Current State and Future of Private Practice Nephrology in the United States.

Chronic kidney disease remains highly prevalent and exerts a heavy economic burden. The practice of nephrology has come a long way in managing this disease, though there remains room for improvement. The private domain, where more than half of the adult nephrology workforce operates, faces serious challenges. Interest has decreased in the field, leading to diminished recruitment. There has been a reduction in both reimbursement rates and revenues. We discuss the current state of private practice nephrology and strategies to reinvigorate our discipline. There needs to be a focus on preparing fellows during training not only for academic careers, but also for effective functioning in the environment of private practice and development of pathways for growth. We believe that private practice nephrology must expand its frontiers to be fulfilling professionally, challenging academically, and successful financially. The United States government has recently announced the Advancing American Kidney Health Executive Order which seeks to prioritize optimal treatments for patients with kidney disease. We are optimistic that there is a renaissance afoot in nephrology and that our field is in the process of rediscovering itself, with its best days yet to come.

Subclinical Cognitive Impairment and Listing for Kidney Transplantation.

BACKGROUND AND OBJECTIVES: Cognitive impairment is common in patients with kidney disease and can affect physicians' perception and/or patients' ability to complete the pretransplant evaluation. We examined whether cognitive impairment influences the likelihood for transplant listing and whether patients with cognitive impairment take longer to be listed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a single-center longitudinal cohort study. Patients presenting for their index kidney transplant evaluation were screened for cognitive impairment using the Montreal Cognitive Assessment. A score <26 indicated cognitive impairment. The transplant selection committee was blinded to the scores. Kaplan-Meier analysis assessed time to active listing by level of cognition. A Cox proportional hazards model that included age, sex, race/ethnicity, smoking, coronary artery disease, and diabetes was constructed to evaluate the association between Montreal Cognitive Assessment score and listing for transplant. RESULTS: In total, 349 patients who underwent Montreal Cognitive Assessment testing at their initial visit were included in the analysis. Patients with cognitive impairment were more likely to be older, black, and smokers. The time to listing in patients with cognitive impairment was longer than the time to listing in those with no cognitive impairment (median time, 10.6 versus 6.3 months; log rank test P=0.01). Cognitive impairment was independently associated with a lower likelihood of being listed for transplant (hazard ratio, 0.93 per unit lower Montreal Cognitive Assessment score; 95% confidence interval, 0.88 to 0.99; P=0.02). A lower proportion of patients with cognitive impairment were listed compared with patients without cognitive impairment at 1 month (2% versus 11%), 6 months (17% versus 37%), and 1 year (23% versus 41%), (P<0.001 for all). CONCLUSIONS: Cognitive impairment is associated with a lower likelihood of being listed for kidney transplant, and is associated with longer time to transplant listing.

Multiple Targets for Novel Therapy of FSGS Associated with Circulating Permeability Factor.

A plasma component is responsible for altered glomerular permeability in patients with focal segmental glomerulosclerosis. Evidence includes recurrence after renal transplantation, remission after plasmapheresis, proteinuria in infants of affected mothers, transfer of proteinuria to experimental animals, and impaired glomerular permeability after exposure to patient plasma. Therapy may include decreasing synthesis of the injurious agent, removing or blocking its interaction with cells, or blocking signaling or enhancing cell defenses to restore the permeability barrier and prevent progression. Agents that may prevent the synthesis of the permeability factor include cytotoxic agents or aggressive chemotherapy. Extracorporeal therapies include plasmapheresis, immunoadsorption with protein A or anti-immunoglobulin, or lipopheresis. Oral or intravenous galactose also decreases Palb activity. Studies of glomeruli have shown that several strategies prevent the action of FSGS sera. These include blocking receptor-ligand interactions, modulating cell reactions using indomethacin or eicosanoids 20-HETE or 8,9-EET, and enhancing cytoskeleton and protein interactions using calcineurin inhibitors, glucocorticoids, or rituximab. We have identified cardiotrophin-like cytokine factor 1 (CLCF-1) as a candidate for the permeability factor. Therapies specific to CLCF-1 include potential use of cytokine receptor-like factor (CRLF-1) and inhibition of Janus kinase 2. Combined therapy using multiple modalities offers therapy to reverse proteinuria and prevent scarring.

Polyclonal and monoclonal antibodies in renal transplant: an update.

PURPOSE OF REVIEW: There are several monoclonal and polyclonal antibodies used in renal transplantation today, this article will discuss several agents, their updates and newer agents. RECENT FINDINGS: Antithymocyte globulin and interleukin-2 (IL-2) receptor blocker continue to be used as induction agents. The risk of acute rejection was higher in IL-2 receptor blockers mainly in the first year, but graft survivals were similar in both groups long term. Belatacept is the only approved intravenous maintenance immunosuppressive therapy which provides the benefit of glomerular filtration rate preservation, but it was associated with a higher risk of acute rejection and post-transplant lymphoproliferative disorder. Bortezomib may help decrease donor-specific antibody levels, but there are limited data to support its use for desensitization or rejection. Eculizumab may help in antibody-mediated rejection in some cases but has not shown promising long-term effects in high-risk individuals. Newer agents have been continuously tested for improved efficacy and safety. SUMMARY: Transplantation is the standard of care for end-stage renal disease patients, but we still have a long way to go, as we need to improve long-term outcomes. The manipulation of the immune system is a delicate undertaking, with risks of adverse events; therefore, risk versus benefit needs to be carefully evaluated and treatment needs to be individualized.

Diabetes and kidney transplantation: past, present, and future.

Diabetes mellitus is the most common etiology for end stage renal disease (ESRD) worldwide and in the United States. The incidence of morbidity and mortality is higher in diabetic patients with ESRD due to increased cardiovascular events. Patients with type 2 diabetes who receive a renal allograft have a higher survival rate compared with patients who are maintained on chronic hemodialysis therapy, but there is scarcity of data on long-term graft outcomes. Most recently the development of new onset diabetes after transplantation (NODAT) poses a serious threat to patient and allograft survival. Pre-emptive transplantation and the use of living donors have improved overall survival. In addition, critical management of glucose, blood pressure, and cholesterol are some of the factors that can help minimize adverse outcomes in both patients with pre-existing diabetes and patients who develop NODAT. Future clinical trials are warranted to improve therapeutic medical management of these patients thus influencing graft attrition.