Biomedical subjects
N D Adams
Publications and source records attributed to N D Adams.
Case report: autosomal dominant polycystic kidney disease.
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Nephrocalcinosis.
The pathogenesis of NC in VLBW infants appears to be multifactorial. The vulnerability of extreme immaturity and the underdevelopment of renal function may be the most important variables. In some ways, we view this problem as similar to that of retinopathy of prematurity. (Clearly the exposure of the retina to high partial pressures of oxygen contributes to the development of retinopathy of prematurity but other variables--some known, such as an immature retina, and others not yet defined--must be present.) Hypercalciuria is common in the VLBW infant, yet not all develop NC. Decreased glomerular filtration rate, low citrate excretion, and frequently an alkaline urine are in part due to the immaturity of renal function of these infants. The need for prolonged hyperalimentation resulting in increased oxalate excretion and the development of BPD frequently requiring diuretics that may cause phosphaturia and magnesium depletion and that may increase calcium excretion are more common in the smallest and sickest of premature infants. Even transient insults to the kidneys, such as hypoxia or hypotension or the use of nephrotoxic drugs that provoke tubular injury and cell death with the probability of crystal formation and growth by way of heterogeneous nucleation, are likely to occur more frequently in this vulnerable population.
Effect of high calcium and phosphorus intake on mineral retention in very low birth weight infants chronically treated with furosemide.
The treatment of premature infants with the diuretic furosemide appears to be a contributory factor in the development of metabolic bone disease presumably because of furosemide-induced hypercalciuria. In this study, we measured calcium and phosphorus balance in furosemide-treated very low birth weight infants (VLBW) infants with bronchopulmonary dysplasia (BPD) who were fed a specialized premature formula containing increased amounts of calcium and phosphorus. Furosemide-treated infants received 166 +/- 37 mg/kg/day and retained 80 +/- 34 mg/kg/day of calcium, and 87 +/- 19 mg/kg/day and retained 52 +/- 14 mg/kg/day of phosphorus. The amounts retained were approximately 65% of the calcium and 72% of the phosphorus requirements for in utero mineral accretion. Compared to a group of similarly fed VLBW infants without BPD and not treated with the diuretic, the furosemide-treated infants excreted a larger percent of the calcium intake in the urine but had similar total urinary calcium and phosphorus losses (mg/kg/day) and serum calcium, phosphorus, alkaline phosphatase, and parathyroid hormone (PTH) levels. From the latter two findings, we suggest that the extra mineral content of the formula may have promoted bone mineralization and prevented the occurrence of secondary hyperparathyroidism.
Absence of anion gap metabolic acidosis in severe methanol poisoning: a case report and review of the literature.
Methanol poisoning in humans is characterized by a latent period with subsequent development of anion gap metabolic acidosis and blindness. We describe a patient with potentially lethal methanol ingestion as evidenced by an admission serum methanol level of 403 mg/dL and sustained serum methanol levels greater than 50 mg/dL for more than 18 hours after ingestion, despite hemodialysis therapy. That anion gap metabolic acidosis or visual impairment did not develop in this patient was attributed to documented prior ethanol ingestion (admission serum ethanol level of 158 mg/dL) and continued ethanol administration during hospitalization (sustained serum ethanol levels greater than 100 mg/dL). This case demonstrates the ability of ethanol to inhibit the metabolism of methanol to formic acid in humans. This inhibition was achieved without induction of lactic acidosis. Thus this case documents the efficacy of ethanol therapy in patients with methanol poisoning.
Review: Renal osteodystrophy--pathogenesis and treatment.
Histologic bone changes of osteitis fibrosa and osteomalacia are commonly present in patients with end-stage renal disease. Although many patients are not symptomatic from these bone changes, some patients are severely disabled. Altered metabolism of vitamin D, calcium, phosphorus, and parathyroid hormone occurs in renal failure and contributes to the development of uremic bone disease. This article reviews the current theories of pathogenesis and treatment of renal osteodystrophy. In addition, the clinical presentation, pathogenesis, and treatment of the various aluminum-associated osteomalacic syndromes in uremia are discussed.
Renal osteodystrophy--pathogenesis and treatment.
Histologic bone changes of osteitis fibrosa and osteomalacia are commonly present in patients with end-stage renal disease. Although many patients are not symptomatic from these bone changes, some patients are severely disabled. Altered metabolism of vitamin D, calcium, phosphorus, and parathyroid hormone occurs in renal failure and contributes to the development of uremic bone disease. This article reviews the current theories of pathogenesis and treatment of renal osteodystrophy. In addition, the clinical presentation, pathogenesis, and treatment of the various aluminum-associated osteomalacic syndromes in uremia are discussed.
Effects of weight loss on serum 1,25-(OH)2-vitamin D concentrations in adults: a preliminary report.
During a review of 42 metabolic studies in healthy women and men we observed that serum 1,25-(OH)2-D concentrations were directly correlated to the observed daily changes in body weight (r = 0.68; P less than 0.001) and to caloric intake/kg/day (r = 0.39; P = 0.01). These relationships could not be accounted for by related and physiologically expected changes in serum Ca or iPTH concentrations. However, serum 1,25-(OH)2-D concentrations were observed to be inversely correlated to serum PO4 levels (r = -0.44; P = 0.004). In addition, serum PO4 levels were inversely correlated to the daily changes in body weight (r = -0.40; P = 0.009). Since dietary sodium intake averaged 142 mmol/day, it is unlikely that the observed changes in weight were the result of changes in salt and water balance. Thus it seems reasonable to speculate that serum 1,25-(OH)2-D concentrations may vary directly with energy balance, as reflected by changes in body weight. This effect may be mediated by alterations in PO4 metabolism. The accurate assessment of serum 1,25-(OH)2-D levels thus appears to require several measurements over time periods during which body weight is stable.
Renal transplantation in primary oxaluria.
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Increased serum 1,25-(OH)2-vitamin D concentrations fail to affect serum or urine phosphate in humans.
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Calcium-oxalate-crystal-induced bone disease.
A 13-year-old boy with primary hyperoxaluria and a successful renal allograft developed symptomatic bone disease, hypercalcemia, and hypercalciuria. Transiliac bone biopsy revealed calcium oxalate crystals in the marrow within mononuclear phagocytes and multinucleated giant cells. Deep resorption bays were seen adjacent to these crystal-cell aggregates. Serum 1,25-(OH)2-vitamin D (calcitriol) and iPTH concentrations were low or normal. We suggest that hypercalcemia results from macrophage-mediated bone resorption initiated by Ca oxalate crystal deposition.
Effects of calcitriol administration on calcium metabolism healthy men.
To evaluate the relationship between daily and fasting urinary calcium excretion and serum 1,25-(OH)2-D concentrations, we studied six healthy men during control and during chronic oral calcitriol administration (0.6, 1.2, or 1.8 nmoles every 6 hours for 6 to 12 days) while they ate normal and low calcium diets (calcium content, 19.2 or 4.2 mmoles/day). Daily urinary calcium excretion was directly related to serum 1,25-(OH)2-D concentrations but increased more (P less than 0.025) while subjects ate the normal calcium diet (slope, 0.081 mmole/day/pmole/liter, r = 0.94) than when eating the low calcium diet (slope, 0.043 mmole/day/pmole/liter; r=0.83). During calcitriol and ingestion of the low calcium diet, daily urinary calcium excretion averaged 7.32 +/- 2.6 mmoles/day, exceeding the dietary calcium intake (P less than 0.02). Moreover, during calcitriol, when serum 1,25-(OH)2-D exceeded 140 pmoles/liter, fasting urinary calcium/creatinine exceeded 0.34 mmole/mmole (the upper limit of normal) on either diet. When serum 1,25-(OH)2-D concentrations are elevated, a high fasting urinary calcium/creatinine or high daily urinary calcium excretion, even on a low calcium diet, is insufficient criteria for the documentation of a renal calcium leak.
The chief medical residency: a description and recommendations.
Individuals occupying the position of chief medical resident have the opportunity to influence significantly the quality and tenor of medical education and medical practice. To assess the status of the position, the authors surveyed chief medical residents completing their tenure in 1980. These residents distributed their time among administrative (41 percent), teaching (35 percent), patient care (21 percent), and research (3 percent) activities. They reported that their experience was quite positive. However, overall satisfaction was significantly negatively correlated with percentage of time spent performing administrative tasks. The percentage of time chief medical residents allocate to administration has increased during the past decade, while time spent teaching and delivering patient care has decreased. Based upon this survey, recommendations for improved utilization of the time and talents of these individuals are presented.
Vitamin D metabolites and parathyroid hormone in Cushing's syndrome: relationship to calcium and phosphorus homeostasis.
We studied the effects of glucocorticoid excess on calcium and phosphorus homeostasis in relation to vitamin D metabolites and parathyroid hormone (PTH) in seven patients with spontaneous ACTH-dependent Cushing's syndrome. Remission of hypercortisolism resulted in a significant increase in tubular reabsorption of phosphate [from 76 +/- 4% to 89 +/- 2% (mean +/- SEM); P less than 0.01] and serum phosphorus (from 3.1 +/- 0.1 to 4.2 +/- 0.2 mg/dl; P less than 0.005). Serum calcium did not change, although there was a reduction in daily urinary calcium excretion from 0.23 +/- 0.02 to 0.107 +/- 0.02 mg calcium/mg creatinine. Serum immunoreactive PTH (iPTH) levels were normal during Cushing's syndrome (34 +/- 5 microleq/ml), but fell significantly after remission to 22 +/- 2 microleq/ml (P less than 0.05). This small decrease in iPTH did not correlate with the improvement of phosphate homeostasis. Plasma 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25-(OH2)D] concentrations in Cushing's syndrome did not differ from measurements in 97 normal subjects. After treatment, 25OHD did not change, but 1,25-(OH)2D fell in each patient from a mean of 44 to 22 pg/ml (P less than 0.02). 1,25-(OH)2D was inversely correlated with serum phosphorus (r = 0.59; P less than 0.01), but did not correlate with iPTH. The known impairment of intestinal calcium absorption in Cushing's syndrome cannot be attributed to a decrease in the circulating levels of 1,25-(OH)2D. Endogenous hypercortisolism decreases tubular phosphate reabsorption and serum phosphorus, increase tubular phosphate reabsorption and serum phosphorus, increases iPTH, and results in an increase in 1,25-(OH)2D. These events may contribute to the severe loss of bone mass in such patients and may account for the calciuria and phosphaturia of Cushing's syndrome.
Synthesis and metabolic clearance of 1,25-dihydroxyvitamin D as determinants of serum concentrations: a comparison of two methods.
We evaluated endogenous renal 1,25-dihydroxyvitamin D (1,25-OH)2D) synthesis by compartmental analysis of the plasma disappearance of injected [3H]1,25-dihydroxyvitamin D3 in 11 subjects with serum 1,25-(OH)2D concentrations varying from 9-154 pM (normal, 89 +/- 25 pM). Estimated renal synthesis ranged from 2-180 pmol/kg . day. Serum 1,25-(OH)2D concentrations in these subjects best fit a log function of renal synthesis: serum 1,25-(OH)2D, pM = -13 + 74 log renal 1,25-(OH)2D production, picomoles per kg/day (r = 0.91). We also evaluated serum 1,25-(OH)2D concentrations in 6 healthy subjects who had been given 0.6, 1.2, or 1.8 nmol calcitriol every 6 h during a period 6--12 days after hormone administration was begun. Steady serum 1,25-(OH)2D concentrations 2, 4, and 6 h after the last calcitriol dose were achieved in proportion to log dose: serum 1,25-(OH)2D, pM = -12 + 103 log 1,25-dihydroxyvitamin D3 dose, picomoles per kg/day (r = 0.94). Estimated 1,25-(OH)2D production rates using these two methods and assuming a normal serum 1,25-(OH)2D concentration of 89 pM range from 10--24 pmol/kg . day or, for a 70-kg subject, 0.6--1.7 nmol/day or 0.25--0.7 microgram/day. Metabolic clearance of 1,25-(OH)2D appears to be accelerated when production rates are increased.
Is there a disorder of phosphate metabolism in idiopathic hypercalciuria?
Hypophosphatemia either as a consequence of secondary hyperparathyroidism or as a consequence of a primary defect in phosphate metabolism appears to be a well established abnormality among subsets of patients with idiopathic hypercalciuria and nephrolithiasis. The detailed biochemical events that lead to hypophosphatemia in those patients who exhibit a primary abnormality of phosphate metabolism remain to be clarified.
The calciuria of increased fixed acid production in humans: evidence against a role for parathyroid hormone and 1,25(OH)2-vitamin D.
We measured mineral and acid balances, serum iPTH, urinary cAMP/creatinine, and plasma concentrations of 25OHD and 1,25(OH)2D in 7 healthy adults during control conditions and during increased fixed acid production achieved either by the administration of NH4Cl (N = 3) or by increased dietary protein intake (N = 4). When acid production was increased, the subjects were in positive acid balance and negative Ca balance because of increased urinary Ca excretion. Serum iPTH fell slightly but urinary cAMP and the plasma levels of vitamin D metabolites did not change. W conclude that the accelerated skeletal and urinary losses of Ca that occur when fixed acid production is increased are not contributed to nor compensated for by the parathyroid-vitamin D endocrine systems.
Urinary calcium excretion in human beings.
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