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Kidney disease, genotype and the pathogenesis of vasculopathy
Patrick S Hayden1, Sudha K Iyengar, Jeffrey R Schelling
1Department of Medicine, School of Medicine, Case Western Reserve University, and Rammelkamp Center for Research and Education, MetroHealth Medical Center, Cleveland, Ohio 44109-1998, USA.
Insights
Genetic factors may play a role in the development of kidney disease, particularly in cases linked to diabetes and hypertension. Understanding these genetic determinants is crucial for developing new treatments for chronic kidney failure.
Area of Science:
- Nephrology
- Genetics
- Vascular Biology
Background:
- Diabetes mellitus and hypertensive nephrosclerosis are the primary causes of end-stage renal disease in the US.
- Vascular complications, including small- and large-vessel disease, are common in these conditions.
- Emerging evidence suggests renal vascular disease may independently contribute to kidney failure progression.
Purpose of the Study:
- To review current understanding of vasculopathy in renal disease.
- To summarize evidence linking genetic factors to renal vascular disease.
- To explore the role of genetic determinants in common causes of chronic kidney failure.
Main Methods:
- Review of population- and family-based epidemiological studies.
- Analysis of segregation in families with diabetic nephropathy.
- Positional cloning of genes associated with rare familial glomerulosclerosis syndromes.
Main Results:
- Genetic factors are hypothesized to regulate renal disease pathogenesis.
- Evidence suggests genetic determinants for vascular phenotypes are associated with chronic renal failure.
- The review highlights developments in understanding vasculopathy's role in kidney disease.
Conclusions:
- Genomics and proteomics offer new avenues for drug discovery in kidney disease.
- Identification of renal susceptibility genes can reveal novel disease mechanisms.
- Novel therapeutic targets for kidney disease can be generated through genetic research.
Purpose Of Review:
The two leading causes of end-stage renal disease in the United States are diabetes mellitus and hypertensive nephrosclerosis, accounting for over two-thirds of all cases. In many patients both diseases are associated with small- and large-vessel disease, commonly attributed to hypertension or accelerated atherosclerosis. Recent investigations, however, have suggested that renal large-vessel and microvascular disease may be independent contributors to progressive kidney failure.
Recent Findings:
Although genes have not been definitely linked to renal vascular disease, population- and family-based epidemiology of kidney disease, segregation analysis of Pima and Caucasian families in which diabetic nephropathy is clustered, and the positional cloning of genes responsible for rare, familial glomerulosclerosis syndromes support the hypothesis that genes regulate the pathogenesis of renal disease. This review highlights developments in our current understanding of vasculopathy and its role in renal disease, and it summarizes evidence suggesting that genetic determinants for the vascular phenotype are associated with common causes of chronic renal failure.
Summary:
With the application of genomics and proteomics methodologies to drug discovery, the identification of renal susceptibility genes should identify new mechanisms of progressive renal disease pathogenesis and generate novel target molecules for the treatment of kidney disease.