Proteinuria In Patients Research Articles

The diagnostic utility of urinary Transferrin excretion rate as predictor for micro albuminuria in patients with Type 2 Diabetes Mellitus among Karbala province

One of the factors responsible of end-stage renal disease and chronic kidney disease is diabetic nephropathy. Microalbuminuria itself is regarded as the initial indication of diabetic nephropathy, and it affects 20% to 40% of patients with diabetes mellitus. Because of the limited accuracy and precision of microalbuminuria, more susceptible markers may be developed to more accurately identify diabetic nephropathy early on. The purpose of this research was to ascertain whether urine transferrin could be used as a marker for diabetic nephropathy. In our research, 80 subjects with type 2 diabetes were divided into two categories: 10 healthy controls and group 1 (normoalbuminuric, with albumin excretion up to 30 mg/d) and group 2 (microalbuminuric, with albumin excretion between 30 and 300 mg/d). all subjects was over the age of 18, had diabetes for further than a year, and had a glomerular filtration rate greater than 60 mL/min/1.73 m2. The concentration of transferrin, serum creatinine, and glycosylated hemoglobin (HbA1c) in both spot urine and 24-hour urine samples were assessed using a super accurate sandwich enzyme - linked immunosorbent assay kit. subjects with microalbuminuria had substantially greater urinary transferrin levels than both normoalbuminuric and healthy control participants. We discovered a significantly positive correlation r = 0.584 (p < 0.001) when we compared these categories based on the urinary transferrin concentration. Urinary transferrin levels did not correlate with glycoregulation, and neither did transferrin levels and the length of diabetes. Urinary transferrin levels may be utilized as an important indicator of diabetic nephropathy, according to the findings of the research.

The effect of the combined treatment with dulaglutide and dapagliflozin in arterial elasticity, cardiac function, albuminuria and endothelial thickness in type 2 diabetes mellitus after 12 months

Abstract Background The association between diabetes mellitus and diabetic nephropathy with vascular and endothelial properties is well established. Purpose In this study, we compared the effect of combined treatment with dulaglutide and dapagliflozin versus DPP-4 inhibitors on endothelial glycocalyx, arterial stiffness, myocardial function and albuminuria in patients with type 2 diabetes mellitus and albuminuria. Methods A total of 60 patients with type 2 diabetes mellitus and albuminuria were randomized to combined dulaglutide and dapagliflozin treatment (n=30) or DPP-4 inhibitors (DPP-4is, n=30). We measured at baseline and 4 and 12 months posttreatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (c) global left ventricular longitudinal strain (GLS) (d) urine albumin-to creatinine ratio (UACR). Results Twelve months post-treatment, the combination of dulaglutide and dapagliflozin showed a greater improvement in all indices compared to DPP-4is, despite a similar reduction in glycosylated hemoglobin. Specifically, dual therapy showed greater improvements vs DPP-4is in PBR (2,10±0,31 to 1,93±0,23 μm vs 2,11±0,31 to 2,08±0,28 μm, p<0,001), in UACR (326±61 to 142±47 mg/g vs 345±48 to 306±60 mg/g, p<0,01), and in PWV (11,77±2,37 to 10,7±2,29 m/s vs 10,64±2,44 to 10,54±2,84 m/s, p<0,001), while only dual therapy showed improvement in cSBP (130,21±17,23 to 123,36±18,42 mmHg). Regarding GLS, both treatments were effective, but dual therapy showed a significantly higher percentage improvement compared to DPP-4is (18,19% vs 6,01%, respectively). Conclusions Twelve-month treatment with dulaglutide and dapagliflozin showed a greater improvement in vascular markers an albuminuria than DPP-4is in patients with type 2 diabetes mellitus and albuminuria. Early initiation of combined therapy as add-on to metformin should be considered in these patients.

Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial.

Semaglutide reduces albuminuria and the risk of kidney disease progression in patients with type 2 diabetes and chronic kidney disease (CKD). We conducted a randomized placebo-controlled double-blind clinical trial in adults with CKD (estimated glomerular filtration rate (eGFR) ≥25 ml min-1 1.73 m-2 and urine albumin-to-creatinine ratio (UACR) ≥30 and <3,500 mg g-1) and body mass index ≥27 kg m-2. Participants were randomized to semaglutide 2.4 mg per week or placebo. The primary endpoint was percentage change from baseline in UACR at week 24. Safety was monitored throughout. Overall, 125 participants were screened, of whom 101 were randomized to semaglutide (n = 51) or placebo (n = 50). Mean age was 55.8 (s.d. 12) years; 40 participants (39.6%) were female; median UACR was 251 mg g-1 (interquartile range 100, 584); mean eGFR was 65.0 (s.d. 25) ml min-1 1.73 m-2; and mean body mass index was 36.2 (s.d. 5.6) kg m-2. Chronic glomerulonephritis (n = 25) and hypertensive CKD (n = 27) were the most common CKD etiologies. Treatment for 24 weeks with semaglutide compared to placebo reduced UACR by -52.1% (95% confidence interval -65.5, -33.4; P < 0.0001). Gastrointestinal adverse events were more often reported with semaglutide (n = 30) than with placebo (n = 15). Semaglutide treatment for 24 weeks resulted in a clinically meaningful reduction in albuminuria in patients with overweight/obesity and non-diabetic CKD. ClinicalTrials.gov registration: NCT04889183 .

Chemerin, TNF − α and the degree of albuminuria in patients with diabetic kidney disease

BackgroundChronic inflammation has been increasingly recognized as an essential pathogenic mechanism for the development and progression of diabetic kidney disease (DKD). Chemerin is an adipokine which has been suggested to be related to inflammation and has been correlated with the development of diabetic complications. We aimed to explore the potential links between chemerin, TNF – α, as a marker of systemic inflammation, and the level of albuminuria in patients with type 2 diabetes mellitus (T2DM). MethodThe study included 84 patients with T2DM and 10 normoalbuminuric non-diabetic controls. Demographic, clinical and laboratory data including chemerin and TNF-α levels were collected. ResultsA total of 84 diabetic patients were enrolled, 32 males (38.1 %), with mean age 57.9 ± 10.7 years. They were divided into 3 groups: A1: 14 with normalbuminuria, A2: 27 with microalbuminuria, and A3: 43 with macroalbuminuria (uACR < 30, 30–300 and > 300 mg/gm respectively). Chemerin and TNF-α levels increased with the progress of albuminuria (control: 21.3 (14.7 –77), A1: 794 (683–925), A2: 1150 (962.9 – 1221.5) and A3: 1466 (1197.5 – 2002.5) ng/ml; p < 0.001) and (control: 77.9 (59 – 96.8), A1: 85.2 (71–116.3), A2: 87.3 (81 – 97.5) and A3: 99 (85.1 – 142.5) pg/ml; p = 0.009) respectively. Among the diabetics, a significant association was evident between serum chemerin and serum TNF-α (r = 0.53; p < 0.001). On linear stepwise regression analysis, chemerin was significantly associated with TNF-α and HbA1c (unstandardized β 10.881 and 272.68 respectively, p < 0.001); and TNF-α was significantly correlated with chemerin, uACR (unstandardized β 0.059 and 0.004 respectively, p < 0.001) and HbA1c (unstandardized β −13.699, p = 0.014). ConclusionOur findings suggest a potential role of chemerin and TNF-α in the development and progression of DKD, and thus support the role of the inflammatory pathway. Larger follow up studies are warranted to further explore the potential links between chemerin, inflammation and DKD.

Effect of Early Spironolactone Treatment on Albuminuria in Patients with CKD and Hypertension: A Randomized Controlled Trial

Effect of Early Spironolactone Treatment on Albuminuria in Patients with CKD and Hypertension: A Randomized Controlled Trial

Predicting the Risk of Albuminuria in Patients with Diabetes: A Systematic Review and Development Study

Predicting the Risk of Albuminuria in Patients with Diabetes: A Systematic Review and Development Study

Association Between Weight-Adjusted Waist Index and Albuminuria in Type 2 Diabetes Mellitus in the Chinese Population.

This study aimed to investigate the relationship between weight-adjusted waist index (WWI) and albuminuria in patients with type 2 diabetes mellitus (T2DM) in the Chinese population. A total of 860 adult patients in the Department of Endocrinology of the Affiliated Hospital of Jiangsu University were retrospectively analyzed from June 2018 to September 2023. Correlations between WWI and albuminuria (albumin-to-creatinine ratio (UACR) ≥ 30 mg/g were defined as albuminuria) were analyzed using the Pearson and Spearman methods. The associations between albuminuria and Age, gender, body mass index (BMI), waist circumference/ hip circumference (WHR), systolic blood pressure(SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2h PG), fasting plasma insulin (FIns), 2-h postprandial insulin (2hINS), glycosylated hemoglobin (HbA1c), WWI, homeostasis model assessment of insulin resistance (HOMA-IR) were analyzed via binary logistic regression. Compared with the normal albumin group, serum urea nitrogen, serum creatinine, UACR, and WWI levels in the albuminuria group were significantly increased, while estimated glomerular filtration rate (eGFR) levels were significantly decreased (P < 0.05). Correlation analyses revealed that WWI was positively correlated with UACR but negatively correlated with urea nitrogen, serum creatinine, and eGFR (P < 0.05). Binary logistic regression analyses indicated that WWI was an independent risk factor for albuminuria in T2DM patients. Receiver operating characteristic curve results showed that the area under the curve for albuminuria as predicted by WWI was 0.605 [95% CI = (0.563-0.646), P < 0.001]. WWI is independently associated with albuminuria in the Chinese patients with type 2 diabetes and may serve as a simple indicator for albuminuria risk assessment.

SGLT2-Inhibition in Patients With Alport syndrome

IntroductionLarge-scale trials showed positive outcomes of sodium–glucose cotransporter-2 inhibitors (SGLT2i) in adults with chronic kidney disease (CKD). Whether the use of SGLT2i is safe and effective in patients with the common hereditary CKD Alport syndrome has not yet been investigated specifically in larger cohorts. MethodsThis observational, multi-center, international study (NCT02378805) assessed 112 patients with Alport syndrome after start of SGLT2i. The study’s primary endpoint was change of albuminuria in albumin/gram creatinine from start of therapy. ResultsCompared to randomized trials investigating the effect of SGLT2i in CKD, the adult patients in this study were younger (38±14 years) and had a better estimated glomerular filtration rate, eGFR, (63±35 ml/min/1.73m2; n=98). Maximum follow up was 32 months. Compared to baseline, at the first three follow-up visits (months 1 to 3, 4 to 8 and 9 to 15) after initiation of SGLT2i-therapy, a significant reduction of albuminuria in milligrams albumin/gram creatinine (>30%) was observed. Mean loss of eGFR was 9±12 ml/min/1.73 m2 almost one year after initiation of SGLT2i-therapy (n=35). At a total of 71 patient-years at risk, 0.24 adverse events per patient year on SGLT2i were reported. ConclusionThis study indicates that, additive to RAS-inhibition, SGLT2i have the potential to reduce the amount of albuminuria in patients with Alport syndrome. Future studies are needed to investigate the long-term effects of SGLT2i on CKD progression in patients with Alport syndrome to assess whether the observed reduction in albuminuria translates to a delay in kidney failure.

Abstract 28: A major effect of aprocitentan on albuminuria in patients with resistant hypertension

Background and Objectives: Micro- and macroalbuminuria measured by urinary albumin-to-creatinine ratio (UACR) (30–300 mg/g and &gt;300 mg/g, respectively), and high normal UACR (10–30 mg/g) are associated with higher risk of mortality, CV disease and CKD progression in patients with hypertension, diabetes, decreased renal function, or even the general population and reduction can lower these risks. The endothelin ETA/ETB receptor antagonist aprocitentan reduced albuminuria in patients with confirmed resistant hypertension (RHT). In the PRECISION trial, in addition to standard background therapy including valsartan, aprocitentan 12.5 mg reduced UACR by 30% compared to placebo (LS Geom Mean [95 CL] 0.70 [0.61, 0.80], p&lt;0.0001) and 25 mg by 34% (0.66 [0.58,0.75], p&lt;0.0001) at the end of double-blind part 1 (4 weeks) in the overall population. In this analysis, we evaluated the effect of aprocitentan on UACR at both doses according to the baseline (BL) albuminuria (30–300 mg/g and &gt;300 mg/g). Methods: 730 patients with RHT on a standardized fixed-dose combination of amlodipine/ valsartan/hydrochlorothiazide were randomized to aprocitentan (12.5 mg or 25 mg) or placebo. Of these, 174 and 90 had BL microalbuminuria or macroalbuminuria, respectively. Changes from BL in UACR and office systolic blood pressure measured at trough (SBP, the primary endpoint in PRECISION) after 4 weeks of double-blind treatment. Results: In subjects with microalbuminuria, aprocitentan reduced UACR by 43% in the 12.5 mg group (0.57 [0.42, 0.78], p=0.0005) and by 45% in the 25 mg group (0.55 [0.40,0.77], p=0.0004) compared to placebo. In subjects with macroalbuminuria, aprocitentan reduced UACR by 48% with 12.5 mg (0.52 [0.37, 0.75], p=0.0006) and by 61% with 25 mg (0.39 [0.27,0.57], p&lt;0.0001) compared to placebo. In contrast, placebo did not have any noticeable effect on albuminuria in any group. The effect of aprocitentan in lowering blood pressure, measured at trough, was independent of the level of albuminuria at baseline. After 4 weeks, 53.3% and 60% of patients achieved a decrease of ≥10 mmHg from baseline with 12.5 mg aprocitentan, respectively in the microalbuminuria and macroalbuminuria groups, compared to 64% with aprocitentan 25 mg (both cohorts) and 48% and 29% in the placebo group. Conclusion: Aprocitentan produced a major decrease of albuminuria regardless of baseline level in patients with RHT. These findings suggest substantial clinical benefit of aprocitentan in CKD patients.

A new perspective on proteinuria and drug therapy for diabetic kidney disease.

Diabetic kidney disease (DKD) is one of the leading causes of end-stage renal disease worldwide and significantly increases the risk of premature death due to cardiovascular diseases. Elevated urinary albumin levels are an important clinical feature of DKD. Effective control of albuminuria not only delays glomerular filtration rate decline but also markedly reduces cardiovascular disease risk and all-cause mortality. New drugs for treating DKD proteinuria, including sodium-glucose cotransporter two inhibitors, mineralocorticoid receptor antagonists, and endothelin receptor antagonists, have shown significant efficacy. Auxiliary treatment with proprietary Chinese medicine has also yielded promising results; however, it also faces a broader scope for development. The mechanisms by which these drugs treat albuminuria in patients with DKD should be described more thoroughly. The positive effects of combination therapy with two or more drugs in reducing albuminuria and protecting the kidneys warrant further investigation. Therefore, this review explores the pathophysiological mechanism of albuminuria in patients with DKD, the value of clinical diagnosis and prognosis, new progress and mechanisms of treatment, and multidrug therapy in patients who have type 2 diabetic kidney disease, providing a new perspective on the clinical diagnosis and treatment of DKD.

Association between oxidative balance score and diabetic kidney disease, low estimated glomerular filtration rate and albuminuria in type 2 diabetes mellitus patients: a cross-sectional study.

The oxidative balance score (OBS) is a comprehensive concept that includes 20 oxidative stressors and can be used to assess individual pro-oxidant versus antioxidant exposure, and the aim of the present study was to investigate the association between OBS and the risk of diabetic kidney disease (DKD), low estimated glomerular filtration rate (low-eGFR) and albuminuria in patients with diabetes mellitus (DM). This cross-sectional study included nationally representative consecutive National Health and Nutrition Examination Survey DM patients aged 18 years and older from 2003-2018. The continuous variable OBS was converted into categorical variables by quartiles, and weighted multiple logistic regression analyses and restricted triple spline models were used to explore the relationships. We also performed subgroup analyses and interaction tests to verify the stability of the results. A total of 5389 participants were included, representing 23.6 million non-institutionalized US residents. The results from both multivariate logistic regression analysis and restricted cubic spline models indicated that OBS and dietary OBS levels were negatively associated with the risk of DKD, low-eGFR, and albuminuria, without finding a significant correlation between lifestyle OBS and these clinical outcomes. Compared to the lowest OBS quartile group, the prevalence risk of DKD (OR = 0.61, 95% CI: 0.46-0.80), low-eGFR (OR = 0.46, 95% CI: 0.33-0.64) and albuminuria (OR = 0.68, 95% CI: 0.51-0.92) decreased by 39%, 54% and 32%, respectively, in the highest OBS quartile group. The results remained stable in subgroup analyses and no interaction between subgroups was found. Higher levels of OBS and dietary OBS were associated with a lower risk of DKD, low-eGFR, and albuminuria. These findings provided preliminary evidence for the importance of adhering to an antioxidant-rich diet and lifestyle among individuals with diabetes.

The High Burden of Asymptomatic Kidney Diseases in Individuals with HIV: A Prospective Study from a Tertiary Care Center in India

Background HIV infection is associated with a significant kidney disease burden. This study is aimed to screen for kidney disease in all HIV patients on highly active anti retroviral therapy (HAART), study clinico-histological correlation, and assess the impact of early diagnosis on the clinical course. Materials and Methods It was a prospective, longitudinal study done in a tertiary care hospital. Adult HIV-infected patients, on HAART for at least 3 months, were screened for kidney disease. Kidney biopsy was done if indicated. Patients were treated as per standard guidelines. Results were analyzed at 3 months. Results Among 1600 patients, 966 were compliant with HAART and were tested. Two hundred and sixty-two patients completed the study duration. Out of these 262 patients 78.2% were receiving tenofovir-based ART regimen. Around 31.2% were hypertensive and 19.8% were diabetic. The mean eGFR was 57.5 ± 24 mL/min/1.73 m2. Around 19.8% had asymptomatic urine abnormalities, 40.1% had proteinuria, and 27.1% had AKI. Acute nephritic syndrome was seen in 16.4%, rapidly progressive renal failure (RPRF) in 13.3%, and CKD in 10.6% patients. Out of 74 patients who underwent biopsy, histology showed chronic tubulointerstitial nephritis in 16 (21.6%), acute tubulointerstitial nephritis in 11 (14.8%), diabetic nephropathy in 10 (13.5%), and thrombotic microangiopathy in 7 patients (9.4%). Higher viral load levels, diabetes mellitus, and age above 60 years were associated with kidney disease. Conclusion Asymptomatic HIV infection has a significant burden of kidney disease. Kidney biopsy is crucial for correct diagnosis and management. The absence of HIV associated nephropathy in proteinuric HIV patients is notable in this study.

Avenciguat reduces albuminuria in patients with chronic kidney disease.

Avenciguat reduces albuminuria in patients with chronic kidney disease.

The relationship between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus.

Diabetic nephropathy is a prevalent cause of chronic kidney disease worldwide. Magnesium plays a critical role in insulin resistance, and insulin, in turn, regulates magnesium levels. We aimed to investigate the association between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus (T2DM). This retrospective single-centre study encompassed 1178 patients aged 18 and above with T2DM, who attended our outpatient clinic between January 2019 and August 2020. Albuminuria levels were categorised according to Kidney Disease Outcomes Quality Initiative guidelines. In the literature, when examining cut-off values for hypomagnesemia, it is observed that studies typically use hospital normal level as a reference point. Hypomagnesemia, defined as magnesium levels below 1.6 mg/dL, was compared to normomagnesemia (magnesium between 1.6 and 2.4 mg/dL). The primary objective was to explore the impact of magnesium levels on albuminuria, while the secondary objective was to determine the prevalence of hypomagnesemia. The multivariate logistic regression analyses were performed according to age, gender (male), HbA1c, and presence of hypomagnesemia. The mean age of the participants was 58.7 ± 12.2 years, with 44% being male. Hypomagnesemia was identified in 5.3% of the patients. Advanced age and female gender were more common among patients with hypomagnesemia (p = .001). Magnesium levels exhibited a negative correlation with HbA1c and fasting blood glucose, and a positive correlation with creatinine levels (r = -.117, r = -.131, r = .117, p < .001 for all three variables). Hypomagnesemia was significantly more prevalent in patients with albuminuria (15.9% vs. 4.7%, p < .001). Moreover, participants with the presence of hypomagnesemia were independently associated with a higher risk of albuminuria (odds ratio 3,64 1.76-7.52, p = .001). Albuminuria is more frequently observed in patients with hypomagnesemia.

Effect of Avenciguat on Albuminuria in Patients with CKD: Two Randomized Placebo-Controlled Trials.

Avenciguat is a novel, potent soluble guanylate cyclase activator in development for CKD. Two trials investigated avenciguat in diabetic (NCT04750577) and non-diabetic (NCT04736628) CKD. A prespecified pooled analysis of two randomized, double-blind, placebo-controlled trials of identical design. Adults with CKD (eGFR ≥20 and <90 mL/min/1.73 m 2 , urine albumin-to-creatinine ratio [UACR] ≥200 and <3500 mg/g) were randomized to 20 weeks of placebo or avenciguat 1, 2, or 3 mg three times daily (TID; adjunctive to angiotensin-converting-enzyme inhibitor or angiotensin receptor blocker. Primary endpoint: change from baseline in UACR in 10-hour urine at week 20, analyzed per protocol. Secondary endpoint: UACR change from baseline in first morning void urine at week 20. Safety was monitored throughout. Overall 500 patients (mean age 62 years [SD 13]; mean eGFR 44 mL/min/1.73 m 2 [SD 18] and median 10-hour UACR 719 [interquartile range 379-1285] mg/g ) received placebo (n=122) or avenciguat 1 mg (n=125), 2 mg (n=126), or 3 mg (n=127) TID. All 243 patients in study one and 27/261 patients in study two had diabetes. Avenciguat 1, 2, and 3 mg TID reduced UACR in 10-hour and first morning void urine versus placebo throughout the treatment period. At week 20, placebo-corrected geometric mean changes (95% confidence interval) from baseline in UACR in 10-hour urine with avenciguat 1, 2, and 3 mg TID were -15.5% (-26.4, -3.0), -13.2% (-24.6, -0.1), and -21.5% (-31.7, -9.8), respectively, analyzed per protocol. Corresponding changes in first morning void urine were -19.4% (-30.0, -7.3), -15.5% (-26.9, -2.5), and -23.4% (-33.5, -11.8), respectively. Avenciguat was well tolerated, overall frequency of adverse events was low and similar to placebo. The number of patients who discontinued study drug due to adverse events with avenciguat 1, 2, and 3 mg TID were 5 (4%), 11 (9%), and 11 (9%), respectively, compared with 4 (3%) in the placebo group. Avenciguat lowered albuminuria, and was well tolerated in patients with CKD.

#983 Identification of gut microbiome signatures associated with albuminuria in diabetes mellitus

Abstract Background and Aims Diabetes is a growing global problem with serious complications, including kidney impairment and cardiovascular morbidity and mortality. Monitoring albuminuria, which is associated with these complications, is crucial in optimal diabetes management. Recent research suggests a link between the gut microbiome, plasma metabolites and albuminuria development in diabetes patients, highlighting the need for further investigation using deep metagenomic sequencing. Method We investigated the relationship between 1002 gut microbial species, 1308 metabolites and albuminuria in 752 participants with diabetes from the Swedish CArdioPulmonary BioImage Study. To determine the relative abundance of species, we employed deep shotgun metagenomic sequencing of fecal samples. Plasma metabolites were analyzed using mass spectrometry-based methods. Results Shannon diversity index was inversely associated with albuminuria after adjusting for confounding factors (Fig. 1). Our multivariable-adjusted models revealed seven metagenomic species that were associated with albuminuria (Fig. 2). Furthermore, employing a global metabolomics approach, we identified phenyl sulfate, among 98 annotated metabolites (Fig. 3), as linked to the species Clostridium sp. AT4 and Eggerthella lenta. Notably, phenyl sulfate is involved in tyrosine metabolism, and we also observed an association between the gut metabolic module of Tyrosine degradation II and albuminuria. Conclusion In the present study, we identified seven gut microbial species linked to albuminuria and established a connection between these species and phenyl sulfate, which previously has been associated with podocyte damage and the development of albuminuria. These findings provided additional evidence of the impact of microbial species and contribute to our understanding of the complex relationship between the gut microbiome, plasma metabolites, and albuminuria in patients with diabetes.

#3115 Effectiveness of SGLT2 inhibitors in patients with glomerulonephritis: a single center experience

Abstract Background and Aims Sodium-glucose cotransporter 2 (SGLT2) inhibitors have become widely used in recent years because of favorable outcomes on kidney function in people with diabetes mellitus and chronic kidney disease (CKD). The main effect of SGLT2 inhibitors is inhibiting sodium and glucose reabsorption, acting precisely in the early proximal tubule of the renal nephron. Although these drugs developed as glucose-lowering agents for their capability to induce glycosuria, cardiovascular outcome studies found that the reduction in kidney function was significantly delayed, and the incidence of severe decline in kidney function was reduced in patients taking SGLT2 inhibitors. Later on, these outcomes were confirmed by the results of the DAPA-CKD, EMPA-KIDNEY, and CREDENCE studies, which were specific outcome trials in patients with CKD. However, data about the use of SGLT2 inhibitors in patients with glomerulonephritis at routine clinical practice are still limited. The purpose of this study is to investigate the impact of SGLT2 inhibitors use in patients with glomerulonephritis. Method Patients diagnosed with biopsy-proven GN who continued their routine follow-up in Etlik City Hospital nephrology clinic were retrospectively examined. Patients with a steroid treatment history for GN were excluded from this study. We identified 29 patients who were treated with SGLT2 inhibitors for proteinuria. We analyzed the baseline characteristics, comorbidities, GN types, and laboratory parameters (baseline, sixth and twelfth months at the follow-up). Each patient was matched to the control with a similar baseline feature under conservative therapy (n = 29). Both patient groups were treated in line with the KDIGO glomerulonephritis guideline and were received RAAS blockers at the maximum tolerated dose. According to baseline levels, the reduction rate in proteinuria and eGFR of the sixth and twelfth months were calculated as percentages. The study was performed in accordance with the Declaration of Helsinki. The local ethical committee approved the study design. Results Our study involved 58 patients diagnosed with 32 (55%) IgA nephropathy, 16 (28%) with membranous nephropathy, and 10 (17%) with focal segmental glomerulosclerosis. In the treatment group, 23 (79%) patients used dapagliflozin, and 6 (21%) used empagliflozin as SGLT2 inhibitors. Baseline proteinuria levels at [1940 (1780-2700 mg/d) vs. 1890 (1670-2400 mg/d); p = 0.8], eGFRs [60 (44-82) vs. 64 (46-80) ml/min/1.73 m2; p = 0.8] and serum albumin levels (39.6 ± 0.3 vs. 39.1 ± 0.2; p = 0.4) were similar between both groups. The proteinuria reduction rate in the sixth month was 34% (27.3-40.5) for the treatment group and 12% (6.9-20.7) for the control group (&amp;lt;0.0001). Besides, the reduction rate was still higher in the treatment group at the 12th month [50.5% (39-52.6) vs. 26.3% (17.2-35.4); p ≤ 0.0001]. eGFR declining rate at 6th months and 12th months were lower in SGLT2 group than the control group [3.1% (0-6.2) vs. 8.6% (4.1-16.6); p = 0.004 and 0.8% (0-5) vs. 5.9% (3.3-15.2); 0.005, respectively] (Table 1). Proteinuria levels at 6th months were 1170 (970-1890) mg/d and 1730 (1180-2100) mg/d for treatment and control group, respectively. At 12th months, median proteinuria level of SGLT2 group was 940 (840-1480) mg/d and control group was 1250 (1120- 2040) mg/d (Fig. 1). Conclusion In this study with a well-matched control group, we found that SGLT2 inhibitors demonstrate efficacy in mitigating the decline in estimated GFR and reducing albuminuria in patients with GN. However, randomized-controlled trials are still required specific to patients with GN.

Expression and localization of HSD17B13 along mouse urinary tract.

17β-Hydroxysteroid dehydrogenase-13 (HSD17B13), a newly identified lipid droplet-associated protein, plays an important role in the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Emerging evidence demonstrates that NASH is an independent risk factor for chronic kidney disease, which is frequently accompanied by renal lipid accumulation. In addition, the HSD17B13 rs72613567 variant is associated with lower levels of albuminuria in patients with biopsy-proven NAFLD. At present, the role of HSD17B13 in lipid accumulation in the kidney is unclear. This study utilized bioinformatic and immunostaining approaches to examine the expression and localization of HSD17B13 along the mouse urinary tract. We found that HSD17B13 is constitutively expressed in the kidney, ureter, and urinary bladder. Our findings reveal for the first time, to our knowledge, the precise localization of HSD17B13 in the mouse urinary system, providing a basis for further studying the pathogenesis of HSD17B13 in various renal and urological diseases.NEW & NOTEWORTHY HSD17B13, a lipid droplet-associated protein, is crucial in nonalcoholic fatty liver disease (NAFLD) development. NAFLD also independently raises chronic kidney disease (CKD) risk, often with renal lipid buildup. However, HSD17B13's role in CKD-related lipid accumulation is unclear. This study makes the first effort to examine HSD17B13 expression and localization along the urinary system, providing a basis for exploring its physiological and pathophysiological roles in the kidney and urinary tract.

#2638 SGLT2i in CKD with high albuminuria: an observational real-world study

Abstract Background and Aims Dapagliflozin, a sodium–glucose co-transporter-2 inhibitor (SGLT2i), is indicated to treat chronic kidney disease (CKD). Clinical trials have shown that dapagliflozin significantly reduces albuminuria in patients with urine albumin-creatinine ratio (UACR) 200–5000 mg/g and has beneficial effects on estimated glomerular filtration rate (eGFR) decline and combined kidney outcomes. In the DAPA-CKD trial, dapagliflozin led to substantial reductions in the composite of sustained eGFR decline of ≥50%, end-stage kidney disease, and renal or cardiovascular death (hazard ratio [HR], 0.61; 95% confidence interval [CI]: 0.51, 0.72; p &amp;lt; 0.001), with similar reductions observed across UACR subgroups. Furthermore, compared with placebo, dapagliflozin reduced geometric mean UACR by 29.3% (95% CI: –33.1, –25.2; p &amp;lt; 0.0001), with no difference in relative UACR reduction by baseline UACR above or below 1000 mg/g. In the ZENITH-CKD study, over 12 weeks the combination of zibotentan (a novel endothelin A receptor antagonist) and dapagliflozin showed a robust reduction in UACR of 47.7% vs 28.3% for dapagliflozin alone, with this effect maintained in patients with UACR &amp;gt;700 mg/g. It is well known that renal disease progresses more quickly in patients with higher degree of albuminuria than in those with lower levels. We aimed to further characterize renal risk in patients with different levels of residual albuminuria despite standard of care treatment with renin–angiotensin system inhibitors (RASi) and SGLT2i. Methods We used a large USA claims database (Optum's de-identified Clinformatics® Data Mart Database [CDM]) to identify patients aged ≥18 years with CKD, defined as either two eGFR measurements ≤60 mL/min/1.73 m2 taken ≥90 days apart or a first eGFR ≤60 mL/min/1.73 m2 and a CKD diagnosis. Patients were indexed at the date of dapagliflozin 10 mg initiation between 30 April 2021 (date of approval for dapagliflozin in CKD) and March 2023. Patients with prior use of SGLT2i, immunosuppressive drugs, hydroxychloroquine, CKD stage 5 (based on eGFR &amp;lt;15 mL/min/1.73 m2 or dialysis), polycystic kidney disease, or type 1 or gestational diabetes were excluded. Patients were indexed on 1st January 2022 and grouped into two UACR groups: ≥700UACR group (≥700 mg/g) and &amp;lt;700UACR group (200–699 mg/g). Outcomes were UACR changes, eGFR slopes and CKD-associated hospitalizations within 1 year after dapagliflozin initiation. Hazard ratios were estimated using adjusted Cox survival regression. UACR follow-up analyses were restricted to patients with at least one follow-up measurement. Results In the 5908 patients with CKD, median UACRs at index in the ≥700UACR and &amp;lt;700UACR groups were 1414 mg/g and 102 mg/g, respectively. Patients in the ≥700UACR group vs &amp;lt;700UACR group had lower eGFR (40 vs 48 mL/min/1.73 m2), were younger (71 vs 74 years), and both groups had a high burden of comorbidities (heart failure: 38% vs 42%; type 2 diabetes: 74% vs 75%). RASi use was 81% and 74%, respectively. During follow-up, 22% of patients in the ≥700UACR group experienced a CKD-related hospitalization (25.1 events per 100 patient years) as compared to 19.5 events per 100 patient years in the &amp;lt;700UACR group (HR 1.38 [95% CI: 1.16, 1.64, p &amp;lt; 0.001]; Fig. panel A). The eGFR slope (95% Cl) of patients in the ≥700UACR group was –2.44 mL/min/1.73 m2 per year (–3.49, –1.65), compared with a flat eGFR trajectory in patients in the &amp;lt;700UACR group (0.39 [–0.11, 0.96]). In the ≥700UACR group with at least one follow-up measurement (n = 431), UACR lowered from 2077 mg/g to 1674 mg/g (–36.3%) within 1 month of dapagliflozin initiation but remained above 1200 mg/g throughout the 12-month follow-up period (Fig. panel B). Conclusions While treatment with RASi and SGLT2i are associated with reduced risk of renal outcomes in patients with CKD, awareness and management of residual albuminuria remains an area of unmet clinical need. The novel combination of zibotentan/dapagliflozin currently under investigation in the ZENITH High Proteinuria phase III trial (NCT06087835) seeks to address this need.

#1549 The effect of sglt2 inhibitors (dapaglifozin) on albuminuria in patients of diabetic nephropathy above standard of care

Abstract Background and Aims Albuminuria is the hallmark of diabetic nephropathy (DN) and progression of albuminuria denotes declining renal functions culminating in End Stage Renal Disease. Intensive blood glucose control (HbA1c &amp;lt;7%), intensive blood pressure control (&amp;lt;130/90 mmHg), blockade of Renin Angiotensin Aldosterone System (RAAS) by Angiotensin converting enzyme inhibitors (ACE-i) and Angiotensin receptor blockers (ARBs) constitute the standard line of care for treatment of DN with proteinuria. Sodium Glucose cotransporter 2 inhibitors (SGLT2i) are drugs are recently introduced for proteinuria reduction with no data available in this part of the world. Hence, I, observed the antiproteinuric effect of SGLT2i in patients who have type2 diabetes mellitus (T2DM) with albuminuria and who are already on maximum doses of ACE-I or ARBs. My study population was on dapaglifozin due to easy availability and low cost. Method it is an observational study including patients who attended the out-patient clinic of Nephrology, at Medica Hospital, Kolkata between July 2022 to February 2023. Inclusion criteria: Exclusion criteria: Quantitative estimation of urine albumin was performed using the VITROS Chemistry Products mALB Reagent along with the VITROS Chemistry Products Calibrator Kit 24 on the VITROS 5,1 FS Chemistry System and the VITROS 5600 Integrated System. Blood sugar was measured by glucose oxidase method. eGFR by CKD EPI equation. Statistical Methodology Continuous variables were presented with mean and standard deviation and tested for normal distribution by the Kolmogorov-Smirnov test. Categorical variables were summarized using frequency and percentages. For testing of related samples, Wilcoxon sign ranked test is used. Statistical analyses were performed using the SPSS software with version 26.0. Results A total of 100 patients were included in the study, of which 3 patients were lost to follow up and 2 patients discontinued the study at 3 months due to fall in eGFR below 25 ml/min/1.73 m2 and 4 patients discontinued after 3 months because of fungal genital infections. After Dapaglifozin administration, a significant reduction in Urine Albumin-creatinine ratio (UACR) was observed, by a percentage decrease of 37.3% (p&amp;lt;0.001) at 3 months and of 70.2% (p&amp;lt;0.001) at 6 months from baseline. Similarly, there was an acute reduction in eGFR from baseline. A percentage decrease by 5.16% (p&amp;lt;0.001) was observed at 3 months &amp; a decrease by 5.69% (p&amp;lt;0.001) at 6 months from baseline. Conclusion Conventional approaches reduce but have not been able to stop disease progression in Diabetic Kidney Disease (DKD). SGLT2i can protect against the onset of DKD, slow disease progression independently. They have an antiproteinuric effect in patients with diabetic nephropathy which was sustained throughout the follow-up period in my study. Studies have also shown that SGLT2i reduce major adverse cardiovascular events in patients with T2DM and established cardiovascular disease. With the new results of EMPA-KIDNEY trial, SGLT2i are being used at even lower eGFR (&amp;lt;25 ml/min/1.73 m2 till on hemodialysis) and such vast health benefits, invention of SGLT2i are is a boon to the mankind.