Sleep apnoea in end-stage renal disease: a short review of mechanisms and potential benefit from its treatment.
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Atrial Natriuretic Factor↗
Biomedical subjects
Ken Farrington
Publications and source records attributed to Ken Farrington.
A dramatic reduction of normalized protein catabolic rate occurs late in the course of progressive renal insufficiency.
BACKGROUND: Spontaneous reduction in dietary protein intake is a recognized feature of severe renal failure, and previous studies have suggested that this may occur at an early stage of renal functional decline. METHODS: We examined the effects of progressive renal insufficiency on the normalized protein catabolic rate (nPCR) in 1282 patients (mean age 55.8+/-15.5 years; 60.4% male) over a 7 year period. All values of nPCR (n = 5082) obtained before commencement of dialysis were included. A total of 361 (28.2%) patients later developed end-stage renal failure and were started on dialysis. RESULTS: Cross-sectional analysis showed nPCR being significantly less at lower creatinine clearance. Mean nPCR was 1.17+/-0.31 at a clearance >50, 1.04+/-0.27 at 25-50, 0.93+/-0.21 at 10-25 and 0.74+/-0.18 at <10 ml/min. Mean nPCR in each clearance group was different from that in all other groups (P<0.001 in all cases). When nPCR was studied longitudinally in relation to time of initiation of dialysis, the fall in nPCR only became significant in the 3 months preceding initiation. Curve fitting suggested a two-phase exponential association between nPCR and renal function, a gentle decline of nPCR in mild and moderate renal failure culminating in a dramatic decline when CrCl reached 15 ml/min and weekly Kt/V(urea) 2.5. nPCR at dialysis initiation predicted survival on dialysis even when corrected for age, diabetes and non-renal co-morbid load. However, it was no longer significant when residual renal function was included in the model. The group initiating dialysis with a normal nPCR maintained this throughout the first 3 years on dialysis whilst the group initiating with a low nPCR, though improving initially, continued to have significantly lower nPCR levels throughout follow-up than their normal nPCR counterparts. CONCLUSION: A significant reduction of nPCR occurs late in progressive renal insufficiency and may predict the need for dialysis initiation. nPCR levels <0.8 at initiation predict future low nPCR levels and mortality on dialysis. The correlation between nPCR and CrCl in early renal insufficiency may be partly artefactual.
Adult↗
Switching from subcutaneous to intravenous erythropoietin alpha in haemodialysis patients requires a major dose increase.
BACKGROUND: A change in the licensing arrangements for the use of erythropoietin alpha in haemodialysis patients has required a switch in the route of administration from subcutaneous (SC) to intravenous (IV). Previous work suggested that the IV route was less efficacious but studies since the enforced switch have not confirmed this. METHODS: We studied haemoglobin levels and the mean weekly dose of erythropoietin alpha in 86 haemodialysis patients at monthly intervals over the 6 month period before and after a change in the route of administration of erythropoietin alpha from SC to IV. Changes in other parameters known to be associated with erythropoietin response were also monitored. RESULTS: Mean haemoglobin level fell following the switch from 11.9 g/dl+/-1.4 at baseline to 11.3 g/dl+/-1.4 at 1 month (P = 0.001) and to a trough of 11.0 g/dl+/-1.3 at 2 months (P<0.001) before partial recovery to 11.4 g/dl+/-1.2 (P = 0.007) at 6 months. Mean weekly dose of erythropoietin after 2 months was significantly higher than baseline (8791 IU+/-5314 vs 8035 IU+/-4893). The dose continued to increase and by 6 months was 10605 IU (P<0.001), 32% higher than baseline. There was a small reduction in residual renal function, which was an independent predictor of change in dose requirement. There was a small increase in parathyroid hormone levels, but no change in serum ferritin, dosing frequency, total Kt/V, serum albumin, normalised protein catabolic rate, C-reactive protein, hospitalization rate and dialyser reuse rate. CONCLUSIONS: Switching from SC to IV erythropoietin alpha caused a significant fall in haemoglobin levels in the first 2 months. This was partially reversed by 6 months at the expense of a 32% dose increase in the dose of erythropoietin alpha by 6 months. The economic impact may be considerable.
Anemia↗
Dialysis amyloid: the bottom line.
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Amyloidosis↗
Acute renal failure following intravesical bacille Calmette-Guérin chemotherapy for superficial carcinoma of the bladder.
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Acute Kidney Injury↗
Waldenstrom's macroglobulinemia presenting as Goodpasture's syndrome.
We report a case of Waldenstrom's macroglobulinemia (WM) presenting as classic Goodpasture's syndrome. Thrombocytopenia, an additional autoimmune phenomenon, further complicated the clinical course. Renal disease is well recognized in Waldenstrom's macroglobulinemia and other B-cell dyscrasias. Similarly, a wide spectrum of autoimmune-mediated conditions has been reported in association with paraproteinemia. However, rapidly progressive glomerulonephritis in association with antiglomerular basement membrane antibodies has never been reported as either an autoimmune or a renal manifestation of WM. This article reviews the current understanding of renal pathology and autoimmune phenomenon associated with WM.
Aged↗
Outcome in glomerulonephritis due to systemic small vessel vasculitis: effect of functional status and non-vasculitic co-morbidity.
BACKGROUND: Previous studies in systemic vasculitis have defined a number of disease-specific factors including histological parameters and clinical vasculitis activity scores as outcome predictors. This study evaluates the previously neglected role of non-vasculitic factors in determining prognosis in this condition. METHODS: We performed a retrospective study of all patients with a diagnosis of small vessel vasculitis (SVV) presenting with renal impairment to our service over a 12-year period. RESULTS: Eighty-six patients were studied (median age 63.5 years, 64% male). Mean plasma creatinine at presentation was 533 micro M (6.3 mg/dl). Forty-seven patients (55%) required immediate dialysis, 21 (45%) recovered renal function on treatment. The presence of crescent fibrosis (P < 0.05) and interstitial fibrosis (P < 0.01) were significantly associated with a failure to recover renal function. There was a trend towards an increased relapse rate in those with a persistently positive ANCA result or a rising titre. Twelve month patient survival was 85.5% and 5-year survival was 63%. Factors independently associated with mortality were Karnofsky performance score at diagnosis (P < 0.00001), intensity of immunosuppressive treatment (P = 0.0007) and vasculitis classification (P = 0.009). Non-vasculitic co-morbidity was not independently associated with mortality. Patients who were, or became after treatment, dialysis-independent had a significant survival advantage (5-year survival 83 vs 42%, P = 0.001). CONCLUSIONS: Non-vasculitic factors, particularly functional status as indicated by the Karnofsky performance score, play a major role in determining prognosis in SVV with renal involvement and should be an integral component of the decision making process when planning therapy, and in comparing outcomes between centres.
Adolescent↗
Simulation model of renal replacement therapy: predicting future demand in England.
BACKGROUND: The demand for renal replacement therapy (RRT) in England has risen steadily, although from a lower base than many other developed countries. Predicting the future demand for RRT and the impact of factors such as the acceptance rate, transplant supply and patient survival, is required in order to inform the planning of such services. METHODS: A discrete event simulation model estimates the future demand for RRT in England in 2010 for a range of scenarios. The model uses current prevalence and current and projected future acceptance rates, survival rates and the transitions between modalities to predict future patient numbers. National population and mortality data, published literature and data from the UK Renal Registry and UK Transplant, are used to estimate unmet need for RRT, the impact of changing demography and incidence of Type 2 diabetes, patient haemodialysis (HD) survival and transplant supply. RESULTS: By 2010 the predicted prevalence will have increased from about 30,000 in 2000 to between 42 and 51,000 (900-1000 p.m.p.), an average annual growth of 4.5-6%. Changing transplant supply has a small effect on overall numbers but changes the proportion of patients with functioning graft by up to 8%. Even with an optimistic increase in transplant supply (11% p.a. for 5 years), numbers on HD will continue to rise substantially, especially in the elderly. The factors most influencing future patient numbers are the acceptance rate and dialysis survival. CONCLUSION: This model predicts a substantial growth in the RRT population to 2010 to a rate approaching 1000 p.m.p., particularly in the elderly and those on HD, with a steady state not being reached for at least 25 years.
Adolescent↗
The haemodynamic response to submaximal exercise during isovolaemic haemodialysis.
INTRODUCTION: Exercise during haemodialysis has potential benefits but may compromise cardiovascular stability. We studied its acute effects on relative blood volume (RBV) and other haemodynamic parameters. METHODS: Two groups of 10 patients were exercised submaximally using a stationary cycle during isovolaemic dialysis whilst RBV was monitored continuously. In study 1, patients exercised for two 10 min periods separated by 10 min rest. Cardiac output (CO), peripheral vascular resistance (PVR), central blood volume (CBV) and stroke volume were measured using ultrasound dilution immediately before and after each exercise session. In study 2, haemoglobin, serum total protein and albumin levels were measured before and immediately after the exercise session and at the nadir of the RBV trace. RESULTS: RBV fell immediately on exercise initiation, the maximum reduction being 2.0+/-1.1% (after 5.9+/-1.4 min of exercise 1: P<0.001) and 2.0+/-1.2% (after 4.7+/-2.3 min of exercise 2: P<0.001). CO increased significantly after both periods of exercise (4.5+/-0.96 and 5.1+/-1.1 to 7.2+/-2.1 and 7.9+/-2.4 l/min, P<0.001 in both). Stroke volume increased significantly and PVR fell significantly during exercise. CBV increased in absolute terms but fell as a proportion of CO. Mean haemoglobin level at the RBV nadir was significantly higher than baseline (12.3+/-1.8 vs 11.8+/-1.7 g/dl: P<0.05: mean change 4.4+/-2.3%), as was mean total protein concentration (66.0+/-6.9 vs 62.0+/-8.1 g/l: P = 0.001: mean change 6.8+/-5.9%) and mean serum albumin concentration (36.0+/-3.9 vs 34.1+/-3.9 g/l: P<0.001: mean change 5.8+/-3.5%). CONCLUSION: The haemodynamic response to exercise during haemodialysis is comparable with that in normal individuals. The rapid reduction in RBV on exercise occurs in spite of a significant increase in CO, mainly as a consequence of fluid shifts from the microvasculature to the interstitium.
Adult↗
The relationship between systemic and whole-body hematocrit is not constant during ultrafiltration on hemodialysis.
The measurement of relative blood volume (RBV) changes during ultrafiltration assume a constant mass and distribution of circulating blood components such as hematocrit. The authors examine the validity of this assumption in 10 subjects undergoing repeated direct measurements of systemic hematocrit and plasma volume (PV(icg)) using indocyanine green dilution at four stages of dialysis with intermittent ultrafiltration. Ultrasonic RBV changes were monitored. Absolute blood volumes (ABV) were initially derived for each PV(icg) estimate, and corresponding measured systemic hematocrit was adjusted by a factor of 0.86 to correct for the difference between the systemic and whole-body hematocrit (constant Fcell ratio). PV(icg) and ABV changes correlated closely (R = 0.98; P <0.001). ABV changes overestimated reduction in PV(icg) during ultrafiltration (mean difference, -140 +/- 202 ml). The calculated red cell mass however was variable (P <0.01). Fcell ratio was then adjusted at each blood volume measurement (Fcell(1), 0.87 +/- 0.02; Fcell(2), 0.89 +/- 0.03; Fcell(3), 0.94 +/- 0.06; Fcell(4), 0.94 +/- 0.04; P <0.01) to maintain a constant red cell mass (2146 +/- 460 ml). When ABV was recalculated using PV(icg), systemic hematocrit and variable Fcell (ABV(Fvariable)), the mean difference between PV(icg) changes and ABV(Fvariable) changes, was negligible (-0.2 +/- 35 ml). During intermittent ultrafiltration, RBV changes systematically underestimated the percentage reduction in ABV (mean difference, 7.7 +/- 10.6%). When corrected for variations in Fcell, ABV(Fvariable) and RBV differences were negligible (mean difference 1.2 +/- 2.6%). Varying Fcell ratio probably reflects microvascular volume change with net fluid shift from the microcirculation to macrocirculation (intravascular refill). This may result in underestimation of changes in systemic hematocrit and RBV during dialysis such that they were less than those predicted by directly measured changes in plasma volume.
Female↗
Stability and in vitro efficacy of antibiotic-heparin lock solutions potentially useful for treatment of central venous catheter-related sepsis.
OBJECTIVES: Increasing numbers of patients for whom infection is a major risk are dependent on central venous catheters. Antibiotic-anticoagulant locks may have a role in preventing or treating catheter-related infections. The aim of this study was to determine the in vitro stability and efficacy of antibiotic-heparin lock solutions. METHODS: Candidate antibiotics (amikacin, ciprofloxacin, flucloxacillin, gentamicin, linezolid, teicoplanin) were investigated in vitro, either individually or in combination, in solution with heparin. The solutions were initially tested for visual precipitation. The efficacy of stable solutions and taurolidine was then tested in a catheter model bioassay system against microorganisms commonly encountered in catheter-related septicaemia. RESULTS: In general, lower concentrations of heparin (</=1000 U/mL) combined with antibiotics resulted in precipitation, whereas high concentrations (3500-10,000 U/mL) were compatible with a broader range of antibiotic concentrations. The stability of each antibiotic-heparin combination required individual assessment. Bioassays identified the following promising antibiotic-anticoagulant solutions: for broad-spectrum empirical cover, a teicoplanin-ciprofloxacin-heparin solution; for directed use, flucloxacillin-heparin for methicillin-susceptible Staphylococcus aureus (MSSA), high dose teicoplanin-heparin for methicillin-resistant S. aureus (MRSA), high-dose linezolid-heparin for vancomycin-resistant enterococci (VRE) and ciprofloxacin-heparin for (susceptible) Pseudomonas aeruginosa; for prophylactic use, taurolidine. CONCLUSION: These solutions now warrant clinical trials to investigate their role in the management of catheter-related septicaemia.
Anti-Bacterial Agents↗
Spinal cord infarction following central-line insertion.
Hemothorax is a recognized complication of central line insertion into the jugular or subclavian vein. We describe a case of hemothorax consequent upon acute dialysis catheter insertion, which resulted in spinal cord infarction and quadriplegia. We postulate that the extensive mediastinal shift induced after insertion of the catheter resulted in stretching of the veins draining the cord with a resultant drop in perfusion pressure and infarction. This case highlights a hitherto unreported complication of this procedure.
Catheterization, Central Venous↗
Serial determinations of absolute plasma volume with indocyanine green during hemodialysis.
Hemodynamic stability during hemodialysis depends largely on plasma volume (PV) preservation during ultrafiltration (UF). Current estimates of blood volume (BV) are indirect or involve the use of radioactive tracers, which does not allow repeated measurements during hemodialysis. Indocyanine green was used to measure PV during hemodialysis. After an initial pilot phase (phase I), PV values were determined before dialysis, repeatedly during isovolemic hemodialysis (phase II), and during stepwise UF (phase III). Absolute BV values were calculated from PV and hematocrit values. Patients were monitored for extracellular fluid volume (bioimpedance monitoring) and relative BV changes (ultrasonic monitoring). Phase I demonstrated dye stability in plasma, peak absorbance at 805 nm, and a short half-life (4.53 +/- 1.5 min). Ten milligrams of dye (2.5 mg/ml) were injected for each PV measurement. Eight plasma samples were obtained beginning 3 min after injection, at 1-min intervals, for assessment of decay characteristics. The isovolemic hemodialysis PV measurements demonstrated excellent reproducibility (r(2) = 0.98; method SD, 356 ml; mean coefficient of variation, 4.07%) and a difference of only 149 +/- 341 ml (mean +/- SD), compared with predialysis PV values (Bland-Altman method). PV values at the beginning of dialysis were significantly correlated with body surface area (r(2) = 0.82, P < 0.001) and extracellular fluid estimates (r(2) = 0.73, P < 0.001). BV prediction formulae significantly underestimated absolute BV at the start of dialysis (P < 0.0001). The findings demonstrate that this method can be used for repeated PV determinations during hemodialysis, with excellent reproducibility. It is a potential tool for further research on hemodynamic stability during UF.
Aged↗
Determinants of left ventricular hypertrophy and its progression in high-flux haemodialysis.
AIM: To identify factors contributing to the development and progression of left ventricular hypertrophy (LVH) in patients on high-flux haemodialysis. METHOD: Fifty patients without clinical cardiac disease underwent baseline echocardiography, related measurements and follow-up studies 6-12 months later. RESULTS: Residual urea clearance was lower (0.7 +/- 1.1 vs. 2.2 +/- 2.4 ml/min; p = 0.034) while systolic blood pressure (162 +/- 21 vs. 147 +/- 11 mm Hg; p = 0.003), duration of dialysis dependence (38 +/- 37 vs. 17 +/- 13 months; p = 0.004) and interdialytic weight gain (1.98 + 0.84 vs. 1.32 + 1.08 kg; p = 0.026) were higher in those with LVH. Parathyroid hormone changed less in those whose LVH regressed (186 +/- 89 vs. 303 +/- 280 pg/ml; p = 0.032). Regression did not occur when parathyroid hormone was >300 pg/ml. ACE gene polymorphism did not affect LVH development or progression. CONCLUSION: Systolic hypertension, duration of dialysis dependence and high interdialytic weight gains promote LVH. Hyperparathyroidism retards LVH regression.
Adult↗
Haemodiafiltration: current status.
Haemodiafiltration combines elements of diffusion and convection in a single treatment modality to provide solute removal over a wide range of molecular weights. Theoretically, it represents the best available form of renal replacement therapy but uptake of the technique has been slow. This pattern may change, given the growing acceptance of the potential benefits of the technique, the maturing technology including cost-efficient online production of substitution fluid, and the demonstration of the long-term safety of the technique. Long-term clinical outcome data are awaited.
Hemodiafiltration↗
Predictors of recurrent hyperparathyroidism after total parathyroidectomy in chronic renal failure.
BACKGROUND/AIMS: Recurrent hyperparathyroidism (HPT) after total parathyroidectomy (TPTX) in chronic renal failure appears more common than might be anticipated. METHODS: To study its predictors, we reviewed all 20 cases of TPTX performed at our hospital in a 10-year period. RESULTS: During follow-up (median 46.8 months (range 9.3-120.3)), 15 patients had measurable PTH levels (>10 pg/ml), 7 had levels above the normal range (recurrent HPT), and 3 had PTH levels >300 pg/ml (severe recurrent HPT). Total follow-up post-TPTX was equal in those who developed recurrent HPT and others, but those with recurrent HPT had spent longer on dialysis post-TPTX (61.9 +/- 34.9 vs. 21.8 +/- 12.0 months; p = 0.001). Patients with recurrent HPT required less vitamin D supplementation during the 10 days post-TPTX (p = 0.025). Log [maximal PTH post-TPTX] correlated with duration of dialysis dependency post-TPTX (r = 0.591, p = 0.006), lowest serum calcium level during the first 30 days post-TPTX (r = 0.449, p = 0.047), and mean serum calcium during the first 30 days post-TPTX (r = 0.546, p = 0.013). Mean log [maximal PTH post-TPTX] was significantly lower in patients with ectopic calcification (p = 0.047). In multiple regression analysis, duration of dialysis post-TPTX and lowest serum calcium level during the first 30 days post-TPTX were the only independent predictors of log [maximal PTH post-TPTX]. CONCLUSION: Recurrent HPT is common following TPTX and predicted by duration of dialysis dependency post-TPTX, a measure of overall exposure to the uraemic stimulus to parathyroid hyperplasia, and the degree of early hypocalcaemia, possibly reflecting the adequacy of operative parathyroid ablation.
Adult↗
Choosing not to dialyse: evaluation of planned non-dialytic management in a cohort of patients with end-stage renal failure.
OBJECTIVES: To study factors influencing the recommendation for palliative (non-dialytic) treatment in patients approaching end-stage renal failure and to study the subsequent outcome in patients choosing not to dialyse. DESIGN: Cohort study of patients approaching end-stage renal failure who underwent multidisciplinary assessment and counselling about treatment options. Recruitment was over 54 months, and follow-up ranged from 3 to 57 months. Groups were defined on the basis of the therapy option recommended (palliative or renal replacement therapy). SETTING: Renal unit in a district general hospital serving a population of about 1.15 million people. SUBJECTS: 321 patients, mean age +/- SD 61.5 +/- 15.4 years (range: 16-92), 57% male, 30% diabetic. MAIN OUTCOME MEASURES: Survival, place of death (hospital or community). RESULTS: Renal replacement therapy was recommended in 258 patients and palliative therapy in 63 (19.6%). By logistic regression analysis, patients recommended for palliative therapy were more functionally impaired (modified Karnofsky scale), older and more likely to have diabetes. The comorbidity severity score was not an independent predictor. Thirty-four patients eventually died during palliative treatment, 26 of whom died of renal failure. Ten patients recommended for palliative treatment opted for and were treated by dialysis. Median survival after dialysis initiation in these patients (8.3 months) was not significantly longer than survival beyond the putative date of dialysis initiation in palliatively treated patients (6.3 months). 65% of deaths occurring in dialysed patients took place in hospital compared with 27% in palliatively treated patients (p = 0.001). CONCLUSIONS: In high-risk, highly dependent patients with renal failure, the decision to dialyse or not has little impact on survival. Dialysis in such patients risks unnecessary medicalisation of death.
Adolescent↗
Identical decline of residual renal function in high-flux biocompatible hemodialysis and CAPD.
BACKGROUND: Patients on conventional hemodialysis lose residual renal function more rapidly than patients on continuous ambulatory peritoneal dialysis (CAPD). The effect of dialysis using synthetic membranes and ultrapure water is less clear. METHODS: The decline of urea clearance was compared in a cohort of 475 incident end-stage renal failure patients who received treatment with CAPD (N=175) or hemodialysis (HD) utilizing high-flux polysulphone membranes, ultrapure water, and bicarbonate as the buffer (N=300). RESULTS: CAPD patients were significantly younger, fitter (lower comorbidity severity score), less dependent (higher Karnofsky performance score) and less likely to have presented late than HD patients. There was no difference in the mean urea clearance in each group at dialysis initiation, or at any 6-month time point during the ensuing 48 months. This was true even after exclusion of patients who had died in the first year after initiation, those transferred to another dialysis modality, or those who had been transplanted. Only age and chronic interstitial disease predicted retention of urea clearance at one year. The rate of decline of urea clearance was similar in pre- and post-dialysis initiation phases, though there may have been a step-decline of about 2 mL/min at initiation, which requires further investigation. CONCLUSIONS: In hemodialysis using high-flux biocompatible membranes and ultrapure water, residual renal function declines at a rate indistinguishable from that in CAPD. This may have important implications, since preservation of residual renal function has major benefits and is a valid therapeutic goal.
Adult↗