULTS: Of the 293,830 total serum potassium tests, 1,382 (0.47%) reports were listed as critical laboratory values. The average reply time was 6.3 min. Their mean age was 67.2 years, while the average GFR was 12.2 mL/min/1.73 m2. The overall mortality rate was 34%. Patients in the emergency department had the highest incidence (0.92%), while inpatients had the worst outcome (51% mortality). The leading cause of mortality was septic shock. The fatal group had higher rates of clinical symptoms, higher potassium values, CCS, and eGFR (all p<0.05). CONCLUSIONS: Most of the responses for the reports were obtained within a short period of time. Patients with reported high critical serum potassium values were characterized by high rates of comorbidity, reduced eGFR, and mortality. The incidence, clinical manifestations, and outcomes varied in the different clinical settings.

Comparison of Solute Clearance, Hospitalization Rate, and Aortic Arch Calcification between Online Hemodiafiltration and High-Flux Hemodialysis: A 6-Year Observational Study.

BACKGROUND/AIMS: Studies on the long-term clinical benefits of hemodiafiltration (HDF) and high-flux hemodialysis (HFHD) are very limited. This study aimed to investigate the hospitalization rate and aortic arch calcification (AAC) of these two dialysis modalities over 6 years. METHODS: Participants who received regular HDF and HFHD in one hospital-facilitated hemodialysis center were prospectively enrolled after matching for age, sex, and diabetes between January 2009 and December 2014. Medical records were reviewed retrospectively on demographics, laboratory variables, calcified scores in aortic arch measured by chest radiography, and rates of hospital admission. Cox proportional hazard regression and linear regression were used to obtain the outcome results. RESULTS: The HDF and HFHD groups consisted of 108 and 102 participants, respectively. Levels of laboratory variables including small soluble solutes and Kt/V were not statistically different over the 6-year period between the HDF and HFHD groups. Calcified scores of the aortic arch increased over 6 years in both groups. The changes in the mean calcified scores were significant when compared between the two groups (0.44-1.82 in HFHD, 0.79-1.8 in HDF, respectively, p = 0.008). Hospitalization rates were 735 per 1,000 patients in the HDF group and 852 per 1,000 patients in the HFHD group, respectively. No significant difference was observed in frequency and days of hospitalization between HDF and HFHD. CONCLUSION: Hospitalization rates and AAC were observed to be equal for HDF and HFHD.

Free actin impairs macrophage bacterial defenses via scavenger receptor MARCO interaction with reversal by plasma gelsolin.

Lung injury can release intracellular actin into the alveolar milieu and is also associated with increased susceptibility to secondary infections. We investigated the effect of free (extracellular) actin on lung macrophage host defense functions. Western blot analysis demonstrated free actin release into the lung lavage fluids of mouse models of ozone injury, influenza infection, and secondary pneumococcal pneumonia and in samples from patients following burn and inhalation injury. Using levels comparable with those observed in lung injury, we found that free actin markedly inhibited murine lung macrophage binding and uptake in vitro of S. pneumoniae, S. aureus, and E. coli, (e.g., S. pneumoniae, mean %inhibition, actin vs. vehicle: 85 ± 0.3 (SD); n = 22, P < .001). Similar effects were observed on the ability of primary human macrophages to bind and ingest fluorescent Saureus (~75% inhibition). Plasma gelsolin (pGSN), a protein that functions to bind and cleave actin, restored bacterial binding and uptake by both murine and human macrophages. Scavenger receptor inhibitors reduced binding of fluorescent actin by murine macrophages [fluorescence index (×10-3) after incubation with vehicle, actin, or actin + polyinosinic acid, respectively: 0.8 ± 0.7, 101.7 ± 50.7, or 52.7 ± 16.9; n = 5-6, P < 0.05]. In addition, actin binding was reduced in a MARCO/SR-AI/II-deficient cell line and by normal AMs obtained from MARCO-/- mice. After release from injured cells during lung injury, free actin likely contributes to impaired host defense by blocking scavenger receptor binding of bacteria. This mechanism for increased risk of secondary infections after lung injury or inflammation may represent another target for therapeutic intervention with pGSN.

Effects of Diet Intervention on Body Composition in the Elderly with Chronic Kidney Disease.

Objective: It has been uncertain that low protein diet for patients with chronic kidney disease (CKD) may predispose to malnutrition. The study aimed to investigate the effects of low protein diet on body composition of CKD patients and analyze the influence of age. Methods: Patients with glomerular filtration rate less than 45 mL/min/1.73m2 including 103 elderly (70.7 ± 6.9 years old) and 56 non-elderly (49.8 ± 9.1 years old) CKD patients were enrolled. All patients were educated by dietitians to take low protein diet and were followed up regularly every three months. Their demographic data, underlying disease and body mass index (BMI) were reviewed and recorded. Results of body composition measurement and laboratory tests were collected every three months for one year. Results: At baseline, the distribution of body composition was similar in non-elderly patients between non-low and low protein groups. In the elderly, patients in low protein group had higher fat and lower muscle percentage. In one-year follow-up, non-elderly patients did not present significant changes in their BMI, serum albumin level and body compositions in both protein groups. Non-low protein group in elderly patients had significant decrease in BMI and estimated glomerular filtration rate (eGFR) after 12 months (both p< 0.05). Determination in body composition showed decrease in fat and increase in muscle component. In low protein group, their BMI was decreased and eGFR was not influenced. Fat component was decreased and muscle percentage was increased in one-year follow-up. Conclusions: In elderly CKD patients, low protein diet maintained good nutritional status and muscle mass was preserved.

Gelsolin and Progression of Aortic Arch Calcification in Chronic Hemodialysis Patients.

BACKGROUND: Vascular calcification (VC) is a key process associated with cardiovascular mortality in dialysis patients. Gelsolin is an actin-binding protein that can modulate inflammation, correlated inversely with hemodialysis (HD) mortality and involved in bone calcification homeostasis. In this report, we aim to characterize progression in aortic arch calcification (AAC) and investigate its association with gelsolin. METHODS: 184 HD patients were enrolled and their annual posterior-anterior chest X-ray films (CXR) in 2009 and 2013 were examined. The severity of AAC was classified as grade 0 to 3. Blood levels of gelsolin were measured by ELISA kits. Biographic and biochemical data at baseline were analyzed with status of AAC at baseline and changes after 4 years. RESULTS: At baseline, 60% of the patients had detectable AAC on CXR. After 4 years, 77% had AAC. Patients with grade 1 and 2 AAC had increased risk of progression (Odds ratio [OR] 2~3, P=0.001) compared to those with grade 0 at baseline. Compared to those with no AAC, patients with AAC progression had older age, lower gelsolin, higher waist circumference and prevalence of vascular disease. Regression analysis confirmed baseline gelsolin (odds ratio 0.845, 95% confidence interval [0.734-0.974]) and waist circumference as the independent factors associated with AAC progression. Gelsolin is positively correlated with serum albumin and negatively with tumor necrosis factor-alpha. CONCLUSION: Our study demonstrated that HD patients with grades 1 or 2 baseline AAC are at increased risk of further progression compared to those with grade 0. We also found lower blood levels of gelsolin associated with progressive AAC. Further investigation into the mechanistic roles of gelsolin in vascular calcification may provide new understanding of this key process.

Plasma gelsolin improves lung host defense against pneumonia by enhancing macrophage NOS3 function.

Plasma gelsolin (pGSN) functions as part of the "extracellular actin-scavenging system," but its potential to improve host defense against infection has not been studied. In a mouse model of primary pneumococcal pneumonia, recombinant human pGSN (rhu-pGSN) caused enhanced bacterial clearance, reduced acute inflammation, and improved survival. In vitro, rhu-pGSN rapidly improved lung macrophage uptake and killing of bacteria (Streptococcus pneumoniae, Escherichia coli, and Francisella tularensis). pGSN triggers activating phosphorylation (Ser(1177)) of macrophage nitric oxide synthase type III (NOS3), an enzyme with important bactericidal functions in lung macrophages. rhu-pGSN failed to enhance bacterial killing by NOS3(-/-) macrophages in vitro or bacterial clearance in NOS3(-/-) mice in vivo. Prophylaxis with immunomodulators may be especially relevant for patients at risk for secondary bacterial pneumonia, e.g., after influenza. Treatment of mice with pGSN challenged with pneumococci on postinfluenza day 7 (the peak of enhanced susceptibility to secondary infection) caused a ∼15-fold improvement in bacterial clearance, reduced acute neutrophilic inflammation, and markedly improved survival, even without antibiotic therapy. pGSN is a potential immunomodulator for improving lung host defense against primary and secondary bacterial pneumonia.

Effects of AST-120 on blood concentrations of protein-bound uremic toxins and biomarkers of cardiovascular risk in chronic dialysis patients.

BACKGROUND: Removal of protein-bound uremic toxins by dialysis therapy is limited. The effect of oral adsorbent AST-120 in chronic dialysis patients has rarely been investigated. METHODS: AST-120 was administered 6.0 g/day for 3 months in 69 chronic dialysis patients. The blood concentrations of indoxyl sulfate, p-cresol sulfate and biomarkers of cardiovascular risk were determined before and after AST-120 treatment. RESULTS: AST-120 significantly decreased both the total and free forms of indoxyl sulfate and p-cresol sulfate ranging from 21.9 to 58.3%. There were significant simultaneous changes of the soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK, 24% increase), malondialdehyde (14% decrease) and interleukin-6 (19% decrease). A significant association between the decrease of indoxyl sulfate and changes of sTWEAK and interleukin-6 was noted. CONCLUSIONS: AST-120 effectively decreased indoxyl sulfate and p-cresol sulfate levels in both total and free forms. AST-120 also improved the profile of cardiovascular biomarkers.

Renin angiotensin system blockade ameliorates lead nephropathy.

Lead intoxication is usually insidious and may cause a variety of complications such as kidney damage and hypertension. The role of intrarenal renin-angiotensin system (RAS) in lead-induced nephropathy has not been investigated. Adult male Sprague-Dawley rats were fed with water containing 250ppm of lead acetate (lead group) and deionized water (control group) for 4weeks. Another two groups started to receive intraperitoneal captopril (50mg/kg/d) or losartan (10mg/kg/d) after 2weeks of lead feeding and continued for another 2weeks. Immunoblotting was used to analyze the protein amount of intrarenal RAS components and transforming growth factor-beta (TGF-ß). Compared with control group, lead exposure resulted in increased proteinuria after 2-week treatment (4.2±0.9mg/100g vs. 1.8±0.8mg/100g, p<0.05) and 4-week (5.2±1.7mg/100g, p<0.05). Serum creatinine level was increased (0.40±0.2 vs. 0.3 ±.04mg/dL, p<0.05) and calculated glomerular filtration rate (GFR) was decreased (2.68±1.03 vs. 3.37±0.11mL/min, p<0.05). Intrarenal angiotensin converting enzyme (ACE), angiotensin II (ANG II), angiotensin II type 1 receptor (AT1R) and transforming growth factor-beta (TGF-ß) were upregulated in lead group. Captopril and losartan administration reduced proteinuria significantly (3.0±0.50mg/100g of captopril and 2.7±0.4mg/100g of losartan group) and lowered systolic blood pressure when compared with lead group. Furthermore, serum creatinine levels and GFR were improved by RAS blockade. Captopril treatment significantly reduced protein abundance of ACE, ANG II, AT1R and TGF-ß. Losartan treatment also decreased ANG II and TGF-ß. We concluded that lead exposure elicited intrarenal RAS activation with associated proteinuria and impaired renal function. RAS blockade was effective in alleviating lead-associated kidney injury and lowering blood pressure.

Interleukin-18 and Gelsolin Are Associated with Acute Kidney Disease after Cardiac Catheterization.

Patients undergoing cardiac catheterization are at high risk of post-procedure acute kidney injury (AKI) and may experience persistent renal damage after an initial insult, a state known as acute kidney disease (AKD). However, the association between AKD and urinary renal biomarkers has not yet been evaluated in this population. We enrolled 94 patients who underwent elective cardiac catheterization to investigate patterns of urinary renal biomarkers and their associations with post-procedure AKD. Serial urinary renal biomarker levels were measured during pre-procedure, early post-procedure (12-24 h), and late post-procedure (7-10 days) periods. In our investigation, 42.55% of the enrolled patients developed AKD during the late post-procedure period. While the liver-type free-fatty-acid-binding protein level increased sharply during the early post-procedure period, it returned to baseline during the late post-procedure period. In contrast, interleukin-18 (IL-18) levels increased steadily during the post-procedure period. Early post-procedure ratios of IL-18 and gelsolin (GSN) were independently associated with subsequent AKD (odds ratio (95% confidence interval), 4.742 (1.523-14.759) for IL-18 ratio, p = 0.007; 1.812 (1.027-3.198) for GSN ratio, p = 0.040). In conclusion, post-procedure AKD is common and associated with early changes in urinary IL-18 and GSN in patients undergoing cardiac catheterization.

Variations of dietary salt and fluid modulate calcium and magnesium transport in the renal distal tubule.

BACKGROUND: The renal distal tubule fine-tunes renal epithelial calcium transport. Dietary intake of salt and fluid varies day-to-day and the kidney adapts accordingly to maintain homeostasis. The alternations in salt and fluid balance affect calcium and magnesium transport in the distal tubule, but the mechanisms are not fully understood. METHODS: Sprague-Dawley rats were grouped into high-salt, low-salt and dehydration treatment. Daily intake, water consumption and urine output were recorded. At the end of the experiment, blood and urine samples were collected for hormonal and biochemical tests. Genetic analysis, immunoblotting and immunofluorescence studies were then performed to assess the alterations of calcium and magnesium transport-related molecules. RESULTS: High-salt treatment increased urinary sodium, calcium and magnesium excretion. Low-salt treatment and dehydration were associated with decreased urinary excretion of all electrolytes. High-salt treatment was associated with increased intact parathyroid hormone levels. A significant increase in gene expression of TRPV5, TRPV6, calbindin-D28k and TRPM6 was found during high-salt treatment, while low salt and dehydration diminished expression. These findings were confirmed with immunofluorescence studies. High-salt and low-salt intake or dehydration did not cause any significant changes in WNK1, WNK3 and WNK4. CONCLUSIONS: Alternations in salt and water intake affect renal calcium and magnesium handling. High-salt intake increases the distal delivery of the divalent cations which upregulates distal tubule calcium and magnesium transport molecules, while the opposite effects are associated with low-salt intake or dehydration.

Predictors of Acute Kidney Disease Severity in Hospitalized Patients with Acute Kidney Injury.

Acute kidney disease (AKD) forms part of the continuum of acute kidney injury (AKI) and worsens clinical outcomes. Currently, the predictors of AKD severity have yet to be established. We conducted a retrospective investigation involving 310 hospitalized patients with AKI and stratified them based on the AKD stages defined by the Acute Dialysis Quality Initiative criteria. Demographic, clinical, hematologic, and biochemical profiles, as well as 30-day outcomes, were compared between subgroups. In the analysis, the use of offending drugs (odds ratio, OR (95% confidence interval, CI), AKD stage 3 vs. non-AKD, 3.132 (1.304−7.526), p = 0.011, AKD stage 2 vs. non-AKD, 2.314 (1.049−5.107), p = 0.038), high AKI severity (OR (95% CI), AKD stage 3 vs. non-AKD, 6.214 (2.658−14.526), p < 0.001), and early dialysis requirement (OR (95% CI), AKD stage 3 vs. non-AKD, 3.366 (1.008−11.242), p = 0.049) were identified as independent predictors of AKD severity. Moreover, a higher AKD severity was associated with higher 30-day mortality and lower dialysis-independent survival rates. In conclusion, our study demonstrated that offending drug use, AKI severity, and early dialysis requirement were independent predictors of AKD severity, and high AKD severity had negative impact on post-AKI outcomes.

Rapamycin attenuates PLA2R activation-mediated podocyte apoptosis via the PI3K/AKT/mTOR pathway.

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults without diabetes. Primary MN has been associated with circulating antibodies against native podocyte antigens, including phospholipase A2 receptor (PLA2R); however, precision therapy targeting the signaling cascade of PLA2R activation is lacking. Both PLA2R and the mammalian target of rapamycin (mTOR) exist in podocytes, but the interplay between these two proteins and their roles in MN warrants further exploration. This study aimed to investigate the crosstalk between PLA2R activation and mTOR signaling in a human podocyte cell line. We demonstrated that podocyte apoptosis was induced by Group IB secretory phospholipase A2 (sPLA2IB) in a concentration- and time-dependent manner via upregulation of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and mTOR, and inhibited by rapamycin or LY294002. Furthermore, aberrant activation of the PI3K/AKT/mTOR pathway triggers both extrinsic (caspase-8 and caspase-3) and intrinsic (Bcl-2-associated X protein [BAX], B-cell lymphoma 2 [BCL-2], cytochrome c, caspase-9, and caspase-3) apoptotic cascades in podocytes. The therapeutic implications of our findings are that strategies to reduce PLA2R activation and PI3K/AKT/mTOR pathway inhibition in PLA2R-activated podocytes help protect podocytes from apoptosis. The therapeutic potential of rapamycin shown in this study provides cellular evidence supporting the repurposing of rapamycin for MN treatment.

Disrupted Sleep Homeostasis and Altered Expressions of Clock Genes in Rats with Chronic Lead Exposure.

Sleep disturbance is one of the neurobehavioral complications of lead neurotoxicity. The present study evaluated the impacts of chronic lead exposure on alteration of the sleep-wake cycle in association with changes of clock gene expression in the hypothalamus. Sprague-Dawley rats with chronic lead exposure consumed drinking water that contained 250 ppm of lead acetate for five weeks. Electroencephalography and electromyography were recorded for scoring the architecture of the sleep-wake cycle in animals. At six Zeitgeber time (ZT) points (ZT2, ZT6, ZT10, ZT14, ZT18, and ZT22), three clock genes, including rPer1, rPer2, and rBmal1b, were analyzed. The rats with chronic lead exposure showed decreased slow wave sleep and increased wakefulness in the whole light period (ZT1 to ZT12) and the early dark period (ZT13 to ZT15) that was followed with a rebound of rapid-eye-movement sleep at the end of the dark period (ZT22 to ZT24). The disturbance of the sleep-wake cycle was associated with changes in clock gene expression that was characterized by the upregulation of rPer1 and rPer2 and the feedback repression of rBmal1b. We concluded that chronic lead exposure has a negative impact on the sleep-wake cycle in rats that predominantly disrupts sleep homeostasis. The disruption of sleep homeostasis was associated with a toxic effect of lead on the clock gene expression in the hypothalamus.

Emergence of SGLT2 Inhibitors as Powerful Antioxidants in Human Diseases.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral glucose-lowering agents. Apart from their glucose-lowering effects, large clinical trials assessing certain SGLT2 inhibitors have revealed cardiac and renal protective effects in non-diabetic patients. These excellent outcomes motivated scientists and clinical professionals to revisit their underlying mechanisms. In addition to the heart and kidney, redox homeostasis is crucial in several human diseases, including liver diseases, neural disorders, and cancers, with accumulating preclinical studies demonstrating the therapeutic benefits of SGLT2 inhibitors. In the present review, we aimed to update recent advances in the antioxidant roles of SGLT2 inhibitors in common but debilitating human diseases. We anticipate that this review will guide new research directions and novel therapeutic strategies for diabetes, cardiovascular diseases, nephropathies, liver diseases, neural disorders, and cancers in the era of SGLT2 inhibitors.

Proinflammatory cytokines, hepatocyte growth factor and adipokines in peritoneal dialysis patients.

Chronic inflammation is a well-recognized complication in dialysis patients and a potential role of the adipose tissue as an important tissue of origin contributing to inflammation has been proposed. Stable peritoneal dialysis (PD) patients were enrolled to investigate the relationship between serum levels of proinflammatory cytokines and adipokines. Our results revealed that there was a strong association between high sensitivity C-reactive protein and interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha) but not with IL-10 and IL-18. IL-6 correlated with TNF-alpha, IL-10, and IL-18. No association was found between IL-10 and IL-18. Adiponectin was positively correlated with all proinflammatory cytokines, except IL-10. No significant association was found between resistin and proinflammatory cytokines. Hepatocyte growth factor (HGF) was directly related to proinflammatory cytokines but not with adipokines. The presence of residual kidney function (RKF) affected IL-6, TNF-alpha, and HGF levels. The peritoneal transport property did not influence inflammatory cytokine and adipokine levels. In conclusion, there was a close relationship between proinflammatory cytokines and adipokines. HGF correlated with proinflammatory cytokines but not with adipokines. The PD-related factors such as RKF, peritoneal property and dialysis glucose load affected levels of proinflammatory cytokines. Body mass index was an important determinant of leptin and adiponectin in PD patients.

Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD). Elucidating the mechanisms underlying proteinuria in DKD is crucial because it is a common problem in DKD-related mortality and morbidity. MicroRNAs (miRs) associated with DKD have been detected in experimental diabetes models and in patients with both diabetes and CKD. Here, we aimed to investigate pathologic miRs in diabetic nephropathy (DN) by prospectively following six nephrotic, biopsy-proven isolated DN patients (enrolled between August 2015 and July 2017) for one year. The urinary exosomes were isolated at the time of the biopsy and the contained miRs were analyzed by next-generation sequencing. The results were compared to the control group, composed of age-, gender-, and CKD stage-matched patients with proteinuric CKD who did not present diabetes. Among the 72 identified miRs, we investigated eight (miR-188-5p, miR-150-3p, miR-760, miR-3677-3p, miR-548ah-3p, miR-548p, miR-320e, and miR-23c) exhibiting the strongest upregulation (13-15 fold) and two (miR-133a-3p and miR-153-3p) with the strongest downregulation (7-9 fold). The functional analysis of these miRs showed that they were involved in known and novel pathways of DN, supporting their pathologic roles. The bioinformatics-based prediction of the target genes of these miRs will inspire future research on the mechanisms underlying DN pathogenesis.

Association between C-reactive protein and biomarkers of bone and mineral metabolism in chronic hemodialysis patients: a cross-sectional study.

OBJECTIVE: Both chronic inflammation and dysregulation of bone and mineral metabolism are closely related with long-term outcomes of dialysis patients. Our objective was to investigate the relationship between these two abnormalities. DESIGN: This was a cross-sectional study. SETTING: This study was performed at a hospital-based hemodialysis center. PATIENTS: We enrolled 448 (male, 198; female, 250) clinically stable hemodialysis patients. Patients with chronic inflammatory disease, malignancy, or viral hepatitis were excluded. Their age (mean +/- SD) was 57.4 +/- 12.5 years. MAIN OUTCOME MEASURES: Biomarkers, including high-sensitivity C-reactive protein (hsCRP), total calcium, phosphate, and intact parathyroid hormone levels, were measured and compared with the recommended range in the K/DOQI guidelines. Correlations between these parameters were analyzed, and factors independently associated with hsCRP and the calcium phosphate product (Ca x P) were identified by regression analysis. RESULTS: Most patients did not achieve the K/DOQI recommended therapeutic range in the four parameters, and only 50 patients (11%) met their treatment goals. The hsCRP level was directly related to calcium, phosphate, and Ca x P. Patients who achieved the guidelines' range had lower hsCRP levels (1.97 mg/L vs. 2.71 mg/L, P < .05). A high hsCRP level (> or = 10 mg/L) was associated with higher calcium, phosphate, and Ca x P levels, and lower albumin levels. Serum albumin, Ca x P, alkaline phosphatase, and diabetes independently predicted hsCRP levels. CONCLUSION: There is a strong association between chronic inflammation and the disturbance of bone mineral metabolism in chronic hemodialysis patients.

Factors determining cardiovascular and renal outcomes after adrenalectomy in patients with aldosterone-producing adrenal adenoma.

Primary aldosteronism is an important cause of secondary hypertension, because it is potentially curable, especially in case of unilateral aldosterone-producing adrenal adenoma (APA). However, the information is limited concerning the cardiovascular and renal outcomes in this patient population. We studied 52 patients with APA in order to determine the pre-operative and post-operative factors predicting cardiovascular and renal outcomes. All 52 patients were hypertensive before the operation. Among 35 patients who underwent pre-operative electrocardiogram, 23 patients had left ventricular hypertrophy (LVH). Patients with LVH had lower estimated glomerular filtration rate (eGFR). Adrenalectomy successfully normalized or improved hypertension, hypokalemia, and aldosterone excess. One month after the adrenalectomy, 32 patients (62%) became normotensive, but 20 patients (38%) remained hypertensive. However, after an average follow-up period of 51 months, only 18 patients remained normotensive, while 34 patients were hypertensive. Thus, the rate of recurrent hypertension after adrenalectomy was high (14/32, 43%). Pre-operative systolic blood pressure (BP), diastolic BP, and post-operative plasma aldosterone concentrations were the only variables significantly different between the hypertensive and normotensive patients. Using pre-operative BP 165/110 mmHg as a cutoff has good positive predictive values (73-92%) for post-operative long-term hypertension. Patients whose renal function worsened after adrenalectomy had significantly higher pre-operative plasma active renin levels. Thus, in patients with APA, the presence of LVH is correlated with impaired renal function (lower eGFR). In conclusion, pre-operative BP and post-operative plasma aldosterone are important in predicting post-adrenalectomy hypertension, and a lower pre-operative plasma renin predicts the improvement in renal function after adrenalectomy.