Kidney Disease Patients Research Articles

Metabolic phenotypes and risk of end-stage kidney disease in patients with type 2 diabetes.

Obesity often initiates or coexists with metabolic abnormalities. This study aimed to investigate the pathological characteristics and the independent or mutual relations of obesity and metabolic abnormalities with end-stage kidney disease (ESKD) in patients with type 2 diabetes (T2D) and associated diabetic kidney disease (DKD). A total of 495 Chinese patients with T2D and biopsy-confirmed DKD between 2003 and 2020 were enrolled in this retrospective study. The metabolic phenotypes were based on the body weight index (BMI)-based categories (obesity, BMI ≥ 25.0 kg/m2) and metabolic status (metabolically unhealthy status, ≥ 1 criterion National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III) excluding waist circumference and hyperglycemia) and were categorized into four types: metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO). The pathological findings were defined by the Renal Pathology Society classification. Cox proportional hazards models were used to estimate hazard ratios (HRs) for ESKD. There are 56 (11.3%) MHNO patients, 28 (5.7%) MHO patients, 176 (35.6%) MUNO patients, and 235 (47.5%) MUO patients. The high prevalence of the Kimmelstiel-Wilson nodule and severe mesangial expansion were associated with obesity, whereas severe IFTA was related to metabolically unhealthy status. In the multivariate analysis, the adjusted HR (aHR) was 2.09 [95% confidence interval (CI) 0.99-4.88] in the MHO group, 2.16 (95% CI 1.20-3.88) in the MUNO group, and 2.31 (95% CI 1.27-4.20) in the MUO group compared with the MHNO group. Furthermore, the presence of obesity was insignificantly associated with ESKD compared with non-obese patients (aHR 1.22, 95% CI 0.88-1.68), while the metabolically unhealthy status was significantly associated with ESKD compared to the metabolically healthy status in the multivariate analysis (aHR 1.69, 95% CI 1.10-2.60). Obesity itself was insignificantly associated with ESKD; however, adding a metabolically unhealthy status to obesity increased the risk for progression to ESKD in T2D and biopsy-proven DKD.

Clinical calculator for the prognosis of rapid progression of chronic kidney disease in patients with type 2 diabetes mellitus

Aim. To develop an applied clinical calculator for the prognosis of rapid progression of CKD in patients with type 2 diabetes, which allows to identify a group of patients at risk of a high rate of decrease in GFR of diabetes in outpatient admission, to assess its informativeness, resolution and diagnostic significance.Material and methods. A single-stage cross-observational study of clinical status indicators was performed in a population sample of patients with type 2 diabetes. Primary medical data were collected using the AWPE 2.0 program; 150 protocols of outpatient consultations, including 69 clinical indicators, were selected according to the compliance criteria. Based on the results of a comprehensive analysis of the relationship between the indicators of clinical status and the stages of development of CKD in type 2 diabetes, the most significant factors of progression of diabetic kidney damage are identified; the original diagnostic parameter "GFR reduction Index" is proposed and clinically justified, which allows to give an objective quantitative characteristic of the dynamics of the pathological process; the measure of the influence of diagnostically significant predictors on the rate of GFR reduction is determined by regression analysis; a logistic model is constructed, on the basis of which a prognostic calculator for rapid progression of CKD is developed.Results. Quantitative assessment of the contribution of individual clinical indicators to the rate of progression of CKD allowed us to identify the following significant factors: duration of diabetes and insulin therapy, acute myocardial infarction in history, age, BMI, concomitant retinopathy, pulsation on the popliteal artery, risk group IV hypertension, treatment with sulfonylureas (without differentiated assessment by pharmacological groups), calcium antagonists; when evaluating the informativeness and predictive ability of the calculator, the area under the AUC ROC curve was 0,90 (0,82; 0,98), p<0,001, which characterizes the quality of the diagnostic technique as very high.Conclusion. The original diagnostic parameter "Glomerular filtration Rate reduction Index" allows us to get a more detailed and accurate idea of the patterns of progression of CKD in DM, the applied clinical calculator of rapid progression of CKD allows us to identify a group of patients at risk of a high rate of GFR reduction, with a high level of diagnostic significance in outpatient settings.

Healthcare costs of the progression of chronic kidney disease in patients with type 2 diabetes mellitus in Colombia

Healthcare costs of the progression of chronic kidney disease in patients with type 2 diabetes mellitus in Colombia

Clinical benefits and risks of anticoagulation therapy according to the degree of chronic kidney disease in patients with atrial fibrillation

BackgroundThe clinical benefits and risks of anticoagulation therapy in patients with chronic kidney disease (CKD) are still inconclusive. We describe the outcomes of patients with atrial fibrillation (AF) after anticoagulation therapy according to differences in creatinine clearance (CrCl). We also aimed to determine the patients who could benefit from anticoagulation therapy.MethodsThis is a retrospective observational review of patients with AF who were managed at Asan Medical Center (Seoul, Korea) between January 1, 2006, and December 31, 2018. Patients were categorized into groups according to their baseline CrCl by Cockcroft–Gault equation and their outcomes were evaluated (CKD 1, ≥ 90 mL/min; CKD2, 60–89 mL/min; CKD3, 30–59 mL/min; CKD4, 15–29 mL/min; CKD 5, < 15 mL/min). The primary outcome was NACE (net adverse clinical events), defined as a composite of all-cause mortality, thromboembolic events, and major bleeding.ResultsWe identified 12,714 consecutive patients with AF (mean 64.6 ± 11.9 years, 65.3% male, mean CHA2DS2-VASc score 2.4 ± 1.6 points) between 2006 and 2017. In patients receiving anticoagulation therapy (n = 4447, 35.0%), warfarin (N = 3768, 84.7%) was used more frequently than NOACs (N = 673, 15.3%). There was a higher 3-year rate of NACE with renal function deterioration (14.8%, 18.6%, 30.3%, 44.0%, and 48.8% for CKD stages 1–5, respectively).The clinical benefit of anticoagulation therapy was most prominent in patients with CKD 1 (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.37–0.67), 2 (HR 0.64 CI 0.54–0.76), and 3 (HR 0.64 CI 0.54–0.76), but not in CKD 4 (HR 0.86, CI 0.57–1.28) and 5 (HR 0.81, CI 0.47–1.40). Among patients with CKD, the benefit of anticoagulation therapy was only evident in those with a high risk of embolism (CHA2DS2-VASc score ≥ 4, HR 0.25, CI 0.08–0.80).ConclusionAdvanced CKD is associated with a higher risk of NACE. The clinical benefit of anticoagulation therapy was reduced with the increasing CKD stage.

Sensing ultrasound localization microscopy for the visualization of glomeruli in living rats and humans

Estimation of glomerular function is necessary to diagnose kidney diseases. However, the study of glomeruli in the clinic is currently done indirectly through urine and blood tests. A recent imaging technique called Ultrasound Localization Microscopy (ULM) has appeared. It is based on the ability to record continuous movements of individual microbubbles in the bloodstream. Although ULM improved the resolution of vascular imaging up to tenfold, the imaging of the smallest vessels had yet to be reported. We acquired ultrasound sequences from living humans and rats and then applied filters to divide the data set into slow-moving and fast-moving microbubbles. We performed a double tracking to highlight and characterize populations of microbubbles with singular behaviors. We decided to call this technique "sensing ULM" (sULM). We used post-mortem micro-CT for side-by-side confirmation in rats. In this study, we report the observation of microbubbles flowing in the glomeruli in living humans and rats. We present a set of analysis tools to extract quantitative information from individual microbubbles, such as remanence time or normalized distance. As glomeruli play a key role in kidney function, it would be possible that their observation yields a deeper understanding of the kidney. It could also be a tool to diagnose kidney diseases in patients. More generally, it will bring imaging capabilities closer to the functional units of organs, which is a key to understand most diseases, such as cancer, diabetes, or kidney failures. This study was funded by the European Research Council under the European Union Horizon H2020 program (ERC Consolidator grant agreement No 772786-ResolveStroke).

Estimated Effect of Parathyroidectomy on Long-Term Kidney Function in Adults With Primary Hyperparathyroidism.

Multidisciplinary guidelines recommend parathyroidectomy to slow the progression of chronic kidney disease in patients with primary hyperparathyroidism (PHPT) and an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. Limited data address the effect of parathyroidectomy on long-term kidney function. To compare the incidence of a sustained decline in eGFR of at least 50% among patients with PHPT treated with parathyroidectomy versus nonoperative management. Target trial emulation was done using observational data from adults with PHPT, using an extended Cox model with time-varying inverse probability weighting. Veterans Health Administration. Patients with a new biochemical diagnosis of PHPT in 2000 to 2019. Sustained decline of at least 50% from pretreatment eGFR. Among 43 697 patients with PHPT (mean age, 66.8 years), 2928 (6.7%) had a decline of at least 50% in eGFR over a median follow-up of 4.9 years. The weighted cumulative incidence of eGFR decline was 5.1% at 5 years and 10.8% at 10 years in patients managed with parathyroidectomy, compared with 5.1% and 12.0%, respectively, in those managed nonoperatively. The adjusted hazard of eGFR decline did not differ between parathyroidectomy and nonoperative management (hazard ratio [HR], 0.98 [95% CI, 0.82 to 1.16]). Subgroup analyses found no heterogeneity of treatment effect based on pretreatment kidney function. Parathyroidectomy was associated with a reduced hazard of the primary outcome among patients younger than 60 years (HR, 0.75 [CI, 0.59 to 0.93]) that was not evident among those aged 60 years or older (HR, 1.08 [CI, 0.87 to 1.34]). Analyses were done in a predominantly male cohort using observational data. Parathyroidectomy had no effect on long-term kidney function in older adults with PHPT. Potential benefits related to kidney function should not be the primary consideration for PHPT treatment decisions. National Institute on Aging.

Integration of Chinese Herbal Medicine into Routine Care Was Related to Lower Risk of Chronic Kidney Disease in Patients with Rheumatoid Arthritis: A Population-Based Nested Case-Control Study in Taiwan.

Non-steroidal anti-inflammatory drugs (NSAIDs) arefrequentlyused asthe first-lineagents for the symptomatic relief of rheumatoid arthritis (RA), but it may insidiously provoke the onset of renal diseases, especially chronic kidney disease (CKD). While Chinese herbal medicine (CHM) has become an increasingly popular adjunctive therapy among RA groups, there are currently no available data on the effect of CHM use towards risk of CKD. This study aimed to explore on a population-level whether CHM use decreases sequent CKD risk among them. In this nested case-control study retrieved from the nationwide insurance database of Taiwan from 2000 to 2012, we looked at the association between CHM use and the likelihood of developing CKD, with a focus on usage intensity. Cases with CKD claims were defined and matched to one randomly selected control case. Conditional logistic regression was then applied to estimate odds ratio (OR) of CKD from CHM treatment measured before the index date. For each OR, we calculated a 95% confidence interval for CHM use relative to the matched control. This nested case-control study included 5464 patients with RA, where after matching comprised 2712 cases and 2712 controls. Among them, there were 706 and 1199 cases that ever received CHM treatment, respectively. After the adjustment, CHM use in RA individuals was related to a lower likelihood of CKD, with an adjusted OR of 0.49 (95% CI: 0.44-0.56). Additionally, a dose-dependent, reverse association was found between the cumulative duration of CHM use and risk of CKD. Integrating CHM into conventional therapy may reduce the likelihood of developing CKD, which could be a reference in instituting novel preventive strategies to improve treatment outcomes and reduce related fatalities for RA subjects.

Eplerenone add-on treatment in resistant hypertension in peritoneal dialysis patient. A case report

Resistant hypertension (RH) is frequently seen in clinical practice in kidney disease patients. Mineralocorticoid receptor antagonists (MRAs) especially spironolactone are highly effective in the management of RH. Eplerenone — highly selective MRA has been also shown to be effective in RH patients but it is rarely used in this clinical condition, especially in kidney disease patients. Eplerenone is mainly recommended in congestive heart failure after myocardial infarction. A case of peritoneal dialysis (PD) patient with RH successfully treated with eplerenone was reported.

The health and budget impact of sodium-glucose co-transporter-2 inhibitors (SGLT2is) in The Netherlands

ObjectivesType-2 Diabetes mellitus (T2DM) increases both the patient risk of cardiovascular disease (CVD) and renal outcomes, such as chronic kidney disease (CKD). Recent clinical trials of the glucose-lowering drug-class of sodium-glucose co-transporter-2 inhibitors (SGLT2is) have shown benefits in preventing CVD events and progression of CKD, leading to an update of the Dutch T2DM treatment guideline for patients at risk. The aim of this study is to assess the health and economic impact of the guideline-recommended utilization of SGLT2is in the Netherlands.MethodsThe patient population at risk was determined by multiplying Dutch T2DM prevalence rates with the total numbers of inhabitants of the Netherlands in 2020. Subsequently, two analyses, comparing a treatment setting before and after implementation of the new guideline for SGLT2is, were conducted. Clinical and adverse event rates in both settings as well as direct healthcare costs were sourced from the literature. Total costs were calculated by multiplying disease prevalence, event rates and costs associated to outcomes. One-time disutilities per event were included to estimate the health impact. The potential health and economic impact of implementing the updated guideline was calculated.ResultsUsing a 5-year time horizon, the guideline-suggested utilization of SGLT2is resulted in a health impact equal to 4835 quality adjusted life years gained (0.0031 per patient per year) and €461 million cost-savings. The costs of treatment with SGLT2is were €813 million. Hence the net budget impact was €352 million for the total Dutch T2DM population, which translated to €0,57 per patient per day.ConclusionSGLT2is offer an option to reduce the number of CVD and CKD related events and associated healthcare costs and health losses in the Netherlands. Further research is needed to include the benefits of improved T2DM management options from a broader societal perspective.HighlightsThe glucose-lowering drug-class of sodium-glucose co-transporter-2 inhibitors (SGLT2is) has shown benefits in preventing cardiovascular events and progression of kidney disease in patients with type-2 diabetes leading to a revision of the respective Dutch treatment guideline.The 5-year budget impact of the adoption of SGLT2is in the new treatment guideline was equal to €352 million or €0.57 per patient per day, with a total of 4385 quality adjusted life years gained.The introduction of SGLT2is for Dutch type-2 diabetes patients has the potential to substantially reduce the number of cardiovascular as well as renal disease events and related healthcare costs while also delivering a health benefit.

A diagnostic criterion for the dynamics of chronic kidney disease in patients with diabetes

Aim to develop and clinically substantiate an objective quantitative diagnostic criterion for the dynamics of chronic kidney disease (CKD) in patients with diabetes mellitus (DM).&#x0D; Material and methods. A comparative cross-observational study of clinical indicators was performed in a general sample of patients with type 2 diabetes, divided into groups according to the parameter "GFR reduction index (RI_GFR)", which characterizes the dynamics of CKD and the development of cardiorenal syndrome in patients with diabetes. 150 protocols of outpatient consultations were selected using the compliance criteria, including the data on 72 clinical indices. The threshold value for dividing the groups of "slow" and "fast" progression of CKD according to the RI_GFR parameter was 4.21 ml/min/1.73 m2. By the method of correlation analysis, the strength of the interrelations of clinical indicators was determined, the Student's t-test and one-factor analysis of variance were used to compare the mean values of independent variables.&#x0D; Results. To quantify the dynamics of the progression of CKD in DM patients, a diagnostic parameter RI_GFR was proposed, calculated according to the original formula based on the value of GFR and the duration of the disease of DM. When assessing the statistical relationships between RI_GFR and clinical indicators, the significance of correlations with creatinine levels, duration of diabetes, insulin therapy, age, history of acute myocardial infarction, dosage of sulfonylureas, as well as the absence of correlation with indicators of achievement of glycemic control goals was noted. When dividing the sample into groups according to the rate of progression of CKD, significant differences were found in the parameters of the duration of DM disease and the use of insulin therapy, the total dose of insulin, the level of glycemia, and body mass index. Insufficient level of reliability was found in the parameters of the dosage of sulfonylureas and age.&#x0D; Conclusion. The developed original diagnostic parameter RI_GFR allows us to give an objective characteristic of the dynamics of CKD in patients with DM. A statistically significant correlation was found between the rate of progression of diabetic kidney damage and cardiovascular risk factors with less influence of the glycemic control factor at the stage of formation of cardiorenal syndrome. To clarify the influence of hemodynamic and glycemic factors on the development of cardiorenal syndrome, it is necessary to continue the study using the logistic regression analysis.

Effects of Sodium-Glucose Co-Transporter-2 Inhibitors on Markers of Vascular Damage

Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce cardiovascular morbidity and delay the progression of kidney disease in patients with type 2 diabetes mellitus (T2DM). However, the mechanisms underpinning these benefits are not entirely clear. More specifically, it is uncertain whether these agents exert cardiorenal protective effects through a direct action on the vascular wall. The aim of the present study was to evaluate the effects of SGLT2 inhibitors on markers of subclinical vascular damage. In total, 40 adult patients with T2DM and glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 and age- and gender-matched patients with T2DM and GFR > 60 mL/min/1.73 m2 were consecutively enrolled. Indices of arterial stiffness (pulse wave velocity, augmentation index (AIx), AIx adjusted to a heart rate of 75 beats/min (Alx@75) and central systolic, diastolic, pulse and mean pressure), carotid atherosclerosis (stenosis, intima-media thickness (cIMT) and maximal plaque thickness) and peripheral arterial disease (ankle brachial index (ABI)) were determined. The chi-squared and Mann-Whitney U-test were used to detect differences in categorical and continuous variables between groups, respectively. In total, 15 patients were treated with SGLT2 inhibitors and 25 patients were not receiving these agents. Serum low-density lipoprotein cholesterol levels were lower in the former whereas other cardiovascular risk factors, the prevalence of established cardiovascular disease, anthropometric and demographic characteristics, and vital signs did not differ between the 2 groups. The AIx was lower in patients treated with SGLT2 inhibitors (21.9 ± 11.3 vs. 29.7 ± 12% in patients not treated with SGLT2 inhibitors; p < 0.05). The AIx@75 was also lower in the former (21.3 ± 10.9 and 32.6 ± 11.3%, respectively, p < 0.005). Other markers of arterial stiffness were similar in the 2 groups. In addition, markers of carotid atherosclerosis and the ABI did not differ between patients treated and not treated with SGLT2 inhibitors. Treatment with SGLT2 inhibitors appears to reduce arterial stiffness. Accordingly, these agents might improve cardiovascular outcomes not only in patients with T2DM and established cardiorenal disease but also in lower-risk patients.

Vegan Diet Is Associated with a Lower Risk of Chronic Kidney Disease in Patients with Hyperuricemia

Hyperuricemia is a well-known risk factor for chronic kidney disease (CKD). Little is known about whether a vegetarian diet is associated with a lower risk of CKD in patients with hyperuricemia. From 5 September 2005, to 31 December 2016, we retrospectively included clinically stable patients with hyperuricemia who received health check-ups at Taipei Tzu Chi Hospital. All participants completed a dietary habits questionnaire to determine whether they were omnivorous, lacto-ovo vegetarian, or vegan. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 or the presence of proteinuria. A total of 3618 patients with hyperuricemia were recruited for this cross-sectional study, consisting of 225 vegans, 509 lacto-ovo vegetarians, and 2884 omnivores. After adjusting for age and sex, vegans had a significantly lower odds ratio (OR) of CKD than omnivores (OR, 0.62; p = 0.006). The OR of CKD remained significantly lower in vegans after adjusting for additional confounders (OR, 0.69; p = 0.04). Additionally, age (per year OR, 1.06; p < 0.001), diabetes mellitus (OR, 2.12; p < 0.001), hypertension (OR, 1.73; p < 0.001), obesity (OR, 1.24; p = 0.02), smoking (OR, 2.05; p < 0.001), and very high uric acid levels (OR, 2.08; p < 0.001) were independent risk factors for CKD in patients with hyperuricemia. Moreover, structural equation modeling revealed that a vegan diet was associated with a lower OR of CKD (OR, 0.69; p < 0.05). A vegan diet is associated with a 31% lower risk of CKD in patients with hyperuricemia. A vegan diet may be beneficial in reducing the occurrence of CKD in patients with hyperuricemia.

Association of Serum Fibroblast Growth Factor 23 and FGF23 Gene Variants with Chronic Kidney Disease in Patients with Type 2 Diabetes and Essential Hypertension

Fibroblast growth factor 23 (FGF23) gene variants could influence the production of FGF23 in subjects at risk for chronic kidney disease (CKD). Our purpose was to analyze the association of serum levels of FGF23 and two FGF23 gene variants with metabolic and renal function parameters in Mexican patients with Type 2 Diabetes (T2D) and/or essential hypertension (HTN). The study included 632 individuals diagnosed with T2D and/or HTN, of which 269 (43%) were diagnosed with CKD. FGF23 serum levels were determined and FGF23 gene variants rs11063112 and rs7955866 were genotyped. Genetic association analysis included binary and multivariate logistic regressions adjusted for age and sex. Patients with CKD were older, had higher systolic blood pressure, uric acid, and glucose levels than those without CKD. Also, patients with CKD had higher FGF23 levels (106 vs. 73 pg/mL p=0.003). No correlation of any gene variants with FGF23 levels was found, but minor allele for rs11063112 and haplotype rs11063112A-rs7955866A were associated with low probability of CKD (Odds Ratio [OR]=0.62 and 0.58, respectively). Conversely, the haplotype rs11063112T-rs7955866A was associated with increased FGF23 levels and risk for CKD (OR=6.90). In addition to the traditional risk factors, levels of FGF23 are higher in Mexican patients with diabetes and/or essential hypertension and CKD, compared to those without renal damage. In contrast, the two minor alleles of two variants of the FGF23 gene, rs11063112 and rs7955866, as well as the haplotype carrying these two alleles, were found to be protective against renal disease in this Mexican patients' sample.

Broadening horizons in mechanisms, management, and treatment of diabetic kidney disease

Diabetic kidney disease (DKD) is the first cause of end-stage kidney disease in patients with diabetes and its prevalence is increasing worldwide. It encompasses histological alterations that mainly affect the glomerular filtration unit, which include thickening of the basement membrane, mesangial cell proliferation, endothelial alteration, and podocyte injury. These morphological abnormalities further result in a persistent increase of urinary albumin-to-creatinine ratio and in a reduction of the estimated glomerular filtration rate. Several molecular and cellular mechanisms have been recognized, up to date, as major players in mediating such clinical and histological features and many more are being under investigation. This review summarizes the most recent advances in understanding cell death mechanisms, intracellular signaling pathways and molecular effectors that play a role in the onset and progression of diabetic kidney damage. Some of those molecular and cellular mechanisms have been already successfully targeted in preclinical models of DKD and, in some cases, strategies have been tested in clinical trials. Finally, this report sheds light on the relevance of novel pathways that may become therapeutic targets for future applications in DKD.

Living with Type 2 Diabetes: Podcast of a Patient-Physician Discussion.

For patients with type 2 diabetes (T2D), the journey to diagnosis may not be straightforward. Patients can present with one of many diabetic complications before a diagnosis of T2D is made. These include heart disease and chronic kidney disease, in addition to cerebrovascular disease, peripheral vascular disease, retinopathy, and neuropathies, all of which can be asymptomatic in the early stages. In their clinical guidelines on standards of care in diabetes, the American Diabetes Association recommends regular screening for conditions such as kidney disease in patients with T2D. Furthermore, the frequent coexistence of diabetes and cardiorenal and/or metabolic conditions often requires a holistic approach to patient management, with specialists from multiple disciplines, including cardiologists, nephrologists, endocrinologists, and primary care physicians, working together. In addition to the use of pharmacological therapies, which can improve prognosis, the management of T2D should include attention to patient self-care, including appropriate dietary changes, consideration of continuous glucose monitoring, and advice on physical exercise. In this podcast, a patient and a clinician discuss a lived experience of the diagnosis of T2D, and the importance of patient education for understanding and managing T2D and its complications. The discussion highlights the central role of the Certified Diabetes Care and Education Specialist, and the role of ongoing emotional support in managing life with T2D, including patient education through reputable online resources and peer support groups. Podcast video with Pamela Kushner (PK) and Anne Dalin (AD) (MP4 92088 KB).

Evaluation of factors that may influence the development of chronic kidney disease in patients with bipolar disorder treated with lithium.

IntroductionBipolar disorder (BD) is a serious and chronic mental disease of mood. Lithium is used for treatment and studies have demonstrated that it is the most efficient drug, reducing suicide risk in a high percentage of patients. However, this drug has well known side effects, such as kidney damage. Lithium could cause chronic kidney disease, specially with the presence of other risk factors.ObjectivesObservational and retrospective study of creatinine levels and glomerular filtration rates observed in blood analysis (follow-up period of 11 years). Sample size of 263 patients diagnosed of BD I and BD II in treatment with lithium. We used socio-demographic (age, sex) and clinic variables (diabetes mellitus, hypertension, use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or diuretics) to generate bivariate and multivariate analysis.MethodsOur main objective is to analyze the deterioration of kidney function and the development of chronic kidney disease that chronic treatment with lithium can induce in patients with BD. Our secondary objective is to determine variables which could promote the development of chronic kidney disease, and to assess if these variables could be considered as risk factors during the treatment with lithium.Results11,3 % of patients in our study developed chronic kidney disease during monitoring. The deterioration of GFR in patients in treatment with lithium was significantly associated with female sex and NSAIDs consumption. A trend towards statistical significance was found regarding the use of diuretics (p=0,060). No statistical significance was found between diabetes mellitus, hypertension or type of BD and the deterioration of kidney function in our sample. An inverse association was found between the GFR decline and the age but no statistical significance was demonstrated.ConclusionsWe conclude that female sex and use of NSAIDs are predicting factors of GFR decline in patients with BD in chronic treatment with lithium. We must take into account these drugs or even avoid concomitant treatment (lithium and NSAIDs) in order to prevent chronic kidney disease. In addition to it, we should recommend careful use of diuretics during treatment with lithium because of risk of dehydration. Diabetes mellitus and hypertension have universally been associated to increase risk of development of chronic kidney disease. However, we have not found statistical significance in our study. Therefore, research should be done in order to determine specific risk factors in this group of patients and, consequently, optimize their treatment.Disclosure of InterestNone Declared

Effect of polymorphisms in drug metabolism and transportation on plasma concentration of atorvastatin and its metabolites in patients with chronic kidney disease.

Dyslipidemia due to renal insufficiency is a common complication in patients with chronic kidney diseases (CKD), and a major risk factor for the development of cardiovascular events. Atorvastatin (AT) is mainly used in the treatment of dyslipidemia in patients with CKD. However, response to the atorvastatin varies inter-individually in clinical applications. We examined the association between polymorphisms in genes involved in drug metabolism and transport, and plasma concentrations of atorvastatin and its metabolites (2-hydroxy atorvastatin (2-AT), 2-hydroxy atorvastatin lactone (2-ATL), 4-hydroxy atorvastatin (4-AT), 4-hydroxy atorvastatin lactone (4-ATL), atorvastatin lactone (ATL)) in kidney diseases patients. Genotypes were determined using TaqMan real time PCR in 212 CKD patients, treated with 20mg of atorvastatin daily for 6weeks. The steady state plasma concentrations of atorvastatin and its metabolites were quantified using ultraperformance liquid chromatography in combination with triple quadrupole mass spectrometry (UPLC-MS/MS). Univariate and multivariate analyses showed the variant in ABCC4 (rs3742106) was associated with decreased concentrations of AT and its metabolites (2-AT+2-ATL: β = -0.162, p = 0.028 in the dominant model; AT+2-AT+4-AT: β = -0.212, p = 0.028 in the genotype model), while patients carrying the variant allele ABCC4-rs868853 (β = 0.177, p = 0.011) or NR1I2-rs6785049 (β = 0.123, p = 0.044) had higher concentrations of 2-AT+2-ATL in plasma compared with homozygous wildtype carriers. Luciferase activity was enhanced in HepG2 cells harboring a construct expressing the rs3742106-T allele or the rs868853-G allele (p < 0.05 for each) compared with a construct expressing the rs3742106G or the rs868853-A allele. These findings suggest that two functional polymorphisms in the ABCC4 gene may affect transcriptional activity, thereby directly or indirectly affecting release of AT and its metabolites from hepatocytes into the circulation.

Urinary Biomarkers for the Assessment of Acute Kidney Injury of Pediatric Sickle Cell Anemia Patients Admitted for Severe Vaso-occlusive Crises.

Sickle cell nephropathy is a progressive morbidity, beginning in childhood, which is incompletely understood partially due to insensitive measures. We performed a prospective pilot study of pediatric and young adult patients with sickle cell anemia (SCA) to assess urinary biomarkers during acute pain crises. Four biomarkers were analyzed with elevations potentially suggesting acute kidney injury: (1) neutrophil gelatinase-associated lipocalin (NGAL), (2) kidney injury molecule-1, (3) albumin, and (4) nephrin. Fourteen unique patients were admitted for severe pain crises and were found to be representative of a larger SCA population. Urine samples were collected at the time of admission, during admission, and at follow-up after discharge. Exploratory analyses compared cohort values to the best available population values; individuals were also compared against themselves at various time points. Albumin was found to be moderately elevated for an individual during admission compared with follow-up ( P = 0.006, Hedge g : 0.67). Albumin was not found to be elevated compared with population values. Neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and nephrin were not found to be significantly elevated compared with population values or comparing admission to follow-up. Though albumin was found to be minimally elevated, further research should focus on alternative markers in efforts to further understand kidney disease in patients with SCA.

Sex differences in risk factors for end-stage kidney disease and death in type 2 diabetes: A retrospective cohort study.

This study investigated the sex differences in the risk of end-stage kidney disease (ESKD) and mortality, as well as the effect modification of sex on associated factors in patients with type 2 diabetes. This multicenter observational cohort study included 4328 patients with type 2 diabetes. Hazard ratios (HRs) with 95% confidence intervals (CIs) of sex for ESKD and death were estimated using Cox proportional regression with adjustment for baseline covariates. For assessing risk modification, HRs and incidence rates for ESKD and death were compared between sexes across patient characteristics using Cox proportional and Poisson regression models. During a median follow-up of 7 years, 276 patients (70% men) developed ESKD, and 241 patients (68% men) died. Men had higher risks of ESKD (HR 1.34; 95% CI 1.02-1.75; p=.034) and death (HR 1.64; 95% CI 1.24-2.16; p=.001) versus women after adjusting for multiple covariates. Among patients with microalbuminuria, men had a substantially higher risk of ESKD versus women, compared to those with normo- and macroalbuminuria (p for interaction .04). Incidence rates were also increased in men versus women with albuminuria of around 300 mg/g. No differences were detected in the association of sex and death across baseline patient subgroups. In type 2 diabetes, men had an increased risk of ESKD and death versus women. Moderately increased albuminuria was strongly associated with sex difference in developing ESKD.

Averrhoa carambola leaves prevent dyslipidemia and oxidative stress in a rat model of poloxamer-407-induced acute hyperlipidemia.

Background: The star fruit [Averrhoa carambola L (Oxalidaceae)] is traditionally used in the treatment of many ailments in many countries. It possesses several pharmacological activities, including antioxidant and anti-inflammatory effects. However, it contains the neurotoxic caramboxin and its high content of oxalic acid limits its consumption by individuals with compromised kidney function. This study assessed the anti-hyperlipidemic and antioxidant activities of different fractions of the methanolic extract of A. carambola leaves (MEACL). Methods: The antioxidant activity was investigated using FRAP, and ABTS and DPPH radical-scavenging assays and the inhibitory activity toward pancreatic lipase (PL) and HMG-CoA reductase was assayed in vitro. Acute hyperlipidemia was induced by poloxamer-407 (P-407) in rats and different fractions of MEACL (n-hexane, chloroform, n-butanol, ethyl acetate (EA), water, and chloroform) were orally administered. Cholesterol and triglycerides were determined at 0, 12, 24, and 48h and LDL-C, vLDL-C, HDL-C, lipid peroxidation (LPO) and antioxidants were assayed after 48h. The expression of ABCA1, ABCG5, ABCG8, LDL-R, SREBP-1, and SREBP-2 and the activity of HMG-CoA reductase were assayed in the liver of P-407-administered rats treated with the EA fraction. Results: The in vitro data revealed potent radical-scavenging activities of MEACL fractions with the most potent effect showed by the EA fraction that also suppressed the activities of HMG-CoA reductase and PL. In P-407-induced hyperlipidemic rats, all fractions prevented dyslipidemia as shown by the decrease in total cholesterol, triglycerides, LDL-C, vLDL-C and atherogenic index. MEACL and its fractions prevented LPO and boosted GSH, superoxide dismutase, glutathione peroxidase, and catalase in P-407-administered rats. The EA fraction showed more effective anti-hyperlipidemic and antioxidant effects than other fractions and downregulated SREBP-2 while upregulated ABCA1 and LDL-R and ameliorated LPL and HMG-CoA reductase in hyperlipidemic rats. Conclusion: MEACL showed in vitro and in vivo antioxidant activity and the EA fraction significantly ameliorated dyslipidemia in a rat model of P-407-induced acute hyperlipidemia by modulating LPL, PL, HMG-CoA reductase, and cholesterolgenesis-related factors. Therefore, the leaves of A. carambola represent a safe alternative for the star fruit particularly in kidney disease patients, and the EA is the most effective anti-hyperlipidemic and antioxidant fraction.