Donald J. Sherrard

The survival experience of 39 patients receiving long-term regular hemodialysis in Seattle since 1960 was studied with particular reference to mortality and morbidity from arteriosclerotic cardiovascular complications. Mean age (± 1 S.D.) was 37.0 ± 9.5 years for the group at the start of dialysis. Mean duration of treatment was 6.5 years (range, one to 13). Overall mortality was 56.4 per cent at the end of the 13-year follow-up period, and 14 of 23 deaths could be attributed to arteriosclerotic complications: myocardial infarction was responsible for eight, strokes for three, and refractory congestive heart failure for three deaths. The incidence of these complications was many times higher than for normal and hypertensive groups of comparable age, and similar to rates found in Type 2 hyperlipoproteinemia. These results indicate that accelerated atherosclerosis is a major risk to long-term survivors on maintenance hemodialysis. (N Engl J Med 290:697–701, 1974)

Elevated serum phosphate levels have been linked with vascular calcification and mortality among dialysis patients. The relationship between phosphate and mortality has not been explored among patients with chronic kidney disease (CKD). A retrospective cohort study was conducted from eight Veterans Affairs' Medical Centers located in the Pacific Northwest. CKD was defined by two continuously abnormal outpatient serum creatinine measurements at least 6 mo apart between 1999 and 2002. Patients who received chronic dialysis, those with a present or previous renal transplant, and those without a recent phosphate measurement were excluded. The primary end point was all-cause mortality. Secondary end points were acute myocardial infarction and the combined end point of myocardial infarction plus death. A total of 95,619 veterans with at least one primary care or internal medicine clinic contact from a Northwest VA facility and two or more outpatient measurements of serum creatinine, at least 6 mo apart, between January 1, 1999, and December 31, 2002, were identified. From this eligible population, 7021 patients met our definition of CKD. After exclusions, 6730 CKD patients were available for analysis, and 3490 had a serum phosphate measurement during the previous 18 mo. After adjustment, serum phosphate levels >3.5 mg/dl were associated with a significantly increased risk for death. Mortality risk increased linearly with each subsequent 0.5-mg/dl increase in serum phosphate levels. Elevated serum phosphate levels were independently associated with increased mortality risk among this population of patients with CKD.

A histochemical stain for bone aluminum allowed us to determine the prevalence and staining characteristics of aluminum in renal osteodystrophy. The staining method correlated well with the results of atomic-absorption studies in 96 samples (r = 0.81; P less than 0.001). We examined 315 bone-biopsy samples. No aluminum was seen in controls or patients with nonrenal bone disease. In renal osteodystrophy, the mean level of stainable aluminum was significantly higher in osteomalacic lesions (1.12 +/- 0.09 mm per square millimeter of tissue area) than in mild, mixed, of fibrotic lesions (0.43 +/- 0.06, 0.34 +/- 0.11, and 0.10 +/- 0.03 mm per square millimeter, respectively; P less than 0.001). Seventy per cent of osteomalacic samples had heavy aluminum staining. The bone-apposition rate, measured by double tetracycline labels, was low in 89 per cent of the samples with high levels of aluminum. The mean level of stainable bone aluminum in patients who had a clinical response to calcitriol was significantly lower than in those who did not respond (0.13 +/- 0.4 vs. 1.06 +/- 0.9 mm per square millimeter; P less than 0.01). We conclude that aluminum deposition is associated with impaired bone formation or mineralization and with a poor response to calcitriol therapy.