Proteinuria In Patients Research Articles

Evaluation of urinary TNF-α and KIM-1 biomarkers in T2DM in Upper Egypt

Abstract Background Diabetes mellitus (DM) is the most frequent cause of chronic kidney failure in both developed and developing countries. Diabetic nephropathy, is a clinical syndrome characterized by albuminuria (>300 mg/day) with permanent and irreversible decrease in glomerular filtration rate (GFR). Aim of the Work To study the role of urinary TNF-α and urine KIM-1 in type 2 diabetic patients as predictors of DN comparative with albuminuria. Patients and Methods This is a cross-sectional study which include 90 type-2 diabetic patients and 30 controls selected from the outpatient clinic of Assiut University hospitals. All patients gave an informed consent and approval for the study was obtained from the IRB committee of the Assiut Medical Faculty. The recruited patients were divided into three groups: Normo-albuminuria Group (A) (n = 30): UACR less than 30 mg/gm, Microalbuminuria Group (B) (n = 30): UACR between 30-299 mg/gm and Macro-albuminuria Group (C) (n = 30): UACR equal or more than 300 mg/gm. Assess Urinary TNF-α and urine KIM-1 in comparision with albuminuria. Results Urinary KIM-1 and urinary TNF-α are statically significant with albuminuria in patients in the early stage of diabetic nephropathy (eGFR _60 mL/min/1.73 m2).Also there are statically significance between patients with macroalbuminuria than microalbuminuria. Conclusion The results of this study recommend the use of KIM-1 and TNF-α as good predictors of early detection of development of diabetic nephropathy.

Albuminuria and its Association with Diabetic Retinopathy among Type-2 Diabetic Patients at a Specialized Diabetic Clinic

Background: Diabetes mellitus is one of the leading non-communicable diseases with an increasing prevalence around the globe. Diabetic Nephropathy and Retinopathy are common complications of diabetes that can be prevented by early interventions. Objective: To assess the association between micro and macro-albuminuria with diabetic retinopathy in patients having Diabetes Mellitus type-2. Methodology: This hospital-based cross-sectional study was conducted on patients having Diabetes Mellitus type-2, visiting eye clinic at AIMS Diabetes Hospital and Research Center Hayatabad, Peshawar from October 2016 to March 2017. All patients having Diabetes Mellitus type-2 were included in the study using purposive sampling. After taking informed consent from patients, data were collected on a pre-designed questionnaire and analyzed using STATA-14. Linear regression was done for the assessment of an association of albuminuria with diabetic retinopathy and other independent variables. Results: A total of 141 type-2 diabetic patients were examined. The mean age of participants was 53.4±9.42 years and 73 (51.77%) were female. Of these patients, microalbuminuria was 88 (62.41%) and macroalbuminuria was 26 (18.4%). Overall, the frequency of Diabetic Retinopathy was 93 (65%), in which 62 (43%) were non-proliferative, and 31 (21.9%) were proliferative DR. On multivariate regression analysis, albuminuria was significantly associated with male gender, old age group (60 years and above), overweight, obesity, and occurrence of both NPDR and PDR (p-value <0.05). Conclusion: Increased level of albuminuria in patients with Diabetes Mellitus type-2 enhances the risk of developing diabetic retinopathy. The risk for developing Diabetic Retinopathy increases with an increase in BMI and age of the patients.

Diastolic hypertension is associated with proteinuria in pediatric patients.

Background and AimsBlood pressure lability has been observed in certain cohorts of pediatric patients with variable degrees of proteinuria; however, the impact of proteinuria on blood pressure is not fully elucidated. The objective of our study was to analyze blood pressure and heart rate in pediatric patients with proteinuria.MethodsWe performed a retrospective chart review of patients (age 1‐18) diagnosed with idiopathic nephrotic syndrome, with varying degrees of proteinuria. Blood pressure and heart rate data were analyzed in relation to anthropometric and biochemical parameters. A total of 72 urine sample analyses, along with associated blood pressure measurements, were obtained from the charts of 33 children (males = 25).ResultsDiastolic blood pressure Z‐scores were significantly higher in proteinuric patients (urine protein/creatinine >0.02 g/mmol) compared to non‐proteinuric patients (P = .006; Cohen‐d 0.97 [0.41; 1.53]). Systolic blood pressure was also significantly higher in proteinuric patients (P = .04), but with a less significant effect size (Cohen‐d 0.54 [−0.002; 1.08]). Proteinuria (>0.02 g/mmol) was the most significant predictor of diastolic (β = .79, P = .04), but not systolic blood pressure elevation on multivariate analysis.ConclusionsWe observed a disproportionate increase in diastolic blood pressure vs systolic blood pressure in patients with proteinuria.

The Effect of Dapagliflozin on Albuminuria in DECLARE-TIMI 58.

OBJECTIVESodium–glucose cotransporter 2 inhibitors (SGLT2i) improve albuminuria in patients with high cardiorenal risk. We report albuminuria change in the Dapagliflozin Effect on Cardiovascular Events (DECLARE-TIMI 58) cardiovascular outcome trial, which included populations with lower cardiorenal risk.RESEARCH DESIGN AND METHODSDECLARE-TIMI 58 randomized 17,160 patients with type 2 diabetes, creatinine clearance >60 mL/min, and either atherosclerotic cardiovascular disease (CVD; 40.6%) or risk-factors for CVD (59.4%) to dapagliflozin or placebo. Urinary albumin-to-creatinine ratio (UACR) was tested at baseline, 6 months, 12 months, and yearly thereafter. The change in UACR over time was measured as a continuous and categorical variable (≤15, >15 to <30, ≥30 to ≤300, and >300 mg/g) by treatment arm. The composite cardiorenal outcome was a ≥40% sustained decline in the estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m2, end-stage kidney disease, and cardiovascular or renal death; specific renal outcome included all except cardiovascular death.RESULTSBaseline UACR was available for 16,843 (98.15%) participants: 9,067 (53.83%) with ≤15 mg/g, 2,577 (15.30%) with >15 to <30 mg/g, 4,030 (23.93%) with 30–300 mg/g, and 1,169 (6.94%) with >300 mg/g. Measured as a continuous variable, UACR improved from baseline to 4.0 years with dapagliflozin, compared with placebo, across all UACR and eGFR categories (all P < 0.0001). Sustained confirmed ≥1 category improvement in UACR was more common in dapagliflozin versus placebo (hazard ratio 1.45 [95% CI 1.35–1.56], P < 0.0001). Cardiorenal outcome was reduced with dapagliflozin for subgroups of UACR ≥30 mg/g (P < 0.0125, Pinteraction = 0.033), and the renal-specific outcome was reduced for all UACR subgroups (P < 0.05, Pinteraction = 0.480).CONCLUSIONSIn DECLARE-TIMI 58, dapagliflozin demonstrated a favorable effect on UACR and renal-specific outcome across baseline UACR categories, including patients with normal albumin excretion. The results suggest a role for SGLT2i also in the primary prevention of diabetic kidney disease.

New Possibilities in Quantitative Assessment of Albuminuria in Patients with Atrial Fibrillation and Chronic Kidney Disease

Aim. To evaluate the relationship between albumin to creatinine ratio (ACR) in a single and 24-hours urine spots and chronic kidney disease (CKD) progression pace in patients with atrial fibrillation, CKD and diabetes mellitus.Material and methods. 60 patients with atrial fibrillation (AF) and CKD were enrolled, study duration was 15 months. The patients were divided into two groups depending on the presence of DM. Total number of ACR tests was 170, dynamics of CKD progression was estimated with CKD-EPI formula for first visit and 15th month’s follow-up.Results. The median score of CHA2DS2VASс scale was 4 [3;5]. The risk of hemorrhagic complications in both groups was low (median score 1 [1;1]. There is a strong statistically significant correlation between ACR in a single and 24-hours urine spots (p&lt;0.001). No significant changes in kidney function within 15 months were found (GFR 53 [46;59] ml/min/1.73 m2 vs 50.5 [45.63] ml/min/1.73 m2 for patients with diabetes mellitus [DM] [p=0.94] and GFR 52.5 [46.58] ml/min/1.73 m2 vs 50 [44.58] ml/min/1.73 m2 for patients without DM [p=0.711]). When comparing the renal function of patients with and without DM after 15 months statistically significant differences were also not found (p = 0.510).Conclusion. In respect that assessment of single sample ACR is much more practical and reliable, this method might replace traditional 24-hours urine assessment in future. However, due to the small sample size and the presence of wide discrepancies in individual cases, which can be associated with preanalytical errors in urine collection, large randomized clinical trials are needed to confirm the obtained data.

Urinary Carnosinase-1 Excretion is Associated with Urinary Carnosine Depletion and Risk of Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Cohort Study

Carnosine affords protection against oxidative and carbonyl stress, yet high concentrations of the carnosinase-1 enzyme may limit this. We recently reported that high urinary carnosinase-1 is associated with kidney function decline and albuminuria in patients with chronic kidney disease. We prospectively investigated whether urinary carnosinase-1 is associated with a high risk for development of late graft failure in kidney transplant recipients (KTRs). Carnosine and carnosinase-1 were measured in 24 h urine in a longitudinal cohort of 703 stable KTRs and 257 healthy controls. Cox regression was used to analyze the prospective data. Urinary carnosine excretions were significantly decreased in KTRs (26.5 [IQR 21.4–33.3] µmol/24 h versus 34.8 [IQR 25.6–46.8] µmol/24 h; p < 0.001). In KTRs, high urinary carnosinase-1 concentrations were associated with increased risk of undetectable urinary carnosine (OR 1.24, 95%CI [1.06–1.45]; p = 0.007). During median follow-up for 5.3 [4.5–6.0] years, 84 (12%) KTRs developed graft failure. In Cox regression analyses, high urinary carnosinase-1 excretions were associated with increased risk of graft failure (HR 1.73, 95%CI [1.44–2.08]; p < 0.001) independent of potential confounders. Since urinary carnosine is depleted and urinary carnosinase-1 imparts a higher risk for graft failure in KTRs, future studies determining the potential of carnosine supplementation in these patients are warranted.

Could urinary kidney injury molecule-1 be a good marker in subclinical acute kidney injury in mild to moderate COVID-19 infection?

PurposeTo evaluate urinary kidney injury molecule-1 (uKIM-1), which is a proximal tubule injury biomarker in subclinical acute kidney injury (AKI) that may occur in COVID-19 infection.MethodsThe study included proteinuric (n = 30) and non-proteinuric (n = 30) patients diagnosed with mild/moderate COVID-19 infection between March and September 2020 and healthy individuals as a control group (n = 20). The uKIM-1, serum creatinine, cystatin C, spot urine protein, creatinine, and albumin levels of the patients were evaluated again after an average of 21 days.ResultsThe median (interquartile range) uKIM-1 level at the time of presentation was 246 (141–347) pg/mL in the proteinuric group, 83 (29–217) pg/mL in the non-proteinuric group, and 55 (21–123) pg/mL in the control group and significantly high in the proteinuric group than the others (p < 0.001). Creatinine and cystatin C were significantly higher in the proteinuric group than in the group without proteinuria, but none of the patients met the KDIGO-AKI criteria. uKIM-1 had a positive correlation with PCR, non-albumin proteinuria, creatinine, cystatin C, CRP, fibrinogen, LDH, and ferritin, and a negative correlation with eGFR and albumin (p < 0.05). In the multivariate regression analysis, non-albumin proteinuria (p = 0.048) and BUN (p = 0.034) were identified as independent factors predicting a high uKIM-1 level. After 21 ± 4 days, proteinuria regressed to normal levels in 20 (67%) patients in the proteinuric group. In addition, the uKIM-1 level, albuminuria, non-albumin proteinuria, and CRP significantly decreased.ConclusionsOur findings support that the kidney is one of the target organs of the COVID-19 and it may cause proximal tubule injury even in patients that do not present with AKI or critical/severe COVID-19 infection.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11255-021-02937-0.

VEGF-VEGFR2 inhibitor-associated hyaline occlusive glomerular microangiopathy: a Japanese single-center experience.

Inhibitors of vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) signaling, such as bevacizumab (Bmab), are used for the treatment of various advanced cancers. However, these inhibitors induce renal thrombotic microangiopathy (TMA). Recently, two European cohort studies showed a distinctive histopathological pseudothrombotic pattern different from TMA in Bmab-treated patients. We analyzed 9 renal biopsies from proteinuric cancer patients treated with VEGF-VEGFR2 inhibitors in our Japanese cohort. Clinical and laboratory features were also assessed in these patients. All 9 patients had moderate to heavy proteinuria with normal or slightly elevated serum creatinine levels. On light microscopy, a patchy pattern of hemispherical/spherical lesions along glomerular capillary walls was a characteristic finding. On immunofluorescence microscopy, staining for immunoglobulins (IgM dominant) at varying intensities was observed mainly along glomerular capillary walls. Especially, hemispherical/spherical positive staining for immunoglobulins was a characteristic pattern. Immunohistochemical studies showed positive staining for immunoglobulins and negative staining for CD61-positive platelets in capillary hemispherical/spherical lesions and positive VEGF staining in podocytes. On electron microscopy, variably electron-dense material in dilated glomerular capillaries and partial effacement of podocyte foot processes were observed. After the withdrawal of VEGF-VEGFR2 inhibitors, proteinuria improved without any specific treatment in 8 patients. Histopathological findings in our patients treated with VEGF-VEGFR2 inhibitors were consistent with those observed in the recently described new form of Bmab-associated hyaline occlusive glomerular microangiopathy. This form should be considered in proteinuric cancer patients treated with VEGF-VEGFR2 inhibitors. Discontinuing VEGF-VEGFR2 inhibitors may lead to improvement of glomerular microangiopathy induced by these drugs.

Association Between Classical and Emerging Risk Factors for Diabetic Kidney Disease and Albuminuria in a Cohort of Type 2 Diabetes Mellitus Patients

Abstract The presence of albuminuria in patients with type 2 diabetes mellitus is a marker of endothelial dysfunction and also one of the criteria for diagnosing diabetic kidney disease. The present study aimed to identify associations between cardiovascular risk factors and renal albumin excretion in a group of 218 patients with type 2 diabetes mellitus. HbA1c values, systolic blood pressure, diastolic blood pressure were statistically significantly higher in patients with microalbuinuria or macroalbuminuria compared to patients with normoalbuminuria (p &lt;0.01). We identified a statistically significant positive association between uric acid values and albuminuria, respectively 25- (OH)2 vitamin D3 deficiency and microalbuminuria (p &lt;0.01).

FC 063DAPAGLIFLOZIN DECREASES ALBUMINURIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE WITH AND WITHOUT TYPE 2 DIABETES: INSIGHTS FROM THE DAPA-CKD TRIAL

Abstract Background and Aims Reductions in albuminuria are consistently associated with a subsequent lower risk of kidney failure. The sodium glucose co-transporter 2 inhibitor dapagliflozin significantly reduced albuminuria in patients with type 2 diabetes. Whether this effect persist in patients with chronic kidney disease (CKD) with and without diabetes is unknown. We therefore assessed and compared the effects of dapagliflozin on albuminuria in patients with CKD with and without type 2 diabetes from the DAPA-CKD trial. Method We randomized 4304 patients with CKD and an eGFR of 25-75 ml/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g to dapagliflozin (10 mg once daily) or placebo. Change in albuminuria was a pre-specified exploratory outcome. We used regression in UACR stage, defined as a transition from macroalbuminuria (≥300 mg/g) to micro- or normoalbuminuria (&amp;lt;300 mg/g), and progression in UACR stage, defined as a transition from non-nephrotic (&amp;lt;3000 mg/g) to nephrotic range albuminuria (≥3000 mg/g), as additional endpoints. Subgroup analyses were performed according to baseline type 2 diabetes status. Results Median (25th to 75th Percentile) UACR was 949 (477-1885) mg/g. In patients with and without type 2 diabetes baseline median UACR was 1017 mg/g and 861 mg/g, respectively. Dapagliflozin, compared to placebo, reduced UACR by 29.3% (95% confidence interval [CI] 25.2, 33.1; p&amp;lt;0.001), with a 35.1% (95%CI 30.6, 39.4) reduction in patients with type 2 diabetes and 14.8% (95%CI 5.9, 22.9) reduction in patients without type 2 diabetes (p for interaction &amp;lt;0.001). Among 3860 patients with UACR ≥300 mg/g at baseline, dapagliflozin significantly increased the likelihood of regression in UACR stage (hazard ratio [HR] 1.81; 95%CI 1.60, 2.05). The corresponding HRs for patients with and without type 2 diabetes were 2.06 (95%CI 1.78, 2.39) and 1.33 (95%CI 1.07, 1.66), respectively (p for interaction 0.001). Among 3820 patients with UACR &amp;lt;3000 mg/g at baseline, dapagliflozin significantly decreased the risk of nephrotic range albuminuria (HR 0.41; 95%CI 0.32, 0.52). The corresponding HRs for patients with and without type 2 diabetes were 0.39 (95%CI 0.29, 0.51) and 0.50 (95%CI 0.30, 0.82), respectively (p for interaction 0.401). Conclusion In patients with CKD with and without type 2 diabetes dapagliflozin significantly reduced albuminuria, with a larger reduction in patients with type 2 diabetes. The similar effects of dapagliflozin on clinical outcomes in patients with or without type 2 diabetes, but different effects on UACR suggest that part of dapagliflozin’s protective effect in patients without diabetes is mediated through pathways unrelated to UACR reduction.

MO516A STRUCTURED EXPERT ELICITATION TO INFORM AND VALIDATE MORTALITY EXTRAPOLATIONS FOR A COST-EFFECTIVENESS ANALYSIS OF DAPAGLIFLOZIN

Abstract Background and Aims Elevated albuminuria in patients with chronic kidney disease (CKD) is associated with increased risks of CKD progression, cardiovascular events and all-cause death. In the DAPA-CKD study, dapagliflozin significantly reduced the risk of all-cause death in patients with elevated albuminuria compared with placebo (hazard ratio: 0.69; 95% confidence interval 0.53–0.88). To assess the cost-effectiveness of new treatments, decision makers require survival estimates over a longer period than that of a typical clinical trial, usually over a lifetime time horizon. A formal elicitation process is currently underway to obtain estimates of long-term survival of patients with albuminuric CKD from clinical experts. Their responses will be used to validate extrapolations of all-cause mortality data from DAPA-CKD, which could inform cost-effectiveness analyses for dapagliflozin. Method Targeted literature searches were conducted to collate data on all-cause mortality in patients with CKD and elevated albuminuria. Clinical trials and observational studies were included if they involved non-dialysis-dependent patients with CKD aged 18 years and over, had more than 500 participants per study arm and reported incidence of all-cause death and/or all-cause mortality/survival Kaplan–Meier (KM) curves. To estimate long-term survival, KM curves were extrapolated to 20 years by calculating standard mortality ratios (SMRs) using age- and sex-adjusted general-population lifetable data. Study and patient characteristics and mortality data from relevant studies were provided to clinical experts to inform their judgements in a formal elicitation process. After receiving training on the elicitation process, six leading disease area experts were invited to complete the elicitation survey using an Excel-based tool, which consisted of 10 calibration questions, and three questions regarding the survival of patients in the placebo arm of the DAPA-CKD study at 10 and 20 years. The elicited estimates will be weighted and aggregated using Cooke’s method. Results Literature searches identified 13 relevant articles (seven clinical trials and six observational studies), with a range of 1094 to 5674 participants. Mean age varied across studies (range: 55–70 years). Where reported, median follow-up was 9–144 months, and mean estimated glomerular filtration rate (eGFR) at baseline was 22.4–56.3 mL/min/1.73 m2. Five studies exclusively included patients with type 2 diabetes (T2D). The incidence of all-cause death was reported in nine studies and was 1.5–9.4 deaths per 100 patient-years, with the highest incidence observed in a study reporting data for patients with CKD stage 4 and 5 (8.0 and 9.4 deaths per 100 patient-years, respectively). Nine studies provided KM curves; from these, estimated survival at 2 years ranged from 86% (study population mean age 67 years, eGFR &amp;lt; 15 mL/min/1.73 m2) to 98% (study population mean age 58 years, mean eGFR 46.2 mL/min/1.73 m2). The SMR-extrapolated survival at 10 and 20 years was 36–80% and 2–69%, respectively. The ranges defined by the expert judgements collected to date for survival at 10 and 20 years are in line with the variability of the extrapolated KM survival curves. The elicitation process is ongoing and therefore, to avoid biasing the judgements that remain to be collected, preliminary results are not reported here. Results of the expert elicitation will be presented in full at the congress. Conclusion Initial results from the survey calibration questions suggest that the expert elicitation process provides expert judgements that are both informative and precise. The elicitation of survival estimates for patients with CKD and elevated albuminuria at 10 and 20 years will provide greater insight than extrapolated data alone, and will increase the validity of long-term survival projections for dapagliflozin cost-effectiveness analyses.

MO260PERFORMANCE ANALYSIS OF AN ARTIFICIAL NEURAL NETWORK TOOL TO PREDICT ESKD IN PATIENTS WITH IMMUNOGLOBULIN A NEPHROPATHY (IGAN)

Abstract Background During the last twenty years many tools, based on mathematical models, have been developed to predict ESKD at the time of kidney biopsy in patients with IgAN. The main limitation of these tools is the time frame to reach the ESKD. Recently, we have developed a Clinical Decision Support System (CDSS) (KI 2020) which includes 6 variables at the time of kidney biopsy: age, sex, hypertension, serum creatinine, daily proteinuria and score of the renal lesions according to the MEST-C classification. The tool (www.igan.poliba.it) is based on two different artificial neural networks of which the first predicts ESKD and the second one predicts the time to reach this outcome. Aim of our study has been to analyze the causes of discordance to predict or not ESKD in a cohort of 1116 IgAN patients (VALIGA cohort and external cohort) with a median follow-up of 88 months (49-135). To our knowledge this is the first report which analyzes the discrepant results of a toll to predict ESKD in IgAN patients. Method Demographic and laboratory data have been analyzed using means and standard deviations (SD) for continuous variables normally distributed, median in presence of non-normally distribution. Categorical variables are expressed as percentages. The means have been compared by the Student’s test and the medians using the Mann-Whitney U test. All the data were collected and stored in a standard Excel database. The statistical significance value p&amp;lt; 0.05 has been adopted. Results Discordance to reach or not ESKD was found in 216 patients (19.4%). In 77 patients with no prediction of ESKD, 25 patients with proteinuria &amp;gt; 0.5 g/day did not receive therapy after kidney biopsy or were cared very late. Failure of therapy (RASBs alone in 44 subjects and corticosteroids in 8 individuals) was observed in 52 patients. In 139 patients who did not reach ESKD but our tool predicted this outcome, interestingly, we found that 106 proteinuric patients (22 with GFR &amp;gt;50 ml/min/1.73 m2 and 84 with GFR &amp;lt; 50 ml/min/1.73 m2) had an improvement of the clinical course (reduction of proteinuria and stabilization of GFR value) after corticosteroid therapy. The remaining 33 patients benefited of RASB therapy. Among 84 patients with GFR&amp;lt; 50 ml/min/1.73 m2 36 had nephrotic proteinuria and were responsive to corticosteroids. These results suggest that we cannot rule out corticosteroid therapy in patients with reduced GFR and proteinuria &amp;gt; 3 g/day. Furthermore, our tool predicts the time frame to reach ESKD and indicates the potential effect of some drugs (RASBs, corticosteroids or their combination) to delay the outcome. We observed that corticosteroids combined with RASBs delayed more than 10 years the time to reach ESKD. Conclusions Our tool predicted ESKD in a percentage higher than that observed but, interestingly, it was found that a high number of patients benefited of corticosteroids in combination with RASBs. Furthermore, our tool predicted time to reach ESKD and indicated the potential benefit of therapy to delay the crude outcome. In fact, therapy delayed the outcome of more than 10 years when combination of corticosteroids and RASBs was administered. Therefore, our tool shows to physicians that their patients may delay the ESKD receiving corticosteroids alone or in combination with RASBs. This approach is important because in many cases it is a strengthen point to convince patients to accept the prescribed therapy. Moreover, this report shows for the first time that predicted ESKD may be delayed administering personalized therapy suggested by our tool. Essentially, in a high percentage of patients the failure of our tool is not an error but the positive effect of therapy or misconduct of patients management.

Effect of continuous positive airway pressure on albuminuria in patients with obstructive sleep apnea: a meta-analysis.

A relationship between albuminuria and obstructive sleep apnea (OSA) has been documented in previous studies. Nevertheless, the impact of continuous positive airway pressure (CPAP) treatment on albuminuria in subjects with OSA is debated. This meta-analysis was carried out to investigate whether or not CPAP treatment affected urinary albumin-to-creatinine ratio (UACR) in subjects with OSA. A comprehensive literature search was conducted on Web of Science, Embase, and PubMed from January 1990 to December 2020. Information on patients' characteristics, features of the studies, and UACR of pre- and post-CPAP treatment was collected. For estimation of the pooled effects, standardized mean difference (SMD) was applied. This meta-analysis included 6 articles and 211 subjects. The pooled analysis suggested that CPAP therapy exerted a favorable effect on the decrease of UACR in subjects with OSA (SMD = 0.415, 95% CI = 0.026 to 0.804, z = 2.09, p = 0.037). Subgroup analyses revealed that the CPAP treatment effect was not influenced by sample size, BMI, age, or AHI. The present meta-analysis indicated that UACR was significantly reduced by CPAP therapy in subjects with OSA. Further well-designed randomized controlled trials with large sample size are required to confirm the benefits.

Animal Fat Intake Is Associated with Albuminuria in Patients with Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome.

Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are associated with chronic kidney disease (CKD). Diet could play a predisposing role in the development of increased albuminuria in patients with NAFLD and MetS; however, published evidence is still limited. The aim of this cross-sectional analysis was to assess whether dietary fats are associated with changes in urinary albumin-to-creatinine ratio (UACR) in 146 patients aged 40–60-years with NAFLD and MetS. Dietary data were collected by food frequency questionnaire; UACR was measured in a single first morning void. Sources and types of dietary fats used in the analysis were total fat, fats from animal and vegetable sources, saturated, monounsaturated, polyunsaturated, and trans fats. One-way analysis of variance was performed to assess differences in dietary fats intakes across stages of UACR. The association between dietary fats and UACR was assessed by Pearson’s correlation coefficient and multivariable linear regression. Patients with increased UACR showed a worse cardiometabolic profile and higher intakes of animal fat, as compared to patients with normal levels of albuminuria. Animal fat intake was associated with mean UACR, independent of potential covariates.

Arterial stiffness and albuminuria as markers of endothelial dysfunction in those with chronic obstructive pulmonary disease

The objective: to assess the state of arterial stiffness and the level of albuminuria in patients with chronic obstructive pulmonary disease (COPD) and to investigate the presence and nature of the association of the studied parameters with clinical and laboratory parameters of COPD.Subjects and methods. 70 patients with COPD were examined, they all were divided into 4 groups depending on severity of clinical symptoms and number of exacerbations suffered in the previous 12 months. Additionally to standard examinations, albuminuria level, the pulse wave velocity in aorta (PWVa), and cardio-ankle vascular index (CAVI) were assessed.Results. The increased albuminuria level was registered in 51.4% of patients mainly suffering from frequent exacerbations. The increased CAVI and PWVa also prevailed in individuals with a high frequency of exacerbation and their higher levels were found in 37.1% and 14.3% of patients, respectively. PWVa and CAVI values were found to be associated with albuminuria level and clinical and laboratory parameters of COPD.

Associations between continuous glucose monitoring-derived metrics and diabetic retinopathy and albuminuria in patients with type 2 diabetes

IntroductionPreventing the development and progression of diabetic microvascular complications through optimal blood glucose control remains an important challenge. Whether metrics based on continuous glucose monitoring are useful for the management...

Hypertension in Kidney Transplant Recipients: Where Are We Today?

Cardiovascular disease is the leading cause of death and allograft loss among kidney transplant recipients, and hypertension is an independent risk factor for cardiovascular morbidity of this patient population. The etiology of hypertension is multifactorial, including pre-transplant volume overload, post-transplant recipient and donor-associated variables, and transplant-specific causes (immunosuppressive medications, allograft dysfunction and surgical complications such as transplant artery stenosis). No randomized controlled trials have assessed the optimal blood pressure targets and explored the best antihypertensive regimen for kidney transplant recipients. According to the large observational studies, it is reasonable to achieve a blood pressure goal of equal to or less than 130/80 mmHg in the long-term follow-up for minimizing the cardiovascular morbidity. The selection of antihypertensive agents should be based on the patient's co-morbidities; however, the initial choice could be calcium channel blockers especially in the first few months of transplantation. In patients with cardiovascular indications of renin-angiotensin-aldosterone system inhibition, given the well-described benefits in diabetic and proteinuric patients, it is reasonable to consider the use of renin-angiotensin-aldosterone system inhibitors. There is a need for future prospective trials in the transplant population to define optimal blood pressure goals and therapies.

The Effect of Bariatric Surgery versus Intensive Medical Care on Prevention of Microalbuminuria in Patients with Type 2 Diabetes: 3 Year Experience of a Prospective Study

BACKGROUND: Bariatric surgery could improve diabetic kidney disease; however, the effect of surgery versus medical therapy on renal out comes needs further evaluation. AIM: The aim of the study was to investigate the effect of sleeve-gastrectomy versus intensive medical therapy on the prevention of albuminuria in patients with Type 2 diabetes mellitus (T2DM). METHODS: This is a prospective study of 33 patients with T2DM undergoing sleeve gastrectomy matched for age, sex, and duration of diabetes to 64 medically treated patients. Urinary albumin/creatinine ratio (uACR) was assessed before and 3–year after intervention. RESULTS: At baseline, there was no significant difference between surgical and medical group regarding body mass index (BMI), blood pressure, Hemoglobin A1c (HbA1c), or uACR. After 3 years of interventions the mean BMI (kg/m2) and HbA1c (%) became significantly lower in the surgical group compared to medical group. Although mean uACR (g/mg) increased after interventions compared to its levels before interventions in both surgical (11.7 ± 4.8 vs.18.2 ± 5.9) g/mg and medical (13.4 ± 4.5 vs.17.1 ± 6) g/mg groups, albuminuria developed in only three surgical patients and two medical patients (p &gt; 0.05). CONCLUSION: Although bariatric surgery is associated with more reduction in body weight and better glycemic control than intensive medical therapy, sleeve-gastrectomy may not be superior to intensive medical care in prevention of microalbuminuria in patients with T2DM.

Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus: an analysis from the randomised VERTIS CV trial

Aims/hypothesisIn previous work, we reported the HR for the risk (95% CI) of the secondary kidney composite endpoint (time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death) with ertugliflozin compared with placebo as 0.81 (0.63, 1.04). The effect of ertugliflozin on exploratory kidney-related outcomes was evaluated using data from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881).MethodsIndividuals with type 2 diabetes mellitus and established atherosclerotic CVD were randomised to receive ertugliflozin 5 mg or 15 mg (observations from both doses were pooled), or matching placebo, added on to existing treatment. The kidney composite outcome in VERTIS CV (reported previously) was time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death. The pre-specified exploratory composite outcome replaced doubling of serum creatinine with sustained 40% decrease from baseline in eGFR. In addition, the impact of ertugliflozin on urinary albumin/creatinine ratio (UACR) and eGFR over time was assessed.ResultsA total of 8246 individuals were randomised and followed for a mean of 3.5 years. The exploratory kidney composite outcome of sustained 40% reduction from baseline in eGFR, chronic kidney dialysis/transplant or renal death occurred at a lower event rate (events per 1000 person-years) in the ertugliflozin group than with the placebo group (6.0 vs 9.0); the HR (95% CI) was 0.66 (0.50, 0.88). At 60 months, in the ertugliflozin group, placebo-corrected changes from baseline (95% CIs) in UACR and eGFR were −16.2% (−23.9, −7.6) and 2.6 ml min−1 [1.73 m]−2 (1.5, 3.6), respectively. Ertugliflozin was associated with a consistent decrease in UACR and attenuation of eGFR decline across subgroups, with a suggested larger effect observed in the macroalbuminuria and Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) high/very high-risk subgroups.Conclusions/interpretationAmong individuals with type 2 diabetes and atherosclerotic CVD, ertugliflozin reduced the risk for the pre-specified exploratory composite renal endpoint and was associated with preservation of eGFR and reduced UACR.Trial registrationClinicalTrials.gov NCT01986881Graphical abstract

The HSD17B13 rs72613567 variant is associated with lower levels of albuminuria in patients with biopsy-proven nonalcoholic fatty liver disease

Background and aimsSeveral susceptibility gene variants predisposing to nonalcoholic fatty liver disease (NAFLD) have been identified in chronic kidney disease (CKD). Evidence supports that 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) rs72613567 plays a role in NAFLD development by affecting lipid homeostasis. Since lipid droplets may accumulate in the kidneys and contribute to renal injury, we investigated the association between the HSD17B13 rs72613567 variant and markers of renal function/injury in NAFLD. Methods and resultsWe measured estimated glomerular filtration rate (eGFR), urinary/serum neutrophil gelatinase-associated lipocalin (NGAL), and urinary albumin-to-creatinine ratio (u-ACR) in individuals with biopsy-proven NAFLD. Multivariable regression analyses were undertaken to examine the associations between the HSD17B13 rs72613567 variant and markers of renal function/injury. Individuals were stratified by HSD17B13 rs72613567 genotypes into −/−, A/- and A/A groups. HSD17B13 rs72613567 genotypes were not significantly associated with eGFR and urinary/serum NGAL levels. Conversely, the prevalence of abnormal albuminuria in the A/- + A/A group was lower than in the −/− group (4.92% vs. 19.35%, p = 0.001). Additionally, the mean u-ACR levels were lower among carriers of the A/- or A/A genotypes with coexisting hypertension or diabetes, than among those with the −/− genotype. The risk of abnormal albuminuria (adjusted-odds ratio 0.16, p = 0.001) remained significantly lower in the A/- + A/A group after adjustment for established renal risk factors and histologic severity of NAFLD. ConclusionHSD17B13 rs72613567: A allele is associated with a lower risk of having abnormal albuminuria, but not with lower eGFR or urinary/serum NGAL levels, in patients with biopsy-proven NAFLD.