Proteinuria In Patients Research Articles

Correlation between adipocyte fatty acid binding protein 4 with albuminuria in patients with diabetic nephropathy

Correlation between adipocyte fatty acid binding protein 4 with albuminuria in patients with diabetic nephropathy

Anatomical and functional remodeling of left ventricle in patients with primary aldosteronism and concomitant albuminuria.

Primary aldosteronism (PA) is the leading cause of secondary hypertension globally and is associated with adverse cardiovascular outcomes. However, the cardiac impact of concomitant albuminuria remains unknown. To compare anatomical and functional remodeling of left ventricle (LV) in PA patients with or without albuminuria. Prospective cohort study. The cohort was separated into two arms according to the presence or absence of albuminuria (>30 mg/g of morning spot urine). Propensity score matching with age, sex, systolic blood pressure, and diabetes mellitus was performed. Multivariate analysis was conducted with adjustments for age, sex, body mass index, systolic blood pressure, duration of hypertension, smoking, diabetes mellitus, number of antihypertensive agents, and aldosterone level. A local-linear model with bandwidth of 2.07 was used to study correlations. A total of 519 individuals with PA were enrolled in the study, of whom 152 had albuminuria. After matching, the albuminuria group had a higher creatinine level, at baseline. With regard to LV remodeling, albuminuria was independently associated with a significantly higher interventricular septum (1.22 > 1.17 cm, p = 0.030), LV posterior wall thickness (1.16 > 1.10 cm, p = 0.011), LV mass index (125 > 116 g/m2, p = 0.023), and medial E/e' ratio (13.61 > 12.30, p = 0.032), and a lower medial early diastolic peak velocity (5.70 < 6.36 cm/s, p = 0.016). Multivariate analysis further revealed that albuminuria was an independent risk factor for elevated LV mass index (p < 0.001) and medial E/e' ratio (p = 0.010). Non-parametric kernel regression also demonstrated that the level of albuminuria was positively correlated with LV mass index. The remodeling of LV mass and diastolic function under the presence of albuminuria distinctly improved after PA treatment. The presence of concomitant albuminuria in patients with PA was associated with pronounced LV hypertrophy and compromised LV diastolic function. These alterations were reversible after treatment for PA. Cardiac Impact of Primary Aldosteronism and Albuminuria Primary aldosteronism and albuminuria has been, respectively, demonstrated to bring about left ventricular remodeling, but the aggregative effect was unknown. We constructed a prospective single-center cohort study in Taiwan. We proposed the presence of concomitant albuminuria was associated with left ventricular hypertrophy and compromised diastolic function. Intriguingly, management of primary aldosteronism was able to restore these alterations. Our study delineated the cardiorenal crosstalk in the setting of secondary hypertension and the role of albuminuria for left ventricular remodeling. Future interrogations toward the underlying pathophysiology as well as therapeutics will facilitate the improvement of holistic care for such population.

Specifičnosti u lečenju hipertenzije kod bolesnika sa hroničnim bubrežnim oboljenjem

Today, it is believed that all over the world about 10% of the population has a kidney lesion, most often chronic kidney disease (CKD). Hypertension and diabetes mellitus are the most common causes of chronic kidney damage, and in everyday clinical practice, we often wonder whether hypertension is a consequence of a lesion of the kidney parenchyma and vasculature or is its cause. Patients with CKD have high cardiovascular (CV) morbidity and most often die from CV disease. The specificity of blood pressure treatment in patients with chronic kidney damage is that good control of hypertension not only leads to a reduction of CV risk but also to a slowing of the progression of chronic to terminal renal failure. There is no doubt that the first line of treatment for hypertension in patients with CKD is angiotensinconverting enzyme inhibitors (ACEi) and angiotensin-2 receptor blockers (ARB). They are recommended especially for those patients with diabetic nephropathy because, in addition to their antihypertensive effect, they reduce proteinuria, slow down the progression of chronic kidney failure, especially if given in the early stages of CKD, and reduce CV risk. However, for a long time, there have been controversial opinions about whether in the advanced stages of renal failure, when the glomerular filtration rate (GFR) is &lt; 30 mL/min/1.73 m2, these drugs should be excluded. According to the latest KDIGO guidelines in 2021, renin-angiotensinaldosterone (RAAS) blockers are the first line in the treatment of proteinuric CKD patients, with and without diabetes mellitus, and in stage 4, with a note that these drugs should be continued in therapy unless there is marked hyperkalemia (potassium &gt; 6 mmol/L), acute kidney damage or decrease in estimated glomerular filtration rate &gt; 30%. The most important thing is to individualize the optimal therapy for each patient. In the guidelines for the treatment of hypertension in patients with CKD, there are no clear recommendations for the treatment of unregulated hypertension when target pressures cannot be achieved with RAAS blockade and when there are contraindications for the administration of this group of drugs. The addition of calcium channel blockers, diuretics, and beta blockers is based on expert opinion.

Association between the triglyceride-glucose index and albuminuria in hypertensive individuals

ABSTRACT Background Previous studies have demonstrated that the triglyceride-glucose (TyG) index is significantly associated with vascular damage. Albuminuria is a marker of hypertension-mediated organ damage (HMOD) and has been linked to a greater risk of cardiovascular disease (CVD). However, the association between the TyG index and albuminuria in patients with hypertension is not clear. This population research focused on subjects with hypertension to investigate the association between an elevated TyG index and albuminuria. Methods From September 2019 to November 2019, 789 hypertensive participants were involved in our research. Logistic regression models were performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for albuminuria according to the quartiles of the TyG index. Results Multivariate logistic regression analysis revealed that the TyG index was significantly associated with albuminuria. Using the lowest TyG index quartile as the reference, the fully adjusted ORs (95% CIs) for albuminuria for TyG index quartile II, quartile III, and quartile IV were 1.90 (1.17–3.12), 1.81 (1.07–3.07), and 3.46 (2.06–5.91), respectively. The results in the subgroup analysis were similar to the main analyses except for the smokers. Restricted cubic spline curves based on logistic regression models evaluated the linear association between the TyG index and albuminuria (P for nonlinear = 0.831). Conclusion The TyG index was positively associated with albuminuria among hypertensive participants.

Traditional Chinese medicine body constitution predicts new-onset diabetic albuminuria in patients with type 2 diabetes: Taichung diabetic body constitution prospective cohort study

This prospective cohort study explored whether body constitution (BC) independently predicts new-onset albuminuria in persons with type 2 diabetes mellitus (T2DM) enrolled in the diabetes care management program (DCMP) of a medical center, providing evidence of integrating traditional Chinese medicine into DCMP for improving care quality. Persons with T2DM (n = 426) originally without albuminuria enrolled in DCMP were recruited in 2010 and were then followed up to 2015 for detecting new-onset albuminuria. The participants received urinalysis and blood test annually. Albuminuria was determined by an elevated urinary albumin/creatinine ratio (≥ 30 µg/mg), and poor glucose control was defined as Glycosylated hemoglobin above or equal to 7%. BC type (Yin deficiency, Yang deficiency, and phlegm stasis) was assessed using a well-validated body constitution questionnaire at baseline. Risk factors for albuminuria (sociodemographic factors, diabetes history, lifestyle behaviors, lipid profile, blood pressure, and kidney function) were also recorded. Hazard ratios (HR) of albuminuria for BC were estimated using multivariate Cox proportional hazards model. During the 4-year follow-up period, albuminuria occurred in 30.5% of participants (n = 130). The HR indicated that Yin deficiency was significantly associated with an increased risk of new-onset albuminuria in persons with T2DM and good glucose control after adjustment for other risk factors (HR = 2.09; 95% confidence interval = 1.05-4.17, P = .04), but not in those with poor glucose control. In persons with T2DM and poor glucose control, phlegm stasis was also significantly associated with a higher risk of albuminuria (2.26; 1.03-4.94, P = .04) after multivariate adjustment, but not in those with good glucose control. In addition to already-known risk factors, BC is an independent and significant factor associated with new-onset albuminuria in persons with T2DM. Our results imply Yin deficiency and phlegm stasis interacting with glucose control status may affect new-onset albuminuria in persons with T2DM.

The Prevalence of Chronic Kidney Disease and Albuminuria in Patients With Type 1 and Type 2 Diabetes Attending a Single Centre.

Background Diabetes is the leading cause of chronic kidney disease worldwide. Diabetic kidney disease is one of the microvascular complications of diabetes and it involves changes in glomerular hemodynamics, interstitial fibrosis, and tubular atrophy. Early detection and management of Diabetic kidney disease (DKD) help to reduce morbidity and mortality. This study aims to assess the prevalence of nephropathy and albuminuria in the diabetic population attending an Irish tertiary care center. Methods Retrospective data collection and analysis of patients diagnosed with Type 1 diabetes mellitus(T1DM) and Type 2 diabetes mellitus (T2DM) through the Development and Integration of Accurate Mathematical Operations in Numerical Data-Processing (DIAMOND) database in a single Irish tertiary care center. An audit tool was used to collect patients' information including gender, age, type of diabetes, serum creatinine, urinary albumin excretion, albumin creatinine ratio (ACR), body mass index, and last available glycated hemoglobin (HbA1c). Results Out of 7394 subjects with T2DM, 3139 (42%) were identified with chronic kidney disease (CKD).There were 1866 subjects with positive ACR out of 3139 subjects with CKD in the T2DM cohort.This shows that 25% of subjects have diabetic kidney disease and 17% have CKD of undetermined etiology.In the T1DM cohort with 1166 subjects, 209 (18%) were identified with CKD.Out of these 209 subjects with CKD, 164 (14%) were ACR-positive.The prevalence of CKD and albuminuria were related to age in both T1DM and T2DM populations. Albuminuria showed a linear relationship with age in subjects with no known CKD, which shows that age causally relates to albuminuria independent of type and duration of diabetes. Conclusion CKD is more prevalent in patients with T2DM as compared to T1DM, whereas the prevalence of albuminuria is higher in the T1DM population.

The Utility of Perirenal Fat in Determining the Risk of Onset and Progression of Diabetic Kidney Disease.

Perirenal fat (PRF) has multiple effects on the kidney through its physical structure and adipocytokine-secreting ability. The present study explored the relationship between PRF thickness and the onset and progression of albuminuria in patients with diabetes. In the cross-sectional analysis, we screened 959 patients from 8764 subjects with type 2 diabetes mellitus (T2DM) who met the inclusion criteria and measured their perirenal fat thickness (PFT) using color Doppler ultrasound. A group of laboratory indexes were included in the analysis models. In a longitudinal study, a total of 218 patients with a baseline UACR <30 mg/g were included in the follow-up study. In a cross-sectional analysis, patients with diabetes and higher PFT presented with higher albuminuria. Multiple logistic regression analysis indicated that PFT was an independent risk factor for the degree of albuminuria in patients with T2DM (odds ratio = 4.186, 95%CI: 2.290-7.653, P < 0.001). In a longitudinal study, 218 albuminuria-free patients with T2DM at the baseline were followed up for a mean of 12.3 months. Based on the cutoff value from the ROC diagnostic test in the cross-sectional study, patients were divided into two groups: higher PFT (H-PFT) and lower PFT (L-PFT). Kaplan-Meier survival curve analysis showed that H-PFT was associated with a higher incidence of albuminuria than L-PFT (log-rank test, χ2 = 4.522, P = 0.033). Cox regression analysis showed that PFT was a risk factor for the earlier onset of albuminuria (hazard ratio 2.83, 95% CI: 1.34-4.88, P < 0.001). PRF evaluated by color Doppler ultrasound is an easy and reliable tool for predicting the onset and progression of albuminuria in patients with T2DM.

Uremic Metabolites Are Associated with Albuminuria and Estimated Glomerular Filtration Rate (eGFR) in Sickle Cell Disease

Introduction: Chronic kidney disease (CKD) is common in patients with sickle cell disease (SCD) and is associated with increased morbidity and mortality. As albuminuria and changes in estimated glomerular filtration rate (eGFR) occur well after substantial functional and structural damage have occurred, identification of novel biomarkers which could predict the development of CKD is necessary. Previous studies have shown an increase in the level of the uremic metabolite indoxyl-sulfate (IS) in urine in patients with SCD. IS and other uremic metabolites are cleared by active secretion in kidney tubule cells and their accumulation in these cells leads to increased oxidative stress, and apoptotic and necrotic cell death. In this single center, cross-sectional study, we investigated the associations between both urinary levels of uremic toxins and biomarkers of kidney tubular injury with persistent albuminuria and eGFR in patients with SCD. Methods: The participants represent a subset of patients with HbSS or HbSβ0 thalassemia enrolled in a prospective cohort study to assess the natural history of kidney disease in SCD. We excluded patients with diabetic nephropathy, cancer, connective tissue disease, other glomerular diseases, known infection with hepatitis (B or C) or HIV, end-stage kidney disease on dialysis and who had undergone bone marrow transplantation. Participants were enrolled during routine clinic visits. Urine levels of uremic toxins, indoxyl sulfate (IS) and trimethylamine-n-oxide (TMAO), and tubular injury biomarkers, monocyte chemoattractant protein-1 (MCP-1; also called CC-chemokine ligand 2 [CCL2]) and neutrophil gelatinase-associated lipocalin (NGAL) were measured using quantitative ELISA assay. All values obtained for urine biomarkers were normalized to urine creatinine. Persistent albuminuria was defined based on at least 2 of 3 spot urine albumin/creatinine ratio (ACR) values ≥30 mg/g of creatinine or a single value ≥100 mg/g. Glomerular filtration rate was estimated using the 2009 creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. As the distribution of the biomarkers were skewed, the data were log-transformed. Associations between both ACR and eGFR with each of the urine biomarkers were assessed using linear regression. Results: One hundred and sixteen subjects, 26 (22.4%; ACR - median 276.5 mg/g [IQR: 156, 802]) with persistent albuminuria (PA), and 90 (77.6%; ACR - median 13 mg/g [IQR: 6.5, 25.5]) without persistent albuminuria (non-PA) were evaluated. Subjects with PA appeared to be older and had lower hemoglobin and fetal hemoglobin levels, but higher reticulocyte counts, lactate dehydrogenase levels and systolic and diastolic blood pressures than subjects with non-PA (Table 1). Log-transformed urine levels of IS (β=0.52, 95% confidence interval [CI]: 0.08, 0.96, p=0.02), MCP-1 (β=0.65, 95% CI: 0.29, 1.01, p=0.0006) and NGAL (β=0.25, 95% CI: 0.02, 0.49, p=0.03) were positively associated with log-transformed ACR (Table 2). Log-transformed urine levels of IS (β=-8.0, 95% CI: -14.7, -1.3, p=0.02), MCP-1 (β=-11.6, 95% CI: -16.9, -6.3, p<0.0001) and NGAL (β=-6.0, 95% CI: -9.4, -2.6, p=0.0008) were inversely associated with eGFR. Log-transformed urine level of TMAO was not associated with either ACR or eGFR. Conclusion: This study demonstrates a novel association of IS with albuminuria and eGFR in patients with SCD. In addition, we confirm the association of biomarkers of tubular injury, MCP-1 and NGAL, with persistent albuminuria and eGFR in SCD. Future studies will determine whether uremic metabolites may predict the development of albuminuria in patients with SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Association of Novel Urinary Protein Biomarkers with Persistent Albuminuria in Patients with Sickle Cell Disease

Introduction: Standard assessments for kidney disease, albuminuria and decline in estimated glomerular filtration rate (eGFR), occur well after substantial functional and structural damage have ensued. Chronic kidney disease (CKD) is common in patients with sickle cell disease (SCD). With its association with increased morbidity and mortality, identification of novel biomarkers that could predict early development of CKD offers opportunities to modify risk factors in hopes of attenuating kidney function loss and decreasing mortality risk. Methods: The participants of this exploratory study represent a subset of patients with HbSS or HbSβ0 thalassemia enrolled in a prospective cohort study to assess the natural history of kidney disease in SCD. We excluded patients with diabetic nephropathy, cancer, connective tissue disease, other glomerular diseases, known infection with hepatitis (B or C) or HIV, end-stage kidney disease on dialysis and those who had undergone bone marrow transplantation. Participants were enrolled during routine clinic visits. Urine levels of clusterin [CLU; also referred to as apolipoprotein J], retinol-binding protein 4 [RBP4], alpha-1-microglobulin [A1M], interleukin-18 [IL-18], beta-2 microglobulin [B1M], insulin-like growth factor-binding protein 7 [IGFBP7], tissue inhibitor of metalloproteinases-2 [TIMP2], angiotensinogen [AGT], podocalyxin, and cysteine-rich with EGF-like domains 2 [CRELD2] were measured using quantitative ELISA assay. All values of urine biomarkers were normalized to urine creatinine. Persistent albuminuria (PA) was defined based on presence of at least 2 of 3 spot urine albumin/creatinine ratio (ACR) values ≥30 mg/g of creatinine or a single value ≥100 mg/g. Glomerular filtration rate was estimated using the 2009 creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Medians are presented with the interquartile range [IQR]. Associations between ACR and eGFR with each urine biomarker were assessed using linear regression. Levels of urinary biomarkers were compared using the Wilcoxon-Mann-Whitney test. Results: Thirty-seven subjects, 13 (35.2%) with PA (ACR - 147mg/g [IQR: 136.4, 223]), and 24 (64.9%) without PA (non-PA) (ACR - 12 mg/g [IQR: [6, 20]) were evaluated. Subjects with PA were older, had higher blood urea nitrogen (BUN), blood aspartate transaminase, and lower eGFR (Table 1). Urinary levels of CLU, RBP4, A1M, and AGT normalized to urine creatinine were significantly higher in subjects with PA vs. those with non-PA (Table 2). In univariate analysis, significant associations were identified between A1M and ACR (p=0.035) as well as between AGT and ACR (p<0.0001) (Table 2). In multivariable analyses, only AGT remained significantly associated with ACR (p=0.0003). Conclusion: The higher urinary levels of RBP4 and A1M, both low molecular weight proteins freely filtered in the glomerulus and reabsorbed by kidney proximal tubule cells, in subjects with PA suggests the presence of tubular injury. Higher levels of clusterin, a ubiquitously expressed glycoprotein that is rapidly upregulated upon acute kidney damage and present in de-differentiated kidney tubule cells, also indicates tubular injury in subjects with PA. Urinary AGT, the only precursor of all angiotensin peptides, is independently associated with ACR in this cohort. Higher levels of AGT indicates increased intrarenal renin-angiotensin system activity in subjects with PA. More studies are required to evaluate the association of these biomarkers with persistent albuminuria in SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

First-in-human autologous implantation of genetically modified adipocytes expressing LCAT for the treatment of familial LCAT deficiency

BackgroundFamilial lecithin: cholesterol acyltransferase (LCAT) deficiency (FLD) is a severe inherited disease without effective treatment. Patients with FLD develop severe low HDL, corneal opacity, hemolytic anemia, and renal injury. ObjectiveWe developed genetically modified adipocytes (GMAC) secreting LCAT (LCAT-GMAC) for ex vivo gene therapy. GMACs were prepared from the patient’s adipocytes to express LCAT by retroviral gene transduction to secrete functional enzymes. This study aimed to evaluate the safety and efficacy of LCAT-GMAC implantation in an FLD patient. MethodsProliferative preadipocytes were obtained from a patient using a ceiling culture and retrovirally transduced with LCAT. After obtaining enough cells by expansion culture of the transduced cells, the resulting LCAT-GMACs were implanted into a patient with FLD. To evaluate the safety and efficacy, we analyzed the outcome of the autologous implantation for 24 weeks of observation and subsequent 240 weeks of the follow-up periods. ResultsThis first-in-human autologous implantation of LCAT-GMACs was shown to be safe by evaluating adverse events. The LCAT-GMAC implantation increased serum LCAT activity by approximately 50% of the baseline and sustained over three years. Consistent with increased LCAT activity, intermediate-density lipoprotein (IDL) and free cholesterol levels of the small and very small HDL fractions decreased. We found the hemoglobin/haptoglobin complex in the hemolyzed pre-implantation sera of the patient. After one week of the implantation, the hemoglobin/haptoglobin complex almost disappeared. Immediately after the implantation, the patient's proteinuria decreased temporarily to mild levels and gradually increased to the baseline. At 48 weeks after implantation, the patient's proteinuria deteriorated with the development of mild hypertension. By the treatment with antihypertensives, the patient's blood pressure normalized. With the normalization of blood pressure, the proteinuria rapidly decreased to mild proteinuria levels. ConclusionsLCAT-GMAC implantation in a patient with FLD is shown to be safe and appears to be effective, in part, for treating anemia and proteinuria in FLD.

Suramin prevents the development of diabetic kidney disease by inhibiting NLRP3 inflammasome activation in KK-Ay mice.

Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes produce IL-18 upon being activated by various stimuli via the P2 receptors. Previously, we showed that serum and urine IL-18 levels are positively associated with albuminuria in patients with type 2 diabetes, indicating the involvement of inflammasome activation in the pathogenesis of diabetic kidney disease (DKD). In the present study, we investigated whether the administration of suramin, a nonselective antagonist of the P2 receptors, protects diabetic KK.Cg-Ay /TaJcl (KK-Ay) mice against DKD progression. Suramin or saline was administered i.p. to KK-Ay and C57BL/6J mice once every 2 weeks for a period of 8 weeks. Mouse mesangial cells (MMCs) were stimulated with ATP in the presence or absence of suramin. Suramin treatment significantly suppressed the increase in the urinary albumin-to-creatinine ratio, glomerular hypertrophy, mesangial matrix expansion, and glomerular fibrosis in KK-Ay mice. Suramin also suppressed the upregulation of NLRP3 inflammasome-related genes and proteins in the renal cortex of KK-Ay mice. P2X4 and P2X7 receptors were significantly upregulated in the isolated glomeruli of KK-Ay mice and mainly distributed in the glomerular mesangial cells of KK-Ay mice. Although neither ATP nor suramin affected NLRP3 expression in MMCs, suramin inhibited ATP-induced NLRP3 complex formation and the downstream expression of caspase-1 and IL-18 in MMCs. These results suggest that the NLRP3 inflammasome is activated in a diabetic kidney and that inhibition of the NLRP3 inflammasome with suramin protects against the progression of early stage DKD.

Semaglutide in Overweight and Obese patients: Cardiovascular and/or Renal Metabolic Benefits

We have read the article published by Kadowaki, et al. 1 “Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes mellitus in an East Asian population (STEP 6): A randomized, double blind, double dummy, placebo controlled, phase 3a trial”, where the authors conclude that semaglutide at a dose of 2.4 mg, in diabetic and non-diabetic patients, reduces obesity and overweight compared to placebo in East Asian patients. These interesting results, demonstrate once again its benefits regarding overweight and obesity1,2. We consider that there should be several relevant aspects to have in mind. The study shows, once again, that semaglutide might have dose dependent effects and some that aren’t dose dependent, with weight loss being a dose-dependent effect. Regarding renal benefits, we consider that including albuminuria as a variable is of importance, given that only eGFR by CKD-EPI was included in the study. The average eGFR of the patients was 97.2 cc/min, patients with an eGFR less than 30 were excluded (eGFR less than 60 in patients receiving SGLT-2 inhibitors). We mention this since it would’ve been interesting to evaluate albuminuric vs non-albuminuric patients, hence seeing if there are any renal benefits, especially in albuminuric patients that may be dose dependent. Recently, Shaman, et al. 3 reported that liraglutide and semaglutide had renal benefits in type 2 diabetes mellitus, but their effect in albuminuria was higher in patients with 1 mg of semaglutide weekly vs 0.5 mg weekly. The latter allows to hypothesize that this effect may be dose dependent. Given this, it would be of interest to assess if higher doses bring increased renal benefits, as seen in weight loss. In summary, having in mind the renal benefits seen by semaglutide in other studies4, it would be of great importance to verify the impact of albuminuria in patients with obesity. Hence, we hope that in the upcoming trials, albuminuria is taken into consideration, so that we can highlight not only the cardio-metabolic benefits, but renal benefits in diabetic and non-diabetic patients that are obese or overweight, and to assess if there is a dose-dependent response.

Albuminuria as a marker of systemic congestion in patients with heart failure.

Albuminuria is common in patients with heart failure and associated with worse outcomes. The underlying pathophysiological mechanism of albuminuria in heart failure is still incompletely understood. The association of clinical characteristics and biomarker profile with albuminuria in patients with heart failure with both reduced and preserved ejection fractions were evaluated. Two thousand three hundred and fifteen patients included in the index cohort of BIOSTAT-CHF were evaluated and findings were validated in the independent BIOSTAT-CHF validation cohort (1431 patients). Micro-albuminuria and macro-albuminuria were defined as urinary albumincreatinine ratio (UACR) 30 mg/gCr and 300 mg/gCr in spot urines, respectively. The prevalence of micro- and macro-albuminuria was 35.4 and 10.0, respectively. Patients with albuminuria had more severe heart failure, as indicated by inclusion during admission, higher New York Heart Association functional class, more clinical signs and symptoms of congestion, and higher concentrations of biomarkers related to congestion, such as biologically active adrenomedullin, cancer antigen 125, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (all P 0.001). The presence of albuminuria was associated with increased risk of mortality and heart failure (re)hospitalization in both cohorts. The strongest independent association with log UACR was found for log NT-proBNP (standardized regression coefficient 0.438, 95 confidence interval 0.350.53, P 0.001). Hierarchical clustering analysis demonstrated that UACR clusters with markers of congestion and less with indices of renal function. The validation cohort yielded similar findings. In patients with new-onset or worsening heart failure, albuminuria is consistently associated with clinical, echocardiographic, and circulating biomarkers of congestion.

Association of Empagliflozin Treatment With Albuminuria Levels in Patients With Heart Failure

Albuminuria, routinely assessed as spot urine albumin-to-creatinine ratio (UACR), indicates structural damage of the glomerular filtration barrier and is associated with poor kidney and cardiovascular outcomes. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been found to reduce UACR in patients with type 2 diabetes, but its use in patients with heart failure (HF) is less well studied. To analyze the association of empagliflozin with study outcomes across baseline levels of albuminuria and change in albuminuria in patients with HF across a wide range of ejection fraction levels. This post hoc analysis included all patients with HF from the EMPEROR-Pooled analysis using combined individual patient data from the international multicenter randomized double-blind parallel-group, placebo-controlled EMPEROR-Reduced and EMPEROR-Preserved trials. Participants in the original trials were excluded from this analysis if they were missing baseline UACR data. EMPEROR-Preserved was conducted from March 27, 2017, to April 26, 2021, and EMPEROR-Reduced was conducted from April 6, 2017, to May 28, 2020. Data were analyzed from January to June 2022. Randomization to empagliflozin or placebo. New-onset macroalbuminuria and regression to normoalbuminuria and microalbuminuria. A total of 9673 patients were included (mean [SD] age, 69.9 [10.4] years; 3551 [36.7%] female and 6122 [63.3%] male). Of these, 5552 patients had normoalbuminuria (UACR <30 mg/g) and 1025 had macroalbuminuria (UACR >300 mg/g). Compared with normoalbuminuria, macroalbuminuria was associated with younger age, races other than White, obesity, male sex, site region other than Europe, higher levels of N-terminal pro-hormone brain natriuretic peptide and high-sensitivity troponin T, higher blood pressure, higher New York Heart Association class, greater HF duration, more frequent previous HF hospitalizations, diabetes, hypertension, lower eGFR, and less frequent use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and mineralocorticoid receptor antagonists. An increase in events was observed in individuals with higher UACR levels. The association of empagliflozin with cardiovascular mortality or HF hospitalization was consistent across UACR categories (hazard ratio [HR], 0.80; 95% CI, 0.69-0.92 for normoalbuminuria; HR, 0.74; 95% CI, 0.63-0.86 for microalbuminuria; HR, 0.78; 95% CI, 0.63-0.98 for macroalbuminuria; interaction P trend = .71). Treatment with empagliflozin was associated with lower incidence of new macroalbuminuria (HR, 0.81; 95% CI, 0.70-0.94; P = .005) and an increase in rate of remission to sustained normoalbuminuria or microalbuminuria (HR, 1.31; 95% CI, 1.07-1.59; P = .009) but not with a reduction in UACR in the overall population; however, UACR was reduced in patients with diabetes, who had higher UACR levels than patients without diabetes (geometric mean for diabetes at baseline, 0.91; 95% CI, 0.85-0.98 and for no diabetes at baseline, 1.08; 95% CI, 1.01-1.16; interaction P = .008). In this post hoc analysis of a randomized clinical trial, compared with placebo, empagliflozin was associated with reduced HF hospitalizations or cardiovascular death irrespective of albuminuria levels at baseline, reduced progression to macroalbuminuria, and reversion of macroalbuminuria. ClinicalTrials.gov Identifiers: NCT03057977 and NCT03057951.

The FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC) trial

As angiotensin II type 1 receptor blockers (ARBs) may have different antiproteinuric effects in diabetic kidney disease (DKD), we ascertained the albuminuria-reducing effect of fimasartan and losartan in patients with DKD. This was a randomized, multicenter, double-blind, 4-parallel-group, dose-titration, phase III study designed to compare the efficacy of fimasartan and losartan in reducing albuminuria in patients with DKD (NCT02620306). The primary endpoint was the rate of change in albuminuria from baseline to week 24. A total of 341 patients were randomized to different groups. The urinary albumin-to-creatinine ratio (ACR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were not different between the fimasartan and losartan groups at baseline (ACR: 1376.84 vs. 1521.07 mg/gCr, SBP: 154.69 vs. 154.47 mmHg, DBP: 83.96 vs. 83.83 mmHg). However, ACR reduction was significantly larger in the fimasartan group than in the losartan group during the entire study period (% changes in the ACR at 4, 8, 12, and 24 weeks were -23.58, -33.06, -35.00, and -38.13 in the fimasartan group vs. -8.74, -10.17, -14.91, and -19.71 in the losartan group, p < 0.01, respectively). The superior antiproteinuric effect of fimasartan compared to losartan was still significant after adjustment for SBP levels. There were no significant differences in adverse events, including the incidences of estimated glomerular filtration decline and hyperkalemia. This study demonstrates that compared to losartan, fimasartan significantly reduces albuminuria in patients with DKD, even after adjustment for SBP and DBP.

Serum isthmin-1 levels are positively and independently correlated with albuminuria in patients with type 2 diabetes mellitus

IntroductionIsthmin-1 (Ism-1), as a novel adipokine, plays a role in glucose homeostasis and lipid metabolism. However, the relationship between Ism-1 and type 2 diabetes mellitus (T2DM) remains unclear. This study...

Pioglitazone in diabetic kidney disease: forgotten but not gone.

Diabetic kidney disease (DKD) is described in approximately 20–40% of all diabetic patients and is associated with significant cardiovascular and all-cause mortality. The involvement of multiple metabolic, haemodynamic, inflammatory, and tubular pathways in the pathophysiology of DKD generates the need for multitargeted treatment approaches to improve its development at all levels and delay or even reverse its progression. Thiazolidinediones are potent exogenous agonists of PPAR-γ, which augment the effects of insulin on its cellular targets, mainly at the level of adipose tissue. Pioglitazone, currently the main thiazolidinedione in clinical practice, has achieved significant improvements of albuminuria in patients with type 2 diabetes. It can also interfere with most cellular pathways involved in the development and evolution of DKD. This paper explores the pathophysiological mechanisms governing its possible nephroprotective activity during a diabetic state. It also discusses its future role to ameliorate the global burden of DKD.

Assessment of the relationship between 25-hydroxyvitamin D and albuminuria in type 2 diabetes mellitus

BackgroundDiabetic nephropathy occurs in about one-third of diabetic patients. This health problem is characterized by increased urinary albumin excretion, leading to decreased glomerular filtration rate and renal failure. In this regard, previous investigations have revealed the possibility of a relationship between vitamin D deficiency and diabetic nephropathy. The present study assessed the relationship between vitamin D deficiency and albuminuria in patients with type 2 diabetes.MethodsThis study was conducted with 200 participants with type 2 diabetes mellitus from December 2019 to January 2021. The patients’ 25-hydroxyvitamin D (25OHD) serum level and urinary albumin-to-creatinine ratio (UACR) were measured concurrently. Afterward, the subjects were divided into three groups based on their albuminuria level. Finally, 25OHD serum level and other clinical characteristics were compared among these albuminuria groups, and the relation between albuminuria level and 25OHD was analyzed.ResultsThe prevalence of vitamin D deficiency in macroalbuminuric patients (UACR≥300 mg/g) was 61.8%, and in microalbuminuric (30 ≤ UACR< 300 mg/g) and normoalbuminuric groups (UACR< 30 mg/g) was 33.3% and 24%, respectively. Further analysis revealed a significant negative relationship between 25OHD and albuminuria(r = − 0.257, p-value< 0.001). According to ROC curve analysis, a 25OHD level ≤ 21 ng/ml was considered an optimal cut-off point value for having macroalbuminuria in diabetic patients.ConclusionsThe current study evaluates the relation between vitamin D deficiency and the prevalence of albuminuria in the setting of diabetes. Overall, the prevalence of macroalbuminuria increased when the 25OHD serum level was less than 20 ng/ml.

Literature review on the cross-link between ocular and renal disease: renin angiotensin aldosterone system is a main actor.

Chronic kidney disease (CKD) and ocular disease share several cardiovascular risk factors as well as pathogenetic mechanisms having Renin-Angiotensin-Aldosterone System (RAAS) as main actor. Moreover, kidney and eyes have common genetic and embryonic origin. In this literature review, we present main evidence supporting this association for early identifying diseases affecting both systems and evaluating potential multi-target therapeutic strategies. We performed a literature review of the current peer-reviewed English-language randomized controlled studies (RCTs), reference lists of nephrology or ophthalmology textbooks, review articles and relevant studies with ocular or eye and kidney or renal diseases as keywords until March 2020. Prospective and retrospective studies as well as meta-analyses and latest systematic reviews were included. We evaluated a total of 683 records, finally selecting 119 articles related to ocular and renal diseases. Records were divided into two areas: chronic and acute kidney disease and ocular or eye diseases. Some of the examined studies were discarded for population biases/intervention or deemed unfit. Based on our results, we conclude that there is evidence of a clear association between kidney and eye diseases, being this cross-link mainly based on RAAS dysregulation. Our review suggests that it may be useful to screen CKD patients for associated ocular diseases, such as cataract, glaucoma, diabetic retinopathy and age-related macular degeneration. A comprehensive study of CKD and proteinuric patients should include careful eye examination. Renal impairment in young patients should prompt a search for ocular disease, such as TUNA syndrome or oculo-renal syndrome, in particular if family history of concurrent ocular and renal disease is present. Anti-RAAS agents are mostly recommended in patients with renal and ocular impairment.

Effect of glucagon-like peptide 1 receptor agonists on albuminuria in adult patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

AimsTo determine the effect of glucagon‐like peptide 1 receptor agonists (GLP‐1RAs) on albuminuria in adult patients with type 2 diabetes mellitus (T2DM).MethodsMedline Ovid, Scopus, Web of Science, EMCARE and CINAHL databases from database inception until 27 January 2022. Studies were eligible for inclusion if they were randomized controlled trials that involved treatment with a GLP‐1RA in adult patients with T2DM and assessed the effect on albuminuria in each treatment arm. Data extraction was conducted independently by three individual reviewers. The PRISMA guidelines were followed regarding data extraction and quality assessment. Data were pooled using a random effects inverse variance model and all analysis was carried out with RevMan 5.4 software. The Jadad scoring tool was employed to assess the quality of evidence and risk of bias in the randomized controlled trials.ResultsThe initial search revealed 2419 articles, of which 19 were included in this study. An additional three articles were identified from hand‐searching references of included reviews. Therefore, in total, 22 articles comprising 39 714 patients were included. Meta‐analysis suggested that use of GLP1‐RAs was associated with a reduction in albuminuria in patients with T2DM (weighted mean difference −16.14%, 95% CI −18.42 to −13.86%; p < .0001) compared with controls.ConclusionsThis meta‐analysis indicates that GLP‐1RAs are associated with a significant reduction in albuminuria in adult patients with T2DM when compared with placebo.