Preemptive renal transplant: too early is not always better-a national cohort study.

BACKGROUND: Preemptive renal transplants (PRT) confer better outcomes than renal transplants performed after initiation of hemodialysis. PRTs are occurring at progressively higher residual recipient renal function. METHODS: We evaluated donor, recipient, and transplant characteristics of 26,384 preemptive transplants between 2010 and 2019 using the United Network of Organ Sharing (UNOS) database. Recipients of PRTs were divided into four distinct groups depending upon the glomerular filtration rate (GFR) (GFR [Formula: see text] 10, 10 < GFR [Formula: see text] 15, 15 < GFR [Formula: see text] 19 and > 19, ml/min/1.73 m2) at the time of transplant. We followed graft and patient survival for five years and assessed donor, recipient, and transplant characteristics such as race, gender, and type of insurance. RESULTS: PRTs occurring at GFR > 19 ml/min (early preemptive renal transplants, ePRT) from live and deceased donors were not associated with improved graft nor patient survival compared to the other preemptive transplants. PRTs occurring at GFR range of 10-15 ml/min conferred the best graft survival. Black donor-recipient pairs were 54% less likely to be involved in ePRT, while non-Hispanic White donor-recipient pairs were 20% more likely to receive ePRT. CONCLUSION: ePRT represents misallocation of valuable organ resources and a waste of native renal function. There is no evidence that ePRT is associated with superior graft or patient survival compared to the other preemptive transplants. Conversely, ePRT produces poorer graft and patient survival outcomes compared to the other PRTs. GFR range of 10-15 ml/min is optimal and associated with superior outcomes.

Relapse of Nephrotic Syndrome after Adrenocorticotropic Hormone-Induced Remission: Implications of Adrenocorticotropic Hormone Antibodies.

BACKGROUND: Prolonged use of corticosteroids continues to be the mainstay in the management of most proteinuric glomerulopathies, but is limited by extensive side effects. Alternative medications such as adrenocorticotropic hormone (ACTH) have been recently used to treat refractory glomerulopathies and have shown superior outcomes when compared with steroids. However, the clinical responsiveness to ACTH therapy varies considerably with a number of patients exhibiting de novo or acquired resistance. The underlying mechanism remains unknown. METHODS: A patient with steroid-dependent focal segmental glomerulosclerosis (FSGS) developed severe steroid side effects impacting quality of life and was converted to repository porcine ACTH therapy. Immediate response in the form of remission of nephrotic syndrome was noted followed by relapse in 10 weeks. Suspecting the role of some ACTH-antagonizing factors, the patient's serum was examined. RESULTS: Immunoblot-based antibody assay revealed high titers of de novo IgG antibodies in the patient's serum that were reactive to the porcine corticotropin with negligible cross-reactivity to human corticotropin. In vitro, in cultured B16 melanoma cells that express abundant melanocortin receptors, addition of the patient's serum substantially abrogated the porcine corticotropin triggered signaling activity of the melanocortinergic pathway, marked by phosphorylation of glycogen synthase kinase 3ß, thus suggesting a mitigating effect on the biological functionality of porcine corticotropin. CONCLUSION: ACTH is a useful alternative therapeutic modality for refractory proteinuric glomerulopathies like FSGS. However, as quintessential therapeutic biologics, natural ACTH, regardless of purity and origin, is inevitably antigenic and may cause the formation of neutralizing antibodies in some sensitive patients, followed by resistance to ACTH therapy. It is imperative to develop ACTH analogues with less immunogenicity for improving its responsiveness in patients with glomerular diseases.