Aneesha Shetty

Treatment of Obstructive Hypertrophic Cardiomyopathy Symptoms and Gradient Resistant to First-Line Therapy With β-Blockade or Verapamil

Background—There is controversy about preferred methods to relieve obstruction in hypertrophic cardiomyopathy patients still symptomatic after &bgr;-blockade or verapamil. Methods and Results—Of 737 patients prospectively registered at our institution, 299 (41%) required further therapy for obstruction for limiting symptoms, rest gradient 61±45, provoked gradient 115±49 mm Hg, and followed up for 4.8 years. Disopyramide was added in 221 (74%) patients and pharmacological control of symptoms was achieved in 141 (64%) patients. Overall, 138 (46%) patients had surgical relief of obstruction (91% myectomy) and 6 (2%) alcohol septal ablation. At follow-up, resting gradients in the 299 patients had decreased from 61±44 to 10±25 mm Hg (P<0.0001); New York Heart Association class decreased from 2.7±0.7 to 1.8±0.5 (P<0.0001). Kaplan–Meier survival at 10 years in the 299 advanced-care patients was 88% and did not differ from nonobstructed patients (P=0.28). Only 1 patient had sudden death, a low annual rate of 0.06%/y. Kaplan–Meier survival at 10 years in the advanced-care patients did not differ from that expected in a matched cohort of the US population (P=0.90). Conclusions—Patients with obstruction and symptoms resistant to initial pharmacological therapy with &bgr;-blockade or verapamil may realize meaningful symptom relief and low mortality through stepped management, adding disopyramide in appropriately selected patients, and when needed, by surgical myectomy.

APOL1‐Associated End‐Stage Renal Disease in a Living Kidney Transplant Donor

Homozygosity for apolipoprotein‐L1 (APOL1) risk variants has emerged as an important predictor of renal disease in individuals of African descent over the past several years. Additionally, these risk variants may be important predictors of renal allograft failure when present in a living or deceased donor. Currently, there is no universal recommendation for screening of potential donors. We present a case of end‐stage renal disease with focal segmental glomerulosclerosis in a living donor 7 years following donor nephrectomy. Genetic assessment revealed homozygosity for the G1 high‐risk APOL1 variant.

Experimental protocol of a randomized controlled clinical trial investigating the effects of personalized exercise rehabilitation on kidney transplant recipients' outcomes.

BACKGROUND This randomized controlled trial (RCT) will investigate the effects of a personalized exercise rehabilitation regimen on return to work and find work rate, vascular health, functional capacity, quality of life, kidney function, and body composition in kidney transplant (KT) recipients. METHODS/DESIGN This RCT will recruit 120 men and/or women who have had a KT to participate in a 12 month exercise intervention or control (standard clinical care only) group. The 12 month exercise intervention will consist of one-on-one, progressive exercise rehabilitation sessions twice a week, for 60 min each session. The control group will continue standard clinical care as recommended by their post-transplant medical team without any intervention. The primary outcomes will be assessments of vascular structure and function, walking and strength measures to assess functional capacity, blood markers to assess kidney function, questionnaires to assess quality of life, DXA body scan to assess body composition, and a 1-week free living physical activity assessment. Additionally, employment status will be assessed. These assessments will be performed at baseline, 6 months, and 12 months. DISCUSSION This investigation will increase the understanding of the role exercise rehabilitation has on managing the physiological and psychological health of the individual as well as on the individuals personal economic impact (via employment status). This study design has the potential to assist in constructing an effective exercise rehabilitation program that can be incorporated into part of standard post-transplant care.

Health-Related Quality of Life Outcomes After Kidney Transplantation

Abstract Health-related quality of life (HRQOL) provides a measure of patients’ perception of their symptoms, overall health or disability, and treatment. As such, HRQOL is an important patient-centered outcome and transplant-oriented clinical research endpoint. HRQOL alone, or in tandem with other objective clinical outcome measures, is useful in monitoring clinical practice, informing treatment decisions, and guiding the allocation of healthcare resources. It comprises three domains: physical, mental, and psychosocial wellbeing; and can be measured by generalized or targeted instruments depending on the degree of specificity desired by the clinician or researcher. Patients with end stage renal disease requiring dialysis report diminished quality of life compared to the general population, which in turn is associated with an increased risk of hospitalization and death, particularly in those with a high comorbidity burden. Renal transplantation confers a global quality of life benefit. Physical symptoms like pain, poor sleep quality, and fatigue are perceived to be improved after transplantation by renal transplant recipients with a functioning allograft. Depression and anxiety also improve after transplantation as does social participation and integration. However, on average, HRQOL following renal transplant remains lower than in the general population, partly due to transplant related complications like infection and malignancy and the adverse effects of immunosuppression. Other factors that negatively impact HRQOL after transplant include older recipient age, deceased donor transplantation, female gender, lack of social support, and comorbid conditions such as diabetes and depression. Improved HRQOL after kidney transplantation, especially in the physical domain, has been associated with better patient and allograft survival. Hence it is imperative for transplant clinicians to familiarize themselves with the concepts, measurement, and interpretation of HRQOL as they strive to provide comprehensive care to kidney transplant patients.

Internal medicine residents' perspectives on effects of 2011 ACGME work hour regulations on patient care.

Background: The Accreditation Council for Graduate Medical Education (ACGME) introduced new work hour limitations in July 2011. Purposes: The aim is to assess internal medicine residents’ perspectives on the impact of these limitations on their ability to discharge patient care duties. Methods: An anonymous survey was administered to 158 medicine residents in an urban university-affiliated internal medicine residency program. Residents’ perspectives on various aspects of patient care were recorded on a 5-point Likert-type scale. Results: The response rate was 62%. The majority of residents (80%) agreed that patients had adequate continuity of care. Most residents agreed that they had enough time to follow up on consult notes (64% agreed) and investigations (80% agreed) daily. Most PGY-1 residents (59%) reported having enough time to prepare sign-outs. Most (60%) residents felt that reducing handoffs would improve patient care. Conclusions: Most residents believe that the new work hour limitations would continue to uphold patient safety, but handoffs in care must be restricted.

Graft and Patient Survival

Abstract Kidney transplantation is the treatment of choice for patients with end-stage renal disease, providing a survival and quality of life benefit to the recipient over patients on dialysis. While the survival trend for kidney transplant recipients has steadily improved over the years, the rate of death with a functioning renal allograft remains largely unchanged. Donor and recipient selection impacts both recipient and graft survival and the newly introduced longevity matching-based Kidney Allocation System attempts to capture this association. It is interesting to note that while short-term graft survival has improved significantly over the years, long-term graft survival has not seen an equivalent rise. Various factors including subclinical rejection, immunosuppressive toxicity and chronic allograft dysfunction have been implicated. Protocol renal allograft biopsies serve to provide biological and immunological markers of these factors and biopsy endpoints have been shown to be associated with long-term graft survival. We used laboratory and pathology data after transplant to independently develop a late outcome surrogate score providing a prediction model for graft survival following kidney transplantation. Further effort into developing novel biomarkers and quality predictive models of long-term graft survival is needed.

Intragraft Molecular Pathways Associated with Tolerance Induction in Renal Transplantation

The modern immunosuppression regimen has greatly improved short-term allograft outcomes but not long-term allograft survival. Complications associated with immunosuppression, specifically nephrotoxicity and infection risk, significantly affect graft and patient survival. Inducing and understanding pathways underlying clinical tolerance after transplantation are, therefore, necessary. We previously showed full donor chimerism and immunosuppression withdrawal in highly mismatched allograft recipients using a bioengineered stem cell product (FCRx). Here, we evaluated the gene expression and microRNA expression profiles in renal biopsy samples from tolerance-induced FCRx recipients, paired donor organs before implant, and subjects under standard immunosuppression (SIS) without rejection and with acute rejection. Unlike allograft samples showing acute rejection, samples from FCRx recipients did not show upregulation of T cell- and B cell-mediated rejection pathways. Gene expression pathways differed slightly between FCRx samples and the paired preimplantation donor organ samples, but most of the functional gene networks overlapped. Notably, compared with SIS samples, FCRx samples showed upregulation of genes involved in pathways, like B cell receptor signaling. Additionally, prediction analysis showed inhibition of proinflammatory regulators and activation of anti-inflammatory pathways in FCRx samples. Furthermore, integrative analyses (microRNA and gene expression profiling from the same biopsy sample) identified the induction of regulators with demonstrated roles in the downregulation of inflammatory pathways and maintenance of tissue homeostasis in tolerance-induced FCRx samples compared with SIS samples. This pilot study highlights the utility of molecular intragraft evaluation of pathways related to FCRx-induced tolerance and the use of integrative analyses for identifying upstream regulators of the affected downstream molecular pathways.