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Obesity as a risk factor for CKD

Stephan J. L. Bakker

UMC Groningen, The Netherlands
MAY 11th  SYMPOSIUM 7 – HALL VICTORIA 14.30-16.00

The prevalence of obesity in children and adults is rapidly increasing in most regions of the world. Obesity is an established risk factor for type 2 diabetes and hypertension, both risk factors for CKD. Many lines of evidence now come together to identify obesity also as an independent risk factor for CKD, even in the absence of type 2 diabetes and hypertension. The early renal phenotype of obesity is characterised by varying degrees of renal hyperperfusion and glomerular hyperfiltration. If measured by conventional methods, this phenotype presents itself as an abnormally “good” rather than a poor renal function, analogous to the early renal phenotype of type 1 diabetes. The early renal phenotype is not only characterised by these changes in intrarenal hemodynamics, but also by structural changes, which include varying degrees of nephromegaly (primarily due to expansion of the tubular compartment) and glomerulomegaly. Obesity seems to recruit otherwise dormant renal reserve capacity for functioning. This renal reserve capacity is otherwise recruited with loss of functioning renal tissue with ageing, and sometimes suddenly with uninephrectomy, which induces intrarenal hemodynamic and structural changes in the remaining kidney similar to those of the early renal phenotype of obesity in both kidneys. Thus, obesity seems to compete with any other renal insult, including ageing, for recruitable renal reserve capacity, and thus offsets kidneys for an earlier and hastened decline of renal function. The moment of the late renal phenotype of obesity to come – although undoubtedly with much intra-individual variation – is characterised by onset of microalbuminuria, when renal function assessed by conventional methods is still frequently abnormally “good” if no other renal insult has been imparted. These kidneys are at high risk for progression to macroalbuminuria and decline in function to end-stage renal disease. Current renoprotective treatment regimens are only partly successful in preventing this. Clues for new and additional renoprotective treatments may come from a better understanding of the pathophysiology of the early renal phenotype of obesity. Increased exposure to growth factors such as hepatocyte growth factor and insulin-like growth factor, possibly released from adipose tissue or “fatty liver”, may play a role. Lipotoxicity is now a well-established phenomenon in pancreatic ß-cells, liver, myocardium, and skeletal muscles, and may also appear to play a role in renal damage associated with obesity in kidneys. Another possibility is that the kidney is just responding to “nutrient waste overflow”, which is also causing obesity. This might imply that it is not obesity itself, but diet or other environmental factors which contribute to the development of obesity which actually underlie the early renal phenotype associated with obesity. Our understanding of the underlying processes is slowly increasing, but meanwhile time to prevent the pandemic of obesity from exploding into a pandemic of end-stage renal disease is ticking away…