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.

High levels of dd-cfDNA identify patients with TCMR 1A and borderline allograft rejection at elevated risk of graft injury.

The clinical importance of subclinical, early T cell-mediated rejection (Banff TCMR 1A and borderline lesions) remains unclear, due, in part to the fact that histologic lesions used to characterize early TCMR can be nonspecific. Donor-derived cell-free DNA (dd-cfDNA) is an important molecular marker of active graft injury. Over a study period from June 2017 to May 2019, we assessed clinical outcomes in 79 patients diagnosed with TCMR 1A/borderline rejection across 11 US centers with a simultaneous measurement of dd-cfDNA. Forty-two patients had elevated dd-cfDNA (≥0.5%) and 37 patients had low levels (<0.5%). Elevated levels of dd-cfDNA predicted adverse clinical outcomes: among patients with elevated cfDNA, estimated glomerular filtration rate declined by 8.5% (interquartile rate [IQR] -16.22% to -1.39%) (-3.50 mL/min/1.73 m2 IQR -8.00 to -1.00) vs 0% (-4.92%, 4.76%) in low dd-cfDNA patients (P = .004), de novo donor-specific antibody formation was seen in 40% (17/42) vs 2.7% (P < .0001), and future or persistent rejection occurred in 9 of 42 patients (21.4%) vs 0% (P = .003). The use of dd-cfDNA may complement the Banff classification and to risk stratify patients with borderline/TCMR 1A identified on biopsy.

Epstein-Barr virus and renal transplantation.

Epstein-Barr virus (EBV) is a gamma herpesvirus associated with diseases ranging from asymptomatic viremia to post-transplant malignancies in kidney transplant recipients. EBV specifically is associated with post-transplantation lymphoproliferative disorder (PTLD), in kidney transplant recipients, with increased risk in EBV seronegative patients with EBV seropositive donors on intensified immunosuppression. The diagnosis of PTLD relies on clinical suspicion plus tissue biopsy with polymerase chain reaction (PCR) testing of blood currently used for risk determination in high-risk recipients. Therapeutic strategies for PTLD include reduction of immunosuppression, chemotherapy and rituximab, and consideration of sirolimus-based immunosuppression. Antivirals such as ganciclovir are used to prevent reactivation of cytomegalovirus and other herpes viruses but are not onco-therapeutic. Radiation therapy or surgery is indicated for bulky, disseminated or recalcitrant disease. Prognosis varies depending on the type of malignancy identified and stage of disease.

Campath induction for kidney transplantation: report of 297 cases.

OBJECTIVE: To evaluate 297 adult renal transplantation patients who received Campath-1H-based induction protocol. METHODS: Single center Institutional Review Board approved retrospective chart review of 297 patients who received alemtuzumab induction between November 2003 and December 2005. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil, and rapidly tapered solumedrol with few exceptional cases. The mean patient follow-up was 362 days. All rejection episodes were biopsy confirmed. Posttransplant infection rates were recorded. RESULTS: There were 153 living donor and 144 deceased donor recipients. One-year survival rates for recipient and kidney allografts were 100% and 98% for living donors, 97.4% and 89.7% for non-extended criteria donors (ECD) deceased donors, and 85.7% and 89.3% for ECD deceased donors. The overall rejection rate was 7%. Overall infectious rate was 19.8%. We had no cases of posttransplant lymphoproliferative disease. Of the 289 recipients discharged off prednisone, 269 (93%) remain steroid free. CONCLUSION: Alemtuzumab and reduced dosages of tacrolimus and mycophenolate without long-term steroids can achieve low rates of rejection and excellent graft and patient survival without excessive risk of infection or malignancy. There is still a need for large randomized trials with long-term follow-up to determine its exact role in solid organ transplantation.

BK virus and immunosuppressive agents.

The last decade has witnessed the introduction of several potent immunosuppressive agents in the field of transplant medicine. Contemporaneously, infection with BK virus (BKV) has emerged as an important complication of immunosuppression and an important cause of allograft loss after kidney transplantation. Rhandhawa et al reported the first case of BKV associated nephropathy (BKVN) in the modern era of transplantation, in 1995. Since then there has been a resurgence of interest in the epidemiology, biology and pathogenic associations of BKV especially in transplant medicine. Up to 90% of adults have serologic evidence of exposure to BKV. However, only 1-5% of normal healthy adults excrete the virus in the urine (asymptomatic viruria). Thus, for a vast majority of the population, the virus remains perfectly latent and this state of latency is of no obvious consequence. Almost all instances of disease by the BKV have been seen in immunocompromised patients. In recent years, BKV has been associated with nephropathy (BKVN) in about 5% of renal transplant patients. Once established, the disease may result in allograft loss in 45-70% of patients. Although not proven by any prospective study, BKVN causing allograft failure has been linked to immunosuppressive regimens containing tacrolimus or mycophenolate mofetil. This is noteworthy, as both these agents have been used increasingly as the primary maintenance immunotherapy in solid organ transplantation since their introduction around 1990. In addition to the immunosuppressed state, other factors like allograft injury have been thought to be involved in the pathogenesis of the disease. We believe that reactivation of the BKV from its latent state crucially depends on an immunocompromised state but more factors than one dictate precipitation of clinical end organ disease. In this Chapter, we will discuss the clinical aspects of BKV infection in the renal transplant recipient. We will focus on the role of immunosuppression as a seminal factor allowing replication of the virus. Not all patients who have replicating BKV go on to develop nephropathy: we will discuss other host factors that may constitute a 'second hit' allowing replicating BKV to precipitate BKVN. Results of our recently concluded prospective study on the issue of current immunosuppressive agents in the development of BKVN will be discussed. Finally, based on our experience, we will provide some guidelines for early diagnosis and management of this disease.

Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction.

Our purposes were to determine the incidence of BK viruria, viremia or nephropathy with tacrolimus (FK506) versus cyclosporine (CyA) and whether intensive monitoring and discontinuation of mycophenolate (MMF) or azathioprine (AZA), upon detection of BK viremia, could prevent BK nephropathy. We randomized 200 adult renal transplant recipients to FK506 (n = 134) or CyA (n = 66). Urine and blood were collected weekly for 16 weeks and at months 5, 6, 9 and 12 and analyzed for BK by polymerase chain reaction (PCR). By 1 year, 70 patients (35%) developed viruria and 23 (11.5%) viremia; neither were affected independently by FK506, CyA, MMF or AZA. Viruria was highest with FK506-MMF (46%) and lowest with CyA-MMF (13%), p = 0.005. Viruria >/= 9.5 log(10) copies/mL was associated with a 3-fold increased risk of viremia and a 13-fold increased risk of sustained viremia. After reduction of immunosuppression, viremia resolved in 95%, without increased acute rejection, allograft dysfunction or graft loss. No BK nephropathy was observed. Choice of calcineurin inhibitor or adjuvant immunosuppression, independently, did not affect BK viruria or viremia. Viruria was highest with FK506-MMF and lowest with CyA-MMF. Monitoring and preemptive withdrawal of immunosuppression were associated with resolution of viremia and absence of BK nephropathy without acute rejection or graft loss.

Systemic amyloidosis associated with pleomorphic sarcoma of the spleen and remission of nephrotic syndrome after removal of the tumor.

We report a case of a 57-year-old woman who was diagnosed with a systemic AA amyloidosis associated with a pleomorphic sarcoma of the spleen. Although the association and causality between chronic inflammatory states and systemic AA amyloidosis have been well established, the evidence linking solid malignancies to reactive AA amyloidosis is scarce. Our patient had a significant systemic amyloid deposition including biopsy-proven renal and cardiac AA amyloidosis. Subsequent evaluation uncovered the presence of a large splenic mass, which was treated by splenectomy. Histologically the splenic tumor was classified as pleomorphic sarcoma. The removal of the tumor resulted in a marked decline in proteinuria, stable renal and cardiac functions, and symptomatic improvement at 1-year follow-up. Based on the noted improvements, we speculate that the pleomorphic sarcoma of the spleen caused secondary amyloidosis in our case. Stromal tumors, although rare, may be associated with and should be considered in the differential diagnosis of the cause of AA amyloidosis.

Short course induction immunosuppression with thymoglobulin for renal transplant recipients.

BACKGROUND: The aim of this study was to demonstrate that 3-days of induction immunosuppression with thymoglobulin was as effective and safe as a 7-day course and reduced initial hospitalization after transplantation. METHODS: This was a prospective, nonrandomized trial of 40 consecutive patients receiving thymoglobulin induction for 3 days and followed for 1 year. An historical group of 48 patients that received 7 days of thymoglobulin served as controls. RESULTS: At 1 year, acute rejection (5 vs. 4%), graft survival (95 vs. 98%) and patient survival were similar; a composite end point of freedom from death, rejection, or graft loss, the event-free graft survival, was similar as was the safety profile. In the 3-day group, lymphocyte depletion was more sustained and initial hospitalization was significantly shorter (6 vs. 8 days). CONCLUSION: Three-day induction with thymoglobulin is as effective and safe as seven days, decreases initial hospitalization and causes more sustained lymphocyte depletion.