Proteinuria In Patients Research Articles

513-P: Adenosine Signal Plays an Important Role in Renoprotective Effects of SGLT2 Inhibitor in Proteinuric Diabetic Mice

Background: SGLT2 inhibitor (SGLT2i) displayed remarkable and early renal protection in overt nephropathy cases in clinical trials. However, detailed molecular mechanisms by which SGLT2i ameliorated renal damage in proteinuric diabetic patients were not elucidated yet. Here, we investigated that SGLT2i exerted renal protective effects via adenosine signal in diabetic mice with overt proteinuria. Methods: STZ (200mg/kgBW) was injected intraperitoneally to induce diabetes in 8-week-old CD-1 mice. Four weeks later, mice were treated with intraperitoneal injection of bovine serum albumin (BSA: 0.3g/30gBW) with or without oral administration of SGLT2i TA-1887 (30mg/kg). Result: In the STZ+BSA, pronounced renal tubular damages and interstitial fibrosis were observed; TA-1887 significantly ameliorated. The mRNA microarray analysis of kidney samples revealed that gene expressions related to TGF-β signaling pathway and epithelial-mesenchymal-transition program were increased in the STZ+BSA compared to the Control+BSA; TA-1887 suppressed them. Furthermore, the expression of ecto 5'-nucleotidase (5'-NT), which is essential for production of adenosine from AMP, was suppressed in STZ+BSA compared to Control+BSA; TA-1887 restored 5’-NT levels. In the immunohistological analysis, 5'-NT was expressed in glomeruli including mesangial cells and renal tubules of cortex/medulla in control kidney. However, 5’-NT was suppressed in all areas of STZ+BSA kidney; TA-1887 reversed the 5'-NT expression and distribution. Glomerular filtration rate (GFR) evaluated by inulin clearance was significantly greater in the STZ+BSA group and suppressed by TA-1887; the administration of the adenosine type 1 receptor inhibitor, DPCPX, cancelled the effects of TA-1887 on GFR and renal tubule damage. Conclusion: The adenosine signal plays an important role in the renal protective effects of SGLT2i in diabetic mice with proteinuria. Disclosure K. Shimada: None. Y. Takagaki: None. K. Kanasaki: Other Relationship; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Sanofi, Taisho Toyama Pharmaceutical. D. Koya: Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Self; Astellas Pharma Inc., Astellas Pharma Inc., AstraZeneca, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Taisho Pharmaceutical Co., Ltd. Funding Japan Society for the Promotion of Science

Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease

Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.

Effect of SGLT2 inhibitor on renal function in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

This study summarizes the evidence from randomized controlled trials (RCTs) to assess the effects of SGLT2 inhibitors on renal function and albuminuria in patients with type 2 diabetes. We searched PubMed, Web of Science, Cochrane Library and EMBASE for reports published up to March 2018 and included RCTs reporting estimated glomerular filtration rate (eGFR) and/or urine albumin/creatinine ratio (UACR) changes. Data extraction and assessment of research quality based on Cochrane risk biasing tools. Data were calculated to represent the standardized mean difference (SMD) for each study, and the SMDs with 95% confidence intervals (CIs) were pooled using a random effects model. Fifty-one studies were included that evaluated eGFR levels, and 17 studies were included that evaluated UACR levels. A meta-analysis showed that SGLT2 inhibitors had no significant effect on eGFR levels (SMD - 0.02, 95% CI - 0.06, 0.03, p = 0.45), and eGFR reduction was observed in the subsets of the duration of the trial 12 < duration ≤ 26 weeks (SMD - 0.08, 95% CI - 0.13, - 0.02, p = 0.005) and mean baseline eGFR < 60ml/min per 1.73 square meters (SMD - 0.22, 95% CI - 0.37, - 0.07, p = 0.004). We found that SGLT2 inhibitors reduced UACR levels in patients with type 2 diabetes (SMD - 0.11, 95% CI - 0.17, - 0.05, p = 0.0001). Compared with monotherapy, the combination with other hypoglycemic agents can reduce albuminuria levels (SMD - 0.13, 95% CI - 0.19, - 0.06, p < 0.0001). The effect of SGLT2 inhibitor on eGFR in patients with T2DM was not statistically significant, but it was effective in reducing albuminuria levels.

Podocyturia in pediatric patients with Fabry disease

IntroductionFabry disease (FD) is a hereditary disorder caused by a deficiency of α-galactosidase A enzyme activity. The transmission of the disorder is linked to the X chromosome. ObjectivesThe objectives of the study were: 1. To quantify the presence of podocytes in pediatric patients with FD and compare them with the value of the measured podocyturia in healthy controls. 2. To determine whether a greater podocyturia is related to the onset of pathological albuminuria in patients with FD. 3. To determine the risk factors associated with pathological albuminuria. MethodsWe performed an analytical, observational study of Fabry and control subjects, which were separated into 2 groups in accordance with the absence of the disease (control group) or the presence of the disease (Fabry group). ResultsWe studied 31 patients, 11 with FD and 20 controls, with a mean age of 11.6 years.The difference between the mean time elapsed from the diagnosis of FD to the measurement of podocyturia (40 months) and the onset of pathological albuminuria (34 months) was not significant (p=0.09). Podocytes were identified by staining for the presence of synaptopodin and the mean quantitative differences between both podocyturias were statistically significant (p=0.001). Albuminuria was physiological in 4 of the patients with FD and the relative risk to develop pathological albuminuria according to podocyturia was 1.1 in the control group and 3.9 in the Fabry group, with a coefficient of correlation between podocyturia and albuminuria in the Fabry group of 0.8354. Finally, the 2 risk factors associated with the development of pathological albuminuria were podocyturia (OR: 14) and being aged over 10 years (OR: 18). We found no significant risk with regard to glomerular filtrate renal (GFR) (OR: 0.5) or gender (OR: 1.3). The mean GFR remained within normal values. ConclusionThe detection of podocyturia in pediatric patients with FD could be used as an early marker of renal damage, preceding and proportional to the occurrence of pathological albuminuria.

Is neutrophil-lymphocyte ratio a novel biomarker for macrovascular and microvascular complications of type 2 diabetes?

Background/aimThe neutrophil-to-lymphocyte (N/L) ratio is a biomarker of inflammation. We aimed to test the hypothesis that macrovascular and microvascular complications of type 2 diabetes mellitus (DM) involve an inflammatory process.Patients and methodsThis is a cross-sectional study conducted on patients with type 2 DM. Demographic and clinical examination data of eligible patients were recorded. The blood samples for laboratory variables were collected and measured by the standard methods. A standard ultrasound examination was done to measure both carotid artery intima-media thickness (cIMT), and the averages of three results of each side were recorded.ResultsThe current study showed that N/L ratio was an independent predictor of cIMT in patients with type 2 DM (B=0.003, t=8.325, P=0.000), in addition to other conventional cardiovascular risk factors including age, male sex, smoking index, duration of diabetes, estimated glomerular filtration rate, low-density lipoprotein-cholesterol, urinary albumin creatinine ratio, and HBA1c. Moreover, N/L ratio was an independent predictor of albuminuria in patients with type 2 DM (B=0.110, t=3.638, P=0.006), in addition to duration of diabetes, HBA1c, SBP, BMI, and estimated glomerular filtration rate.ConclusionN/L ratio was an independent predictor of cIMT and albuminuria. This supports the hypothesis that diabetic macrovascular and microvascular complications involve an inflammatory process. Therefore, NLR may serve as a cost-effective and readily accessible marker of diabetic vascular complications.

Efficacy of Co-administration of Liuwei Dihuang Pills and Ginkgo Biloba Tablets on Albuminuria in Type 2 Diabetes: A 24-Month, Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

Purpose: We investigated the effects of Traditional Chinese Medicine (TCM) on the occurrence and progression of albuminuria in patients with type 2 diabetes.Methods: In this randomized, double-blind, multicenter, controlled trial, we enrolled 600 type 2 diabetes without diabetic nephropathy (DN) or with early-stage DN. Patients were randomly assigned (1:1) to receive Liuwei Dihuang Pills (LWDH) (1.5 g daily) and Ginkgo biloba Tablets (24 mg daily) orally or matching placebos for 24 months. The primary endpoint was the change in urinary albumin/creatinine ratio (UACR) from baseline to 24 months.Results: There were 431 patients having UACR data at baseline and 24 months following-up in both groups. Changes of UACR from baseline to follow-up were not affected in both groups: −1.61(−10.24, 7.17) mg/g in the TCM group and −0.73(−7.47, 6.75) mg/g in the control group. For patients with UACR ≥30 mg/g at baseline, LWDH and Ginkgo biloba significantly reduced the UACR value at 24 months [46.21(34.96, 58.96) vs. 20.78(9.62, 38.85), P < 0.05]. Moreover, the change of UACR from baseline to follow-up in the TCM group was significant higher than that in the control group [−25.50(−42.30, −9.56] vs. −20.61(−36.79, 4.31), P < 0.05].Conclusion: LWDH and Ginkgo biloba may attenuate deterioration of albuminuria in type 2 diabetes patients. These results suggest that TCM is a promising option of renoprotective agents for early stage of DN.Trial registration: The study was registered in the Chinese Clinical Trial Registry. (no. ChiCTR-TRC-07000037, chictr.org)

Association between Sleep Duration and Albuminuria in Patients with Hypertension: Korean National Health and Nutrition Examination Survey 2011-2012

Association between Sleep Duration and Albuminuria in Patients with Hypertension: Korean National Health and Nutrition Examination Survey 2011-2012

Podocyte histone deacetylase activity regulates murine and human glomerular diseases

We identified 2 genes, histone deacetylase 1 (HDAC1) and HDAC2, contributing to the pathogenesis of proteinuric kidney diseases, the leading cause of end-stage kidney disease. mRNA expression profiling from proteinuric mouse glomeruli was linked to Connectivity Map databases, identifying HDAC1 and HDAC2 with the differentially expressed gene set reversible by HDAC inhibitors. In numerous progressive glomerular disease models, treatment with valproic acid (a class I HDAC inhibitor) or SAHA (a pan-HDAC inhibitor) mitigated the degree of proteinuria and glomerulosclerosis, leading to a striking increase in survival. Podocyte HDAC1 and HDAC2 activities were increased in mice podocytopathy models, and podocyte-associated Hdac1 and Hdac2 genetic ablation improved proteinuria and glomerulosclerosis. Podocyte early growth response 1 (EGR1) was increased in proteinuric patients and mice in an HDAC1- and HDAC2-dependent manner. Loss of EGR1 in mice reduced proteinuria and glomerulosclerosis. Longitudinal analysis of the multicenter Veterans Aging Cohort Study demonstrated a 30% reduction in mean annual loss of estimated glomerular filtration rate, and this effect was more pronounced in proteinuric patients receiving valproic acid. These results strongly suggest that inhibition of HDAC1 and HDAC2 activities may suppress the progression of human proteinuric kidney diseases through the regulation of EGR1.

Interest of albuminuria in nephrology, diabetology and as a marker of cardiovascular risk.

Albuminuria is associated with the progression of chronic kidney disease and the occurrence of cardiovascular events in patients with and without diabetes. The evolution of albuminuria appears to be associated with patient's prognosis. How exactly microalbuminuria is linked to cardiovascular risk remains unclear. This association is probably explained by endothelial dysfunction or chronic low-grade inflammation. Albuminuria/creatininuria ratio allows reduction of potential errors in urine collection. In France, the recommendations for the monitoring of albuminuria depend on the cause of albuminuria. An increase in urinary albumin excretion could signify the need for an intensive multifactorial intervention strategy and albuminuria is a relevant biological marker to monitor therapeutic effectiveness, since a reduction of albuminuria in patients, irrespective of their diabetic status, predicts reduction of cardiovascular risk.

The evaluation of thiol/disulphide homeostasis in diabetic nephropathy

AimsThiol/disulphide homeostasis plays a critical role in antioxidant defense, and detoxification in body. Although alteration of thiol/disulfide homeostasis had been shown in patients with diabetes, the thiol/disulfide balance in patients with type 2 diabetes and nephropathy is not yet known. MethodsTwenty-six healthy volunteers (group 1), and 17 normal albuminuric (group 2), 24 middle albuminuric (group 3), 20 severe proteinuric (group 4) patients with type 2 diabetes were included. Proteinuria was tested by measuring microalbumin/creatinine ratio in spot urine. Thiol/disulphide homeostasis concentrations were measured using method developed by Erel et al. ResultsMean blood urea and creatinine levels were found to be significantly higher and GFR level was found to be significantly lower in group 4 than in the other groups. Native thiol levels are significantly lower in groups with diabetes than in healthy group and in groups 3 and 4, compared to group 2. Total thiol level was significantly lower in groups 3 and 4 than group 1 and 2. Disulphide/native thiol and disulfide/total thiol ratios were significantly higher in the groups with diabetes than in group 1 and in the group 4 than in the group 2. ConclusionThe level of native and total thiols were found to be decreased significantly with the grade of nephropathy in patients with type 2 diabetes and the balance had been disrupted in favor of disulphide. We suggest that deteriorated thiol/disulphide balance may be one of the important factors in the development or progression of diabetes induced nephropathy.

Empagliflozin and kidney outcomes in Asian patients with type2 diabetes and established cardiovascular disease: Results from the EMPA-REG OUTCOME® trial.

Aims/IntroductionIn the EMPA‐REG OUTCOME® trial, empagliflozin added to standard of care improved clinically relevant kidney outcomes by 39%, slowed progression of chronic kidney disease, and reduced albuminuria in patients with type 2 diabetes and established cardiovascular disease. This exploratory analysis investigated the effects of empagliflozin on the kidneys in Asian patients.Materials and MethodsParticipants in the EMPA‐REG OUTCOME® trial were randomized (1:1:1) to empagliflozin 10 mg, 25 mg or a placebo. In patients of Asian race, we analyzed incident or worsening nephropathy (progression to macroalbuminuria, doubling of serum creatinine, initiation of renal‐replacement therapy or renal death) and its components, estimated glomerular filtration rate (eGFR) and urine albumin‐to‐creatinine ratio changes, and renal safety.ResultsOf 7,020 treated patients, 1,517 (26.1%) were Asian. In this subgroup, consistent with the overall trial population, empagliflozin reduced the risk of incident or worsening nephropathy (hazard ratio 0.64, 95% confidence interval 0.49–0.83), progression to macroalbuminuria (hazard ratio 0.64, 95% confidence interval 0.49–0.85) and the composite of doubling of serum creatinine, initiation of renal‐replacement therapy or renal death (hazard ratio 0.48, 95% confidence interval 0.25–0.92). Furthermore, empagliflozin‐treated participants showed slower eGFR decline versus placebo, and showed rapid urine albumin‐to‐creatinine ratio reduction at week 12, maintained through week 164, with effects most pronounced in those with baseline microalbuminuria or macroalbuminuria. The kidney safety profile of empagliflozin in the Asian subgroup was similar to the overall trial population.ConclusionsIn Asian patients from the EMPA‐REG OUTCOME® trial, empagliflozin improved kidney outcomes, slowed eGFR decline and lowered albuminuria versus placebo, consistent with the overall trial population findings.

The effect of interactions between proteinuria, activity of fibroblast growth factor 23 and serum phosphate on renal progression in patients with chronic kidney disease: a result from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease study.

Recent experimental study reported that proteinuria increases serum phosphate by decreasing biologic activity of fibroblast growth factor 23 (FGF-23). We examined this relationship in a large chronic kidney disease (CKD) cohort and evaluated the combined effect of proteinuria, FGF-23 activity and serum phosphate on CKD progression. The activity of FGF-23, measured by the fractional excretion of phosphate (FEP)/FGF-23 ratio, was compared according to the degree of proteinuria in 1909 patients with CKD. Primary outcome was CKD progression defined as ≥50% decline of estimated glomerular filtration rate, doubling of serum creatinine and start of dialysis. There was a negative relationship between 24-h urine protein (24-h UP) and FEP/FGF-23 ratio (γ -0.07; P = 0.005). In addition, after matching variables associated with serum phosphate, patients with more proteinuria had higher serum phosphate (P < 0.001) and FGF-23 (P = 0.012), and lower FEP/FGF-23 ratio (P = 0.007) compared with those with less proteinuria. In the matched cohort, low FEP/FGF-23 ratio was an independent risk factor for CKD progression (hazard ratio 0.87 per 1 log increase; 95% confidence interval 0.79-0.95; P = 0.002), and there was significant interaction between 24-h UP and FEP/FGF-23 ratio (P = 0.039). Furthermore, 24-h UP and serum phosphate also had a significant interaction on CKD progression (P < 0.001). Proteinuria is associated with decreased biologic activity of FGF-23 and increased serum phosphate. Furthermore, diminished activity of FGF23 is an independent risk factor for renal progression in proteinuric CKD patients.

The Risk of Stroke and Stroke Type in Patients With Atrial Fibrillation and Chronic Kidney Disease.

Background:Atrial fibrillation (AF) and chronic kidney disease (CKD) are known to increase the risk of stroke.Objectives:We set out to examine the risk of stroke by kidney function and albuminuria in patients with and without AF.Design:Retrospective cohort study.Settings:Ontario, Canada.Participants:A total of 736 666 individuals (>40 years) from 2002 to 2015.Measurements:New-onset AF, albumin-to-creatinine ratio (ACR), and an estimated glomerular filtration rate (eGFR).Methods:A total of 39 120 matched patients were examined for the risk of ischemic, hemorrhagic, or any stroke event, accounting for the competing risk of all-cause mortality. Interaction terms for combinations of ACR/eGFR and the outcome of stroke with and without AF were examined.Results:In a total of 4086 (5.2%) strokes (86% ischemic), the presence of AF was associated with a 2-fold higher risk for any stroke event and its subtypes of ischemic and hemorrhagic stroke. Across eGFR levels, the risk of stroke was 2-fold higher with the presence of AF except for low levels of eGFR (eGFR < 30 mL/min/1.73 m2, hazard ratio [HR]: 1.38, 95% confidence interval [CI]: 0.99-1.92). Similarly across ACR levels, the risk of stroke was 2-fold higher except for high levels of albuminuria (ACR > 30 mg/g, HR: 1.61, 95% CI: 1.31-1.99). The adjusted risk of stroke with AF differed by combinations of ACR and eGFR categories (interaction P value = .04) compared with those without AF. Both stroke types were more common in patients with AF, and ischemic stroke rates differed significantly by eGFR and ACR categories.Limitations:Medication information was not included.Conclusions:Patients with CKD and AF are at a high risk of total, ischemic, and hemorrhagic strokes; the risk is highest with lower eGFR and higher ACR and differs based on eGFR and the degree of ACR.

Curcumin as a major active component of turmeric attenuates proteinuria in patients with overt diabetic nephropathy.

Background:Diabetic nephropathy (DN) is a common cause of end-stage renal disease (ESRD). The benefits and effects of renin–angiotensin system blocker drugs are obvious in decreasing albuminuria, but there is a need to find other drugs that can decrease albuminuria. The aim of our study is to evaluate the effect of short-term administration of curcumin on overt albuminuria in patients with type 2 diabetes mellitus (T2DM).Materials and Methods:A randomized, double-blind clinical trial was performed on 46 patients with T2DM, overt albuminuria ≥300 mg/24 h, and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. After the random allocation of the patients, they were divided into two groups. In the curcumin group, the patients received 500 mg (one capsule) of curcumin with each meal (three times/day after meal) for 16 weeks. Other variables including blood urea nitrogen (BUN), creatinine (Cr), fasting blood sugar (FBS), 2-h postprandial blood sugar (2-h pp BS), lipid profile, 24-h urine analysis for albuminuria, serum albumin, and hemoglobin A1C (HbA1C) were checked at baseline and bimonthly too.Results:two groups at baseline were comparable in terms of basic characteristics (P > 0.05). Albuminuria decreased significantly from 900.42 ± 621.91 at the baseline to 539.68 ± 375.16 at the end of the study in the curcumin group (PTime = 0.002); however, no statistically significant changes were observed in the placebo group (519.94 ± 214.33 at the baseline vs. 444.00 ± 219.10 at the end of the trial; PTime = 0.43), and the decrease was significantly higher in the curcumin group than that of the placebo group (PIntervention = 0.01). No significant differences were observed between the placebo and curcumin in terms of changes in serum BUN, Cr, FBS, 2-h pp BS, HbA1C, lipid profile, and albumin.Conclusion:Our study showed that curcumin as an active turmeric metabolite was an effective adjuvant therapy for ameliorating macroscopic proteinuria in type 2 diabetic patients. Its effect may appear after 2 months of therapy and even in patients with a mild decrease in GFR. Further studies with larger sample size and longer duration are recommended.

Frequency and possible associations of albuminuria in patients with essential hypertension: a single-center experience

Background Microalbuminuria is associated with a high incidence of morbidity and mortality. It is considered as an early marker of kidney damage and a predictor for end-stage renal disease and cardiovascular disease. Thus, it is of great importance to study albuminuria in high-risk groups such as the hypertensive patients to decrease the morbidity and mortality by decreasing the progression of kidney diseases on those groups. Aims The present study was undertaken to find out the frequency and association of microalbuminuria in newly diagnosed essential hypertension. Patients and methods This is a cross-sectional hospital analytic study enrolling all the outpatients nephrology and internal medicine clinics within the period from 2016 January to 2017 March. We enrolled all the patients with the positive inclusion criteria and divided them into two groups; those who are recently diagnosed as essential hypertensive patients (85 patients) aged between 25 and 65 years and (415 normotensive) as normotensive healthy participants with the same age groups. Exclusion criteria were age less than 25 years and more than 65 years, diabetes mellitus, chronic kidney disease, end-stage renal failure, nephrotic syndrome, pregnancy, and under steroid therapy. Results The study showed that 17% of the patients were hypertensive; 28.8% of hypertension cases and 13.1% of normotensive patients had microalbuminuria in the total population (P = 0.000). Twenty-two percent of the hypertensive cases had macroalbuminuria and 3% of the normotensive patients had macroalbuminuria with a P value of 0.000. Advanced age is associated with the increase in the albumin–creatinine ratio (P = 0.000). Conclusion By showing the strong association between microalbuminuria and hypertension, our findings suggest that microalbuminuria could be a useful marker to assess risk management of cardiovascular disease and renal disease.

The glycosylated haemoglobin A1c and albuminuria in patients with type 2 diabetes in the Republic of Srpska: A cross sectional study

Background/Aim. Glycosylated haemoglobin (HbA1c) is currently the gold standard for glucose monitoring in the patients with diabetes. The aim of the present study was to examine the level of success in implementing international guideline targets with regard to glycaemic control in the patients with type 2 diabetes in the Republic of Srpska. This study also aimed to determine the association of albuminuria with the glycaemic control and lipid levels in this patient population. Methods. The participating diabetic patients were those registered in the project titled ??Estimation of the quality of glycoregulation and presence of vascular complications in the persons with diabetes in the Republic of Srpska.? The study was conducted as a cross-sectional study including 1037 patients. HbA1c was determined by a turbidimetric inhibition immunoassay used Roche Diagnostics. Total cholesterol, triglycerides, LDL-C, and HDL-C were determined by reagents from Roche Diagnostics (Roche Diagnostics, Mannheim, Germany) as well as albumin and creatinine in the urine. Results. Mean value for HbA1c was 7.35 ? 1.61% (57 ? 18 mmol/moL). The 49.46% of all participants achieved target values of HbA1c (&lt; 7% or 53 mmol/moL) and 40.30% had albumin to creatinine ratio (ACR) &lt; 30 mg/g. When the patients were divided according to HbA1c (with HbA1c &lt; 7%, 519 patients, and HbA1c ? 7.0%, 510 patients) the ACR values were different between these groups (39.00 vs. 79.50, p &lt; 0.001). We found no significant difference with respect to lipid status between the groups. Conclusion. The patients with type 2 diabetes in the Republic of Srpska, in a large percentage, did not meet targets for glycaemic control. Improvements are necessary in the treatment and maintenance of this disease process to ensure achievement of goals in management of diabetes, which in turn would decrease longstanding complications of type 2 diabetes.

Paucity of high-quality studies reporting on salt and health outcomes from the science of salt: A regularly updated systematic review of salt and health outcomes (April 2017 to March 2018).

The purpose of this review is to identify, summarize, and critically appraise studies on dietary salt and health outcomes that were published from April 2017 to March 2018. The search strategy was adapted from a previous systematic review on dietary salt and health. Identified studies were screened based on a priori defined criteria to identify publications eligible for detailed critical appraisals. Overall, 6747 citations were identified by the search strategy, and 42 health outcome studies were identified. Three of the 42 studies met the criteria for methodological quality and health outcomes and underwent detailed critical appraisals and commentary. In addition, a systematic review and meta-analysis was critically appraised, although it did not strictly meet our methodological criteria. All four of the studies critically appraised found that sodium reduction improved blood pressure, especially in individuals with hypertension. In addition, sodium reduction reduced albuminuria in patients with stage 1-3 chronic kidney disease. Examination of the time course of blood pressure responses to sodium reduction revealed lowering sodium in the context of an average American diet may not produce maximal blood pressure reductions within a 4-week intervention period. This review provides further evidence of the benefit of sodium reduction for blood pressure lowering and gives insights into the subgroups of the population that may derive the greatest benefit from sodium reduction and the time course required to see benefit. Only three high-quality studies were identified during this 12-month review period, highlighting the critical need for more well-conducted rigorous studies in this area.

Metformin or Acarbose Treatment Significantly Reduced Albuminuria in Patients with Newly Diagnosed Type 2 Diabetes Mellitus and Low-Grade Albuminuria.

BackgroundA urine albumin to creatinine ratio (UACR) >30 mg/g is considered to represent albuminuria, but in type 2 diabetes mellitus, even low-grade albuminuria is associated with increased risk of cardiovascular disease. This study aimed to investigate the effects of metformin and acarbose treatment on urine albumin excretion in Chinese patients with newly diagnosed diabetes and low-grade albuminuria.Material/MethodsPatients with newly diagnosed diabetes (n=589) were divided into Group I (with a baseline UACR <10 mg/g) (n=331), and Group II (with a baseline UACR of 10–30 mg/g) (n=258). Following 48 weeks of treatment with metformin or acarbose, the UACR, blood pressure, body mass index (BMI), blood glucose, lipid profiles, and homeostasis model assessment of insulin resistance (HOMA-IR) were compared.ResultsBaseline diastolic blood pressure, levels of blood glucose and low-density lipoprotein cholesterol (LDL-C), and HOMA-IR were significantly increased in Group II compared with Group I (all P<0.05). In Group II, both metformin and acarbose treatment significantly reduced the UACR (P<0.001); the effect was significantly greater following acarbose treatment compared with metformin treatment (P<0.05). In Group I, neither metformin nor acarbose treatment significantly changed the UACR, but both Group I and Group II showed a significant and comparable reduction in BMI, blood glucose, blood pressure, and HOMA-IR.ConclusionsIn a group of Chinese patients with newly diagnosed type 2 diabetes mellitus, low-grade albuminuria (baseline UACR of 10–30 mg/g) was associated with metabolic factors before treatment. Treatment with either metformin or acarbose significantly reduced albumin excretion.

Impact of Hyperfiltration during Early Childhood on the Natural History of Albuminuria in Pediatric Sickle Cell Anemia

Introduction: Pediatric patients with Sickle Cell Anemia (SCA) are at risk for developing albuminuria. Hyperfiltration precedes the development of albuminuria in patients with diabetes but the natural history of hyperfiltration on the progression to albuminuria has not been studied in children with SCA.Methods: We have enrolled 185 participants with HbSS or SB0 thalassemia in a prospective pediatric cohort study evaluating progression to chronic kidney disease; the mean current age of participants in this cohort is 14 years. We have abstracted 817 urine microalbumin creatinine measurements and 891 estimations of GFR (eGFR) by Cystatin C. Abnormal urine albumin/creatinine is defined as >30mg/g. We defined persistent albuminuria as two abnormal spot urine microalbumin/creatinine measurements over three consecutive measurements and intermittent albuminuria as one abnormal urine measurement with two consecutive repeat measurement as normal. We performed descriptive and univariate statistics to characterize the natural history of the development of albuminuria. Next, as standard of care definitions of hyperfiltration (>140 ml/min/1.87) are not appropriate in SCA during early childhood (4-10 years of age), we a priori defined hyperfiltration as an eGFR ≥180 ml/min/1.87. We categorized patients with hyperfiltration during early childhood if the mean eGFR was >180 ml/min/1.87. We abstracted the mean white blood cell count (WBC), hemoglobin (Hb), and SCA therapy during early childhood and performed estimates of the odds ratio and used chi-squared test to compare the proportion of those who progressed to persistent albuminuria. Finally, we performed time to event analysis to obtain the estimated Kaplan-Meier curves for participants with and without hyperfiltration and used logrank test to compare their survival distributions.Results: Among the 185 participants, 55 participants (30%) were identified with at least one episode of albuminuria and 130 patients (70%) have not yet developed an episode of albuminuria. Among the 55 participants identified with an albuminuria event, 36 participants (66%) are categorized as having persistent albuminuria while 19 patients (34%) demonstrated intermittent or only one episode of albuminuria. The mean age at the identification of a first albuminuria event was 11.0 years (range 2-18 years). Comparing patients that progressed to persistent vs intermittent albuminuria, we identified no significant differences for age at first episode of albuminuria (13.2 vs 11.9 years, p=0.3) or type of SCA modifying therapy at first episode of albuminuria (p=0.4).We identified 90 participants with eGFR obtained between 4-10 years; 39 (43%) participants were categorized with hyperfiltration and 51 participants had a mean eGFR < 180 ml/min/1.87. Nine of the 39 (23%) participants categorized with hyperfiltration have progressed to develop persistent albuminuria as compared to 3 (6%) of the 51 without hyperfiltration progressed to persistent albuminuria; hyperfiltration was associated with a 4.8 higher odds of developing persistent proteinuria. (p=0.02). The mean eGFR during early childhood was also significantly higher among participants that progressed to albuminuria (186 vs 169 ml/min/1.87, p=0.04). We identified no significant impact of mean WBC (p=0.13), mean hemoglobin (p=0.07), or SCA therapy (p=0.22) in this subset of patients on progression to persistent albuminuria. As the current age of participants impacts identifying albuminuria outcomes, we performed a time to event analysis; participants identified with hyperfiltration during early childhood develop persistent albuminuria at an earlier age than participants without persistent albuminuria (logrank p=0.004). Finally, while persistent albuminuria was significantly associated with hyperfiltration during early childhood, we did not identify a difference in eGFR between patients with and without albuminuria during adolescence (Figure 1).Conclusion: Although 30% of patients with SCA will develop an episode of albuminuria during childhood, only 19% of cohort participants developed persistent albuminuria. Early hyperfiltration is predictive for developing albuminuria and therapies should target reducing hyperfiltration in the first decade of life. DisclosuresNo relevant conflicts of interest to declare.

Chronic kidney cortical damage is associated with baseline kidney function and albuminuria in patients managed with radical nephrectomy for kidney tumours

This study evaluated the relationship between histological markers of chronic kidney damage in patients undergoing radical nephrectomy for kidney tumours and preoperative kidney function, degree of albuminuria, and changes in glomerular volume. A schema to grade chronic kidney damage could be used to identify patients at risk of developing CKD following nephrectomy. Non-neoplastic cortical tissue was sourced from 150 patients undergoing radical nephrectomy for suspected kidney cancer. This tissue was evaluated for indicators of chronic damage, specifically: glomerulosclerosis, arteriosclerosis, interstitial fibrosis, and tubular atrophy. Glomerular volume was determined using the Weibel and Gomez method. Associations between these parameters and both estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) were determined using either a Mann-Whitney U-test or a Kruskal-Wallis ANOVA. Associations between both eGFR and ACR and glomerular volume were assessed using linear regression. eGFR was inversely associated with the degree of glomerulosclerosis (p < 0.001), vascular narrowing (p= 0.002), tubular atrophy (p < 0.001), and interstitial fibrosis (p < 0.001). ACR was associated only with the degree of interstitial fibrosis (p= 0.02) and tubular atrophy (p= 0.02). Glomerular volume was greater for males, diabetics, hypertensive patients, and patients with a greater degree of interstitial fibrosis. Glomerular volume was positively associated with ACR. A schema to grade chronic damage was developed. The proposed schema is associated with baseline clinical indices of kidney function and damage. Longitudinal validation is necessary to determine the prognostic utility of this schema.