An unexpected cause of muscle pain in diabetes.

Diabetic muscle infarction is a rare condition which may present to a rheumatologist. It was first reported in 1965. Two illustrative cases are described here and the mechanisms of pathogenesis discussed. Analysis of the published data, results of the muscle biopsies, and a technetium-99m sestamibi scan suggest that the condition, which occurs against a background of diabetic microangiopathy, can be triggered by an ischaemic event and causes extensive muscle necrosis through hypoxia-reperfusion injury and compartment syndrome.

How should we treat tophaceous gout in patients with allopurinol hypersensitivity?

We studied purine metabolism in gouty patients from three categories: primary gout, familial juvenile hyperuricaemic nephropathy (FJHN) and partial HPRT deficiency.

Increased erythropoietin requirements in patients with failed renal transplants returning to a dialysis programme.

The response to erythropoietin (Epo) is dose dependent but, for various poorly understood reasons, variable. In a cross-sectional study we determined the Epo requirement of 60 patients in a dialysis population to identify those patients requiring a high dose of Epo, and ascertained the reasons for higher requirements, paying particular attention to the effect of previous transplantation. All 289 patients attending a single centre were surveyed. Of these, 164 were receiving renal replacement therapy by continuous ambulatory peritoneal dialysis (CAPD) and 125 were on haemodialysis (HD). Patients on HD needed more Epo than those on CAPD (129.0 +/- 14.9 U/kg/week versus 86.9 +/- 10.7 U/kg/week, P < 0.05). However, this difference was accounted for by a subgroup of patients who had a previously failed transplant. The Epo requirement in those patients on HD with a failed transplant was significantly greater than those on HD who had never been transplanted (164.0 +/- 24.5 U/kg/week versus 96.6 +/- 11.9 U/kg/week, P < 0.05). The seven patients who retain their transplanted kidney had the highest Epo requirement of all (213.4 +/- 46.6 U/kg/week). These studies have shown that previous transplantation is a significant determinant of Epo requirement upon return to dialysis. They also show that it is necessary to 'correct' for the effect of previous transplantation when investigating generally accepted determinants of Epo need. Interpretation of previously published studies needs to take account of this.

A double-blind, randomized, placebo-controlled study of nifedipine on early renal allograft function.

A double-blind, randomized, placebo-controlled study was conducted to determine the effect of nifedipine on early renal allograft function when added to a triple therapy immunosuppression regime comprising low-dose cyclosporin (CsA), prednisolone and azathioprine. Fifty adult cadaveric renal allograft recipients were randomized to placebo (group P n = 17), nifedipine 10 mg preoperatively and 20 mg b.d. postoperatively for 48 h, followed by matching placebo for 3 months (group NS n = 16) or nifedipine 10 mg preoperatively and 20 mg b.d. postoperatively for 3 months (group NL n = 17). Donor and recipient exclusion criteria included recent calcium antagonist treatment. At 3 months after transplantation mean GFR adjusted for graft loss was significantly higher in group NL than in NS (mean +/- SD 61 +/- 28 versus 34 +/- 25 ml/min/1.73 m2; P < 0.05), group P being intermediate (45 +/- 34 ml/min/1.73 m2). Similarly, effective renal blood flow (ERBF) at 3 months was higher in group NL than in groups P and NS (mean +/- SD 351 +/- 175 versus 216 +/- 166 and 220 +/- 162 ml/min/1.73 m2; P < 0.05). The differences were not significant by 6 months post-transplantation. This study suggests that oral nifedipine commenced preoperatively and continued for 3 months following transplantation has beneficial effects on early renal allograft function when incorporated as part of an immunotherapy regimen based on cyclosporin.

Effects of indomethacin and misoprostol on renal function in healthy volunteers.

We have examined the effects on renal function of indomethacin and misoprostol, alone and in combination. Eight healthy volunteers took indomethacin 50 mg tds for one week, and indomethacin plus misoprostol (a synthetic PGE1 analogue) 200 micrograms qds for one week in a crossover design. A separate group (n = 5) took misoprostol alone for one week. 51Cr EDTA GFR rose significantly from baseline after the combination of indomethacin and misoprostol (from mean +/- SD 117 +/- 7.1 to 123 +/- 8.0 mls/min/1.73 m2, p = 0.05). When indomethacin alone was given 51Cr EDTA GFR did not change significantly (120 +/- 9.0 to 117 +/- 9.0 mls/min/1.73 m2). However in 4 of these subjects 51Cr EDTA GFR fell (range 7-19 mls/min/1.73 m2); in each of these the reduction was reversed when the indomethacin was given together with misoprostol. In the whole group the change in 51Cr EDTA GFR, from baseline, after indomethacin plus misoprostol was significantly different from that after indomethacin alone (+6 +/- 8 vs -3 +/- 5 mls/min/1.73 m2 p = 0.05). Misoprostol alone had no effect on GFR. We conclude that misoprostol and indomethacin in combination increase GFR in healthy volunteers, and further studies are now warranted to determine whether misoprostol is beneficial in the prophylaxis and treatment of NSAID-induced renal impairment.

Mycobacterial infection is an important infective complication in British Asian dialysis patients.

To define the extent and nature of mycobacterial infection in patients on an adult dialysis unit whose catchment population contains a large proportion of non-Caucasian subjects, a retrospective survey of all new patients accepted onto our maintenance dialysis programme between January 1987 and December 1989 was carried out. Twenty-six Asian, 13 Afro-Caribbean, two Oriental and 170 Caucasian patients were accepted onto the dialysis programme in the three-year recruitment period. Eight of the 26 Asian patients, but none of the others, had developed mycobacterial infection by the end of December 1990. One patient had a cerebral tuberculoma with miliary mottling on chest X-ray, one pulmonary tuberculosis, one tuberculous adenitis and 5 tuberculous peritonitis (four due to Mycobacterium tuberculosis and one Mycobacterium kansasii). All the patients had been living in the UK for an average of 15 (range 6-24) years, with no known recent exposure to tuberculosis. Five patients are now alive and well, one developed malabsorption following M. kansasii peritonitis, but two with tuberculous peritonitis died before treatment could be instituted. Mycobacterial infections were associated with a high level of mortality and morbidity. No Asian patient developed mycobacterial infection during post-transplant immunosuppressive therapy in the study period, probably because of the routine anti-tuberculous chemoprophylaxis employed in this group of patients. The diagnosis of mycobacterial infection should be suspected when an Asian dialysis patient develops a pyrexia of unknown origin. It is likely, though not proven, that anti-tuberculous chemoprophylaxis might reduce this high incidence of tuberculous infection in Asian dialysis patients.

Carbamylated haemoglobin, urea kinetic modelling and adequacy of dialysis in haemodialysis patients.

Urea kinetic modelling (UKM) has increasingly been used for assessing adequacy of dialysis and protein nutritional status of dialysis patients. Using a precise HPLC method we developed, we measured carbamylated haemoglobin (CarHb) values in 20 stable twice-weekly dialysed patients and attempted to correlate their CarHb values with their UKM-derived indices. Based on these indices, 11 patients were found to have been adequately dialysed with sufficient protein intake, three patients were adequately dialysed but malnourished and six patients were under-dialysed. Estimated dietary protein intake correlated poorly with calculated daily protein catabolic rate in our patients. CarHb values were found to correlate strongly with the time-averaged urea concentrations, suggesting that CarHb might be a time-integrated urea-derived index. Those adequately dialysed patients have a mean (SD) CarHb value of 142 (29) micrograms CV/gHb against the underdialysed patients, 197 (30) micrograms CV/gHb (t-test, P = 0.002). We suggest that a CarHb value less than 175 micrograms CV/gHb may represent satisfactory uraemic exposure, whereas CarHb value greater than 175 micrograms CV/gHb is undesirable.

Immunoglobulin heavy chain switch region gene polymorphisms in glomerulonephritis.

Much evidence suggests that primary IgA nephropathy (IgAN) and idiopathic membranous nephropathy (MN) are immune complex mediated diseases. Moreover, genetic factors may play an important role in their pathogenesis. Recently, restriction fragment length polymorphisms (RFLPs) of the immunoglobulin heavy chain genes have been described which appear to associate with glomerulonephritis. We have studied RFLPs of the switch region of the IgM (S mu) and IgA1 (S alpha 1) heavy chain in MN and IgAN. DNA obtained from British Caucasoids with IgAN (N = 75), MN (N = 43), and normal controls (N = 73), was digested with the restriction enzyme Sac1, and studied using Southern blot techniques and hybridization with a 32P labelled DNA probe homologous to S mu. This probe detects RFLPs at the S mu and S alpha 1 loci. The genotypic and allelic frequencies of the S mu and S alpha 1 alleles in IgAN and MN was similar to normal controls. Caucasoid subjects with IgAN from Northern and Southern Europe (Finland and Italy, respectively) were also studied to determine whether an ethnic variation in genetic susceptibility to IgAN exists. The frequency of the S mu and S alpha 1 alleles was similar between the patient groups and their respective local healthy controls. These results do not support the recent findings of an association with RFLPs of the S mu and S alpha 1 loci in IgAN and MN, and suggest that the immunoglobulin heavy chain switch region genes are not important in conferring disease susceptibility to IgAN or MN.

Effect of direction and rate of change of calcium on parathyroid hormone secretion in uraemia.

We have studied the control of amino-terminal parathyroid hormone (PTH) secretion in haemodialysis patients in response to slow or fast calcium infusion and during acute hypocalcaemia. In nine patients, fast calcium infusion (0.4 mmol/kg bodyweight per hour) for 15 min increased ionised calcium and reduced PTH, with an initial t 1/2 of 12.8 min. After the infusion had ceased, calcium decreased steadily, and PTH increased, mean PTH reaching baseline values when calcium was still significantly greater than pre-infusion values. During slow calcium infusion for 2.5 h (0.1 mmol/kg bodyweight per hour), parathyroid suppression was evident at 15 min, when the calcium increment was only 0.03 mM. After 60 min, PTH did not decrease further despite progressive hypercalcaemia. Hypocalcaemic haemodialysis led to rapid increases in PTH. After 15 min, the mean calcium decrement was 0.09 mM (P less than 0.01) and the mean PTH increment was 283 pg/ml (P less than 0.01). The parathyroid response was maximal at 30 min, and did not increase subsequently, despite progressive hypocalcaemia for a further 90 min. During recovery from hypocalcaemia, PTH reduced and, despite comparable hypocalcaemia, PTH during periods of increasing calcium was always lower at a given calcium concentration than while calcium was decreasing. This influence of the direction of change of calcium was not seen during hypocalcaemia. The results showed that even in-advanced renal disease, the parathyroid glands are highly responsive to small initial increments (0.03 mM) and decrements (0.09 mM) in blood calcium, though less so to further perturbation of blood calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term CAPD--some U.K. experience.

As many UK renal units commence more patients on CAPD than hemodialysis (HD) as the first mode of therapy a retrospective study of long-term CAPD (greater than 4 years continuous CAPD) was performed in 4 centers with substantial CAPD programs. One hundred and seventy-seven patients (103M, 74F) started CAPD before December, 1981. There was no difference in primary renal disease. Age was significantly greater in 2 units (51.9 +/- 11.7 and 53.2 +/- 12.1 vs 40.6 +/- 16.2 and 42.5 +/- 14.6 years, p less than 0.05) and correlates with pre-CAPD activity scores (Scale 3-0). After 4 years: 34 patients (19.2%) remained on CAPD: the proportion was similar in all centers. Sixty-five percent of patients were alive but 54% transferred to HD mainly due to peritonitis (overall 2.0 episodes/intercenter variation p less than 0.001). Fourty-four patients were transplanted. Significant increases occurred in hemoglobin, albumin, calcium and creatinine; a decrease in activity score (2.4 +/- 0.7 to 1.5 +/- 0.9, p less than 0.005); no change in weight, BP, urea or bone disease. Thirty-eight patients died, mainly cardiac (14) or sepsis (11). Using Cox's method of analysis significant risk multipliers were age (2.07 per decade), male sex (2.18), frequency of peritonitis (1.36), activity score less than 2 (4.45) and amyloidosis (12.45). Despite differing techniques in different centers CAPD offered a satisfactory mode of therapy for many patients; peritonitis was the main reason for transfer to HD and several significant factors were identified.

Residual renal function in hemodialysis patients may protect against hyperaluminemia.

We investigated 106 home hemodialysis patients whose mean [+/- SEM] serum aluminum (Al) concentration was 60.9 +/- 4.1 micrograms/liter. Serum Al concentration was inversely related to daily urine output (r = -0.52, P less than 0.001). Urine volume and measurements of Al exposure were included in a multivariate analysis of serum Al concentration in the 62 patients whose urine output was greater than 10 ml/day. The multiple correlation coefficient (r) was 0.70 (P less than 0.001) and the percentage contributions to r2 (indicating the relative importance of each factor) were: urine output 57%, oral Al intake 36%, total dialysis hours 7%. The additional contribution from cumulative water Al was negligible. In a subgroup of 26 patients with a urine output exceeding 10 ml/day, urinary Al excretion averaged 15.4 micrograms/day, and renal Al clearance and serum Al concentration were inversely related (r = -0.69, P less than 0.001). We conclude that Al-containing phosphate binders were a more important source of Al than was dialysate in these patients and that residual renal function can reduce the severity of hyperaluminemia in hemodialysis patients.

Controlled trial of calcitriol in hemodialysis patients.

We report on a 5-year, prospective, double-blind trial of 1,25 dihydroxycholecalciferol (calcitriol) versus placebo in 76 hemodialysis patients without biochemical or radiological evidence of bone disease. Calcitriol, 1 microgram daily, regularly induced hypercalcemia. Doses of 0.25 microgram daily or less proved satisfactory in most patients. During calcitriol treatment, plasma calcium concentration was significantly higher and serum parathyroid hormone concentration significantly lower than on placebo. There was no difference in the rates of development or of progression of vascular calcification in the two groups. Significantly more patients on placebo (17 vs. 6, p less than 0.05) developed a sustained elevation of plasma alkaline phosphatase concentration. Calcitriol appeared to protect against the development of histological evidence of osteitis fibrosa but not of osteomalacia, but accumulation of aluminum in bone occurred during the study. We conclude that calcitriol delays and may prevent the development of osteitis fibrosa in patients receiving regular hemodialysis and may reasonably be prescribed routinely in hemodialysis patients without biochemical or radiological abnormality, unless there is a substantial prospect of early renal transplantation.

Acute renal failure with polyarteritis nodosa and multiple myeloma.

A patient who presented with acute renal failure due to renal cortical necrosis is described. Renal biopsy showed cortical infarction and angiography demonstrated aneurysms in the renal, splenic and hepatic circulations. Concurrently he was found to have an IgA kappa paraprotein with bone marrow changes diagnostic of multiple myeloma. He was treated with haemodialysis, immunosuppressive drugs and plasma exchange but died 3 months after presentation.

Effect of dialysate buffer on potassium removal during haemodialysis.

There is a linear relationship between potassium removal during haemodialysis and plasma potassium (Kp). Kp falls rapidly during the first hour of dialysis but very little during the last two hours of a five hour dialysis. There is a fairly constant movement of potassium from the intracellular to extracellular space throughout dialysis. Total potassium removal is best predicted by pre-dialysis Kp, but change in Kp is related to the impact of dialysis on acid-base status. The choice of acetate or bicarbonate buffered dialysate does not effect potassium removal during dialysis.