Interaction between cold ischemia time and Kidney Donor Profile Index on postrenal transplant outcomes.

We analyzed whether there is an interaction between the Kidney Donor Profile Index (KDPI) and cold ischemia time (CIT) in recipients of deceased donor kidney transplant (KTs). Adults who underwent KTs in the United States between 2014 and 2020 were included and divided into 3 KDPI groups (≤20%, 21%-85%, >85%) and 4 CIT strata (<12, 12-17.9, 18-23.9, ≥24 hours). Multivariate analyses were used to test the interaction between KDPI and CIT for the following outcomes: primary graft nonfunction (PGNF), delayed graft function (DGF), estimated glomerular filtration rate (eGFR) at 6 and 12 months, patient survival, graft survival, and death-censored graft survival (DCGS). A total of 69,490 recipients were analyzed: 18,241 (26.3%) received a graft with KDPI ≤20%, 46,953 (67.6%) with KDPI 21%-85%, and 4,296 (6.2%) with KDPI >85%. Increasing KDPI and CIT were associated with worse post-KT outcomes. Contrary to our hypothesis, howerver, the interaction between KDPI and CIT was statistically significant only for PGNF and DGF and eGFR at 6 months. Paradoxically, the negative coefficient of the interaction suggested that increasing duration of CIT was more detrimental for low and intermediate-KDPI organs relative to high-KDPI grafts. Conversely, for mortality, graft survival, and DCGS, we found that the interaction between CIT and KDPI was not statistically significant. We conclude that, high KDPI and prolonged CIT are independent risk factors for inferior outcomes after KT. Their interaction, however, is statistically significant only for the short-term outcomes and more pronounced on low and intermediate-KDPI grafts than high-KDPI kidneys.

Radiographic Contrast Media and the Kidney.

AKI is a potential complication of intravascular iodinated contrast exposure. Contrast-associated AKI, which typically manifests as small and transient decrements in kidney function that develop within several days of contrast administration, is associated with serious adverse outcomes, including progressive kidney dysfunction and death. However, a causal link between the small increases in serum creatinine that characteristically occur with contrast-associated AKI and serious adverse outcomes remains unproven. This is important given mounting evidence that clinically indicated, potentially lifesaving radiographic procedures are underutilized in patients with CKD. This has been hypothesized to be related to provider concern about precipitating contrast-associated AKI. Intravascular gadolinium-based contrast, an alternative to iodinated contrast that is administered with magnetic resonance imaging, has also been linked with potential serious adverse events, notably the development of nephrogenic systemic fibrosis in patients with severe impairment in kidney function. Patients hospitalized in the intensive care unit frequently have clinical indications for diagnostic and therapeutic procedures that involve the intravascular administration of contrast media. Accordingly, critical care providers and others treating critically ill patients should possess a sound understanding of the risk factors for and incidence of such outcomes, the ability to perform evidence-based risk-benefit assessments regarding intravascular contrast administration, and knowledge of empirical data on the prevention of these iatrogenic complications.

Polypharmacy and mortality association by chronic kidney disease status: The REasons for Geographic And Racial Differences in Stroke Study.

Many Americans take multiple medications simultaneously (polypharmacy). Polypharmacy's effects on mortality are uncertain. We endeavored to assess the association between polypharmacy and mortality in a large U.S. cohort and examine potential effect modification by chronic kidney disease (CKD) status. The REasons for Geographic And Racial Differences in Stroke cohort data (n = 29 627, comprised of U.S. black and white adults) were used. During a baseline home visit, pill bottle inspections ascertained medications used in the previous 2 weeks. Polypharmacy status (major [≥8 ingredients], minor [6-7 ingredients], and none [0-5 ingredients]) was determined by counting the total number of generic ingredients. Cox models (time-on-study and age-time-scale methods) assessed the association between polypharmacy and mortality. Alternative models examined confounding by indication and possible effect modification by CKD. Over 4.9 years median follow-up, 2538 deaths were observed. Major polypharmacy was associated with increased mortality in all models, with hazard ratios and 95% confidence intervals ranging from 1.22 (1.07-1.40) to 2.35 (2.15-2.56), with weaker associations in more adjusted models. Minor polypharmacy was associated with mortality in some, but not all, models. The polypharmacy-mortality association did not differ by CKD status. While residual confounding by indication cannot be excluded, in this large American cohort, major polypharmacy was consistently associated with mortality.

Source of Post-Transplant Care and Mortality among Kidney Transplant Recipients Dually Enrolled in VA and Medicare.

BACKGROUND AND OBJECTIVES: Many kidney transplant recipients enrolled in the Veterans Health Administration are also enrolled in Medicare and eligible to receive both Veterans Health Administration and private sector care. Where these patients receive transplant care and its association with mortality are unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective cohort study of veterans who underwent kidney transplantation between 2008 and 2016 and were dually enrolled in Veterans Health Administration and Medicare at the time of surgery. We categorized patients on the basis of the source of transplant-related care (i.e., outpatient transplant visits, immunosuppressive medication prescriptions, calcineurin inhibitor measurements) delivered during the first year after transplantation defined as Veterans Health Administration only, Medicare only (i.e., outside Veterans Health Administration using Medicare), or dual care (mixed use of Veterans Health Administration and Medicare). Using multivariable Cox regression, we examined the independent association of post-transplant care source with mortality at 5 years after kidney transplantation. RESULTS: Among 6206 dually enrolled veterans, 975 (16%) underwent transplantation at a Veterans Health Administration hospital and 5231 (84%) at a non-Veterans Health Administration hospital using Medicare. Post-transplant care was received by 752 patients (12%) through Veterans Health Administration only, 2092 (34%) through Medicare only, and 3362 (54%) through dual care. Compared with patients who were Veterans Health Administration only, 5-year mortality was significantly higher among patients who were Medicare only (adjusted hazard ratio, 2.2; 95% confidence interval, 1.5 to 3.1) and patients who were dual care (adjusted hazard ratio, 1.5; 95% confidence interval, 1.1 to 2.1). CONCLUSIONS: Most dually enrolled veterans underwent transplantation at a non-Veterans Health Administration transplant center using Medicare, yet many relied on Veterans Health Administration for some or all of their post-transplant care. Veterans who received Veterans Health Administration-only post-transplant care had the lowest 5-year mortality.

Multivitamin Use and Serum Vitamin B12 Concentrations in Older-Adult Metformin Users in REGARDS, 2003-2007.

Metformin, an insulin-sensitizing drug, is a first line treatment for type 2 diabetes. Long-term use of metformin has been associated with subsequent reductions in vitamin B12 concentrations. The objective of our study was to determine whether metformin use is associated with lower serum vitamin B12 concentrations in older adults, and whether concurrent use of multivitamins modifies this association. We examined 2,510 participants aged 50 years and over, participating in the national population-based Reasons for Geographic And Racial Differences in Stroke (REGARDS) Study. Multivariable linear and logistic regression models were used to assess associations between multivitamin use and serum vitamin B12 concentrations. We estimated adjusted odds ratios (aOR)s and confidence intervals (CI)s. Results were stratified by three metformin/diabetes sub-groups: 1) participants with diabetes who were metformin users; 2) participants with diabetes who were not metformin users; and 3) participants without diabetes. We found that diabetic metformin users had significantly lower geometric mean serum B12 concentrations (409 pmol/L) than the group with diabetes not taking metformin (485 pmol/L; P<0.01), and the group without diabetes (445 pmol/L; P = 0.02). The geometric mean serum B12 concentrations were greater for multivitamin users (509 pmol/L) compared to those who did not use multivitamins (376 pmol/L; p<0.01). Among the participants with diabetes who were on metformin therapy, multivitamin use was associated with geometric mean serum vitamin B12 concentrations that were 50% (or 161 pmol/L) higher, compared to those not using multivitamins. Among metformin users, multivitamin use was associated with lower prevalence of combined low and borderline vitamin B12 concentrations (aOR = 0.14; 95% CI = 0.04, 0.54) compared to those not using multivitamins. In conclusion, metformin use was associated with lower geometric mean serum vitamin B12 concentrations among diabetic older adults compared to their counterparts. Concurrent multivitamin use may potentially protect against low or borderline vitamin B12 concentrations in long-term metformin users. Additional research is needed to further examine this association as low or borderline vitamin B12 concentrations can be preventable, or treatable if detected at an early stage, in long-term metformin users.

Geographic region and racial variations in polypharmacy in the United States.

PURPOSE: Medications can have unintended effects. High medication use populations may benefit from increased regimen oversight. Limited knowledge exists concerning racial and regional polypharmacy variation. We estimated total medication distributions (excluding supplements) of American black and white adults and assessed racial and regional polypharmacy variation. METHODS: REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort data (n = 30,239 U.S. blacks and whites aged ≥45 years) were analyzed. Home pill bottle inspections assessed the last two weeks' medications. Polypharmacy (≥8 medications) was determined by summing prescription and/or over-the-counter ingredients. Population-weighted logistic regression assessed polypharmacy's association with census region, race, and sex. RESULTS: The mean ingredient number was 4.12 (standard error = 0.039), with 15.7% of REGARDS using 8 ingredients or more. In crude comparisons, women used more medications than men, and blacks and whites reported similar mean ingredients. A cross-sectional, logistic model adjusting for demographics, socioeconomics, and comorbidities showed increased polypharmacy prevalence in whites versus blacks (OR [95% CI]: 0.63, [0.55-0.72]), women (1.94 [1.68-2.23]), and Southerners (broadly Southeasterners and Texans; 1.48 [1.17-1.87]) versus Northeasterners (broadly New England and upper Mid-Atlantic). Possible limitations include polypharmacy misclassification and model misspecification. CONCLUSION: Polypharmacy is common. Race and geography are associated with polypharmacy variation. Further study of underlying factors explaining these differences is warranted.

Rotational spectroscopy and molecular structure of the 1,1,2-trifluoroethylene-acetylene complex.

Guided by ab initio calculations, Fourier transform microwave rotational spectra in the 6-22 GHz region are obtained for the complex formed between 1,1,2-trifluoroethylene and acetylene, including the normal isotopomer, three of four singly substituted (13)C species obtained in natural abundance, and using commercially available isotopic varieties of acetylene, species containing HCCD and H(13)C(13)CH. Although the ab initio calculations suggest two possible low energy planar arrangements for the molecules in the complex, only a single, unique structure is obtained from a combined analysis of the rotational constants derived from the spectra and atomic positions determined using Kraitchman [Am. J. Phys. 21, 17 (1953)] substitution coordinates. This structure is similar to that obtained for the CF(2)CHF[Single Bond]HF complex [H. O. Leung and M. D. Marshall, J. Chem. Phys. 126, 114310 (2007)] in which both the primary and secondary interactions occur between the HCCH molecule and a F atom and a H atom bonded to the same carbon of CF(2)CHF. The 2.748(15) A hydrogen bond has acetylene as the donor and 1,1,2-trifluoroethylene as the acceptor and forms a 104.49(15) degrees C[Single Bond]Fcdots, three dots, centeredH angle. The 2.8694(9) A secondary interaction between the pi bond of acetylene and the H atom geminal to the acceptor F atom causes the hydrogen bond to deviate 69.24(67) degrees from linearity. This large deviation from linearity and the similarity of the two intermolecular bond lengths suggest that the two interactions are becoming comparable in importance.

Nuclear quadrupole hyperfine structure in the microwave spectrum of HCl-N2O: electric field gradient perturbation of N2O by HCl.

The microwave spectra of six isotopomers of HCl-N(2)O have been obtained in the 7-19 GHz region with a pulsed molecular beam, Fourier transform microwave spectrometer. The nuclear quadrupole hyperfine structure due to all quadrupolar nuclei is resolved and the spectra are analyzed using the Watson S-reduced Hamiltonian with the inclusion of nuclear quadrupole coupling interactions. The spectroscopic constants determined include rotational constants, quartic and sextic centrifugal distortion constants, and nuclear quadrupole coupling constants for each quadrupolar nucleus. Due to correlations of the structural parameters, the effective structure of the complex cannot be obtained by fitting to the spectroscopic constants of the six isotopomers. Instead, the parameters for each isotopomer are calculated from the A and C rotational constants and the chlorine nuclear quadrupole coupling constant along the a-axis, chi(aa). There are two possible structures; the one in which hydrogen of HCl interacts with the more electronegative oxygen of N(2)O is taken to represent the complex. The two subunits are approximately slipped parallel. For H (35)Cl-(14)N(2)O, the distance between the central nitrogen and chlorine is 3.5153 A and the N(2)O and HCl subunits form angles of 72.30 degrees and 119.44 degrees with this N-Cl axis, respectively. The chlorine and oxygen atoms occupy the opposite, obtuse vertices of the quadrilateral formed by O, central N, Cl, and H. Nuclear quadrupole coupling constants show that while the electric field gradient of the HCl subunit remains essentially unchanged upon complexation, there is electronic rearrangement about the two nitrogen nuclei in N(2)O.