Early Stages Of Renal Dysfunction Research Articles

#1682 Myocardial remodeling in Wistar rats with renal dysfunction treated with a high-salt ration

Abstract Background and Aims High food intake of NaCl is the traditional factor of increase in blood pressure (BP) and cardiovascular risks also hurts kidneys. The purpose of the paper is to evaluate the morphological changes in the myocardium of normotensive Wistar rats with an early stage of renal dysfunction treated with a diet with increased concentration of salt for a long time. Method 30 Wistar rats (age 2.5-3 months) were studied and divided into three groups of 10 each. In the first, control, sham-operated (SO) rats, receiving standard diet (0.34% NaCl), in the second, rats subjected to resection of ¾ of the kidney parenchyma, receiving a standard diet (NE group), in the third, rats subjected to ¾ NE and those receiving a high-sodium diet (4% NaCl, high-salt diet, HSD). The feeds differed only in the %NaCl content. The ¾ NE model was created in two stages with an interval of 7 days. 20 mg/kg Zoletil 100 and 0.05 ml of Xylazine were used as anesthesia. At the first stage, the poles of the left kidney (1/2 part of the kidney) were removed, at the second stage, the right kidney was completely removed. The duration of the experiment was 4 months. At the end of the experiment, systolic BP at the tail was measured in awake rats using the cuff method (ELEMA electromanometer, Sweden). After removal from the experiment, blood was collected from the rats for biochemical analysis, and the LVMI was calculated as the ratio of LV mass to the body weight of the animal (mg/g). Myocardial fragments were placed in formalin, and sections 1.5–2 µm thick were prepared from paraffin blocks. The preparations were stained with Hematoxylin and Eosin and Masson's trichrome and used for histological analysis. The statistical significance of intergroup differences was determined using the Mann–Whitney test and Student's t test. Results During the observation period, BP in the SO group of animals did not change: initially - 120 [120;125] mm Hg, after 4 months - 120 [120;125] mmHg, p = 0.527. In the group with NE on a standard diet, an increase in BP was noted - from 120 [120; 125] mmHg up to 135.0 [132.5;137.5] mmHg, p = 0.011. In the group with NE + HSD, the increase in BP levels was more pronounced - up to 140[140;148] mmHg, (p = 0.001, relative to the SO group). The serum urea level in the SO group was 4.7 [4.5;5.4] mmol/l, creatinine −32.5 [29.0;36.0] µmol/l, in the NE group - 10.0 [9.1;10.9] mmol/l, (p = 0.0001, relative to the SO group) and 69.0[64.0;74.0] µmol/l, (p = 0.0001), in the NE+ HSD group – 10.7 [9.8;11.0] mmol/l, (p = 0.0001) and 64.5[46.3;69.5] µmol/l, (p = 0.001), respectively. Thus, the groups of rats with early-stage kidney dysfunction, although they had higher levels of urea and creatinine in the blood serum relative to the SO group, did not differ significantly from each other in these indicators. LVMI increased in rats with NE on a standard diet (LR −2.07±0.05 mg/g, NE −2.14 ± 0.06 mg/g, p = 0.1591). Consumption of a high-salt diet aggravated the growth of myocardial mass in rats with NE (NE + HSD - 2.41 ± 0.14 mg/g, p = 0.0084 and p = 0.0372, respectively). At the histological level, the increase in LV myocardial mass in rats with NE was characterized by hypertrophy of cardiomyocytes and the formation of interstitial fibrosis. The changes were more pronounced in the group with NE + HSD. The diameter of cardiomyocytes in rats of the SO group was 12.9 ± 0.4 µm, in animals with NE on standard diet - 14.5 ± 0.6 µm, in rats with NE + HSD - 15.5 ± 1.6 µm (p<0 .01 and p < 0.02, relative to the SO group). The area of interstitial fibrosis also increased in rats with NE (10.5 ± 2.6%, in the SO group - 0.6 ± 0.2%, p = 0.0000) and was slightly higher in the NE + HSD group (13.6 ± 2.8%, p = 0.0000, relative to the SO group). In rats with NE, both on a standard diet and with HSD, at this stage of the formation of kidney pathology, the thickness of the nutrimyocardial arteries did not differ significantly from the SO indicator rats. Conclusion Long-term salt intake with increased salt addition in Wistar rats in the initial stages of renal dysfunction does not affect the level of urea and creatinine in the blood serum, but promotes an increase in BP and myocardial remodeling, constantly progressing in the progression of cardiomyocyte hypertrophy and interstitial fibrosis.

Birth weight and hypertension: nature or nurture?

Birth weight and hypertension: nature or nurture?

Abstract P220: Dietary Patterns and Lower Risk of Early Stage of Renal Dysfunction in 9-Year Follow-Up in a Japanese General Population: Tanushimaru Cohort Study

Introduction: Chronic kidney disease (CKD) is a growing public health problem with aging society and a progression to end-stage renal disease is associated with a higher risk of death. Previous studies have suggested that healthy dietary patterns like vegetable-based diet may reduce risk of incident CKD in general populations. However, there is less evidence on whether dietary patterns have impact on early stage of renal dysfunction (RD). Therefore, we investigated the longitudinal association between dietary patterns and early stage of RD in a general population. Methods: We recruited 1943 men and women aged 40 to 95 years in the prospective Tanushimaru cohort study in Japan in 2009. Their dietary intake was assessed using a brief self-administered diet history questionnaire (BDHQ). Principal component analysis (PCA) identified the main dietary patterns. In 984 participants re-examined in 2018, estimated glomerular filtration rate (eGFR) was calculated by CKD-EPI method in 2009 and 2018. RD and early RD were defined as eGFR < 60 and < 90 mL/min/1.73m 2 , respectively . Multivariable linear and logistic regression analyses were performed to examine the association of the main dietary patterns in 2009 with RD and early RD in 2018. Covariates included cardiovascular risk factors and eGFR at baseline. Results: Mean levels of eGFR in 2009 and 2018 were 94.0 and 84.3 mL/min/1.73m 2 . The prevalence of RD and early RD in 2018 were 8.8% (n=87) and 58.5% (n=576), respectively. The PCA revealed three major dietary patterns: vegetable pattern (vegetables, mushrooms and seaweeds); rice pattern (rice, bread and miso soup); and alcohol pattern (alcoholic beverages, cakes and snacks). The higher vegetable pattern score was significantly associated with higher eGFR in 2018 (p=0.006) and modestly associated with lower risk of early RD (p=0.06), but not RD (p=0.1) in the fully-adjusted models. Conclusions: The vegetable pattern was significantly associated with higher eGFR and may prevent an early stage of RD in a 9-year follow-up.

Distinctive accumulation of globotriaosylceramide and globotriaosylsphingosine in a mouse model of classic Fabry disease

Fabry disease (FD) is an inherited disease caused by deficient α-galactosidase A activity that is characterized by the accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3). Although plasma lyso-Gb3 is a sensitive biomarker of FD, the correlation between its concentration and clinical symptoms remains unclear. To clarify the influence of plasma Gb3 and lyso-Gb3 in a symptomatic GlatmTg(CAG-A4GALT) FD mouse model, the total contents of Gb3, lyso-Gb3 and their analogs in various organs and plasma were determined in mice with early- (5-week-old) and late-stage (20-week-old) renal dysfunction. A marked increase in total Gb3 content in the heart, kidneys, spleen, liver, small intestine, lungs, brain, and plasma was observed in the 20-week-old mice compared to that in 5-week-old mice. In contrast, the increase in lyso-Gb3 was relatively small, and the total content in the lungs and plasma was unchanged. Lyso-Gb3 analogs {lyso-Gb3(−2) and lyso-Gb3(+18)} and Gb3 analogs {Gb3(−2) and Gb3(+18)} were observed in all organs and plasma at both ages, and the percentages of the analogs were unique to specific organs. The pattern of 37 Gb3 analogs/isoforms of liver Gb3 corresponded well with that of plasma Gb3. Although the analog pattern of plasma lyso-Gb3 did not resemble that of any organ lyso-Gb3, the relative content {lyso-Gb3: lyso-Gb3(−2)} in the sum of all organs corresponded well to that of the plasma at both ages. These data indicate that liver Gb3 may contribute to the plasma Gb3 level, while plasma lyso-Gb3 may be released from all organs, and the capacity of the plasma lyso-Gb3 pool may reach a maximum at an early stage of renal dysfunction.

Cystatin C as a marker of the rapid development of the atherosclerosis in patients with diabetes mellitus and chronic kidney disease

Introduction. The relationship between kidney dysfunction and cardiovascular system is multifaceted. Thus, the value of such a potential marker of glomerular filtration rate (GFR) as cystatin C cannot be underestimated as a predictor of the development of cardiovascular complications and atherogenesis factor in diabetes mellitus (DM) and chronic kidney disease (CKD). Objective was to evaluate the role of cystatin C as an atherogenesis factor in patients with DM and CKD. Materials and methods. The study involved 514 patients aged 25 to 80 years (the group of interest (n=449), the control group (n=65)). All patients underwent clinical and laboratory tests, sonography of the lower extremities vessels and brachiocephalic arteries (BCA). Results. The thickness of the intima-media complex increased with an increase of cystatin C level in the right carotid artery (CA) (from 0.80 [0.70; 0.90] mm to 0.97 [0.90; 1.02] mm) and in the left CA (from 0.90 [0.80; 0.94] mm to 0.92 [0.90; 1.10] mm). Logistic regression analysis demonstrated that an increase of cystatin C level > 0.93 mg/l raises the risk of intima-media thickening by 2.5 times (OR 2.505, p=0.042) and by 5 times when increase of cystatin C>1.38 mg/l (OR 4.718, p=0.001). At the same time, the association with homocysteine was unreliable (p=0.058). The level of cystatin C ≥0.82 mg/l with a sensitivity of 72 % and a specificity of 52 % allowed to predict the development of subclinical atherosclerosis in patients with DM and CKD (ROC AUC – 0.739). Conclusion. Cystatin C is not only a highly sensitive and accurate indicator of GFR, capable of detecting early stages of renal dysfunction, but also a highly effective predictive marker of atherosclerotic process in patients with DM and CKD.

Association of Metabolically Healthy Obesity and Glomerular Filtration Rate among Male Steelworkers in North China.

This study aims to investigate the association between metabolically healthy obesity (MHO) and the early stages of renal dysfunction and whether systemic inflammation affects the study’s outcome. Male steelworkers in northern China were investigated in this cross-sectional survey (n = 6309). A decrease in estimated glomerular filtration rate (eGFR) was used as the primary outcome, which was defined as an eGFR of ≤89 mL/min/1.73 m2. A BMI ≥ 25 kg/m2 was used to determine obesity. In the definition of metabolic health, the absence of metabolic syndrome components is considered metabolically healthy. An assessment of inflammation was carried out using a surrogate marker called high-sensitivity C-reactive protein (hs-CRP). The adjusted odds ratio (OR) and confidence intervals (CIs) were estimated using the multivariable logistic regression model. After adjusting for hs-CRP, MHO (OR = 1.97; 95% CI: 1.21 to 3.21) was significantly associated with decreased eGFR compared to metabolically healthy non-obesity (MHNO). With the MHNO/hs-CRP ≤ 0.01 mg/dL group as a reference, the OR was 2.17 (95% CI: 1.17 to 4.02) for decreased eGFR in the group with MHO/hs-CRP > 0.01 mg/dL. MHO is associated with renal dysfunction at an early stage. To some degree, this risk can be explained by the level of inflammation.

Vitamin D Binding Protein and Renal Injury in Acute Decompensated Heart Failure.

BackgroundRenal function in acute decompensated heart faiulre (ADHF) is a strong predictor of disease evolution and poor outcome. Current biomarkers for early diagnostic of renal injury in the setting of ADHF are still controversial, and their association to early pathological changes needs to be established. By applying a proteomic approach, we aimed to identify early changes in the differential urine protein signature associated with development of renal injury in patients hospitalised due to ADHF.Materials and MethodsPatients (71 [64–77] years old) admitted at the emergency room with ADHF and hospitalised were investigated (N = 64). Samples (urine/serum) were collected at hospital admission (day 0) and 72 h later (day 3). Differential serum proteome was analysed by two-dimensional electrophoresis and matrix-assisted laser desorption/ionisation-time of flight (MALDI-ToF/ToF). Validation studies were performed using ELISA.ResultsProteomic analysis depicted urinary vitamin D binding protein (uVDBP) as a two spots protein with increased intensity in ADHF and significant differences depending on the glomerular filtration rate (GFR). Urinary VDBP in patients with ADHF at hospitalisation was > threefold higher than in healthy subjects, with the highest levels in those patients with ADHF already presenting renal dysfunction. At day 3, urine VDBP levels in patients maintaining normal renal function dropped to normal values (P = 0.03 vs. day 0). In contrast, urine VDBP levels remained elevated in the group developing renal injury, with values twofold above the normal range (P < 0.05), while serum creatinine and GF levels were within the physiological range in this group. Urinary VDBP in ADHF positively correlated with markers of renal injury such as cystatin C and Kidney Injury Molecule 1 (KIM-1). By ROC analysis, urinary VDBP, when added to cystatin C and KIM-1, improved the prediction of renal injury in patients with ADHF.ConclusionWe showed increased urine VDBP in patients with ADHF at hospital admission and a differential uVDBP evolution pattern at early stage of renal dysfunction, before pathological worsening of GFR is evidenced.

High-Density Lipoproteins and the Kidney.

Dyslipidemia is a typical trait of patients with chronic kidney disease (CKD) and it is typically characterized by reduced high-density lipoprotein (HDL)-cholesterol(c) levels. The low HDL-c concentration is the only lipid alteration associated with the progression of renal disease in mild-to-moderate CKD patients. Plasma HDL levels are not only reduced but also characterized by alterations in composition and structure, which are responsible for the loss of atheroprotective functions, like the ability to promote cholesterol efflux from peripheral cells and antioxidant and anti-inflammatory proprieties. The interconnection between HDL and renal function is confirmed by the fact that genetic HDL defects can lead to kidney disease; in fact, mutations in apoA-I, apoE, apoL, and lecithin–cholesterol acyltransferase (LCAT) are associated with the development of renal damage. Genetic LCAT deficiency is the most emblematic case and represents a unique tool to evaluate the impact of alterations in the HDL system on the progression of renal disease. Lipid abnormalities detected in LCAT-deficient carriers mirror the ones observed in CKD patients, which indeed present an acquired LCAT deficiency. In this context, circulating LCAT levels predict CKD progression in individuals at early stages of renal dysfunction and in the general population. This review summarizes the main alterations of HDL in CKD, focusing on the latest update of acquired and genetic LCAT defects associated with the progression of renal disease.

Rotating Night Shift Work, Exposure to Light at Night, and Glomerular Filtration Rate: Baseline Results from a Chinese Occupational Cohort.

The misalignment between the circadian clock and behavioral cycles has been implicated in pathogenesis of many diseases. The main purpose of this study is to examine the association between rotating night shift work, exposure to light at night, and glomerular filtration rate among steelworkers in north China. A total of 6869 steelworkers, aged 22 to 60 years, were included in this study. Multivariable logistic regression was used to examine the association between night shift work, the brightness of bedroom ambient light at night (LAN), and estimated glomerular filtration rate (eGFR), with adjustment for potential confounders. Mediation analysis was performed to examine the mediation effect of potential mediators on the association of duration of night shifts and eGFR. Long duration of night shift work (≥29 years) had elevated odds of decreased eGFR (≤89 mL/min/1.73 m2) (odds ratio (OR), 1.37, 95% confidence interval (CI) 1.09–1.73) compared with day work after adjustment for potential confounders. The association between duration of night shifts and eGFR (continuous) was partially modified by diastolic blood pressure (average causal mediation effect (ACME), –0.077, 95% CI –0.134 to −0.030, p < 0.001). No significant associations were observed among the different brightness of bedroom ambient light levels: middle level (OR, 0.90, 95% CI 0.77–1.05), lightest level (OR, 0.94, 95% CI 0.75–1.18), and decreased eGFR compared with the darkest level. Long-term night-shift work, rather than the brightness of bedroom ambient LAN, is associated with early stage of renal dysfunction in steelworkers, and blood pressure may mediate the relationship between night shift work and decreased eGFR.

Renal dysfunction is associated with decline of cognitive function in community-dwelling older adults: Korean frailty and aging cohort study

BackgroundCognitive decline is common in older adults. Similarly, the prevalence of renal dysfunction is also increased in the elderly population. We conducted this study to clarify the relationship between renal dysfunction and decline of cognitive function in community-dwelling elderly population.MethodsA cross-sectional analysis was performed using data from the Korean Frailty and Aging Cohort Study, a nationwide cohort study. Total 2847 (1333 men, 1514 women) eligible participants were enrolled for this study. The estimated glomerular filtration rate (eGFR, mL/min/1.73m2) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Global cognitive function was assessed with the Mini-mental State Examination-Korean version. Other domains of cognitive function were tested with the Consortium to Establish a Registry for Alzheimer’s disease and the Frontal Assessment Battery.ResultsThe mean age of all participants was 76.0 ± 3.9 years and eGFR (all in mL/min/1.73 m2) was 77.5 ± 14.3. And the mean eGFR was 91.7 ± 3.2 in quartile 1, 84.9 ± 1.8 in quartile 2, 76.1 ± 3.7 in quartile 3, and 57.2 ± 10.8 in quartile 4. In baseline characteristics, participants with lower eGFR tend to have lower cognitive function scores than participant with higher eGFR. In linear regression analysis, eGFR was correlated with the word list memory (β = 0.53, P = 0.005), word list recall (β = 0.86, P < 0.001), and word list recognition (β = 0.43, P = 0.030) after adjustment of confounding variables. Moreover, after multivariate adjustment the association with cognitive impairment in quartile 2 was stronger (adjusted OR: 1.535, 95% CI: 1.111–2.120, P = 0.009), and the ORs of cognitive impairment were 1.501 (95% CI: 1.084–2.079, P = 0.014) in quartile 3 and 1.423 (95% CI: 1.022–1.983, P = 0.037) in quartile 4.ConclusionIn older adults, the immediate, recent memory, and recognition domains were significantly related to renal function. Also, the mild renal dysfunction was independently associated with impairment of global cognitive function. These results suggest that the early stages of renal dysfunction could be an effective target to prevent worsening of cognitive impairment. Therefore, regular monitoring and early detection of mild renal dysfunction in elderly population might be needed.

Factors Associated with Vitamin D Levels in Patients with Chronic Obstructive Pulmonary Disease in Combination with Renal Dysfunction

The goal of the study was to analyze factors associated with vitamin D levels in patients diagnosed with chronic obstructive pulmonary disease (COPD) in combination with the early stages of renal dysfunction. The study covered 338 patients with first- and second-degree COPD (including 66.9% men with a mean age of 69.4 ± 6.1 years and an average COPD duration of 18.5 ± 4.1 years and 33.1% women with a mean age of 64.8 ± 7.3 years and an average COPD duration of 12.1 ± 5.1 years). All patients were diagnosed with first- and second-degree chronic kidney disease (CKD). In addition to general clinical examinations, potential risk factors for vitamin D deficiency were assessed in all patients. In multiple regression with step-by-step inclusion of signs, the following identified factors made a significant contribution to the levels of vitamin D synthesis in patients with COPD in combination with the early stages of renal dysfunction: annualized relapse rate of COPD (3 (2–4), β = –0.932, p = 0.003), smoking index (SI) (44 (15–87), β = –0.038, p = 0.006), fibrinogen level (5 (3–7), β = –0.413, p = 0.016), GFR (74.9 (68.4–89), β = –0.119, p = 0.041), insolation (94.5 (38.5–152), β = 0.026, p = 0.0008), the total score on the GDS scale (9 (8–11), β = –0.536, p = 0.014). R2 for this model was 0.87. BMI made a significant contribution to the level of vitamin D synthesis at the stage of inclusion in multivariate analysis, but the connection weakened and completely disappeared with the inclusion of smoking index values when insolation indicators were added to the analysis. FEV1 values do not affect the vitamin D level in COPD patients in combination with early stages of kidney dysfunction.

Sex specificity of kidney markers to assess prognosis in cirrhotic patients with TIPS.

Renal function assessed by creatinine is a key prognostic factor in cirrhotic patients. However, creatinine is influenced by several factors, rendering interpretation difficult in some situations. This is especially important in early stages of renal dysfunction where renal impairment might not be accompanied by an increase in creatinine. Other parameters, such as cystatin C (CysC) and beta-trace protein (BTP), have been evaluated to fill this gap. However, none of these studies have considered the role of the patient's sex. The present study analysed CysC and BTP to evaluate their prognostic value and differentiate them according to sex. CysC and BTP were measured in 173 transjugular intrahepatic portosystemic shunt (TIPS)-patients from the NEPTUN-STUDY(NCT03628807) and analysed their relationship with mortality and sex. Propensity score for age, MELD, etiology and TIPS indication was used. Cystatin C and BTP showed excellent correlations with creatinine values at baseline and follow-up. CysC was an independent predictor of overall mortality (HR=1.66(1.33-2.06)) with an AUC of 0.75 and identified a cut-off of 1.55mg/L in the whole cohort. Interestingly, CysC was significantly lower in females, also after propensity score matching. In males, the only independent predictor was the creatinine level (HR=1.54(1.25-1.58)), while in females CysC levels independently predicted mortality (HR=3.17(1.34-7.52)). This study demonstrates for the first time that in TIPS-patients creatinine predicts mortality in males better than in females, whereas CysC is a better predictor of mortality in females. These results may influence future clinical decisions on therapeutic options for example, allocation for liver transplantation in TIPS-patients.

Quantitative Proteomics Identify Urinary Hgfl Protein As a Potential Marker for the Development of Chronic Kidney Disease in Sickle Cell Disease Patients

BACKGROUND: Chronic kidney disease (CKD) is common in patients with sickle cell disease (SCD). However, the progression of CKD in SCD and factors associated with such progression remain poorly defined. Liquid chromatography mass spectrometry (LC-MS) based quantitative proteomics has become a highly potent method for biomarker discovery due to growing capabilities for broad proteome coverage and good accuracy and precision in quantification.OBJECTIVES: The purpose of this study was to identify the potential markers associated with CKD progression in patients with SCD using quantitative proteomics.METHODS: Urine samples were collected from healthy controls and SCD patients with different CKD stages from University of Illinois at Chicago (UIC). Mass-spectrometry analysis was performed on an LTQ Orbitrap XL mass spectrometer (Thermo Fisher Scientific) coupled to a Prominence Nano LC (Shimadzu) using the Xcalibur version 2.7.0 (Thermo Scientific). Proteome Discoverer 1.4 and SIEVE 2.1 programs were used for protein identification and label-free quantification. Heavy isotope labeled peptide EDQTSPAPGLR(13C6, 15N) was used as an internal standard for high resolution/selected ion monitoring (HR/SIM) analysis of HGFL. Urinary HGFL protein together wiht creatinine and albumin were also measured by ELISA.RESULTS: Since glomerular hyperfiltration is an early stage of renal dysfunction. We performed label-free quantitative proteomic analysis for urine samples collected from SCD patients with hyperfiltration (N=3) and normal (N=3). Hepatocyte growth factor-like (HGFL) protein was found to be significantly downregulated (5.52-fold, p=8.05 × 10-5) in samples with glomerular hyperfiltration compared to normal group. Next, we developed a high resolution/selected ion monitoring (HR/SIM) method by measuring the HGFL peptide (m/z 585.79) with isotope labeled-HGFL peptide (m/z 590.80) as internal standard (IS). HR/SIM quantification was performed for 19 urine samples from SCD patients and 12 urine samples from healthy controls. HGFL levels were found to be significantly downregulated (p=0.0084) in the SCD urine samples compared to samples from healthy controls (Figure 1). To further assess the correlation between HGFL level and CDK stage, we expanded the analysis to SCD patients with different CKD stage ranging from 0 to 5 and 19 healthy individuals by ELISA. The result confirmed the finding of HR/SIM quantification, moreover, showed that urinary HGFL level highly correlated with CKD stage (r= ̶ 0.4106, p=0.002, Figure 1) and showed high sensitivity and specificity by Receiver Operating Characteristic (ROC) curve analysis (AUC=0.78).CONCLUSIONS: HGFL protein has been identified as a negative regulator of phosphatidylinositol 3-kinase (PI3K), and PI3K/Akt pathway was found to be activated in the progress of CKD. Therefore, the decrease of HGFL level in urines from SCD patients may indicate the development of CKD. Combination of LC-MS based quantitative proteomics and ELISA validation is an useful approach for biomarker discovery.ACKNOWLEDGMENTS: This work was supported by NIH Research Grants 1P50HL118006, 1R01HL125005, 5G12MD007597 and K23HL125984. The content is solely the responsibility of the authors and does not necessarily represent the official view of NHLBI, NIMHD or NIH. [Display omitted] DisclosuresGordeuk:Emmaus Life Sciences: Consultancy.

Dyslipidemia in patients with chronic kidney disease.

Chronic kidney disease (CKD) is associated with high risk for cardiovascular disease (CVD). This association is multifactorial, but CKD is often associated with dyslipidemia, which likely contributes. Patients with CKD have dyslipidemia even at early stages of renal dysfunction and dyslipidemia tends to progress with deterioration of kidney function. The dyslipidemia in CKD is largely due to increased triglyceride levels, decreased HDL-C and varying levels of LDL-C. Current management of CKD may also affect lipid levels. Robust clinical trials demonstrate that statins are safe and efficacious in both lipid lowering and prevention of CVD events in pre-end stage CKD and post-transplant. However, there is no evidence of improved CVD outcomes with statin use in dialysis patients. This review will focus on mechanisms underlying dyslipidemia in CKD and clinical trial evidence for lipid lowering therapy in patients with CKD.

Use of urinary PO2 for early detection of renal dysfunction in cardiac surgical patients

Background: Medullary hypoxia is a critical initiating event in the development of multiple forms of acute kidney injury (AKI), and the urinary PO2 provides an index of medullary oxygenation. This biomarker has the potential to aid in the management of patients at risk of AKI and, so, to possibly prevent development of AKI. Objective: To evaluate the effect of cardiopulmonary bypass (CPB) on urine oxygen tension (PO2) and determine whether perioperative PO2 can predict postoperative renal dysfunction in patients undergoing cardiac surgery. Materials and Methods: This prospective, observational study has enrolled a total of 63 patients who were undergoing on-pump cardiac surgery. On the basis of the AKI guideline, the patients were distributed into two groups. Group A patients did not develop AKI (n = 45), and the remaining patients developed AKI: group B (n = 12). Preoperative renal data and intraoperative and postoperative data were collected. Result: Urine PO2 data were recorded for 63 patients from blood gas analyzer. Prebypass and postbypass urine PO2 was similar up to 24-h postoperative in all patients. Even in patients who develop AKI, we did not find any difference in urine PO2 prebypass and postbypass. Conclusion: These results suggest the possibility of PO2 detecting an early stage of renal dysfunction in cardiac surgery although further studies will be required to substantiate it.

The Efficacy of Serum Cystatin C and Creatinine to Diagnose Impaired Renal Function in Cancer Patients Under Treatment with Cisplatin

Renal function can be impaired in cancer patients treated with cisplatin. Currently, serum creatinine is used to diagnose renal dysfunction. This study aims to determine the efficacy of serum cyatatin C and ceratinine in contrast to the 24-hour urine creatinine clearance [CrCl] as the gold standard method in diagnosis of renal dysfunction in cancer patients under treatment with cisplatin. Seventy patients under treatment with cisplatin included. Serum cystatin C and creatinine were measured. CrCl in 24-hour urine was calculated. Measurements were done two times; before initiation of chemotherapy and before the fourth cycle of the chemotherapy. Then, using Receive Operating Curve [ROC] curve and at different cut-off points, sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV] of both cystatin C and creatinine to detect renal dysfunction were calculated. 24-hour urine CrCl was the gold standard method to define renal dysfunction. Sensitivity and specificity values of cystatin C of > 1.28 mg/L to predict CrCl< 78 mL/min were 77% and 95%, respectively. PPV and NPV of cystatin C were 95% and 79%, respectively with a diagnostic accuracy of 86%. On the other hand, sensitivity and specificity of creatinine were 64% and 47%, respectively. Serum cystatin C concentration had better sensitivity, specificity, PPV, and NPV compared to creatinine in detection of early stages of renal dysfunction in cancer patients under treatment with cisplatin. This marker can be used as an effective screening method in such patients to find renal dysfunction at its early stages.

Correlation of Chronic Renal Dysfunction and Albuminuria with Severity of Coronary Artery Lesions in Patients with Coronary Artery Disease

This study was conducted to investigate the possible correlation of chronic renal dysfunction and albuminuria with the severity of coronary artery lesions in patients with coronary artery disease (CAD). Two-hundred and ninety-nine patients who had undergone coronary angiography for suspected CAD were stratified into three groups according to the glomerular filtration rate (GFR): group I included 144 patients with normal renal function GFR >90 ml/(min × 1.73 m(2)), group II included 97 patients with mild renal impairment GFR 60-89 ml/(min × 1.73 m(2)), and group III included 58 patients with moderate renal impairment GFR <60 ml/(min × 1.73 m(2)). Patients were then stratified into two groups according to the albuminuria level (0; minimal, 1+, 2+, 3+): the albuminuria negative group (negative = 0) included 171 patients and the albuminuria positive group (positive = minimal, 1+, 2+, 3+) included 128 patients. Clinical features and coronary lesion characteristics were compared among these groups. Patients with more severe renal dysfunction and positive albuminuria had a higher incidence of CAD (66.7 vs. 70.1 vs. 72.4%, p = 0.025 and 64.2 vs. 75.0%, p = 0.032), more multi-vessel disease (31.2 vs. 41.2 vs. 53.4 %, p = 0.004 and 33.3 vs. 46.1%, p = 0.015), more left anterior descending branch lesions (50.7 vs. 56.7 vs. 60.3%, p = 0.012 and 49.1 vs. 61.7 %, p = 0.009), and a higher Gensini score (42.3 ± 14.7 vs. 46.1 ± 19.9 vs. 52.8 ± 21.2, p = 0.026 and 44.0 ± 16.0 vs. 50.5 ± 20.2, p = 0.017). In conclusion, chronic renal dysfunction and albuminuria may be important factors determining the occurrence and the severity of CAD. Albuminuria was an especially significant indicator at the early stage of renal dysfunction.

Evaluation of snake envenomation-induced renal dysfunction in dogs using early urinary biomarkers of nephrotoxicity

Renal dysfunction in dogs envenomed by poisonous snakes is currently detected using traditional serum and urinary biomarkers such as creatinine and proteinuria. However, these markers lack sensitivity at the early stages of renal dysfunction and their diagnostic accuracy is affected by pre-analytical factors commonly occurring in these dogs, such as haemolysis and haemoglobinuria. Early detection of renal dysfunction would allow for the identification of dogs requiring intensive treatment and monitoring and may help inform prognosis. The aim of this study was to evaluate the performance of several novel urinary biomarkers of glomerular dysfunction, namely, urinary albumin (uAlb), immunoglobulin G (uIgG) and C-reactive protein (uCRP) and of proximal tubular dysfunction (urinary retinol binding protein (uRBP)) compared to traditional end points in dogs with renal damage caused by snake envenomation. Biomarker results were compared between 19 dogs bitten by snakes producing either neurotoxins or cytotoxins and 10 clinically healthy controls.uAlb, uIgG, and uRBP were significantly increased in snake-envenomed dogs at presentation compared to controls, whereas only uIgG and uCRP were significantly elevated 24h post-envenomation. The urinary protein:creatinine ratio was also increased in envenomed dogs compared to controls, but because of the presence of haematuria and haemoglobinuria, differentiation between pre-renal and renal proteinuria was not possible. The results showed that these novel urinary biomarkers may assist in better detecting renal dysfunction in dogs envenomed by poisonous snakes at the acute disease stage compared to traditional laboratory endpoints.

The risk of atherosclerosis in patients with chronic kidney disease.

BackgroundChronic kidney disease (CKD) is becoming a serious health problem; the number of people with impaired renal function is rapidly rising, especially in industrialized countries. A major complication of CKD is cardiovascular disease. Accelerated atherosclerosis has been observed in early stages of renal dysfunction. The purpose of this study was to examine the relationship between the degree of renal insufficiency and both the prevalence and intensity of coronary artery disease (assessed on the basis of number of vessels with stenosis).Methods446 individuals with both serum creatinine >120 μmol/l (men) or >96 μmol/l (women) and acute coronary syndrome were included in the study. All patients included in this analysis underwent urgent coronarography. Data concerning glomerular filtration rate (GFR), number of vessels with stenosis, hypertension, lipid disorders, creatinine concentration, C-reactive protein, glucose and lipid profile were analyzed.ResultsThis study confirmed that moderate to severe renal impairment is associated with accelerated atherosclerosis. Moreover, patients with GFR values below 60 ml/min/1.73 m2 are predisposed to accelerated, multivessel cardiovascular disease.ConclusionsGFR seems to be an independent risk factor for multivessel cardiovascular disease. Due to the fact that patients with renal dysfunction are at high risk of cardiovascular events, they should obtain optimal treatment resulting not only in kidney protection but also in the elimination of cardiovascular risk factors.

Development of a liquid chromatography tandem mass spectrometry method for iothalamate measurement to assess renal function for potential kidney donation

BackgroundChronic kidney disease often goes undetected due to the insensitivity of current methods to accurately assess glomerular filtration rate (GFR) in early stages of renal dysfunction. The clearance of exogenously introduced iothalamate, a commonly used radiopaque agent, is an alternative to inulin clearance for the assessment of renal function and its use in calculating GFR can serve as a screening tool for kidney transplant donors. MethodsA method was developed to measure iothalamate in plasma and urine samples by HPLC combined with electrospray positive ionization tandem mass spectrometry (MS/MS). Iothalamate is isolated from plasma by methanol extraction and urine using a quick-spin filtration approach, then monitored by multiple reaction monitoring using the hydrogen adduct mass transitions. Iohexol was used as an internal standard. ResultsIothalamate was measured within an analytical run time of 5min, with a lower limit of quantification of 18.75ng/ml. The intraassay and interassay variations of the plasma and urine iothalamate assays were both <9%. Recovery from plasma and urine samples ranged from 93.6% to 104.1%. GFR was calculated using the patient's urine flow rate and plasma and urine iothalamate values. Linear correlations tested by LC–MS/MS and an accepted capillary electrophoresis (CE) assay showed similar results (GFR, r=0.92, Sy/x=10.3). ConclusionsWe developed and validated an LC-MS/MS method for quantitating iothalamate in plasma and urine to calculate GFR used for screening potential kidney donors in our hospital system. A less sensitive mass spectrometry system does not sacrifice analytical or clinical sensitivity for measuring GFR.