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Photon absorptiometric measurements of the right lower femur were carried out at regular intervals of one to three months in 58 recipients of renal transplant. (1) During the first six months after transplant 57% showed a significant and abnormal rate of loss of bone mineral (mean 11.7% per year. +/- 1.1% S.E.M.) while 30 months' after transplantation only 17% showed such a significant loss (p=0.025). (2) Eighteen months after transplantation both male and female recipients of transplants had a significantly lower mean bone mineral index than controls (p less than 0.001). (3) Male patients who developed new post-transplant fractures had a lower mean bone mineral content compared with age and sex-matched controls taken from transplant recipients without such fractures (p less than 0.01). Similarly male patients with post-transplant fractures had a significantly longer mean period on regular haemodialysis (p less than 0.05) compared with patients without such fractures. Regular photon absorptiometric measurements provide an accurate, informative and non-invasive technique for following changes of bone mineral content after successful renal transplantation.

Lymphocytotoxic antibodies can be induced by the immunologic stimulus of pregnancy, blood transfusion, or tissue allograft. The presence of such antibodies can delay or prevent renal transplantation. However, a history of prior transfusion exposure has been strongly associated with excellent renal allograft survival. The problem of ensuring this ‘transfusion effect’ while minimizing the risk of alloimmunization is real for patients awaiting renal allografts. We examined the influence of pregnancy, allograft rejection, and transfusions on the levels of lymphocytotoxic antibodies in the sera of patients awaiting renal transplantation. The results indicate that transfusions alone have a minimal effect on alloimmunization in men and in nulliparous women. The influence of transfusions alone was seen with 77% of men and 86% of women showing less than 10% panel reactivity. Deliberate transfusion policies for patients awaiting renal allografts should be designed to minimize transfusion exposure to parous patients or those who have previously rejected a renal graft.

A disabling osteomalacic syndrome seen only during regular hemodialysis is described. Its features include skeletal fractures, pain, suppression of pre-existing hyperparathyroidism, and failure to improve with any of the vitamin-D metabolites. Phosphate depletion may be an important etiological factor but this could not explain all cases. A trial with phosphate-enriched dialysate and 1alphaOHD3 resulted in sustained clinical improvement in 54% of the patients and healing of fractures in 33%. Other etiological factors independent of 1,25(OH)2D3 deficiency and phosphate depletion must be considered. Current, indirect evidence suggests that accumulation of water toxins including aluminium may be important.

Assessment of 18 azotaemic patients treated with long-term 1alpha-hydroxyvitamin D3 (1alpha-OHD3) confirms the generally favourable effect of this analogue of 1,25-dihydroxyvitamin D3 in azotaemic osteodystrophy. Growing children with radiological rickets respond very well as do adults showing mild hyperparathyroidism with or without osteomalacia. However, patients with severe 'pure' hyperparathyroidism and features of autonomy do not respond well and in such patients 1alpha-OHD3 alone should be avoided. Phosphate restriction and occasionally a sub-total parathyroidectomy may be indicated in these patients.

Separate ultrafiltration followed by haemodialysis (U.F.-H.D.) using Gambro Major or Cordis-Dow hollow-fiber dialyzers were evaluated in 10 dialysis patients over a mean period of 4 1/2 months and 455 U.F.-H.D. procedures. Fluid control was facilitated in oedema-tous patients but the number of hypotensive episodes during the combined procedure requiring intravenous 57. saline did not significantly decrease. No significant improvement in hypertension was noted.Ultrafiltration (U.F.) alone for acutely water overloaded, azotaemic patients proved very useful. Two to five liters of oedema fluid could be removed asymptomatically in one to three hours using transmembrane pressures of 250 to 500 mmHg and U.F. rates of 10 to 42 ml/tnin. Two patients became acutely and symptomatically hypotensive. One was an insulin dependent diabetic in whom 3800 ml were removed in 75 minutes and the other a hypertensive patient undergoing treatment with Minoxidil and propranolol.

(1) The bone histology of 233 non-dialysed and 276 haemodialysed patients with chronic renal failure is reviewed. In non-dialysed patients osteitis fibrosa occurred in 83.7% and osteomalacia in 23.6% of patients. Osteomalacia was not found in the absence of osteitis fibrosa. In haemodialysed patients there was a more variable bone histology, sometimes resembling non-dialysed bone disease, but in general with a greater incidence of osteomalacia, especially with increasing time on dialysis. In some patients there was a predominance of osteomalacia accompanied by no or only mild osteitis fibrosa and the serum alkaline phosphatase was normal. (2) The results of treating twenty-six haemodialysed patients with 1alpha-hydroxyvitamin D3 (1alpha-OHD3) are described. Patients with osteomalacia and minimal or no osteitis fibrosa and a normal serum alkaline phosphatase (Group I) in general failed to respond and it is suggested that 1,25-dihydroxyvitamin D3 deficiency is not the sole factor responsible for the osteomalacia in these patients. In contrast, 1alpha-OHD3 therapy was effective in improving osteitis fibrosa and osteomalacia in some patients with moderate to severe degrees of osteitis fibrosa and osteomalacia (Group IIa) and in improving osteitis fibrosa where this occurred alone (Group IIb).

Perfusion studies in 9 D-31 Redy acetate dialysis cartridges revealed a significant release of aluminum in a form that could diffuse across a dialysis membrane. 8 azotemic patients undergoing dialysis on the Redy system for periods of 18-36 months developed signs and symptoms of aluminum-induced osteomalacic bone disease, and 6 of them also had symptoms and electroencephalographic abnormalities of dialysis encephalopathy. 7 patients have died with these complications. In view of the significant release of aluminum, the D-31 Redy dialysis cartridge may not be ideal or safe for long-term hemodialysis.

Marrow mast cells have been counted in iliac bone from patients with chronic renal failure treated by renal transplantation. Mast cell numbers were initially increased but returned to the normal range in many patients after renal transplantation. Improvement in osteitis fibrosa and osteomalacia after transplant was not clearly related to this diminution in the number of mast cells. The use of prednisone in renal transplant patients may have some effect in reducing the numbers of mast cells. There is no fully acceptable explanation for the increase in marrow mast cells which occurs in chronic renal failure.

Three children with azotaemic renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25(OH)2D3). All showed clinical, biochemical, and radiological improvement within 6 months of starting treatment. There were no complications. The dose of 1,25(OH)2D3 required was 0-5 microgram per day for 2 children aged 22 and 30 months, and 2 microgram per day for a 15-year-old boy. 2 of the patients were receiving phenobarbitone and phenytoin and in one of them prior treatment with dihydrotachysterol 0-5 mg daily and 6 microgram 1alpha-hydroxycholecalciferol (1alphaOHD3) daily had failed to induce improvement. In one patient, in whom serial iliac bone samples were available, 2 microgram 1,25(OH)2D3 resulted in histological improvement in previously severe osteomalacia. 1,25(OH)2D3 appears to be an effective and safe drug in the treatment of uraemic osteodystrophy.

Using a 2-hour 47Ca absorption test, significant depression of active calcium absorption was demonstrated in 48 vitamin D untreated haemodialysis patients. This malabsorption of calcium could be corrected by the daily oral administration of 1–2 µg of 1αOHD3 and 1–1.5 µg of 1,25(OH)2D3. 5 µg daily for 2 weeks of 3-deoxy-1αOHD3 and 16 and 64 µg daily for 1 week of 24R, 25(OH)2D3 proved ineffective. In 32 successfully transplanted patients, restoration of normal or near normal renal function (serum creatinine

Hemodialysis encephalopathy with osteomalacic fractures and muscle weakness. The hemodialysis unit at Columbia, South Carolina, opened in April, 1974. By June of 1977, 7 patients had died from dialysis encephalopathy, and 16 of the 51 surviving patients showed speech disorders, fits, and myoclonic jerks. Pathologic fractures were seen in 22 patients. Bone histomorphometry showed severe osteomalacia with minimal, if any, osteitis fibrosa, and serum alkaline phosphatase activity was normal. The mean serum aluminum concentration in 33 random patients was elevated at 83.5 µg/liter (control group, 13.9 µg/liter, P < 0.001). The mean bone aluminum concentration in 4 patients who died from this syndrome was 307ppm of bone ash (normal, < 10 ppm). Dialysis fluid aluminum was high at 140 µg/liter. Purification of the dialysis fluid with a water softener, reverse osmosis and a deionizer and abandoning extra-strength Basaljel® resulted in a notable clinical and EEG improvement. None of 81 new patients who started hemodialysis between July of 1977 and July of 1979 after the change in treatment have developed any such symptoms. A syndrome of hemodialysis encephalopathy accompanied by pathologic osteomalacic fractures is described. Recovery is possible. The syndrome was eradicated after purification of the dialysis fluid.Encéphalopathie de l'hémodialyse avec fractures ostéomalaciques et faiblesse musculaire. Le centre d'hémodialyse à Columbia, South Carolina, USA, a ouvert en Avril 1974. De cette date à Juin 1977, 7 malades étaient morts d'encéphalopathie de la dialyse et 16 des 51 malades survivants avaient des troubles du langage, des convulsions et des secousses myocloniques. Des fractures pathologiques ont été observées chez 22 malades. L'histomorphométrie osseuse a montré une ostéomalacie sévère avec peu ou pas d'ostéite fibreuse. Les phosphatases alcalines sériques étaient normales. La concentration moyenne d'aluminium dans le sérum chez 33 malades choisis au hasard était élevée à 83,5 µg/liter (groupe contrôle: 13,9 µg/liter, P < 0,001). La concentration osseuse moyenne chez 4 malades décédés de ce syndrome était de 307ppm de résidu sur de l'os (normal < 10 ppm). L'aluminium du liquide de dialyse était élvé, à 140 µg/liter. La purification du liquide de dialyse au moyen d'un adoucisseur, de l'osmose inverse et d'un désionisant et l'abandon du Basaljel® ont eu pour conséquence une amélioration importante, clinique et électromyographique. Aucun des 81 nouveaux malades dont G hémodialyse a commencé entre Juillet 1977 et Juillet 1979, après la modification de la stratégie, n'a développé de tels symptômes. Un syndrome d'encéphalopathie de l'hémodialyse associé à des fractures pathologiques ostéomalaciques est décrit. La récupération est possible. Ce syndrome a disparu après la purification du liquide de dialyse.

The term vitamin D is generally used to describe a number of chemically related compounds with common antirachitic properties, but which have differences in the rapidity of their action, the way they are produced in the body, and the conditions under which their results are optimal. Ergocalciferol, cholecalciferol, 25-hydroxycholecalciferol (calcifediol), dihydrotachysterol, 1 alpha-hydroxycholecalciferol (alfacalcidol), and 1,25-dihydroxycholecalciferol (calcitriol) are currently the most commonly used vitamin D metabolites. In man, cholecalciferol produced on the skin and the fraction obtained from the diet in the gastrointestinal tract are converted in the liver to 25-hydroxycholecalciferol and then in the kidney to 1,25-dihydroxycholecalciferol. The demonstration of these metabolic pathways has helped to elucidate the aetiology of such conditions a hepatobiliary osteodystrophy, drug-induced anticonvulsant osteomalacia, the hypocalcaemia of hypoparathyroidism and above all azotaemic osteodystrophy. In the therapy of azotaemic osteodystrophy, the period of 'vitamin D resistance' when large doses of vitamin D2 and D3 had to be used is now over, and these patients can be efficiently and successfully treated with almost physiological doses of 1 alpha-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol. Attention to diet, calcium supplements and oral phosphate binders are also important. During repetitive haemodialysis, the above principles still hold true, but in some of these patients an osteomalacic syndrome resistant to 1,25-dihydroxycholecalciferol has been recognised. These patients readily become hypercalcaemic when given 1,25-dihydroxycholecalciferol and their fractures and osteomalacia do not improve. Aluminium intoxication, possibly related to the use of impure dialysis fluid, is currently thought to be the most likely explanation of this dialysis osteomalacic syndrome.

Ten uraemic patients on regular haemodialysis were treated with 1alpha-hydroxycholecalciferol (1alpha-H.C.C.) for 5 to 14 months. Five patients who had histological osteitis fibrosa with or without osteomalacia responded well, with resolution of musculoskeletal pain, return of raised serum-alkaline-phosphatase concentrations to normal, resolution of radiological subperiosteal erosions, and improvement in histological signs of osteitis fibrosa and osteomalacia. In these patients 1alpha-H.C.C. proved a safe and effective drug. Five other patients did not improve. Characteristically these patients started with moderately severe histological osteomalacia and minimal, if any, osteitis fibrosa. Proximal myopathy was a prominent symptom and serum-alkaline-phosphatase was normal in four of them. Treatment with 1alpha-H.C.C. resulted in early troublesome hypercalcaemia, and repeat bone histology 5--11 months later showed no improvement. It is suggested that in these patients lack of 1,25-dihydroxycholecalciferol may not have been wholly responsible for the observed osteomalacia, hence 1alpha-H.C.C. alone was ineffective. Phosphate depeltion may have been an important contributing factor.

Elimination kinetics of captopril in patients with renal failure. Captopril kinetics were determined after a 100-mg oral dose of14C-captopril in 21 patients with various degrees of renal impairment. Elimination kinetics of captopril were evaluated by model-independent methods. The body clearance (ClB) of captopril decreased steadily with decreasing creatinine clearance (ClCr) from 5.2 ml/min/kg for mild renal failure patients to 1.6 ml/min/kg for hemodialysis patients during an interdialytic period. In patients with mild renal impairment, renal and nonrenal clearances of captopril averaged 2.2 and 3.0 ml/min/kg, respectively, and fell (P < 0.001) to 0.2 and 1.5 ml/min/kg in patients with severe renal impairment. There were no significant differences in the extent of total cumulative excretion (fecal plus urinary) of radioactivity over a 96- to 120-hr period between the patients with mild, moderate, and severe renal impairment. The 48-hr renal excretion of captopril averaged 29, 21, and 8% of the dose in the mild, moderate, and severe renally impaired groups. In five additional hemodialysis patients, the mean dialyzer clearance of captopril averaged 120ml/min. Approximately 35% of the dose was recovered in the 4-hr dialysate. Based on the above findings, a reduction in the dose of captopril is necessary in patients with renal failure.Cinétique d'élimination du captopril chez les malades en insuffisance rénale. La cinétique du captopril a été déterminée après une dose orale de 100mg del4C-captopril chez 21 malades atteints d'insuffisance rénale à des degrés divers. La cinétique d'élimination du captopril a été évaluée par des méthodes indépendants du modèle. La clearance corporelle (ClB) du captopril diminuait progressivement avec la baisse de la clearance de la créatinine (ClCr) de 5,2 mg/min/kg chez les malades en insuffisance rénale modérée à 1,6 ml/min/kg chez les malades en hémodialyse lors d'une période interdialytique. Chez les malades en insuffisance rénale modérée, les clearances rénales et non rénales du captopril étaient en moyenne de 2,2 et 3,0 ml/min/kg, respectivement, et chutaient (P < 0,001) à 0,2 et 1,5 ml/min/kg chez les malades avec une altération rénale sévère. Il n'y avait pas de différences significatives dans l'importance de l'excrétion cumulative totale (fécale et urinaire) de radioactivité sur une période de 96 à 120 heures entre les malades atteints d'une altération rénale modérée, moyenne ou sévère. L'excrétion rénale de 48 heures du captopril était en moyenne 29, 21, et 8% de la dose dans les groupes avec des altérations rénales modérées, moyennes ou sévères. Chez cinq malades hémodialysés supplémentaires, la clearance dialytique moyenne du captopril était de 120ml/min. Environ 35% de la dose était retrouvée dans un dialysat de 4 heures. D'après ces résultats, une diminution de la dose de captopril est nécessaire chez les malades en insuffisance rénale.

Measurement of serum lipids in 75 patients on regular haemodialysis showed that they had a higher mean serum triglyceride level than normal subjects. Cholesterol levels were not significantly different. Amongst haemodialysis patients men had higher serum triglycerides than women and women had higher cholesterol levels than men, a situation analogous to that found in normal subjects. In men, serum triglycerides correlated with percent body fat and treatment with Sustanon 250(R) intramuscularly weekly caused a significant rise.

The clinical and histopathological features of 37 patients with idiopathic membranous nephropathy are presented. Males were four times as commonly affected as females and the age at presentation ranged from nine to 70 years. The period of observation varied from three months to 23 years. Twenty-eight patients (76 percent) presented with the nephrotic syndrome and nine patients (24 per cent) presented with non-nephrotic proteinuria. At the end of the study, of the patients presenting with the nephrotic syndrome, seven (25 per cent) were in remission, seven (25 per cent) remained nephrotic, nine (32 per cent) showed only proteinuria and five (18 per cent) were dead or on dialysis. Altogether eight patients (28 per cent) developed renal failure. The nine patients who presented with non-nephrotic proteinuria appeared to do better, and none developed renal failure. The occurrence of spontaneous remission makes assessment of benefit from immunosuppressive therapy difficult. However, analysis of our data and a review of the literature suggest that in this condition oral prednisone, cyclophosphamide and azathioprine have no significant therapeutic properties. Histological assessment confirmed the occurrence of mild (Grade 1) changes in patients biopsied soon after presentation, and tubular atrophy increased with the duration of illness. Immunofluorescence confirmed deposition of mainly IgG and complement. Repeat biopsies in 14 patients showed no histological improvement and remission was not accompanied by resolution of histological abnormalities.

Eleven patients with Alport's syndrome had renal transplantation between 1963 and 1980. The mean follow-up is 6 years (6 months to 14 years). All 11 patients are currently alive. Ten have functioning grafts, and in nine the serum creatinine concentration is less than 2 mg/dl. Three patients received a second allograft. Histologic study of the allografts that were lost revealed a diffuse crescentic glomerulonephritis with strongly positive linear IgG staining of the glomerular basement membrane in the allografts of two of the three patients; circulating antiglomerular basement membrane antibodies were present in one patient. These two patients had successful retransplantation and they remain well 1 1/2 and 4 1/2 years later. Renal transplantation in patients with Alport's syndrome is a worthwhile and very satisfactory procedure.

Summary A patient with recurrent convulsions in childhood and associated ketotic hypoglycaemia is described. Hypoglycaemic attacks started at the age of 3 years and 4 months and continued until 9. At present (aged 15) the patient is mentally retarded, has epilepsy, high tone deafness and a major behaviour disturbance. Prednisone therapy failed to prevent hypoglycaemic convulsions and eventually irreversible brain damage. Intramuscular glucagon and adrenaline were ineffective in raising the blood glucose during acute hypoglycaemic attacks. Investigations at 3 years and 7 months and at 14 years showed a persistent and markedly abnormal sensitivity to a small dose of exogenous insulin with severe hypoglycaemia with convulsions, absence of clinical hyperadrenalism during hypoglycaemia, and a metabolic block in gluconeogenesis. The demonstration of a persistent biochemical abnormality of glucose metabolism at the age of 14 strongly suggests that ketotic hypoglycaemia of childhood is not another aspect of nutritional deprivation, as recently suggested (Buist, 1974), but the result of a defect in glucose homeostasis.

Two regular hemodialysis patients were assessed before, during and after therapy for 8 1/2 months with 1alpha-hydroxycholecalciferol (1alphaOHD3). The first patient (F.S.), treated with 2 mug daily, improved considerably with complete resolution of histological osteomalacia (O.M.), reduction in osteitis fibrosa (O.F.) and healing of Looser zones. The second patient (T.Y.), who was treated at the same time with a combination of phenobarbitone and phenytoin, showed no improvement while taking 3 mug of 1alphaOHD3 daily. It is suggested that hepatic microsomal enzyme inducing drugs antagonize the action of 1alphaOHD3 by interfering with its subsequent hepatic 25-hydroxylation.

Five patients with haemodialysis bone disease were treated with 1 to 1.5 mug of 1,25 (OH)2D3 daily for periods ranging from 6 -8 months. There was a significant improvement in calcium absorption but no troublesome hypercalcaemia was encountered. Secondary hyperparathyroidism improved, both histologically and radiologically, and there was a fall in serum PTH and return of serum alkaline phosphatase to within normal limits. There was also improvement in the patients' mineralisation status, but this change was slower and less marked. Muscle power improved significantly, both clinically and electromyographically.

Serial histological studies in patients after successful renal transplantation indicate that with restoration of adequate renal function osteomalacia invariably improves with symptomatic relief in bone pain. Histological changes of osteitis fibrosa resolve more slowly and radiological changes may persist longer, occasionally in the absence of confirmatory histological evidence of secondary hyperparathyroidism. For accurate and sensitive follow-up a combination of biochemistry, histology and radiology is desirable.

Zomepirac sodium (Zomax) is a nonsteroidal anti-inflammatory agent with analgesic properties which was recently released for clinical use in this country. We report here a case of nonoliguric acute renal failure associated with zomepirac sodium therapy. This acute renal failure improved upon cessation of zomepirac treatment. Renal biopsy disclosed the presence of a tubulointerstitial nephritis, which was thought to have been responsible for the acute renal failure in this patient. Clinicians should be aware of the potential nephrotoxicity of zomepirac sodium and use caution in its administration, especially in patients with compromised intravascular volume status, hypertension, or preexistent chronic renal disease.

The clinical and histopathological features of 37 patients with idiopathic membranous nephropathy are presented. Males were four times as commonly affected as females and the age at presentation ranged from nine to 70 years. The period of observation varied from three months to 23 years. Twenty-eight patients (76 percent) presented with the nephrotic syndrome and nine patients (24 per cent) presented with non-nephrotic proteinuria. At the end of the study, of the patients presenting with the nephrotic syndrome, seven (25 per cent) were in remission, seven (25 per cent) remained nephrotic, nine (32 per cent) showed only proteinuria and five (18 per cent) were dead or on dialysis. Altogether eight patients (28 per cent) developed renal failure. The nine patients who presented with non-nephrotic proteinuria appeared to do better, and none developed renal failure. The occurrence of spontaneous remission makes assessment of benefit from immunosuppressivet herapy difficult. However, analysis of our data and a review of the literature suggest that in this condition oral prednisone, cyclophosphamide and azathioprine have no significant therapeutic properties. Histological assessment confirmed the occurrence of mild (Grade 1) changes in patients biopsied soon after presentation, and tubular atrophy increased with the duration of illness. Immunofluorescence confirmed deposition of mainly IgG and complement. Repeat biopsies in 14 patients showed no histological improvement and remission was not accompanied by resolution of histological abnormalities.

Among 39 patients treated by regular haemodialysis for four years or more pathological fractures and histological evidence of osteomalacia were significantly more common in those taking barbiturates. Out of 58 transplant recipients surveyed after one year, seven had osteomalacia; four of these had been taking phenobarbitone and phenytoin and one had taken barbiturates alone. Sedatives and other drugs such as phenobarbitone and phenytoin that induce hepatic microsomal enzymes should probably be avoided when possible in patients with chronic renal failure and after transplantation.

Two patients with central pontine myelinolysis are described. Both were middle aged women presenting with a history of protracted vomiting and drowsiness. Hyponatraemia (serum sodium 96 to 100 mmol/L) was a feature in both patients. No underlying malignancy, alcoholism, malnutrition or other serious disease was identified. Correction of electrolyte abnormalities was accompanied by deterioration in level of consciousness and development of a neurological syndrome characterized by quadriparesis, dysphasia and mutism. Death followed and histopathological examination confirmed classical myelinolysis in the central pons and extensive similar, though not identical, lesions in the cerebral hemispheres in both cases. The pathophysiological basis of the lesions is likely to be a special metabolic susceptibility of oligodendroglial cells in areas where neurones, glial cells and myelin sheaths lie in close proximity to one another.

Muscle weakness and tenderness together with a rise in serum creatine kinase (C.K.) were noted in five uraemic patients treated with 1-2 g of clofibrate ('Atromid-S') daily. Excessive accumulation of both total and free serum chlorophenoxyisobutyric acid (C.P.I.B.), the active circulating metabolite after clofibrate therapy, was found in three patients in whom it was sought. It is suggested that chronic renal failure should be regarded as a contraindication to the use of clofibrate for the treatment of any coexisting hyperlipidaemia. If such therapy is contemplated it must be cautiously instituted at low dosage and the patient monitored by regular assessment of serum C.K. and levels of both total and free C.P.I.B.

One hundren seventy-eight azotemic patients, 114 on hemodialysis, had measurements of total serum ALP, and definition of isoenzyme patterns on acrylamide gel electrophoresis. In addition, bone histomorphometry was defined in all of the patients by means of transiliac bone biopsies. Serial estimations over 2 years were carried out on several patients, including some being treated with vitamin D2, 1alphaOHD3, and 1,25(OH)2D3. (1) In both nondialyzed and dialyzed patients, serum ALP showed a significant positive correlation with osteitis fibrosa due to secondary hyperparathyroidism irrespective of the presence or absence of concurrent osteomalacia. Increases in the bone isoenzyme were largely responsible for the rise in total ALP. (2) A higher incidence of osteomalacia (p less than 0.001) was observed in patients on hemodialysis in Newcastle Upon Tyne. In hemodialyzed patients where osteomalacia was accompanied by either no secondary hyperparathyroidism (21 patients) or minimal secondary hyperparathyroidism (14 patients), serum ALP remained within normal limits, giving no indication of the existing osteomalacic bone disease. Isoenzyme studies revealed a high prevalence of the intestinal type and also varied combinations of hepatic, intestinal, and bone types. (3) Good response to vitamin D depended on the presence of significant amounts of the bone isoenzyme. Azotemic osteodystrophy characterized by a raised serum ALP and a prominent bone isoenzyme predicted a good response to vitamin D, and the decrease in serum ALP following vitamin D was the result of a reduction in the bone isoenzyme. Patients with symptomatic dialysis osteomalacic bone disease, accompanied by normal total serum ALP and no elevation of the bone isoenzyme, responded less well.

Assessment of 18 azotaemic patients treated with long-term 1alpha-hydroxyvitamin D3 (1alpha-OHD3) confirms the generally favourable effect of this analogue of 1,25-dihydroxyvitamin D3 in azotaemic osteodystrophy. Growing children with radiological rickets respond very well as do adults showing mild hyperparathyroidism with or without osteomalacia. However, patients with severe 'pure' hyperparathyroidism and features of autonomy do not respond well and in such patients 1alpha-OHD3 alone should be avoided. Phosphate restriction and occasionally a sub-total parathyroidectomy may be indicated in these patients.

One hundred fourteen nondialyzed azotemic adult patients (creatinine connentration 1.2 to 17.6 mg/dl), 78 stable renal transplant recipients (creatinine less than 1.9 mg/dl), 50 patients with idiopathic nephrolithiasis, 36 patients with surgically proven primary hyperparathyroidism, and 62 normal volunteers were studied with simultaneous serum ionized calcium, total calcium, parathyroid hormone (PTH), phosphorus, and creatinine measurements. Ionized calcium could not be reliably predicted from total calcium. Although in all patient groups values for serum ionized calcium correlated significantly with those for total calcium, the scatter around the regression line was such that a direct interpretation was not precise. With respect to reference values, significant differnces were found between ionized and total calcium in 26% of all studied patients. When compared with total serum calcium, ionized calcium appeared to be a more sensitive index of calcium metabolism. All correlations with ionized calcium had a higher r value compared with those with total serum calcium. Two findings were particularly rewarding. In patients with chronic renal failure, serum PTH showed a negative correlation with serum ionized calcium, indicating that the latter may have been largely responsible for the secondary increase in PTH; in patients after a successful transplant, serum PTH showed a positive correlation with serum ionized calcium, indicating that in the presence of normal kidney function the previously hypertrophied parathyroid glands may be largely responsible for the daily study of a large number of specimens, determinations of serum ionized calcium should be encouraged in all patients suspected of having abnormalities of renal calcium metabolism.