Bridging the Evidence and Practice Gap in Chronic Kidney Disease: A System Thinking Approach to Population Health.

Chronic kidney disease (CKD) is common, costly, and life-limiting, requiring dialysis and transplantation in advanced stages. Although effective guideline-based therapy exists, the asymptomatic nature of CKD together with low health literacy, adverse social determinants of health, unmet behavioral health needs, and primary care providers' (PCP) limited understanding of CKD result in defects in screening and diagnosis. Care is fragmented between PCPs and specialty nephrologists, with limited time, expertise, and resources to address systemic gaps.

Fever, infection, and rejection after kidney transplant failure.

Background: Patients returning to dialysis therapy after renal transplant failure have high morbidity and retransplant rates. After observing frequent hospitalizations with fever after failure, it was hypothesized that maintaining immunosuppression for the failed allograft increases the risk of infection, while weaning immunosuppression can lead to symptomatic rejection mimicking infection.

Methods: One hundred eighty-six patients with failed kidney transplants were analyzed for rates of hospitalization with fever within 6 months of allograft failure.

Effects of cellular sensitization and donor age on acute rejection and graft function after deceased-donor kidney transplantation.

Background: Allografts from older donors may be more immunogenic than those from younger donors. Pretransplantation cellular sensitization may interact with advanced donor age to increase the risk of immune injury after deceased-donor kidney transplantation.

Methods: The outcomes of 118 consecutive deceased-donor kidney transplant recipients with available pretransplantation donor-stimulated enzyme-linked immunosorbent spot (ELISPOT) assays for interferon gamma were analyzed retrospectively to determine the impact of cellular sensitization and other clinical variables, including donor age, on the incidence of acute rejection (AR) in the first year after deceased-donor transplantation and on estimated glomerular filtration rate 12 months after transplantation.

Independent of nephrectomy, weaning immunosuppression leads to late sensitization after kidney transplant failure.

Background: Patients returning to dialysis therapy after renal transplant failure have a high rate of human leukocyte antigen antibody sensitization, and sensitization has been linked to allograft nephrectomy. We hypothesized that nephrectomy for cause is a consequence of weaning immunosuppression and that weaning leads to sensitization even in the absence of nephrectomy.

Methods: We examined outcomes in 300 consecutive patients with kidney allograft failure and survival of more than 30 days after failure.

Immune factors influencing ethnic disparities in kidney transplantation outcomes.

An influence of ethnicity on the outcomes of kidney transplant recipients has been recognized for several decades. Both immune and nonimmune factors have been explored as potential explanations. Most studies have focused on the inferior outcomes of African-Americans.

TM4SF10 and ADAP interaction in podocytes: role in Fyn activity and nephrin phosphorylation.

TM4SF10 [transmembrane tetra(4)-span family 10] is a claudin-like cell junction protein that is transiently expressed during podocyte development where its expression is downregulated in differentiating podocytes coincident with the appearance of nephrin at the slit diaphragm. In a yeast two-hybrid screen, we identified adhesion and degranulation-promoting adaptor protein (ADAP), a well-known Fyn substrate and Fyn binding partner, as a TM4SF10 interacting protein in mouse kidney. Using coimmunoprecipitation and immunohistochemistry experiments in cultured human podocytes, we show that TM4SF10 colocalizes with Fyn and ADAP but does not form a stable complex with Fyn.

Donor phosphorus levels and recipient outcomes in living-donor kidney transplantation.

Background And Objectives: In living-donor kidney transplantation, various donor factors, including gender, age, and baseline kidney function, predict allograft function and recipient outcomes after transplantation. Because higher phosphorus is predictive of vascular injury in healthy adults, the effect of donor phosphorus levels on recipient renal function after transplantation was investigated.

Design, Setting, Participants, And Measurements: Phosphorus levels in 241 living donors were analyzed from a 7-year period, and recipient renal function and acute rejection at 1 year posttransplantation were examined controlling for other influencing factors, including multiple donor variables, HLA matching, and acute rejection.

Induction antibody therapy in kidney transplantation.

Antilymphocyte antibodies have been used for the prevention or treatment of acute rejection in kidney transplant recipients since the 1960s. Both monoclonal and polyclonal agents now are available and generally are classified as either lymphocyte-depleting or nondepleting agents. Use of such antibodies for induction therapy in the immediate postoperative period has varied over the years.

Nonpharmacologic management of hypertension in the elderly.

Nonpharmacologic management of hypertension is all too often overlooked in the elderly. The Dietary Approaches to Stop Hypertension (DASH) diet, weight loss, physical activity, moderation of alcohol, and salt restriction, particularly when used in combination, are effective strategies to help control hypertension and reduce overall cardiovascular risk. Behavioral modification should form the cornerstone of hypertension treatment in the elderly.

Reduction in erythropoietin resistance after conversion from sirolimus to enteric coated mycophenolate sodium.

Background: Anemia is a known adverse effect of sirolimus (SRL) therapy. Sirolimus may contribute to anemia by a direct antiproliferative effect or by increasing inflammation, worsening kidney function, or decreasing iron utilization. After observing the need for high dose exogenous erythropoietin dosage in some patients on SRL, we hypothesized that SRL therapy may influence anemia by inducing a state of erythropoietin resistance.

Management of the kidney transplant recipient.

The short-term outcomes of kidney transplant recipients have improved dramatically in the past 20 years, in large part resulting from the availability of more potent immunosuppressive drugs capable of preventing or treating acute allograft rejection. Ironically, side effects from these same immunosuppressants play a role in the long-term morbidity and mortality of this patient population. As kidney transplant recipients survive for longer periods of time with functioning allografts, primary care physicians will likely become more involved in their management, mandating at least a basic understanding of immunosuppression and its complications.

Ambulatory blood pressure monitoring: an argument for wider clinical use.

Ambulatory blood pressure monitoring predicts cardiovascular risk better than office readings do. It can detect white-coat hypertension, masked hypertension, and normal and aberrant patterns of circadian variation in blood pressure. Though the clinical role of ambulatory blood pressure monitoring is currently limited, its use can be considered in many common clinical situations, eg, resistant hypertension, transplantation, pregnancy, chronic kidney disease, and dialysis.

A WT1 co-regulator controls podocyte phenotype by shuttling between adhesion structures and nucleus.

Glomerular podocyte differentiation state is critical for filtration barrier function and is regulated by WT1, a zinc finger transcription factor. A yeast two-hybrid assay identified a novel, WT1-interacting protein (WTIP) that maps to human chromosome 19q13.1, a region with genes linked to familial focal segmental glomerulosclerosis.