Do patients receiving regular haemodialysis need folic acid supplements?
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Biomedical subjects
Publications and source records attributed to F J Goodwin.
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Thirteen patients receiving regular haemodialysis, with biochemical or radiological evidence of renal osteodystrophy, were treated with alfacalcidol (1 alpha hydroxy vitamin D3) for four years. During the first eighteen months of treatment plasma alkaline phosphatase and serum parathyroid hormone concentrations fell and subperiosteal phalangeal erosions improved. Thereafter plasma alkaline phosphatase and serum parathyroid hormone concentrations rose and after four years' treatment only four patients had a normal plasma alkaline phosphatase, only five a normal serum parathyroid hormone level and in only six had the erosions healed completely. Hypercalcaemia occurred in twelve patients, plasma calcium exceeding 3.0 mmol/l in ten. Plasma calcium rose abruptly close to the time when plasma alkaline phosphatase became normal and often remained raised despite reduction in dosage of alfacalcidol. We have reservations about the ultimate value of long-term treatment with alfacalcidol in haemodialysed patients with renal osteodystrophy and urge caution in its use.
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The blood pressures (BP) of the parents of a group of students were determined and two subgroups of students were defined, one with (PHT group) and one without (PNT group) a familial predisposition to hypertension. Observations were made in both groups during three periods of modified dietary electrolyte intake: (i) no-added sodium (low Na), (ii) no added sodium with potassium supplementation (low Na/high K), and (iii) sodium supplementation (high Na). The diets were given in random order. At the start of the trial, while the students continued their customary diet, the PHT group had higher systolic and diastolic pressures and plasma noradrenaline levels than the PNT group. At the end of 4 weeks of the high Na diet, the BP levels of both groups were significantly higher than those after the low Na diet. In contrast, when the low Na diet was supplemented for 2 weeks with potassium, BPs of the PHT group fell significantly, while those of the PNT group rose slightly. BP in the PHT group was significantly lower during the low Na/high K than during the high Na diet (systolic 10.5 mm Hg +/- 2.3 SE; diastolic 11.2 +/- 2.5, the changes being significantly different from those in the PNT group. The changes in plasma renin and aldosterone were similar in both groups during the different diets. Plasma noradrenaline fell in the PHT group, but rose in the PNT group when the low Na diet was supplemented with potassium. This fall in plasma noradrenaline in the PHT group during the low Na/high K diet correlated with the falls in systolic and diastolic BP. It is concluded that whereas young adults with a familial predisposition to hypertension behave similarly to those without such a predisposition in having a pressor response to a high sodium intake, they are peculiar in showing a depressor response to a high potassium intake.
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1. Changes in plasma renin activity, plasma noradrenaline, pulse rate and blood pressure after tilting were measured in normal subjects and in patients with renal transplants. 2. There was a marked difference between the renin responses in the two groups, the increases in plasma renin activity in the control subjects being much greater than those in the transplanted patients. 3. Activation of the sympathetic nervous system after tilting, as indicated by changes in pulse rate, blood pressure and plasma noradrenaline, was similar in the two groups. 4. We conclude that the ability of the transplanted kidney to increase plasma renin activity after tilting is impaired, probably as a result of sympathetic denervation of the kidney during transplantation. The results suggest a dominant role of the sympathetic nervous system in the mediation of renin release after tilting.
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Hypercalcaemia regularly occurs when "prophylactic" 1,25-dihydroxyvitamin D3 (1,25[OH)2D3) in a dose of 1.0 microgram daily is given to haemodialysis patients without clinical biochemical or radiological evidence of osteodystophy. This dose is too large for such patients. Hypercalcaemia may persist for several weeks after withdrawal of 1,25(OH)2D3, particularly when previous attempts at control by dosage reduction have failed. Hypercalcaemia is better managed by stopping 1,25(OH)2D3, albeit temporarily, than by reducing the dose.
A patient with hemolytic uremic syndrome complicating chicken pox is described. At post mortem, the glomeruli showed diffuse capillary wall thickening and extensive wrinkling of the basement membrane with subendothelial deposition of granular material. Although a number of viruses and other infective agents have been implicated in its etiology, this appears to be the first report of an association between hemolytic uremic syndrome and chicken pox.
Eight patients with treated Addison's disease were studied whilst receiving different doses of fludrocortisone together with a constant intake of glucocorticoid. Plasma renin activity (PRA), blood pressure, pulse rate and plasma potassium and urea concentrations were measured after 2-week periods on each dose. In two patients, PRA measurements indicated that mineralocorticoid replacement therapy had been inadequate. In four others, PRA remained normal throughout the study, even after fludrocortisone had been discontinued, suggesting that the drug was unnecessary for the maintenance of normal sodium balance in these patients. Asymptomatic fludrocortisone overdosage was indicated by a low plasma potassium concentration, but not by PRA measurements which failed in this study to distinguish between adequate and excessive mineralocorticoid replacement.
Fourteen patients with renal osteodystrophy were treated for at least one year with 1-alpha-hydroxycholecalciferol (1-alpha-OHD3) in a dose varying from 1 microgram/week to 3 microgram/day. Plasma calcium and inorganic phosphorus concentrations increased significantly. The plasma alkaline phosphatase concentration fell in 11 of the 12 patients in whom it was initially raised and returned to normal in seven. Serum parathyroid hormone concentrations were initially raised in all patients, but they decreased significantly with treatment and became normal in eight patients within one year. The 10 patients with radiological abnormalities showed some improvement. Hypercalcaemia occurred in 11 patients, and necessitated a reduction in the dose of 1-alpha-OHD3 in some. 1-alpha-OHD3 was effective in reducing the biochemical and radiological abnormalities of renal osteodystrophy, but it should be used wtih care, and plasma calcium concentrations should be monitored.
The high circulating concentrations of immunoassayable parathyroid hormone observed in chronic renal failure are due to a number of factors. These include altered metabolism of the hormone and also end-organ unresponsiveness which may, indirectly, cause increased secretion of parathyroid hormone. The response of the overactive parathyroid glands to changes in plasma calcium and magnesium is variable and caution is needed in evaluating the suppressibility of parathyroid hormone secretion in acute studies. 1alpha-Hydroxylated derivatives of vitamin D can effectively suppress parathyroid gland overactivity. This effect may not necessarily be medicated through hypercalcaemia and vitamin D metabolites may act directly on the parathyroid glands.
The role of the kidney in hypertension is reviewed in terms of sodium and water homeostasis, of the secretion of renin inappropriate to the state of sodium and water balance and of other renal humoral factors which might be implicated in the hypertensive process. Fundamental to the long-term maintenance of hypertension is an alteration in the relationship between renal perfusion pressure and the excretion of sodium and water. This alteration may be brought about as a result of renal structural damage, sympathetically mediated renal vasoconstriction or the action of renal or extrarenal hormones which modulate sodium and water excretion. When renin is secreted in excess of the prevailing level of sodium and water balance, the generated angiotensin contributes to the hypertension directly through peripheral and renal vasoconstriction. The level of blood pressure in two hypertensive patients with chronic renal failure was found to be highly correlated with the level of plasma renin activity as this was lowered by the administration of a beta-blocking drug. In rats deprived of sodium, renal artery constriction and contralateral nephrectomy was followed by hypertension without any elevation of plasma angiotensin and with a minimal expansion of plasma volume unaccompanied by expansion of extracellular fluid volume. The possible role of this small volume change and of other possible factors in producing hypertension is discussed. Studies in the nephrectomised rat confirmed eariler reports that renal medullayr auto-explants inhibited renoprival hypertension, but neither the identity nor mode of action of the medullary hypotensive factor were further clarified.
The effect of propranolol has been studied in two patients with chronic renal failure and hypertension which remained refractory despite the removal of excess sodium and water by dialysis. Measurements of plasma-renin, exchangeable sodium, and blood-volume demonstrated that in both patients hypertension was due to excess renin. The administration of propranolol was followed by a rapid fall in blood-pressure to normal, thereby obviating the need for bilateral nephrectomy. In both patients the fall in blood-pressure was accompanied by a striking fall in plasma-renin, and in one there was a highly significant association between plasma-renin activity and mean arterial pressure.
A pregnancy in a patient undergoing regular dialysis treatment was successfully managed. Premature labour occurred at 32 weeks. Fetal nutrition was satisfactory and the infant developed normally and showed no congenital abnormality during 12 months' observation.
A case of hypertension in a patient with neurofibromatosis and renal artery stenosis with aneurysm formation in a solitary kidney is described. Studies of plasma renin activity and body sodium content are presented and have been related to findings in patients and experimental animals with renovascular hypertension. A reconstructive operative procedure is described in which the kidney is perfused in situ.
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