Living Donation and Pregnancy-Related Complications: State of the Evidence and Call To Action for Improved Risk Assessment.

Living kidney donation and living liver donation significantly increases organ supply to make lifesaving transplants possible, offering survival benefits to the recipients and cost savings to society. Of all living donors, 40% are women of childbearing age. However, limited data exist regarding the effect of donation on future pregnancies and of pregnancy-related complications on postdonation outcomes. In February 2023, the American Society of Transplantation Women's Health Community of Practice held a virtual Controversies Conference on reproductive health, contraception, and pregnancy after transplantation and living donation. Experts in the field presented the available data. Smaller breakout sessions were created to discuss findings, identify knowledge gaps, and develop recommendations. We present the conference findings related to living donation. The evidence reviewed shows that gestational hypertension and gestational diabetes mellitus before kidney donation have been associated with an increased risk of developing postdonation hypertension and diabetes mellitus, respectively, without increasing the risk of developing an eGFR <45 ml/min after donation. The risk of preeclampsia in living kidney donors increases to 4%-10%, and low-dose aspirin may help reduce that risk. Little is known about the financial burden for living donors who become pregnant, their risk of postpartum depression, or the optimal time between donation and conception. The data on living liver donors are even scarcer. The creation of a registry of donor candidates may help answer many of these questions and, in turn, educate prospective donors so that they can make an informed choice.

Dialysis Facility Profit Status and Early Steps in Kidney Transplantation in the Southeastern United States.

BACKGROUND AND OBJECTIVES: Dialysis facilities in the United States play a key role in access to kidney transplantation. Previous studies reported that patients treated at for-profit facilities are less likely to be waitlisted and receive a transplant, but their effect on early steps in the transplant process is unknown. The study's objective was to determine the association between dialysis facility profit status and critical steps in the transplantation process in Georgia, North Carolina, and South Carolina. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective cohort study, we linked referral and evaluation data from all nine transplant centers in the Southeast with United States Renal Data System surveillance data. The cohort study included 33,651 patients with kidney failure initiating dialysis from January 1, 2012 to August 31, 2016. Patients were censored for event (date of referral, evaluation, or waitlisting), death, or end of study (August 31, 2017 for referral and March 1, 2018 for evaluation and waitlisting). The primary exposure was dialysis facility profit status: for profit versus nonprofit. The primary outcome was referral for evaluation at a transplant center after dialysis initiation. Secondary outcomes were start of evaluation at a transplant center after referral and waitlisting. RESULTS: Of the 33,651 patients with incident kidney failure, most received dialysis treatment at a for-profit facility (85%). For-profit (versus nonprofit) facilities had a lower cumulative incidence difference for referral within 1 year of dialysis (-4.5%; 95% confidence interval, -6.0% to -3.2%). In adjusted analyses, for-profit versus nonprofit facilities had lower referral (hazard ratio, 0.84; 95% confidence interval, 0.80 to 0.88). Start of evaluation within 6 months of referral (-1.0%; 95% confidence interval, -3.1% to 1.3%) and waitlisting within 6 months of evaluation (1.0%; 95% confidence interval, -1.2 to 3.3) did not meaningfully differ between groups. CONCLUSIONS: Findings suggest lower access to referral among patients dialyzing in for-profit facilities in the Southeast United States, but no difference in starting the evaluation and waitlisting by facility profit status.

Posttransplant Malignancy.

Posttransplant malignancy is a leading cause of death after solid organ transplantation (SOT). Recipients of SOT are at significantly higher risk of multiple cancers compared with the general population, most notably nonmelanoma skin cancer and posttransplant lymphoproliferative disorders. Risk factors for posttransplant malignancy include history of malignancy, immunosuppression, oncogenic viral infections, sun exposure, and disease-specific associations. Early detection and treatment of malignancies can improve survival.

Tailored Rabbit Antithymocyte Globulin Induction Dosing for Kidney Transplantation.

BACKGROUND: Rabbit antithymocyte globulin (rATG) is the most widely used kidney transplant induction immunotherapy in the United States. It was recently Food and Drug Administration approved for this indication with typical dose recommendations of 1.5 mg/kg for up to 7 days given via a central line. METHODS: We theorized that reduced rATG dosing when compared with conventional dosing (6-10.5 mg/kg) is safe and effective, leading to development of a risk-stratified treatment protocol. Five-year data from a retrospective cohort of 224 adult kidney transplants (2008-2013) with follow-up through 2015 is presented. Cumulative rATG doses of 3 mg/kg were administered peripherally to nonsensitized living donor recipients, 4.5 mg/kg to nonsensitized deceased donor recipients. A subset of higher immunologic risk recipients (defined as history of prior transplant, panel reactive antibody greater than 20%, or flow cytometry crossmatch positivity) received 6 mg/kg. RESULTS: There were no differences in patient or graft survival between the 3 groups. One-year rejection rates in the first 2 groups were 8.3% and 8.8%, respectively, comparable to contemporaneous rates reported to the Scientific Registry of Transplant Recipients. Dose tailoring permitted substantial cost savings estimated at US $1 091 502. Mean length of stay fell by almost 3 days as the protocol was refined. There were no episodes of phlebitis. Infection rates were comparable with those reported to the Scientific Registry of Transplant Recipients. CONCLUSIONS: The novel findings of the current study include peripheral administration, reduced dosing, favorable safety, excellent allograft outcomes, and clear associative data regarding reduced costs and length of stay.

Acute Kidney Disease After Liver and Heart Transplantation.

After transplantation of nonrenal solid organs, an acute decline in kidney function develops in the majority of patients. In addition, a significant number of nonrenal solid organ transplant recipients develop chronic kidney disease, and some develop end-stage renal disease, requiring renal replacement therapy. The incidence varies depending on the transplanted organ. Acute kidney injury after nonrenal solid organ transplantation is associated with prolonged length of stay, cost, increased risk of death, de novo chronic kidney disease, and end-stage renal disease. This overview focuses on the risk factors for posttransplant acute kidney injury after liver and heart transplantation, integrating discussion of proteinuria and chronic kidney disease with emphasis on pathogenesis, histopathology, and management including the use of mechanistic target of rapamycin inhibition and costimulatory blockade.

Hypertension, living kidney donors, and transplantation: where are we today?

Hypertension is a prevalent problem in kidney transplant recipients that is known to be a "traditional" risk factor for atherosclerotic cardiovascular disease leading to premature allograft failure and death. Donor, peritransplant, and recipient factors affect hypertension risk. Blood pressure control after transplantation is inversely associated with glomerular filtration rate (GFR). Calcineurin inhibitors, the most commonly used class of immunosuppressives, cause endothelial dysfunction, increase vascular tone, and sodium retention via the renin-angiotensin-aldosterone system resulting in systemic hypertension. Steroid withdrawal seems to have little impact on blood pressure control. Newer agents like belatacept appear to be associated with less hypertension. Transplant renal artery stenosis is an important, potentially treatable cause of hypertension. Dihydropyridine calcium channel blockers mitigate calcineurin inhibitor nephrotoxicity and may be associated with improved estimated GFR. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are not recommended in the first 3 to 6 months given their effects on reduced estimated GFR, anemia, and hyperkalemia. The use of ß-blockers may be associated with improved patient survival, even for patients without cardiovascular disease. Living donation may increase blood pressure by 5 mm Hg or more. Some transplant centers accept Caucasian living donors with well-controlled hypertension on a single agent if they agree to close follow-up.

Effects of a renal rehabilitation exercise program in patients with CKD: a randomized, controlled trial.

BACKGROUND AND OBJECTIVES: Patients with CKD have a high prevalence of cardiovascular disease associated with or exacerbated by inactivity. This randomized, controlled study investigated whether a renal rehabilitation exercise program for patients with stages 3 or 4 CKD would improve their physical function and quality of life. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 119 adults with CKD stages 3 and 4 were randomized, and 107 of these patients proceeded to usual care or the renal rehabilitation exercise intervention consisting of usual care plus guided exercise two times per week for 12 weeks (24 sessions). Physical function was determined by three well established performance-based tests: 6-minute walk test, sit-to-stand test, and gait-speed test. Health-related quality of life was assessed by the RAND 36-Item Short Form Health Survey. RESULTS: At baseline, no differences in self-reported level of activity, 6-minute walk test, and sit-to-stand test scores were observed between the usual care (n=48) and renal rehabilitation exercise (n=59) groups, although baseline gait-speed test score was higher in the renal rehabilitation exercise group (P<0.001). At follow-up, the renal rehabilitation exercise group but not the usual care group showed significant improvements in the 6-minute walk test (+210.4±266.0 ft [19% improvement] versus -10±219.9 ft; P<0.001), the sit-to-stand test (+26.9±27% of age prediction [29% improvement] versus +0.7±12.1% of age prediction; P<0.001), and the RAND-36 physical measures of role functioning (P<0.01), physical functioning (P<0.01), energy/fatigue levels (P=0.01), and general health (P=0.03) and mental measure of pain scale (P=0.04). The renal rehabilitation exercise regimen was generally well tolerated. CONCLUSIONS: A 12-week/24-session renal rehabilitation exercise program improved physical capacity and quality of life in patients with CKD stages 3 and 4. Longer follow-up is needed to determine if these findings will translate into decreased mortality rates.

Use of computer alerts to prevent the inappropriate use of metformin in an inpatient setting.

BACKGROUND: Metformin is recommended as initial therapy for most patients with type 2 diabetes mellitus. Its most serious adverse effect, lactic acidosis, is a rare entity with a high mortality rate. Despite well-publicized contraindications, metformin is inappropriately prescribed to many hospitalized patients. OBJECTIVE: To determine the efficacy of computer alerts at reducing inappropriate metformin prescribing. METHODS: Retrospective chart review of all hospitalized patients who received an order for metformin, before (n = 144) and after (n = 147) an intervention designed to reduce inappropriate administration. This intervention included 2 "hard-stop" computer alerts that prevented prescribing metformin to patients with renal dysfunction and in critical care or postoperative units; and 2 "soft" alerts that fired when no serum creatinine was available or the patient was in an outpatient surgical unit. Charts were reviewed for the presence of contraindications: renal insufficiency, congestive heart failure, recent myocardial infarction, surgery, or intravenous contrast use within 48 hours of metformin administration. RESULTS: In the preintervention group there were 47 violations compared with 13 violations in the postintervention group (P < .001). The greatest improvement was in surgical patients (39 violations vs 11, P < .001). CONCLUSIONS: Computer alerts at order entry were effective in decreasing the inappropriate prescribing of metformin in an inpatient setting.

A meta-analysis of anticoagulation for calf deep venous thrombosis.

OBJECTIVE: This meta-analysis was initiated to assess the efficacy and safety of anticoagulation therapy for adult patients with isolated calf vein deep venous thrombosis (DVT). METHODS: We searched MEDLINE (1950-October 2010), the Cochrane Library (1993-October 2010), trial registries, meeting abstracts, and selected references, using no limits. Included studies compared the results of anticoagulation (vitamin K antagonist or therapeutic heparin) for a minimum of 30 days vs the results of no anticoagulation in adults with calf vein DVT proved by ultrasound imaging or venograph who were monitored for at least 30 days. Two independent reviewers extracted data using a piloted standardized form. Methodologic quality was assessed using the Cochrane Risk of Bias tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies. Discrepancies were resolved by consensus or by a third reviewer. Authors were contacted for additional information if necessary. Outcomes were pooled using Peto fixed-effects models. RESULTS: Of 2328 studies identified, two RCTs and six cohorts (126 patients treated with anticoagulation and 328 controls) met selection criteria. The methodologic quality of most studies was poor. Pulmonary embolism (PE; odds ratio, 0.12; 95% confidence interval, 0.02-0.77; P = .03) and thrombus propagation (odds ratio, 0.29; 95% confidence interval, 0.14-0.62; P = .04) were significantly less frequent in those who received anticoagulation. Significant heterogeneity existed in studies reporting mortality rates, but these demonstrated a trend toward fewer deaths with anticoagulation. When limited to randomized trials, the protective effect of anticoagulation for PE was no longer statistically significant, but the benefit for preventing thrombus progression persisted. Adverse events such as bleeding were sparsely reported but favored controls (P = .65). CONCLUSIONS: Our review suggests that anticoagulation therapy for calf vein DVT may decrease the incidence of PE and thrombus propagation. However, due to poor methodologic quality and few events among included studies for PE, this finding is not robust. Thrombus propagation appears reduced with anticoagulation treatment. A rigorous RCT will assist in treatment decisions for calf vein DVT.

Recurrent takotsubo cardiomyopathy associated with pheochromocytoma.

OBJECTIVE: To describe a case of recurrent takotsubo cardiomyopathy in a patient with pheochromocytoma. METHODS: We present a case report, including clinical and laboratory data. In addition, the current relevant literature pertaining to pheochromocytoma and takotsubo syndrome is reviewed and summarized. RESULTS: In 2004, an 81-year-old woman with no history of cardiac disease presented with chest discomfort, and takotsubo syndrome was diagnosed. No emotional or physical stressors were identified at that time. Her left ventricular systolic function normalized during that hospitalization. In 2007, the patient was readmitted to the hospital with chest discomfort and ST-segment elevation. Cardiac catheterization demonstrated only minor nonobstructive coronary artery disease. She was again found to have takotsubo syndrome with a classic apical hypokinetic segment. Treatment with a heart failure regimen was initiated, and she was screened for pheochromocytoma as the precipitant for her recurrent takotsubo cardiomyopathy. A 24-hour urine collection showed minimally elevated normetanephrine excretion of 719 microg (reference range, 148 to 560) and vanillylmandelic acid of 8.3 mg (reference range, <8.0). The plasma normetanephrine level was 1.57 pg/mL (reference range, <0.9). Subsequent magnetic resonance imaging revealed a left adrenal mass (2 cm by 1 cm). Ultimately, the patient underwent left adrenalectomy, and the pathology report was consistent with pheochromocytoma. She has been asymptomatic since then, and a repeated echocardiogram demonstrated normal left ventricular systolic function. CONCLUSION: In patients presenting with takotsubo cardiomyopathy, a precipitating factor, such as emotional or physical stress, can often be identified. In some patients (such as our current case), however, pheochromocytoma may be the underlying disease and should be considered.