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Leveraging melanocortin pathways to treat glomerular diseases.

ABSTRACT: The melanocortin system is a neuroimmunoendocrine hormone system that constitutes the fulcrum in the homeostatic control of a diverse array of physiological functions, including melanogenesis, inflammation, immunomodulation, adrenocortical steroidogenesis, hemodynamics, natriuresis, energy homeostasis, sexual function, and exocrine secretion. The kidney is a quintessential effector organ of the melanocortin hormone system with melanocortin receptors abundantly expressed by multiple kidney parenchymal cells, including podocytes, mesangial cells, glomerular endothelial cells, and renal tubular cells. Converging evidence unequivocally demonstrates that the melanocortin-based therapy using the melanocortin peptide adrenocorticotropic hormone (ACTH) is prominently effective in inducing remission of steroid-resistant nephrotic syndrome caused by various glomerular diseases, including membranous nephropathy, minimal change disease and focal segmental glomerulosclerosis, suggesting a steroidogenic-independent mechanism. Mechanistically, ACTH and other synthetic melanocortin analogues possess potent proteinuria-reducing and renoprotective activities that could be attributable to direct protection of glomerular cells and systemic immunomodulation. Thus, leveraging melanocortin signaling pathways using ACTH or novel synthetic melanocortin analogues represents a promising and pragmatic therapeutic strategy for glomerular diseases. This review article introduces the biophysiology of the melanocortin hormone system with an emphasis on the kidney as a target organ, discusses the existing data on melanocortin therapy for glomerular diseases, and elucidates the potential mechanisms of action.

SUBMITTER: Gong R

PROVIDER: S-EPMC3950821 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Leveraging melanocortin pathways to treat glomerular diseases.

Gong Rujun R

Advances in chronic kidney disease 20140301 2

The melanocortin system is a neuroimmunoendocrine hormone system that constitutes the fulcrum in the homeostatic control of a diverse array of physiological functions, including melanogenesis, inflammation, immunomodulation, adrenocortical steroidogenesis, hemodynamics, natriuresis, energy homeostasis, sexual function, and exocrine secretion. The kidney is a quintessential effector organ of the melanocortin hormone system with melanocortin receptors abundantly expressed by multiple kidney parenc ...[more]

PMID: 24602463

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Project description:Background and objectivesSocial deprivation is a recognized risk factor for undifferentiated CKD; however, its association with glomerular disease is less well understood. We sought to investigate the relationship between socioeconomic position and the population-level incidence of biopsy-proven glomerular diseases.Design, setting, participants, & measurementsIn this retrospective cohort study, a provincial kidney pathology database (2000-2012) was used to capture all incident cases of membranous nephropathy (n=392), IgA nephropathy (n=818), FSGS (n=375), ANCA-related GN (ANCA-GN, n=387), and lupus nephritis (n=389) in British Columbia, Canada. Quintiles of area-level household income were used as a proxy for socioeconomic position, accounting for regional differences in living costs. Incidence rates were direct standardized to the provincial population using census data for age and sex and were used to generate standardized rate ratios. For lupus nephritis, age standardization was performed separately in men and women.ResultsA graded increase in standardized incidence with lower income was observed for lupus nephritis (P<0.001 for trend in both sexes) and ANCA-GN (P=0.04 for trend). For example, compared with the highest quintile, the lowest income quintile had a standardized rate ratio of 1.7 (95% confidence interval, 1.19 to 2.42) in women with lupus nephritis and a standardized rate ratio of 1.5 (95% confidence interval, 1.09 to 2.06) in ANCA-GN. The association between income and FSGS was less consistent, in that only the lowest income quintile was associated with a higher incidence of disease (standardized rate ratio, 1.55; 95% confidence interval, 1.13 to 2.13). No significant associations were demonstrated for IgA nephropathy or membranous nephropathy.ConclusionsUsing population-level data and a centralized pathology database, we observed an inverse association between socioeconomic position and the standardized incidence of lupus nephritis and ANCA-GN.

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Leveraging melanocortin pathways to treat glomerular diseases.

Publications

Leveraging melanocortin pathways to treat glomerular diseases.

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