Background Studies suggest an association between acute kidney injury (AKI) and long-term risk for chronic kidney disease (CKD), even following apparent renal recovery. Whether the pattern of renal ...recovery predicts kidney risk following AKI is unknown. Study Design Retrospective cohort. Setting & Participants Patients in the Veterans Health Administration in 2011 hospitalized (>24 hours) with at least 2 inpatient serum creatinine measurements, baseline estimated glomerular filtration rate > 60 mL/min/1.73 m2 , and no diagnosis of end-stage renal disease or non−dialysis-dependent CKD: 17,049 (16.3%) with and 87,715 without AKI. Predictor Pattern of recovery to creatinine level within 0.3 mg/dL of baseline after AKI: within 2 days (fast), in 3 to 10 days (intermediate), and no recovery by 10 days (slow or unknown). Outcome CKD stage 3 or higher, defined as 2 outpatient estimated glomerular filtration rates < 60 mL/min/1.73 m2 at least 90 days apart or CKD diagnosis, dialysis therapy, or transplantation. Measurements Risk for CKD was modeled using modified Poisson regression and time to death-censored CKD was modeled using Cox proportional hazards regression, both stratified by AKI stage. Results Most patients’ AKI episodes were stage 1 (91%) and 71% recovered within 2 days. At 1 year, 18.2% had developed CKD (AKI, 31.8%; non-AKI, 15.5%; P < 0.001). In stage 1, the adjusted relative risk ratios for CKD stage 3 or higher were 1.43 (95% CI, 1.39-1.48), 2.00 (95% CI, 1.88-2.12), and 2.65 (95% CI, 2.51-2.80) for fast, intermediate, and slow/unknown recovery. A similar pattern was observed in subgroup analyses incorporating albuminuria and sensitivity analysis of death-censored time to CKD. Limitations Variable timing of follow-up and mostly male veteran cohort may limit generalizability. Conclusions Patients who develop AKI during a hospitalization are at substantial risk for the development of CKD by 1 year following hospitalization and timing of AKI recovery is a strong predictor, even for the mildest forms of AKI.
Food, gastrointestinal pH, and models of oral drug absorption Abuhelwa, Ahmad Y.; Williams, Desmond B.; Upton, Richard N. ...
European journal of pharmaceutics and biopharmaceutics,
March 2017, 2017-Mar, 2017-03-00, 20170301, Letnik:
112
Journal Article
Recenzirano
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This article reviews the major physiological and physicochemical principles of the effect of food and gastrointestinal (GI) pH on the absorption and bioavailability of oral drugs, and ...the various absorption models that are used to describe/predict oral drug absorption. The rate and extent of oral drug absorption is determined by a complex interaction between a drug’s physicochemical properties, GI physiologic factors, and the nature of the formulation administered. GI pH is an important factor that can markedly affect oral drug absorption and bioavailability as it may have significant influence on drug dissolution & solubility, drug release, drug stability, and intestinal permeability. Different regions of the GI tract have different drug absorptive properties. Thus, the transit time in each GI region and its variability between subjects may contribute to the variability in the rate and/or extent of drug absorption. Food-drug interactions can result in delayed, decreased, increased, and sometimes un-altered drug absorption. Food effects on oral absorption can be achieved by direct and indirect mechanisms. Various models have been proposed to describe oral absorption ranging from empirical models to the more sophisticated “mechanism-based” models. Through understanding of the physicochemical and physiological rate-limiting factors affecting oral absorption, modellers can implement simplified population-based modelling approaches that are less complex than whole-body physiologically-based models but still capture the essential elements in a physiological way and hence will be more suited for population modelling of large clinical data sets. It will also help formulation scientists to better predict formulation performance and to develop formulations that maximize oral bioavailability.
Background Awareness of chronic kidney disease (CKD), defined by kidney damage or reduced glomerular filtration rate, remains low in the United States, and few estimates of its future burden exist. ...Study Design We used the CKD Health Policy Model to simulate the residual lifetime incidence of CKD and project the prevalence of CKD in 2020 and 2030. The simulation sample was based on nationally representative data from the 1999 to 2010 National Health and Nutrition Examination Surveys. Setting & Population Current US population. Model, Perspective, & Timeline Simulation model following up individuals from current age through death or age 90 years. Outcomes Residual lifetime incidence represents the projected percentage of persons who will develop new CKD during their lifetimes. Future prevalence is projected for 2020 and 2030. Measurements Development and progression of CKD are based on annual decrements in estimated glomerular filtration rates that depend on age and risk factors. Results For US adults aged 30 to 49, 50 to 64, and 65 years or older with no CKD at baseline, the residual lifetime incidences of CKD are 54%, 52%, and 42%, respectively. The prevalence of CKD in adults 30 years or older is projected to increase from 13.2% currently to 14.4% in 2020 and 16.7% in 2030. Limitations Due to limited data, our simulation model estimates are based on assumptions about annual decrements in estimated glomerular filtration rates. Conclusions For an individual, lifetime risk of CKD is high, with more than half the US adults aged 30 to 64 years likely to develop CKD. Knowing the lifetime incidence of CKD may raise individuals’ awareness and encourage them to take steps to prevent CKD. From a national burden perspective, we estimate that the population prevalence of CKD will increase in coming decades, suggesting that development of interventions to slow CKD onset and progression should be considered.
Preventive care for adults with diabetes has improved substantially in recent decades. We examined trends in the incidence of diabetes-related complications in the United States from 1990 through ...2010.
We used data from the National Health Interview Survey, the National Hospital Discharge Survey, the U.S. Renal Data System, and the U.S. National Vital Statistics System to compare the incidences of lower-extremity amputation, end-stage renal disease, acute myocardial infarction, stroke, and death from hyperglycemic crisis between 1990 and 2010, with age standardized to the U.S. population in the year 2000.
Rates of all five complications declined between 1990 and 2010, with the largest relative declines in acute myocardial infarction (-67.8%; 95% confidence interval CI, -76.2 to -59.3) and death from hyperglycemic crisis (-64.4%; 95% CI, -68.0 to -60.9), followed by stroke and amputations, which each declined by approximately half (-52.7% and -51.4%, respectively); the smallest decline was in end-stage renal disease (-28.3%; 95% CI, -34.6 to -21.6). The greatest absolute decline was in the number of cases of acute myocardial infarction (95.6 fewer cases per 10,000 persons; 95% CI, 76.6 to 114.6), and the smallest absolute decline was in the number of deaths from hyperglycemic crisis (-2.7; 95% CI, -2.4 to -3.0). Rate reductions were larger among adults with diabetes than among adults without diabetes, leading to a reduction in the relative risk of complications associated with diabetes. When expressed as rates for the overall population, in which a change in prevalence also affects complication rates, there was a decline in rates of acute myocardial infarction and death from hyperglycemic crisis (2.7 and 0.1 fewer cases per 10,000, respectively) but not in rates of amputation, stroke, or end-stage renal disease.
Rates of diabetes-related complications have declined substantially in the past two decades, but a large burden of disease persists because of the continued increase in the prevalence of diabetes. (Funded by the Centers for Disease Control and Prevention.).
Despite concerns about hypoglycemia events from overly aggressive glycemic reduction, population trends in hypoglycemia and hyperglycemic crisis incidence are unclear. To address this gap, we ...examined changes in emergency department (ED) visit rates for hypoglycemia and hyperglycemic crisis 2006-2011.
Using data from the Nationwide Emergency Department Sample, we estimated the number of ED visits for hypoglycemia and hyperglycemic crisis via ICD-9-CM among adults with diabetes. Using data from the National Health Interview Survey, we estimated the population of adults with diabetes and calculated ED visit rates.
From 2006 to 2011, ED visit rates for hypoglycemia declined by 22% from 1.8 to 1.4 per 100 adults (p = 0.003). The rates decreased in all age groups (all P<0.05) except those aged 18 to 44 years (P = 0.31). Hypoglycemia rates displayed a J-shaped curve across age, with the highest rates among adults aged 75 years or older (P <0.001). ED visit rates for hyperglycemic crisis did not change overall but increased 17% for adults aged 65 to 74 years (P = 0.02) and 29% for women (P = 0.01). Hyperglycemic crisis rates were highest among adults aged 18 to 44 years (P <0.001).
Hypoglycemia rates have declined for all adults but persons aged 18-44 years while rates for hyperglycemic crisis remained stable. Future preventive efforts should target on the susceptible population of adults aged 18 to 44 years and those aged 75 years or older.
Aims:
Our study aims were to determine the frequency of MODY mutations (HNF1A, HNF4A, glucokinase) in a diverse population of youth with diabetes and to assess how well clinical features identify ...youth with maturity-onset diabetes of the young (MODY).
Methods:
The SEARCH for Diabetes in Youth study is a US multicenter, population-based study of youth with diabetes diagnosed at age younger than 20 years. We sequenced genomic DNA for mutations in the HNF1A, HNF4A, and glucokinase genes in 586 participants enrolled in SEARCH between 2001 and 2006. Selection criteria included diabetes autoantibody negativity and fasting C-peptide levels of 0.8 ng/mL or greater.
Results:
We identified a mutation in one of three MODY genes in 47 participants, or 8.0% of the tested sample, for a prevalence of at least 1.2% in the pediatric diabetes population. Of these, only 3 had a clinical diagnosis of MODY, and the majority was treated with insulin. Compared with the MODY-negative group, MODY-positive participants had lower FCP levels (2.2 ± 1.4 vs 3.2 ± 2.1 ng/mL, P < .01) and fewer type 2 diabetes-like metabolic features. Parental history of diabetes did not significantly differ between the 2 groups.
Conclusions/Interpretation:
In this systematic study of MODY in a large pediatric US diabetes cohort, unselected by referral pattern or family history, MODY was usually misdiagnosed and incorrectly treated with insulin. Although many type 2 diabetes-like metabolic features were less common in the mutation-positive group, no single characteristic identified all patients with mutations. Clinicians should be alert to the possibility of MODY diagnosis, particularly in antibody-negative youth with diabetes.
Background Little is known about patterns of kidney function decline leading up to the initiation of long-term dialysis. Study Design Retrospective cohort study. Setting & Participants 5,606 Veterans ...Affairs patients who initiated long-term dialysis in 2001-2003. Predictor Trajectory of estimated glomerular filtration rate (eGFR) during the 2-year period before initiation of long-term dialysis. Outcomes & Measurements Patient characteristics and care practices before and at the time of dialysis initiation and survival after initiation. Results We identified 4 distinct trajectories of eGFR during the 2-year period before dialysis initiation: 62.8% of patients had persistently low level of eGFR <30 mL/min/1.73 m2 (mean eGFR slope, 7.7 ± 4.7 SD mL/min/1.73 m2 per year), 24.6% had progressive loss of eGFR from levels of approximately 30-59 ml/min/1.73 m2 (mean eGFR slope, 16.3 ± 7.6 mL/min/1.73 m2 per year), 9.5% had accelerated loss of eGFR from levels >60 mL/min/1.73 m2 (mean eGFR slope, 32.3 ± 13.4 mL/min/1.73 m2 per year), and 3.1% experienced catastrophic loss of eGFR from levels >60 mL/min/1.73 m2 within 6 months or less. Patients with steeper eGFR trajectories were more likely to have been hospitalized and have an inpatient diagnosis of acute kidney injury. They were less likely to have received recommended predialysis care and had a higher risk of death in the first year after dialysis initiation. Conclusions There is substantial heterogeneity in patterns of kidney function loss leading up to the initiation of long-term dialysis perhaps calling for a more flexible approach toward preparing for end-stage renal disease.
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Warming the skin is a key means of promoting solute permeation through the skin. Changes in solute permeation associated with variations in skin temperature also assist in ...understanding the mechanism by which solutes permeate the skin. However, few studies have considered the relative impact of temperature on the main determinants of the maximum flux for a solute across the skin, the solubility of a solute and its diffusivity in the stratum corneum. In this study, we quantified for the first time the thermodynamics associated with the maximum skin fluxes for a series of phenolic compounds of similar size but with varying lipophilicity (defined by the logarithms of their octanol/water partition coefficient, logP). These studies were undertaken using aqueous donor solutions (along with testosterone as a reference solute) across human epidermal membranes in vertical Franz diffusion cells at 4 °C, 24 °C and 37 °C with intermittent receptor sampling and volume replacement over 24 h. Kinetic and thermodynamic analyses included the estimation of the stratum corneum (SC) apparent SC diffusivity from the SC maximum fluxes and SC solubilities and the associated activation energies, enthalpies and entropies for diffusion. The key findings were that the differences in the maximum flux of phenolic compounds varying in lipophilicity mainly arose from differences in SC solubility at the various temperatures and that, at the highest temperature, SC permeability and SC diffusion were affected by SC lipid fluidisation and that variations in SC - water partitioning enthalpies explain some of the previously low activation energies for permeation of the more lipophilic phenols. Higher enthalpies for diffusion were seen for solutes with addition hydrogen bonding capacity and the highest negative entropy was observed with the more compact solutes. Various relationships between the derived thermodynamic parameters were explored and interpreted in a proposed model for solute partitioning into and permeation through the SC intercellular lipid lamellae.
OBJECTIVE:--We examined the prevalences of diagnosed diabetes, and undiagnosed diabetes and pre-diabetes using fasting and 2-h oral glucose tolerance test values, in the U.S. during 2005-2006. We ...then compared the prevalences of these conditions with those in 1988-1994. RESEARCH DESIGN AND METHODS--In 2005-2006, the National Health and Nutrition Examination Survey included a probability sample of 7,267 people aged greater-than-or-equal12 years. Participants were classified according to glycemic status by interview for diagnosed diabetes and by fasting and 2-h glucoses measured in subsamples. RESULTS:--In 2005-2006, the crude prevalence of total diabetes in people aged greater-than-or-equal20 years was 12.9%, of which ~40% was undiagnosed. In people aged greater-than-or-equal20 years, the crude prevalence of impaired fasting glucose was 25.7% and of impaired glucose tolerance was 13.8%, with almost 30% having either. Over 40% of individuals had diabetes or pre-diabetes. Almost one-third of the elderly had diabetes, and three-quarters had diabetes or pre-diabetes. Compared with non-Hispanic whites, age- and sex-standardized prevalence of diagnosed diabetes was approximately twice as high in non-Hispanic blacks (P < 0.0001) and Mexican Americans (P = 0.0001), whereas undiagnosed diabetes was not higher. Crude prevalence of diagnosed diabetes in people aged greater-than-or-equal20 years rose from 5.1% in 1988-1994 to 7.7% in 2005-2006 (P = 0.0001); this was significant after accounting for differences in age and sex, particularly in non-Hispanic blacks. Prevalences of undiagnosed diabetes and pre-diabetes were generally stable, although the proportion of total diabetes that was undiagnosed decreased in Mexican Americans. CONCLUSIONS:--Over 40% of people aged greater-than-or-equal20 years have hyperglycemic conditions, and prevalence is higher in minorities. Diagnosed diabetes has increased over time, but other conditions have been relatively stable.
Medical Costs of CKD in the Medicare Population HONEYCUTT, Amanda A; SEGEL, Joel E; XIAOHUI ZHUO ...
Journal of the American Society of Nephrology,
09/2013, Letnik:
24, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Estimates of the medical costs associated with different stages of CKD are needed to assess the economic benefits of interventions that slow the progression of kidney disease. We combined laboratory ...data from the National Health and Nutrition Examination Survey with expenditure data from Medicare claims to estimate the Medicare program's annual costs that were attributable to CKD stage 1-4. The Medicare costs for persons who have stage 1 kidney disease were not significantly different from zero. Per person annual Medicare expenses attributable to CKD were $1700 for stage 2, $3500 for stage 3, and $12,700 for stage 4, adjusted to 2010 dollars. Our findings suggest that the medical costs attributable to CKD are substantial among Medicare beneficiaries, even during the early stages; moreover, costs increase as disease severity worsens. These cost estimates may facilitate the assessment of the net economic benefits of interventions that prevent or slow the progression of CKD.
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