A Simple Tool to Predict End‐Stage Renal Disease within 1 Year in Elderly Adults with Advanced Chronic Kidney Disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98206/1/jgs12223.pd

Special Feature CKD as a Model for Improving Chronic Disease Care through Electronic Health Records

Abstract Electronic health records have the potential to improve the care of patients with chronic medical conditions. CKD provides a unique opportunity to show this potential: the disease is common in the United States, there is significant room to improve CKD detection and management, CKD and its related conditions are defined primarily by objective laboratory data, CKD care requires collaboration by a diverse team of health care professionals, and improved access to CKD-related data would enable identification of a group of patients at high risk for multiple adverse outcomes. However, to realize the potential for improvement in CKD-related care, electronic health records will need to provide optimal functionality for providers and patients and interoperability across multiple health care settings. The goal of the National Kidney Disease Education Program Health Information Technology Working Group is to enable and support the widespread interoperability of data related to kidney health among health care software applications to optimize CKD detection and management. Over the course of the last 2 years, group members met to identify general strategies for using electronic health records to improve care for patients with CKD. This paper discusses these strategies and provides general goals for appropriate incorporation of CKD-related data into electronic health records and corresponding design features that may facilitate (1) optimal care of individual patients with CKD through improved access to clinical information and decision support, (2) clinical quality improvement through enhanced population management capabilities, (3) CKD surveillance to improve public health through wider availability of population-level CKD data, and (4) research to improve CKD management practices through efficiencies in study recruitment and data collection. Although these strategies may be most effectively applied in the setting of CKD, because it is primarily defined by laboratory abnormalities and therefore, an ideal computable electronic health record phenotype, they may also apply to other chronic diseases

Assay platform for clinically relevant metallo-beta-lactamases

Metallo-β-lactamases (MBLs) are a growing threat to the use of almost all clinically used β-lactam antibiotics. The identification of broad-spectrum MBL inhibitors is hampered by the lack of a suitable screening platform, consisting of appropriate substrates and a set of clinically relevant MBLs. We report procedures for the preparation of a set of clinically relevant metallo-β-lactamases (i.e., NDM-1 (New Delhi MBL), IMP-1 (Imipenemase), SPM-1 (São Paulo MBL), and VIM-2 (Verona integron-encoded MBL)) and the identification of suitable fluorogenic substrates (umbelliferone-derived cephalosporins). The fluorogenic substrates were compared to chromogenic substrates (CENTA, nitrocefin, and imipenem), showing improved sensitivity and kinetic parameters. The efficiency of the fluorogenic substrates was exemplified by inhibitor screening, identifying 4-chloroisoquinolinols as potential pan MBL inhibitors

Advances in understanding the renin-angiotensin-aldosterone system (RAAS) in blood pressure control and recent pivotal trials of RAAS blockade in heart failure and diabetic nephropathy [version 1; referees: 3 approved]

The renin-angiotensin-aldosterone system (RAAS) plays a fundamental role in the physiology of blood pressure control and the pathophysiology of hypertension (HTN) with effects on vascular tone, sodium retention, oxidative stress, fibrosis, sympathetic tone, and inflammation. Fortunately, RAAS blocking agents have been available to treat HTN since the 1970s and newer medications are being developed. In this review, we will (1) examine new anti-hypertensive medications affecting the RAAS, (2) evaluate recent studies that help provide a better understanding of which patients may be more likely to benefit from RAAS blockade, and (3) review three recent pivotal randomized trials that involve newer RAAS blocking agents and inform clinical practice

Pharmacist-based antihypertensive medication review and assignment of morning versus evening dosing of once-daily antihypertensive medications: A pilot study to assess feasibility and efficacy in chronic kidney disease patients

Evening dosing of antihypertensive medications lowers nighttime blood pressure, and in one large randomized trial, it reduced the risk for cardiovascular outcomes. However, the feasibility of nighttime dosing in routine clinical practice is unknown. The purpose of this pilot study was to evaluate the effect of a brief pharmacist intervention to assign patients to take antihypertensive medications at specific times of the day. In this pilot, randomized controlled trial, 79 patients with moderate to severe chronic kidney disease (CKD) taking one or more antihypertensive medications once daily were randomized to take one once-daily antihypertensive either in the morning or in the evening. A total of 79 patients were randomized (39 to morning dosing, 40 to evening dosing). Average (SD) age was 56.5 (14) years, 68% were male, and average (SD) estimated glomerular filtration rate (eGFR) was 36.6 (8.9) mL/min/1.73m2. Adherence, defined as taking the once-daily medication at the time indicated six or seven times in the last 7 days and not taking it at any other time during the day, was 91% in the morning arm and 95% in the evening arm (p = 0.57). This pilot demonstrates the feasibility and efficacy of a pharmacist–physician collaborative to assign once-daily antihypertensive medications to either morning or evening dosing

Impact of a chronic kidney disease registry and provider education on guideline adherence – a cluster randomized controlled trial

Abstract Background Low adherence to chronic kidney disease (CKD) guidelines may be due to unrecognized CKD and lack of guideline awareness on the part of providers. The goal of this study was to evaluate the impact of provider education and access to a CKD registry on guideline adherence. Methods We conducted a cluster randomized controlled trial at the Louis Stokes Cleveland VAMC. One of two primary care clinics was randomized to intervention. Providers from both clinics received a lecture on CKD guidelines at study initiation. Providers in the intervention clinic were given access to and shown how to use a CKD registry, which identifies patients with CKD and is automatically updated daily. Eligible patients had at least one primary care visit in the last year, had CKD based on eGFR, and had not received renal replacement therapy. The primary outcome was parathyroid hormone (PTH) adherence, defined by at least one PTH measurement during the 12 month study. Secondary outcomes were measurement of phosphorus, hemoglobin, proteinuria, achievement of goal blood pressure, and treatment with a diuretic or renin-angiotensin system blocker. Results There were 418 and 363 eligible patients seen during the study in the control and intervention clinics, respectively. Compared to pre-intervention, measurement of PTH increased in both clinics (control clinic: 16% to 23%; intervention clinic: 13% to 28%). Patients in the intervention clinic were more likely to have a PTH measured during the study (adjusted odds ratio = 1.53; 95% CI (1.01, 2.30); P = 0.04). However, the intervention was not associated with a consistent improvement in secondary outcomes. Only 5 of the 37 providers in the intervention clinic accessed the registry. Conclusions An intervention that included education on CKD guidelines and access to a CKD patient registry marginally improved guideline adherence over education alone. Adherence to the primary process measure improved in both clinics, but no improvement was seen in intermediate clinical outcomes. Improving the care of patients with CKD will likely require a multifaceted approach including system redesign. ClinicalTrials.Gov registration number NCT00921687</p

TNFR2 interposes the proliferative and NF-κB-mediated inflammatory response by podocytes to TNF-α

The development of proliferative podocytopathies has been linked to ligation of TNFR2 expressed on the renal parenchyma; however, the TNFR2 positive cells within the kidney responsible for podocyte injury are unknown. We detected de novo expression of TNFR2 on podocytes prior to hyperplastic injury in crescentic glomerulonephritis of mice with nephrotoxic nephritis, and in collapsing glomerulopathy of Tg26 HIV/nl mice, kd/kd mice, and humans. We further found that serum levels of soluble TNF-α and TNFR2 correlated significantly with renal injury in Tg26 HIV/nl mice. Thus, we asked whether ligand binding of TNFR2 on podocytes ex vivo precipitates the characteristic proliferative and pro-inflammatory diseased podocyte phenotypes. Soluble TNF-α activated NF-κB and dose-dependently induced podocyte proliferation, marked by expression of the podocyte G 1 cyclin and NF-κB target gene, cyclin D1. Microarray gene and chemokine protein expression profiling showed a marked pro-inflammatory NF-κB signature, and activated podocytes secreting CCL2 and CCL5 induced macrophage migration in transwell assays. Neutralization of TNFR2 on podocytes with blocking antibodies abrogated NF-κB activation and the induction of cyclin D1 by TNF-α, and identified TNFR2 as the primary receptor that induced IκBα degradation, the initiating event in NF-κB activation. These results suggest that TNFR2 expressed on podocytes and its canonical NF-κB signaling may directly interpose the compound pathogenic responses by podocytes to TNF-α, absent other TNFR2 positive renal cell-types in proliferative podocytopathies

Kidney disease among patients with sickle cell disease, hemoglobin SS and SC

Background and objectives Sickle cell disease (SCD) is an inherited anemia that afflicts millions worldwide. Kidney disease is a major contributor to its morbidity and mortality. We examined contemporary and historical SCD populations to understand how renal disease behaved in hemoglobin SS (HbSS) compared with HbSC.Design, setting, participants, & measurements Kidney function was examined in the multicentered Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) Trial (HbSS=463; HbSC=127; years 2007–2009) and historical comparator populations from the Cooperative Study of Sickle Cell Disease (CSSCD; HbSS=708) and the Multicenter Study of Hydroxyurea in Sickle Cell Disease (MSH; HbSS=299).Results In adults with SCD, eGFR was lower among older individuals: −1.78 ml/min per 1.73 m2 per year of age (95% confidence interval [95% CI], −2.06 to −1.50; Walk-PHaSST Trial), −1.75 ml/min per 1.73 m2 per year of age (95% CI, −2.05 to −1.44; MSH), and −1.69 ml/min per 1.73 m2 per year of age (95% CI, −2.00 to −1.38; CSSCD) in HbSS compared with −1.09 ml/min per 1.73 m2 per year of age (95% CI, −1.39 to −0.75) in HbSC (Walk-PHaSST Trial). Macroalbuminuria was seen in 20% of participants with SCD (HbSS or HbSC;P=0.45; Walk-PHaSST Trial), but microalbuminuria was more prevalent in HbSS (44% versus 23% in HbSC; P\u3c0.002). In the Walk-PHaSST Trial, albuminuria was associated with hemolysis (higher lactate dehydrogenase, P\u3c0.001; higher absolute reticulocyte count, P\u3c0.02; and lower Hb, P=0.07) and elevated systolic BP (P\u3c0.001) in HbSS. One half of all participants with HbSS (20 of 39) versus one fifth without (41 of 228) elevated tricuspid regurgitant jet velocity (≥3 m/s; adverse prognostic indicator in SCD) had macroalbuminuria (P\u3c0.001). In the CSSCD, overt proteinuria, detected (less sensitively) by urine dipstick, associated with higher 3-year mortality (odds ratio, 2.48; 95% CI, 1.07 to 5.77). Serum bicarbonate was lower in HbSS (23.8 versus 24.8 mEq/dl in HbSC; P\u3c0.05) and associated with reticulocytopenic anemia and decreased renal function. Conclusions In SCD, albuminuria or proteinuria was highly prevalent, in HbSS more than in HbSC. Proteinuria associated with mortality in HbSS. Older individuals had a lower than expected eGFR, and this was more prominent in HbSS. Current management does not routinely address renal complications in SCD, which could plausibly reduce morbidity and mortality