Chronic Kidney Disease Stages G3-G5 Research Articles

Metabolic Acidosis and Adverse Outcomes and Costs in CKD: An Observational Cohort Study

Metabolic acidosis is a risk factor for progression of chronic kidney disease (CKD), but little is known about its effect on health care costs and resource utilization. We describe the associations between metabolic acidosis, adverse kidney outcomes, and health care costs inpatients with CKD stages G3-G5 and not receiving dialysis. Retrospective cohort study. An integrated claims-clinical data set of US patients with CKD stages G3-G5, with serum bicarbonate values of 12 to<22 mEq/L (metabolic acidosis group) or 22 to 29 mEq/L (normal serum bicarbonate level group). The primary exposure variable was the baseline serum bicarbonate level. The primary clinical outcome was the composite of all-cause mortality, maintenance dialysis, kidney transplant, or a decline in the estimated glomerular filtration rate of≥40% (DD40). The primary cost outcome was all-cause predicted per-patient per-year cost, assessed over a 2-year outcome period. Logistic and generalized linear regression models, adjusted for key covariates such as age, sex, race, kidney function, comorbidities, and pharmacy insurance coverage, were used to assess serum bicarbonate levels as a predictor of DD40 and health care costs, respectively. 51,558 patients qualified. The metabolic acidosis group experienced higher rates of DD40 (48.3% vs. 16.7%, P<0.001) and higher all-cause yearly costs ($65,172 vs. $24,681, P<0.001). Two-year adjusted odds ratio of DD40 per 1-mEq/L increase in serum bicarbonate levels was 0.873 (95% CI, 0.866-0.879); the parameter estimate (±SE) for costs was-0.070±0.0075 (P<0.001). Possible residual confounding. Patients with CKD and metabolic acidosis had higher costs and rates of adverse kidney outcomes compared with patients with normal serum bicarbonate levels. Each 1-mEq/L increase in serum bicarbonate levels was associated with a 13% decrease in 2-year DD40 events and a 7% decrease in per-patient per-year cost.

Metabolic Acidosis is Associated With Acute Kidney Injury in Patients With CKD

IntroductionMetabolic acidosis in patients with chronic kidney disease (CKD) results from a loss of kidney function. It has been associated with CKD progression, all-cause mortality, and other adverse outcomes. We aimed to determine whether metabolic acidosis is associated with a higher risk of acute kidney injury (AKI).MethodsThis was a retrospective cohort study. Using electronic health records and administrative data, we enrolled 2 North American cohorts of patients with CKD Stages G3–G5 as follows: (i) 136,067 patients in the US electronic medical record (EMR) based cohort; and (ii) 34,957 patients in the Manitoba claims-based cohort. The primary exposure was metabolic acidosis (serum bicarbonate between 12 mEq/l and <22 mEq/l). The primary outcome was the development of AKI (defined using ICD-9 and 10 codes at hospital admission or a laboratory-based definition based on Kidney Disease: Improving Global Outcomes guidelines). We applied Cox proportional hazards regression models adjusting for relevant demographic and clinical characteristics.ResultsIn both cohorts, metabolic acidosis was associated with AKI: hazard ratio (HR) 1.57 (95% confidence interval [CI] 1.52–1.61) in the US EMR cohort, and HR 1.65 (95% CI 1.58–1.73) in the Manitoba claims cohort. The association was consistent when serum bicarbonate was treated as a continuous variable, and in multiple subgroups, and sensitivity analyses including those adjusting for albuminuria.ConclusionMetabolic acidosis is associated with a higher risk of AKI in patients with CKD. AKI should be considered as an outcome in studies of treatments for patients with metabolic acidosis.

Prescription patterns of sodium and calcium polystyrene sulfonate in patients with hyperkalemia and chronic kidney disease receiving RAAS inhibitors.

ABSTRACTBackgroundSodium and calcium polystyrene sulfonate (SPS/CPS) cation-exchange resins have had long-standing clinical use for hyperkalemia in patients with chronic kidney disease (CKD). However, uncertainty exists regarding the real-world usage of SPS/CPS for acute and chronic management of hyperkalemia. We evaluated the prescription patterns of SPS/CPS and their impact on renin–angiotensin–aldosterone system inhibitor (RAASi) treatment in patients with CKD Stages G3–G5 after an episode of de novo hyperkalemia.MethodsWe conducted a retrospective cohort study using population-level administrative databases in Manitoba, Canada, which included adults with CKD and a RAASi prescription who had an episode of de novo hyperkalemia (≥5.5 mmol/L) between January 2007 and December 2017.ResultsA total of 10 009 individuals were included in our study cohort. Among the study population, 4% received an SPS/CPS prescription within 30 days of their hyperkalemia episode. Of those, 22% received a 1-day supply of SPS/CPS and 7% received a prescription for more than 30 days. There were 8145 patients using RAASi at baseline who survived 90 days after their first hyperkalemia episode. Of those, 1447 (18%) discontinued their RAAS inhibitor and 339 (5%) received a prescription of SPS/CPS. Also, the proportion of patients who discontinued their RAASi was similar among those who did and did not receive a prescription of SPS/CPS.ConclusionIn patients with CKD receiving RAASi therapy, there is a low frequency of SPS/CPS prescription after an episode of hyperkalemia. RAASi discontinuation or downtitration is the most used pharmacologic approach for the management of hyperkalemia, a strategy that deprives patients of the cardiac and renal protective benefits of RAASi. New options for the management of hyperkalemia in this population are needed.

FC 070USE OF POTENTIALLY NEPHROTOXIC MEDICATIONS IN PERSONS WITH CHRONIC KIDNEY DISEASE: PARALLEL COHORT STUDIES IN SWEDISH AND U.S ROUTINE CARE

Abstract Background and Aims Many adverse drug events are preventable, such as those potentially resulting from the prescription of nephrotoxic drugs to persons with chronic kidney disease (CKD). We here quantify the extent of contemporary nephrotoxic medication use in patients with CKD. Method In two observational cohorts of Swedish (Stockholm CREAtinine Measurements [SCREAM] project, Stockholm, Sweden) and U.S. (Geisinger Health System, Pennsylvania) adults with confirmed CKD stages G3-G5 undergoing routine care during 2016-2018, we explored the prescription (in U.S.) and dispensation (in Sweden) of 115 different ambulatory drugs with proven or purported nephrotoxicity during the 12 months following study inclusion. We evaluated the proportion of participants receiving nephrotoxic drugs, ranked main contributors and identified clinical predictors. Results In the Swedish cohort, there were 57880 patients (54.6% women) with median age of 80.00 (inter-quartile range [IQR]: 73.0-86.0) years and eGFR 48.9 ([IQR]: 39.9-55.0) mL/min/1.73 m2. In the U.S. cohort, there were 16255 patients (59% women) with median age of 76 years and eGFR 44 mL/min/1.73 m2. During observation, 20% (Sweden) and 17% (U.S.) of patients received at least one nephrotoxic drug. The top 3 potentially inappropriate nephrotoxic drugs identified were NSAIDs (9% and 11% of participants in U.S. and Sweden received it), antivirals (2.0% and 2.5%) and immunosuppressants (1.5% and 2.7%). Bisphosphonate use was common in Sweden (3.3% of participants), but not in U.S. (0.5%). Conversely, fenofibrates were common in U.S. (3.6%), but not in Sweden (0.13%). In adjusted analyses, patients with young age (&amp;lt;65 years old), women, or with CKD G3 were at higher risk of receiving nephrotoxic medications in both cohorts (P&amp;gt;0.05 for all). Notably, patients aware of their CKD (identified either by issued diagnosis or recent visit to a nephrologist), were at lower risk of nephrotoxic drug use (OR 0.87, 95% CI 0.82-0.92 in Sweden and 0.89, 95% CI 0.81-1.01 in U.S.). Conclusion In two geographically distinct health systems, one in five patients with CKD received potentially inappropriate nephrotoxic medications, mainly NSAIDs. Strategies to increase CKD awareness and physician’s knowledge of drug nephrotoxicity may reduce inappropriate ambulatory prescriptions and prevent iatrogenic kidney injury.

The Relationship between Advanced Oxidation Protein Products, Vascular Calcifications and Arterial Stiffness in Predialysis Chronic Kidney Disease Patients.

Background and Objectives: Cardiovascular morbidity and mortality are increased in patients with chronic kidney disease (CKD). It is likely that the accumulation of uremic toxins resulting in increased oxidative stress (OS) is a major contributing factor, but no clear link has been identified. The purpose of this research is to establish if advanced oxidation protein product (AOPP) levels in the serum of predialysis patients are a contributing factor to vascular calcification and increased arterial stiffness. Materials and Methods: After obtaining the informed consent, 46 predialysis patients (CKD stages G3–G5) were included in the study. In order to identify vascular calcifications, hand and pelvic radiographs were performed. Valvular calcifications were identified using cardiac ultrasound. AOPP were measured using a commercially available ELISA kit. The relationships between serum AOPP values and biochemical parameters relevant in the evaluation of CKD patients were analyzed. In addition to identifying the differences in AOPP levels between patients with/without vascular or valvular calcifications, the research focused on describing the relationship between OS and arterial stiffness assessed by oscillometric pulse-wave velocity (PWV) measurement. Results: No significant relationship between serum AOPP and vascular or valvular calcifications was highlighted, but significant correlations of AOPP with C-reactive protein (p = 0.025), HDL-cholesterol levels (p = 0.04), HbA1c (p = 0.05) and PWV values (p = 0.02) were identified. Conclusions: The usefulness of (OS) measurement in clinical practice remains debatable; however, the relationship between AOPP and arterial stiffness could be valuable in improving cardiovascular risk assessment of patients with CKD.

Glycemic Control and the Risk of Acute Kidney Injury in Patients With Type 2 Diabetes and Chronic Kidney Disease: Parallel Population-Based Cohort Studies in U.S. and Swedish Routine Care.

Patients with diabetes and chronic kidney disease (CKD) have increased susceptibility to acute kidney injury (AKI), but mechanisms are unclear. We investigated the association of glycemic control with risk of AKI. In two observational cohorts of U.S. (Geisinger Health System, Danville, PA) and Swedish (Stockholm CREAtinine Measurements [SCREAM] project, Stockholm, Sweden) adults with type 2 diabetes and confirmed CKD stages G3-G5 undergoing routine care, we evaluated associations between baseline and time-varying hemoglobin A1c (HbA1c) with the incident AKI (defined as increase in creatinine ≥0.3 mg/dL over 48 h or 1.5 times creatinine over 7 days). In the U.S. cohort, there were 22,877 patients (55% women) with a median age of 72 years and estimated glomerular filtration rate (eGFR) 52 mL/min/1.73 m2. In the Swedish cohort, there were 12,157 patients (50% women) with a median age of 77 years and eGFR 51 mL/min/1.73 m2. During 3.1 and 2.3 years of follow-up, 7,060 and 2,619 AKI events were recorded in the U.S. and Swedish cohorts, respectively. The adjusted association between baseline HbA1c and AKI was similar in both cohorts. Compared with baseline HbA1c 6-6.9% (42-52 mmol/mol), the hazard ratio for AKI in patients with HbA1c >9% (75 mmol/mol) was 1.29 (95% CI 1.18-1.41) in Geisinger and 1.33 (95% CI 1.13-1.57) in the Swedish cohort. Results were consistent in stratified analysis, when using death as competing risk, and when using time-varying HbA1c. Higher HbA1c was associated with AKI in adults with type 2 diabetes and CKD, suggesting that improving glycemic control may reduce the risk of AKI.

An independent validation of the kidney failure risk equation in an Asian population

Predicting the risk of end-stage renal disease (ESRD) progression facilitates appropriate nephrology care of patients with chronic kidney disease (CKD). Previously, the kidney failure risk equations (KFREs) were developed and validated in several cohorts. The purpose of this study is to validate the KFREs in a Korean population and to recalibrate the equations. A total of 38,905 adult patients, including 13,244 patients with CKD stages G3–G5, who were referred to nephrology were recruited. Using the original KFREs (4-, 6- and 8-variable equations) and recalibration equations, we predicted the risk of 2- and 5-year ESRD progression. All analyses were conducted in CKD stages G3-G5 patients as well as the total population. In CKD stages G3–G5 patients, All the original 4-, 6- and 8-variable equations showed excellent areas under the receiver operating characteristic curve of 0.87 and 0.83 for the 2- and 5-year risk of ESRD, respectively. The results of net reclassification improvement, integrated discrimination index and Brier score showed that recalibration improved the prediction models in some cases. The original KFREs showed high discrimination in both CKD stages G3–G5 patients and the total population referred to nephrology in this large Korean cohort. KFREs can be implemented in Korean health systems and can guide nephrology referrals and other CKD-related treatment decisions.

MO050GLYCEMIC CONTROL AND THE RISK OF AKI IN PATIENTS WITH DIABETES AND CKD: PARALLEL POPULATION-BASED COHORT STUDIES IN U.S. AND SWEDEN ROUTINE CARE

Abstract Background and Aims Patients with diabetes and chronic kidney disease (CKD) have increased susceptibility to acute kidney injury (AKI), but the underlying mechanisms are not well known. We here explore the association between glycemic control and risk of AKI. Method We created two parallel observational cohort studies of Swedish (SCREAM project, Stockholm, 2006-2011) and U.S. (Geisinger Heath system, Pennsylvania, 1996-2018) adult patients with diabetes mellitus and confirmed CKD stages G3-G5. Glycemic control was evaluated through repeated HbA1c measurements, which were categorized into 5 levels of glycemic control intensity, with HbA1c 6-6.9% as referent category, and continuously using cubic splines. We evaluated the association between baseline and time-varying HbA1c levels with AKI (defined as increase in creatinine &amp;gt;=0.3 mg/d over 48 hours or 1.5x creatinine over 7 days) using Cox proportional hazards regression and, in sensitivity analyses, Fine and Gray competing risk models accounting for death. Results In the Swedish cohort, there were 13932 patients with median age 76 years, 51% women, median eGFR 50.8 (Interquartile Range (IQR) 41.4-57.1) ml/min/1.73. In the U.S. cohort, there were 26520 patients with median age 71 years, 55% women and 52.1 (IQR 43.4-57.5) ml/min/1.73 m2. During a median of 2.3 and 3.1 years of follow up, 3172 and 8671 AKI events were recorded in the Swedish and US cohorts, respectively. The adjusted association between baseline HbA1c and AKI was similar in both cohorts, with the lowest risk between 6-6.9% and higher risk at higher levels of HbA1c. Compared to baseline HbA1c 6-6.9%, baseline HbA1c&amp;gt;9% associated with a 1.28 fold (95% CI 1.11-1.47) higher risk of AKI in the Swedish cohort, and a 1.14 (95% CI 1.04-1.25) higher risk in the U.S. cohort. Conversely, baseline HbA1c&amp;lt;6% did not associate with AKI. When using time-varying HbA1c, AKI risk was higher for HbA1c&amp;gt;9% (HR 1.18, 95% CI 1.03-1.37 in Swedish cohort and 1.27, 1.17-1.37 in U.S. cohort); AKI risk was also higher for HbA1c&amp;lt;6% in the U.S. cohort (1.12, 1.04-1.19), but not in the Swedish cohort (1.06, 0.97-1.16)). Conclusion Higher A1c was associated with AKI in adults with diabetes and CKD, suggesting that better glycemic control may also reduce risk of AKI.

P123: Emergency department utilization by patients with advanced chronic kidney disease and dialysis: A population based study

Introduction: Chronic Kidney Disease (CKD) is a potent risk factor for kidney failure, cardiovascular events and all cause hospitalizations. In addition to higher outpatient resource use, patients with CKD may present more frequently to the emergency department (ED) and may be more likely to be admitted for hospitalization. In Manitoba, we previously demonstrated an 8-fold increase in the frequency of ED presentations by patients on dialysis as compared to a non-dialysis population. Comparable data on ED visits remain sparse for patients with CKD G3-G5, not on dialysis. Here, we aim to describe the frequency of ED visits and highlight differences in reasons for visit in patients with CKD stages G3-G5 and those on dialysis when compared to a non-CKD population. Methods: We performed a retrospective cohort study using administrative health data from the Winnipeg Regional Health Authority, Canada. We included all adults (≥ 18 years) with CKD stages G3-G5 and patients undergoing dialysis between January 1st, 2010 and December 31, 2014. Secular trends in the in the rates of ED visits were calculated for those with CKD, those on dialysis and in the non-CKD population. Results: Over the study period, patients undergoing dialysis had the highest incidence of ED visits, followed by patients with CKD and those with normal kidney function (150 vs 106 vs 34 per 100 persons per year respectively). These rates were stable over the period studied. Among the non-CKD population, the most common reasons for an ED visit were musculoskeletal complaints (25.6%), followed by gastrointestinal (11.04%) and cardiovascular complaints (10.26%). In the CKD and dialysis cohort, ED visits were more commonly secondary to cardiovascular complaints (21.54% and 18.99% respectively), followed by respiratory and gastrointestinal complaints. . Admission to hospital was higher in CKD and dialysis populations than in the non-CKD population (29.56%, 26.07% vs 10.61%, respectively). Conclusion: Patients with CKD present frequently to the ED, and are often admitted after presentation. Cardiovascular and respiratory complaints are more common in the CKD population when compared to the general population.

Predicting renal disease progression in a large contemporary cohort with type 1 diabetes mellitus

Aims/hypothesisThe aim of this study was to provide data from a contemporary population-representative cohort on rates and predictors of renal decline in type 1 diabetes.MethodsWe used data from a cohort of 5777 people with type 1 diabetes aged 16 and older, diagnosed before the age of 50, and representative of the adult population with type 1 diabetes in Scotland (Scottish Diabetes Research Network Type 1 Bioresource; SDRNT1BIO). We measured serum creatinine and urinary albumin/creatinine ratio (ACR) at recruitment and linked the data to the national electronic healthcare records.ResultsMedian age was 44.1 years and diabetes duration 20.9 years. The prevalence of CKD stages G1, G2, G3 and G4 and end-stage renal disease (ESRD) was 64.0%, 29.3%, 5.4%, 0.6%, 0.7%, respectively. Micro/macroalbuminuria prevalence was 8.6% and 3.0%, respectively. The incidence rate of ESRD was 2.5 (95% CI 1.9, 3.2) per 1000 person-years. The majority (59%) of those with chronic kidney disease stages G3–G5 did not have albuminuria on the day of recruitment or previously. Over 11.6 years of observation, the median annual decline in eGFR was modest at −1.3 ml min−1 [1.73 m]−2 year−1 (interquartile range [IQR]: −2.2, −0.4). However, 14% experienced a more significant loss of at least 3 ml min−1 [1.73 m]−2. These decliners had more cardiovascular disease (OR 1.9, p = 5 × 10−5) and retinopathy (OR 1.3 p = 0.02). Adding HbA1c, prior cardiovascular disease, recent mean eGFR and prior trajectory of eGFR to a model with age, sex, diabetes duration, current eGFR and ACR maximised the prediction of final eGFR (r2 increment from 0.698 to 0.745, p < 10−16). Attempting to model nonlinearity in eGFR decline or to detect latent classes of decliners did not improve prediction.ConclusionsThese data show much lower levels of kidney disease than historical estimates. However, early identification of those destined to experience significant decline in eGFR remains challenging.

Women and renal replacement therapy in Europe: lower incidence, equal access to transplantation, longer survival than men.

In 2018, World Kidney Day (WKD) and International Women’s Day coincide. The WKD editorial focuses on women’s kidney health. The European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report 2015 summary provides an excellent snapshot of renal replacement therapy (RRT) epidemiology and women in Europe. The WKD editorial reports a lower incidence of RRT in women in major registries and potential limitations to women’s access to transplantation. What is the situation in Europe? In Europe, the incidence of RRT is also lower in women: 38% of incident RRT patients are women. Does it represent milder chronic kidney disease (CKD) in women or barriers to RRT access? The question arises from the higher prevalence of CKD Stages G3–G5 in women than in men. However, in some European countries, such as Spain, non-dialysis CKD Stages G4–G5 is less frequent in women than in men, recapitulating the difference in RRT incidence. In the ERA-EDTA Registry, the incidence of transplantation as a first modality on Day 1 was slightly higher for women and survival on RRT was similar for women and men in the first 3 months, but an intergender gap favouring women increased as RRT vintage increased. However, women on RRT are worse off regarding survival when compared with women in the general population than men on RRT compared with men in the general population. In conclusion, the ERA-EDTA Registry Annual Report 2015 and European epidemiology data suggest a lower incidence of end-stage kidney disease in women, no gender differences in access to transplantation and better RRT survival in women.