Urinary retinol binding protein predicts renal outcome in systemic immunoglobulin light-chain (AL) amyloidosis.

Renal risk stratification in systemic immunoglobulin light-chain (AL) amyloidosis is according to estimated glomerular filtration rate (eGFR) and urinary protein creatinine ratio (uPCR), the latter attributed to glomerular dysfunction, with proximal tubular dysfunction (PTD) little studied. Urinary retinol binding protein 4 (uRBP), a low molecular weight tubular protein and highly sensitive marker of PTD, was prospectively measured in 285 newly diagnosed, untreated patients with systemic AL amyloidosis between August 2017 to August 2018. At diagnosis, the uRBP/creatinine ratio (uRBPCR) correlated with serum creatinine (r = 0·618, P < 0·0001), uPCR (r = 0·422, P < 0·0001) as well as both fractional excretion of phosphate and urate (r = 0·563, P < 0·0001). Log uRBPCR at diagnosis was a strong independent predictor of end-stage renal disease {hazard ratio [HR] 2·65, [95% confidence interval (CI) 1·06-6·64]; P = 0·038}, particularly in patients with an eGFR >30 ml/min/1.73 m2 [HR 4·11, (95% CI 1·45-11·65); P = 0·008] and those who failed to achieve a deep haematological response to chemotherapy within 3 months of diagnosis [HR 6·72, (95% CI 1·83-24·74); P = 0·004], and also predicted renal progression [HR 1·91, (95% CI 1·18-3·07); P = 0·008]. Elevated uRBPCR indicates PTD and predicts renal outcomes independently of eGFR, uPCR and clonal response in systemic AL amyloidosis. The role of uRBPCR as a novel prognostic biomarker merits further study, particularly in monoclonal gammopathies of renal significance.

Cardiorenal AL amyloidosis: risk stratification and outcomes based upon cardiac and renal biomarkers.

Systemic AL amyloidosis is a cause of type 5 cardiorenal syndrome. Response to treatment is currently reported according to organ-specific amyloidosis consensus criteria (ACC), which are not validated in cardiorenal AL amyloidosis. Of 1000 patients prospectively enrolled into the UK ALchemy study, 318 (32%) had combined cardiac and renal amyloidotic organ dysfunction at diagnosis, among whom 199 (63%) died; median survival by Kaplan-Meier analysis was 18·5 months. Fifty (16%) patients required renal replacement therapy (RRT). At diagnosis, independent predictors of death and dialysis were N-terminal pro-B-type natriuretic peptide (NT-proBNP) >8500 ng/l (hazard ratio [HR] 3·30, P < 0·001; HR 3·00, P < 0·001), and estimated glomerular filtration rate (eGFR) < 30 ml/min/1·73 m2 (HR 1·89, P = 0·011; HR 6·37, P < 0·001). At 6 months, an increase in NT-proBNP of >30% and a reduction in eGFR of ≥25% were independent predictors of death (HR 2·17, P = 0·009) and dialysis (HR 3·07, P = 0·002), respectively. At 12 months, an increase in NT-proBNP >30% was highly predictive of death (HR 3·67, P < 0·001) and dialysis (HR 2·85, P = 0·010), whereas ACC renal response was predictive of neither. Cardiorenal AL amyloidosis is associated with high early mortality. Outcomes are dictated by NT-proBNP and eGFR at diagnosis rather than proteinuria, and thereafter predominantly by changes in NT-proBNP concentration.

Serum free light chain levels and renal function at diagnosis in patients with multiple myeloma.

BACKGROUND: Renal impairment (RI) is common in multiple myeloma (MM) and is associated with poor survival. This study reports the associations between renal function and disease characteristics including serum free light chain (FLC) level at diagnosis in patients with MM. METHODS: Using data from the Medical Research Council Myeloma IX trial, a multicentre, randomized, open-label, phase III and factorial-design trial, we assessed the relationships between renal function, demographic, and disease characteristics, including serum FLC levels, in 1595 newly diagnosed MM patients. Multivariable linear regression was utilised to identify factors that were associated with renal function at diagnosis. A receiver operating characteristic curve (ROC) was used to identify the optimal threshold for serum FLC level at diagnosis to predict severe RI. RESULTS: 52.8% of patients had an estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 (no RI), 37.3% an eGFR 30-59 ml/min/1.73 m2 (mild to moderate RI), and 9.8% an eGFR < 30 ml/min/1.73 m2 (severe RI). In a multivariable analysis, factors independently and negatively associated with eGFR at diagnosis were: higher serum FLC level, female gender, and older age. Elevated serum FLC level at diagnosis, irrespective of the paraprotein type, was strongly associated with severe RI. Receiver operating characteristic curve analysis showed a serum FLC level of > 800 mg/L as the optimal cut-off associated with severe RI (area under curve 0.86, 95% confidence interval 0.77-0.84). CONCLUSION: There was a strong relationship between higher serum FLC levels at diagnosis and the severity of RI that was irrespective of the paraprotein type. We report an increased risk of severe RI in patients presenting with serum FLC levels above 800 mg/L at diagnosis.

Prolonged renal survival in light chain amyloidosis: speed and magnitude of light chain reduction is the crucial factor.

Renal involvement causing progressive chronic kidney disease (CKD) is present in 70% of patients with systemic Ig light-chain (AL) amyloidosis at diagnosis. Chemotherapy that substantially suppresses free light chain production is associated with improved patient survival, but its benefit in delaying the onset of renal replacement therapy among patients who present with established advanced CKD has not been studied. To evaluate this, we studied 1000 patients enrolled in the prospective UK AL amyloidosis chemotherapy study (ALchemy). Of these, 84 patients had advanced amyloid-related CKD defined by an estimated glomerular filtration rate (eGFR) under 20 ml/min/1.73 m2. We determined outcomes among these 84 patients, who had a median eGFR of 10 ml/min/1.73 m2, in relation to response to chemotherapy evaluated at three, six, and 12 months from baseline. Patients who achieved suppression of 90% or more in their amyloidogenic free light chain (dFLC) within three months of baseline had significantly better overall survival, prolonged time to dialysis, and prolonged time to the composite endpoint of 'death or dialysis' compared to those who achieved lesser degrees of clonal response at the same time point. Even when this target of greater than 90% dFLC response was achieved but was delayed beyond 3 months, it was associated with worse outcomes. Cox regression analyses confirmed that a 90% or better dFLC response within 3 months was the only significant independent predictor of all three of these outcome measures. Thus, renal survival among patients with systemic immunologic light chain amyloidosis who present with advanced CKD is strongly dependent upon the magnitude and speed with which the underlying hematologic disorder is suppressed by chemotherapy.

Increased fracture risk in plasma cell dyscrasias is associated with poorer overall survival.

Pathological fractures are a common complication of plasma cell dyscrasias (PCD) and are associated with significant morbidity. Routine use of bisphosphonates over the past decade has aimed to reduce the risk of fractures in patients with multiple myeloma, but despite this, fractures continue to represent a significant burden of disease. In this study we report the fracture rate of hospital in-patients with PCD in England. Data from the national registry Hospital Episode Statistics between 2001 and 2015 were used to determine fracture rate and its effect on overall survival. Fracture rates were 17·8 times higher than the general population in the first year after admission with PCD, and remained elevated for up to 10 years after first admission. The increased fracture risk preceded the first admission with PCD and, conversely, the incidence of PCD increased after admission with one or more fractures. Overall survival is improving with PCD, however poorer survival is found in patients with a preceding fracture (Hazard ratio 1·20). Despite widespread bisphosphonate use, fractures remain common in PCD, and are associated with poorer outcomes.

Facing the facts: The Runx2 gene is associated with variation in facial morphology in primates.

The phylogenetic and adaptive factors that cause variation in primate facial form-including differences among the major primate clades and variation related to feeding and/or social behavior-are relatively well understood. However, comparatively little is known about the genetic mechanisms that underlie diversity in facial form in primates. Because it is essential for osteoblastic differentiation and skeletal development, the runt-related transcription factor 2 (Runx2) is one gene that may play a role in these genetic mechanisms. Specifically, polymorphisms in the QA ratio (determined by the ratio of the number of polyglutamines to polyalanines in one functional domain of Runx2) have been shown to be correlated with variation in facial length and orientation in other mammal groups. However, to date, the relationship between variation in this gene and variation in facial form in primates has not been explicitly tested. To test the hypothesis that the QA ratio is correlated with facial form in primates, the current study quantified the QA ratio, facial length, and facial angle in a sample of 33 primate species and tested for correlation using phylogenetic generalized least squares. The results indicate that the QA ratio of the Runx2 gene is positively correlated with variation in relative facial length in anthropoid primates. However, no correlation was found in strepsirrhines, and there was no correlation between facial angle and the QA ratio in any groups. These results suggest that, in primates, the QA ratio of the Runx2 gene may play a role in modulating facial size, but not facial orientation. This study therefore provides important clues about the genetic and developmental mechanisms that may underlie variation in facial form in primates.

Multiple myeloma can be accurately diagnosed in acute kidney injury patients using a rapid serum free light chain test.

BACKGROUND: Acute kidney injury (AKI) is common in patients with multiple myeloma (MM). Whether serum free light chain (sFLC) measurements can distinguish between myeloma and other causes of AKI requires confirmation to guide early treatment. A rapid and portable sFLC test (Seralite®) is newly available and could reduce delays in obtaining sFLC results and accelerate diagnosis in patients with unexplained AKI. This study evaluated the accuracy of Seralite® to identify MM as the cause of AKI. METHOD: sFLCs were retrospectively analysed in patients with AKI stage 3 as per KDIGO criteria (i.e. serum creatinine ≥354 µmol/L or those on dialysis treatment) (n = 99); 45/99 patients had a confirmed MM diagnosis. RESULTS: The Seralite® κ:λ FLC ratio accurately diagnosed all MM patients in the presence of AKI: a range of 0.14-2.02 returned 100% sensitivity and specificity for identifying all non-myeloma related AKI patients. The sFLC difference (dFLC) also demonstrated high sensitivity (91%) and specificity (100%): an optimal cut-off of 399 mg/L distinguished between myeloma and non-myeloma AKI patients. We propose a pathway of patient screening and stratification in unexplained AKI for use of Seralite® in clinical practice, with a κ:λ ratio range of 0.14-2.02 and dFLC 400 mg/L as decision points. CONCLUSIONS: Seralite® accurately differentiates between AKI due to MM and AKI due to other causes in patients considered at risk of myeloma. This rapid test can sensitively screen for MM in patients with AKI and help inform early treatment intervention.

Patients with multiple myeloma have excellent long-term outcomes after recovery from dialysis-dependent acute kidney injury.

OBJECTIVES: The aim of this study was to report the long-term outcomes in patients with multiple myeloma (MM) who receive dialysis treatment for acute kidney injury (AKI) due to myeloma cast nephropathy and subsequently recover renal function. METHODS: Patients presenting with dialysis-dependent AKI secondary to myeloma cast nephropathy and subsequently recovering independent renal function between January 2005 and December 2012 were included in this study. Both renal and haematological parameters were collected at multiple time points as part of routine clinic practice. Factors associated with renal function and overall survival (OS) were determined. RESULTS: Twenty-four patients fulfilled the criteria for inclusion. Mean age was 62.1 years; 75% were male and 75% were of White ethnicity. The median OS was 64.1 months (95% confidence interval [CI] 34.8-93.3). Twenty-three (95.8%) patients remained dialysis-independent until death or end of follow-up; one patient required further haemodialysis treatment during the follow-up period. The independent determinant of worse OS was a known history of chronic kidney disease (CKD) at presentation. Shorter length of time on haemodialysis and higher percentage reduction in clonal serum FLC at day 21 from baseline predicted better excretory renal function (estimated glomerular filtration rate) at 6 months. CONCLUSION: In this series, the large majority of patients with MM and dialysis-dependent AKI secondary to myeloma cast nephropathy who recovered independent renal function had no requirement for further dialysis. Survival following recovery of renal function is good, and early variables are independently associated with survival and future renal function.

Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival.

Bortezomib has shown great promise in the treatment of amyloid light-chain (AL) amyloidosis. We present our experience of 43 patients with AL amyloidosis who received cyclophosphamide, bortezomib, and dexamethasone (CVD) upfront or at relapse. Of these, 74% had cardiac involvement and 46% were Mayo Cardiac Stage III. The overall hematologic response rate was 81.4%, including complete response (CR) in 41.9% and very good partial response with >90% decrease in difference between involved/uninvolved light chain (VGPR-dFLC) in 51.4%. Patients treated upfront had higher rates of CR (65.0%) and VGPR-dFLC (66.7%). The estimated 2-year progression-free survival was 66.5% for patients treated upfront and 41.4% for relapsed patients. Those attaining a CR or VGPR-dFLC had a significantly better progression-free survival (P=.002 and P=.026, respectively). The estimated 2-year overall survival was 97.7% (94.4% in Mayo Stage III patients). CVD is a highly effective regimen producing durable responses in AL amyloidosis; the deep clonal responses may overcome poor prognosis in advanced-stage disease.

Extending the reach of expert amyloidosis care: A feasibility study exploring the staged implementation of a UK amyloidosis network.

There has been an exponential increase in the diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CA). In response, the Midlands Amyloidosis Service was launched with the aim of providing patients with a timely diagnosis, remote expertise from the National Amyloidosis Centre and access to emerging transthyretin (TTR)-directed therapies. This was a descriptive study of a pilot hub-and-spoke model of delivering specialist amyloidosis care. Patients with suspected amyloidosis were referred from the wider Midlands region, and seen in a consultant-led multidisciplinary clinic. The diagnosis of ATTR-CA was established according to either the validated non-biopsy criteria or histological confirmation of ATTR deposits with imaging evidence of amyloid. Study endpoints were the volume of service provision and the time to diagnosis from the receipt of referral. Patients (n=173, age 75±2 years; male 72 %) were referred between 2019 and 2021. Eighty patients (46 %) were found to have cardiac amyloidosis, of whom 68 (85 %) had ATTR-CA. The median time from referral to diagnosis was 43 days. By removing the need for patients to travel to London, an average of 187 patient-miles was saved. Fifteen (9 %) patients with wild-type ATTR-CA received tafamidis under the Early Access to Medicine scheme; 10 (6 %) were enrolled into phase 3 clinical trials of RNA interference or antisense oligonucleotide therapies. Our results suggest that implementing a UK amyloidosis network appears feasible and would enhance equity of access to specialised amyloidosis healthcare for the increasing numbers of older patients found to have ATTR-CA.

Systemic amyloidosis in England: an epidemiological study.

Epidemiological studies of systemic amyloidosis are scarce and the burden of disease in England has not previously been estimated. In 1999, the National Health Service commissioned the National Amyloidosis Centre (NAC) to provide a national clinical service for all patients with amyloidosis. Data for all individuals referred to the NAC is held on a comprehensive central database, and these were compared with English death certificate data for amyloidosis from 2000 to 2008, obtained from the Office of National Statistics. Amyloidosis was stated on death certificates of 2543 individuals, representing 0·58/1000 recorded deaths. During the same period, 1143 amyloidosis patients followed at the NAC died, 903 (79%) of whom had amyloidosis recorded on their death certificates. The estimated minimum incidence of systemic amyloidosis in the English population in 2008, based on new referrals to the NAC, was 0·4/100 000 population. The incidence peaked at age 60-79 years. Systemic AL amyloidosis was the most common type with an estimated minimum incidence of 0·3/100 000 population. Although there are various limitations to this study, the available data suggest the incidence of systemic amyloidosis in England exceeds 0·8/100 000 of the population.

A prospective study of nutritional status in immunoglobulin light chain amyloidosis.

Weight loss is common in systemic immunoglobulin light chain amyloidosis but there are limited data on the impact of nutritional status on outcome. Using the Patient-Generated Subjective Global Assessment (PG-SGA) score, we prospectively examined nutritional status in 110 consecutive newly-diagnosed, treatment-naïve patients with immunoglobulin light chain amyloidosis attending the UK National Amyloidosis Centre. At study entry, 72 of 110 (66%) patients had a PG-SGA score of 4 or over, indicating malnutrition requiring specialist nutritional intervention. Number of amyloidotic organs, elevated alkaline phosphatase, presence of autonomic neuropathy and advanced Mayo disease stage were independently associated with poor nutritional status (P<0.05). Quality of life was substantially poorer among those with higher PG-SGA scores (P<0.001). Furthermore, PG-SGA score was a powerful independent predictor of patient survival (P=0.02). Malnutrition is prevalent and is associated with poor quality of life and reduced survival among patients with systemic immunoglobulin light chain amyloidosis. The PG-SGA score would be an appropriate tool to evaluate whether nutritional intervention could improve patient outcomes.

Inflammatory bowel disease and systemic AA amyloidosis.

BACKGROUND: Systemic AA amyloidosis is a recognised complication of inflammatory bowel disease. AA amyloidosis is a potential cause of end-stage renal failure and mortality but little is known of the natural history of this condition in inflammatory bowel disease. METHODS: We evaluated the clinical phenotype, disease progression and outcome amongst 26 patients with inflammatory bowel disease and AA amyloidosis followed prospectively at a single center between 1989 and 2010. RESULTS: Twenty-two patients had Crohn's disease and four had ulcerative colitis. Fistulae and abscesses occurred in ten cases, all of whom had Crohn's disease. Amyloidotic proteinuric renal dysfunction occurred in all of the cases. It resolved in five patients with well-controlled inflammation, but was progressive in all of the other patients. Fifteen patients reached end-stage renal disease after a median time of 6.3 years from development of renal dysfunction (by Kaplan-Meier estimate), six of whom subsequently proceeded to renal transplantation. There were five functioning grafts at census 0.8, 3.2, 4.2, 20.1 and 24.6 years after transplantation. One graft failed 14.5 years after renal transplantation because of amyloid recurrence in a patient with sustained chronic inflammatory activity. CONCLUSIONS: AA amyloidosis remains a serious complication of both Crohn's disease and ulcerative colitis, and is characterized by proteinuric renal dysfunction that may resolve following suppression of inflammatory activity. Patient and graft survival are excellent in patients who undergo renal transplantation.

Systemic AA amyloidosis.

Systemic AA amyloidosis is a rare complication of chronic inflammatory disorders. The amyloid fibrils are derived from serum amyloid A protein, an acute phase protein synthesized in the liver. Clinical presentation is most commonly due to the consequences of renal involvement, with proteinuria and progressive renal decline. Progression to end stage renal failure is common. Management is currently centred on reducing the supply of the precursor protein by treating the underlying inflammatory condition, whilst supporting the affected organs. Monitoring of the serum amyloid A protein is vital to assess whether there is adequate suppression of the underlying disease. The level of serum amyloid A protein is a powerful predictor of both patient survival and renal outcome. In patients with adequate suppression of the serum amyloid A protein amyloid deposits can be seen to regress and renal function can be stabilised and even improve.

Cardiac phenotype and clinical outcome of familial amyloid polyneuropathy associated with transthyretin alanine 60 variant.

AIMS: Familial amyloid polyneuropathy (FAP) is a dominantly inherited multi-system disease associated with transthyretin (TTR) mutations. Previous series have predominantly described patients with the TTR variant Val30Met (V30M), which is the most prevalent cause of FAP worldwide. Here, we report the dominant cardiac phenotype and outcome of FAP associated with TTR Thr60Ala (T60A), the most common UK variant. METHODS AND RESULTS: Sixty consecutive patients with FAP associated with TTR T60A (FAP T60A) were prospectively evaluated in two centres between 1992 and 2009. Median (range) age of symptom development was 63 (45-78) years. A family history of amyloidosis was present in only 37%. Autonomic and peripheral neuropathy were present in 44 and 32 patients, respectively, at diagnosis. Cardiac involvement was evident on echocardiography at diagnosis in 56 patients, but was associated with reduced QRS voltages on electrocardiography in only 16% evaluable cases. Seventeen patients received implantable anti-arrhythmic devices. Median survival was 6.6 years following onset of symptoms and 3.4 years from diagnosis, and correlated with serum N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentration and certain echocardiographic parameters at the latter. Orthotopic liver transplantation (OLT), performed to eliminate the predominant hepatic source of variant TTR T60A protein, was performed in eight patients including one who received a concomitant cardiac transplant. Cardiac amyloidosis progressed in all lone OLT recipients, of whom four died within 5 years. CONCLUSION: Cardiac amyloidosis is almost always present at diagnosis in FAP T60A, and is a major determinant of its poor prognosis. Outcome of liver transplantation in FAP T60A has been discouraging.

The electrocardiographic features associated with cardiac amyloidosis of variant transthyretin isoleucine 122 type in Afro-Caribbean patients.

BACKGROUND: About 4% of African Americans possess the isoleucine 122 (V122I) variant of transthyretin, associated with cardiac amyloidosis beyond ages of 55 to 60 years. Transthyretin amyloidosis associated with variant V122I (ATTR V122I) is likely to be an important cause of heart failure in Afro-Caribbean populations, but the high prevalence of left ventricular hypertrophy (LVH) and lack of awareness of this genetic disorder pose diagnostic hurdles. We report the electrocardiographic (ECG) features of ATTR V122I in the largest clinical series to date. METHODS: Patients with ATTR V122I were identified in collaboration with the UK National Amyloidosis Centre. The ECG at presentation was assessed for cardiac rhythm, axis, and voltage complex size. RESULTS: We include 64 patients with ATTR V122I, with a median age of 74 years (range, 57-88 years). Normal or increased ECG voltage was present in 44.3% of patients, and overall 25% met the criteria for LVH. A significant negative correlation between voltage complex size and duration of illness was seen (P < .05). First-degree heart block was evident in 56% of patients in sinus rhythm. During follow-up (n = 17; median, 28 months), 50% of patients with initial first-degree heart block required pacing. CONCLUSION: Electrocardiographic voltages meet the criteria for LVH in one quarter of patients with ATTR V122I cardiac amyloidosis. The widely held belief that cardiac amyloidosis is associated with low-voltage complexes is likely to contribute to underdiagnosis of ATTR V122I. First-degree heart block is common at diagnosis and identifies patients at high risk for subsequent pacing requirement.

Haemodiafiltration versus high-flux haemodialysis: Effects on phosphate control and erythropoietin response.

INTRODUCTION: Haemodiafiltration (HDF) has been reported to improve erythropoietin (EPO) responsiveness and phosphate clearance. We prospectively audited the effect of HDF on EPO dosages, weight and serum phosphate. METHODS: 34 patients dialyzing on Tu/Th/Sa switched to HDF, and 44 dialyzing on M/W/F remained on high-flux haemodialysis (HD) and were followed for 12 months. RESULTS: Dialysis adequacy (Kt/V start HDF 1.56 ± 0.03 vs. HD 1.58 ± 0.04 and 12 months 1.55 ± 0.03 vs. 1.59 ± 0.03), haemoglobin (start 11.7 ± 0.3 vs. 11,8 ± 0.2 g/dl and end 11.5 ± 0.1 vs. 11.3 ± 0.3 g/dl), weight (start 69.8 ± 2.4 vs. 67.8 ± 2.5 kg and end 67.4 ± 2.5 vs. 66.1 ± 2.3 kg), or EPO prescription (start 83 (61-186) vs. 123 (71-225) IU/kg/weeks and 12 months 142 (48-188) vs. 124 (59-223) IU/kg/weeks) did not differ. There were no differences in serum albumin, CRP, calcium and parathyroid hormone. Serum beta-2-microglobulin (B2M) decreased with HDF (32.7 ± 1.9 vs. 28.1 ± 1.1 mg/l, p < 0.01), but not with HD (31.6 ± 1.4 vs. 31.5 ± 1.1 mg/l). Serum phosphate fell with HDF (start 1.48 ± 0.08 vs. 1.57 ± 0.07 mmol/l (p = NS); 3 months 1.35 ± 0.07 vs. 1.61 ± 0.08; 6 months 1.34 ± 0.06 vs. 1.57 ± 0.06, and 12 months 1.36 ± 0.07 vs. 1.67 ± 0.07, all p < 0.05). CONCLUSION: HDF did not lead to weight gain or improved EPO responsiveness in this prospective observational study. However, predialysis serum phosphate and B2M fell with HDF.

The effect of vascular access modality on changes in fluid content in the arms as determined by multifrequency bioimpedance.

INTRODUCTION: Intradialytic hypotension remains the commonest complication of routine outpatient haemodialysis treatments. Multifrequency bioimpedance allows assessment of body fluid volumes. Multifrequency bioimpedance can potentially monitor changes in extracellular volume during dialysis and may therefore help to reduce intradialytic hypotension. Hypotension-prone patients have been reported to start dialysis with relatively more fluid distributed in the trunk than the arms. However, as arterio-venous fistulae are the preferred form of vascular access and fistulae could potentially affect fluid retention in the arm, we investigated whether multifrequency bioimpedance could detect differences in fluid distribution in the arms with haemodialysis in patients with different vascular access modalities. METHODS: We audited the change in extracellular water (ECW) and total body water (TBW) in the arms following haemodialysis in 100 patients attending for routine outpatient haemodialysis at a university centre by multifrequency bioimpedance using an eight-electrode contact technique. RESULTS: Patients with fistulae had greater ECW/TBW % in the fistula arm both prior to and post dialysis compared with central venous catheter (CVC) (pre 38.9 ± 0.1 vs 38.3 ± 0.1 and post 38.4 ± 0.1 vs 37.8 ± 0.1, P < 0.01), with a greater absolute difference between arms (0.53 ± 0.01 vs 0.05 ± 0.01, P < 0.01) and greater arm ECW/TBW % compared with total body ECW/TBW % predialysis (forearm fistula 99.4 ± 0.4 vs CVC 97.2 ± 0.3, P < 0.01). CONCLUSION: Absolute and also relative extracellular fluid volumes are increased in the fistula arm of haemodialysis patients. Thus, if algorithms are to be developed to monitor relative segmental changes in extracellular volumes to help prevent intradialytic hypotension using bioimpedance, then the dialysis vascular access and site will have to be considered, particularly if using relative changes in the upper limbs. Thus, alterative sites which are not so affected by vascular access, such as the calf, may prove advantageous.