Incidence and Outcomes of Patients Receiving Chronic Kidney Replacement Therapy Admitted to Scottish ICUs Between 2009 and 2019-A National Observational Cohort Study.

OBJECTIVES: To determine the incidence and characteristics of ICU admissions in the Scottish population of patients treated with chronic kidney replacement therapy (KRT) over an 11-year period and determine factors associated with post-ICU admission mortality. DESIGN: Retrospective observational cohort study. SETTING: We analyzed admissions to Scottish intensive care environments between January 1, 2009, and December 31, 2019. PATIENTS: All patients receiving chronic KRT-including maintenance dialysis and kidney transplant-in Scotland. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Descriptive statistics and factors associated with mortality using logistic regression and Cox proportional hazard models. From 10,657 unique individuals registered in the Scottish Renal Registry over the 11-year study period and alive as of January 1, 2009, 1,402 adult patients were identified as being admitted to a Scottish critical care setting. Between 2009 and 2019, admissions to ICU increased in a nonlinear manner driven by increases in admissions for renal causes and elective cardiac surgery. The ICU admission rate was higher among patients on chronic dialysis than in kidney transplant recipients (59.1 vs 19.9 per 1,000 person-years), but post-ICU mortality was similar (about 24% at 30 d and 40% at 1 year). Admissions for renal reasons were most common (20.9%) in patients undergoing chronic dialysis, whereas kidney transplant recipients were most frequently admitted for pneumonia (19.3%) or sepsis (12.8%). Adjusted Cox PH models showed that receiving invasive ventilation and vasoactive drugs was associated with an increased risk of death at 30 days post-ICU admission (HR, 1.75; 95% CI, 1.28-2.39 and 1.72; 95% CI, 1.28-2.31, respectively). CONCLUSIONS: With a growing population of kidney transplant recipients and the improved survival of patients on chronic dialysis, the number of ICU admissions is rising in the chronic KRT population. Mortality post-ICU admission is high for these patients.

The Impact of Vaccination on Incidence and Outcomes of SARS-CoV-2 Infection in Patients with Kidney Failure in Scotland.

BACKGROUND: Patients with kidney failure requiring KRT are at high risk of complications and death following SARS-CoV-2 infection, with variable antibody responses to vaccination reported. We investigated the effects of COVID-19 vaccination on the incidence of infection, hospitalization, and death from COVID-19 infection. METHODS: The study design was an observational data linkage cohort study. Multiple health care datasets were linked to ascertain all SARS-CoV-2 testing, vaccination, hospitalization, and mortality data for all patients treated with KRT in Scotland from the start of the pandemic over a period of 20 months. Descriptive statistics, survival analyses, and vaccine effectiveness were calculated. RESULTS: As of September 19, 2021, 93% (n=5281) of the established KRT population in Scotland had received two doses of an approved SARS-CoV-2 vaccine. Over the study period, there were 814 cases of SARS-CoV-2 infection (15.1% of the KRT population). Vaccine effectiveness rates against infection and hospitalization were 33% (95% CI, 0 to 52) and 38% (95% CI, 0 to 57), respectively. Within 28 days of a SARS-CoV-2-positive PCR test, 9.2% of fully vaccinated individuals died (7% patients on dialysis and 10% kidney transplant recipients). This compares to <0.1% of the vaccinated general Scottish population admitted to the hospital or dying due to COVID-19 during that period. CONCLUSIONS: These data demonstrate that a primary vaccine course of two doses has limited effect on COVID-19 infection and its complications in patients with KRT. Adjunctive strategies to reduce risk of both COVID-19 infection and its complications in this population are urgently required.

COVID-19 in patients undergoing chronic kidney replacement therapy and kidney transplant recipients in Scotland: findings and experience from the Scottish renal registry.

BACKGROUND: Infection with the severe acute respiratory coronavirus 2 (SARS-CoV-2) has led to a worldwide pandemic with coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2, overwhelming healthcare systems globally. Preliminary reports suggest a high incidence of infection and mortality with SARS-CoV-2 in patients receiving kidney replacement therapy (KRT). The aims of this study are to report characteristics, rates and outcomes of all patients affected by infection with SARS-CoV-2 undergoing KRT in Scotland. METHODS: Study design was an observational cohort study. Data were linked between the Scottish Renal Registry, Health Protection Scotland and the Scottish Intensive Care Society Audit Group national data sets using a unique patient identifier (Community Health Index (CHI)) for each individual by the Public Health and Intelligence unit of Public Health, Scotland. Descriptive statistics and survival analyses were performed. RESULTS: During the period 1st March 2020 to 31st May 2020, 110 patients receiving KRT tested positive for SARS-CoV-2 amounting to 2% of the prevalent KRT population. Of those affected, 86 were receiving haemodialysis or peritoneal dialysis and 24 had a renal transplant. Patients who tested positive were older and more likely to reside in more deprived postcodes. Mortality was high at 26.7% in the dialysis patients and 29.2% in the transplant patients. CONCLUSION: The rate of detected SARS-CoV-2 in people receiving KRT in Scotland was relatively low but with a high mortality for those demonstrating infection. Although impossible to confirm, it appears that the measures taken within dialysis units coupled with the national shielding policy, have been effective in protecting this population from infection.

Symptomatic fracture risk in the renal replacement therapy population.

BACKGROUND: Bone fractures are an important cause of morbidity and mortality in patients on renal replacement therapy (RRT). The aim of this multicentre observational study was to quantify the incidence of radiologically proven bone fracture by anatomical site in prevalent RRT groups and study its relationship to potential risk factors. METHODS: We performed a retrospective analysis of electronic records of all 2096 adults prevalent on RRT in the West of Scotland on 7 July 2010 across all hospitals (except one where inception was 1 August 2011) to identify all subsequent radiologically proven fractures during a median 3-year follow-up. RESULTS: There were 340 fractures, with an incidence of 62.8 per 1000 patient-years. The incidences were 37.6, 99.2 and 57.6 per 1000 patient-years in the transplant, haemodialysis (HD) and peritoneal dialysis (PD) groups, respectively (P < 0.05). In the multivariable model, age and HD (relative to transplant or PD) were independently associated with increased risk of fractures, while primary glomerular disease, increasing serum albumin and taking alfacalcidol or lanthanum were associated with decreased risk. In a multivariable model of only HD patients, age was independently associated with an increased risk of fractures, while glomerular disease, high serum albumin and being on alfacalcidol and lanthanum were associated with decreased risk. In a multivariable model in transplant patients, there were no significant independent predictors of fracture. CONCLUSIONS: The risk of symptomatic bone fracture is high in RRT patients and is ∼2.5 times higher in HD than in renal transplant patients, with the increased risk being independent of baseline factors. Fracture risk increases with age and lower serum albumin and is reduced if the primary renal diagnosis is glomerular disease. The possible protective role of alfacalcidol and lanthanum in HD patients deserves further exploration.

Telehealth: Acceptability, clinical interventions and quality of life in peritoneal dialysis.

INTRODUCTION: Telehealth technologies are being widely adopted across the globe for management of long-term conditions. There are limited data on its use, effectiveness and patient experience in end-stage renal disease. The aim of this pilot project was to explore patient acceptability of technology and evaluate its effect on clinical interventions and quality of life in patients undergoing peritoneal dialysis. METHODS: Peritoneal dialysis patients were provided with computer tablets (PODs). PODs contained a knowledge database with treatment- and symptom-based questionnaires that generated alerts for the clinical team. Alerts were reviewed daily and followed up by a telephone call or clinic visit. Interventions were at the discretion of clinicians. Data were recorded prospectively and quality of life and Quebec User Evaluation of Satisfaction with assistive Technology questionnaires evaluated at the start and end of the programme. RESULTS: In all, 22 patients have participated over 15 months. The mean age was 61.6 years and PODs were utilised for an average of 341.9 days with 59.1% choosing to continue beyond the study period. We received a total of 1195 alerts with an average of 2.6 alerts per day. A total of 36 admissions were avoided and patients supported to self-manage on 154 occasions. Quebec User Evaluation of Satisfaction with assistive Technology scores remained high throughout the programme although no improvement in quality of life was seen. DISCUSSION: Telehealth is useful to monitor patients with renal failure on peritoneal dialysis. It is acceptable across age groups and provides an additional resource for patients to self-manage. Satisfaction scores and retention rates suggest a high level of acceptability.

Factors influencing withdrawal from dialysis: a national registry study.

BACKGROUND: Dialysis withdrawal is the third most common cause of death in patients receiving dialysis for established renal failure (ERF) in Scotland. We describe incidence, risk factors and themes influencing decision-making in a national renal registry. METHODS: Details of deaths in those receiving renal replacement therapy (RRT) for ERF in Scotland are reported to the Scottish Renal Registry via a unique mortality report. We extracted patient demographics and comorbidity, cause and location of death, duration of RRT and pertinent free text comments from 1 January 2008 to 31 December 2014. Withdrawal incidence was calculated and logistic regression used to identify significantly influential variables. Themes emerging from clinician comments were tabulated for descriptive purposes. RESULTS: There were 2596 deaths; median age at death was 68 [interquartile range (IQR) 58, 76] years, 41.5% were female. Median duration on RRT was 1110 (IQR 417, 2151) days. Dialysis withdrawal was the primary cause of death in 497 (19.1%) patients and withdrawal contributed to death in a further 442 cases (17.0%). The incidence was 41 episodes per 1000 patient-years. Regression analysis revealed increasing age, female sex and prior cerebrovascular disease were associated with dialysis withdrawal as a primary cause of death. Conversely, interstitial renal disease, angiographically proven ischaemic heart disease, valvular heart disease and malignancy were negatively associated. Analysis of free text comments revealed common themes, portraying an image of physical and psychological decline accelerated by acute illnesses. CONCLUSIONS: Death following dialysis withdrawal is common. Factors important to physical independence-prior cerebrovascular disease and increasing age-are associated with withdrawal. When combined with clinician comments this study provides an insight into the clinical decline affecting patients and the complexity of this decision. Early recognition of those likely to withdraw may improve end of life care.

Thrice-Weekly Nocturnal In-Centre Haemodiafiltration: A 2-Year Experience.

BACKGROUND: Adequate control of plasma phosphate without phosphate binders is difficult to achieve on a thrice-weekly haemodialysis schedule. The use of quotidian nocturnal dialysis is effective but not practical in the in-centre setting. This quality improvement project was set up as an exercise allowing the evaluation of small-solute clearance by combining convection with extended-hour dialysis in a thrice-weekly hospital setting. METHODS: A single-centred, prospective analysis of patients' electronic records was performed from August 2012 to July 2014. The duration of haemodiafiltration was increased from a median of 4.5 to 8 h. Dialysis adequacy, biochemical parameters and medications were reviewed on a monthly basis. A reduction in plasma phosphate was anticipated, so all phosphate binders were stopped. RESULTS: Since inception, 14 patients have participated with over 2,000 sessions of dialysis. The pre-dialysis phosphate level fell from a mean of 1.52 ± 0.4 to 1.06 ± 0.1 mmol/l (p < 0.05). The average binder intake of 3.26 ± 2.6 tablets was eliminated. A normal plasma phosphate range has been maintained with increased dietary phosphate intake and no requirement for intradialytic phosphate supplementation. CONCLUSION: Phosphate control can be achieved without the need for binders or supplementation on a thrice-weekly in-centre haemodiafiltration program.

Optimal fluid control can normalize cardiovascular risk markers and limit left ventricular hypertrophy in thrice weekly dialysis patients.

Increased hemodialysis frequency can make fluid overload easier to treat, although most patients are still treated thrice weekly. Chronic fluid overload is associated with left ventricular hypertrophy and elevated serum cardiac biomarkers, recognized as mortality risk factors. Serum cardiac troponin T (cTnT), N-terminal prohormone brain natriuretic peptide (NT-proBNP), left ventricular mass index by cardiac magnetic imaging, and ambulatory blood pressure was measured in 30 thrice weekly hemodiafiltration patients. Time-averaged fluid overload (TAFO) was quantified by bioimpedance spectroscopy. In the study group, left ventricular hypertrophy was found to be 26% by cardiac magnetic resonance. Ambulatory blood pressure was 130 mmHg (112-151) requiring a low equivalent dose of medication of 0.25 units (0-1). Significantly, lower levels of left ventricular mass index (P < 0.05) were associated in those patients with TAFO <1 L or NT-proBNP <1200 pg/mL or cTnT <0.1 ug/L. In the subgroups, 16 patients had normal cTnT (<0.03 ug/L), 16 patients had NT-proBNP <400 pg/mL, and 20 patients had TAFO <1 L. Nine patients had both cTnT <0.03 ug/L and NT-proBNP <400 pg/mL. Normally hydrated thrice-weekly hemodiafiltration patients can have cardiac biomarker and TAFO levels indistinguishable from the normal healthy population. Obtaining TAFO by bioimpedance monitoring can offer a practical alternative to serum cardiac biomarkers.

Effect of high haematocrit on the efficiency of high-flux dialysis therapies.

BACKGROUND: There is a concern that high haematocrit (Hct) levels will reduce the efficiency of dialysis treatments, particularly in post-dilution haemodiafiltration (HDF) where there is the potential for intense haemoconcentration within the dialyser. METHODS: We measured serial Hct and performed serial clearance measurements for urea, phosphate, beta(2)-microglobulin and myoglobin in 12 patients with Hct >35% on high-flux haemodialysis (HFHD) or HDF. We assessed whether changes in the intra-dialyser Hct influenced solute clearance and whether there were differences between the two modalities. RESULTS: Hct rose significantly in all treatments studied. Convective and total solute clearances were higher in the HDF group when compared to the HFHD group. Phosphate clearance in HFHD fell towards the end of dialysis when the Hct was highest but no differences were detected for the other solutes. CONCLUSION: Despite marked haemoconcentration, the impact on solute clearance across the range of molecular size studied is small. These findings are reassuring in the current era of widespread erythropoietin use.

Kt/V underestimates the hemodialysis dose in women and small men.

Current guidelines suggest a minimum Kt/V of 1.2 for three weekly hemodialysis sessions; however, using V as a normalizing factor has been questioned. Parameters such as weight(0.67) (W(0.67)) and body surface area (BSA) that reflect the metabolic rate may be preferable. To determine this, we studied 328 hemodialysis patients (221 male) with a target Kt/V of 1.2. Using this relationship and the individual's Watson Volume, we calculated the Kt, Kt/BSA, and Kt/W(0.67) equivalent to the target and measured the effects of body size and gender on these parameters for each patient. The target corresponded to a range of equivalent Kt/BSA and Kt/W(0.67) each significantly higher in males than females and in larger than smaller males. V/BSA and V/W(0.67), the conversion factors of Kt/V to Kt/BSA and Kt/W(0.67) respectively, were significantly greater in males than females and heavier than lighter men. Our study shows that if Kt/BSA and Kt/W(0.67) reflect the true required dose, prescribing a target Kt/V of 1.2 would underestimate this in females and in small males. Further work is required to develop clinical outcome-based adequacy targets.

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.

Phosphate kinetics during hemodialysis: Evidence for biphasic regulation.

BACKGROUND: Hyperphosphatemia in the hemodialysis population is ubiquitous, but phosphate kinetics during hemodialysis is poorly understood. METHODS: Twenty-nine hemodialysis patients each received one long and one short dialysis, equivalent in terms of urea clearance. Phosphate concentrations were measured during each treatment and for one hour thereafter. A new model of phosphate kinetics was developed and implemented in VisSim. This model characterized additional processes involved in phosphate kinetics explaining the departure of the measured data from a standard two-pool model. RESULTS: Pre-dialysis phosphate concentrations were similar in long and short dialysis groups. Post-dialysis phosphate concentrations in long dialysis were higher than in short dialysis (P < 0.02) despite removal of a greater mass of phosphate (P < 0.001). In both long and short dialysis serum phosphate concentrations initially fell in accordance with two-pool kinetics, but thereafter plateaued or increased despite continuing phosphate removal. Implementation of an additional regulatory mechanism such that a third pool liberates phosphate to maintain an intrinsic target concentration (1.18 +/- 0.06 mmol/L; 95% confidence intervals, CI) explained the data in 24% of treatments. The further addition of a fourth pool hysteresis element triggered by critically low phosphate levels (0.80 +/- 0.07 mmol/L, CI) yielded an excellent correlation with the observed data in the remaining 76% of treatments (cumulative standard deviation 0.027 +/- 0.004 mmol/L, CI). The critically low concentration correlated with pre-dialysis phosphate levels (r=0.67, P < 0.0001). CONCLUSION: Modeling of phosphate kinetics during hemodialysis implies regulation involving up to four phosphate pools. The accuracy of this model suggests that the proposed mechanisms have physiological validity.