The challenges of dialysis in systemic sclerosis: between the devil and the deep blue sea?

We present the case of a patient with systemic sclerosis (SSc) and end stage renal disease (ESRD) who experienced complications of both peritoneal and haemodialysis. We review previously reported outcomes of patients with systemic sclerosis on dialysis and discuss potential shared mechanisms in both the disease pathogenesis and dialysis-related complications, particularly with regards to encapsulating peritoneal sclerosis (EPS).

Factor H mutations in hemolytic uremic syndrome cluster in exons 18-20, a domain important for host cell recognition.

Several recent studies have established an association between abnormalities of complement factor H (FH) and the development of hemolytic uremic syndrome (HUS). To identify the relative importance of mutations in FH as a cause of HUS, we have undertaken mutation screening of the FH gene in 19 familial and 31 sporadic patients with FH. Mutations were found in two familial and three sporadic patients, and these clustered in exons 18-20, a domain important for host recognition. Moreover, this study demonstrates that familial HUS is likely to be a heterogeneous condition.

Long-hours home haemodialysis--the best renal replacement therapy method?

Two hundred and eighty-six patients (190 males and 96 females) with end-stage renal failure (ESRD) started haemodialysis (HD) at Withington Hospital between 1 January 1968 and 31 December 1986. Of these, 152 (53.1%) were successfully transplanted, while 134 had only HD or one transplant lasting < 3 months (i.e. total HD interruption < 3 months). For the whole group, the probabilities of being alive on long-hours home HD at 10 and 20 years were 58.7% and 33.2%, respectively. Mean gross mortality 1968-1986 was 6.5 +/- 3.2% per year. The main causes of death were cardiovascular (36.6%), infection-related (19.2%) and malignancy (9.6%). Males and younger cohorts had a significantly (p < 0.05) higher probability of being alive on long-hours home HD than did females and older cohorts. Eighty-two patients (29% of the total group) survived more than 10 years, of whom 54 were still alive at 1 January 1996: 44 continuing on HD while the other ten had been successfully transplanted. In these 54 patients, mean 24-h ambulatory blood pressure recorded at the date of the study was 117.6/68.9 mmHg; mean BP for the last 5 years on HD was 136.4/81.2 mmHg. Only four (7.4%) were regularly taking antihypertensive medication. Left ventricular hypertrophy (LVH) (by ECG) was present in 64.8% of the 54 patients; its prevalence by echocardiography (LVM index > 130 g/m2 for men and > 110 g/m2 for women) was 77.5%. Only 10 (18.5%) had symptoms or clinical signs of ischaemic heart disease and/or peripheral vascular disease. None had cardiac failure symptoms NYHA class 3-4. Our data show a low incidence of all-cause and cardiovascular mortality, confirming those from the Tassin unit in France, and make a medical case for extended haemodialysis treatment hours.

Urea kinetic modelling--are any of the 'bedside' Kt/V formulae reliable enough?

BACKGROUND: Longevity on dialysis is determined by many factors. One of these has increasingly been seen to be 'dialysis dose'. There are several methods for calculating dialysis dose. We wanted prospectively to test 'gold-standard' UKM-Kt/V with various shortcut bedside formulae, to see whether reliance on the latter approach was likely to lead to errors in over- or underprescribing dialysis regimens. METHODS: Ten bedside formulae for the calculation of Kt/V (urea) were compared with UKM Kt/V values, in a month-long study involving 507 dialysis sessions in 50 patients in a single-centre in-patient haemodialysis unit. RESULTS: For patients with UKM Kt/V<0.8 (median 0.69, n=140), simplified formulae had a difference (delta) of 0.094-0.396 from the calculated UKM resulting in an inter-method variability ranging from 13 to 57%. The least difference was seen with the Calzavara formula (P=NS), maximum difference with the Barth formulae (P<0.05). No statistically significant differences were seen when comparing Daugirdas 1 and 2 and Keshaviah formulae with UKM, for patients with UKM Kt/V<0.8. For patients with UKM Kt/V in the range 0.8-1.4 (median 1.06, n=285) the extreme recorded values from simplified formulae were 0.012 (least different) and 0.245 (most different) from the UKM mean, with an inter-method variability ranging between 1.1% (Basile method) to 23.1% (Calzavara). No statistically significant difference were seen when comparing Daugirdas 1 and 2, Keshaviah, and Lowrie formulae with UKM, for patients with UKM Kt/V 0.8-1.4. For patients with the highest UKM Kt/V values (>1.4; median 1.58, n=72), all simplified formulae gave Kt/V values lower than UKM Kt/V: the minimum difference was 0.070 using Jindal (P=NS, intermethod variability of 4.4%), while the maximum was seen when using Calzavara (P<0.05; difference = 0.69; intermethod variability of 43.7%). There was also no statistically significant difference for Basile and Kerr methods. For the group as a whole the biggest difference from UKM mean values was obtained using Barth's and Calzavara's formulae (delta of 0.171 and 0.140 respectively (P<0.05)). CONCLUSIONS: The best correlations were seen with the Daugirdas 2 formula (r2=0.953). Also, comparing grouped formulae containing ln(Co/Ct) terms with those incorporating the (Co-Ct)/Co ratio (i.e. the urea reduction) there was a better correlation for all formulae employing the logarithmic transformation (r2=0.951-0.953 cf. r2=0.939-0.940). Nevertheless no bedside formula had the accuracy of UKM-Kt/V.

The treatment of nephrotic syndrome caused by primary (light chain) amyloid with vincristine, doxorubicin and dexamethasone.

Three out of four patients with primary (light chain) amyloid nephrotic syndrome treated with vincristine, doxorubicin and dexamethasone (VAD) induction obtained a partial response and are alive in continuing remission at 4.1, 6.5 and 9.3 years. These preliminary results are of considerable interest and suggest that prospective evaluation of this regimen is warranted in patients with this condition.

Ambulatory blood pressure monitoring in renal dialysis and transplant patients.

Blood pressure (BP) elevation and left ventricular hypertrophy are important factors in the high cardiovascular mortality rate in patients on the renal replacement program. Ambulatory BP monitoring is widely regarded as superior to random BP monitoring in predicting end-organ damage from elevated BP. One hundred seventeen patients (60 on hemodialysis [35 with long sessions and 25 with short sessions], 29 on continuous ambulatory peritoneal dialysis, and 28 transplant recipients) underwent ambulatory BP monitoring, with target organ assessment by electrocardiography. Mean 24-hour BP for the patients with the long hemodialysis sessions (LHD) was 115.5/66.6 mm Hg, without the regular use of antihypertensive drugs. The parathormone (PTH) level was the major determinant of BP on ambulatory BP monitoring analysis, with interdialytic weight gain and age each having weaker associations. The BPs of the other three patient cohorts were much higher (short hemodialysis session [SHD], 143.2/82.1 mm Hg; continuous ambulatory peritoneal dialysis, 137.1/76.8 mm Hg; transplant recipients, 135.9/79.2 mm Hg). Overall, two thirds of the patients had reduced diurnal BP variability. Electrocardiogram voltage criteria for left ventricular hypertrophy were exceeded in approximately one third to one half of the patients. Our findings show that good control of BP is possible without recourse to antihypertensive drugs in the context of dialysis with slow ultrafiltration.

Cyclosporin A and multiple fibroadenomas of the breast.

Multiple bilateral fibroadenomas are uncommon. This finding in four women who had received renal transplants prompted further inquiry. A prospective study was performed on 39 women under the age of 55 years who had received a renal transplant at least 1 year earlier. Clinical examination and breast ultrasonography were performed. Factors considered included immunosuppressive therapy, concurrent medication and renal function. Blood was taken for estimation of oestradiol, prolactin, follicle-stimulating hormone (FSH) and sex hormone binding globulin levels. Fibroadenomas were found in 13 of 29 women who had received cyclosporin A: multiple in ten and bilateral in five. No abnormal breast findings were seen in 10 patients immunosuppressed with steroids and azathioprine alone (chi 2 = 7.30, 1 d.f., P < 0.01). Serum oestradiol concentration was raised in women with fibroadenomas compared with that in those with normal breasts (P < 0.05) and the level of FSH was lower (P < 0.01). Cyclosporin A may act on breast fibroblasts by humoral mechanisms and direct action.

Blood pressure reduction after parathyroidectomy for secondary hyperparathyroidism: further evidence implicating calcium homeostasis in blood pressure regulation.

A link between plasma calcium, dietary cations, and blood pressure has been suspected for some time, with human, experimental animal, and epidemiological data adduced to support this hypothesis. We identified 21 patients receiving regular maintenance hemodialysis, but not receiving any regular antihypertensive treatment, who had undergone 22 surgical removals of the parathyroid glands in the period 1978 to 1992. These patients' records were then scrutinized. The group preparathyroidectomy mean systolic blood pressure (BP) was 142.6 +/- 19.4 mm Hg. After the operation, the mean systolic BP was 133.6 +/- 21.9 mm Hg (P = 0.004). Plasma calcium decreased from 2.72 +/- 0.18 mmol/L to 2.52 +/- 0.19 mmol/L (P < 0.001). There was a correlation between the decreases in systolic blood pressure (SBP) (9.4%) and plasma calcium (7.3%); r = 0.60, P = 0.012. The decrease in SBP was not immediate, but delayed some months and complete by approximately 9 months after the operation. Furthermore, using ambulatory BP monitoring in a group of long-term hemodialysis patients, we found that parathyroidectomized patients had lower BP and pulse rates than those with intact parathyroid glands (SBP, 122.9 +/- 16.3 mm Hg v 102.9 +/- 9.9 mm Hg; pulse rates, 87.5 +/- 12.7 v 72.0 +/- 7.5 beats/min, P < .001, nonparathyroidectomy v postparathyroidectomy, both comparisons). These data support a link between plasma calcium and BP in patients receiving maintenance hemodialysis.

Treating paracetamol overdose by charcoal haemoperfusion and long-hours high-flux dialysis.

After serious paracetamol overdose, charcoal haemoperfusion was used to remove paracetamol from the circulation, aiming to reduce the severity of subsequent hepatic damage. Daily long-hours high-flux dialysis was given to patients with grade III-IV hepatic encephalopathy, and also to those at risk of developing encephalopathy. We reviewed patients treated in this manner who had not received N-acetylcysteine within the first 15 h after overdose. From January 1983 to January 1993, 73 patients with serious paracetamol overdose were seen, of whom 51 received charcoal haemoperfusion and/or high-flux dialysis. Patients who were admitted within the first 42 h after overdose and who received haemoperfusion and/or dialysis had significantly lower peak levels of prothrombin time, bilirubin and creatinine than those who were admitted after 42 h. Mortality was also lower amongst patients admitted before 42 h, at 2/18 (11%) vs. 15/33 (45%), p < 0.05.

Echocardiographic findings in long-term, long-hour hemodialysis patients.

This article describes the echocardiographic structural and functional findings in a cohort of 30 patients on ten or more years of uninterrupted long-hour (24 hours per week dialysis schedule) hemodialysis (mean duration 187.7 months, range 120 to 299 months). Cardiac structural analysis was remarkable for the prevalence of LVH (76%), very rarely asymmetric (3%). Hemoglobin and (log) plasma renin activity were determinants of the LV wall thickness ratio (r = -0.57 and 0.54, p = 0.003 and 0.044 respectively). Markers of systolic contractile function were frequently normal (100% MVCFS; 85% FSI). Diastolic ventricular compliance was abnormal in 59% of patients. Blood pressure history appeared important in determining LVH, but office/ABPM measures of BP were not. Patients after parathyroidectomy (PTx) had a smaller LVPWTN (8.68 mm/m2 without PTx cf 7.01 mm/m2 after PTx, p = 0.036). Left ventricular cavity size was rarely enlarged (10%), with hemoglobin (r = -0.47, p = 0.012) and PTH (r = -0.65, p < 0.001) the major determinants of EDDN. Left atrial diameter was increased in 77% of patients. Cardiac valvular calcification was seen in 50% of patients. Our findings show that despite good BP control without recourse to antihypertensive drugs, LVH with good LV systolic function is very common in these long-survivors.

Is peritoneal permeability an adverse risk factor for malnutrition in CAPD patients?

In light of the correlation between the dialysate to plasma ratio of creatinine (D/P Cr), peritoneal (PD) protein loss and hypoalbuminaemia, peritoneal permeability has been implicated as a risk factor for malnutrition in CAPD patients. However, serum albumin is also affected by hydration which is itself influenced by peritoneal permeability. In a cross-sectional study of 147 CAPD patients we investigated the relationship between peritoneal permeability, PD protein loss and nutritional state. Stepwise regression analysis revealed D/P Cr to be the only significant predictor of serum albumin independent of PD protein loss. No significant relationship was demonstrated between D/P Cr, body fat, lean muscle mass and dietary protein intake. Increased peritoneal permeability does not cause hypoalbuminaemia as a consequence of increased PD protein loss, and does not adversely affect somatic fat and protein status.

Vasculitis and rapidly progressive glomerulonephritis in the elderly.

The proportion of patients with vasculitis and rapidly progressive nephritis aged 70 years or over has risen from about 10% in the 1980s to over 30% in series reported in the 1990s. This study was undertaken to examine the presentation and outcome of such older patients. Seventeen of 56 patients (30%) who presented at two renal units were aged 70 years or over. Mean creatinine level at presentation was 530 mumol/l, and five patients received dialysis at presentation. Outcome was dependent on three factors, namely comorbid pathology, response to immunosuppressive therapy, and the occurrence in three cases of temporary spontaneous partial remission. Overall patient survival at one and two years was 62.5% and 50%, respectively, and 90% and 100% of surviving patients were independent of dialysis at one and two years, respectively. Response to chemotherapy was excellent, with full rehabilitation in many cases and no deaths directly attributable to adverse effects of immunosuppressive therapy. We conclude that diagnosis of vasculitis and rapidly progressive glomerulonephritis by renal biopsy and the subsequent administration of chemotherapy (including cyclophosphamide in many cases) resulted in a worthwhile benefit in these elderly patients.

Severe theophylline poisoning: charcoal haemoperfusion or haemodialysis?

Theophylline poisoning with a blood level of 183 mg/l in a 38-year-old man was treated with activated charcoal by mouth, but despite this the blood level of theophylline rose and there was circulatory collapse with rhabdomyolysis, acute renal failure and hyperthermia. Treatment with charcoal haemoperfusion and simultaneous haemodialysis was given, followed by continuous arteriovenous haemodialysis (CAVHD). Mean extraction rates of theophylline were 26% during CAVHD, and 86% during combined dialysis and charcoal haemoperfusion. During combined treatment, the mean extraction rate of haemodialysis was 62%, compared with 48% for charcoal haemoperfusion. In summary, activated charcoal given by mouth may be unable to prevent a rise in blood levels and the development of complications after substantial theophylline overdose. If theophylline is to be removed from the blood, a combination of charcoal haemoperfusion and haemodialysis will give the best clearance, but haemodialysis alone may be effective.

Limitations of the peritoneal equilibration test in prescribing and monitoring dialysis therapy.

Based on correlation analysis with 24-h dialysis collections the peritoneal equilibration test (PET) has been promoted as an aid to prescribe and monitor dialysis dose. However correlation is an incorrect statistical technique to demonstrate the similarity of one measure to another. The closeness (or limits) of agreement should be measured using the technique of Bland and Altman. One hundred and nineteen patients underwent a 24-h dialysate collection and a PET. D/P ratios for urea and creatinine, dialysate volume, urea and creatinine clearance and KT/V (urea) were calculated using both methods and compared using correlation analysis. In addition the limits of agreement, reflecting the potential margins of difference between the two methods, were determined. When used to calculate a daily dialysate volume required to achieve adequacy targets, the PET was found to result in a prescription error range of -0.6 to +1.51/day for creatinine clearance and -0.9 to +0.61/day for urea clearance. The tendency of the PET to exaggerate clearance resulted in 14% of patients incorrectly achieving a target creatinine clearance of 50 1/week and 17% incorrectly reaching a target KT/V of 1.7. The PET cannot be used in place of 24-h dialysis collections to prescribe or monitor dialysis therapy.

Elective rather than emergency intervention for acute renal artery occlusion with anuria.

We describe a case in which surgical revascularisation was electively delayed until 27 days after acute renal artery occlusion, allowing surgery to be performed after a period of haemodialysis and pre-operative cardiac assessment. Owing to the collateral blood supply to the kidney, emergency surgery in cases of acute renal artery occlusion may not be necessary, and may be hazardous.

Wegener's granulomatosis and the heart.

Three cases of Wegener's granulomatosis with cardiac complications are described and the relevant published reports are reviewed. The first case of Wegener's granulomatosis was associated with aortic regurgitation and required aortic valve replacement. The second and third cases were associated with pericardial disease requiring pericardiectomy for constructive pericarditis in one case, and haemorrhagic pericarditis with pericardial effusion in the other. Aortic valve involvement in Wegener's granulomatosis is uncommon and valve replacement has been described on only one previous occasion. Pericardial involvement is relatively common pathologically, but pericardial surgery has been described in this condition only twice, once for tamponade and once for constrictive pericarditis after pericardiocentesis. Cardiac involvement is not uncommon in patients with Wegner's granulomatosis and may be clinically important. Diagnosis is aided by estimation of the anti-neutophil cytoplasmic antibody titre.

The normalized protein catabolic rate is a flawed marker of nutrition in CAPD patients.

For both hemodialysis and CAPD patients nutrition has been linked to mortality. Protein calorie malnutrition is present in 20 to 40% of CAPD patients. The normalized protein catabolic rate (NPCR), has been proposed as a useful measure of dietary protein intake and ultimately nutrition. However, the NPCR value has not been consistently predictive of outcome in CAPD patients. We have performed a cross sectional study on 147 clinically stable CAPD patients, who had a mean dialysis duration 22 months, to evaluate the relationship between the NPCR and conventional markers of nutrition. The NPCR was significantly correlated with normalized models of dialysis adequacy including KT/V (urea), total weekly creatinine clearance and the dialysis index. A significant negative correlation was found between individual anthropometric measures and the NPCR. Using a composite nutritional index to nutritionally categorize our population we found a significantly higher NPCR value in the severely malnourished group. The unadjusted protein catabolic rate (PCR) was significantly correlated with individual nutritional measures and was significantly greater in the well-nourished group. The NPCR, obtained by dividing the PCR by body weight (itself a nutritional measure), is lowest in well-nourished or obese patients, and thus as a marker of nutrition may be flawed. The PCR has nutritional relevance, however, adjusting its value to take into account patient size will require prospective evaluation of the influence of small solute removal on body composition.