Sandip Mitra

A Randomized Double-Blind Controlled Trial of Taurolidine-Citrate Catheter Locks for the Prevention of Bacteremia in Patients Treated With Hemodialysis

BACKGROUND Bacteremia is a major cause of morbidity in patients using intravascular catheters. Interdialytic locking with antibiotics decreases the incidence of bacteremia, but risks antibiotic resistance. Taurolidine is a nontoxic broad-spectrum antimicrobial agent that has not been associated with resistance. Preliminary evidence suggests that taurolidine-citrate locks decrease bacteremia, but cause flow problems in established catheters. STUDY DESIGN Double-blind randomized controlled trial. INTERVENTION Interdialytic locking with taurolidine and citrate (1.35% taurolidine and 4% citrate) compared with heparin (5,000 U/mL) started at catheter insertion. SETTING & PARTICIPANTS 110 adult hemodialysis patients with tunneled cuffed intravascular catheters inserted at 3 centers in Northwest England. OUTCOMES & MEASUREMENTS Primary end points were time to first bacteremia episode from any cause and time to first use of thrombolytic therapy. RESULTS There were 11 bacteremic episodes in the taurolidine-citrate group and 23 in the heparin group (1.4 and 2.4 episodes/1,000 patient-days, respectively; P = 0.1). There was no significant benefit of taurolidine-citrate versus heparin for time to first bacteremia (hazard ratio, 0.66; 95% CI, 0.2-1.6: P = 0.4). Taurolidine-citrate was associated with fewer infections caused by Gram-negative organisms than heparin (0.2 vs 1.1 infections/1,000 patient-days; P = 0.02); however, there was no difference for Gram-positive organisms (1.1 vs 1.2 infections/1,000 patient-days; P = 0.8). There was a greater need for thrombolytic therapy in the taurolidine-citrate versus heparin group (hazard ratio, 2.5; 95% CI, 1.3-5.2; P = 0.008). LIMITATIONS Small sample size. The study included bacteremia from all causes and was not specific for catheter-related bacteremia. CONCLUSIONS Taurolidine-citrate use did not decrease all-cause bacteremia and was associated with a greater need for thrombolytic treatment. There was a decrease in infections caused by Gram-negative organisms and a trend to a lower frequency of bacteremia, which warrants further study.

A randomized, crossover design study of sevelamer carbonate powder and sevelamer hydrochloride tablets in chronic kidney disease patients on haemodialysis

Background. Sevelamer carbonate is an improved, buffered form of sevelamer hydrochloride developed for the treatment of hyperphosphataemia in CKD patients. Sevelamer carbonate formulated as a powder for oral suspension presents a novel, patient-friendly alternative to tablet phosphate binders. This study compared the safety and efficacy of sevelamer carbonate powder with sevelamer hydrochloride tablets in CKD patients on haemodialysis. Methods. This was a multi-centre, open-label, randomized, crossover design study. Thirty-one haemodialysis patients were randomly assigned to either sevelamer carbonate powder or sevelamer hydrochloride tablets for 4 weeks followed by a crossover to the other regimen for an additional 4 weeks. Results. The mean serum phosphorus was 1.6 ± 0.5 mmol/L (5.0 ± 1.5 mg/dL) during sevelamer carbonate powder treatment and 1.7 ± 0.4 mmol/L (5.2 ± 1.1 mg/dL) during sevelamer hydrochloride tablet treatment. Sevelamer carbonate powder and sevelamer hydrochloride tablets are equivalent in controlling serum phosphorus; the geometric least square mean ratio was 0.95 (90% CI 0.87–1.03). No statistically significant or clinically meaningful differences were observed in calcium × phosphorus product and lipid levels between sevelamer carbonate powder and sevelamer hydrochloride tablets. Serum bicarbonate levels increased 2.7 ± 3.7 mmol/L (2.7 ± 3.7 mEq/L) during sevelamer carbonate treatment. No statistically significant change in bicarbonate was observed during sevelamer hydrochloride treatment. Sevelamer carbonate powder and sevelamer hydrochloride were well tolerated during this study. Conclusions. Sevelamer carbonate powder and sevelamer hydrochloride tablets are equivalent in controlling serum phosphorus and well tolerated in CKD patients on haemodialysis. Bicarbonate levels improved only during sevelamer carbonate treatment. Sevelamer carbonate powder should provide a welcomed new option for the treatment of hyperphosphataemia for CKD patients on dialysis.

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.

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.

Subcutaneous interstitial pressure and volume characteristics in renal impairment associated with edema.

The kidneys and the interstitial compartment play a vital role in body fluid regulation. The latter may be significantly altered in renal dysfunction, but experimental studies are lacking. To help define this we measured the subcutaneous interstitial pressure, bioimpedance volumes, and edema characteristics in 10 healthy subjects and 21 patients with obvious edema and chronic kidney disease (CKD). Interstitial edema was quantified by the time taken for a medial malleolar thumb pit to refill and termed the edema refill time. Interstitial pressure was significantly raised in CKD compared to healthy subjects. Total body water (TBW), extracellular fluid volume (ECFV), interstitial fluid volume, the ratio of the ECFV to the TBW, and segmental extracellular fluid volume were raised in CKD. The ratio of the ECFV to the TBW and the interstitial fluid volume were the best predictors of interstitial pressure. Significantly higher interstitial pressures were noted in edema of 2 weeks or less duration. A significant nonlinear relationship defined interstitial pressure and interstitial fluid volume. Edema refill time was significantly inversely related to interstitial pressure, interstitial compartment volumes, and edema vintage. Elevated interstitial pressure in CKD with obvious edema is a combined function of accumulated interstitial compartment fluid volumes, edema vintage, and tissue mechanical properties. The edema refill time may represent an important parameter in the clinical assessment of edema, providing additional information about interstitial pathophysiology in patients with CKD and fluid retention.

Home hemodialysis: Beliefs, attitudes, and practice patterns

There is increasing interest of the worldwide kidney community in home hemodialysis (HHD). This is due to emerging evidence of its superiority over conventional hemodialysis (HD), largely attributed to improved outcomes on intensive schedule HD, best deployed in patients own homes. Despite published work in this area, universal uptake remains limited and reasons are poorly understood. All those who provide HD care were invited to participate in a survey on HHD, initiated to understand the beliefs, attitudes, and practice patterns of providers offering this therapy. The survey was developed and posted on the Nephrology Dialysis Transplantation‐Educational (NDT‐E) website. Two hundred and seventy‐two responses were deemed suitable for complete analysis. It is apparent from the survey that there is great variability in the prevalence of HHD. Physicians have a great deal of interest in this modality, with majority viewing home as being the ideal location for the offer of intensive HD schedules (55%). A significant number (21%) feel intensive HD may be offered even outside the home setting. Those who offer this therapy do not see a financial disadvantage in it. Many units identify lack of appropriately trained personnel (35%) and funding for home adaptation (50.4%) as key barriers to widespread adoption of this therapy. Despite the interest and belief in this therapy among practitioners, HHD therapy is still not within reach of a majority of patients. Modifiable organizational, physician, and patient factors exist, which could potentially redefine the landscape of HHD provision. Well‐designed systematic research of national and local barriers is needed to design interventions to help centers facilitate change.

Technique survival in home haemodialysis: a composite success rate and its risk predictors in a prospective longitudinal cohort from a tertiary renal network programme

BACKGROUND Resurgence of interest in home haemodialysis (HHD) is, in part, due to emerging evidence of the benefits of extended HD regimens, which are most feasibly provided in the home setting. Although specific HHD therapy established at home such as nocturnal HD (NHD) has been reported from individual programmes, little is known about overall HHD success. METHODS The study included 166 patients who were accepted in the Manchester (UK) HHD training programme through liberal selection criteria. All patients were followed up prospectively until a switch to alternative modality, to include 4528 patient-months of follow-up and about 81 508 HHD sessions during an 8-year period (January 2004-December 2011). Twenty-four patients switched to an alternative modality during the period. Combined technique survival (HHDc) as a composite of training (HHDtr) and at home (HHDhome) was analysed and clinical predictors of HHD modality failure since the commencement of the programme were calculated using Cox regression analysis. Technology-related interruptions to dialysis over a 12-month period and patient-reported reasons for quitting the programme were analysed. RESULTS Technique survival at 1, 2 and 5 years was 90.2, 87.4, 81.5% (HHDc) and 98.4, 95.4 and 88.9% (HHDhome) when censored for training phase exits, death and transplantation. The combined HHDc modality switch rate is 1 in 192 patient-months of dialysis follow-up. Age >60 years, diabetes, cardiac failure, unit decrease in Hb and increasing score of age-adjusted Charlson--comorbidity index were significantly associated with technique failure. Significant clinical predictors of HHD technique failure in a multivariate model were diabetes (P = 0.002) and cardiac failure (P = 0.05). The majority (61%) switched to an alternative modality for non-medical reasons. The composite of operator error and mechanical breakdown resulting in temporary HHD technique failure was 0.7% per year. CONCLUSIONS HHD training and technique failure rate are low. Technical errors are infrequent too. Diabetes and cardiac failure are associated with significant risk of technique failure. Although absolute rates are low, training failure is proportionally quite significant, highlighting the importance of reporting the composite technique failure rate (to include early HHD training phase) in HHD programmes.

UK National Survey of Practice Patterns of Fluid Volume Management in Haemodialysis Patients: A Need for Evidence

Background: Fluid management in haemodialysis (HD) affects patient experience, morbidity and mortality. Standards for best practice are lacking. A national survey of the United Kingdom was undertaken to define prevalent practice. Methods: An online questionnaire was distributed to all UK renal centres. Results: Forty-five of 74 centres (173 dialysis units), serving 62% (n = 14,697) of UK HD population responded. Seventy-eight per cent had no agreed policy for managing fluid balance in patients on HD; 44% did not assess fluid status routinely. Clinical assessment was the norm; 27% used bio-impedance-based device. To achieve a target-weight, 53% reduced weight as far as tolerated. Twenty-two per cent measured residual renal function (RRF). Ninety-one per cent had no policy for fluid overload. Sixty-four per cent restricted salt and water. Ninety-three per cent used diuretics in patients with RRF. Thirty-eight per cent felt management was adequate; 77% felt there was a need for better evidence. Ninety-one per cent would participate in a study addressing this. Conclusion: There is an urgent need for establishing an evidence base on the optimal approaches to fluid management.

Arteriovenous fistula failure: Is there a role for accessory draining vein embolization?

Purpose Arterio-venous fistulae (AVFs) are accepted as the best form of haemodialysis vascular access (VA) but are plagued by high primary failure. Accessory drainage veins (ADVs) may account for up to 40% of these failures. Furthermore, they may also lead to low flow in ‘mature’ AVFs. Methods We analysed the results of 42 patients who underwent endovascular coiling of ADVs at our centre over a 4-year period. Results Indications were failure to mature in 34%, low flow or cannulation difficulty in 56% and thrombosis in 10% of cases. 95% procedures involved a combination of angioplasty and coiling with only 5% patients having coiling of ADV alone. Forearm AVFs constituted the majority of the cases as opposed to upper arm AVFs (74% vs. 26% respectively). Primary patency at 3, 6, 12, 18 and 24 months was 90%, 87%, 76%, 70% and 55% respectively. Successful dialysis was achieved in 10 of the 14 fistulae that had hitherto failed to mature. Coil migration was observed in 1 patient, which led to fistula occlusion. Conclusion Coil embolisation of ADVs is an effective treatment option for dysfunctional fistulae that can be performed at the same time as angioplasty.

Home hemodialysis: Beliefs, attitudes, and practice patterns: beliefs, attitudes, and practice patterns

There is increasing interest of the worldwide kidney community in home hemodialysis (HHD). This is due to emerging evidence of its superiority over conventional hemodialysis (HD), largely attributed to improved outcomes on intensive schedule HD, best deployed in patients own homes. Despite published work in this area, universal uptake remains limited and reasons are poorly understood. All those who provide HD care were invited to participate in a survey on HHD, initiated to understand the beliefs, attitudes, and practice patterns of providers offering this therapy. The survey was developed and posted on the Nephrology Dialysis Transplantation‐Educational (NDT‐E) website. Two hundred and seventy‐two responses were deemed suitable for complete analysis. It is apparent from the survey that there is great variability in the prevalence of HHD. Physicians have a great deal of interest in this modality, with majority viewing home as being the ideal location for the offer of intensive HD schedules (55%). A significant number (21%) feel intensive HD may be offered even outside the home setting. Those who offer this therapy do not see a financial disadvantage in it. Many units identify lack of appropriately trained personnel (35%) and funding for home adaptation (50.4%) as key barriers to widespread adoption of this therapy. Despite the interest and belief in this therapy among practitioners, HHD therapy is still not within reach of a majority of patients. Modifiable organizational, physician, and patient factors exist, which could potentially redefine the landscape of HHD provision. Well‐designed systematic research of national and local barriers is needed to design interventions to help centers facilitate change.