Urinary Albumin Levels Research Articles

To Evaluate the Level of Serum Cholesterol, Uric Acid, Urea, Creatinine and Urine Albumin in Diabetic Patients from Peshawar

Diabetes Mellitus is a metabolic disorder that causes chronic hyperglycemia. Its progression may lead to the dysfunction of multiple organs such as kidneys, eyes, blood vessels and neurons. It is caused by a combination of two basic factors that are abnormal insulin secretion and sensitivity of tissues to insulin. Group of parameters were selected in this study that have some relation with diabetes mellitus which included serum uric acid, cholesterol, urea, creatinine and urine albumin. The aim of this study was to find the impact of diabetes mellitus on these parameters. The blood and urine samples were collected according to the recommended protocol. The biochemical parameters had been determined by Micro-lab 300 biochemistry analyzer and urine qualitative was performed through uric-v3 strips. A cross-sectional study was carried out by 105 diabetic subjects and their samples were collected from different laboratories of district Peshawar. The mean age was 44 ± 12.54 years and samples were comprised of 50.48%male and 49.52% females. According to our findings among 105 diabetic patients 29% had elevated uric acid, 69% cholesterol, 57% urea, 39%creatinine and 40% urine albumin levels respectively. The overall result concluded that these parameters must be considered or taken seriously to monitor and to limit its progression to irreversible changes. Keywords: cholesterol, creatinine, diabetes mellitus, nephropathy, serum urea, uric acid, urine albumin.

Trametenolic Acid Ameliorates the Progression of Diabetic Nephropathy in db/db Mice via Nrf2/HO-1 and NF-κB-Mediated Pathways.

Diabetic nephropathy (DN) is a fatal complication of diabetes and the main cause of end-stage renal disease. Due to the suboptimal effects of current treatments, there is an urgent need to develop new therapeutic strategies for DN. Trametenolic acid (TA), a lanostane-type tetracyclic triterpenoid, is one of the main active ingredients extracted from the natural product Inonotus obliquus. Our study was aimed at clarifying the potential protective effects of TA on DN and its underlying mechanism. In this research, C57BLKS/db (db/db) mice were used as the spontaneous DN model, and TA (10 mg/kg/d) was intraperitoneally injected for 4 consecutive weeks. Ratio of right kidney weight/body weight was calculated, and the contents of serum creatinine (Scr), blood urea nitrogen (BUN), and urine albumin were detected. The activities of superoxide dismutase (SOD) and catalase (CAT) and the contents of reductive glutathione (GSH) and malondialdehyde (MDA) were measured. The histopathological changes of renal tissues were observed by hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and Masson staining. The protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase-1 (NQO-1), nuclear factor kappa B (NF-κB), proinflammation cytokine tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), Nephrin, and Podocin were detected by western blot assay. Immunohistochemistry was utilized to detect expressions of collagen III (COL-III) and fibronectin (FN). Our results showed that TA administration significantly reduced the ratio of right kidney weight/body weight, BUN, Scr, and urine albumin levels and alleviated the histopathological changes of DN mice. Moreover, TA administration remarkably increased GSH content and SOD and CAT activities and decreased MDA content. Western blot assay demonstrated that TA activated Nrf2 signaling and increased the expression of downstream antioxidant enzymes HO-1 and NQO-1. Further studies illustrated that NF-κB signaling was inhibited, and downstream proinflammation cytokine expressions of TNF-α, IL-6, and IL-1β were also downregulated. In addition, we also found that TA administration significantly increased the expression of nephrin and podocin proteins and reduced the protein expression of COL-III and FN. These findings suggested that TA exhibited a renoprotective effect by ameliorating oxidative stress and inflammation via Nrf2/HO-1 and NF-κB signaling pathways.

Activation of angiotensin-converting enzyme 2 ameliorates metabolic syndrome-induced renal damage in rats by renal TLR4 and nuclear transcription factor κB downregulation.

BackgroundMetabolic syndrome (MetS) is an independent risk factor for chronic kidney disease (CKD) through many mechanisms, including activation of the renin–angiotensin system. The deleterious effects of angiotensin II (Ang II) can be counterbalanced by angiotensin-converting enzyme 2 (ACE2). Diminazene aceturate (DIZE), an anti-trypanosomal drug, can activate ACE2.ObjectiveThis study aimed to investigate the possible reno-protective effects of DIZE in MetS rats with elucidation of related mechanisms.Materials and methodsThirty adult male Wistar albino rats were divided equally into control, MetS, and MetS + DIZE groups. Body weight, systolic blood pressure (SBP), and urinary albumin levels were measured. Serum levels of fasting blood glucose (FBG), insulin, uric acid, lipid profile, urea, and creatinine were measured. Homeostasis Model Assessment Index (HOMA-IR) was estimated. Subsequently, renal levels of ACE2, Ang II, malondialdehyde (MDA), reduced glutathione (GSH), and tumor necrosis factor-α (TNF-α) were measured with histopathological and immunohistochemical assessment of TLR4 and NF-κB in renal tissues.ResultsMetS caused dyslipidemia with significant increases in body weight, SBP, FBG, serum insulin, HOMA-IR, uric acid, urea, creatinine, urinary albumin, and renal levels of Ang II, MDA, and TNF-α, whereas renal ACE2 and GSH were significantly decreased. Renal TLR4 and NF-κB immunoreactivity in MetS rats was upregulated. DIZE supplementation of MetS rats induced significant improvements in renal function parameters; this could be explained by the ability of DIZE to activate renal ACE2 and decrease renal Ang II levels with downregulation of renal TLR4 and NF-κB expression.ConclusionDIZE exerts a reno-protective effect in MetS, mainly by downregulating renal TLR4 and NF-κB levels.

Upregulation of VSIG4 in Type 2 Diabetic Kidney Disease.

Fibrosis is the final common finding in patients with advanced diabetic kidney disease. V-set Ig domain containing 4 (VSIG4) is related to fibrosis in several diseases. It also contributes to fibrosis under high-glucose conditions in renal tubule cells. To determine the role of VSIG4 in type 2 diabetes, we examined VSIG4 expression in a type 2 diabetic animal model and podocyte. Urinary excretion of albumin and VSIG4 was significantly higher in db/db mice than in the control group. Urine VSIGs levels for 6 h were about three-fold higher in db/db mice than in db/m mice at 20 weeks of age: 55.2 ± 37.8 vs. 153.1 ± 74.3 ng, p = 0.04. Furthermore, urinary VSIG4 levels were significantly correlated with urinary albumin levels (r = 0.77, p < 0.01). Intrarenal VSIG4 mRNA expression was significantly higher in db/db mice than in control mice (1.00 ± 0.35 vs. 1.69 ± 0.77, p = 0.04). Further, VSIG4 expression was almost twice as high in db/db mice at 20 weeks of age. Intrarenal VSIG immunoreactivity in db/db mice was also significantly higher than that in control mice. In cultured podocytes, both high glucose and angiotensin II significantly upregulated the expression of VSIG4 mRNA and protein. In conclusion, VSIG4 was upregulated in an animal model of type 2 diabetes and was related to albuminuria and pro-fibrotic markers. Considering these relationships, VSIG4 may be an important mediator of diabetic nephropathy progression.

Study of purine derivatives and their relation to renal disorders in patients with psoriasis.

Psoriasis (Pso) is a chronic proliferative skin condition associated with hyperuricemia that may impair renal function. The current study investigates the correlation between purine derivatives (PDs) and renal function in patients with Pso. This case-control study comprises 30 psoriatic patients and 30 age- and sex-matched healthy controls. The enzyme-linked immunosorbent assay (ELISA) was used to assess serum xanthine oxidase (XO) and urine albumin levels. Serum uric acid (SUA) and urinary creatinine were measured using the colorimetric method. There was a rise in the related PDs levels in patients with Pso compared to controls, as evidenced by the enhanced SUA levels (p < 0.001) and XO levels (p < 0.001). The presence of the related PDs in the serum was linked to the severity of Pso, and there was also a connection between the related PDs levels in the blood and indicators of renal dysfunction. Moreover, SUA and urinary albumin creatinine ratio (UACR) were found to be significantly correlated (r = 0.371 and p = 0.044), as were XO and UACR (r = 0.422 and p = 0.020). In psoriatic patients with itching and palmoplantar affection, mean SUA levels were considerably more significant than those in other instances (p = 0.005 and p = 0.018, respectively). Pso, being a hyperproliferative disease, is associated with hyperuricemia, which has a harmful effect on kidney function. The related PDs may be unique serological biomarkers for patients with Pso who are at high risk of developing renal abnormalities, especially with higher severity scores.

Association of glycosylated hemoglobin with urinary albuminuria for early detection and progression of renal damage in patients with type 2 diabetes mellitus

Background: Regular screening of levels of glycosylated hemoglobin and microalbuminuria (MA), diabetic nephropathy can be prevented.Recent studies found some of the sensitive and specific biomarker for early detection and progression of nephropathy in type 2 diabetes mellitus (T2DM) patients. Aim and Objectives: This study was carried out to correlation of glycosylated hemoglobin with urinary albuminuria for early detection and progression of nephropathy in patients with T2DM. Materials and Methods: This was a case–control study was conducted at tertiary care institute of India. A total 300 subjects included in the present study diagnosed with T2DM according to American diabetes association criteria and the cases are sub grouped based on albumin creatinine ration, the 100 patients T2DM with normoalbuminuria (NA) (ACR Ratio: &lt;30 mg/dL) and 100 patients T2DM with MA (ACR Ratio: 30–299 mg/dL) along with that 100 healthy subjects were included in the study.FBS, PPBS, Urea, Creatinine, Uric acid, HbA1C, and Urinary Albumin was analyzed using laboratory standard methods. Results: The plasma fasting blood sugar, post-prandial blood sugar, serum urea, creatinine, uric acid, Glycosylated hemoglobin, and urinary albumin levels were increased in two groups of T2DM Patients when compared to healthy controls. Significantly elevated levels of plasma fasting blood sugar, post-prandial blood sugar, serum urea, creatinine, uric acid, Glycosylated hemoglobin, and urinary albumin are observed in all the parameters elevated in between patients T2DM with MA when compared to patients T2DM NA. Conclusion: Elevated levels of Glycated hemoglobin as well as urinary albumin were useful for detection and progression of different stages of nephropathy in patients with T2DM and also this study suggest that continuous monitoring of these investigations were useful for treatment of different stages of T2DM.

ACE gene polymorphism and features of kidney disorders in patients with type 2 diabetes mellitus

Objective — to determine the prevalence of the Alu Ins/Del polymorphism of the angiotensin‑converting enzyme (ACE) gene in patients with type 2 diabetes mellitus (DM 2) with nephropathy and to identify possible associative relationship between the course of the disease and the genetic profile of the examined subjects.&#x0D; Materials and methods. Examinations involved 73 patients with diabetic nephropathy (DN), treated in the hospital of L. T. Mala Therapy National Institute. The control group consisted of 19 healthy individuals. After the initial examination and depending on the polymorphic variant of the ACE gene, patients were divided into three groups: group I — carriers of D/D polymorphism of the ACE gene (n = 23); group II — patients with I/D polymorphism of the ACE gene (n = 32); Group III — patients with I/I polymorphism of the ACE gene (n = 18). DNA amplification and genotyping were carried out by real‑time polymerase chain reaction (PCR) using the SNP‑Express‑Shot reagent kit (Litech, RF) and the CFX96 touch real‑time PCR product detection system (BioRad).&#x0D; Results. The distribution of the genotypes of the Alu I/D polymorphism of the ACE gene corresponded to the Hardy‑Weinberg equilibrium in all studied groups and did not differ significantly from European populations. Comparison of patients with DN, carriers of different Ins/Del polymorphic variants of the ACE gene, did not show significant differences in the stages of chronic kidney disease, creatinine level, and glomerular filtration rate (GFR). Patients with type 2 DM, homozygous for the I/I allele of the ACE gene, had significantly lower levels of urinary albumin (16.80 [12.61 — 34.20] mk/ mL), compared with I/D heterozygotes (26.07 [20.91 — 44.27] mkg/mL), p &lt; 0.05, which demonstrates the negative effects of D allele on the kidney damage progression in this category of patients, even under the same GFR.&#x0D; Conclusions. Patients with DN who are homozygous for the ACE gene allele I, have significantly lower albumin levels than I/D heterozygotes, demonstrating an association between the D allele and the progression of renal disease in type 2 DM. Determining the ACE gene polymorphism in patients with type 2 DM allows to identify risk groups for the DN development and will help to make individualized adjustments to the scheme of pharmacological therapy.&#x0D;

Synergistic effects of liver fibrosis and sarcopenia on endothelial dysfunction and arterial stiffness in patients with type 2 diabetes.

AimsTo investigate synergistic effects of liver fibrosis evaluated by FibroScan and sarcopenia on endothelial function and arterial stiffness in patients with type 2 diabetes.MethodsThis cross-sectional study evaluated liver fibrosis (LF) and sarcopenia in 115 patients with type 2 diabetes. LF was assessed as the liver stiffness measurement (LSM) in transient elastography (FibroScan) and was defined as an LSM greater than or equal to 8.0 kPa. Sarcopenia was defined as a ratio of appendicula skeletal muscle mass to body mass index of<0.789 in men and<0.512 in women. Endothelial function was measured by reactive hyperemia index (RHI) with tonometry, and arterial stiffness was evaluated by the cardio-ankle vascular index (CAVI). Endothelial dysfunction was defined an RHI value below 1.67, while arterial stiffness was defined a CAVI value above 9.0. Patients were divided into four groups: no LF and no sarcopenia; LF but no sarcopenia; no LF but sarcopenia; and LF and sarcopenia. The composite of endothelial dysfunction of arterial stiffness was defined as an outcome.ResultsIn patients with LF, RHI was significantly lower and CAVI was significantly higher than in patients without LF. Furthermore, RHI was significantly lower in patients with sarcopenia than in those without it. Patients with both LF and sarcopenia had the lowest RHI and the highest CAVI and urinary albumin levels. Sarcopenia and HDL cholesterol were independent factor the composite of endothelial dysfunction and arterial stiffness.ConclusionLF and sarcopenia are independently associated with endothelial dysfunction and arterial stiffness in patients with type 2 diabetes. Coexistence of LF and sarcopenia may synergistically lead to vascular damage and thus contribute to the high risk of cardiovascular disease in people with type 2 diabetes.

RHO KINASE BLOCKADE ALLEVIATE BLOOD PRESSURE ELEVATION AND INHIBIT VASCULAR REMODELING IN APATINIB-INDUCED HYPERTENSION–TO BE CONFERMED

Objective: Hypertension and kidney injury are two of the major adverse effects of the targeted anti-tumor drug apatinib, it was suspected that hypertension may be the result of renal dysfunction in some of the previous studies. The present study was designed to explore the different responses of blood pressure and kidney in the apatinib-induced hypertensive rat model. Design and method: 30 Wistar-Kyoto rat were randomly divided into 3 groups, each group was administered with 2 mL 0.9% saline, 30 mg/d of apatinib or 15 mg/d of apatinib by oral gavage for 2 weeks. Blood pressure was monitored at the baseline and during the treatment. Level of creatinine, urea nitrogen, sodium, albumin and protein in blood and urine were tested both at baseline and at the end of the treatment. Urinary sodium excretion and glomerular filtration rate was calculated. Specific mRNA and proteins were detected at the end of the treatment. Results: Average mean blood pressure (MBP) in the high dose apatinib group was 105 mmHg at the 9th day and 113 mmHg at the 15th day, average MBP in the low dose apatinib was 98 mmHg at the 9th day and 108 mmHg at the 15th day. MBP were significantly high in apatinib group, no matter in the high dose or low dose (p &lt; 0.01). Compared with the control group, the level of endothelin 1(ET-1) and college-1 were significantly high in both apatinib group (p &lt; 0.01). There was no significant differences of urinary sodium excretion, glomerular filtration rate and microalbuminuria between the control group and the low dose apatinib group, while that in the high dose apatinib group were significantly high (p &lt; 0.01). Conclusions: There are differences in the response to different doses of apatinib between blood pressure and kidney, blood pressure was elevated even at a relevantly lower dose of apatinib, which was accompanied with the elevation of ET-1 level and vascular emodelling, while the kidney injury occurred only at higher dose of apatinib. The hypertension induced by apatinib was independent with kidney injury caused by the drug, not the consequence of it.

Thalidomide Mitigates Apoptosis via Endoplasmic Reticulum Stress in Diabetic Nephropathy.

Previous studies have shown that endoplasmic reticulum (ER) stress is related to the apoptosis in the development of diabetic nephropathy (DN) and thalidomide (Thd) has renalprotective effects by suppressing inflammation and proliferation of MCs in DN. However, the effect of Thd on the apoptosis of MCs in DN remains largely unclear. The present research is designed to explore the effect of Thd on apoptosis in DN and the related mechanisms. The study is designed to examine the effect and mechanism of Thd on apoptosis in type 2 diabetic mice and high glucose (HG)-induced MCs. We first evaluated the ER stress markers and apoptosis-related proteins with the treatment of Thd in type 2 diabetic mice and MCs in vitro under HG conditions. MTT assay was used to assess cell viability. Additionally, we evaluated the effect of Thd treatment upon MC apoptosis through flow cytometry. Real-time polymerase chain reaction (RT-PCR) and Western blot were performed to evaluate genes and protein expression related to ER stress and apoptosis. The levels of blood urea BUN, CREA, Urine albumin, and UACR in diabetic mice were observed to be significantly reduced after 8 weeks of intervention with Thd. And also, there were upregulated glucose-regulated protein 78 (GRP78), Caspase-12, and downregulated B-cell lymphoma 2 (Bcl-2) in glomeruli of DN mice. In vitro, compared with the HG group, MC apoptosis reduced dramatically with Thd treatment along with upregulation of Bcl-2 and downregulation of Bax. At the same time, ER stress markers GRP78, C/EBP homologous protein (CHOP), and Caspase-12 were also mitigated following the Thd treatment. The present study indicates that Thd might reduce the ER stress in DN via downregulating GRP78, CHOP, and Caspase12 expressions, ultimately mitigating MCs apoptosis.

69-Year-Old Man With Dysuria and Right Lower Abdominal Pain

69-Year-Old Man With Dysuria and Right Lower Abdominal Pain

Xanthine oxidoreductase activity in marathon runners: potential implications for marathon-induced acute kidney injury.

Excess activation of circulating xanthine oxidoreductase (XOR) may contribute to the pathogenesis of widespread remote organ injury, including kidney injury. The purpose of this study was to determine the acute impact of marathon running on plasma XOR activity and to examine whether plasma XOR activity is associated with marathon-induced elevations in biomarkers of acute kidney injury (AKI). Twenty-three young men (aged 20-25 yr) who participated in the 38th Tsukuba Marathon were included. Blood and urine samples were collected before, immediately, 2 h (only blood sample), and 24 h after a full marathon run. Plasma XOR activity was evaluated using a highly sensitive assay utilizing a combination of [13C2,15N2] xanthine and liquid chromatography-triple quadrupole mass spectrometry. The levels of several AKI biomarkers, such as serum creatinine and urinary liver-type fatty acid-binding protein (L-FABP) were measured in each participant. Marathon running caused a transient elevation in plasma XOR activity and levels of purine degradation products (hypoxanthine, xanthine, and uric acid) as well as serum creatinine, urinary albumin, and urinary L-FABP levels. Immediately after the marathon, individual relative changes in plasma XOR activity were independently correlated with corresponding changes in serum creatinine and urinary L-FABP levels. In addition, the magnitude of marathon-induced elevation in plasma XOR activity and levels of purine degradation products were higher in individuals who developed AKI. These findings collectively suggest that marathon running substantially influences the purine metabolism pathway including XOR activity. Moreover, activated circulating XOR can be partly associated with elevated biomarkers of AKI after marathon running.NEW & NOTEWORTHY This study is the first to show marathon running transiently increases plasma XOR activity and levels of purine degradation products (hypoxanthine, xanthine, and uric acid), and further to demonstrate that activated plasma XOR may contribute to marathon-induced elevations in biomarkers of AKI. These findings significantly extend our prior knowledge of the purine metabolic pathway and several AKI biomarkers under strenuous exercise conditions.

Correlation of urinary nephrin with albubinuria to predict early onset of nephropathy in patients with type 2 diabetes mellitus

Nephropathy is a major microvascular complication in patients with type 2 diabetes mellitus (T2DM), where urinary albumin a gold standard and clinically using marker for detection of nephropathy. Some of the studies reported urinary albumin is not a marker for detection of nephropathy. Moreover, recent studies reported urinary nephrin was considered to be a predictable marker for nephropathy. The present study has been designed to evaluate the status of urinary albumin and nephrin to predict early onset of nephropathy in T2DM. The present study included 120 subjects, among these 80 subjects with T2DM again sub grouped into 2 based on ACR ratio (40 T2DM with Normoalbuminuria, 40 T2DM with Microalbuminuria) and 40 healthy controls. Routine biochemical parameters, urinary albumin were analysed by using standard laboratory methods and Urinary nephrin were analysed by using ELISA and statistical analysis was done by using Microsoft Excel Spread Sheets and SPSS Version 20.0. In T2DM Patients with Normoalbuminuria shows a significant elevation of urinary nephrin but no variation in urinary albumin levels. The urinary albumin levels were significantly elevated in Group 3 subjects when compared to Group 1 and Group 2 ( P .0001**).

G Protein‐coupled Estrogen Receptor 1 and Pregnancy Confer Protection against Renal Injury in Aged Female Mice

Chronic kidney disease, which is a leading risk factor impacting 1 in 7 American women, is more frequent in aged compared to younger women. Along with the natural aging process, aged women undergo a decline in circulating estrogen level, which is a predisposing factor for renal disease. Estrogen activates the G protein‐coupled estrogen receptor 1 (GPER1), which elicits cardiovascular and renal protective actions. Additionally, pregnancy augments GPER1‐induced vasodilation in rats. However, there is limited information on the potential interaction between GPER1 and pregnancy in the renal health later in life. We hypothesize that GPER1 signaling, and pregnancy confer protection against renal injury in aged female mice. In our study, 14‐16 months‐old GPER1 knock‐out (KO) and wild‐type (WT) female mice with and without a history of former pregnancies were placed into metabolic cages for collection of 24h urine samples. Then, animals were euthanized, plasma and kidneys were harvested for assessment of renal injury. No significant differences in body weight were observed between groups. GPER1 deletion in virgin mice did not impact food intake or urinary Na+ excretion (UNaV). Former pregnancies reduced food intake (p=0.0003) and UNaV (p&lt;0.0001) in GPER1 KO mice. To assess renal function, we measured urinary albumin excretion and plasma creatinine (Cr). GPER1 deletion increased urinary albumin excretion in virgin mice (KO: 16.47±2.08; WT: 6.06±1.04 μg/day; n=6 &amp; 7 respectively; p=0.0005). Interestingly, prior pregnancies eliminated this genotypic difference in albuminuria (KO: 6.12±1.44; WT: 5.79±1.66 μg/day; n=6 &amp; 8 respectively; p=0.986). GPER1 deletion also resulted in higher plasma Cr level in virgin mice (KO: 1.36±0.08; WT: 0.97±0.05 mg/mL; n=6 &amp; 7 respectively; p=0.0018). Prior pregnancies decreased plasma Cr levels in GPER1 KO mice (0.84±0.10 mg/dL, n= 5; p= 0.0012). We also measured urinary excretion of endothelin (ET‐1) and aldosterone which are causally linked to renal injury. GPER1 KO elicited greater levels of urinary ET‐1 compared to WT virgin mice (0.37±0.06 vs.0.17±0.01 pg/day; n=6 &amp; 7, respectively; p=0.0063). Previous pregnancies lowered urinary levels of ET‐1 and aldosterone in GPER1 KO mice (ET‐1: p=0.0049; aldosterone: p=0.0099). Furthermore, histological assessment of kidney sections revealed diffuse proliferative glomerulonephritis (GN) with intracapillary hyaline/protein thrombi, in GPER1 KO virgin mice only. No significant acute tubular injury was observed in any group. Further experiments will determine blood pressure and characterize the glomerular lesions evident in aged GPER1 KO virgin mice. Overall, our data demonstrate significant glomerular injury (GN), greater plasma Cr and greater urinary levels of albumin and ET‐1 in GPER1 KO virgin mice compared to WT virgin and previously‐pregnant GPER1 KO aged mice. The current data suggest that GPER1 and former pregnancies provide protection against glomerular injury in aged females.

Analysis of cadmium accumulation in community adults and its correlation with low-grade albuminuria

ObjectiveTo investigate the effects of chronic non-occupational exposure to cadmium (Cd) on renal injury in residents living in the urban areas of China. MethodsIn this cross-sectional study, we recruited 1000 participants in Shanghai from August 2015 to August 2017 and collected data on their socio-demographic characteristics, lifetime occupation, and lifestyle factors. The urinary Cd, urinary albumin, urinary creatinine, serum creatinine, urea, and uric acid levels were tested, and 683 participants completed those measurements. ResultsThe median urinary Cd concentration of this study population was 0.77 μg/g. The urinary Cd concentration was significantly higher in the female, older, and lower body mass index populations. There were 148 participants with dominant albuminuria who had higher urinary Cd levels than those without dominant albuminuria (0.98 vs. 0.72 μg/g; P < 0.001). Among participants without dominant albuminuria, there were 134 participants with low-grade albuminuria (13.84 ≤ ACR < 30 mg/g) and 401 participants who had normal urinary albumin excretion (ACR < 13.84 mg/g). Compared with those who had normal urinary albumin excretion, those with low-grade albuminuria had significantly higher urinary Cd levels (0.83 vs. 0.69 μg/g; P < 0.001). Among those without dominant albuminuria, participants in the highest quartile of urinary Cd were more likely to have low-grade albuminuria than those in the lowest quartile (Odd's ratio = 2.98; P < 0.001). Further adjustment for age, sex, and BMI or other potential confounding factors did not change the magnitudes of the associations. Moreover, we conducted multivariable stepwise linear regression analysis within 134 low-grade albuminuria participants and demonstrated that urinary Cd concentration (P < 0.001) were independent determinants of urine albumin after adjusting for relevant confounders. ConclusionThe urinary Cd levels observed in Chinese urban adults are substantial and associated with an increased risk of low-grade albuminuria. Our findings suggest that potential sources of environmental Cd exposure should be explored, and the associated renal toxicity should be studied in more detail in future.

328 Urine Biomarker Predictors of Incident Hospitalization in People Living with HIV

OBJECTIVES/GOALS: This study aims to determine 1) which urine biomarkers of kidney health measured in the ambulatory setting predict incident hospitalization; 2) to determine whether time-updated measures of ambulatory urine biomarkers and their changes/trajectories have added value over baseline alone. METHODS/STUDY POPULATION: Participants in the Predictors of Acute Renal Injury Study (PARIS), a prospective cohort of 478 HIV+ patients followed at the Johns Hopkins HIV Clinic, had sociodemographic, clinical data, and biosamples taken until hospitalization or up to 3 years annually. Among those hospitalized, clinical data and biosamples were collected serially during hospitalization and at 3 and 12 months post-discharge. For each of the 10 biomarkers measured, we will evaluate the association of the biomarker and risk of incident hospitalization using Cox hazards regression, adjusting for sociodemographics, comorbidities, HIV history, and medications. Biomarkers will be evaluated at baseline and as time-updated and change over time. RESULTS/ANTICIPATED RESULTS: We anticipate that higher baseline levels and increasing levels of urine albumin, α1M, β2M, NGAL, IL-18, KIM-1, MCP-1, YKL-40 will be independently associated with increased risk of incident hospitalization whereas higher and increasing levels of uromodulin and EGF will be associated with lower risk of incident hospitalization. These biomarkers collectively capture the following dimensions of kidney health: endothelial injury, tubular injury and function, inflammation, and fibrosis. We anticipate increased risk of incident hospitalization in HIV+ persons in the highest tertile of baseline, time-updated, and change over time biomarkers, relative to those within the lowest tertile. DISCUSSION/SIGNIFICANCE: This study will improve our understanding of the evolution of biomarkers of kidney health from the ambulatory to the hospitalized setting and will quantify the clinical implications of subclinical kidney damage among people living with HIV, a high-risk patient population with unique kidney pathophysiology.

Steatosis is involved in the progression of kidney disease in a high-fat-diet-induced non-alcoholic steatohepatitis mouse model.

Chronic kidney disease (CKD) and non-alcoholic steatohepatitis (NASH) are major health issues associated with the metabolic syndrome. Although NASH is a known risk factor of CKD, the mechanisms linking these two diseases remain poorly understood. We aimed to investigate alterations in the kidney complicated with dyslipidemia in an established NASH mouse model. Male C57BL6/J mice were fed with control diet or high-fat diet (HFD), containing 40% fat, 22% fructose, and 2% cholesterol for 16 weeks. Metabolic characteristics, histological changes in the kidney, endoplasmic reticulum (ER) stress, apoptosis, and fibrosis were evaluated by histological analysis, immunoblotting, and quantitative reverse transcription-polymerase chain reaction. Levels of serum aspartate aminotransferase, alanine aminotransferase, alkali-phosphatase, total cholesterol, and urinary albumin were significantly higher in mice fed with HFD. Remarkable steatosis, glomerular hypertrophy, and interstitial fibrosis were also shown in in the kidney by leveraging HFD. Furthermore, HFD increased the mRNA expression levels of Casp3, Tgfb1, and Nfe2l2 and the protein level of BiP. We observed the early changes of CKD and speculate that the underlying mechanisms that link CKD and NASH are the induction of ER stress and apoptosis. Further, we observed the activation of Nfe2l2 in the steatosis-induced CKD mouse model. This NASH model holds implications in investigating the mechanisms linking dyslipidemia and CKD.

Preclinical evidence of the effect of quercetin on diabetic nephropathy: A meta-analysis of animal studies

Quercetin, which is present in numerous fruits and vegetables, has shown promise in improving inflammation, lipid profiles, and blood pressure in humans. However, the efficacy of quercetin in diabetic nephropathy (DN) remains preclinical and unclear. Therefore, a meta-analysis based on preclinical animal data is needed to assess the efficacy, optimal dosage, and underlying mechanism of DN treatment to accelerate new drug research and clinical translation. We conducted a literature search in PubMed, Embase, Web of Science, and Cochrane Library to retrieve randomized controlled trials evaluating the effects of quercetin in rat or mouse diabetic models. We assessed the quality of the studies individually according to SYRCLE's risk of bias tool for animal studies. Twenty animal studies, including 378 animals, were included in the meta-analysis. Meta-analysis data showed that renal function indices, such as renal index, urine protein, uric acid, urine albumin, and serum creatinine levels, significantly improved with quercetin administration. However, no significant association was observed between quercetin and creatinine clearance. Quercetin remarkably alleviated oxidative stress by reducing malondialdehyde (MDA) and increasing superoxide dismutase (SOD) and catalase (CAT) activities. In addition, quercetin exhibits anti-inflammatory activity by reducing tumor necrosis factor-α（TNF-α）and interleukin-1β（IL-1β）levels. Subgroup analysis performed using quercetin doses and animal species indicated that animal species were a source of heterogeneity. This meta-analysis suggests that quercetin is a promising drug for DN treatment, facilitating clinical prediction and therapy.

The effects of two different dietary regimens during exercise on outcome of experimental acute kidney injury

BackgroundAcute kidney injury (AKI) is a syndrome characterized by rapid loss of excretory function of kidney. Both exercise and some diets have been shown to increase silent information regulator (SIRT1) expression leading to reduction of kidney injury. In this study, the effect of two different diets during exercise on kidney function, oxidative stress, inflammation and also SIRT1 in AKI was investigated.Materials and methodsA number of rats were randomly divided into four groups; control without exercise, control with exercise, exercise + calorie restriction (CR), and exercise + time restriction (TR). Each group was divided into two subgroups of without AKI and with AKI (six rats in each group). Endurance exercise and diets were implemented before AKI. Serum urea and creatinine, urinary albumin, kidney malondialdehyde (MDA), total antioxidant capacity (TAC), transforming growth factor (TGF-β1), and SIRT1 levels, glomerular filtration rate (GFR) and relative kidney weight were measured before and 24 h after AKI induction.ResultsAfter induction of kidney injury, serum urea and creatinine, urinary albumin, kidney MDA and TGF-β1 levels increased in rats with both previous exercise and no previous exercise, while GFR, and kidney TAC and SIRT1 levels significantly decreased. These changes after AKI were less in the group with previous exercise than in the group that had no exercise (p <0.001). The TR diet during exercise caused a less increase in serum urea (p <0.01) and creatinine (p <0.01), and urinary albumin (p <0.001) levels after the injury compared to the just exercise group. Also, both CR and TR diets during exercise caused less change in MDA (p <0.001) and TAC (p <0.05, p <0.001, respectively) levels compared to just exercise group.ConclusionsThe results showed that exercise alone had no effect on preventing function impairment of kidney, oxidative stress, inflammation and also SIRT1 alteration following AKI, although these indexes were less among those with exercise than those without exercise. However, when the CR and TR diets were implemented during exercise, strong renoprotective effects appeared, and the protective effect of TR diet was greater.

Renal Parameters in Mild, Moderate, and Chronic Cigarette Smokers

Objective: To explore the link between cigarette smoking and kidney function through renal parameter assessment. Methods: The present study was performed at the Department of Biochemistry Santosh Medical College, Ghaziabad, India, from September 2019 to April 2021. In this study, 140 subjects were included, out of which 35 were non-smokers, 35 smoked &lt;5 cigarette per day, 35 smoked 5-10 cigarette per day, and the remaining 35 smoked more than 10 cigarettes per day. Results: Blood urea, serum creatinine, urinary albumin, and uACR levels were found to increase significantly (p&lt;0.001) in smokers as compared to non-smokers. These increases were higher among chronic cigarette smokers (p&lt;0.001) as opposed to mild and moderate smokers. In contrast, serum uric acid, e-GFR, and urinary creatinine levels decreased significantly (p&lt;0.001) in smokers when compared to non-smokers, with a higher decrease observed in chronic cigarette smokers (p&lt;0.001) as opposed to the mild and moderate cigarette smokers. Conclusion: Alterations in urinary albumin, serum urea, serum creatinine, urinary creatinine, and e-GFR are associated with the risk of renal dysfunction.