Markers Of Renal Dysfunction Research Articles

Urinary Extracellular Vesicles and Salt-Losing Tubulopathies: A Proteomic Approach.

Renal tubular cells release urinary extracellular vesicles (uEV) that are considered a promising source of molecular markers for renal dysfunction and injury. We investigated uEV proteomes of patients with hereditary salt-losing tubulopathies (SLTs), focusing on those caused by Gitelman and Bartter (BS) syndromes, to provide potential markers for differential diagnosis. Second morning urine was collected from patients with genetically proven SLTs and uEV were isolated by the ultracentrifugation-based protocol. The uEV proteome was run through a diagonal bidimensional electrophoresis (16BAC/SDS-PAGE), to improve hydrophobic protein resolution. Sixteen differential spots from the proteome of two variants (BS2 and BS3) were analysed by nLC-ESI-MS/MS after in-gel tryptic digestion. A total of 167 protein species were identified from 7 BS2 spots and 9 BS3 spot. Most of these proteins were membrane-associated proteins, in particular transmembrane proteins, and were related to typical renal functions. The differential content of some uEV was then validated by immunoblotting. Our work suggests that uEV proteomics represents a promising strategy for the identification of differential SLT proteins. This could play a role in understanding the pathophysiological disease mechanisms and may support the recognition of different syndromes.

Prevalence and Risk Factors of Proteinuria in Pediatric Heart Transplantation

Renal dysfunction is a common complication of heart transplantation (HTx) in children that affects overall outcome. Proteinuria reflects renal glomerular and tubular damage and is an early marker of renal dysfunction, even when excreted in small amounts, termed microalbuminuria. The prevalence of microalbuminuria in pediatric HTx has not been previously described. We report the prevalence of proteinuria as measured by microabuminuria to creatinine ratio (UACR) and its associated risk factors in pediatric HTx recipients. Since 2015, UACR is collected annually at rejection surveillance catheterization. Patients aged <21 years with at least one UACR were identified. Patients with dual heart/kidney transplant retransplantation, and presence of diabetes pre-transplant were excluded. 116 patients were identified, of whom 51 (44%) were female and 68 (58%) Caucasian. Mean age at HTx was 5.4 ± 6.2 years. Ninety-two (79%) were listed status 1A, and 74 (64%) had congenital heart disease. Perioperative therapies included mechanical circulatory support in 23 (20%), dialysis in 4 (3%), mechanical ventilation in 34 (29%). No patients had insulin dependent diabetes pre-HTx and 2 (2%) developed diabetes in the first year post-HTx. Mean pre-HTx eGFR was 99 ± 35.5 ml/min/1.73m2. At a latest follow-up of 5.8 ± 3.8 years, 7 (6%) patients developed diabetes, 42% (n=35) had an abnormal UACR (≥ 31 units). Mean UACR was 85 ± 182.5 and 25% had eGFR <60 ml/min/1.73m2. Using univariate regression adjusted for time from HTx, younger age at HTx was protective against abnormal UACR (RR 0.94, p <0.05) and post-HTx dialysis was associated with abnormal UACR (R 3.1, p<0.001).Development of diabetes in the first year post-txp was associated with abnormal UACR (β -80, p=0.001). Microalbuminuria as a marker of renal injury is a highly prevalent finding in medium-term follow up of pediatric HTx. Post-Htx dialysis and diabetes is a risk factor for developing microalbuminuria and younger age at transplant may be protective. These observations may have implications on early identification of chronic renal disease and its medical intervention.

COMPARATIVE RENAL DISPOSITION OF CREATINE, AND TECHNETIUM DIAGNOSTIC CONTRAST AGENTS IN THE PIGEON (COLUMBA LIVIA).

Clinical assessment of renal function in avian species often involves the measurement of plasma uric acid and blood urea nitrogen, relatively insensitive markers of renal dysfunction and dehydration. In mammals, endogenous creatinine is widely used as an indicator of renal glomerular dysfunction. However, avian species produce primarily creatine. Here, renal creatine, 99mTc99-DTPA (diethylenepentaacetic acid, DTPA) and 99mTc-MAG3 (mercaptoacetyl triglycine, MAG3) renal clearances are characterized in the pigeon avian model by infusing DTPA with inulin and creatine with each tracer and examining the slope of their blood disappearance curves. Clearance curves for inulin and DTPA were parallel, suggesting DTPA is cleared by renal filtration. MAG3 clearance (slope: -2.74 × 105, r2 = 0.97) had a slope almost 10-fold steeper than for DTPA (slope: -6.29 × 104, r2 = 0.90), and orders of magnitude steeper than for creatine (slope: -1.4, r2 = 1.0). These results suggest that DTPA is cleared by glomerular filtration like inulin, while MAG3 is filtered and actively excreted in a manner similar to mammals. In contrast, creatine is filtered and resorbed, has a larger volume of distribution (Vd), or exhibits a greater blood protein binding, making it more complex as a renal marker, when compared with creatinine handling in mammals. The two radiotracers can be readily adapted for use in birds, inviting both qualitative and semiquantitative functional evaluation of avian renal function for research and clinical purposes. The elimination of creatine appears to be more complex requiring further study.

Impact of the use of nephrotoxic drugs in critically ill pediatric patients.

ObjectiveTo evaluate the association between the use of nephrotoxic drugs and acute kidney injury in critically ill pediatric patients.MethodsThis was a retrospective cohort study involving all children admitted to the intensive care unit of a pediatric hospital during a 1-year period. Acute kidney injury was defined according to the KDIGO classification. Patients with a length of hospital stay longer than 48 hours and an age between 1 month and 14 years were included. Patients with acute or chronic nephropathy, uropathy, congenital or acquired heart disease, chronic use of nephrotoxic drugs, rhabdomyolysis and tumor lysis syndrome were excluded. Patients were classified according to the use of nephrotoxic drugs during their stay at the pediatric intensive care unit.ResultsThe sample consisted of 226 children, of whom 37.1% used nephrotoxic drugs, 42.4% developed acute kidney injury, and 7.5% died. The following drugs, when used alone, were associated with acute kidney injury: acyclovir (p < 0.001), vancomycin (p < 0.001), furosemide (p < 0.001) and ganciclovir (p = 0.008). The concomitant use of two or more nephrotoxic drugs was characterized as an independent marker of renal dysfunction (p < 0.001). After discharge from the pediatric intensive care unit, renal function monitoring in the ward was inadequate in 19.8% of cases.ConclusionIt is necessary for intensivist physicians to have knowledge of the main nephrotoxic drugs to predict, reduce or avoid damage to their patients.

Microalbuminuria in Type 2 Diabetes Mellitus and Glycemic Control

Objective: To determine the frequency of microalbuminuria in Type 2 Diabetes Mellitus with good glycemic control. Introduction: Diabetes Mellitus is a chronic illness, frequently not diagnosed until complications appear. Microalbuminuria is a renal marker of generalized vascular endothelial damage and early atherosclerosis. Patients with microalbuminuria are at increased risk of microvascular and macrovascular complications of Diabetes Mellitus like myocardial infarction, stroke, and nephropathy. Poor glycemic control increases the risk of microalbuminuria. Methodology: A cross-sectional study is conducted at the Department of Medicine, Bolan Medical College/ Sandeman Provincial Hospital Quetta, Pakistan. The duration of the study is six months from September 2016 to March 2017. A total of 140 Type 2 DM patients with good glycemic control is included in this study. 63 (45%) were female, and 77 (55%) were male with a mean age of 44.47 ± 4.99 years. The mean duration of DM is found to be 4.21 ± 0.94 years. The mean HbA1c level was found to be 6.74 ± 0.17. 21 patients (15%) were found to have microalbuminuria. Conclusion: There is an association of microalbuminuria in diabetic patients with good glycemic control; however, the prevalence is low, but it is still positive. Uncontrolled DM is strongly associated with the prevalence of microalbuminuria. Screening for microalbuminuria and HbA1c test should be done both in new and already diagnosed type 2 diabetic patients as an early marker of renal dysfunction and glycemic control.

Evaluating the antiproteinuric efficacy of cilnidipine in diabetic kidney disease

Background: Diabetic kidney disease is a life threatening and disabling complication of uncontrolled diabetes mellitus. Clinical proteinuria is a well-established marker of renal dysfunction. A dual L/N-type calcium channel blocker cilnidipine dilates the afferent and efferent arterioles of the glomerulus decreasing the intraglomerular pressure and showing antiproteinuric effects. The present study was conducted to assess the antiproteinuric efficacy of cilnidipine in patients of diabetic kidney disease.Methods: This interventional study was conducted on 50 patients of both genders aged 18 years and above with diabetic nephropathy (stage-2 to stage 4) visiting the medicine OPD at HIMS, Dehradun over a period of six months, the patients were given tablet cilnidipine (5-20 mg) once or twice a day. Baseline urine protein creatinine ratio (UPCR), serum creatinine and the estimated glomerular filtration rate (eGFR) was recorded at baseline and repeated after a period of 12 weeks. The end point was the decrease in UPCR after a period of 12 weeks. Students-paired T test was used for analysing the intragroup data.Results: After 12 weeks of treatment with cilnidipine, a significant reduction was observed in the urinary protein creatine ratio (mean±SD) from 3.2±1.23 at baseline to 3.09±1.09 respectively (p&lt;0.05). Along with this there was also a reduction in the in serum creatinine which was significant (p&lt;0.05) as well as an increase in the eGFR value which was also statistically significant (p&lt;0.001).Conclusions: Cilnidipine reduces the UPCR as well as improves the kidney function in patients with diabetic kidney disease.

Utility of Urinary Neutrophil Gelatinase Associated Lipocalin (NGAL) in Decompensated Cirrhosis.

Background and Aims:Renal failure occurring in the setting of cirrhosis increases mortality by more than threefold. Serum creatinine, the conventional marker for renal dysfunction has inherent limitations in identifying and categorizing renal dysfunction in patients with chronic liver disease (CLD). Neutrophil gelatinase associated lipocalin (NGAL) is a novel biomarker which gets upregulated as early as 2-6 hours following the insult to renal tubules. In this study, we aim to check the utility of uNGAL to identify the different phenotypes of renal dysfunction in patients with CLD. We also intend to assess the utility of NGAL to predict 90-day transplant-free survival in patients with CLD.Methods:A total number of 120 adult patients, with cirrhosis of liver were recruited. Those with pre-existing renal parenchymal disease, receiving nephrotoxic medications, spontaneous bacterial peritonitis, septic shock, proteinuria, hematuria, urinary tract infection and anuria were excluded. Urine samples for NGAL was measured at admission and at 48 hours thereafter. Patients were followed up for 90 days post admission.Results:Among the study population, 16 patients (13.3%) had normal kidney function, 43 (35.8%) had prerenal azotemia and 54 (45%) had Hepatorenal Syndrome (HRS - AKI) and 7 (5.8%) had acute tubular necrosis (ATN). Urinary NGAL (uNGAL) levels were considerably lower in patients with normal kidney function and prerenal azotemia. An uNGAL level of 124 ng/ml on admission could distinguish severe forms of renal injury, with a sensitivity of 86% and specificity of 84%. The non survivors had higher uNGAL levels at admission [209.6 ng/ml (118.7-376.8) vs. 123 (33.6-344.3); P = 0.013].The receiver operated curves for uNGAL and serum creatinine at admission did not show any significant difference for predicting 90 day mortality (AUC for uNGAL: 0.632 vs 0.580 for serum creatinine; difference in AUC 0.053, P value 0.17).Conclusion:uNGAL levels are elevated in patients with HRS-AKI and ATN. A higher uNGAL level at admission was suggestive of severe renal dysfunction. An elevated uNGAL on admission is associated with inferior survival. However, uNGAL is not superior to serum creatinine in predicting 90-day mortality.

Early Renal Dysfunction in Obese Patients with Insulin Resistance

Abstract Background and aims. Obese individuals have insulin resistance status assessed in the present study by the HOMA index (“Homeostasis model assessment”). This prospective study assessed renal disorders in the insulin resistance in obese patients. Material and Methods. The study included 73 young obese patients. The assessment included the HOMA index before meal and parameters of renal function (glomerular filtration rate, albuminuria, β2-microglobulinuria). Results. In young obese, insulin-resistance patients, glomerular hyperfiltration and β2-microglobulinuria are found in 77.0 and 93.4% of cases respectively. The albuminuria is noted in some cases, which reduces diagnostic value. Conclusions. In young obese patients with insulin resistance, glomerular hyperfiltration and β2-microglobulinuria are main diagnostic markers of renal dysfunction.

Abstract P106: Elevated Fasting Glucose and Proteinuria in Offspring Born to Gestational Hypertensive African Green Monkeys

Preeclampsia (PreE), or gestational hypertension (GH) concurrent with proteinuria, is a leading cause of maternal and fetal mortality worldwide. PreE often leads to fetal growth restriction resulting in low birth weight offspring. Low birth weight infants are at higher risk of developing cardiovascular disease later in life. The African Green Monkey (AGM; Chlorocebus aethiops sabaeus ) develops spontaneous GH with proteinuria and fetal growth restriction. We hypothesize that GH will developmentally program offspring to reduced kidney function and metabolic disease. Maternal systolic arterial pressure (SAP) was measured via forearm plethysmography prior to pregnancy and during the 3 rd trimester of pregnancy. At 1-3 years of age, offspring were single-housed for water intake and urine flow rate collections followed by blood pressure measurement and venous blood sampling. Animals were grouped by pregnancy phenotype. SAP for normotensive (NT, n=23) mothers did not change in pregnancy, but increased during third trimester for GH (Δ=35 ± 7 mmHg, n=34). NT pregnancies resulted in a 4% stillbirth rate (1/23) compared with 29% in GH (10/34). Surviving GH offspring had reduced birth weight (NT 336 ± 11g vs. GH 295 ± 8g, p&lt;0.05). Fasting glucose was higher in progeny born to GH pregnancies (NT 69 ± 8 mg/dl, n=13; GH 92 ± 6 mg/dl, n=20). Urinary protein excretion was higher in offspring born to GH pregnancies (NT 152 ± 27 mg/day; GH 318 ± 46 mg/day). SAP of offspring was similar between maternal phenotype (NT 107 ± 8 mmHg; GH 109 ± 5 mmHg). Juvenile SAP was unrelated to fasting glucose or urinary protein excretion, indicating that these factors are determined by maternal SAP during pregnancy, rather than juvenile phenotype. Thus, GH is associated with fetal growth restriction in the form of high stillbirth rates and lower surviving-offspring birth weights in the AGM. GH offspring have elevated fasting glucose and possible decreased kidney function as evidenced by proteinuria. GH could be programming offspring for early life metabolic risk factors and declining renal function. Future studies include oral glucose tolerance tests and additional markers of renal dysfunction to further assess in utero programming of the pathogenesis of cardiovascular and metabolic disease.

Роль "Новых" маркеров ренальной дисфункции в оценке риска развития неблагоприятных сердечно-сосудистых осложнений у пациентов с острым коронарным синдромом.

Роль "Новых" маркеров ренальной дисфункции в оценке риска развития неблагоприятных сердечно-сосудистых осложнений у пациентов с острым коронарным синдромом.

Sickle cell disease nephropathy: an update on risk factors and potential biomarkers in pediatric patients.

One of the major chronic complications of sickle cell disease (SCD) is sickle cell nephropathy. The aim of this review is to discuss the pathophysiology, natural history, clinical manifestations, risk factors, biomarkers and therapeutic approaches for sickle cell nephropathy, focusing on studies with pediatric patients. The earliest manifestation of renal disease is an increase in the glomerular filtration rate. A finding that may also be observed in early childhood is microalbuminuria. Nephrin, KIM-1, VGFs, chemokines and renin-angiotensin system molecules have emerged as potential early markers of renal dysfunction in SCD. In regards to a therapeutic approach, renin-angiotensin system inhibitors and angiotensin receptor blockers seem to be effective for the control of albuminuria in adults with SCD, although new studies in children are needed. The precise moment to begin renoprotection in SCD patients who should be treated remains to be determined.

Determination of urinary retinol and creatinine as an early sensitive marker of renal dysfunction

Determination of urinary retinol, which is a new promising early biomarker of renal damage typically expressed in the clinical environment as retinol/creatinine ratio, is currently difficult to accomplish. We have developed and validated the new ultra-high-performance liquid chromatography method with UV and mass spectrometry detection for the separation and quantification of retinol and creatinine in human urine in a single run. The separation of these two substances with completely different physicochemical properties was achieved using a column packed with fluorinated stationary phase and acetonitrile and aqueous ammonium formate buffer as the mobile phases. The separation was completed within 4 min. Our new method involves very fast and simple sample preparation requiring small amount of sample matrix and solvents. Deuterium labeled internal standard was used for the more precise quantification. The method was tested with real-life samples using urine collected from patients suffering from breast, colorectal, head, and neck cancer.

Evaluation of Preoperative Abdominal Adipose Tissue–, Inflammation-, Muscle Mass–, and Nutritional Status–based Prognostic Markers to Assess Renal Dysfunction in Living Kidney Donors

BackgroundLiving kidney donors (LKDs) are at high risk of renal dysfunction after undergoing a donor nephrectomy (DN), resulting in poor prognosis associated with the development of cardiovascular or cerebrovascular disease. Decreasing this risk can improve the survival rate of LKDs. We investigated the effects of preoperative conditions in LKDs on renal dysfunction after DN using abdominal adipose tissue, inflammation, nutritional status, and muscle mass as markers for this assessment. MethodsOur retrospective study included 79 LKDs. Body composition markers were assessed using preoperative unenhanced computed tomographic images. Inflammation- and nutritional status–based markers were assessed using preoperative laboratory blood tests. The association between each marker was investigated, and prognostic markers for renal dysfunction after DN were identified. ResultsThe LKDs in this cohort comprised 30 men and 49 women. The median age at the time of DN and the preoperative estimated glomerular filtration rate were 58 years and 81.9 mL/min/1.73 m2, respectively. Abdominal subcutaneous adipose tissue and muscle mass significantly differed between the sexes. Each adipose tissue–, inflammation-, nutritional status–, and muscle mass–based marker showed an association with each other. Abdominal visceral adipose tissue and nutritional status could be independent prognostic markers for renal dysfunction after DN. ConclusionsOur findings suggest that the preoperative condition of LKDs (assessed using specific markers such as abdominal visceral adipose tissue mass per volume and nutritional status) could affect renal dysfunction after DN. Optimal preoperative management can lead to better outcomes in LKDs. Further research is needed to establish appropriate exercise programs and nutritional interventions.

TO FIND OUT THE CORRELATION OF MICROALBUMIN WITH FBS, PPBS, BLOOD UREA &amp; SERUM CREATININE

Background: The Aim is to find out the Correlation of Microalbumin with Fbs, Ppbs, Blood Urea &amp; Serum Creatinine. The target population of this study was individuals who have Type-2 DM for different period of time and resident in Dehradun.&#x0D; Result: The percentage distribution of urinary microalbumin at different levels in controls and cases are shown in table (11) and the graph of figure (11), in which 100%of control group had urinary cases of diabetes mellitus had value &gt;15mg/1.this microalbumin value&lt;15mg/l where as 100% caese diabetes mellitus has value &gt; 15mg/l. This increase in urinary microalbumin values statistically highly significant with p&lt;.001 in cases as compared to controls.&#x0D; The Mean values of Urinary Microalbumin in cases &amp; controls are shown in table 02 and the mean values are 10.57±2.47 &amp; 110.76±56.081 in diabetes mellitus cases respectively. This increase mean values of Urinary Microalbumin in cases compares to control is statistically significant.&#x0D; Conclusion: In present study a very large correlation was observed between microalbumin and other parameter in cases&#x0D; It was also observed the microalbumin conc., Were strongly associated with several risk factor glycemic control, renal dysfunction and other complication these marker were clinically correlate with in with increasing the concentration of microalbumin.&#x0D; It is concluded that increase in microalbumin is an early manifestation of diabetic renal disease and hence microalbumin can be used as a marker of renal dysfunction in diabetic nephropathy further studies world help to clarify its role in pathogenesis of diabetic renal disease.&#x0D; Keywords: Microalbumin, FBS, PPBS, Blood Urea &amp; Serum Creatitine.

Prevention of lipopolysaccharide-induced CD11b+ immune cell infiltration in the kidney: role of AT2 receptors.

Immune cell infiltration plays a central role in mediating endotoxemic acute kidney injury (AKI). Recently, we have reported the anti-inflammatory and reno-protective role of angiotensin-II type-2 receptor (AT2R) activation under chronic low-grade inflammatory condition in the obese Zucker rat model. However, the role of AT2R activation in preventing lipopolysaccharide (LPS)-induced early infiltration of immune cells, inflammation and AKI is not known. Mice were treated with AT2R agonist C21 (0.3 mg/kg), with and without AT2R antagonist PD123319 (5 mg/kg) prior to or concurrently with LPS (5 mg/kg) challenge. Prior-treatment with C21, but not concurrent treatment, significantly prevented the LPS-induced renal infiltration of CD11b+ immune cells, increase in the levels of circulating and/or renal chemotactic cytokines, particularly interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) and markers of renal dysfunction (blood urea nitrogen and albuminuria), while preserving anti-inflammatory interleukin-10 (IL-10) production. Moreover, C21 treatment in the absence of LPS increased renal and circulating IL-10 levels. To investigate the role of IL-10 in a cross-talk between epithelial cells and monocytes, we performed in vitro conditioned media (CM) studies in human kidney proximal tubular epithelial (HK-2) cells and macrophages (differentiated human monocytes, THP-1 cells). These studies revealed that the conditioned-media derived from the C21-treated HK-2 cells reduced LPS-induced THP-1 tumor necrosis factor-α (TNF-α) production via IL-10 originating from HK-2 cells. Our findings suggest that prior activation of AT2R is prophylactic in preventing LPS-induced renal immune cell infiltration and dysfunction, possibly via IL-10 pathway.

Cardiorenal relationships in the focus of risks of atrial fibrillation in patients after acute ST-elevated myocardial infarction (observational program FAKEL)

Aim. To study markers of renal dysfunction in relation to the likelihood of atrial fibrillation (AF) in patients after ST-segment elevated myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Material and methods . The study was conducted with the inclusion of 1 52 patients discharged for outpatient monitoring after STEMI. There were 4 visits: V 1 - inclusion visit, V 2 - in 12 months, V 3 - in 18 months, V 4 - in 24 months with determination of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP), cystatin C, erythropoietin, galectin-3, von Willebrand factor (fW), left ventricular ejection fraction. Endpoint: new cases of AF, cardioembolic stroke, deaths. Results. After 24 months 35 patients (23.0%) were diagnosed with AF, 6 of them (3.9%) - developed cardioembolic stroke. The multivariate model of risk factors for AF included indicators: cystatin C (odds ratio [OR] 1.31; 95% confidence interval [95%CI] 1.03-1.67), NT-ProBNP (OR 1.11; 95%CI 1.03-1.19), galectin-3 (OR 0.71; 95%CI 0.55-0.91), fV (OR 0.71; 95%CI 0.55-0.91). Conclusion. The prognostic significance of cystatin C in relation to the risk of AF was established, which should be considered when assessing the prognosis in patients after STEMI.

Mesenchymal stromal cells (Cyto-MSC) are well-tolerated and associated with renal function improvement in patients with chronic kidney disease: an observational retrospective study

Background & Aim Background Microvascular disease and structural damage are hallmarks of chronic kidney disease (CKD). We have demonstrated previously that mesenchymal stromal cells (MSCs) could differentiate into mesangial cells in animal models of glomerular injury. We further demonstrated that MSCs promoted angiogenesis in diabetic patients with critical limb ischemia. Given the ability to improve vascularity and structure, MSCs may potentially improve renal function in CKD. Objective In this study, we evaluated the safety, tolerability and renal function of patients with CKD who had participated in MSC-related clinical trials. Methods, Results & Conclusion Methodology There were 4 clinical trials approved at the National University Malaysia in collaboration with Cytopeutics (Cyberjaya, Malaysia) which provided the mesenchymal stromal cells (Cyto-MSC) for treatment of acute stroke, heart failure, diabetes with critical limb ischemia and severe deforming osteoarthritis. All patients received 65-130 × 106 Cyto-MSC intravenously. Severity of chronic kidney disease is based on baseline estimated glomerular filtration rate (eGFR) and serum creatinine which are markers of renal dysfunction. These and other blood tests including fasting blood sugar (FBS) and Hba1c (marker of glycemic control) were measured at baseline and 12 months post infusion. Results 82 patients (53 men, 29 women; age 38-92 years) with different CKD stages (stage 3, n=65; stage 4, n=5; stage 5, n=12) were identified. 33 patients have type 2 diabetes. All patients tolerated the treatment well. There was significant improvement in serum creatinine (170±148 vs. 144±123 μmol/L; p=0.013) and eGFR values (37±17 vs. 41±18 mL/min/1.73m2; p=0.001). Patients with stage 3 CKD have the most significant eGFR value improvement (45±9 vs. 50±10 mL/min/1.73m2; p=0.006). Among diabetic patients, improvements were observed in creatinine (167±138 vs. 145±115 μmol/L, p=0.011), eGFR (37±15 vs. 41±16, p=0.05), HbA1c (7.4±2.1 vs. 6.2±1.4 %, p=0.011) and FBS (7.1±1.1 vs. 6.8±0.8 mmol/L %, p=0.021). There was also modest positive correlation between FBS with urea (p=0.001) and eGFR (p=0.016). Conclusion Cyto-MSC appears to be safe and well-tolerated by patients with moderate-severe CKD and associated with improvement in renal function particularly for moderate CKD patients. Further randomized prospective studies are warranted.

Prevention of Lipopolysaccharide‐Induced CD11b+ Leukocytes Infiltration in the Kidney: Role of AT2 Receptors

Leukocyte infiltration plays a central role in mediating endotoxemic acute kidney injury (AKI). We have recently shown the anti‐inflammatory and reno‐protective role of angiotensin‐II type‐2 receptor (AT2R) activation under chronic low‐grade inflammatory condition using the obese Zucker rat model. The present study tests the hypothesis that prior activation of AT2R attenuates LPS‐mediated early infiltration of leukocytes, inflammation, and AKI. Mice were pre‐treated with AT2R agonist C21 (0.3 mg/kg), with and without AT2R antagonist PD123319 (5 mg/kg) prior to or concurrently with lipopolysaccharide (LPS, 5 mg/kg) challenge. Pre‐treatment with C21, but not concurrent treatment, significantly prevented the LPS‐induced renal infiltration of CD11b+ leukocytes, increase in the levels of circulating and renal chemotactic cytokines, particularly interleukin‐6 (IL‐6) and markers of renal dysfunction (blood urea nitrogen and albuminuria), while preserving anti‐inflammatory interleukin‐10 (IL‐10) production. Moreover, C21 treatment in the absence of LPS increases renal and circulating IL‐10 levels. To investigate the role of IL‐10 in a cross talk between epithelial cells and monocytes, we performed in vitro conditioned media studies in human kidney proximal tubular epithelial (HK‐2) cells and human monocytes (THP‐1 cells). These studies revealed that the conditioned‐media derived from the C21‐treated HK‐2 cells reduced LPS‐induced THP‐1 TNF‐α production via IL‐10 originating from HK‐2 cells. Our findings suggest that activation of AT2R prior to LPS challenge prevents monocyte infiltration and inflammatory renal injury, possibly via an increase in renal IL‐10 production.Support or Funding InformationThis study was supported by NIH grants R01 DK117495 and R01 DK61578.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

3'-O-β-d-glucopyranosyl-α,4,2',4',6'-pentahydroxy-dihydrochalcone, from Bark of Eysenhardtia polystachya Prevents Diabetic Nephropathy via Inhibiting Protein Glycation in STZ-Nicotinamide Induced Diabetic Mice.

Previous studies have shown that accumulation of advanced glycation end products (AGEs) can be the cause of diabetic nephropathy (DN) in diabetic patients. Dihydrochalcone 3′-O-β-d-glucopyranosyl α,4,2′,4′,6′-pentahydroxy–dihydrochalcone (1) is a powerful antiglycation compound previously isolated from Eysenhardtia polystachya. The aim was to investigate whether (1) was able to protect against diabetic nephropathy in streptozotocin (STZ)-induced diabetic mice, which displayed renal dysfunction markers such as body weight, creatinine, uric acid, serum urea, total urinary protein, and urea nitrogen in the blood (BUN). In addition, pathological changes were evaluated including glycated hemoglobin (HbA1c), advanced glycation end products (AGEs) in the kidney, as well as in circulation level and pro-inflammatory markers ICAM-1 levels in diabetic mice. After 5 weeks, these elevated markers of dihydrochalcone treatment (25, 50 and 100 mg/kg) were significantly (p < 0.05) attenuated. In addition, they ameliorate the indices of renal inflammation as indicated by ICAM-1 markers. The kidney and circulatory AGEs levels in diabetic mice were significantly (p < 0.05) attenuated by (1) treatment. Histological analysis of kidney tissues showed an important recovery in its structure compared with the diabetic group. It was found that the compound (1) attenuated the renal damage in diabetic mice by inhibiting AGEs formation.

Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: A pooled analysis of 26 clinical trials

Objective:Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has been associated with improvement in markers of renal dysfunction in individual randomized trials; however, the comparative incidence of clinically significant renal events remains unclear.Design:We used a po