HDCN Article Review/Hyperlink

Merkel PA, Chang Y, Pierangeli SS, Convery K, Harris EN, Polisson RP

Prevalence and clinical associations of anti-cardiolipin antibodies in a large inception cohort of patients with connective tissue diseases

Am J Med (Dec) 101:576-583 1996

Hypertension is the second most common cause of end-stage renal disease in the U.S. overall and the most common cause in African-Americans. The relative incidence of new ESRD caused by hypertension in AAs is 6-fold higher than non AAs. There are probably many reasons for this rather large discrepancy in rates of disease including higher prevalence of hypertension, more severe hypertension, access to better medical care and others. However, the entire difference cannot be accounted for on the basis of known risk factors. Moreover, the proof that ESRD is actually caused by hypertension in any population has not been forthcoming because very few individuals undergo renal biopsy.

In this study 46 of 95 participants in the AASK study underwent renal biopsy either prior to or at the time of enrollment into baseline of the pilot study. Study entry criteria included hypertension (seated diastolic > 95 mmHg), age range 18-70 and a GFR range of 2-70 ml/min/1.73 m2. Patients with diabetes and heavy urine protein/creatinine ratio > 2.5 were excluded. Biopsy material was subjected to light, immunofluorescence and electron microscopy. Adequate biopsies were available in 39 of the 46 participants and 38 of those showed arteriosclerosis and/or arteriolosclerosis. Segmental sclerosis was present in 5 of these cases and 1 patient had clinical findings suggesting focal segmental glomerulosclerosis. Interestingly, global glomerulosclerosis was present in 43% of cases and this lesion correlated positively with systolic blood pressure, serum cholesterol, reciprocal of serum creatinine and interstitial fibrosis.

The authors concluded that renal biopsies in AA with mild to moderate renal insufficiency in the absence of marked proteinuria are overwhelmingly likely to reveal vascular lesions consistent with hypertensive nephrosclerosis.

Comment: This is an important study for several reasons. First, the demographic characteristics of this study population match those of published at high risk populations for ESRD attributed to hypertension indicating that this is the target population sought for in the AASK study. Second, the kidney biopsy in this situation strongly supports the clinical diagnosis of hypertensive nephrosclerosis. Third, it possible that there is an important pathogenetic link between the global glomerulosclerosis and systolic hypertension and perhaps hypercholesterolemia.

These data may help to find additional markers that indicate increased risk of progressive renal disease and perhaps point a way towards better therapies that can reduce risk or halt disease progression in the future. (Robert D. Toto, M.D., University of Texas Southwestern