Urinary Albumin Levels Research Articles

Cardiorenal damages in mice at early phase after intervention induced by angiotensin II, nephrectomy, and salt intake.

The interconnection of heart performance and kidney function plays an important role for maintaining homeostasis through a variety of physiological crosstalk between these organs. It has been suggested that acute or chronic dysfunction in one organ causes dysregulation in another one, like patients with cardiorenal syndrome. Despite its growing recognition as global health issues, still little is known on pathophysiological evaluation between the two organs. Previously, we established a preclinical murine model with cardiac hypertrophy and fibrosis, and impaired kidney function with renal enlargement and increased urinary albumin levels induced by co-treatment with vasopressor angiotensin II (A), unilateral nephrectomy (N), and salt loading (S) (defined as ANS treatment) for 4 weeks. However, how both tissues, heart and kidney, are initially affected by ANS treatment during the progression of tissue damages remains to be determined. Here, at one week after ANS treatment, we found that cardiac function in ANS-treated mice (ANS mice) are sustained despite hypertrophy. On the other hand, kidney dysfunction is evident in ANS mice, associated with high blood pressure, enlarged glomeruli, increased levels of urinary albumin and urinary neutrophil gelatinase-associated lipocalin, and reduced creatinine clearance. Our results suggest that cardiorenal tissues become damaged at one week after ANS treatment and that ANS mice are useful as a model causing transition from early to late-stage damages of cardiorenal tissues.

A Network Pharmacology Approach to Understand the Action Mechanisms of the TangShenKangPing Decoction for Diabetic Nephropathy Treatment

ABSTRACT Background: TangShenKangPing decoction (TSKPD) has been used to treat patients with diabetic nephropathy (DN) for more than 10 years. However, its active ingredients and their pharmacological mechanisms of action remain unclear. In this study, we aimed to identify the key targets, major active ingredients, and pathways of TSKPD using network pharmacology. Methods: Human phenotypic disease, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed and 37 candidates targets of 40 active TSKPD ingredients were identified. Enrichment analyses revealed that TSKPD reduced podocyte apoptosis via vitamin metabolic processes, regulated the inflammatory response via the advanced glycation end product–receptor for AGE (AGE-RAGE) signaling, and reduced abnormal angiogenesis via vascular endothelial growth factor (VEGF) signaling in patients with DN. Furthermore, we verified the therapeutic roles and action mechanism of TSKPD in db/db mice with DN. The medicine was administered via gavage for 12 weeks. Fasting blood glucose, blood lipid, pro-inflammatory cytokine, and 24 h urinary albumin levels and pathological alterations in the renal tissues were evaluated. KHDRBS1, NLRP3 and VEGF relative mRNA and protein expression levels in renal tissues were determined using reverse transcription-quantitative olymerase chain reaction (RT-qPCR) and western blotting, respectively. Results: Treatment with TSKPD decreased proteinuria and lipid levels in the serum, significantly decreased the kidney weight, ameliorated renal histopathological alterations, and reduced pro-inflammatory cytokine expression and oxidative stress in db/db mice. Conclusion: TSKPD exerts therapeutic effects by regulating multiple factors, reducing oxidative stress and inflammation, and protecting the podocytes.

Urine Albumin/Creatinine Ratio and Serum Uric Acid as Predictors of Severity in Patients with Chronic Obstructive Pulmonary Disease

Background and Objective: As a global healthcare issue, Chronic Obstructive Pulmonary Disease (COPD) is mainly associated with smoking. Nonetheless, environmental and occupational issues are also linked to its development. The present study aimed to assess the urine albumin-to-creatinine ratio (ACR) and serum uric acid (SUA) levels as predictors of disease severity in COPD patients. Materials and Methods: This cross-sectional study was conducted on 67 patients diagnosed with COPD using the Global Initiative for Obstructive Lung Disease diagnostic criteria. The participants were patients who were either referred to the subspecialty clinic of the pulmonology and spirometry unit of Hamadan Shahid Beheshti Hospital or were hospitalized in the pulmonology ward. Blood and urine samples were taken from the COPD patients, and the serum uric acid, urine albumin, and urine creatinine levels were assessed and recorded in a checklist. The data were analyzed in SPSS software (version 23) at a significance level of 0.05. Results: In terms of gender, 5.7% of the participants were male and 34.3% were female. The mean age of patients was 61.77 years. The stages of disease severity in the patients were as follows: 20.89%, 22.38%, 5.73%, and 2.98% of cases had very severe, severe, moderate, and mild COPD, respectively. The regression analysis results demonstrated that SUA levels could significantly predict the FEV1 in COPD patients; nonetheless, urine ACR could not predict the FEV1 scores. Conclusion: As evidenced by the result of the present study, the FEV1 in COPD patients and disease severity could be predicted by the SUA levels. Therefore, it is recommended to consider monitoring and assessing non-pulmonary factors, especially SUA levels, in the treatment of COPD patients.

Glycolytic enzyme PFKFB3 regulates sphingosine 1-phosphate receptor 1 in proangiogenic glomerular endothelial cells under diabetic condition.

Glomerular angiogenesis is a characteristic feature of diabetic nephropathy (DN). Enhanced glycolysis plays a crucial role in angiogenesis. The present study was designed to investigate the role of glycolysis in glomerular endothelial cells (GECs) in a mouse model of DN. Mouse renal cortex and isolated glomerular cells were collected for single-cell and RNA sequencing. Cultured GECs were exposed to high glucose in the presence (proangiogenic) and absence of a vascular sprouting regimen. MicroRNA-590-3p was delivered by lipofectamine in vivo and in vitro. In the present study, a subgroup of GECs with proangiogenic features was identified in diabetic kidneys by using sequencing analyses. In cultured proangiogenic GECs, high glucose increased glycolysis and phosphofructokinase/fructose bisphosphatase 3 (PFKFB3) protein expression, which were inhibited by overexpressing miRNA-590-3p. Mimics of miRNA-590-3p also increased receptor for sphingosine 1-phosphate (S1pR1) expression, an angiogenesis regulator, in proangiogenic GECs challenged with high glucose. Inhibition of PFKFB3 by pharmacological and genetic approaches upregulated S1pR1 protein in vitro. Mimics of miRNA-590-3p significantly reduced migration and angiogenic potential in proangiogenic GECs challenged with high glucose. Ten-week-old type 2 diabetic mice had elevated urinary albumin levels, reduced renal cortex miRNA-590-3p expression, and disarrangement of glomerular endothelial cell fenestration. Overexpressing miRNA-590-3p via perirenal adipose tissue injection restored endothelial cell fenestration and reduced urinary albumin levels in diabetic mice. Therefore, the present study identifies a subgroup of GECs with proangiogenic features in mice with DN. Local administration of miRNA-590-3p mimics reduces glycolytic rate and upregulates S1pR1 protein expression in proangiogenic GECs. The protective effects of miRNA-590-3p provide therapeutic potential in DN treatment.NEW & NOTEWORTHY Proangiogenetic glomerular endothelial cells (GECs) are activated in diabetic nephropathy. High glucose upregulates glycolytic enzyme phosphofructokinase/fructose bisphosphatase 3 (PFKFB3) in proangiogenetic cells. PFKFB3 protects the glomerular filtration barrier by targeting endothelial S1pR1. MiRNA-590-3p restores endothelial cell function and mitigates diabetic nephropathy.

The Fruit and Veggies for Kidney Health Study: A Prospective Randomized Trial

Providing fruits and vegetables (F&Vs) to health care system patients with elevated urine albumin-creatinine ratio (ACR) reduced ACR, slowed chronic kidney disease (CKD) progression and reduced cardiovascular disease (CVD) risk factors in previous studies. This study evaluated a community-based strategy in lower-income populations to identify African Americans with elevated ACR before health care system involvement and sustain them in a 6-month F&V protocol with (F&V+Cook) and without (F&V Only) cooking instructions, with the hypothesis that adjuvant cooking instructions with F&Vs would further reduce ACR. Prospective, randomized, parallel 2-arm design. African American adults with ACR>10mg/g creatinine randomized to 1 of 2 study arms. Two cups/day of F&Vs with or without cooking instructions in participants followed 6 months. Participants sustaining the F&V protocol and between-group indicators of CVD risk, kidney injury, and dietary intake at 6 weeks and 6 months. A total of 142 African American adults (mean age, 57.0 years; ACR, 27.4mg/g; body mass index, 34.4; 24.9% CKD 1; 24.8% CKD 2; 50.4% CKD 3; 55% female) randomized to F&V Only (n=72) or F&V+Cook (n=70), and 71% were retained at 6 months. Participants received 90% of available F&V pick-ups over 6 weeks and 69% over 6 months. In the adjusted model, 6-month ACR was 31% lower for F&V+ Cook than F&V Only (P=0.02). Net 6-week F&V intake significantly increased and biometric variables improved for participants combined into a single group. Small sample size, low-baseline ACR, and potential nonresponse bias for 24-hour dietary recall measure. These data support the feasibility of identifying community-dwelling African Americans with ACR indicating elevated CVD and CKD risk and sustaining a F&V protocol shown to improve kidney outcomes and CVD risk factors and provides preliminary evidence that cooking instructions adjuvant to F&Vs are needed to lower ACR. National Institute on Diabetes, Digestive, and Kidney Diseases grant "Reducing chronic kidney disease burden in an underserved population" (R21DK113440). NCT03832166. African Americans, particularly those in low-income communities, have increased rates of chronic kidney disease (CKD) with worsening outcomes over time. Giving fruits and vegetables to individuals with CKD identified in health care systems was previously shown to reduce kidney damage, measured by urine protein albumin, and slow kidney function decline. We recruited African Americans in low-income communities with increased urine albumin levels. They received fruits and vegetables for 6 months, and we tested whether added cooking instructions further reduced urine albumin levels. Most participants continued to receive fruits and vegetables throughout the 6 months. Those given cooking instructions had lower urine albumin levels after 6 months, indicating decreased kidney damage. Providing cooking instructions with fruits and vegetables appears to lessen kidney damage more than just fruits and vegetables alone.

Severe kidney dysfunction in sialidosis mice reveals an essential role for neuraminidase 1 in reabsorption.

Sialidosis is an ultra-rare multisystemic lysosomal disease caused by mutations in the neuraminidase 1 (NEU1) gene. The severe type II form of the disease manifests with a prenatal/infantile or juvenile onset, bone abnormalities, severe neuropathology, and visceromegaly. A subset of these patients present with nephrosialidosis, characterized by abrupt onset of fulminant glomerular nephropathy. We studied the pathophysiological mechanism of the disease in 2 NEU1-deficient mouse models, a constitutive Neu1-knockout, Neu1ΔEx3, and a conditional phagocyte-specific knockout, Neu1Cx3cr1ΔEx3. Mice of both strains exhibited terminal urinary retention and severe kidney damage with elevated urinary albumin levels, loss of nephrons, renal fibrosis, presence of storage vacuoles, and dysmorphic mitochondria in the intraglomerular and tubular cells. Glycoprotein sialylation in glomeruli, proximal distal tubules, and distal tubules was drastically increased, including that of an endocytic reabsorption receptor megalin. The pool of megalin bearing O-linked glycans with terminal galactose residues, essential for protein targeting and activity, was reduced to below detection levels. Megalin levels were severely reduced, and the protein was directed to lysosomes instead of the apical membrane. Together, our results demonstrated that desialylation by NEU1 plays a crucial role in processing and cellular trafficking of megalin and that NEU1 deficiency in sialidosis impairs megalin-mediated protein reabsorption.

COMPARISON BETWEEN RENOPROTECTIVE EFFECTS OF FEBUXOSTAT AND ALLOPURINOL IN CHRONIC KIDNEY DISEASE PATIENTS WITH HYPERURICEMIA

Objective: The objective of the study was to compare the renoprotective effects of febuxostat versus allopurinol in chronic kidney disease patients with hyperuricemia. Methods: One hundred and ten patients were divided randomly into two equal groups: group F (febuxostat) and group A (allopurinol). Group F patients received tablet febuxostat 40 mg OD for 4 months and group A patients received tablet allopurinol 100 mg TDS for 4 months. Following parameters such as estimated glomerular filtration (eGFR) assessment, serum creatinine, serum uric acid (SUA), total serum protein, urine creatinine, urine protein, blood urea, and number of dialysis were carried out and repeated at the end of 1st–4th month to check for the effect of the test drugs on the status of kidney function. Observations: Febuxostat caused more rise in eGFR than allopurinol. Meanwhile, the number of patients with eGFR ≤15/mL/min/1.73 m2 showed no difference between the groups. No patient showed >10% decrease in the eGFR values. Febuxostat showed more decline in SUA levels than allopurinol, although the number of patients reaching the target SUA levels was the same in both groups. Febuxostat led to a more reduction in serum creatinine levels than allopurinol. Urine creatinine and urine albumin levels decline were associated more with febuxostat. No remarkable difference in comparison of both the groups in terms of total serum protein and serum globulin, although a significant rise was seen with febuxostat in serum albumin levels. Both drugs had a similar sequel in declining blood urea nitrogen levels. No discernible difference in the number of dialysis sessions needed by patients in the previous month was seen in the study groups. Conclusion: The present study concluded that febuxostat appears to be a better alternative to allopurinol for chronic kidney disease patients with hyperuricemia. Febuxostat has a superior renoprotective effect than allopurinol.

Protective effect of eriodictyol against hyperglycemia-induced diabetic nephropathy in rats entails antioxidant and anti-inflammatory effects mediated by activating Nrf2

The pathogenesis of diabetic nephropathy (DN) involves cellular activation of oxidative stress and inflammation. Eriodictyol is a citrus-derived flavonoid with multiple pharmacological and protective effects in various conditions. The protective role of Eriodictyol against diabetes and diabetic nephropathy is less investigated. The current research aimed to explore the role of eriodictyol in protecting against DN prompted by streptozotocin in male rats and investigate some possible mechanisms of action. Diabetes was brought about in rats by an i.p injection of a lone dose (65 mg/kg). Five groups of rats were included (n = 8 each) as control (non-diabetic), eriodictyol (20 mg/kg, orally), STZ-diabetic, STZ + eriodictyol (20 mg/kg, orally), and STZ + eriodictyol (20 mg/kg, orally) + ML385 (30 µg/kg, i.p.). Kidney histology and the levels of some markers of kidney function, renal oxidative stress, and renal inflammation were analyzed in all groups of rats. Treatment with eriodictyol prevented the damage in the renal glomeruli and tubules and reduced renal immune cell infiltration in STZ-treated animals. It also spiked urinary creatinine excretion and reduced urine volume and urinary levels of albumin, monocyte chemoattractant protein 1 (MCP-1), urinary kidney injury molecule-1 (KIM-1), and nephrin in these diabetic rats. In addition, eriodictyol stimulated the nuclear protein accumulation of Nrf2 and boosted the expression of superoxide dismutase (SOD), glutathione (GSH), heme oxygenase-1 (HO-1), and catalase (CAT) in the diabetic rat kidneys. In concomitance, it reduced the nuclear levels of NF-κB and levels of interleukine-6 (IL-6), malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) and attenuated the reduction in renal ATP levels and the increase in the mitochondria transition pore opening (mtTPT). However, the administration of eriodictyol did not affect rats’ body weights and fasting glucose and insulin levels but significantly reduced serum levels of cholesterol, triglycerides, LDL-c, and oxidized LDL-c (ox-LDL-c). In conclusion, eriodictyol prevents STZ-induced nephropathy by a hypolipidemic effect and concomitant antioxidant and anti-inflammatory effects mediated by activating Nrf2/NF-κB/antioxidant axis.

THU388 Insulin Edema Associated With Glargine: A Case Report And Brief Review Of Literature

Abstract Disclosure: J. Wood: None. V. Samji: None. F.S. Celi: None. P. Majety: None. Introduction: Insulin edema is an uncommon and poorly understood complication of insulin therapy in patients with diabetes. We report a patient with type 1 diabetes (T1DM) who developed edema within days of initiating insulin glargine that resolved with discontinuation of this medication. Case Report: A 20-year-old man with no past medical history presented with nausea, vomiting, polydipsia, and a 15-pound weight loss and was noted to have a hemoglobin A1c greater than 14.0%. Diabetic ketoacidosis (DKA) was ruled out and was started on weight-based insulin therapy with glargine and lispro three units with meals. Additional diabetes workup was notable for positive Anti-IA2 antibodies. Blood glucose levels improved prior to discharge. A week after discharge, he complained of swelling of limbs. Patient denied any shortness of breath, cough, chest pain, orthopnea, or nocturnal dyspnea. He was found to have extensive 2+ pitting edema in bilateral feet extending up to his calves. Dorsalis Pedis pulses were 2+ bilaterally. No warmth or erythema of legs was noted. His weight in clinic was 70.2 kg (154.4 lbs), up 11.6 kg (25.5 lbs) ten days post discharge. Evaluation for bilateral pedal edema was performed. Labs were notable for normal liver enzymes, creatinine, glomerular filtration rate and urine albumin levels, ruling out hepatic and renal causes of edema. Thyroid function tests were normal. His presentation was discussed with cardiology and brain natriuretic peptide level was drawn which was also normal. No further cardiac workup was recommended at that time given the patient’s history and lack of other clinical signs or symptoms of heart failure. After ruling out other systemic causes of edema in our patient, a diagnosis of insulin edema was made. Based on prior case reports of glargine associated insulin edema, he was switched from insulin glargine to insulin degludec. He noted significant improvement within 24 hours of switching insulin with a 6.4-pound weight loss in just one day and complete resolution of edema within 3 days. He had no recurrence of edema once glargine was discontinued despite increasing insulin dosing for glycemic control. Conclusion: The pathophysiology of insulin edema is unclear. Insulin’s role in renal sodium handling, vasodilation, and increased vascular permeability, have been postulated as possible mechanisms. Risk factors for developing insulin edema include T1DM, high A1C, high dose of insulin, rapid correction of hyperglycemia, DKA on presentation and poor nutritional status. Additional risk factors for developing insulin edema include thiamine deficiency and an underlying genetic predisposition related to a mitochondrial mutation, although this seems to be rare. Insulin edema is a diagnosis of exclusion. Clinicians should be aware of this rare complication, and its occurrence should be documented and differentiated from other causes of edema. Presentation: Thursday, June 15, 2023

THU257 Retrospective Analysis Of Hemoglobin A1c Utility At A SafetyNet County Hospital

Abstract Disclosure: J. Joseph: None. I.A. Hashim: None. Background: Diabetes remains a prevalent chronic health condition. Measurement of glycated hemoglobin (A1c) is central to both diagnosis and to monitoring response to therapy and hence the extent of diabetes control. Use of A1c continues to increase in compliance with recommendations by the American Diabetes Association. The utility of A1c measurement at a large SafetyNet county hospital was assessed. In this analysis, our goal is to help guide utilization of A1c testing. Method: All A1c values performed over a period of 14 months between January 2021 to March 2022 were retrieved from the electronic health records system (Beaker, EPIC®). Statical analysis of all A1c data were performed using Excel Microsoft® and NCSS statistical software. A1c data were analyzed for prevalence of abnormalities (>6.5%). Results: A total of 28,760 A1c measurements were performed during the study period. Overall values ranged from 0.06% to >17.6% (Median 6.1%). Patients with A1c <5.7% (n=9535) representing 33% of tested patients. Patients with A1c values between 5.7% and 6.5% (n=7619) representing 26% of patients. Patients with A1c values between 6.5% and 11.0% (n = 10,001) representing 35% of patients. Patient in control with A1c values between 6.5% and 7.5% (n=1350) represented 35.8% of the diabetic population. Those poorly controlled A1c >9% (n=734) represented 19.4% of patients. The remaining patients (n=1605) representing 6% of patients had A1c values >11%. Conclusion: A1c testing is widely practiced with 35 % of patients being diabetic. A1c measurement identified 26% of patients in the pre-diabetic stage and that 33% were non-diabetic. The high HbA1c among some patients indicate a need for more proactive approach to their management. The high percentage of the measured population had A1c below 5.7% and thus raises the question of whether routine screening of A1c is cost-effective. Additional analysis for diabetic patients for degree of control and for assessment of urinary albumin levels is required. Presentation: Thursday, June 15, 2023

Fuling-Zexie formula attenuates hyperuricemia-induced nephropathy and inhibits JAK2/STAT3 signaling and NLRP3 inflammasome activation in mice

Ethnopharmacological relevanceFuling-Zexie (FZ) formula, a traditional Chinese herbal prescription composed of Poria cocos (Schwan.) Wolf. (Poria), Pueraria lobate (Willd.) Howe. (Puerariae Lobatae Radix), Alisma orientale (Sam.) Julep. (Alismatis Rhizoma), and Atractylodes lancea (Thunb.) Dc. (Atractylodis Rhizoma), has been clinically used to ameliorate hyperuricemia (HUA) and its associated renal injury. Aim of studyThis study aims to explore the action and mechanism of FZ on renal inflammation and dysfunction caused by HUA. Materials and methodsFZ was orally administered to rapid HUA mouse induced by potassium oxonate (PO) and hypoxanthine (HX) for 7 days. Serum levels of uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), xanthine oxidase (XOD), adenosine deaminase (ADA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urine levels of UA, CRE and urinary albumin were determined by biochemical assays. Serum levels of interleukin (IL)-1β and IL-6 were tested by ELISA. Hematoxylin-eosin and Masson staining were used to examine kidney and liver histopathological alterations. The expressions of renal glucose transporter 9 (GLUT9), ATP-binding cassette subfamily G member 2 (ABCG2), organic anion transporter 1 (OAT1), phospho-janus kinase 2 (p-JAK2), p-signal transducer and activator of transcription 3 (p-STAT3), suppression of cytokine signaling 3 (SOCS3), NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and cleaved-cysteinyl aspartate specific proteinase-1 (cleaved-Cas-1) were detected by western blots. The potential protein targets and pathways of FZ intervention on HUA were predicted by network pharmacology. The constituents in FZ aqueous extract were analyzed by UPLC-MS. ResultsFZ reduced serum UA, CRE, BUN, and urinary albumin and increased urine UA, CRE levels in HUA mice. In addition, the treatment with FZ to HUA mice inhibited the elevated serum levels of XOD and ADA, and regulated renal urate transports including OAT1, GLUT9 and ABCG2. FZ also attenuated kidney inflammation and fibrosis and downregulated the expressions of IL-1β, p-JAK2, p-STAT3, SOCS3, IL-6, NLRP3, ASC, and cleaved-Cas-1. Thirteen compounds were identified in the FG, including L-phenylalanine, D-tryptophan, 3′-hydroxypuerarin, Puerarin, 3′-Methoxy Puerarin, Daidzin, Pueroside A, formononetin-8-C- [xylosyl (1→6)]-glucoside, Ononin, Alisol I 23-acetate, 16-oxo-alisol A, Alisol C and Alisol A. ConclusionFZ inhibits serum UA generation and promotes urine UA excretion as well as attenuates kidney inflammation and fibrosis in HUA mouse with nephropathy. The underlying mechanism of its action may be associated with suppression of the JAK2/STAT3 signaling pathway and NLRP3 inflammasome activation. This formula may offer a novel source for developing anti-HUA drugs.

Description of Albuminuria Levels in Patients with Type 2 Diabetes Mellitus According to Length of Diagnosis at West Nusa Tenggara Provincial Hospital

Albuminuria is a condition in which there is albumin in the urine, albuminuria often occurs in patients with type 2 DM which occurs due to persistently elevated blood sugar levels and poor glycemic control. This will risk the occurrence of complications of them diabetic nephropathy but it takes about 5-10 years after the diagnosis of DM is established to become a significant problem of kidney damage. The purpose of this study was to find out how the description of albuminuria levels in patients with type 2 DM based on the duration of diagnosis at RSUP NTB. The method used was analytic observation with a cross sectional design. The results of this study analyzed 30 subjects, consisting of 14 men (47%) and 16 women (53%) with an age range of 30-71 years, with the prevalence of urine albumin levels based on the duration of being diagnosed with type 2 diabetes, which is ≤ 5 years. DM ≥ 5 years with a prevalence of 3 (10%) samples having normoalbuminuria levels, 18 (60%) samples having micro albuminuria levels, and 3 (10%) samples having macro albuminuria levels

CLINICAL STUDY TO EVALUATE THE NEPHROPROTECTIVE EFFECT OF ELADI CHURNA IN DIABETIC KIDNEY DISEASE.

Diabetic Kidney Disease is now a worldwide health crisis. It is a spectrum of different pathophysiologic processes associated with abnormal kidney function and a progressive decline in glomerular filtration rate. Globally it is the 12th cause of death and 17th cause of disability. Clinically this condition can be correlated to Madumeha and Mutrakshaya. The present study focuses on the efficacy of the Poly herbo-mineral compound, Eladi Churna in the nephroprotective effect in DKD. Consent from all the selected patients was taken before the study. Ethical clearance was accredited by the Government Ayurvedic college and Hospital, Guwahati Assam and CTRI registration was done for the trial. The patients were given the trial drug 1gm twice daily after food with Tandulodak 25 ml and Swadangstradi kwath 25 ml as Anupana for 3 months. A marked improvement was found in eGFR, Serum Creatinine, Blood Urea and Urine Albumin levels. Satisfactory results were noted in chief complaints like urine output, oedema, nausea, vomiting and muscle cramps and Serum Uric acid level. No change was observed in Serum Sodium and Serum Potassium levels at the end of the course.

A Cross-Sectional Study on the Estimation of Urine Albumin for the Early Diagnosis of Diabetic Nephropathy Among Patients With Diabetes Mellitus at a Tertiary Care Hospital in Central India.

Background Diabetic nephropathy is a significant concern among individuals with diabetes mellitus, warranting early diagnosis for effective management. This study focuses on the potential of urine albumin estimation as an early diagnostic tool for diabetic nephropathy among patients in central India. Methods A cross-sectional methodology involved 65 individuals diagnosed with diabetes mellitus at a tertiary care hospital. Demographic factors, including age, gender, family history, duration of diabetes, and dietary patterns, were gathered. Urine albumin levels were categorized as "normal," "microalbuminuria," and "macroalbuminuria." The collected data were analyzed using IBM SPSS Statistics, version 24.0 (IBM Corp., Armonk, NY). Qualitative variables were presented as percentages and counts. The comparison between groups was conducted using the chi-square exact test. Quantitative variables were described as mean (±standard deviation) and median. Results The study reveals that 78.5% of cases exhibited normal levels below 30 mg, with a mean value of 1.00 ± 0.414. Microalbuminuria, characterized by 30-300 mg levels, was observed in 21.5% of cases. Importantly, no instances of macroalbuminuria, with levels exceeding 300 mg, were detected among the participants.There are associations between demographic variables and diabetic nephropathy findings. Age and gender displayed non-significant associations. Family history of diseases, particularly diabetes, showed significance. Diabetes duration demonstrated a significant link, while diet patterns displayed no significant associations. Conclusion This study contributes insights into the complex interactions of demographic factors in diabetic nephropathy. Early identification and intervention, guided by the associations observed, could enhance patient outcomes and mitigate the burden of diabetic nephropathy-related complications. Further research is warranted to validate and extend these findings to diverse populations.

Abstract P221: Soluble (pro)renin Receptor Contributes To 2-kidney, 1-clip-induced Renovascular Hypertension And Ischemic Nephropathy In Mice

The Goldblatt two-kidney, one-clip (2K1C) model features renovascular hypertension and ischemic nephropathy due to overactivated renin-angiotensin system (RAS). Soluble (pro)renin receptor (sPRR), the extracellular domain of (pro)renin receptor (PRR), is primarily generated by site-1 protease (S1P) and implicated as a potential regulator of the RAS and renal function. Here, we examined the function and underlying mechanism of sPRR in 2K1C model by pharmacological inhibition of S1P and genetic mutagenesis of S1P cleavage site. Male 2-mo-old C57BL/6 mice were subjected to the 2K1C procedure or sham operation for 1 month, followed by a 14-day infusion of vehicle or a specific S1P inhibitor PF429242 (PF) (30 mg/kg/day via minipump). The 2K1C procedure induced a 2-fold increase in plasma sPRR, which was reduced by 50% following PF treatment. This was paralleled by improvement of renovascular hypertension (MAP:142.1±1.3 vs. 129.9±2.8mmHg, n=7, p < 0.05) and cardiac hypertrophy (HW/BW:6.3±0.3 vs. 5.0 ± 0.3mg/g, n=7, p < 0.01) accompanied with suppressed cortical and medullary renin activity, active renin content, prorenin content and total renin content in clipped kidney. Meanwhile, cortical and medullary renin mRNA level in clipped kidney was increased 3.8-fold and 5.3-fold, which was reduced by 41% and 55% respectively, following PF treatment. The level of urinary albumin, KIM-1 and NGAL was elevated 5.1-fold, 4.0-fold and 5.7-fold after 2K1C surgery, which was blunted 35%, 49% and 59%, respectively, following PF treatment. Secondly, we employed a novel mouse model with mutagenesis of the cleavage site in PRR (termed as Mutant mice) to verify the role of endogenous sPRR in 2K1C model. Similarly, the hypertensive response and ischemic nephropathy of Mutant mice to 2K1C procedure was blunted (24-day MAP: 2K1C/WT 142.5±2.1 vs. 2K1C/Mutant 128.2±3.2mmHg; 24-day urinary albumin/creatinine: 2K1C/WT 64.9±7.2 vs. 2K1C/Mutant 33.0±1.9mg/g, n=6, p < 0.05), in parallel with attenuated response of systemic and intrarenal RAS. Together, consistent results with the different approaches have established an important role of S1P-derived sPRR in regulation of the RAS and thus the pathogenesis of 2K1C-induced renovascular hypertension and ischemic nephropathy.

Early Detection of Preeclampsia Through Urine Protein Examination as a Means of Maternal Emergency Prevention

A decrease in urine albumin levels in pregnant women, which can be checked through urine protein examination, is an indicator used to determine whether a pregnant woman is experiencing preeclampsia. Preeclampsia has become a cause of increasing morbidity and mortality rates which affects both mothers and newborns. This research aimed to early detect the preeclampsia through urine protein examination and see the correlation between the characteristics of the research subjects and urine protein. Used a descriptive design with a correlational design, the urine protein from 36 pregnant women was examined in their second and third trimesters of pregnancy. Next, univariate analysis was carried out and Spearman Correlation test was used in bivariate analysis for abnormally distributed ordinal data while the Contingency Coefficient Correlation test was carried out for data that used abnormally distributed nominal scale. Based on the bivariate analysis, the variables of age, education, employment, and obstetric history obtained a significant value of p value>0,05, showed no correlation with urine protein. Contrarily, the blood pressure variable had a significant value of p 0,049 < 0,05. Pregnant women in gestational age of >20 weeks with high blood pressure must examine the urine protein immediately to early detect preeclampsia and prevent maternal emergencies.

Iron Chelator Deferoxamine Alleviates Progression of Diabetic Nephropathy by Relieving Inflammation and Fibrosis in Rats.

Diabetic nephropathy (DN) is one of the most devastating diabetic microvascular complications. It has previously been observed that iron metabolism levels are abnormal in diabetic patients. However, the mechanism by which iron metabolism levels affect DN is poorly understood. This study was designed to evaluate the role of iron-chelator deferoxamine (DFO) in the improvement of DN. Here, we established a DN rat model induced by diets high in carbohydrates and fat and streptozotocin (STZ) injection. Our data demonstrated that DFO treatment for three weeks greatly attenuated renal dysfunction as evidenced by decreased levels of urinary albumin, blood urea nitrogen, and serum creatinine, which were elevated in DN rats. Histopathological observations showed that DFO treatment improved the renal structures of DN rats and preserved podocyte integrity by preventing the decrease of transcripts of nephrin and podocin. In addition, DFO treatment reduced the overexpression of fibronectin 1, collagen I, IL-1β, NF-κB, and MCP-1 in DN rats, as well as inflammatory cell infiltrates and collagenous fibrosis. Taken together, our findings unveiled that iron chelation via DFO injection had a protective impact on DN by alleviating inflammation and fibrosis, and that it could be a potential therapeutic strategy for DN.

The diagnostic value of lipoprotein-associated phospholipase A2 in early diabetic nephropathy.

The aim of this study was to investigate diagnosis of lipoprotein-associated phospholipase A2 (Lp-PLA2) in early diabetic nephropathy (DN). A total of 342 type 2 diabetes mellitus (T2DM) patients hospitalized in department of metabolism and nephrology in our hospital from January 2019 to December 2019 were randomly selected. Patients were divided into three groups via urine albumin level: diabetes mellitus (DM) group, simple diabetes group (114 patients, urinary albumin creatinine ratio (UACR)<30 mg/g); DN1 group, early DN group (114 patients, UACR: 30-300 mg/g); DN2 group: clinical DN group (114 patients, UACR > 300mg/g). Eighty healthy adults were examined at the same time. Lp-PLA2, fasting blood glucose (FBG), creatinine (Cr), triglyceride (TG), total cholesterol (TCHOL), high-density lipoprotein (HDL), low-density lipoprotein (LDL), haemoglobin A1c (HbA1c), blood urea nitrogen/creatinine (BUN/Cr), estimated glomerular filtration rate (eGFR), 24-h urine protein, albumin and creatinine of all subjects were detected and compared. Pearson's correlation analysis and multiple ordered logistic regression were used to investigate the correlation between serum Lp-PLA2 level and DN. The possibility of Lp-PLA2 in the diagnosis of early DN was studied by using the subject working curve. Lp-PLA2 level in DN1 and DN2 groups was significantly higher than that in DM group, with statistical difference (p<.05). With the progression of DN, the level of Lp-PLA2 gradually increased p<.05. Lp-PLA2 was positively correlated with FBG, TG, LDL and HbA1c (R=0.637, p<.01; R=0.314, p=.01; R=0.213, p=.01; R=0.661, p≤.01), was negatively correlated with HDL (r=-0.230, p<.01). The results showed that Lp-PLA2 was an independent factor in the evaluation of early DN. The area under the curve for the evaluation of serum Lp-PLA2 level in early DN was 0.841, the optimal critical value was 155.9 ng/mL, the sensitivity was 88% and the specificity was 76.2%. Lp-PLA2 is an independent factor for the evaluation of early DN, and can be used as an important potential specific indicator for the diagnosis of early DN, meanwhile monitoring the progression of DN.

Integrating network pharmacology and experimental validation to decipher the mechanism of the Chinese herbal prescription modified Shen-Yan-Fang-Shuai formula in treating diabetic nephropathy

Context Diabetic nephropathy (DN) is the main cause of end-stage renal disease. Modified Shen-Yan-Fang-Shuai formula (M-SYFSF) has excellent clinical efficacy in treating diabetic kidney disease. However, the potential mechanism of M-SYFSF remains unknown. Objective To investigate the mechanism of M-SYFSF against DN by network pharmacological analysis and biological experiments. Materials and methods Utilizing a web-based pharmacology database, the potential mechanisms of M-SYFSF against DN were identified. In vivo experiments, male SD rats were injected with streptozotocin (50 mg/kg) and got uninephrectomy to construct a model of DN. M-SYFSF (11.34 g/kg/d) was gavaged once per day for 12 weeks after model establishment. In vitro experiments, human proximal tubular cells (HK-2) were performed with advanced glycation end-products (AGEs) (100 μg/mL), then intervened with M-SYFSF freeze-dried powder. Pathological staining, WB, IHC, ELISA were conducted to explore the mechanism of M-SYFSF against DN. Results Network pharmacological analysis showed that MAPK pathway was the potential pathway. Results showed that compared with the Model group, M-SYFSF significantly reduced 24h urine albumin, UACR, and serum creatinine levels (54.90 ± 26.67 vs. 111.78 ± 4.28, 8.87 ± 1.69 vs. 53.94 ± 16.01, 11.56 ± 1.70 vs. 118.70 ± 49.57, respectively), and improved renal pathological changes. Furthermore, the intervention of M-SYFSF reduced the expression of pro-inflammatory cytokines and inhibited the activation of MAPK pathway in AGEs-treated HK-2 cells. Discussion and conclusion M-SYFSF is likely to reduce inflammation in DN by inhibiting the MAPK pathway. It provides a theoretical basis for the clinical application of M-SYFSF in the treatment of DN.

HP1 induces ferroptosis of renal tubular epithelial cells through NRF2 pathway in diabetic nephropathy.

The aim of this study was to investigate the role of ferroptosis in diabetic nephropathy (DN) and the mechanism of its regulatory genes. HK-2 cells were cultured with high glucose and mice were intraperitoneally injected with streptozotocin to establish DN models. GSE111154 was analyzed to identify the abnormal expression of genes associated with DN. Cell injury was evaluated through CCK-8 assay and 4',6-diamidino-2-phenylindole/phenylindole double staining. The levels of iron, glutathione, malondialdehyde, urinary albumin, and urinary creatinine were determined by ELISA. Furthermore, western blot and RT-qPCR were used to detect protein and mRNA levels, respectively. Our data showed that heterochromatin protein 1 is an abnormally elevated gene related to DN and is further elevated by ferroptosis activators. Inhibition of HP1 significantly inhibited ferroptosis but promoted cell viability. In addition, nuclear factor erythroid2-related factor2 (NRF2) was decreased in DN cell model, but increased under the action of ferroptosis activators. NRF2 silencing reversed the protective effects of HP1 inhibition on HK-2 cells. Additionally, HP1 silencing also alleviated kidney damage in DN mice. Collectively, these findings suggest that inhibiting HP1 inhibits ferroptosis via NRF2 pathway, thereby protecting renal tubular epithelial cells from damage.