Ultrasound changes in the wrist and hand in hemodialysis patients.

Dialysis related amyloidosis (DRA) is a common complication of chronic dialysis, but diagnosis can be difficult. Hand involvement, as carpal tunnel syndrome (CTS) or particularly amyloid hand, can affect dexterity. To investigate the prevalence and extent of hand involvement, ultrasound evaluation of the carpal tunnel and tendons of the hand was performed in 25 chronic hemodialysis patients. Clinical symptoms of CTS were present in 18/50 wrists (36%); symptomatic patients had undergone hemodialysis for a significantly longer period than those without symptoms (16 +/- 2.9 years vs 5.3 +/- 3.0 years). The ultrasound indicators suggestive of DRA in the wrist which correlated with CTS were 1) increased carpal tunnel depth (15 +/- 2.3 mm vs 11 +/- 1.5 mm), 2) increased displacement of flexor tendons from the radius (3.4 +/- 2.4 mm vs 11 +/- 0.6 mm), and 3) presence of hypoechoic masses, erosions and fluid collections (16% of wrists). There was no relationship between symptoms and either flexor retinaculum thickness or median nerve surface area index. Five patients (20%) had severe stiffness of their fingers; ultrasound revealed thickening of the tendons of the hand in all these cases. Ultrasound technology allows the non-invasive examination of the wrist and hand for DRA and may be valuable in diagnosis and planning surgery.

Gastrin processing and secretion in patients with end-stage renal failure.

Gastrin circulates at higher than normal concentrations in patients with end-stage renal failure (ESRF). However, it remains unclear which forms of gastrin are elevated and whether there is also an alteration in the secretory profile after stimulation. In the present study all processed and partially processed forms of circulating gastrin were measured in plasma before and after meal stimulation in ESRF patients and control subjects. Since Helicobacter pylori (HP) infection affects gastrin secretion, HP status was determined. Fasting gastrin-amide (36 +/- 8 pmol/L), gastrin-Gly (55 +/- 16 pmol/L), and total gastrin (218 +/- 32 pmol/L) measured in ESRF/HP-patients were all significantly greater than those in the control group (10 +/- 1, 15 +/- 3, and 17 +/- 2 pmol/L, respectively; P < 0.01). Plasma gastrin-amide (126 +/- 67 pmol/L) and total gastrin (397 +/- 164 pmol/L) were highest in the ESRF/HP+ patients. The proportion of nonamidated gastrin products was 4-fold higher in ESRF patients than in control subjects, suggesting structure-specific changes in gastrin secretion and metabolism, and this was confirmed by chromatography. The meal-stimulated increments in control/HP- and ESRF/HP-groups were similar. However, the ESRF/HP+ group had a markedly potentiated gastrin response. Fasting plasma somatostatin, an inhibitor of gastrin secretion, was also measured and was significantly lower in the ESRF patients than that in the control group. These studies show that the hypergastrinemia associated with renal failure has been underestimated. This is because only amidated products were measured. The potentiated gastrin meal response in ESRF attributed previously to changes in gastrin metabolism are in part explained by the effect of HP infection. The observed diminished somatostatin response suggests that the increase in circulating gastrin in ESRF is the result of loss of inhibition of secretion as well as decreased metabolism. As both amidated and nonamidated gastrin are now considered to have trophic and secretory effects, these findings may explain the gastrointestinal tract hypertrophy often associated with ESRF.

Familial focal glomerulosclerosis: a genetic linkage to the HLA locus?

The aetiology and pathogenesis of focal glomerulosclerosis is poorly understood and many conflicting reports suggest HLA locus associations in both familial and non-familial glomerulosclerosis. We report a family in which 4 of 5 sisters developed proteinuria, 2 with hypertension and 1 progressing to end-stage renal failure (index case). Three underwent renal biopsy which displayed characteristic features of focal glomerulosclerosis and all shared the HLA alleles HLA-A1, B8, DR3, DR7. The index case received two cadaveric renal transplants from HLA-A1, B8, DR3 donors and developed chronic rejection with no histological evidence of recurrent glomerulonephritis in either kidney. The frequency of this haplotype in the Australian dialysis and transplant population with focal glomerulosclerosis was compared to that seen in the general Australian Caucasian population and was not significantly different suggesting that the presence of the HLA alleles HLA-A1, B8, DR3, DR7 may increase the predisposition to familial glomerulosclerosis but additional factors are required for disease development and progression.

Haemodynamic changes and physical performance at comparative levels of haemoglobin after long-term treatment with recombinant erythropoietin.

Physical performance and haemodynamic parameters at rest and with exercise were compared in a prospective, cross-over fashion in 12 anaemic haemodialysis patients (Hb 6.4 +/- 0.5, mean +/- SEM) at two levels of haemoglobin (Hb 9 and 12 g/dl) before and after long-term treatment with recombinant human erythropoietin (rHuEpo). Patients were divided into two groups and measurements made prior to treatment, upon reaching, and after 4 months at the first target Hb (9 g/dl group A, 12 g/dl group B), and after 4 months at the alternative target Hb. Tests included an exercise radionuclide ventriculogram, Doppler echocardiogram, and respiratory function exercise test. Compared to pretreatment, there was a significant reduction in resting pulse rate (P < 0.001), and in pulse rate (P < 0.001) and arterial lactate (P < 0.01) concentrations at specified levels of exercise. Work capacity improved 60% (P < 0.001), and left ventricular mass fell by 26% (P < 0.001). Although cardiac output (CO) during and after exercise was reduced (P < 0.05), resting CO, cardiac index, stroke volume and ejection fraction (rest and exercise) were not significantly altered. There appeared little benefit in having the higher target Hb: no significant difference could be found between target levels for almost any measure. In addition, despite marked improvement from pretreatment levels, performance parameters were still below those of non-uraemic age-matched controls. These results demonstrate the beneficial but incomplete effect of rHuEpo on resting and exercise-related factors, and suggest that most improvement is achieved with modest increments in haemoglobin.

Subjective quality of life assessment in hemodialysis patients at different levels of hemoglobin following use of recombinant human erythropoietin.

The quality of life of 12 hemodialysis (HD) patients was assessed in a prospective, blinded, cross-over fashion before treatment with recombinant human erythropoietin (r-HuEPO) and at two different levels of hemoglobin (Hb, 9 and 12 g/dl) by means of an interviewer-based questionnaire, the sickness impact profile (SIP). Patients were matched into two groups with no significant difference for age, weight, Hb (6.3 +/- 0.5, mean +/- SEM, group A, vs. 6.4 +/- 0.9 group B), length of hemodialysis or number of years of prior transplantation. SIP was assessed prior to treatment, after reaching the first target Hb (Hb 9 g/dl group A, 12 g/dl group B), after 4 months at that target Hb and after 4 months at the alternative target Hb for each group. For all patients, there was a highly significant improvement in quality of life as assessed by lower SIP scores between the initial and second assessments. This was evident for the physical (8.9 +/- 1.4 vs. 2.8 +/- 1.0; p less than 0.001) and psychosocial (14.9 +/- 3.9 vs. 4.4 +/- 1.1; p less than 0.01) dimensions. Total scores (16.3 +/- 2.4 vs. 5.7 +/- 0.9; p less than 0.001) showed similar changes, reflecting significant improvement in 10 of 12 possible categories between the first two assessments (p less than 0.05 to p less than 0.001). Improved scores were maintained but did not change appreciably after the 2nd assessment. There was no significant difference in any score (category, dimensional or total) obtained after 4 months at Hb 9 g/dl compared to those after the same period at Hb 12 g/dl.(ABSTRACT TRUNCATED AT 250 WORDS)

Shoulder ultrasound in dialysis related amyloidosis.

Ultrasonographic changes around the shoulder joint were compared in ten symptomatic patients with dialysis related amyloid (DRA) and seventeen patients without symptoms. All patients had been on long-term (greater than 7 years) hemodialysis (HD). Three control groups were used: 8 predialysis patients, 10 continuous ambulatory peritoneal dialysis (CAPD) and 9 HD patients who had been on dialysis for less than two years. Dry bodyweight, sex, handedness, length of hemodialysis and fistula side were not significantly different between the study groups. Proven amyloid patients were significantly older than other groups (p less than 0.001). Parameters assessed included cross-sectional area of long head of biceps tendon (LHB), diameter of supraspinatus tendon (SS), and general features (bursae, deposits) around the joint. Results demonstrated significant differences in all parameters in patients with symptomatic amyloid compared with other long-term patients: [SS: 7.4 mm +/- 0.7, mean +/- SEM, vs 5.1 +/- 0.2 (right, R), p = 0.001; 6.7 +/- 0.7 vs 4.9 +/- 0.2 (left, L), p = 0.01. LHB: 140.0 mm2 +/- 11.1 vs 79.6 +/- 5.1 (R), p less than 0.001; 114.5 +/- 10.5 vs 80.8 +/- 5.4 (L), p = 0.004. Bursae: 5 vs 1 (patients), p = 0.006]. Compared with controls changes in the amyloid group were less marked though in most cases still significant. There was no significant difference between control groups nor between controls and asymptomatic long-term HD patients in any parameter. We conclude that shoulder ultrasound may have a role in identifying patients with dialysis related amyloid. Serial measurements may also help to elucidate the pathogenesis of the tendon changes.

Experience with low dose intravenous and subcutaneous administration of recombinant human erythropoietin.

Twelve stable haemodialysis patients were divided into two groups and given recombinant human erythropoietin (r-HuEPO) for 14 weeks either intravenously (i.v.) or subcutaneously (s.c.). Dosage was 25 units/kg either thrice (i.v.) or twice (s.c.) per week for 7 weeks, and then 50 units/kg for a further 7 weeks. Response to s.c. therapy was comparable to i.v. despite a 33% lower weekly dosage, and was significant at both 7 (i.v.: 1.1 +/- 0.3, mean +/- SEM, p = 0.02; s.c.: 0.8 +/- 0.3 g/dl, p = 0.03) and 14 weeks (i.v.: 2.8 +/- 0.5, p = 0.003; s.c.: 2.6 +/- 0.6 g/dl, p = 0.009). A correlation was observed between response to r-HuEPO and initial ferritin levels (r = 0.63, p = 0.04). One patient required an increase in antihypertensive medication and there was one arteriovenous fistula thrombosis. Results suggest that overall s.c. therapy is as effective as i.v. therapy, and that a good response with few side effects can be obtained using relatively low doses of r-HuEPO.

Assessment of the symptomatic benefit of cool dialysate.

Symptoms were evaluated in 13 haemodialysis patients at dialysate temperatures between 37 and 35 degrees C. After a control period at 37 degrees C (stage 1) dialysate flow rate was increased from 300 ml/min in half the patients but no change in temperature was made (stage 2). In stage 3 dialysate temperature was reduced to 36.5 degrees C and in stage 4 to 35 degrees C. Blood pressure and temperature were measured pre- and post dialysis and patient completed a questionnaire indicating if they experienced any of nine specified symptoms: itch, restless legs, nausea, vomiting, headache, cramp, lethargy, hypotension and change in temperature. Trial stages were compared with chi 2 analysis using Yates correction. Symptoms per dialysis fell from 1.11 to 0.71 between stage 1 and 2 (p less than 0.0005). This was considered to be a trial effect. There was no further significant improvement in symptoms overall as the temperature was reduced to 35 degrees C. However, if complaints of coldness are excluded, there was a progressive reduction in symptoms from stage 1 to stage 4. Dialysate flow rate did not affect symptom reporting. There was no effect on body core temperature or blood pressure due to cool dialysate. Our results suggest there may be some benefit in lowering the dialysate temperature but this is small in relation to the placebo effect. Caution must be used in assessing similar studies using small numbers of dialyses.

Bilateral pelviureteric junction obstruction causing renal failure in two elderly patients.

Two elderly patients presented with renal failure due to pelviureteric junction (PUJ) obstruction. After dialysis, obstruction was relieved by percutaneous nephrostomy and the diagnosis was established radiologically. Differential renal function was assessed by direct measurement or isotope scanning. Surgical correction resulted in both patients remaining free of dialysis at follow-up 2 years later. PUJ obstruction is an uncommon cause of renal failure, particularly in the elderly, but is potentially correctable.

Dialysis osteomalacia: a possible role for zirconium as well as aluminium.

Six patients with dialysis osteomalacia were studied before and after treatment with desferrioxamine. Before treatment, all six had severe osteomalacia with histochemical evidence of metals at the mineralization front, confirmed by energy dispersive X-ray microanalysis to include Al, Zr and Fe. Zr was not detected by histological staining in patients without dialysis osteomalacia. After treatment a decrease of Al and Zr was associated with improvement in clinical, biochemical, radiological and histological parameters. These observations suggest the possibility of a role for metals other than Al in the pathogenesis of dialysis osteomalacia.

Comparison of high and low sodium bicarbonate and acetate dialysis in stable chronic hemodialysis patients.

Eight stable center dialysis patients completed four, 10-week study periods in which either acetate or bicarbonate dialysis was used, each with high or low sodium concentration. During high sodium dialysis, blood pressure was better controlled, weight loss more easily tolerated and dialysis was most satisfactory from the patient's point-of-view with regard to dialysis-associated symptoms. Low sodium dialysis, whether with acetate or bicarbonate, was less satisfactory. In contrast to the beneficial effect of an increased sodium concentration, the use of bicarbonate instead of acetate appeared to make little difference either to the patient's symptoms, to the control of blood pressure or to changes in blood gases or biochemistry. Careful choice of dialysate sodium concentration appears to be important in lessening dialysis side-effects. Substitution of bicarbonate for acetate in chronic stable dialysis patients has comparatively little benefit and the choice can legitimately be made on the basis of cost and technical considerations.

Metabolism of neurotensin and pancreatic polypeptide in man: role of the kidney and plasma factors.

Neurotensin (NT) is a 13 amino acid peptide found predominantly in the ileum and it is released into the circulation by a meal. Much of the circulating NT consists of N terminal fragments which have no known biological activity. However, the sites and rates of NT metabolism are not known. In the present study the MCR and half-disappearance time of NT were estimated by infusing NT(1-13) into 10 normal subjects. The role of the kidney was assessed by studies in patients with chronic renal failure (CRF). The nature of the metabolites was characterized using region specific antisera and high pressure liquid chromatography (HPLC). The plasma pancreatic polypeptide response to the NT infusion was also measured. The NT MCR in normal subjects was 88 +/- 25 (SEM) ml/min X kg measured with the C terminal antiserum but only 9.9 +/- 0.8 ml/min X kg measured with the N terminal antiserum, a result consistent with the presence of long lasting N terminal fragments. HPLC of the plasma at equilibrium established that only 20% of the immunoreactivity was present as NT(1-13), with the majority as NT(1-8). No C terminal fragment were detected. Similarly, incubation of NT(1-13), 1-8, and 8-13 in plasma in vitro showed that N terminal fragments were stable in plasma, whereas C terminal fragments were completely metabolized. In patients with CRF, basal plasma NT (measured with the C terminal antisera) was significantly elevated and C terminal MCR was reduced by 82% and N terminal MCR by 32%. Thus the major effect of CRF was on the initial degradation of NT(1-13) to N terminal fragments. HPLC showed that over 60% of the NT was present as NT(1-13). In vitro degradation of NT was also slowed in CRF plasma. The increased proportion of intact biologically active NT in the circulation of the CRF patients could also explain the greater increase in pancreatic polypeptide levels during the NT(1-13) infusion. These studies have established that the metabolism of NT is influenced by the kidney and that the presence of predominantly N terminal fragments of NT in the peripheral circulation of normal subjects can be explained by a combination of renal and extrarenal factors.

Parathyroidectomy in chronic renal failure.

Parathyroidectomy was carried out in 26 patients over a 14-year period. Excellent results were obtained in patients with severe hyperparathyroidism. Vascular calcification, hypercalcaemia and pruritus did not justify surgery unless associated with unequivocal hyperparathyroidism. 13 patients required intravenous calcium infusion for up to 2 weeks to control post-operative hypocalcaemia. Calcium requirements could be predicted from the pre-operative plasma alkaline phosphatase level. Following operation continued treatment with vitamin D was necessary to prevent hypocalcaemia. Hyperparathyroidism recurred in 1 patient after 8 years and 4 patients developed osteomalacia. Since parathyroid hormone may have toxic effects other than those on bone, maintenance of normal levels should be a long-term objective in the treatment of patients with chronic renal failure. Where large parathyroid glands are present, surgical reduction in gland mass is a logical prelude to long-term suppression of parathyroid hormone with vitamin D and phosphate-binding agents.

Treatment of dialysis osteomalacia with desferrioxamine.

Two patients with severe dialysis osteomalacia, whose fractures and deformities had become progressively worse over 3 years, were treated with desferrioxamine (DFO). They improved rapidly and over 6 months were able to stop taking analgesics and return to normal activities. Pre-treatment bone biopsy samples contained extensive osteoid covering trabecular surfaces. Electron microscopy showed morphological abnormalities in the matrix. Treatment brought about a decrease in the extent and depth of osteoid, but matrix abnormalities remained. Energy-dispersive X-ray microanalysis showed the presence of several metals not seen in normal bone. The changes in trace metals after DFO treatment were not consistent. Atomic absorption analysis showed no significant change in the aluminium content of bone with treatment. DFO appears to be an effective treatment for severe dialysis osteomalacia.

Assessment of osteodystrophy in patients with chronic renal failure.

Nine patients with chronic renal failure were followed for more than one year by serial bone biopsies which were assessed by quantitative histological techniques. All patients had evidence of bone disease; this progressed during the interbiopsy period in eight. Patients who had the most advanced histologic disease at initial biopsy showed the most progression in resorption and demineralization, but with greater progression of hyperparathyroid bone disease than osteomalacia. The type of bone disease and its rate of progression could only be accurately assessed histologically. No predictive parameters of early bone disease were found from clinical history, biochemistry or radiology. Raised serum alkaline phosphatase occurred only in advanced hyperparathyroid bone disease. Minor radiological abnormalities in magnified views of the hands were indicative of histologically advanced asymptomatic hyperparathyroidism.

Left ventricular function in uremia: echocardiographic assessment in patients on maintenance dialysis.

Echocardiographic assessment of left ventricular function was performed in twenty-two unselected patients on stable, chronic maintenance dialysis. The statistically significant abnormalities were enlargement of the left ventricular cavity (end diastolic internal dimension or "diameter" 5.4 +/- 0.2 cm, normal 4.4 +/- 0.3 cm), thickening of the left ventricular wall (end diastolic thickness 1.1 +/- 0.05 cm, normal 0.9 +/- 0.03 cm) and a reduction in myocardial contraction (fractional shortening 28.2 +/- 2.0%, normal 35.7 +/- 0.9%). Myocardial impairment could not be attributed to the effects of hypertension or to ischemic heart disease. There was, however, a significant negative correlation between fractional shortening and total plasma catecholamines (r = 0.45, P less than 0.05) suggesting that excessive catecholamines may contribute to the decreased myocardial contraction seen in uremic patients.