3a Chronic Kidney Disease Research Articles

Identification of Potential Biomarkers of Chronic Kidney Disease in Individuals with Diabetes: Protocol for a Cross-sectional Observational Study.

BackgroundThe importance of identifying people with diabetes and progressive kidney dysfunction relates to the excess morbidity and mortality of this group. Rates of cardiovascular disease are much higher in people with both diabetes and kidney dysfunction than in those with only one of these conditions. By the time these people are identified in current clinical practice, proteinuria and renal dysfunction are already established, limiting the effectiveness of therapeutic interventions. The identification of an epigenetic or blood metabolite signature or gut microbiome profile may identify those with diabetes at risk of progressive chronic kidney disease, in turn providing targeted intervention to improve patient outcomes.ObjectiveThis study aims to identify potential biomarkers in people with diabetes and chronic kidney disease (CKD) associated with progressive renal injury and to distinguish between stages of chronic kidney disease. Three sources of biomarkers will be explored, including DNA methylation profiles in blood lymphocytes, the metabolomic profile of blood-derived plasma and urine, and the gut microbiome.MethodsThe cross-sectional study recruited 121 people with diabetes and varying stages (stages 1-5) of chronic kidney disease. Single-point data collection included blood, urine, and fecal samples in addition to clinical data such as anthropometric measurements and biochemical parameters. Additional information obtained from medical records included patient demographics, medical comorbidities, and medications.ResultsData collection commenced in January 2018 and was completed in June 2018. At the time of submission, 121 patients had been recruited, and 119 samples remained after quality control. There were 83 participants in the early diabetes-associated CKD group with a mean estimated glomerular filtration rate (eGFR) of 61.2 mL/min/1.73 m2 (early CKD group consisting of stage 1, 2, and 3a CKD), and 36 participants in the late diabetic CKD group with a mean eGFR of 23.9 mL/min/1.73 m2 (late CKD group, consisting of stage 3b, 4, and 5), P<.001. We have successfully obtained DNA for methylation and microbiome analyses using the biospecimens collected via this protocol and are currently analyzing these results together with the metabolome of this cohort of individuals with diabetic CKD.ConclusionsRecent advances have improved our understanding of the epigenome, metabolomics, and the influence of the gut microbiome on the incidence of diseases such as cancers, particularly those related to environmental exposures. However, there is a paucity of literature surrounding these influencers in renal disease. This study will provide insight into the fundamental understanding of the pathophysiology of CKD in individuals with diabetes, especially in novel areas such as epigenetics, metabolomics, and the kidney-gut axis.International Registered Report Identifier (IRRID)DERR1-10.2196/16277

Lactic acidosis incidence with metformin in patients with type 2 diabetes and chronic kidney disease: A retrospective nested case-control study.

ObjectiveCompare rates of lactic acidosis (LA) among metformin‐exposed and unexposed patients with type 2 diabetes mellitus and varying degrees of chronic kidney disease (CKD).Research Design and MethodsRetrospective, nested case‐control study using data from national VA Corporate Data Warehouse. All adult patients with type 2 diabetes and CKD newly dispensed any antihyperglycaemic medication during FY 2003‐13 were included. The outcome was LA hospitalization or serum lactate >5 mEq/L. Exposure to metformin was evaluated in the three months prior to event. Estimates were adjusted for 31 covariates, including demographics, comorbidities and medications.ResultsOverall, 320 882 patients were included, contributing a total of 1 331 784 person‐years of follow‐up. LA occurred in 2 665 patients, generating an overall incidence rate of 2.00 (95% CI 1.93‐2.08) per 1000 person‐years. Metformin exposure in the prior 3 months was associated with an elevated adjusted hazard of LA (HR 1.97, 95% CI 1.69‐2.29). No association was evident in patients with CKD stage 1 or 2 (HR 1.05, 95% CI 0.71‐1.57), but associations were present and progressively greater in patients with CKD stage 3a through 5: HR 3.09, 95% CI 2.19‐4.35 in CKD 3a, HR 3.34, 95% CI 1.95‐5.72 in CKD 3b, HR 7.87, 95% CI 3.51‐17.61 in CKD stage 4&5.ConclusionMetformin was not associated with an elevated risk of LA in persons with stage 1‐2 CKD, but was associated with a progressively higher risk at more advanced stages of CKD.

The impact of chronic kidney disease in women undergoing transcatheter aortic valve replacement: Analysis from the Women's INternational Transcatheter Aortic Valve Implantation (WIN-TAVI) registry.

The prevalence of both chronic kidney disease (CKD) and aortic stenosis (AS) increase with age. Although baseline CKD is frequent in patients undergoing transcatheter aortic valve replacement (TAVR), its significance among women is largely unknown. Women's INternational Transcatheter Aortic Valve Implantation (WIN-TAVI) is a multinational, prospective registry of women undergoing TAVR for severe AS. We included patients with available baseline estimated glomerular filtration rate (eGFR) and completed 1-year follow-up. Patients were categorized into three groups based on their eGFR: No CKD (normal kidney function to stage 2 CKD: eGFR ≥60 ml/min/1.73 m2 ); (b) mild CKD (stage 3a CKD: eGFR = 45-59 ml/min/1.73 m2 ); and (c) moderate/severe CKD (stage ≥3b CKD: eGFR <45 ml/min/1.73 m2 ). All events were adjudicated according to the Valve Academic Research Consortium (VARC)-2 criteria. Out of 852 women undergoing TAVR, 326 (38.3%) had no CKD, 225 (26.4%) had mild CKD, and 301 (35.3%) had moderate/severe CKD. Women with higher stage of CKD at baseline were more likely to have a history of hypertension, diabetes, atrial fibrillation, anemia, chronic lung disease, hemodialysis, prior percutaneous coronary intervention, and pacemaker implantation. After multivariate adjustment, moderate/severe CKD was associated with a greater risk of 1-year VARC-2 safety endpoints [hazard ratio (HR) 1.68, 95% confidence interval (CI): 1.10-2.60], all-cause death (HR 2.00, 95% CI: 1.03-3.90), and composite of death, myocardial infarction, stroke or life-threatening bleeding (HR 1.70, 95% CI: 1.04-2.76). There were no differences in 30-day and 1-year VARC-2 efficacy and 30-day VARC-2 safety outcomes. CKD is associated with substantial and independent risk for mortality and morbidity at 1-year follow-up in women undergoing TAVR.

Clinical Characteristics of and Risk Factors for Chronic Kidney Disease Among Adults and Children

Chronic kidney disease (CKD) is serious and common, yet recognition and public health responses are limited. To describe clinical features of, prevalence of, major risk factors for, and care for CKD among patients treated in 2 large US health care systems. This cohort study collected data from the Center for Kidney Disease Research, Education, and Hope (CURE-CKD) registry, an electronic health record-based registry jointly curated and sponsored by Providence St Joseph Health and the University of California, Los Angeles. Patients were adults and children with CKD (excluding end-stage kidney disease) and adults at risk of CKD (ie, with diabetes, hypertension, or prediabetes) identified by laboratory values, vital signs, prescriptions, and administrative codes. Data were collected from January 2006 through December 2017, with analyses performed from March 2019 through November 2019. Diabetes, hypertension, and prediabetes. Clinical and demographic characteristics, prevalence, and prescribed medications. Of 2 625 963 adults and children in the sample, 606 064 adults (23.1%) with CKD had a median (interquartile range [IQR]) age of 70 (59-81) years, with 338 785 women (55.9%) and 434 474 non-Latino white individuals (71.7%). A total of 12 591 children (0.4%) with CKD had a median (IQR) age of 6 (1-13) years, with 7079 girls (56.2%) and 6653 non-Latino white children (52.8%). Median (IQR) estimated glomerular filtration rate was 53 (41-61) mL/min/1.73 m2 among adults and 70 (50-95) mL/min/1.73 m2 in children. Prevalence rates for CKD in adults were 4.8% overall (606 064 of 12 669 700) with 1.6% (93 644 of 6 011 129) during 2006 to 2009, 5.7% (393 455 of 6 903 084) during 2010 to 2013, and 8.4% (683 574 of 8 179 860) during 2014 to 2017 (P < .001). A total of 226 693 patients (37.4%) had category 3a CKD; 100 239 (16.5%), category 3b CKD; 39 125 (6.5%), category 4 CKD; and 20 328 (3.4%), category 5 CKD. Among adults with CKD, albuminuria and proteinuria assessments were available in 52 551 (8.7%) and 25 035 (4.1%) patients, respectively. A renin-angiotensin system inhibitor was prescribed to 124 575 patients (20.6%), and 204 307 (33.7%) received nonsteroidal anti-inflammatory drugs or proton pump inhibitors. Of 1 973 258 adults (75.1%) at risk, one-quarter had diabetes or prediabetes (512 299 [26.0%]), nearly half had hypertension (955 812 [48.4%]), and one-quarter had both hypertension and diabetes or prediabetes (505 147 [25.6%]). This registry-based cohort study revealed a burgeoning number of patients with CKD and its major risk factors. Rates of identification and use of kidney protective agents were low, while potential nephrotoxin use was widespread, underscoring the pressing need for practice-based improvements in CKD prevention, recognition, and treatment.

Anti-Müllerian hormone concentrations in women with chronic kidney disease.

BackgroundSerum anti-Müllerian hormone (AMH) is a biomarker of ovarian reserve. There are limited data to guide the clinical interpretation of AMH in women with chronic kidney disease (CKD). The purpose of this study was to examine AMH concentrations in women with CKD compared with women without CKD.MethodsWe conducted a prospective cohort study of serum AMH concentrations in 163 non-pregnant women with CKD. Serum AMH concentrations were compared with age-specific AMH centiles from 887 healthy female controls.ResultsParticipants included 30 women with Stage 1 CKD, 37 women with Stage 2 CKD, 26 women with Stage 3a CKD, 31 women with Stage 3b CKD and 39 women with Stages 4 and 5 CKD. The median estimated glomerular filtration rate (eGFR) was 51 (interquartile range 31–80) mL/min/1.73 m2. Serum AMH concentrations were lower in all CKD stages compared with women without CKD. Women ages 20–24 years with CKD had comparable serum AMH concentrations (median 1.959 ng/mL) to women ages 35–39 years without CKD (median 1.995 ng/mL). There was no evidence that eGFR was an independent modifier of serum AMH concentrations. More than half of women with CKD (58%) were predicted to have a low response to gonadotrophin stimulation.ConclusionsWomen with CKD have a lower ovarian reserve and are predicted to have a lower ovarian response to gonadotrophin stimulation compared with women without CKD of a similar age. Women with CKD who fail to conceive within 6 months of regular unprotected intercourse should be considered for fertility assessment and intervention.

Renal BOLD MRI in patients with chronic kidney disease: comparison of the semi-automated twelve layer concentric objects (TLCO) and manual ROI methods

Blood oxygenation level dependent (BOLD) MRI technique is used to evaluate changes in intra-renal oxygenation in chronic kidney disease (CKD). The purpose of this study was to evaluate if the novel twelve layer concentric objects (TLCO) method has advantages over the manually defined regions of interest (ROI) analysis. Existing renal BOLD MRI data acquired before and after furosemide on a 3T scanner from 41 CKD patients and 13 age matched healthy controls were analyzed using TLCO method and compared with previously reported ROI analysis. Regional R2* measurements were strongly correlated between the two methods, while ΔR2* was moderately correlated. Medullary R2* by ROI analysis showed higher values compared to R2*_Inner by TLCO, probably due to the contributions from the cortex to R2*_Inner. R2*_Slope and Δ(R2*_Slope), unique parameters based on the TLCO method provided the most significant differences between stage 3a CKD patients and controls and were correlated with eGFR. There was a high degree of agreement between the two methods in terms of regional R2* measurements and both methods did not show differences between moderate CKD patients and controls. However, R2*_Slope and Δ(R2*_Slope) showed the largest sensitivity in distinguishing CKD from controls.

Use of Potentially Nephrotoxic Medications by U.S. Adults with Chronic Kidney Disease: NHANES, 2011-2016.

People with chronic kidney disease (CKD) are at risk for adverse events and/or CKD progression with use of renally eliminated or nephrotoxic medications. To examine the prevalence of potentially inappropriate medication (PIM) use by U.S. adults by CKD stage and self-reported CKD awareness. Cross-sectional analysis of National Health and Nutrition Examination Surveys, 2011-2016 PARTICIPANTS: Non-pregnant adults with stages 3a (eGFR 45-59 mL/min/1.73 m2), 3b (eGFR 30-44), or 4-5 (eGFR < 30) CKD, stratified as CKD-aware/unaware. PIMs were identified on the basis of KDIGO guidelines, label information, and literature review. We calculated proportions using any and individual PIMs, assessing for differences over CKD awareness within each CKD stage. Analyses were adjusted for age, sex, race/ethnicity, education, comorbidities, and insurance type. Adjusted proportions of U.S. adults taking any PIM(s) exceeded 50% for all CKD stages and awareness categories, and were highest among CKD-unaware patients with stages 4-5 CKD: 66.6% (95% CI, 55.5-77.8). Proton pump inhibitors, opioids, metformin, sulfonylureas, and non-steroidal anti-inflammatory drugs (NSAIDs) were all used frequently across CKD stages. NSAIDs were used less frequently when CKD-aware by patients with stage 3a CKD (2.2% [95% CI, - 0.3 to 4.7] vs. 10.7% [95% CI, 7.6 to 13.8]) and stages 4-5 CKD (0.8% [95% CI, - 0.9 to 2.5] vs. 16.5% [95% CI, 4.0 to 29.0]). Metformin was used less frequently when CKD-aware by patients with stage 3b CKD (8.1% [95% CI, 0.3-15.9] vs. 26.5% [95% CI, 17.4-35.7]) and stages 4-5 CKD (none vs. 20.8% [95% CI, 1.8-39.8]). The impact of CKD awareness was statistically significant after correction for multiple comparisons only for NSAIDs in stage 3a CKD. PIMs are frequently used by people with CKD, with some impact of CKD awareness on NSAID and metformin use. This may lead to adverse outcomes or hasten CKD progression, reinforcing the need for improved medication management among people with CKD.

Impact of rapid weight loss after bariatric surgery on the prevalence of arterial hypertension in severely obese patients with chronic kidney disease.

Arterial hypertension (HTN) is one of the most important risk factors for the development and progression of chronic kidney disease (CKD). Rapid weight loss after bariatric interventions has a positive impact on blood pressure levels of hypertensive patients. The aim of our study is to assess the prevalence of HTN in patients with CKD after bariatric surgery (BS). We retrospectively reviewed severely obese patients who underwent BS from 2010 to 2017. We used guidelines of the American College of Cardiology to define HTN. Only patients meeting ACC criteria and the calculation of estimated glomerular filtration rate (eGFR) using CKD epidemiology collaboration study equation preoperatively and at 12-month follow-up were included in the analysis. From a total of 2900 patients, 29.13% (845) met the required criteria and had variables for the calculation of eGFR recorded preoperatively. 36.92% (312) had preoperative HTN and s classified as CKD stage ≥ 2. We observed a predominantly female population 63.83% (203) with mean age of 54.10 ± 11.58. Patients preoperatively classified in CKD 2, 3a, and 3b exhibited the greatest prevalence reduction of HTN at 12-month follow-up (68.59%, n = 214 vs. 36.59%, n = 114; 16.67%, n = 52 vs. 6.41%, n = 20; 7.69%, n = 24 vs. 1.28%, n = 4; p < 0.0001). A marked improvement in CKD was also observed along with improvement in HTN. The greatest benefit corresponded to patients classified preoperatively in CKD 2, 3a and 3b. A total of n = 70 (62.5%) patients with HTN were classified as CKD 2 preoperatively compared to n = 55 (49.11%) at 12-month follow-up (p = 0.0436). Similarly, n = 22 (19.64%) patients with HTN were classified preoperatively as CKD 3a compared to n = 7 (6.25%) and n = 12 (10.71%) patients as CKD 3b compared to n = 4 (3.57%) during the same time period (p = 0.0028, p = 0.0379, respectively). Rapid weight loss after BS significantly reduces prevalence of HTN in all stages of CKD at 12-month follow-up. Additionally, there was a positive impact on classification of CKD at 12-month follow-up.

Comparison of verbal encouragement and avatar-based virtual reality feedback on treadmill walking in children with cerebral palsy.

Morbid obesity is a barrier to kidney transplant in patients with end-stage renal disease (ESRD). Laparoscopic sleeve gastrectomy (SG) is an increasingly considered intervention, but the safety and long-term outcomes are uncertain. We reviewed prospectively collected data on patients with ESRD and chronic kidney disease (CKD) undergoing SG from 2011 to 2018. There were 198 patients with ESRD and 45 patients with CKD (stages 1-4) who met National Institutes of Health guidelines for bariatric surgery and underwent SG; 72% and 48% achieved a body mass index of ≤ 40 and ≤ 35 kg/m2, respectively. The mean percentages of total weight loss and excess weight loss were 18.9 ± 10.8% and 38.2 ± 20.3%, respectively. SG reduced hypertension (85.8% vs 52.1%), decreased antihypertensive medication use (1.6 vs 1.0) (P < .01 each), and reduced incidence of diabetes (59.6% vs 32.5%, P < .01). Of the 71 patients with ESRD who achieved a body mass index of ≤ 40 kg/m2, 45 were waitlisted and received a kidney transplant, whereas 10 remain on the waitlist. Mortality rate after SG was 1.8 per 100 patient-years, compared with 7.3 for non-SG. Patients with stage 3a or 3b CKD exhibited improved glomerular filtration rate (43.5 vs 58.4 mL/min, P = .01). In conclusion, SG safely improves transplant candidacy while providing significant, sustainable effects on weight loss, reducing medical comorbidities, and possibly improving renal function in stage 3 patients.

SUN-249 STUDY OF CHINESE HERBAL COMPOUND IN PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 3:A MULTICENTER DOUBLE-BLIND RANDOMIZED PLACEBO-CONTROLLED CLINICAL TRIAL

How to delay the progression of chronic kidney disease (CKD) is a clinical challenge worldwide. Accumulating studies documented that Chinese medicine (CM) maybe an alternative therapy to some kinds of CKD. In this study, we aimed to evaluate the efficacy and safety of Chinese herbal compound in stage 3 CKD. We did a multicenter, double-blind, randomized, placebo-controlled clinical trial in patients with CKD stage 3 from 9 hospitals. Patients in CM group self-administered Chinese herbal granules twice daily for 24 weeks, while patients in control received masked granules. All patients continued the routine therapy such as low-protein diet, control of blood pressure and so on. 24-hour urine total protein (UTP)，serum creatinine (Scr) and eGFR were analyzed at week 24. Between April 2014 and Oct 2016, a total of 343 randomised patients were treated and 343 patients (171 in CM group versus 172 in control) were eligible for the full analysis set. Overall, at 24 weeks there was no statistical difference in UTP between the two groups (0.97±1.14g/d versus 0.97±1.25g/d). The levels of Scr in CM group decreased significantly compared with the control (130.78±32.55µmol/L versus 149.12±41.27µmol/L). eGFR in CM group remained stable while in control eGFR reduced statistically (55.74±50.82 ml/min/1.73m2 versus 44.46±12.60ml/min/1.73m2). There were 4.35% patients with stage 3a CKD in CM group progressed to stage 3b, and 57.97% reverse to stage 1 or stage 2, while that in control was 20.59% and 17.65%. There were 9.21% patients with stage 3b CKD in CM group progressed to stage 4, and 40.79% reverse to stage 1 or 2 or 3a, while that in control was 17.11% and 22.37%. Our data indicated that Chinese herbal compound combined with routine therapy maintains the kidney function in patients with stage 3 CKD for 24 weeks.

Increased carotid stiffness and remodelling at early stages of chronic kidney disease.

Increased carotid stiffness and remodelling is reported in patients with moderate and advanced chronic kidney disease (CKD) and is associated with cardiovascular events. Here, we tested the hypothesis that carotid artery alterations start earlier, during mild CKD. Within the Paris Prospective Study 3, a large prospective observational survey of nonreferred people aged 50-75 who received an extensive health check-up, there were 294 participants with glomerular filtration rate (GFR) of at least 45 and less than 60 ml/min per 1.73 m (Stage 3A CKD), 840 participants with GFR 60-89 ml/min per 1.73 m with proteinuria (Stage 2 CKD), 4666 participants with GFR 60-89 ml/min per 1.73 m without proteinuria and 3317 individuals with GFR at least 90 ml/min per 1.73 m at study recruitment. Carotid artery measurements were performed using a high-resolution echotracking device. Compared with patients with GFR at least 90 ml/min per 1.73 m, the carotid distensibility and strain progressively decreased (P for trend <0.0001), whereas carotid stiffness progressively increased (P for trend <0.0001) across GFR categories starting at early stage from GFR 60-89 ml/min per 1.73 m without proteinuria. Higher Young's elastic modulus was observed only for Stage 3A CKD, whereas carotid internal diastolic diameter did not differ between groups. The large arterial stiffening starts early during CKD, even in participants with a very mild reduction in renal function.

Prevalence of chronic kidney disease in the elderly using the ASPirin in Reducing Events in the Elderly study cohort.

The prevalence of chronic kidney disease (CKD) in the elderly is controversial because age-related decline in kidney function may not truly reflect underlying kidney disease. We estimate the baseline prevalence and predictors of CKD using the CKD Epidemiology Collaboration (CKD-EPIeGFR ) and Berlin Initiative Study 1 (BIS1eGFR ) eGFR equations in the ASPirin in Reducing Events in the Elderly (ASPREE) trial cohort of healthy older participants. GFR was estimated using CKD-EPI and BIS1 equations. CKD was defined as eGFR <60 mL/min/1.73 m2 or ≥ 60 mL/min/1.73 m2 with urine albumin creatinine ratio (UACR) ≥ 3 mg/mmol. Logistic regression was used to identify predictors of CKD prevalence defined by each eGFR equation. Data for analysis were complete for 17,762 participants. Mean age was 75.1 years (SD 5); 56.4% were female, 76.4% had hypertension, 9% had diabetes mellitus. Mean CKD-EPIeGFR was 73.0 (SD 14.2), compared with mean BIS1eGFR of 62.7 (11.4). Median UACR was 0.8 (IQR 0.5, 1.5) mg/mmol. Prevalence of CKD by CKD-EPIeGFR was 27% (predominantly due to normoalbuminuric stage 3a CKD), substantially lower than 47.1% by BIS1eGFR ; the difference was predominantly driven by reclassification of individuals from G1 and G2 CKD to stage G3a without albuminuria. Increased prevalence of CKD by either equation was related to older age, hypertension, diabetes, or higher body mass index. Prevalence of CKD with CKD-EPIeGFR was 27%, and doubled using the elderly specific BIS1eGFR , with most participants reclassified from stage 2 to stage 3a. Increased prevalence of CKD was related older age, hypertension, diabetes, or increased body mass index.

Chronic kidney disease, cardiovascular risk markers and total mortality in older men: cystatin C versus creatinine

BackgroundIt remains uncertain whether cystatin C is a superior marker of renal function than creatinine in older adults. We have investigated the association between estimated glomerular filtration rate (eGFR) using...

Advanced Kidney Disease in the Left Ventricular Assist Device Population: Impact on Disease Progression, Morbidity and Mortality

Purpose Advanced kidney disease is often considered a relative contraindication to LVAD implantation and many implanting centers view stage 4 and 5 chronic kidney disease (CKD) as an absolute contraindication. We sought to analyze the impact of CKD at the time of LVAD implant on outcomes. Methods All LVAD patients between September 2007 and September 2017 with CKD at the time of LVAD implantation from a single institution were analyzed. Patients were stratified by CKD stage (CKD 1 through 5) at the time of implant and rates of worsening renal function, need for renal replacement therapy (RRT), hospitalizations, LVAD-related complications and death were analyzed. Results Of the 405 total patients, 191 patients (59% centrifugal, 80% male, average age 59 ± 11 years) had varying degrees of renal dysfunction at the time of LVAD implantation (17% CKD 1 or 2, 35% CKD 3a, 34% CKD 3b and 15% CKD 4 or 5). Patients with CKD 4 or 5 were more likely to require RRT than lesser CKD Stages 3b, 3a, and 1 or 2 (37.9% vs. 3.1%, vs. 7.6% vs. 0%, p trend Conclusion Patients with advanced CKD at the time of LVAD implant were more likely to have persistent renal dysfunction and require RRT thereafter. However, there were no statistically significantly differences in LVAD-related morbidity and mortality across the stages of CKD.

Plasma Levels of Preβ1-HDL Are Significantly Elevated in Non-Dialyzed Patients with Advanced Stages of Chronic Kidney Disease.

In chronic kidney disease (CKD), the level of high-density lipoprotein (HDL) decreases markedly, but there is no strong inverse relationship between HDL-cholesterol (HDL-C) and cardiovascular diseases. This indicates that not only the HDL-C level, but also the other quantitative changes in the HDL particles can influence the protective functionality of these particles, and can play a key role in the increase of cardiovascular risk in CKD patients. The aim of the present study was the evaluation of the parameters that may give additional information about the HDL particles in the course of progressing CKD. For this purpose, we analyzed the concentrations of HDL containing apolipoprotein A-I without apolipoprotein A-II (LpA-I), preβ1-HDL, and myeloperoxidase (MPO), and the activity of paraoxonase-1 (PON-1) in 68 patients at various stages of CKD. The concentration of HDL cholesterol, MPO, PON-1, and lecithin-cholesterol acyltransferase (LCAT) activity were similar in all of the analyzed stages of CKD. We did not notice significant changes in the LpA-I concentrations in the following stages of CKD (3a CKD stage: 57 ± 19; 3b CKD stage: 54 ± 15; 4 CKD stage: 52 ± 14; p = 0.49). We found, however, that the preβ1-HDL concentration and preβ1-HDL/LpA-I ratio increased along with the progress of CKD, and were inversely correlated with the estimated glomerular filtration rate (eGFR), even after adjusting for age, gender, triacylglycerols (TAG), HDL cholesterol, and statin therapy (β = −0.41, p < 0.001; β = −0.33, p = 0.001, respectively). Our results support the earlier hypothesis that kidney disease leads to the modification of HDL particles, and show that the preβ1-HDL concentration is significantly elevated in non-dialyzed patients with advanced stages of CKD.

Personalized Treatment for Small Renal Tumors: Decision Analysis of Competing Causes of Mortality.

Purpose To compare the effectiveness of personalized treatment for small (≤4 cm) renal tumors versus routine partial nephrectomy (PN), accounting for various competing causes of mortality. Materials and Methods A state-transition microsimulation model was constructed to compare life expectancy of management strategies for small renal tumors by using 1 000 000 simulations in the following ways: routine PN or personalized treatment involving percutaneous ablation for risk factors for worsening chronic kidney disease (CKD), and otherwise PN; biopsy, with triage of renal cell carcinoma (RCC) to PN or ablation depending on risk factors for worsening CKD; active surveillance for growth; and active surveillance when MRI findings are indicative of papillary RCC. Transition probabilities were incorporated from the literature. Effects of parameter variability were assessed in sensitivity analysis. Results In patients of all ages with normal renal function, routine PN yielded the longest life expectancy (eg, 0.67 years in 65-year-old men with nephrometry score [NS] of 4). Otherwise, personalized strategies extended life expectancy versus routine PN: in CKD stages 2 or 3a, moderate or high NS, and no comorbidities, MRI guidance for active surveillance extended life expectancy (eg, 2.60 years for MRI vs PN in CKD 3a, NS 10); and with Charlson comorbidity index of 1 or more, biopsy or active surveillance for growth extended life expectancy (eg, 2.70 years for surveillance for growth in CKD 3a, NS 10). CKD 3b was most effectively managed by using MRI to help predict papillary RCC for surveillance. Conclusion For patients with chronic kidney disease and small renal tumors, personalized treatment selection likely extends life expectancy. © RSNA, 2019 Online supplemental material is available for this article.

Epidemiology of chronic kidney disease in Australian general practice: National Prescribing Service MedicineWise MedicineInsight dataset.

ABSTRACTAimTo describe sociodemographic characteristics and comorbidities of a large cohort of Australian general practice‐based patients identified as having chronic kidney disease (CKD), using data from National Prescribing Service (NPS) MedicineWise's MedicineInsight dataset, and compare this dataset to the 2011–2012 Australian Health Survey's (AHS) CKD prevalence estimates.MethodsThis was a cohort study using deidentified, longitudinal, electronic health record data collected from 329 practices and 1 483 416 patients distributed across Australia, from 1 June 2013 until 1 June 2016. Two methods were used to calculate the CKD prevalence. One used the same method as used by the 2011–2012 AHS, based on one estimate of the estimated glomerular filtration rate (eGFR) or albumin/creatinine ratios (ACR). The other defined CKD more rigorously using eGFR or ACR results at least 90 days apart.ResultsIn 2016, of 1 310 602 active patients, 710 674 (54.2%) did not have an eGFR or ACR test, while 524 961 (40.1%) had an eGFR or ACR test but did not meet AHS criteria for CKD. Age–sex adjusted rates of CKD (compared to AHS) were CKD 1–0.45% (3.9%), CKD 2–0.62% (2.5%), CKD 3a: 3.1% (2.7%), CKD 3b: 1.14% (0.6%), CKD 4–5: 0.41% (0.3%). The CKD cohort defined more rigorously using eGFR and ACR measures >90 days apart, had comorbidities of atrial fibrillation (30.5%), cardiovascular disease (25.0%), diabetes mellitus (17.1%) and hypertension (14.8%).ConclusionThe MedicineInsight dataset contains valuable and timely information about Australian patients with CKD, and provides prevalence estimates similar to those from AHS data.

Clinical features and risk factors of the kidney function progression in elderly patients with stage 3-4 chronic kidney disease

Objective To investigate the clinical features of elderly patients with stage 3-4 chronic kidney disease (CKD) and to analyze the risk factors of the kidney function progression. Methods This was a cross-sectional study.The clinic data of elderly patients (≥60 years) with stable clinical manifestation in Beijing Hospital from January, 2014 to December, 2015 was collected.Based upon the eGFR derived from Cockcroft-Gault (CG) equation, all patients were divided into groups of CKD 3a group, CKD 3b group and CKD 4 group, respectively.Moreover, patients were separated into the old group (< 80 years) and the very old group (≥80 years) based on the age.The demographic features, primary diseases history, body mass index (BMI), blood routine, urine routine, blood biochemistry, Cystatin C and iPTH were recorded.Logistic regression analysis of kidney function progression was also conducted. Results One-hundred and eighty-three cases were enrolled with a mean age of(80±9)years.Along with the descent of kidney function, the age, levels of proteinuria and iPTH gradually ascended (F=12.352, 5.910, 5.910; P=0.000, 0.003, 0.003, respectively) and the BMI and serum albumin gradually descended (F=9.758, 11.088; P=0.000, 0.000, respectively). In addition, compared to the old group, very old group was associated with decreased level of eGFR[(37.1±9.9) ml·min-1·1.73 m-2vs.(44.0±12.0) ml·min-1·1.73 m-2,t=-4.280, P=0.000] and increased level of CystatinC[(1.71±0.84) mg/L vs. (1.40±0.69) mg/L, t=3.484, P=0.001]. The Logistic regression analysis indicated that the proteinuria was an independent risk factor for the progression of kidney function ( OR =3.856, P=0.004). Conclusions As the gradually descended of the eGFR level in elderly patients with stage 3-4 CKD, age, proteinuria and iPTH gradually ascended, BMI and serum albumin descended, respectively.The level of eGFR decreased and CystatinC increased significantly with the increasing age.Proteinuria was an independent risk factor for progression of the kidney function. Key words: Chronic kidney disease; Glomerular filtration rate; Risk factor

Clinical factors predicting blood pressure reduction after catheter-based renal denervation.

IntroductionRenal denervation (RD) can lead to a significant and sustained decrease in mean values of arterial blood pressure (BP). However, there is still a subset of patients without a significant BP drop after RD (non-responders).AimTo compare characteristics of RD responders to RD non-responders and to identify the clinical predictors of BP reduction.Material and methodsThirty-one patients with diagnosed resistant hypertension underwent RD. Three years after RD the analysis of BP reduction was performed in regard to the baseline patient characteristics.ResultsAfter 3 years’ follow-up a 10% or more reduction of systolic baseline BP was observed in 74% of patients. Ten percent or more reduction of diastolic baseline BP was observed in 71% of patients. Among responders we observed the following risk factors: hypercholesterolemia in 70%, body mass index (BMI) > 30 kg/m2 in 55%, diabetes mellitus in 35%, current smoking in 5%. Comorbidity included coronary artery disease (CAD) in 30%, cardiomyopathy in 10%, chronic obstructive pulmonary disease (COPD) in 10%, renal insufficiency in 10%, and ventricular arrhythmia in 5%. Among non-responders we observed the following risk factors: hypercholesterolemia in 38%, diabetes mellitus type 2 in 38% and BMI > 30 kg/m2 in 86%. Comorbidity included CAD in 50% and cardiomyopathy in 13% of patients.ConclusionsA 10% reduction of systolic baseline BP was observed in 74% of patients 3 years after renal denervation. Clinical factors like COPD, chronic kidney disease 3a, female sex and hypercholesterolemia increase the chances of effective reduction of BP.

Ertugliflozin in Patients with Stage 3 Chronic Kidney Disease and Type 2 Diabetes Mellitus: The VERTIS RENAL Randomized Study.

IntroductionErtugliflozin is a sodium-glucose cotransporter 2 inhibitor in development for type 2 diabetes mellitus (T2DM). The safety and efficacy of ertugliflozin were evaluated over 52 weeks in patients with chronic kidney disease (CKD).MethodsIn this double-blind randomized study (NCT01986855), patients with glycated hemoglobin (A1C) 7.0–10.5% and stage 3 CKD [estimated glomerular filtration rate (eGFR) ≥ 30 to < 60 mL/min/1.73 m2] who were undergoing treatment with standard diabetes therapy (or therapies) including insulin and/or sulfonylureas were randomized to once-daily ertugliflozin 5 mg, 15 mg, or placebo. Patients on metformin underwent a pre-randomization ≥ 10-week wash-off period. The primary endpoint was change from baseline in A1C at week 26 in the overall cohort. Secondary efficacy endpoints were assessed in the stage 3A CKD cohort (eGFR ≥ 45 to < 60 mL/min/1.73 m2) at weeks 26 and 52. Safety was assessed in the overall cohort.Results468 patients were randomized (baseline mean A1C 8.2%). At week 26, reductions from baseline in A1C were observed across groups in the overall cohort [least squares mean changes (95% confidence interval) – 0.3% (– 0.4, – 0.1), – 0.3% (– 0.4, – 0.1), and – 0.4% (– 0.6, – 0.3) for placebo and for ertugliflozin 5 mg and 15 mg, respectively]. Prohibited use of metformin was identified in ~ 17% of patients and impacted evaluation of the primary endpoint. Greater reductions from baseline in body weight, fasting plasma glucose, and systolic blood pressure were observed with ertugliflozin versus placebo at week 26 (stage 3A CKD cohort). The incidences of urinary tract infections, genital mycotic infections, and hypoglycemia adverse events were not meaningfully different between groups. The incidence of hypovolemia-related adverse events was higher with ertugliflozin relative to placebo.ConclusionAlthough surreptitious metformin use impacted the primary analysis, reductions in blood glucose and body weight were observed with ertugliflozin in patients with T2DM and stage 3 CKD; ertugliflozin had an acceptable safety profile.FundingMerck Sharp & Dohme Corp. a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and Pfizer Inc.Trial RegistrationClinicaltrials.gov identifier NCT01986855.Electronic supplementary materialThe online version of this article (10.1007/s13300-017-0337-5) contains supplementary material, which is available to authorized users.