Recipient Obesity and Kidney Transplant Outcomes: A Mate-Kidney Analysis.

RATIONALE & OBJECTIVE: The impact of extreme recipient obesity on long-term kidney transplant outcomes has been controversial. This study sought to evaluate the association of various levels of recipient obesity on kidney transplantation outcomes by comparing mate-kidney recipient pairs to address possible confounding effects of donor characteristics on posttransplant outcomes. STUDY DESIGN: Nationwide observational cohort study using mate-kidney models. SETTING & PARTICIPANTS: In analysis based on the Organ Procurement and Transplant Network/United Network of Organ Sharing database, 44,560 adult recipients of first-time deceased-donor kidney transplants from 2001 through 2016 were paired by donor. PREDICTORS: Recipient body mass index (BMI) categorized as 18-25 (n = 12,446), >25-30 (n = 15,477), >30-35 (n = 11,144; obese), and >35 (n = 5,493; extreme obesity) kg/m2. OUTCOMES: Outcomes included patient survival, graft survival, death-censored graft survival, delayed graft function (DGF), and hospital length of stay. ANALYTICAL APPROACH: Conditional logistic regression and stratified proportional hazards models were used to compare outcomes as odds ratios and hazard ratios (HRs), adjusted for recipient and transplant factors, using recipients with a BMI >35 kg/m2 as a reference. RESULTS: At a median follow-up of 3.9 years, adjusted odds ratios for DGF were 0.42 (95% CI, 0.36-0.48), 0.55 (95% CI, 0.48-0.62), and 0.73 (95% CI, 0.64-0.83) for BMI 18-25, >25-30, and >30-35 kg/m2, respectively (P < 0.001 for all). Death-censored graft failure was less frequent for BMI ≤25 and >25-30 kg/m2 (HRs of 0.66 [95% CI, 0.59-0.74] and 0.79 [95% CI, 0.70-0.88], respectively; P < 0.001 for both), but not for BMI >30-35 kg/m2 (HR, 0.91 [95% CI, 0.81-1.02]; P = 0.09). Length of stay and patient survival did not differ by recipient BMI. LIMITATIONS: Observational study with limited detail regarding potential confounders. CONCLUSIONS: Despite an increased risk of DGF likely unrelated to donor organ quality, long-term transplant outcomes among recipients with a BMI >35 kg/m2 are similar to those among recipients with a BMI >30-35 kg/m2, supporting a flexible approach to kidney transplantation candidacy in candidates with extreme obesity.

The Epidemiologic Burden of Tacrolimus Variability among Kidney Transplant Recipients in the United States.

BACKGROUND: Within-patient tacrolimus level variability >30% has been shown to be a risk factor for de novo donor-specific antibody formation and death-censored graft failure among kidney transplant recipients. The burden of tacrolimus variability and the correlation between variability and subtherapeutic tacrolimus levels were examined in a large national data set. METHODS: All tacrolimus levels drawn at LabCorp® facilities in the United States with a diagnosis code for kidney transplant between November 2011 and September 2017 were examined, excluding values that could represent new allografts. Tacrolimus variability was calculated if at least 3 levels were available. The percentage of subtherapeutic (<4.0 ng/dL) tacrolimus levels (%subT) was also calculated. Interdependence between %subT and tacrolimus variability was assessed with correlation analysis and linear regression. RESULTS: There were 410,257 tacrolimus levels among 27,375 patients, who had 11 (interquartile range [IQR] 6-20) tacrolimus levels over a median follow-up of 26.5 (IQR 12.8-46.1) months. Median tacrolimus variability was 30.6%, and 51.6% of patients exceeded 30% variability. Median %subT was 11.1% (IQR 0-30.8%), and 34.3% of patients had no subtherapeutic levels. The correlation coefficient between tacrolimus variability and %subT was 0.253 (p< 0.001). In linear regression, tacrolimus variability increased 1.86% for each 10% increase in %subT (p < 0.001), but R-squared for this model was only 0.06. CONCLUSION: More than half of established kidney transplant patients from a large national sample exhibited levels of tacrolimus variability that have been associated with inferior transplant outcomes. Tacrolimus variability has a weak association with subtherapeutic levels, but represents a more complicated constellation of clinical factors.

Risk of adverse maternal and fetal outcomes during pregnancy in living kidney donors: A matched cohort study.

BACKGROUND: We examined the risk of adverse pregnancy outcomes in primiparous kidney donors compared to matched controls. METHODS: Fifty-nine women with a history of kidney donation prior to their first pregnancy with normal renal function and no history of kidney disease, diabetes or chronic hypertension were matched 1:4 by age (within 2 years) and race to women with two kidneys using data from an integrated healthcare delivery system. Adverse pregnancy outcomes were defined as preterm delivery (delivery <37 weeks), delivery via cesarean section, gestational hypertension, preeclampsia/eclampsia, gestational diabetes, length of stay in the hospital >3 days, infant death/transfer to acute facility and low birthweight (<2500 g). RESULTS: Living kidney donors did not have a higher risk of adverse outcomes compared to matched controls. There was a trend toward an increased risk of preeclampsia/eclampsia in kidney donors but it did not reach statistical significance (Odds ratio [OR]: 2.96, 95% CI: 0.98-8.94, P = 0.06). However, in kidney donors ≤30 years of age, there was a fourfold increased risk of preeclampsia/eclampsia (OR: 4.09, 95% CI: 1.07-15.59, P = 0.04). CONCLUSION: Overall, the risk of pregnancy-associated complications following kidney donation is small but potential female kidney donors should be counseled on the possible increased risk of preeclampsia.

Preeclampsia Risks in Kidney Donors and Recipients.

PURPOSE OF REVIEW: To review the studies and practice guidelines on the preeclampsia risks in kidney donors and recipients. RECENT FINDINGS: There is a small increased risk of gestational hypertension and preeclampsia in pregnancies that follow kidney donation. Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline (2017) and the 2015 American Society of Transplantation (AST) consensus conference statement recommends counseling kidney donors about this increased risk. There is no observed increase in fetal complications or eclampsia post-kidney donation. Preeclampsia is more commonly observed in kidney transplant recipients than the general population and these patients should be co-managed with an obstetrician with experience in managing high risk pregnancies. Although preeclampsia has not been found to have a deleterious effect on renal graft function, it can cause premature delivery. Risk calculators have been proposed and an elevated pre-pregnancy creatinine seems to be an important risk. KDIGO Clinical Practice Guidelines (2009) recommends attempting pregnancy when kidney function is stable with proteinuria of less than 1 g per day. The use of novel biomarkers for preeclampsia has not been published in this population. Preeclampsia is an important concern for female kidney donors and recipients of child-bearing age. These individuals should be appropriately counseled.

Immediate Consequences of Acute Kidney Injury: The Impact of Traditional and Nontraditional Complications on Mortality in Acute Kidney Injury.

Acute kidney injury (AKI) that requires renal replacement therapy is associated with a mortality rate that exceeds 50% in the intensive care unit, which is greater than other serious illnesses such as acute lung injury and myocardial infarction. Much information is now available regarding the complications of AKI that contribute to mortality and may be usefully categorized as "traditional" and "nontraditional". Traditional complications are the long-recognized complications of AKI such as hyperkalemia, acidosis, and volume overload, which may be typically corrected with renal replacement therapy. "Nontraditional" complications include complications such as sepsis, lung injury, and heart failure that may arise due to the effects of AKI on inflammatory cytokines, immune function, and cell death pathways such as apoptosis. In this review, we discuss both traditional and nontraditional complications of AKI with a focus on factors that contribute to mortality, considering both pathophysiology and potential remedies. Because AKI is the most common inpatient consult to nephrologists, it is essential to be aware of the complications of AKI that contribute to mortality to devise appropriate treatment strategies to prevent and manage AKI complications with the ultimate goal of reducing the unacceptably high mortality rate of AKI.

Investigating the interface of superhydrophobic surfaces in contact with water.

Neutron reflectivity (NR) is used to probe the solid, liquid, vapor interface of a porous superhydrophobic (SH) surface submerged in water. A low-temperature, low-pressure technique was used to prepare a rough, highly porous organosilica aerogel-like film. UV/ozone treatments were used to control the surface coverage of hydrophobic organic ligands on the silica framework, allowing the contact angle with water to be continuously varied over the range of 160 degrees (superhydrophobic) to <10 degrees (hydrophilic). NR shows that the superhydrophobic nature of the surface prevents infiltration of water into the porous film. Atomic force microscopy and density functional theory simulations are used in combination to interpret the NR results and help establish the location, width, and nature of the SH film-water interface.