Chapter 22. Slowing the Progression of Chronic Kidney Disease

• Estimated glomerular filtration rate (GFR) <60 mL/minute/1.73 m2.
• Proteinuria or hematuria.
• Hypertension.
• Focal and segmental sclerosis and tubulointerstitial fibrosis on renal biopsy.

End-stage renal disease (ESRD) represents a major challenge to health care providers around the globe. It is estimated that in 2001 there were approximately 1.1 million people receiving dialysis worldwide and this number is projected to rise by 7% per year to over 2 million by 2010. The financial costs of dialysis provision are considerable and projected worldwide expenditure on dialysis treatment for the decade 2000–2010 is expected to exceed US$ 1 trillion. Whereas chronic dialysis does prolong life in ESRD, it is associated with an annual mortality of approximately 20%, representing a survival rate worse that many common forms of cancer. Renal transplantation does offer improved survival and quality of life, but the majority of patients are not medically suitable for transplantation and a universal shortage of donor organs continues to restrict the number of transplants performed.

Against this background it is critical to appreciate that the majority of cases of ESRD result from the slow progression of chronic kidney disease (CKD) over many months or years. There is therefore an opportunity to intervene in the course of CKD to slow the rate of decline in renal function and thereby reduce the number of patients requiring renal replacement therapy. In this chapter we review the mechanisms that contribute to CKD progression as well as clinical aspects and interventions that are effective in slowing the rate of decline in renal function.

CKD should be viewed as a clinicopathologic syndrome (defined above) that ensues after renal injury resulting from a wide range of kidney pathologies. This suggests that the progressive decline in renal function that is characteristic of CKD results from a common set of mechanisms that is largely independent of the initiating renal pathology. Intensive research over the past three decades has identified several interacting mechanisms that together produce a vicious cycle of progressive nephron loss resulting in ESRD (Figure 22–1).

Glomerular Hemodynamic Factors

Studies in animal models of CKD reported that when the nephron number was severely reduced by surgical ablation, marked hemodynamic changes were observed in the remaining glomeruli, characterized by a substantial increase in the filtration rate of each glomerulus (single nephron glomerular filtration rate, SNGFR) that resulted in part from an increase in glomerular capillary hydraulic pressure (Pgc). Whereas these adaptations initially allowed partial compensation for ...