The case of stainless statins.

Two cases of hypercholesterolaemic patients are presented in whom raised plasma creatine kinase was noted during treatment with statins. The plasma creatine kinase failed to fall following cessation of therapy. Further investigation revealed the aetiology of the raised plasma creatine kinase to be due to previously undiagnosed glycogen storage diseases (McArdle's and Pompe's diseases).

A novel technique to demonstrate disturbed appetite profiles in haemodialysis patients.

BACKGROUND: Malnutrition is common among dialysis patients and is associated with an adverse outcome. One cause of this is a persistent reduction in nutrient intake, suggesting an abnormality of appetite regulation. METHODS: We used a novel technique to describe the appetite profile in 46 haemodialysis (HD) patients and 40 healthy controls. The Electronic Appetite Rating System (EARS) employs a palmtop computer to collect hourly ratings of motivation to eat and mood. We collected data on hunger, desire to eat, fullness, and tiredness. HD subjects were monitored on the dialysis day and the interdialytic day. Controls were monitored for 1 or 2 days. RESULTS: Temporal profiles of motivation to eat for the controls were similar on both days. Temporal profiles of motivation to eat for the HD group were lower on the dialysis day. Mean HD scores were not significantly different from controls. Dietary records indicated that dialysis patients consumed less food than controls. CONCLUSIONS: Our data indicate that the EARS can be used to monitor subjective appetite states continuously in a group of HD patients. A HD session reduces hunger and desire to eat. Patients feel more tired after dialysis. This does not correlate with their hunger score, but does correlate with their fullness rating. Nutrient intake is reduced, suggesting a resetting of appetite control for the HD group. The EARS may be useful for intervention studies.

The measurement of total body potassium in patients on peritoneal dialysis.

OBJECTIVES: To assess the validity of measuring total body potassium (TBK) to estimate fat-free mass (FFM) and body cell mass (BCM) in patients on peritoneal dialysis (PD). METHODS: We studied 29 patients on PD (14 men, 15 women) and 30 controls (15 men, 15 women). We calculated TBK by using a whole-body counter to measure 1.46 MeV gamma-ray emissions from naturally occurring 40K. We measured total body water (TBW) by deuterium oxide dilution, and extracellular water (ECW) from bromide dilution. These measurements allowed us to estimate intracellular water (ICW), fat-free mass dilution (FFM(Dilution)), and body cell mass dilution (BCM(Dilution)). RESULTS: The FFM(TBK) in male PD patients (55.7 +/- 7.0 kg) did not differ from that in male controls (57.0 +/- 10.9 kg). The FFM(TBK) in female PD patients (38.4 +/- 6.8 kg) was less than that in female controls (44.7 +/- 4.5, p < 0.01). The FFM(Dilution) did not differ from the FFM(TBK). Correlation of FFM(TBK) and FFM(Dilution) was r = 0.90, p < 0.0001 for all subjects; r = 0.90, p < 0.0001 for PD patients; and r = 0.90, p < 0.0001 for controls. Bland-Altman comparison of FFM(Dilution) with FFM(TBK) in individuals showed bias 0.6 kg, range -8.5 kg to 9.7 kg for the whole group; bias 1.4 kg, range -7.9 kg to 10.7 kg for PD patients; and bias -0.2 kg, range -9.0 kg to 8.6 kg for controls. The BCM(TBK) in male PD patients (30.1 +/- 4.5 kg) did not differ from that in male controls (31.9 +/- 6.2 kg). The BCM(TBK) in female PD patients (19.0 +/- 4.4 kg) was less than that in female controls (23.1 +/- 2.9 kg, p < 0.01). The BCM(Dilution) results did not differ from those for the BCM(TBK). Correlation of BCM(TBK) and BCM(Dilution) was r = 0.90, p < 0.0001 for all subjects; r = 0.87, p < 0.0001 for PD patients; and r = 0.93, p < 0.0001 for controls. Bland-Altman comparison of BCM(Dilution) with BCM(TBK) in individuals showed bias 0.1 kg, range -5.9 kg to 6.1 kg for the whole group; bias 0.0 kg, range -6.9 kg to 6.9 kg for PD patients; and bias 0.1 kg, range -5.0 kg to 5.2 kg for controls. The [K+]ICW did not differ between PD patients and controls (148.0 +/- 25.1 mmol/L vs 148.1 +/- 14.3 mmol/L, p = nonsignificant). CONCLUSIONS: Total body potassium is a valid, noninvasive technique for measuring FFM and BCM in PD patients. In our PD patient group, depletion of FFM and BCM as compared with controls was identified in the women but not in the men.

Effects of icodextrin in automated peritoneal dialysis on blood pressure and bioelectrical impedance analysis.

BACKGROUND: Glucose absorption from glucose-based dialysis fluids limits ultrafiltration from the daytime dwell in automated peritoneal dialysis (APD). Icodextrin may allow greater ultrafiltration during the daytime period in APD, enhancing fluid control. METHODS: A 7.5% icodextrin dialysate was compared with a 2. 27% glucose dialysate for the daytime dwell in 14 subjects on APD. Blood pressure, weight and body water compartments estimated by multifrequency bioelectrical impedance (MFBIA) were determined in subjects using 2.27% glucose as the daytime dwell and then repeated 1 month after switching to icodextrin. RESULTS: Icodextrin resulted in symptomatic hypotension requiring reduction of antihypertensive medication in six of the 14 patients. Despite this reduction in treatment, systolic blood pressure fell from 142.4 (23.9) mmHg to 122.9 (17.7) mmHg, P<0.005, and diastolic blood pressure tended to fall from 82.8 (9.8) mmHg to 76.8 (10.1) mmHg, P=0.075. Change in systolic blood pressure significantly correlated with changes in weight (r=0.62, P<0.05) and MFBIA estimates of total body water (TBW) (r=0.56, P<0.05), extracellular water (ECW) (r=0.79, P<0.002), extra/intracellular water ratio (ECW/ICW) (r=0.72, P<0.01) and derived resistances R(ecf) of ECW (r=-0.69, P<0.01) and R(inf) of TBW (r=-0.66, P<0.02). Changes in diastolic blood pressure significantly correlated with changes in ECW (r=0.64, P<0.02) and ECW/ICW ratio (r=0.58, P<0.05), and almost significantly with R(ecf) (r=-0.51, P=0.08) and R(inf) (r=-0.52, P=0.07) estimated by MFBIA, but not with changes in weight or TBW. CONCLUSIONS: Use of icodextrin for the daytime dwell in APD results in improved fluid balance and blood pressure control compared with 2.27% glucose. MFBIA detected clinically important changes in fluid content in these patients.

Effect of peritoneal fluid on whole body and segmental multiple frequency bioelectrical impedance in patients on peritoneal dialysis.

OBJECTIVE: We investigated the ability of whole body and segmental multiple frequency bioelectrical impedance (MFBIA) to detect peritoneal fluid in peritoneal dialysis patients. DESIGN: Prospective study. SETTING: Teaching hospital renal unit. SUBJECTS: Patients on regular peritoneal dialysis. INTERVENTIONS: Whole body and segmental MFBIA measurements before and after drainage of peritoneal fluid. RESULTS: Changes estimated by MFBIA in total body water (-0.4 (0.8) litres) and extracellular water (-0.3 (0.3) litres) were much lower than the actual changes (2.0 (0.4) litres), P<0.0001. Derived resistances Recf and Ricf increased significantly for the trunk but not for total body measurements and changes did not correlate with volumes of fluid drained. CONCLUSIONS: MFBIA is limited in its ability to detect intraperitoneal fluid, using both whole body and segmental techniques.

Low thrombogenicity of polyethylene glycol-grafted cellulose membranes does not influence heparin requirements in hemodialysis.

Heparin is the most commonly used anticoagulant for hemodialysis despite potentially serious side effects. Polyethylene glycol-grafted cellulose (PGC) membranes produce less activation of the coagulation cascade than cuprophane membranes. Anecdotally, we found some patients required a surprisingly low level of anticoagulation using these membranes. We compared the anticoagulant requirement of the PGC membrane with that of the cuprophane membrane in this randomized, prospective, crossover study. Sixty-three patients were randomized to treatment using either membrane, and heparin administration was progressively reduced to the lowest dose that prevented visible clotting in excess of that normally encountered. Patients underwent dialysis at this dose for 1 month, after which the heparin requirement and Kt/Vurea (1.162 x ln [urea pre/urea post]) were assessed. This process was then repeated for each patient using the other membrane, and the results were compared. Heparin administration during dialysis was reduced from a mean loading dose of 29.0 +/- 9.4 to 1.5 +/- 3.2 IU/kg for both membranes and a mean maintenance infusion of 14.0 +/- 6.7 to 0.77 +/- 1.6 IU/kg/h for both membranes (both P < 0.0001 v full anticoagulation; no difference between membranes). The Kt/Vurea was not significantly altered. Forty-six patients with PGC and 45 patients with cuprophane membranes underwent dialysis successfully without heparin during dialysis, and the other patients were using considerably reduced doses. Aspirin and warfarin had no effect on the heparin requirement. These results do not support the theory that PGC membranes have a lower anticoagulant requirement than cuprophane membranes; however, they suggest that dialysis can be performed successfully with much smaller anticoagulant doses than are currently in common use.

Comparison of icodextrin and glucose solutions for the daytime dwell in automated peritoneal dialysis.

BACKGROUND: The sustained ultrafiltration achieved by icodextrin is more suited for the daytime dwell in automated peritoneal dialysis (APD) than glucose solutions. METHODS: Seventeen patients receiving APD underwent assessment using three different solutions for the daytime dwell: 2.27% glucose, 3.86% glucose and 7.5% icodextrin. Patients were then observed on icodextrin for a 6 month period. RESULTS: Daytime ultrafiltration was greater for 3.86% glucose (median 0.10, IQR 0.01 to 0.321) P<0.01 and icodextrin (median 0.26, IQR 0.14 to 0.361) P<0.001 than 2.27% glucose (median -0.19, IQR -0.54 to -0.081), with 3.86% glucose and icodextrin not being significantly different. Positive ultrafiltration occurred in 3/17 patients with 2.27% glucose, 13/17 patients with 3.86% glucose and 16/17 patients with icodextrin (chi2 P<0.0001). The difference in ultrafiltration of icodextrin and 3.86% glucose correlated with the 4 h dialysate/plasma creatinine ratio in a PET test (r = 0.51, P<0.05). Daytime Kt/V urea was greater for 3.86% glucose (median 0.27, IQR 0.20 to 0.48 per week, P<0.01) and icodextrin (median 0.31, IQR 0.27 to 0.49 per week, P<0.0001) than for 2.27% glucose (median 0.22, IQR 0.15 to 0.38 per week), with the difference between 3.86% glucose and icodextrin not reaching statistical significance (P = 0.06). Daytime creatinine clearance was greater for 3.86% glucose (median 10.2, IQR 6.9 to 13.61/week/1.73 m2, P<0.02) and icodextrin (median 12.1, IQR 9.3 to 15.71/week/1.73 m2, P<0.005) than for 2.27% glucose (median 8.8, IQR 4.9 to 11.91/week/1.73 m2). Daytime creatinine clearance was greater for icodextrin than for 3.86% glucose (P<0.005). The effects of icodextrin were sustained for the 6 month observation period. CONCLUSIONS: Icodextrin produced enhanced ultrafiltration and clearances compared with 2.27% glucose, without the exposure of the peritoneum to hypertonic glucose solutions.

Assessment of ultrasound guided percutaneous ethanol injection and parathyroidectomy in patients with tertiary hyperparathyroidism.

BACKGROUND: Tertiary hyperparathyroidism continues to cause significant morbidity in patients with chronic renal failure. This is frequently resistant to medical management and may ultimately require a surgical parathyroidectomy. Recent studies have reported upon the technique of percutaneous ethanol ablation for both primary and tertiary hyperparathyroidism. In this study we report on a 5 year experience using ethanol injection and compare the results with surgical parathyroidectomy. METHODS: A prospective study in 39 patients with tertiary hyperparathyroidism, 25 were dialysis dependent and 14 had a functioning renal allograft. Twenty-two patients underwent percutaneous fine needle ethanol injection (PFNEI) and 17 underwent surgical parathyroidectomy. RESULTS: A > 30% reduction in intact parathyroid hormone (iPTH) was achieved in 11 of 22 patients undergoing PFNEI after a mean of 1.8 +/- 1.4 injections per gland. In four patients, symptomatic hyperparathyroidism recurred and they required further PFNEI or surgical parathyroidectomy at 17, 28, 46, and 48 months later. There was no significant reduction in iPTH in 11 patients following PFNEI after a mean of 2.5 +/- 1.3 injections per gland. They all required a subsequent surgical parathyroidectomy for symptomatic hyperparathyroidism. Four patients developed a laryngeal nerve palsy following PFNEI, two of which were permanent. Seventeen patients underwent successful surgical parathyroidectomy as a primary procedure. CONCLUSION: Whilst PFNEI is successful in primary hyperparathyroidism, when typically only one adenoma is present, the effectiveness of PFNEI is unpredictable and the long term results are poor compared with those of surgical parathyroidectomy in tertiary hyperparathyroidism. The procedure is not without complications and makes subsequent surgery more difficult. Therefore it can only be recommended for patients with a known single parathyroid gland such as patients in whom hyperparathyroidism has recurred following a previous surgical subtotal parathyroidectomy and who are unsuitable for further surgery.

Association of anticardiolipin antibodies with intraglomerular thrombi and renal dysfunction in lupus nephritis.

We studied positivity for anti-cardiolipin antibody, intraglomerular capillary thrombi on renal biopsy, and the progression of renal disease in 51 patients (10 male and 41 female), mean age 37 years (range 17-65 years), with a diagnosis of systemic lupus erythematosis and clinically evident nephritis confirmed by renal biopsy. Serum creatinine, serum indicators of disease activity and biopsies were analysed in subgroups according to thrombi and anticardiolipin status. End-points were death or chronic dialysis requirement and survival. Degree of sclerosis, crescent formation and necrosed glomeruli were all greater in those specimens positive for thrombi and in those specimens of patients who were serum ACA-positive, suggesting a relationship to disease activity/severity at presentation. The increase in serum anti-DNA antibodies and ANA and the reduction in C3 and C4 were significant in ACA-positive patients, with a strong relationship to disease activity when compared with changes in the ACA-negative patients (p < 0.05 in all cases). There was no significant difference when patients were separated according to the presence or absence of thrombi. Renal function at presentation was worse in patients with intracapillary thrombi and ACA positivity (p = 0.085 and p = 0.042, respectively). All patients progressed, but only those with intracapillary thrombi or anti-cardiolipin antibody positivity had a significant deterioration in renal function. Twenty-one thrombotic episodes occurred in 14 patients, of whom 13 were ACA-positive. Anticardiolipin antibody is a strong predictor of the presence of intraglomerular thrombi in SLE patients with renal involvement. The presence of thrombi and/or anticardiolipin antibodies indicate a worse long-term renal outcome. Anti-cardiolipin antibody positivity is a strong predictor of systemic vascular thrombotic complications.

Reticulocyte indices in patients with end stage renal disease on hemodialysis.

The diagnosis of iron deficiency anaemia in haemodialysis patients is difficult. Two states of deficiency occur, storage (absolute) and functional iron deficiency. Conventional measures, lack precision in assessing both storage and functional iron deficiency. This study investigated the accuracy of reticulocyte indices in comparison to the conventional haematological measures in the identification of haemodialysis patients with iron deficiency. A cross-sectional study of 72 haemodialysis patients was performed. Mean haemoglobin was 9.6 +/- 0.16 g/dl. Mean haemoglobin content of reticulocytes (CHr) was normally distributed and correlated with MCV, MCH and red cell ferritin. Mean haemoglobin concentration of reticulocytes (CHCMr) correlated with MCH. CHr and CHCMr had positive predictive values of 0.61 and 0.54 respectively. A low CHr or CHCMr identified 5 and 4 and 17 and 21 further patients with iron deficiency with normal serum ferritin or transferrin saturation respectively. Reticulocyte measures provide a direct measure of adequacy of haemoglobin synthesis in haemodialysis patients. In this study their usefulness was somewhat limited, but requires further investigation.

'Surgical' peritonitis in the CAPD patient.

Peritonitis is the most frequent cause for emergency hospital admission in continuous ambulatory peritoneal dialysis (CAPD) patients. Patients may present with 'surgical' peritonitis from other intra-abdominal pathology, but are treated initially as CAPD-related peritonitis. We present nine such cases, each failing to respond to standard conservative treatment, and ultimately coming to laparotomy. Of the nine patients, six survived, five transferring to long-term haemodialysis and one patient returning to CAPD. Failure to respond to standard measures should alert the physician to the possibility of an intra-abdominal emergency. The presence of enteric organisms, particularly E. coli, is an additional suspicious feature. The diagnosis may be difficult and we recommend early surgical referral and appropriate surgical measures (laparotomy rather than simple catheter removal) in order to decrease morbidity and mortality.

Novel Haematological Parameters in Patients Receiving Recombinant Human Erythropoietin and Undergoing Haemodialysis.

Recombinant Human Erythropoietin (EPO) replacement therapy effectively treats the chronic anaemic associated with end stage renal disease. However due to an increase in demand, a functional iron deficiency state may arise which is characterised by an inability to supply iron and subsequent EPO resistance. Indicators of iron status are potentially misleading in this situation. Red cell ferritin (RCFer) and reticulocyte indices may be more reliable measures of functional iron deficiency. We investigated, prospectively, the value of RCFer and reticulocyte indices to detect functional iron deficiency in 11 patients, 10 male and 1 female, mean age 51 years (ranges 20-74) commencing subcutaneous EPO therapy. All patients had received oral ferrous sulphate 600 mg, total dose, daily for 6 weeks prior to starting EPO. Study subjects had a mean aluminium of 1.1 mmol/L (28.9 µg/L) and parathyroid hormone (PTH) 109pg/L. Serum folate, vitamin B12 deficiencies and bleeding diathesis were excluded. Dialysis adequacy was maintained with a mean Kt/V (a measure of the amount of plasma cleared of urea divided by the urea distribution volume V) of 1.0 and urea reduction ratio of 64%. Haemoglobin rose from a mean value of 8.0-9.9g/dl (p < 0.01). There was an associated significant fall in both serum ferritin (SF) (205.5-62.88 µg/1, p< 0.01) and RCFer (19.96-10.8 ag/red cell, p < 0.001). After 96 days of EPO therapy, 18% of patients had a demonstrably reduced RCFer (< 7 ag/red cell) whilst none had a reduced SF (< 15 µg/L) and 75% had a transferrin saturation (TS) < 20%. Mean SF levels remained consistently above 50µg/L. There was no significant change in TS verifying its poor sensitivity as a marker of functional iron deficiency. Mean haemoglobin content of reticulocytes (CHr) and mean haemoglobin concentration of reticulocytes (CHCMr) fell (p < 0.001, p < 0.01 respectively) to levels suggesting iron deficiency at 3 months. These results suggest that RCFer and CHr may help detect the onset of functional iron deficiency in patients commencing EPO therapy despite oral iron. EPO therapy leads to a significant depletion of both erythroid and storage iron.