The Genetic Landscape of Renal Complications in Type 1 Diabetes

Diabetes is the leading cause of end stage renal disease. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2,843 subjects, we estimated that the heritability of diabetic kidney disease was 35% ( p=6x10-3 ). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index ( p=2.2×10-5) and the risk of type 2 diabetes (p=6.1x10-4 ) were associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation ( p=1.1×10-4 ). Pathway analysis implicated ascorbate and aldarate metabolism ( p=9×10-6), and pentose and glucuronate interconversions ( p=3×10-6) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.  

Renal palliative care – where to after the PACKS study?

The PAlliative Care in chronic Kidney diSease study (PACKS study) is examining quality of life, decision making and decisional conflict, costs and mortality in patients with advanced chronic kidney disease who have opted for palliative care. It is also exploring the impact of the decision on the quality of life of carers. The study includes adult patients with end stage (stage 5) chronic kidney disease who have opted for palliative care, adult carers of these patients and renal physicians/clinical nurse specialists who have experience of treating patients with end stage chronic kidney disease who have opted for palliative care.
Early initial findings relate to clinician perspectives on patient decisional conflict, in making complex decisions between dialysis and conservative management. Interviews were conducted with nephrologists and clinical nurse specialists across 10 renal centres in the UK. Themes with associated subthemes include “Frequent changing of mind regarding treatment options,” “A paternalistic approach to decision-making and “Intricacy of the decision”. These findings will be presented and recommendations for future research and education made. Clinicians need to take a more patient centered approach to decision-making. Interventions aimed at increasing understanding of renal disease and its treatments may reduce decisional conflict and raise decisional quality but require testing in the renal specialty.