Proteinuria Research Articles

Features of preeclampsia in patients with chronic kidney disease

Aims: to study the characteristics of preeclampsia (PE) in women with chronic kidney disease (CKD) compared to PE in the general population.Method: a prospective observational study analyzed the course of PE in 24 women with a previously established diagnosis of CKD (Group 1) and 39 women in the general population (Group 2) without a complicating somatic history. In patients with CKD with a known pregestational creatinine level, the physiological response of the kidneys to pregnancy was assessed, defined as a decrease in serum creatinine by more than 10% in the first trimester. The angiogenic ratio (sFlt-1/PLGF) was studied in 13 patients with CKD.Results: the two groups did not differ in age or parity. In the first group, 16 patients had CKD stage 1-2, 5 had CKD 3A, and one patient each had CKD 3B, 4 and 5 (the later receiving hemodialysis). Nineteen (79%) of women with CKD had hypertension, proteinuria (PU), renal impairment or a combination of these factors before conception. Only 3 out of 16 patients had a physiological renal response. Early PE developed in 58.3% of patients with CKD compared to 35.3% in second group (p = 0.082). The duration of PE inversely correlated with the stage of CKD (r = -0.630; p = 0.001). As pregnancy progressed in patients with CKD, PU increased, reaching nephrotic level in 54% of women by the time of PE. HELLP syndrome or isolated hematological signs of TMA were noted in 8 patients in the general population group, and in 1 in the CKD group. The average sFlt-1/PLGF value in patients with early stages of CKD (n = 9) was 81.0±24.0, with late stages (n = 4) it was 14±8.Conclusion: the study identified the features of PE in CKD: early onset, increased PU reaching nephrotic level in half of the cases by the time PE is diagnosed, and the absence of a histological renal response to pregnancy in the 1st trimester. The lack of changes in the angiogenic coefficient in women with PE and late-stage CKD requires further study in a larger group of patients.

Prediction of People With Type 2 Diabetes Not Achieving HbA1c Target After Initiation of Fast-Acting Insulin Therapy: Using Machine Learning Framework on Clinical Trial Data

Background and Aims: Glycemic control is crucial for people with type 2 diabetes. However, only about half achieve the advocated HbA1c target of ≤7%. Identifying those who will probably struggle to reach this target may be valuable as they require additional support. Thus, the aim of this study was to develop a model to predict people with type 2 diabetes not achieving HbA1c target after initiating fast-acting insulin. Methods: Data from a randomized controlled trial (NCT01819129) of participants with type 2 diabetes initiating fast-acting insulin were used. Data included demographics, clinical laboratory values, self-monitored blood glucose (SMBG), health-related quality of life (SF-36), and body measurements. A logistic regression was developed to predict HbA1c target nonachievers. A potential of 196 features was input for a forward feature selection. To assess the performance, a 20-repeated stratified 5-fold cross-validation with area under the receiver operating characteristics curve (AUROC) was used. Results: Out of the 467 included participants, 98 (21%) did not achieve HbA1c target of ≤7%. The forward selection identified 7 features: baseline HbA1c (%), mean postprandial SMBG at all meals 3 consecutive days before baseline (mmol/L), sex, no ketones in urine, baseline albumin (g/dL), baseline low-density lipoprotein cholesterol (mmol/L), and traces of protein in urine. The model had an AUROC of 0.745 [95% CI = 0.734, 0.756]. Conclusions: The model was able to predict those who did not achieve HbA1c target with promising performance, potentially enabling early identification of people with type 2 diabetes who require additional support to reach glycemic control.

Establishment and external validation of an early warning model of diabetic peripheral neuropathy based on random forest and logistic regression

ObjectiveThe primary objective of this study was to investigate the risk factors for diabetic peripheral neuropathy (DPN) and to establish an early diagnostic prediction model for its onset, based on clinical data and biochemical indices.MethodsRetrospective data were collected from 1,446 diabetic patients at the First Affiliated Hospital of Anhui University of Chinese Medicine and were split into training and internal validation sets in a 7:3 ratio. Additionally, 360 diabetic patients from the Second Affiliated Hospital were used as an external validation cohort. Feature selection was conducted within the training set, where univariate logistic regression identified variables with a p-value < 0.05, followed by backward elimination to construct the logistic regression model. Concurrently, the random forest algorithm was applied to the training set to identify the top 10 most important features, with hyperparameter optimization performed via grid search combined with cross-validation. Model performance was evaluated using ROC curves, decision curve analysis, and calibration curves. Model fit was assessed using the Hosmer-Lemeshow test, followed by Brier Score evaluation for the random forest model. Ten-fold cross-validation was employed for further validation, and SHAP analysis was conducted to enhance model interpretability.ResultsA nomogram model was developed using logistic regression with key features: limb numbness, limb pain, diabetic retinopathy, diabetic kidney disease, urinary protein, diastolic blood pressure, white blood cell count, HbA1c, and high-density lipoprotein cholesterol. The model achieved AUCs of 0.91, 0.88, and 0.88 for the training, validation, and test sets, respectively, with a mean AUC of 0.902 across 10-fold cross-validation. Hosmer-Lemeshow test results showed p-values of 0.595, 0.418, and 0.126 for the training, validation, and test sets, respectively. The random forest model demonstrated AUCs of 0.95, 0.88, and 0.88 for the training, validation, and test sets, respectively, with a mean AUC of 0.886 across 10-fold cross-validation. The Brier score indicates a good calibration level, with values of 0.104, 0.143, and 0.142 for the training, validation, and test sets, respectively.ConclusionThe developed nomogram exhibits promise as an effective tool for the diagnosis of diabetic peripheral neuropathy in clinical settings.

Personalized Prediction of Long-Term Renal Function Prognosis Following Nephrectomy Using Interpretable Machine Learning Algorithms: Case-Control Study.

Acute kidney injury (AKI) is a common adverse outcome following nephrectomy. The progression from AKI to acute kidney disease (AKD) and subsequently to chronic kidney disease (CKD) remains a concern; yet, the predictive mechanisms for these transitions are not fully understood. Interpretable machine learning (ML) models offer insights into how clinical features influence long-term renal function outcomes after nephrectomy, providing a more precise framework for identifying patients at risk and supporting improved clinical decision-making processes. This study aimed to (1) evaluate postnephrectomy rates of AKI, AKD, and CKD, analyzing long-term renal outcomes along different trajectories; (2) interpret AKD and CKD models using Shapley Additive Explanations values and Local Interpretable Model-Agnostic Explanations algorithm; and (3) develop a web-based tool for estimating AKD or CKD risk after nephrectomy. We conducted a retrospective cohort study involving patients who underwent nephrectomy between July 2012 and June 2019. Patient data were randomly split into training, validation, and test sets, maintaining a ratio of 76.5:8.5:15. Eight ML algorithms were used to construct predictive models for postoperative AKD and CKD. The performance of the best-performing models was assessed using various metrics. We used various Shapley Additive Explanations plots and Local Interpretable Model-Agnostic Explanations bar plots to interpret the model and generated directed acyclic graphs to explore the potential causal relationships between features. Additionally, we developed a web-based prediction tool using the top 10 features for AKD prediction and the top 5 features for CKD prediction. The study cohort comprised 1559 patients. Incidence rates for AKI, AKD, and CKD were 21.7% (n=330), 15.3% (n=238), and 10.6% (n=165), respectively. Among the evaluated ML models, the Light Gradient-Boosting Machine (LightGBM) model demonstrated superior performance, with an area under the receiver operating characteristic curve of 0.97 for AKD prediction and 0.96 for CKD prediction. Performance metrics and plots highlighted the model's competence in discrimination, calibration, and clinical applicability. Operative duration, hemoglobin, blood loss, urine protein, and hematocrit were identified as the top 5 features associated with predicted AKD. Baseline estimated glomerular filtration rate, pathology, trajectories of renal function, age, and total bilirubin were the top 5 features associated with predicted CKD. Additionally, we developed a web application using the LightGBM model to estimate AKD and CKD risks. An interpretable ML model effectively elucidated its decision-making process in identifying patients at risk of AKD and CKD following nephrectomy by enumerating critical features. The web-based calculator, found on the LightGBM model, can assist in formulating more personalized and evidence-based clinical strategies.

Quercetin ameliorates diabetic kidney injury in rats by inhibiting the HMGB1/RAGE/NF-κB signaling pathway

To explore the effect of quercetin on renal inflammation and cell apoptosis in diabetic rats and its possible mechanisms. Twenty-four adult male SD rats were randomized equally into normal control group, high-glucose and high-fat feeding group, streptozotocin (STZ) -induced diabetic model group, and quercetin treatment (daily dose 100 mg/kg) group. Pathological changes of the renal tissues of the rats were observed with HE staining, serum inflammatory factor levels were determined with ELISA, and renal expression of NF‑κB was observed by immunohistochemistry. Fast blood glucose (FBG), serum levels of triglyceride (TG), BUN, and Scr, and 24-h urine protein content of the rats were measured, and renal expressions of HMGB1, RAGE, NF‑κB, Bax, Bcl-2, and caspase-3 were detected with Western blotting. The diabetic rats showed significantly increased levels of FBG, TG, BUN, and Scr, renal hypertrophy index, 24-h urinary protein content, serum IL-1β, IL-6 and TNF-α levels and renal expressions HMGB1, RAGE, NF‑κB, Bax, and caspase-3 with decreased renal expression of Bcl-2. All these changes were significantly alleviated by quercetin treatment of the rats. Quercetin can ameliorate kidney injury in diabetic rats possibly by inhibiting the HMGB1/RAGE/NF-κB inflammatory signaling pathway to reduce renal inflammation and renal cell apoptosis.

Lung-Kidney Axis in Cystic Fibrosis: Early Urinary Markers of Kidney Injury Correlate with Neutrophil Activation and Worse Lung Function.

Adult people with cystic fibrosis (PwCF) have a higher risk of end-stage kidney disease than the general population. The nature and mechanism of kidney disease in CF are unknown. This study quantifies urinary kidney injury markers and examines the hypothesis that neutrophil activation and lung infection are associated with early kidney injury in CF. Urinary total protein, albumin, and markers of kidney injury and neutrophil activation, normalized to creatinine, as well as urinary immune cells, were quantified in CF (n = 48) and healthy (n = 33) cohorts. Infection burden and chronicity were defined by sputum culture and serum titers of anti-bacterial antibodies. PwCF had increased urinary protein levels, consisting of low-molecular-weight tubular injury markers, independent of glomerular filtration rate (eGFR). This finding suggests subclinical renal injury processes. Urinary analysis of the CF cohort identified different associations of urinary injury markers with aminoglycoside exposure, lung function, and neutrophil activation. High urinary KIM-1 levels and increased prevalence of neutrophils among urine immune cells correlated with decreased lung function in PwCF. The relationship between tubular injury and decreased lung function was most prominent in patients harboring chronic Pseudomonas aeruginosa infection. Increased urinary tubular injury markers in PwCF suggest early subclinical renal injury not readily detected by eGFR. The strong association of high urinary KIM-1 and neutrophils with diminished lung function and high Pseudomonas aeruginosa burden suggests that pulmonary disease may contribute to renal injury in CF.

Association of urinary albumin excretion with all-cause and cardiovascular mortality among patients with rheumatoid arthritis: a national prospective study.

Rheumatoid arthritis (RA) patients suffering from chronic renal insufficiency tend to exhibit subtle manifestations at the beginning. Urine albumin to creatinine ratio (ACR) is a sensitive indicator for early assessment of renal function. However, it is unclear whether it serves as an independent risk factor influencing the prognosis of RA patients. National Health and Nutrition Examination Survey (NHANES) data from 2009-2018 were included. Kaplan-Meier (K-M) curves were plotted to compare the cumulative survival probability of RA patients with different urinary albumin excretion. The association of ACR with mortality among RA patients was investigated with Cox regression model, restricted cubic spline (RCS) and stratified analyses. The prognostic efficacy of ACR and estimated glomerular filtration rate (eGFR) was evaluated by receiver operating characteristic (ROC) curves. The Cox regression model adjusted with covariates showed a 53% (HR 1.53, 95% CI 1.06-2.21) increase in all-cause mortality and a statistically non-significant increase in cardiovascular disease (CVD) mortality in RA patients with microalbuminuria (30mg/g ≤ACR<300mg/g). ACR≥300mg/g was associated with an increase in all-cause mortality (HR 2.62, 95% CI 1.55-4.45) and CVD mortality (HR 5.67, 95% CI 1.96-16.39). RCS demonstrated a nonlinear correlation between ACR and all-cause mortality in RA patients with microalbuminuria. Subgroup analysis showed that CVD mortality was higher in RA patients with microalbuminuria characterized by the following features: female, other ethnicity, eGFR≥60 ml/min/1.73 m2, hypertension or hyperlipidemia. Compared with eGFR, ACR provided better prognostic efficacy than eGFR with higher values of the area under the curve (AUC) for all-cause mortality (AUC=0.683, 95% CI 0.613-0.754) and CVD mortality (AUC=0.681, 95% CI 0.541-0.820). ACR is an independent risk factor affecting the prognosis of RA patients. The all-cause mortality was increased in RA patients with albuminuria. There was an upward trend in the CVD mortality of those with macroalbuminuria when ACR increased.

A case of protein-losing gastroenteropathy due to Sjögren's syndrome detected by foggy vision with refractive error of the intraocular lens.

A woman in her forties visited an ophthalmologist for rapidly progressive foggy vision. Naked visual acuity had decreased to 0.15, and although her eyes showed no abnormalities, internal disease was suspected and albumin 2.6g/dL was found. Protein leakage from the intestinal tract was suspected since there was no urinary protein excretion. 99mTechnetium-labeled albumin D scintigraphy showed protein leakage from the intestinal tract. A stool α1-antitrypsin clearance test showed an increase to 56.3mL/day, leading to a diagnosis of protein-losing gastroenteropathy. Blood biochemistry revealed abnormally high levels of anti-SS-A and anti-SS-B antibodies (≥ 1200U/mL and ≥ 1000U/mL, respectively). A lip salivary gland biopsy revealed lymphocytic infiltrate at least 1 focus per 2mm × 2mm > 50 lymphocytes per conduit). The Schirmer test result was 5mm/5min or less, which led to the diagnosis of Sjögren's syndrome. The serum albumin level increased with intravenous administration of methylprednisolone 50mg (1mg/kg), and the patient is currently on oral prednisolone at a gradually decreasing dose. After administration of prednisolone, visual acuity recovered to 1.2 with recovery of albumin.

Research on the Improvement of Endothelial Cell Function and Trophoblast Apoptosis in Rats with Preeclampsia by Tanshinone IIA

Background Preeclampsia is a pregnancy complication characterized by high blood pressure and signs of damage to another organ system, often the kidneys. Recent studies suggest that endothelial dysfunction and trophoblast apoptosis are involved in the pathogenesis of preeclampsia. Purpose To investigate the effects of tanshinone IIA (TIIA) on clinical symptoms, vascular endothelial function, and placental trophoblast apoptosis in preeclampsia rats. Materials and Methods Twenty-four pregnant Sprague-Dawley rats, between 8 and 10 weeks old, were randomly divided and allocated into three groups: Control, model, and treatment, with each group consisting of 8 rats. The control group received normal saline injections via the tail vein; the model group received NG-nitro-l-arginine methyl ester (l-NAME) to induce preeclampsia, followed by normal saline injections; and the treatment group received TIIA (10 mg/kg) via tail vein injection after preeclampsia induction with l-NAME. Various parameters were measured, including tail artery systolic pressure, 24-hour proteinuria, offspring and placental weight, levels of endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), placental growth factor (PLGF), and soluble FMS-like tyrosine kinase 1 (sFlt-1) in serum, and expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2-related X protein (Bax) in placental trophoblasts. Results TIIA treatment led to decreased tail artery systolic pressure and 24-hour urine protein levels, increased body and placental weights of offspring, and favorable changes in serum levels of ET-1, sFlt-1, eNOS, and PLGF. Moreover, TIIA treatment resulted in decreased Bax levels and apoptosis in placental trophoblasts, along with increased Bcl-2 levels. Conclusion TIIA can improve the clinical symptoms of preeclampsia in rats induced by l-NAME, alleviate the apoptosis of placental trophoblast cells, and improve vascular endothelial function.

Inter-laboratory variation for urine albumin among laboratories in a Swedish external quality assessment scheme 2005–2023

IntroductionIncreased albuminuria is associated with elevated mortality. Urine albumin (U-ALB) above 20 mg/L or albumin-to-creatinine ratio (U-ACR) of 3 g/mol are indicative of moderately increased albuminuria. Due to limited standardization among U-ALB methods, diagnosis of increased albuminuria might prove difficult. Materials and methodsData from Equalis’s external quality assessment scheme for low U-ALB levels during 2005–2023 were categorized according to manufacturer and divided into central laboratory (CLAB) and point-of-care testing (POCT) methods. Manufacturer median values were compared to total group mean consensus values and manufacturer CV% was compared at different U-ALB levels. ResultsCLAB was generally closer to consensus values and had lower CV% than POCT at U-ALB levels around 20 mg/L. For CLAB, Roche methods were approximately equal to consensus U-ALB, Abbott 4 % above, and Siemens 5 % below. For POCT, HemoCue was 1 % below, Siemens 7 % above, and Abbott 8 % below. For U-Creatinine, all manufacturers generally had a good agreement differing on average by 1–4 % from consensus. ConclusionsAlthough U-ALB methods generally meet The National Kidney Disease Education Program (NKDEP) recommendations of method bias less than 13 % and imprecision less than 30 %, differences among manufacturers have increased over the last years, with 2023 showing the largest differences between methods. This highlights the need for guidelines for albuminuria and ACR to take method differences into consideration, but also for implementation of suitable urine reference materials.

Cellulose acetate electrophoretic separation of serum and urine proteins in Nigerian children with autism spectrum disorders

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) characterized by social communication challenges and restricted, repetitive behaviors. While genetic and environmental factors are known to contribute to ASD, the role of the immune system remains unclear. This study investigated the separation patterns of serum and urine proteins in Nigerian children with ASD compared to typically developing children and children with other NDDs.MethodsForty-seven participants aged 3–8 years were recruited, including 16 children diagnosed with ASD and 16 children with other NDDs, both according to DSM-5 criteria, along with 15 neurotypical children. Blood and urine samples were collected for protein analysis. Total protein and albumin levels were measured in both serum and urine using established methods. Protein separation in serum and urine was performed using cellulose acetate electrophoresis, followed by densitometry analysis of the electrophoretic patterns.ResultsThe results revealed no significant differences in total serum protein levels and most protein fractions between the groups. However, children with other NDDs exhibited significantly lower levels of alpha-2 globulin compared to neurotypical children. Conversely, both ASD and NDD groups showed significantly higher gamma globulin levels compared to the control group. Interestingly, spot urine protein levels were significantly higher in children with ASD compared to neurotypical children.ConclusionThe observed changes in alpha-2 and gamma globulin levels suggest potential immune system involvement in ASD and other NDDs. The higher urine protein excretion in the ASD group warrants further investigation to explore the potential of urinary protein biomarkers for ASD diagnosis.

Serum uric acid-lowering effect of sacubitril/valsartan in hypertensive patients: evaluation by switching from angiotensin II receptor blockers.

Since hyperuricemia is a risk factor for cardiovascular disease and chronic kidney disease, it is necessary to pay attention to trends in uric acid levels when treating hypertensive patients with drugs. The present study investigated the effect of switching from angiotensin II receptor blocker (ARB) to sacubitril/valsartan on serum uric acid levels in treated hypertensive patients and further examined what factors could be associated with its effect. In 75 hypertensive patients under treatment with at least one antihypertensive agent including ARB, clinic blood pressure and biochemical parameters were assessed before and after drug switching to sacubitril/valsartan (200 mg/day). Clinic SBP and DBP significantly decreased after drug switching to sacubitril/valsartan (P < 0.0001, respectively). Serum creatinine, estimated glomerular filtration rate (eGFR), and urinary protein did not change after switching to sacubitril/valsartan, but serum uric acid significantly decreased (5.70 ± 1.44 to 5.40 ± 1.43 mg/dl, P = 0.0017). The degree of uric acid lowering was greater in patients switching from ARB plus diuretic than in those switching from ARB, but switching to sacubitril/valsartan from ARB only (except losartan) also significantly decreased uric acid levels. In all subjects, the change in serum uric acid after drug switching to sacubitril/valsartan was closely correlated with the change in eGFR (r = -0.5264, P < 0.0001). Our findings indicate that switching from ARB to sacubitril/valsartan reduces serum uric acid levels in hypertensive patients and suggest that this uric acid-lowering effect may be associated with an increase in eGFR.

Use of belimumab in treating patients with systemic lupus erythematosus: a single-center, real-world retrospective study

ObjectiveTo investigate the efficacy and safety of belimumab in the treatment of systemic lupus erythematosus (SLE) in a real-world setting and provide a valuable reference for clinical treatment.MethodsIn this retrospective study, 101 patients with SLE who came to our hospital from March 2020 to September 2022, 56 of whom with lupus nephritis (LN), were selected. All patients received belimumab in combination with standard of care(SoC)therapy regimen for more than 52 weeks and their clinical/laboratory data, assessment of disease activity, glucocorticoids dosage and occurrence of adverse events were recorded. Lupus Low Disease Activity State (LLDAS) and DORIS remission as a primary goal in the treatment of SLE. The groups were classified according to the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K): SLEDAI-2 K < 6 was categorized as the mild group (mild activity) and SLEDAI-2 K ≥ 6 was categorized as the active group (moderate-severe activity). The disease of the two groups mentioned above were assessed using the SELENA-SLEDAI Flare Index (SFI) and the SLE Responder Index-4 (SRI-4), respectively. Furthermore, we used complete remission (CR) and partial remission (PR) in the kidney as the standard for efficacy evaluation for LN patients.ResultsAfter 52 weeks of treatment with belimumab, patients’ complement levels increased significantly (p < 0.05); Other indicators such as 24-hour urine protein quantification and daily glucocorticoids dose decreased compared to pretreatment (p < 0.05). At 52 weeks, (i) after evaluation, the whole group of patients showed significant improvement in their condition; (ii) 55.4% of patients achieved LLDAS and 23.8% achieved DORIS remission; (iii) 73.2% of patients with LN achieved CR, 16.1% achieved PR. Adverse reactions were observed in 15 patients (14.9%), all of which normalized after symptomatic treatment.ConclusionsIn general, during treatment with belimumab, immunological and biochemical indices improved in SLE patients, urinary protein levels were reduced in LN patients, and the rate of renal function remission was effectively increased; At the same time, the use of belimumab is associated with a low frequency of side effects, good overall tolerability and a favorable safety profile.

The hidden impact: the rate of nicotine metabolism and kidney health.

The effects of nicotine metabolism on the kidneys of healthy individuals have not been determined. The nicotine metabolite ratio (NMR) indicates the rate of nicotine metabolism and is linked to smoking behaviors and responses to tobacco treatments. We conducted this study in order to investigated the relationship between nicotine metabolite ratio (NMR) and kidney function. An analysis of cross-sectional data of adults was conducted using a population survey dataset (National Health and Nutrition Examination Survey Data 2013/2018 of the United States). A weighted multivariate regression analysis was conducted to estimate the correlation between NMR and kidney function. Furthermore, we apply fitting smooth curves to make the relationship between NMR and estimated glomerular filtration rate (eGFR) more visualized. The research included a total of 16153 participants. Weighted multivariate regression analyses adjusted for possible variables showed a negative relationship between NMR and estimated glomerular filtration rate (eGFR).The β (95%CI) of the regression equation between NMR and eGFR was -2.24 (-2.92, -1.55), the trend testing showed consistent results. NMR is positively correlated with urinary albumin creatinine ratio (uACR), but it is not statistically significant. A stratified analysis found a negative correlation between NMR and eGFR in all age, gender and diabetes subgroups, the results were not statistically significant among Mexican Americans and other races. Notably, each unit rise in NMR corresponded to a 4.54 ml/min·1.73m² lower eGFR in diabetic participants and a 6.04 ml/min·1.73m² lower eGFR in those aged 60 and above. Our study shows that nicotine metabolite ratio is negatively associated with kidney function among most adults. It will be necessary to conduct more well-designed prospective clinical trials in order to determine the exact causal interactions between NMR and kidney function. Specific mechanisms also need to be further explored in basic experiments.

Clinical analysis of sirolimus therapy in children with refractory nephrotic syndrome

To investigate the clinical efficacy of sirolimus in treating children with refractory nephrotic syndrome, the clinical data for 22 children from the Children's Hospital of Hebei Province were analyzed retrospectively. There were 16 boys and six girls, and the treatment period was from September 2015 to April 2021. There were two patients with steroid-dependent nephrotic syndrome (SDNS), six patients with frequently relapsing nephrotic syndrome (FRNS), and 14 patients with steroid-resistant nephrotic syndrome (SRNS). All patients were defined as having refractory nephrotic syndrome. There were 12 patients (including nine SRNS patients and three FRNS patients) with minimal change disease (MCD), three patients (three SRNS patients) with focal segmental glomerular sclerosis (FSGS), one FRNS patient with mesangial proliferative glomerulonephritis (MsPGN), and six patients without a kidney biopsy. Compared with levels before sirolimus treatment, 24-hour urine protein (24-h UP), low-density lipoprotein cholesterol (LDL-C), urea (Ur) and serum creatinine (SCr) levels were significantly lower (all p < 0.05). Moreover, albumin (Alb) was significantly increased (p < 0.05), and there were no significant differences in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), immunoglobulin A (IgA), immunoglobulin G (IgG) or immunoglobulin M (IgM) (all p > 0.05) at the first follow-up. Sirolimus is effective as the first treatment of some children with refractory nephrotic syndrome, but its long-term efficacy and adverse reactions still require follow-up.

Association of different obesity indexes with diabetic kidney disease in patients with type 2 diabetes mellitus: a cross-sectional study

The objective of this study is to investigate the association between diabetic kidney disease (DKD) and various adiposity indexes, including the visceral adiposity index (VAI), lipid accumulation product index (LAPI), visceral fat area (VFA), and subcutaneous fat area (SFA) in type 2 diabetes mellitus (T2DM) patients. 1176 T2DM patients was stratified into normoalbuminuria (NO), microalbuminuria (MI), and macroalbuminuria (MA) groups based on their urinary albumin-creatinine ratio (UACR) levels. To analyse the correlation between DKD and VAI, LAPI, VFA, and SFA. Multiple linear, restricted cubic spline (RCS), subgroup analyses, and multinomial logistic regression were employed. After adjusting for confounding variables, UACR levels were positively associated with VAI, LAPI, and VFA. RCS curves demonstrated a J-shaped dose-response relationship between VAI and LAPI levels with UACR levels, while a linear correlation was observed between UACR levels and VFA. Using the NO and MI as reference groups, the MA group was analysed as the observational group. DKD severity was positively associated with VAI, LAPI and VFA. When evaluating DKD prognostic risk, with the low-risk and medium-risk groups serving as reference categories, a significant positive correlation was identified with prognostic risk and VAI, LAPI, and VFA in the high-risk or very high-risk groups. In patients with T2DM, DKD severity and prognostic risk were positively correlated with VAI, LAPI, and VFA levels.

Proteinuria and albuminuria among a global primary CVD prevention cohort of PWH: prevalence and associated factors.

To determine baseline prevalence of proteinuria and albuminuria among REPRIEVE participants and evaluate associated risk factors. Cross sectional analysis of a baseline sample of participants from the REPRIEVE Trial. REPRIEVE is an international primary cardiovascular prevention RCT of pitavastatin calcium vs. placebo among PWH on antiretroviral therapy. A representative subset (2791 participants) had urine collected at study entry. Urine protein to creatinine ratios (uPCR) and albumin to creatinine ratios (uACR) were classified as normal, moderately increased and severely increased. These were dichotomized to Normal or Abnormal for log-binomial regression analysis. Demographic, cardiometabolic, and HIV-specific data were compared among those with normal versus abnormal results. Overall, median age 49 years, 41% female sex, 47% black or African American race, 36% had eGFR <90 mL/min/1.73 mm2. For uPCR, 27% had moderately or severely increased values. For uACR, 9% had moderately or severely increased values. In the fully adjusted model for proteinuria, female sex, older age, residence in sub-Saharan Africa or East Asia, lower BMI, lower CD4 cell count, and use of TDF were associated with abnormal values. In the fully adjusted model for albuminuria, a diagnosis of HTN was associated with abnormal values. Abnormal proteinuria and albuminuria remain common (27% and 9%) despite controlled HIV. Lower current CD4 count and TDF use were strongly associated with proteinuria. Certain modifiable comorbidities, including HTN and smoking, were associated with abnormal values. In PWH with preserved eGFR, urine measures identify subclinical kidney disease and afford the opportunity for intervention.

Abstract B018: UroPanc: A large prospective observational study for validation of urinary biomarker test for the earlier detection of pancreatic adenocarcinoma

Abstract Introduction. A bleak prognosis of Pancreatic ductal adenocarcinoma (PDAC) is largely due to late diagnosis and highly accurate, non-invasive diagnostic tests are urgently needed to improve patients’ survival. Our group has previously reported on urinary biomarker panel, comprising of LYVE1, REG1B and TFF1 (1-2), which distinguished controls from PDAC stages I-II with AUC 0.936 and sensitivity/specificity (SN/SP)&amp;gt;85%. We constructed the logistic regression based algorithm for interpretation of the data, PancRISK (3), which enables the stratification of high- risk patients into those with ‘average’ or ‘elevated’ risk of developing PDAC. Recently, we showed that our panel combined with CA19-9 can detect PDAC up to 2 years before clinical diagnosis (4). Aim. Here, we report on the design and interim analysis of the UroPanc Trial (ClinicalTrials.gov NCT04449406), which aims to evaluate the accuracy of the urinary biomarker panel and the affiliated PancRISK. We plan to recruit two cohorts: the first one comprises asymptomatic individuals that have high risk of developing PDAC due to familial history and genetic syndroms - these will be recruited through the EUropean Registry Of familial PAncreatic Cancer and hereditary pancreatitis (EUROPAC) (PI: Prof W Greenhalf and team, Liverpool, UK). The second cohort comprises patients with symptoms suggestive of PDAC – such patients are recruited at gastrointestinal clinics at University College London Hospitals (UCLH, PI: Prof S Pereira and team), and The Royal London Hospital (PI: Dr P Wilson).Methods. The urinary proteins are assayed by commercially available ELISAs. Plasma CA19-9 is measured at The Doctors Laboratory in London, UK using Cobas601E, Roche platform. The statistical analysis and accuracy of the test is measured by c-statistics, SN/SP and positive/negative predictive value. The results are compared to imaging and histopathology records (where available). Human factor and budget impact analysis of the future inclusion of the urine test into the diagnostic and surveillance pathways for PDAC patients is ongoing (PI: Dr M Z Ni and the team, Imperial College London, UK). Results and conclusions. At present, 1067 patients have been recruited, and urine samples from 825 patients have been assayed. An interim analysis has shown promising results with SP of 91% and SN of 86%, and accuracy of cancer detection of 90%. Combined with the health economic analysis, we currently work towards the future implementation of this test into clinical practice, with the potential to significantly improve the current diagnostic pathway for individuals at risk of pancreatic cancer. 1. Radon, TP, et al. Clin Cancer Res, 2015; 21:3512-21. 2. Debernardi, S, et al. PLOSMed, 17(12); e1003489. 3. Blyuss, O, et al. Br J Cancer, 2020; 122:692-6. 4. Debernardi, S, et al. Int J Cancer, 2023; 152:769–80. Citation Format: Silvana Debernardi, Evelyn Kurotova, Nurshad Ali, Mariam Mahamood, Ismita Chhetri, Steve Pereira, Patrick Wilson, Bill Greenhalf, Melody Z Ni, Oleg Blyuss, Tatjana Crnogorac-Jurcevic. UroPanc: A large prospective observational study for validation of urinary biomarker test for the earlier detection of pancreatic adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B018.

Protection Effect of Soy Isoflavones (Genistein and Daidzein) on Hematologic Parameters in Acute Kidney Injury

Background: Acute kidney injury (AKI) is a severe, high-morbidity condition with limited effective preventative and therapeutic strategies despite advancements in understanding and treatment. Specific Background: Rhabdomyolysis-induced acute kidney injury (AKI) presents significant challenges in renal research, but soy isoflavones, particularly GN and DZ, have shown potential in mitigating oxidative stress and inflammation. Knowledge Gap: Soy isoflavones, while potentially providing renal protection, their impact on renal and hematologic parameters in glycerol-induced AKI models has not been thoroughly studied. Aims: The study evaluated the effectiveness of soy isoflavones in regulating renal and hematologic parameters in a glycerol-induced AKI rat model, assessing their potential as therapeutic agents. Results: The study involving adult female Wistar rats showed that pretreatment with glycerol or dihydroxystilbene significantly reduced urinary β2-microglobulin, albumin, BUN, and serum creatinine levels in the AKI-induced group, reversing hematological changes. Novelty: The study explores the protective effects of soy isoflavones on renal function and hematologic parameters in AKI, highlighting GN's superior efficacy over DZ. Implications: Soy isoflavones, particularly GN, may be potential preventive or therapeutic strategies for AKI caused by rhabdomyolysis, warranting further research for clinical applications. Highlights: GN and DZ reduce kidney damage in glycerol-induced AKI. GN is more effective than DZ in kidney and blood parameters. Soy isoflavones could treat or prevent AKI. Keywords: Acute kidney injury, soy isoflavones, glycerol-induced AKI, renal protection, hematologic parameters

Comparison of cat stone matrix and cat urine proteomes to human calcium oxalate stone matrix and urine proteomes.

Cat calcium oxalate monohydrate kidney stone matrix proteome showed great similarity to human calcium oxalate monohydrate stone matrix proteome, but inference of mechanistic similarity was limited by the absence of cat urine proteomic data. In this study, urine proteome distributions were measured by the same methods in 7 healthy cats for comparison to both the published human urine and cat calcium oxalate stone matrix proteomes to assess for similar enrichment patterns in both species. Furthermore, proteomic distributions were determined in cat struvite stone matrix to test for similarity to calcium oxalate monohydrate stone matrix and urine proteomes. Cat urine proteins demonstrated a similar distribution of abundance as a function of isoelectric points or net charge to human urine samples, and consequently the similarly altered patterns of protein distributions seen in calcium oxalate monohydrate stone matrix seen from both cat and human stones likely derives from the same preferential adsorption mechanism. Furthermore, the fact that protein abundance patterns seen in cat struvite stone matrix samples differ from both urine and calcium oxalate monohydrate stone matrix proteomes in systematic ways suggests that a combination of protein-protein and protein crystal interactions underly the formation of the crystal aggregates that comprise stones.