High-impact and transformative science (HITS) metrics: Definition, exemplification, and comparison.

Countries, research institutions, and scholars are interested in identifying and promoting high-impact and transformative scientific research. This paper presents a novel set of text- and citation-based metrics that can be used to identify high-impact and transformative works. The 11 metrics can be grouped into seven types: Radical-Generative, Radical-Destructive, Risky, Multidisciplinary, Wide Impact, Growing Impact, and Impact (overall). The metrics are exemplified, validated, and compared using a set of 10,778,696 MEDLINE articles matched to the Science Citation Index ExpandedTM. Articles are grouped into six 5-year periods (spanning 1983-2012) using publication year and into 6,159 fields constructed using comparable MeSH terms, with which each article is tagged. The analysis is conducted at the level of a field-period pair, of which 15,051 have articles and are used in this study. A factor analysis shows that transformativeness and impact are positively related (ρ = .402), but represent distinct phenomena. Looking at the subcomponents of transformativeness, there is no evidence that transformative work is adopted slowly or that the generation of important new concepts coincides with the obsolescence of existing concepts. We also find that the generation of important new concepts and highly cited work is more risky. Finally, supporting the validity of our metrics, we show that work that draws on a wider range of research fields is used more widely.

Philanthro-metrics: Mining multi-million-dollar gifts.

The Million Dollar List (MDL, online at http://www.milliondollarlist.org) is a compilation of publicly announced charitable donations of $1 million or more from across the United States since 2000; as of December 2016, the database contains close to 80,000 gifts made by U.S. individuals, corporations, foundations, and other grant-making nonprofit organizations. This paper discusses the unique value of the Million Dollar List and provides unique insights to key questions such as: How does distance affect giving? How do networks impact million-dollar-plus gifts? Understanding the geospatial and temporal dimensions of philanthropy can assist researchers and policymakers to better understand the role of private funding in innovation and discovery. Moreover, the results from the paper emphasize the importance of philanthropy for fueling research and development in science, the arts, environment, and health. The paper also includes the limitations of the presented analyses and promising future work.

Global multi-level analysis of the 'scientific food web'.

We introduce a network-based index analyzing excess scientific production and consumption to perform a comprehensive global analysis of scholarly knowledge production and diffusion on the level of continents, countries, and cities. Compared to measures of scientific production and consumption such as number of publications or citation rates, our network-based citation analysis offers a more differentiated picture of the 'ecosystem of science'. Quantifying knowledge flows between 2000 and 2009, we identify global sources and sinks of knowledge production. Our knowledge flow index reveals, where ideas are born and consumed, thereby defining a global 'scientific food web'. While Asia is quickly catching up in terms of publications and citation rates, we find that its dependence on knowledge consumption has further increased.

Design and update of a classification system: the UCSD map of science.

Global maps of science can be used as a reference system to chart career trajectories, the location of emerging research frontiers, or the expertise profiles of institutes or nations. This paper details data preparation, analysis, and layout performed when designing and subsequently updating the UCSD map of science and classification system. The original classification and map use 7.2 million papers and their references from Elsevier's Scopus (about 15,000 source titles, 2001-2005) and Thomson Reuters' Web of Science (WoS) Science, Social Science, Arts & Humanities Citation Indexes (about 9,000 source titles, 2001-2004)-about 16,000 unique source titles. The updated map and classification adds six years (2005-2010) of WoS data and three years (2006-2008) from Scopus to the existing category structure-increasing the number of source titles to about 25,000. To our knowledge, this is the first time that a widely used map of science was updated. A comparison of the original 5-year and the new 10-year maps and classification system show (i) an increase in the total number of journals that can be mapped by 9,409 journals (social sciences had a 80% increase, humanities a 119% increase, medical (32%) and natural science (74%)), (ii) a simplification of the map by assigning all but five highly interdisciplinary journals to exactly one discipline, (iii) a more even distribution of journals over the 554 subdisciplines and 13 disciplines when calculating the coefficient of variation, and (iv) a better reflection of journal clusters when compared with paper-level citation data. When evaluating the map with a listing of desirable features for maps of science, the updated map is shown to have higher mapping accuracy, easier understandability as fewer journals are multiply classified, and higher usability for the generation of data overlays, among others.

Long-term retinal, renal and cardiovascular outcomes in diabetic chronic kidney disease without proteinuria.

BACKGROUND: Patients with diabetes mellitus (DM) with chronic kidney disease (CKD) often have no proteinuria. METHODS: To compare the characteristics that differ between DM + CKD patients with and without proteinuria, we conducted a cross-sectional study followed by surveillance over a decade for 'hard' cardiovascular, renal and retinal outcomes. Groups were stratified by presence (n = 129) and absence (n = 284) of DM. Each stratum had three groups: no CKD, CKD without proteinuria and CKD with proteinuria. RESULTS: Compared to DM + CKD + proteinuria patients, those with DM + CKD but without proteinuria had similar clinical characteristics including estimated glomerular filtration rate. However, they had lower 24-h ambulatory systolic and diastolic blood pressure. Crude all-cause mortality rates per 1000 patient-years in the nondiabetic group with no CKD, CKD with no proteinuria and CKD with overt proteinuria were 29.3, 68.5 and 111.1, respectively. Respective rates in the diabetic group were 50.1, 105.7 and 136.8. Diabetes increased the risk of coronary (P = 0.01) and end-stage renal disease (ESRD) events (P = 0.05) even after multivariate adjustments. Proteinuria aggravated the risk of cardiovascular events, ESRD, death and time to first of these events similarly among diabetics with CKD compared to nondiabetics with CKD. Diabetic patients with CKD but no overt proteinuria were much more likely than nondiabetics to progress to overt proteinuria [adjusted hazard ratio 5.28 (95% confidence interval 1.64-17.02), P < 0.01). CKD was a risk factor for prevalent retinopathy and proteinuria was a risk factor for incident diabetic retinopathy. CONCLUSIONS: To protect sight, those with proteinuria and DM need regular retinal examinations. Since diabetic CKD patients without proteinuria are more likely to develop overt proteinuria, close follow-up and risk factor management among these patients appear to be more important than among nondiabetic patients with CKD and no proteinuria.

Toward a definition of masked hypertension and white-coat hypertension among hemodialysis patients.

BACKGROUND AND OBJECTIVES: Among people with essential hypertension, ambulatory BP measurement is superior to BP obtained in the clinic in predicting cardiovascular outcomes. In part, this is because it can detect white-coat hypertension and masked hypertension. Whether the same is true for hemodialysis patients is not known. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using a threshold of 140/80 mmHg for median midweek dialysis-unit BP and 135/85 mmHg for 44-hour ambulatory BP, we defined four categories of BP: sustained normotension (SN), white-coat hypertension (WCH), masked hypertension (MHTN), and sustained hypertension (SHTN). RESULTS: Among 355 long-term hemodialysis patients, the prevalence of SN was 35%, WCH 15%, MHTN 15%, and SHTN 35%. Over a mean follow-up of 29.6 (SD 21.7) months, 102 patients died (29%), yielding a crude mortality rate of 121/1000 patient-years. Unadjusted and multivariate-adjusted analyses showed increasing all-cause mortality with increasing severity of hypertension (unadjusted hazard ratios from SN, WCH, MHTN, SHTN: 1, 1.12, 1.70, 1.80, respectively [P for trend < 0.01]; adjusted hazard ratios: 1, 1.30, 1.36, 1.87, respectively [P for trend 0.02]). When a predialysis BP threshold of 140/90 mmHg was used to classify patients into BP categories, the prevalence of SN was 24%, WCH 26%, MHTN 4%, and SHTN 47%. Hazard ratios for mortality were similar when compared with median midweek dialysis-unit BP. CONCLUSIONS: As in the essential hypertension population, MHTN and WCH have prognostic significance. The prognostic value of BP obtained in the dialysis unit can be refined with ambulatory BP monitoring.

Short-term vitamin D receptor activation increases serum creatinine due to increased production with no effect on the glomerular filtration rate.

Vitamin D receptor activation has been associated with increased serum creatinine and reduced estimated glomerular filtration rates, raising concerns that its use may be detrimental to kidney function. Here we studied the effect of vitamin D receptor activation on serum creatinine, creatinine generation, and its clearance. We measured baseline serum creatinine and 24-h urine creatinine in 16 patients with chronic kidney disease. The measurements were repeated every day for 7 days, during which time the patients received 2 µg paricalcitol, an orally active vitamin D receptor activator, every morning. At 4 days after stopping the vitamin analog, measurements were continued for 3 days. Geometric mean parathyroid hormone levels decreased from 77 pg/ml at baseline to 43 pg/ml at the end of treatment and significantly rebounded to 87 pg/ml following paricalcitol withdrawal, thereby supporting the biological efficacy of the analog dose used. With this therapy, the serum creatinine significantly increased at a rate of 0.010 mg/dl/day and urine creatinine at a rate of 17.6 mg/day. Creatinine and iothalamate clearances did not change, whereas urine albumin decreased insignificantly. Thus, short-term vitamin D receptor activation increases creatinine generation and serum creatinine, but it does not influence the glomerular filtration rate.

Relationship between glycosylated hemoglobin and blood glucose during progression of chronic kidney disease.

BACKGROUND: The value of measurement of glycosylated hemoglobin (HgbA(1C)) in determining the degree of glycemic control in patients with chronic kidney disease (CKD) is unclear. METHODS: A single-center, prospective cohort study was conducted in 128 veterans with diabetes mellitus and CKD. HgbA(1C) was measured as clinically indicated and its relationship with random blood glucose (RBG) measurement evaluated prospectively over up to 10 years in three groups (end-stage renal disease (ESRD), CKD and controls who had diabetes but no CKD). RESULTS: Between 1995 and 2011, in the control group, glycemic control as assessed by HgbA(1C) was stable but improved when assessed by RBG. However, both the CKD and ESRD groups experienced declines in RBG and HgbA(1C). Declining HgbA(1C) and RBG were noted prior to onset of dialysis. A fall in HgbA(1C) remained after adjustment for RBG. A strong inverse relationship was seen between CKD stage and HgbA(1C) even after adjusting for RBG such that the relationship between RBG levels and HgbA(1C) was modified by CKD. CONCLUSIONS: In diabetic patients with late-stage CKD, glycemic control shows an improvement. However, HgbA(1C) <7% may overestimate the degree of glycemic control. Therefore, reliance on HgbA(1C) without home blood glucose monitoring may result in poor diabetes control.

Patterns and prognostic value of total and differential leukocyte count in chronic kidney disease.

BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the levels and patterns of total and differential leukocyte counts and their prognostic importance in a cohort of people with and without chronic kidney disease (CKD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 153 veterans without CKD and 267 with, blood leukocyte count was measured at baseline and then repeatedly over a decade. The patterns of change in leukocyte count between the two groups were compared. In the CKD cohort, the spikes in leukocyte counts were compared to the combined endpoint of ESRD and death. RESULTS: Patients with CKD had more granulocytes and eosinophils and fewer lymphocytes. Over time, granulocytes increased and lymphocytes decreased in those with and without CKD. In addition, in those with CKD, over time eosinophils fell and monocytes increased. Compared with their non-CKD counterparts, patients with CKD had between 1.5- and 3.0-fold more spikes in leukocyte counts. Independent risk factors for the combined endpoint were associated with spikes in the leukocyte counts of absolute and percent eosinophil count, percent granulocyte, and percent monocyte counts. In a multivariate adjusted joint model, both granulocyte and monocyte spikes were independently associated with ESRD and death (hazard ratio 1.67 and 1.52 respectively, P < 0.05). CONCLUSIONS: Compared with those without CKD, patients with CKD have more eosinophils and granulocytes and fewer lymphocytes. Greater variation in leukocytes is seen. Spikes in granulocyte and monocyte percentages among patients with CKD are of independent prognostic importance.

Sleep and activity in chronic kidney disease: a longitudinal study.

BACKGROUND AND OBJECTIVES: Commonly sleep is disrupted and physical activity is restricted among patients with CKD and those on long-term dialysis. However, few studies have assessed patients longitudinally. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We compared the prevalence of sleep disturbances measured both subjectively using a questionnaire and objectively using actimetry among patients with CKD (n = 145), those on hemodialysis (n = 116), and people without kidney disease (n = 19). Activity level during the day was measured using actimetry, and patients were then followed for up to 2 years. RESULTS: Compared with people without kidney disease, patients with CKD not on dialysis had disruption of sleep that was independent of several risk factors. However, disrupted sleep was correlated with neither estimated GFR in cross-sectional nor longitudinal assessment. Those on hemodialysis had sleep disruption that was of much greater severity than that found among those with CKD not on dialysis. Furthermore, missing or shortening the prescribed duration of dialysis was associated with greater severity of sleep disturbance in cross-sectional but not in longitudinal assessment. Day-time activity declined both in duration and intensity from controls to CKD to hemodialysis. CONCLUSIONS: The loss of kidney function is related to both reduced duration and intensity of day time physical activity. Although patients with CKD have disrupted sleep, this is independent of estimated GFR. However, compared with those with CKD, dialysis patients have more severely disrupted sleep; this is related to missing dialysis. Thus, shortening patients' dialysis may reduce their sleep.

Chronic kidney disease as a coronary disease equivalent--a comparison with diabetes over a decade.

BACKGROUND AND OBJECTIVES: Whether chronic kidney disease (CKD) should also be considered a coronary disease equivalent like diabetes is not clear. DESIGN, SETTING, PARTICIPANTS, & METHODS: Veterans with and without diabetes and with and without CKD were prospectively recruited. A competing Cox regression model was used to describe the risk of myocardial infarction (MI) in the two groups (CKD and diabetes) over a decade of follow-up. RESULTS: The incidence rate of MI in those without CKD was 0.047/yr and in those with CKD was 0.206/yr. Multivariate adjustment revealed the incident rate ratio for MI in CKD as 3.5 and for diabetes mellitus as 2.5. The cumulative incidence for MI was influenced by CKD and diabetes. CKD was associated with a subhazard ratio for MI of 3.74; in contrast, diabetes was associated with a subhazard ratio for MI of 2.6. For the outcome of all-cause mortality, after multivariate adjustment, CKD was associated with a hazard ratio (HR) of 1.86, which was similar to the HR of 2.27 for prevalent coronary artery disease. The HR for diabetes was NS at 1.35. CONCLUSIONS: CKD is associated with a risk of death similar to that of established coronary artery disease and higher than that of diabetes mellitus. CKD is associated with a risk of MI that is at least as much as that from diabetes mellitus. Among veterans, CKD appears to be a coronary disease equivalent.

Probing dry-weight improves left ventricular mass index.

BACKGROUND: Although probing dry-weight improves blood pressure control, its effect on echocardiographic left ventricular mass index (LVMI) is unknown. METHODS: Shortly following dialysis, 292 echocardiograms in 150 patients participating in the DRIP trial were obtained at baseline and longitudinally every 4 weeks on 2 occasions. RESULTS: At baseline, LVMI was 136.3 g/m(2) in the control group and 138.7 g/m(2) in the ultrafiltration group (p > 0.2 for difference). The change from baseline in LVMI in the control group was +3.5 g/m(2) at 4 weeks and +0.3 g/m(2) at 8 weeks (p > 0.2 for both changes). The change from baseline in LVMI in the ultrafiltration group was -7.4 g/m(2) at 4 weeks (p = 0.005) and -6.3 g/m(2) at 8 weeks (p = 0.045). With ultrafiltration, the change in LVMI diameter was -10.9 g/m(2) more compared to the control group at 4 weeks (p = 0.012) and -6.6 g/m(2) more compared to the control group at 8 weeks (p = 0.21). The reduction in interdialytic ambulatory blood pressure was also greater in response to probing dry-weight in those in the top half of LVMI at baseline (p = 0.02 for interaction effect at week 8). CONCLUSION: LVMI, an important determinant of prognosis among long-term dialysis patients, is responsive to probing dry-weight.

Inferior vena cava diameter and left atrial diameter measure volume but not dry weight.

BACKGROUND AND OBJECTIVES: Hypervolemia is an important and modifiable cause of hypertension. Hypertension improves with probing dry weight, but its effect on echocardiographic measures of volume is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Shortly after dialysis, echocardiograms were obtained at baseline and longitudinally every 4 weeks on two occasions. Among 100 patients in the additional ultrafiltration group, 198 echocardiograms were performed; among 50 patients in the control group, 104 echocardiograms were performed. RESULTS: Baseline inferior vena cava (IVC)(insp) diameter was approximately 5.1 mm/m(2); with ultrafiltration, change in IVC(insp) diameter was -0.95 mm/m(2) more compared with the control group at 4 weeks and -1.18 mm/m(2) more compared with the control group at 8 weeks. From baseline IVC(exp) diameter of approximately 8.2 mm/m(2), ultrafiltration-induced change at 4 weeks was -1.06 mm/m(2) more and at 8 weeks was -1.07 mm/m(2) more (P=0.044). From a baseline left atrial diameter of 2.1 cm/m(2), ultrafiltration-induced change at 4 weeks was -0.14 cm/m(2) more and at 8 weeks was -0.15 cm/m(2) more. At baseline, there was no relationship between interdialytic ambulatory BP and echocardiographic parameters of volume. The reduction in interdialytic ambulatory BP was also independent of change in the echocardiographic volume parameters. CONCLUSIONS: The inferior vena cava and left atrial diameters are echocardiographic parameters that are responsive to probing dry weight; thus, they reflect excess volume. However, echocardiographic volume parameters are poor determinants of interdialytic BP, and their change does not predict the BP response to probing dry weight.

Role of home blood pressure monitoring in overcoming therapeutic inertia and improving hypertension control: a systematic review and meta-analysis.

Hypertension remains the most common modifiable cardiovascular risk factor, yet hypertension control rates remain dismal. Home blood pressure (BP) monitoring has the potential to improve hypertension control. The purpose of this review was to quantify both the magnitude and mechanisms of benefit of home BP monitoring on BP reduction. Using a structured review, studies were selected if they reported either changes in BP or percentage of participants achieving a pre-established BP goal between randomized groups using home-based and office-based BP measurements. A random-effects model was used to estimate the magnitude of benefit and relative risk. The search yielded 37 randomized controlled trials with 9446 participants that contributed data for this meta-analysis. Compared with clinic-based measurements (control group), systolic BP improved with home-based BP monitoring (-2.63 mm Hg; 95% CI, -4.24, -1.02); diastolic BP also showed improvement (-1.68 mm Hg; 95% CI, -2.58, -0.79). Reductions in home BP monitoring-based therapy were greater when telemonitoring was used. Home BP monitoring led to more frequent antihypertensive medication reductions (relative risk, 2.02 [95% CI, 1.32 to 3.11]) and was associated with less therapeutic inertia defined as unchanged medication despite elevated BP (relative risk for unchanged medication, 0.82 [95% CI, 0.68 to 0.99]). Compared with clinic BP monitoring alone, home BP monitoring has the potential to overcome therapeutic inertia and lead to a small but significant reduction in systolic and diastolic BP. Hypertension control with home BP monitoring can be enhanced further when accompanied by plans to monitor and treat elevated BP such as through telemonitoring.

Determinants and prognostic significance of electrocardiographic left ventricular hypertrophy criteria in chronic kidney disease.

BACKGROUND AND OBJECTIVES: The diagnosis of left ventricular hypertrophy (LVH) has prognostic value in the general population. However, among those with chronic kidney disease (CKD), the determinants of electrocardiographic (EKG) LVH and its prognostic value are not clear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A cross-sectional study was performed among 387 consenting consecutive patients from a veterans hospital with a longitudinal follow-up. RESULTS: The overall prevalence of EKG-LVH by the Sokolow-Lyon criteria was 8% and by the Cornell voltage-duration product was 11%. Compared with non-CKD controls, CKD patients had unadjusted odds ratio (OR) for LVH by Cornell criteria of 2.52 (95% CI 1.18 to 5.42). Significance was lost after adjustment. The unadjusted OR for LVH by Sokolow-Lyon criteria was 2.24 (95% CI 0.95 to 5.33). This OR remained statistically insignificant after multivariate adjustment. Anemia, proteinuria, and 24-hour ambulatory systolic BP were associated with EKG-LVH regardless of diagnostic criteria. After a 7.5-year median follow-up, the hazard ratio for all-cause mortality was not associated with EKG-LVH diagnosed by the Sokolow-Lyon criteria; however, multivariable adjustments made EKG-LVH significant. A statistically significant relationship was seen between mortality and Cornell criteria; however, multivariable adjustments made EKG-LVH nonsignificant. CONCLUSIONS: The Sokolow-Lyon and Cornell EKG-LVH criteria cannot be used interchangeably to diagnose LVH or determine prognosis. Among those with CKD, ambulatory systolic BP predicts all-cause mortality. Moreover, the duration and severity of BP elevation presumably reflected in EKG-LVH diagnosed by Sokolow-Lyon criteria is also of prognostic significance; the Cornell criteria do not carry independent prognostic information.

Diagnosing obesity by body mass index in chronic kidney disease: an explanation for the "obesity paradox?".

Although obesity is associated with poor outcomes, among patients with chronic kidney disease (CKD), obesity is related to improved survival. These results may be related to poor diagnostic performance of body mass index (BMI) in assessing body fat content. Accordingly, among 77 patients with CKD and 20 controls, body fat percentage was estimated by air displacement plethysmography (ADP), skinfold thickness, and body impedance analysis. Defined by BMI ≥30 kg/m(2), the prevalence of obesity was 20% in controls and 65% in patients with CKD. Defined by ADP, the prevalence increased to 60% among controls and to 90% among patients with CKD. Although sensitivity and positive predictive value of BMI to diagnose obesity were 100%, specificity was 72%, but the negative predictive value was only 30%. BMI correctly classified adiposity in 75%. Regardless of the presence or absence of CKD, subclinical obesity (defined as BMI <30 kg/m(2) but excess body fat by ADP) was often missed in people with low lean body mass. The adjusted odds ratio for subclinical obesity per 1 kg of reduced lean body mass by ADP was 1.14 (95% CI: 1.06 to 1.23; P<0.001). Skinfold thickness measurements correctly classified 94% of CKD patients, but bioelectrical impedance analyzer-assessed body fat estimation did so in only 65%. Air displacement plethysmography-, skinfold thickness-, and bioelectrical impedance analyzer-assessed body fat all provided reproducible estimates of adiposity. Skinfold thickness measurements may be a better test to classify obesity among those with CKD. Given the low negative predictive value of BMI for obesity, our study may provide an explanation of the "obesity paradox."

Intradialytic hypertension is a marker of volume excess.

BACKGROUND: Intradialytic blood pressure (BP) profiles have been associated with all-cause mortality, but its pathophysiology remains unknown. We tested the hypothesis that intradialytic changes in BP reflect excess volume. METHODS: The dry weight reduction in hypertensive haemodialysis patients (DRIP) trial probed dry weight in 100 prevalent haemodialysis patients; 50 patients who did not have their dry weight probed served as time controls. In this post hoc analysis, intradialytic BP was recorded at each of the 30 dialysis treatments during the trial. The slope of intradialytic BP over dialysis was calculated by the log of BP regressed over time. Using a linear mixed model, we compared these slopes between control and ultrafiltration groups at baseline and over time, tested the effect of dry weight reduction on these slopes and finally tested the ability of change in intradialytic slopes to predict change in interdialytic systolic BP. RESULTS: At baseline, intradialytic systolic and diastolic BP dropped at a rate of ~3%/h (P < 0.0001). Over the course of the trial, compared to the control group, the slopes steepened in the ultrafiltration group for systolic but not diastolic BP. Those who lost the most post-dialysis weight from baseline to 4 weeks and baseline to 8 weeks also experienced the greatest steepening of slopes. Each percent per hour steepening of the intradialytic systolic BP slope was associated with 0.71 mmHg [95% confidence interval (CI) 0.01-1.42, P = 0. 048] reduction in interdialytic ambulatory systolic pressure. CONCLUSIONS: Intradialytic BP changes appear to be associated with change in dry weight among haemodialysis patients. Among long-term haemodialysis patients, intradialytic hypertension may, thus, be a sign of volume overload.

Median intradialytic blood pressure can track changes evoked by probing dry-weight.

BACKGROUND: Median BP obtained over a single dialysis treatment can diagnose hypertension among hemodialysis patients. Whether median BP is as useful to track change in BP is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among patients participating in the dry-weight reduction in hypertensive hemodialysis patients (DRIP) trial, interdialytic ambulatory BP was recorded at baseline, 4 weeks, and 8 weeks. The mean interdialytic ambulatory BP was compared to the following recordings: predialysis on one dialysis treatment (Pre1), predialysis averaged over 2 weeks of dialysis treatment (Pre6), postdialysis on one dialysis treatment (Post1), postdialysis averaged over 2 weeks of dialysis treatment (Post6), and median intradialytic BP over one treatment. RESULTS: Pre1 was unable to detect change in ambulatory BP. Although Pre6 was able to detect change, it overestimated the ambulatory BP. On average, the magnitude of reduction in Post1 in response to probing dry-weight was nearly twice that obtained by ambulatory BP monitoring. Even Post6 overestimated the magnitude of reduction in BP at 8 weeks. Median systolic BP was responsive to probing dry-weight and neither overestimated nor underestimated the interdialytic ambulatory systolic BP at baseline or over time. However, the SD of the differences between median systolic BP and interdialytic ambulatory systolic BP varied from 16 to 20 mmHg. CONCLUSIONS: Median intradialytic BP recordings can detect change in ambulatory BP evoked by reduction in dry-weight at the population level. Because of wide agreement limits between intradialytic and interdialytic BP, the individual prediction of ambulatory BP from median intradialytic BP can be misleading.

A longitudinal study of kidney structure and function in adults.

BACKGROUND: Although kidney size is commonly measured in patients with chronic kidney disease (CKD), its relationship with kidney function is poorly understood. We conducted this longitudinal study to better understand the relationship between kidney size and function. METHODS: We retrospectively studied 178 kidneys measured by ultrasound in 93 patients with CKD who did not have autosomal polycystic kidney disease. Renal function was measured using estimated glomerular filtration rate (GFR). A mixed model that accounted for repeated measurements or nested observations was used for statistical analysis. RESULTS: In cross-sectional analyses, the following independent variables emerged as predictors of kidney size: estimated GFR along with its squared term, height, age and interactions of each of these two independent variables with aetiology of CKD. In longitudinal analyses over a median follow-up of 3.7 years, after accounting for predictors of baseline kidney size such as aetiology, height and estimated GFR, we found that kidney atrophy occurred at a rate of 0.072 cm/year (SD 0.016, P = 0.007). This atrophy was 'blunted' with declining GFR. Each 1 mL/min/1.73 m(2)/year greater decline in eGFR abrogated kidney atrophy by 0.015 cm/year (P = 0.024). CONCLUSION: Although in cross-sectional surveys kidney size is directly related to function, the longitudinal relationship between form and function is inverted. Since the rate of change in GFR determines kidney atrophy, we conclude that kidney size is a determinant of renal prognosis.

Physical activity is a determinant of circadian blood pressure variation in chronic kidney disease.

BACKGROUND: Circadian variation in blood pressure (BP), which is commonly blunted among patients with chronic kidney disease (CKD), has been associated with increased cardiovascular risk. The causes of this blunted circadian variation remain incompletely understood. METHODS: We hypothesized that physical activity is a determinant of circadian BP variation. Accordingly, we studied 101 patients with CKD (mean age 69 years, mostly men) with 24-hour ambulatory BP monitoring and simultaneous monitoring of physical activity on 2 occasions 4 weeks apart. RESULTS: Measured by wrist actigraphy, a higher level of physical activity was associated with lower overall mean BP. A higher level of activity also altered the circadian systolic BP rhythm; this alteration was characterized by both a higher amplitude of variation (and thus greater dipping) and restoration of acrophase (time at peak BP) to a less vulnerable period for cardiovascular events. Among the most sedentary participants, both systolic and pulse pressure acrophases were seen in the early hours of the morning which is also the most vulnerable period for cardiovascular events. CONCLUSION: Physical activity is an independent determinant of circadian variation in BP. We speculate that among patients with CKD, a sedentary lifestyle, rather than non-dipping, mediates increased cardiovascular risk.