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A prospective study of 31 chronically hemodialyzed patients was made to investigate the incidence and pathology of pulmonary calcification and the relation of the latter to ventilatory function. Fifteen of the patients have died thus far; 9 had evidence of lung calcification. The lesions occurred predominately in alveolar septa and were associated with varying degrees of fibrosis and alveolar septal thickening. Only one patient had X-ray evidence of calcification. An X-ray diffraction analysis showed a predominant pattern of whitlockite (CaMg)3(Po4)2 in deposits. Patients with the severest pulmonary calcification had abnormalities of vital capacity, carbon monoxide diffusion, and Po2. Serum calcium levels were slightly higher in patients with calcification, but there was no measurable association with the duration of dialysis, serum phosphorus, calcium X phosphorus product, magnesium, bicarbonate, or arterial pH. These data show that pulmonary calcification occurs with high frequency in patients undergoing long-term hemodialysis and that such lesions are associated with restrictive and diffusion ventilatory defects.

The aluminum content of muscle, bone and brain was measured in control subjects and in uremic patients on dialysis who had been maintained on phosphate-binding aluminum gels. The mean muscle aluminum was 14.8 ppm, and the trabecular-bone aluminum 98.5 ppm in the patients on dialysis, as compared with 1.2 and 2.4 in control subjects (P less than 0.05). Brain gray-matter aluminum values in a group of uremic patients on dialysis who died of a neurologic syndrome of unknown cause were 25 ppm as compared with 6.5 ppm in a group of uremic patients on dialysis who died of other causes and 2.2 ppm in control subjects. The fact that brain gray-matter aluminum was higher in all patients with the dialysis-associated encephalopathy syndrome than any of the control subjects or other uremic patients on dialysis suggests that this syndrome may be due to aluminum in intoxication.

To evaluate the mechanism by which phosphate induces renal injury, we placed uninephrectomized, partially nephrectomized, and intact rats on dietary phosphorus intakes varying between 0.5 and 2% for 18 weeks. None of the animals on a normal phosphorus intake (0.5%) had any abnormalities. Four out of six intact animals on a 1% phosphorus diet had kidney calcium concentrations within the normal range, and only one showed any histologic changes. In contrast, all but one partial and uninephrectomized animals on a 1% phosphorus diet had increased kidney calcium content concentration, and five of the six studied had histologic changes. The degree of calcification and histologic changes in the uninephrectomized animals on a 1% phosphorus diet was similar to that found in the intact animals on a 2% phosphorus diet. Animals on a 3% phosphorus diet plus disodium ethane-1-hydroxy-1-1-diphosphonate (EHDP) had significantly less calcification and histologic changes than did animals on a similar diet without EHDP. Conclusion. As renal functional mass is reduced, the nephrotoxicity of phosporus is greatly enhanced. Phosphorus-induced renal injury is mediated through calcium phosphate deposition in the kidney. This results from intrarenal caused, because the kidney calcification can be related to phosphate excreted per functional unit rather than plasma phosphate concentrations.

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To investigate the possibility that premature infants may be vulnerable to aluminum toxicity acquired through intravenous feeding, we prospectively studied plasma and urinary aluminum concentrations in 18 premature infants receiving intravenous therapy and in 8 term infants receiving no intravenous therapy. We also measured bone aluminum concentrations in autopsy specimens from 23 infants, including 6 who had received at least three weeks of intravenous therapy. Premature infants who received intravenous therapy had high plasma and urinary aluminum concentrations, as compared with normal controls: plasma aluminum, 36.78 +/- 45.30 vs. 5.17 +/- 3.1 micrograms per liter (mean +/- S.D., P less than 0.0001); urinary aluminum:creatinine ratio, 5.4 +/- 4.6 vs. 0.64 +/- 0.75 (P less than 0.01). The bone aluminum concentration was 10 times higher in infants who had received at least three weeks of intravenous therapy than in those who had received limited intravenous therapy: 20.16 +/- 13.4 vs. 1.98 +/- 1.44 mg per kilogram of dry weight (P less than 0.0001). Creatinine clearances corrected for weight did not reach expected adult values until 34 weeks of gestation. Many commonly used intravenous solutions are found to be highly contaminated with aluminum. We conclude that infants receiving intravenous therapy have aluminum loading, which is reflected in increased urinary excretion and elevated concentrations in plasma and bone. Such infants may be at high risk for aluminum intoxication secondary to increased parenteral exposure and poor renal clearance.

Aluminum levels were measured in a variety of tissues obtained from 36 control subjects, 30 nondialyzed uremic patients, 57 dialyzed uremic patients dying of a variety of different causes, and 38 dialyzed uremic patients dying of dialysis encephalopathy. The low aluminum levels consistently found in the control tissues support the fact that in health aluminum is largely excluded from the body. However, this ability to prevent aluminum accumulation is overcome with renal failure. Bone and liver aluminum levels were found to be significantly increased in 82% and 56% respectively in nondialyzed uremic patients and in 100% of the tissues examined from dialyzed uremic patients. In patients dying of dialysis encephalopathy, tissue aluminum levels were not only the highest but also affected in a different manner than that found in other dialyzed patients. It is suggested that dialysis encephalopathy occurs as a result of such rapid aluminum loading during dialysis that bone's ability to sequester this element is overcome, and it is shunted to liver and brain with resulting toxicity.

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