Effective blood pressure control, especially of the systolic component, is of primary importance in both primary and secondary prevention of Cardiovascular and Cerebrovascular Events. Similarly, systolic blood pressure control is important in the primary and secondary prevention of chronic kidney disease (CKD), and in patients for whom kidney function is already affected, the focus is on preventing the worsening of their current condition, which is described as slowing the “progression” of CKD. Progression of CKD is usually quantified as the linear slope with time of changes in the glomerular filtration rate, expressed as ml/min/1.73 m2/year. In addition to systolic blood pressure, control of hyperlipidemia, anemia management, smoking cessation and dietary salt intake at the recommended daily allowance of 2.4 grams of sodium are part of the general approach to optimizing outcomes in patients with CKD.
Proteinuria is an important biomarker is many forms of CKD, including type I, and type II diabetes mellitus. Even in forms of CKD not usually associated with proteinuria (e.g., autosomal dominant polycystic kidney disease), reduction of urine protein excretion with “anti-proteinuric” therapy can have a beneficial effect on the rate of progression CKD. Proteinuria is a biomarker of kidney damage, and may also directly contribute to the ongoing damage to the kidney in CKD associated with proteinuria. Angiotensin converting enzyme inhibitors (ACEIs), and angiotensin type 1-receptor blockers (ARBs), used either alone or in combination are the mainstays of antiproteinuric therapy. This effect is well described, and seems greater than that seen with other classes of antihypertensive therapy, giving rise to the feeling that these agents have beneficial effects above and beyond what can be achieved with blood pressure control alone.
At present, there is a balancing act between the control of blood pressure and control of proteinuria. Even in the most well defined outcome studies of type I, and type II diabetes, the outcomes with respect to slowing the rate of progression of CKD, though significant, do not achieve the ultimate goal of reducing the progression rate to < 1 ml/min/1.73 m2/year.
A new paradigm is emerging that focuses directly on the control of proteinuria to less than 0.5 grams/day with ACEI/ARB therapy and also other non-traditional forms of therapy including other forms of RAS blockers, vitamin D, and other agents.
These issues will be put in focus for the case of Fabry nephropathy. Fabry disease is a rate multi-system disease caused by a mutation in the alpha-galactosidase A gene on the X-chromosome. It is a progressive form of proteinuric CKD, but in contrast to diabetes, the systolic blood pressure is not usually elevated, which makes the utilization of traditional anti-proteinuric therapy challenging.
In conclusion, the importance of control of proteinuria in slowing the progression of CKD will be emphasized with the use of a combination of treatment approaches to achieve this goal. In this context, control of proteinuria, per se, rather than lowering the systolic blood pressure to an arbitrary, fixed goal becomes the primary outcome measure. While this approach clearly has merit, long-term outcome studies are need before reduction of urinary protein excretion can be accepted as a surrogate endpoint for slowing the progression of CKD.
