Nephrology:  Back to the Basics

John C. Wang, M.D., Ph.D.

(CAMS 2003 Annual Scientific Award Lecture)

          Although there are many new advances in the treatment, renal disease continues to be a significant problem among the U.S. population.  End-stage renal disease (ESRD), an all too common end result of renal disease, is a major health care issue.  There has been a steady increase in the reported prevalence and incidence of ESRD over the past two decades, as determined by the U.S. Renal Data System.  Factors contributing to the increase include (1) increased prevalence of diabetic mellitus (2) improved survival of patients with chronic diseases, and (3) aging of the U.S. population.

          The economic and social costs of renal disease are increasing steeply.  It is important to understand the causes of renal diseases, to prevent the progression, and to provide adequate care for patients with renal disease, including ESRD.

         At present an estimated 16 million Americans have diabetes mellitus ( > 90% type II).  Approximately 800,000 new cases are diagnosed every year.  In adults, diabetes may be one of the most common causes of renal disease, as reflected in the ESRD patient population.  The number of ESRD patients in the U.S. is projected to reach more than half a million by the year 2008.  Diabetes is the most common cause, serving as the primary diagnosis for 50.1% of patients who start dialysis.  Hypertension is the second most common primary diagnosis, accounting for 27% of new dialysis cases.  Other diagnoses, such as glomerulopathy, together account for only 23%.

        The deleterious cardiovascular effects of diabetes began even before the onset of overt diabetes, when functional changes in the microvasculature and early signs of diabetes may be evident.  Hypertension and the development of microalbuminuria also occur early in the course of disease pathogenesis, whereas evidence of advanced renal disease, such as the presence of overt proteinuria, renal failure, and, ultimately, ESRD are relatively late occurrences in the natural history of diabetes.

       The early development of cardiovascular disease in patients with diabetes may reflect the underlying vascular and endothelial damage caused by insulin resistance and hyperglycemia.  Since the kidneys are an integral part of the cardiovascular system, it is not surprising that clinical evidence of cardiovascular disease accompanies the development of diabetic nephropathy.

      The large United Kingdom Prospective Diabetes Study evaluated the role of glycemic control in reducing microvascular and macrovascular complications of type II diabetes.  The risk of any diabetes – related end point was 12% lower with intensive glucose control vs less intensive control.  The effect of tight vs less tight blood pressure control were also examined in the cohort of diabetes patients with hypertension in this study.  Compared with less tight control, tight BP control was associated with a 24% reduction in diabetes – related end points with 37% reduction in microvascvular disease.

       The most recent NHANES III documents only 31% of all those identified as hypertensive had their BP controlled to a goal of < 140/90 mmHg.  Among diabetics, approximately 75% receiving treatment for hypertension did not have blood pressure goal currently recommended by the JNC VII of <130/80 mmHg.

      Both diuretics and β-blockes can be valuable in the treatment of patients with hypertension.  However, the evolving paradigm of hypertension treatment emphasizes the need for multi drug therapy in high-risk conditions with compelling indication.  In patients with diabetes, agents that block the rennin-angiotension system (ie, ACE inhibitors and ARB) and calcium channel blockers provide complementary effects in terms of cardio-renal protection.

      In conclusion, setting aggressive treatment targets will lead to better cardio-renal protection in the hypertension patient with diabetes.  And, hopefully, via tight glycemic control and BP control, the explosion of prevalence and incidence of renal disease / ESRD will be halted.

(Dr. Wang is Associate Professor of Clinical Medicine & Surgery, Weill Medical College of Cornell University)