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1.  Long-term outcome in ICU patients with acute kidney injury treated with renal replacement therapy: a prospective cohort study 
Critical Care  2016;20:256.
In intensive care unit (ICU) patients, acute kidney injury treated with renal replacement therapy (AKI-RRT) is associated with adverse outcomes. The aim of this study was to evaluate variables associated with long-term survival and kidney outcome and to assess the composite endpoint major adverse kidney events (MAKE; defined as death, incomplete kidney recovery, or development of end-stage renal disease treated with RRT) in a cohort of ICU patients with AKI-RRT.
We conducted a single-center, prospective observational study in a 50-bed ICU tertiary care hospital. During the study period from August 2004 through December 2012, all consecutive adult patients with AKI-RRT were included. Data were prospectively recorded during the patients’ hospital stay and were retrieved from the hospital databases. Data on long-term follow-up were gathered during follow-up consultation or, in the absence of this, by consulting the general physician.
AKI-RRT was reported in 1292 of 23,665 first ICU admissions (5.5 %). Mortality increased from 59.7 % at hospital discharge to 72.1 % at 3 years. A Cox proportional hazards model demonstrated an association of increasing age, severity of illness, and continuous RRT with long-term mortality. Among hospital survivors with reference creatinine measurements, 1-year renal recovery was complete in 48.4 % and incomplete in 32.6 %. Dialysis dependence was reported in 19.0 % and was associated with age, diabetes, chronic kidney disease (CKD), and oliguria at the time of initiation of RRT. MAKE increased from 83.1 % at hospital discharge to 93.7 % at 3 years. Multivariate regression analysis showed no association of classical determinants of outcome (preexisting CKD, timing of initiation of RRT, and RRT modality) with MAKE at 1 year.
Our study demonstrates poor long-term survival after AKI-RRT that was determined mainly by severity of illness and RRT modality at initiation of RRT. Renal recovery is limited, especially in patients with acute-on-chronic kidney disease, making nephrological follow-up imperative. MAKE is associated mainly with variables determining mortality.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-016-1409-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4983760  PMID: 27520553
Acute kidney injury (AKI); Long-term survival; Major adverse kidney events (MAKE); Renal recovery; Renal replacement therapy (RRT); Modality of renal replacement therapy; Timing of renal replacement therapy; Acute-on-chronic kidney failure
2.  Long-term quality of life in critically ill patients with acute kidney injury treated with renal replacement therapy: a matched cohort study 
Critical Care  2015;19(1):289.
Acute kidney injury (AKI) is a common complication in intensive care unit (ICU) patients and is associated with increased morbidity and mortality. We compared long-term outcome and quality of life (QOL) in ICU patients with AKI treated with renal replacement therapy (RRT) with matched non-AKI-RRT patients.
Over 1 year, consecutive adult ICU patients were included in a prospective cohort study. AKI-RRT patients alive at 1 year and 4 years were matched with non-AKI-RRT survivors from the same cohort in a 1:2 (1 year) and 1:1 (4 years) ratio based on gender, age, Acute Physiology and Chronic Health Evaluation II score, and admission category. QOL was assessed by the EuroQoL-5D and the Short Form-36 survey before ICU admission and at 3 months, 1 and 4 years after ICU discharge.
Of 1953 patients, 121 (6.2 %) had AKI-RRT. AKI-RRT hospital survivors (44.6 %; N = 54) had a 1-year and 4-year survival rate of 87.0 % (N = 47) and 64.8 % (N = 35), respectively. Forty-seven 1-year AKI-RRT patients were matched with 94 1-year non-AKI-RRT patients. Of 35 4-year survivors, three refused further cooperation, three were lost to follow-up, and one had no control. Finally, 28 4-year AKI-RRT patients were matched with 28 non-AKI-RRT patients. During ICU stay, 1-year and 4-year AKI-RRT patients had more organ dysfunction compared to their respective matches (Sequential Organ Failure Assessment scores 7 versus 5, P < 0.001, and 7 versus 4, P < 0.001). Long-term QOL was, however, comparable between both groups but lower than in the general population. QOL decreased at 3 months, improved after 1 and 4 years but remained under baseline level. One and 4 years after ICU discharge, 19.1 % and 28.6 % of AKI-RRT survivors remained RRT-dependent, respectively, and 81.8 % and 71 % of them were willing to undergo ICU admission again if needed.
In long-term critically ill AKI-RRT survivors, QOL was comparable to matched long-term critically ill non-AKI-RRT survivors, but lower than in the general population. The majority of AKI-RRT patients wanted to be readmitted to the ICU when needed, despite a higher severity of illness compared to matched non-AKI-RRT patients, and despite the fact that one quarter had persistent dialysis dependency.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-015-1004-8) contains supplementary material, which is available to authorized users.
PMCID: PMC4527359  PMID: 26250830
3.  Type of Referral, Dialysis Start and Choice of Renal Replacement Therapy Modality in an International Integrated Care Setting 
PLoS ONE  2016;11(5):e0155987.
Integrated Care Settings (ICS) provide a holistic approach to the transition from chronic kidney disease into renal replacement therapy (RRT), offering at least both types of dialysis.
To analyze which factors determine type of referral, modality provision and dialysis start on final RRT in ICS clinics.
Retrospective analysis of 626 patients starting dialysis in 25 ICS clinics in Poland, Hungary and Romania during 2012. Scheduled initiation of dialysis with a permanent access was considered as planned RRT start.
Modality information (80% of patients) and renal education (87%) were more frequent (p<0.001) in Planned (P) than in Non-Planned (NP) start. Median time from information to dialysis start was 2 months. 89% of patients started on hemodialysis, 49% were referred late to ICS (<3 months from referral to RRT) and 58% were NP start. Late referral, non-vascular renal etiology, worse clinical status, shorter time from information to RRT and less peritoneal dialysis (PD) were associated with NP start (p<0.05). In multivariate logistic regression analysis, P start (p≤0.05) was associated with early referral, eGFR >8.2 ml/min, >2 months between information and RRT initiation and with vascular etiology after adjustment for age and gender. “Optimal care,” defined as ICS follow-up >12 months plus modality information and P start, occurred in 23%.
Despite the high rate of late referrals, information and education were widely provided. However, NP start was high and related to late referral and may explain the low frequency of PD.
PMCID: PMC4882011  PMID: 27228101
4.  End-Stage Renal Disease From Autosomal Dominant Polycystic Kidney Disease in the United States, 2001-2010 
Autosomal dominant polycystic kidney disease (ADPKD) is amenable to early detection and specialty care. Thus, while important to patients with the condition, end-stage renal disease (ESRD) from ADPKD may also be an indicator of the overall state of nephrology care.
Study Design
Retrospective cohort study of temporal trends in renal replacement therapy (RRT)-requiring ESRD from ADPKD and pre-RRT nephrologist care, 2001-2010 (n = 23,772).
Setting & Participants
US patients who initiated maintenance RRT between 2001 and 2010 (n = 1,069,343), from United States Renal Data System data.
RRT-requiring ESRD from ADPKD.
Death, wait-listing for renal transplant, renal transplant.
US census data were used as population denominators. The Poisson distribution was used to compute incidence rates. Incidence ratios were standardized to rates in 2001-2002 for age, sex, and race/ethnicity. Patients with and without ADPKD were matched to compare clinical outcomes. Poisson regression was used to calculate incidence rates and adjusted hazards ratios for clinical events after inception of RRT.
General population incidence ratios in 2009-2010 were unchanged from 2001-2002 (incidence ratio 1.02). Of patients with ADPKD, 48.1% received > 12 months of nephrology care before RRT; preemptive transplant was the initial RRT in 14.3% and fistula the initial hemodialysis access in 35.8%. Over 4.9 years of follow-up, patients with ADPKD were more likely to be listed for transplant (11.7 [95% CI 11.5-12.0] per 100 person-years vs. 8.4 [8.2-8.7]) and to undergo transplant (9.8 [9.5-10.0] vs. 4.8 [4.7-5.0]), and less likely to die (5.6 [5.4-5.7] vs. 15.5 [15.3-15.8]) than matched controls without ADPKD.
Retrospective, nonexperimental, registry-based study of associations; cause-and-effect relationships cannot be determined.
While outcomes on dialysis are better for ADPKD than for non-ADPKD patients, access to predialysis nephrology care and non-declining ESRD rates may be a cause for concern.
PMCID: PMC4396817  PMID: 25134777
Dialysis; end-stage renal disease; polycystic kidney disease; renal replacement therapy; renal transplant
5.  Acute kidney injury treated with renal replacement therapy and 5-year mortality after myocardial infarction-related cardiogenic shock: a nationwide population-based cohort study 
Critical Care  2015;19:452.
Myocardial infarction-related cardiogenic shock is frequently complicated by acute kidney injury. We examined the influence of acute kidney injury treated with renal replacement therapy (AKI-RRT) on risk of chronic dialysis and mortality, and assessed the role of comorbidity in patients with cardiogenic shock.
In this Danish cohort study conducted during 2005–2012, we used population-based medical registries to identify patients diagnosed with first-time myocardial infarction-related cardiogenic shock and assessed their AKI-RRT status. We computed the in-hospital mortality risk and adjusted relative risk. For hospital survivors, we computed 5-year cumulative risk of chronic dialysis accounting for competing risk of death. Mortality after discharge was computed with use of Kaplan-Meier methods. We computed 5-year hazard ratios for chronic dialysis and death after discharge, comparing AKI-RRT with non-AKI-RRT patients using a propensity score-adjusted Cox regression model.
We identified 5079 patients with cardiogenic shock, among whom 13 % had AKI-RRT. The in-hospital mortality was 62 % for AKI-RRT patients, and 36 % for non-AKI-RRT patients. AKI-RRT remained associated with increased in-hospital mortality after adjustment for confounders (relative risk = 1.70, 95 % confidence interval (CI): 1.59–1.81). Among the 3059 hospital survivors, the 5-year risk of chronic dialysis was 11 % (95 % CI: 8–16 %) for AKI-RRT patients, and 1 % (95 % CI: 0.5–1 %) for non-AKI-RRT patients (adjusted hazard ratio: 15.9 (95 % CI: 8.7–29.3). The 5-year mortality was 43 % (95 % CI: 37–53 %) for AKI-RRT patients compared with 29 % (95 % CI: 29–31 %) for non-AKI-RRT patients. The adjusted 5-year hazard ratio for death was 1.55 (95 % CI: 1.22–1.96) for AKI-RRT patients compared with non-AKI-RRT patients. In patients with comorbidity, absolute mortality increased while relative impact of AKI-RRT on mortality decreased.
AKI-RRT following myocardial infarction-related cardiogenic shock predicted elevated short-term mortality and long-term risk of chronic dialysis and mortality. The impact of AKI-RRT declined with increasing comorbidity suggesting that intensive treatment of AKI-RRT should be accompanied with optimized treatment of comorbidity when possible.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-015-1170-8) contains supplementary material, which is available to authorized users.
PMCID: PMC4699352  PMID: 26715162
Acute kidney injury; Epidemiology; Mortality; Myocardial infarction; Shock
6.  Inter-hospital transfers and outcomes of critically ill patients with severe acute kidney injury: a multicenter cohort study 
Critical Care  2014;18(5):513.
Patients with severe acute kidney injury (AKI) who are hospitalized at centers that do not provide renal replacement therapy (RRT) are frequently subjected to inter-hospital transfer for the provision of RRT. It is unclear whether such transfers are associated with worse patient outcomes as compared with the receipt of initial care in a center that provides RRT. This study examined the relationship between inter-hospital transfer and 30-day mortality among critically ill patients with AKI who received RRT.
We conducted a retrospective cohort study of all critically ill patients who commenced RRT for AKI at two academic hospitals in Toronto, Canada. The exposure of interest was inter-hospital transfer for the administration of RRT. We evaluated the relationship between transfer status and 30-day mortality (primary outcome) and RRT dependence at 30 days following RRT initiation (secondary outcome), by using multivariate logistic regression with adjustment for patient demographics, clinical factors, biochemical indices, and severity of illness.
Of 370 patients who underwent RRT for AKI, 82 (22.2%) were transferred for this purpose from another hospital. Compared with non-transferred patients who started RRT, transferred patients were younger (61 ± 15 versus 65 ± 15 years, P = 0.03) and had a higher serum creatinine concentration at RRT initiation (474 ± 295 versus 365 ± 169 μmol/L, P = 0.002). Inter-hospital transfer was not associated with mortality (adjusted odds ratio 0.61, 95% confidence interval 0.33 to 1.12) or RRT-dependence (adjusted odds ratio 1.64, 95% confidence interval 0.70 to 3.81) at 30 days.
Within the limitations of this observational study and the potential for residual confounding, inter-hospital transfer of critically ill patients with AKI was not associated with a higher risk of death or dialysis dependence 30 days after the initiation of acute RRT.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-014-0513-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4189586  PMID: 25228166
7.  Long-Term Survival and Dialysis Dependency Following Acute Kidney Injury in Intensive Care: Extended Follow-up of a Randomized Controlled Trial 
PLoS Medicine  2014;11(2):e1001601.
Martin Gallagher and colleagues examine the long-term outcomes of renal replacement therapy (RRT) dosing in patients with acute kidney injury randomized to normal vs. augmented RRT.
Please see later in the article for the Editors' Summary
The incidence of acute kidney injury (AKI) is increasing globally and it is much more common than end-stage kidney disease. AKI is associated with high mortality and cost of hospitalisation. Studies of treatments to reduce this high mortality have used differing renal replacement therapy (RRT) modalities and have not shown improvement in the short term. The reported long-term outcomes of AKI are variable and the effect of differing RRT modalities upon them is not clear. We used the prolonged follow-up of a large clinical trial to prospectively examine the long-term outcomes and effect of RRT dosing in patients with AKI.
Methods and Findings
We extended the follow-up of participants in the Randomised Evaluation of Normal vs. Augmented Levels of RRT (RENAL) study from 90 days to 4 years after randomization. Primary and secondary outcomes were mortality and requirement for maintenance dialysis, respectively, assessed in 1,464 (97%) patients at a median of 43.9 months (interquartile range [IQR] 30.0–48.6 months) post randomization. A total of 468/743 (63%) and 444/721 (62%) patients died in the lower and higher intensity groups, respectively (risk ratio [RR] 1.04, 95% CI 0.96–1.12, p = 0.49). Amongst survivors to day 90, 21 of 411 (5.1%) and 23 of 399 (5.8%) in the respective groups were treated with maintenance dialysis (RR 1.12, 95% CI 0.63–2.00, p = 0.69). The prevalence of albuminuria among survivors was 40% and 44%, respectively (p = 0.48). Quality of life was not different between the two treatment groups. The generalizability of these findings to other populations with AKI requires further exploration.
Patients with AKI requiring RRT in intensive care have high long-term mortality but few require maintenance dialysis. Long-term survivors have a heavy burden of proteinuria. Increased intensity of RRT does not reduce mortality or subsequent treatment with dialysis.
Trial registration NCT00221013
Please see later in the article for the Editors' Summary
Editors' Summary
Throughout life, the kidneys perform the essential task of filtering waste products (from the normal breakdown of tissues and from food) and excess water from the blood to make urine. Chronic kidney disease (caused, for example, by diabetes) gradually destroys the kidneys' filtration units (the nephrons), eventually leading to life-threatening end-stage kidney disease. However, the kidneys can also stop working suddenly because of injury, infection, or poisoning. Acute kidney injury (AKI) is much more common than end-stage kidney disease and its incidence is increasing worldwide. In the US, for example, the number of hospitalizations that included an AKI diagnosis rose from 4,000 in 1996 to 23,000 in 2008. Moreover, nearly half of patients with AKI will die shortly after the condition develops. Symptoms of AKI include changes in urination, swollen feet and ankles, and tiredness. Treatments for AKI aim to prevent fluid and waste build up in the body and treat the underlying cause (e.g., severe infection or dehydration) while allowing the kidneys time to recover. In some patients, it is sufficient to limit the fluid intake and to reduce waste build-up by eating a diet that is low in protein, salt, and potassium. Other patients need renal replacement therapy (RRT), life-supporting treatments such as hemodialysis and hemofiltration, two processes that clean the blood by filtering it outside the body.
Why Was This Study Done?
The long-term outcomes of AKI (specifically, death and chronic kidney disease) and the effects of different RRT modalities on these outcomes are unclear. A recent controlled trial that randomly assigned patients with AKI who were managed in intensive care units (ICUs) to receive two different intensities of continuous hemodiafiltration (a combination of hemodialysis and hemofiltration) found no difference in all-cause mortality (death) at 90 days. Here, the researchers extend the follow-up of this trial (the Randomized Evaluation of Normal vs. Augmented Levels of renal replacement therapy [RENAL] study) to investigate longer-term mortality, the variables that predict mortality, treatment with long-term dialysis (an indicator of chronic kidney disease), and functional outcomes in patients with AKI treated with different intensities of continuous RRT.
What Did the Researchers Do and Find?
For the Prolonged Outcomes Study of RENAL (POST-RENAL), the researchers extended the follow-up of the RENAL participants up to 4 years. Over an average follow-up of 43.9 months, 63% of patients in the lower intensity treatment group died compared to 62% of patients in the higher intensity group. Overall, a third of patients who survived to 90 days died during the extended follow-up. Among the survivors to day 90, 5.1% and 5.8% of patients in the lower and higher intensity groups, respectively, were treated with maintenance dialysis during the extended follow-up. Among survivors who consented to analysis, 40% and 44% of patients in the lower and higher intensity groups, respectively, had albuminuria (protein in the urine, an indicator of kidney damage). Patients in both groups had a similar quality life (determined through telephone interviews). Finally, increasing age, APACHE III score (a scoring system that predicts the survival of patients in ICU), and serum creatinine level (an indicator of kidney function) at randomization were all predictors of long-term mortality.
What Do These Findings Mean?
These findings indicate that patients with AKI in ICUs who require RRT have a high long-term mortality. They show that few survivors require maintenance dialysis for chronic kidney disease but that there is a substantial rate of albuminuria among survivors despite relative preservation of kidney function. The findings also suggest that the intensity of RRT has no significant effect on mortality or the need for dialysis. Because these findings were obtained in a randomized controlled trial, they may not be generalizable to other patient populations. Moreover, although data on mortality and maintenance dialysis were available for all the trial participants, clinical and biochemical outcomes were only available for some participants and may not be representative of all the participants. Despite these study limitations, these findings suggest that survivors of AKI may be at a high risk of death or of developing chronic kidney disease. Survivors of AKI are, therefore, at high risk of further illness and long-term albuminuria reduction strategies may offer a therapeutic intervention for this group of patients.
Additional Information
Please access these websites via the online version of this summary at
The US National Kidney and Urologic Diseases Information Clearinghouse provides information about the kidneys and about all aspects of kidney disease and its treatment; the US National Kidney Disease Education Program provides resources to help improve the understanding, detection, and management of kidney disease (in English and Spanish)
The Mayo Clinic provides information for patients about acute kidney injury
Wikipedia has a page on acute kidney injury (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The not-for-profit UK National Kidney Federation provides support and information for patients with kidney disease and for their carers, including a link to a video about acute kidney injury
World Kidney Day, a joint initiative between the International Society of Nephrology and the International Federation of Kidney Foundations (IFKF), aims to raise awareness about kidneys and kidney disease; its website provides information about acute kidney injury
The MedlinePlus Encyclopedia has a pages about acute kidney failure and about renal dialysis
The UK National Institute for Health and Care Excellence (NICE) recently published new guidelines on the treatment of acute kidney injury; a clinical practice guideline for acute kidney injury produced by KDIGO (a not-for-profit organization that aims to improve the care and outcomes of kidney disease patients worldwide through the development and implementation of global clinical practice guidelines) is available; the Acute Kidney Injury app provides a fast and simple way to explore guidelines on the diagnosis, prevention, and management of AKI
PMCID: PMC3921111  PMID: 24523666
8.  Timing of renal replacement therapy initiation by AKIN classification system 
Critical Care  2013;17(2):R62.
Previous studies using Acute Kidney Injury Network (AKIN)/RIFLE criteria to classify early initiation of renal replacement therapy (RRT) have defined it as the therapy started in less severe AKIN/RIFLE stages. Generally, these studies failed in demonstrating measurable benefits.
We compared RRT initiation in critically ill patients and defined early or late RRT in reference to timing after stage 3 AKIN was met: patients beginning RRT within 24 hours after acute kidney injury (AKI) stage 3 were considered early starters. AKIN criteria were evaluated by both urine output (UO) and serum creatinine (sCr) and patients with acute-on-chronic kidney disease were excluded. A propensity score methodology was used to control variables.
A total of 358 critically ill patients were submitted to RRT. Only 150 patients with pure AKI at stage 3 were analyzed. Mortality was lower in the early RRT group (51.5 vs. 77.9%, P = 0.001). After achieving balance between the groups using a propensity score, there was a significant 30.5 (95% confidence interval [CI] 14.4 to 45.2%, P = 0.002) relative decrease of mortality in the early RRT group. Moreover, patients on the early RRT group had lower duration of mechanical ventilation, time on RRT and a trend to lower intensive care unit (ICU) length of stay.
For the first time, AKIN was used with UO criterion to evaluate early and late RRT. Using a time-based approach could be a better parameter to access the association between RRT initiation and outcomes in patients with AKI.
PMCID: PMC4057476  PMID: 23548002
9.  Outcomes of patients with acute kidney injury with regard to time of initiation and modality of renal replacement therapy – first data from the Silesian Registry of Intensive Care Units 
Acute kidney injury (AKI) remains a serious clinical problem in the intensive care unit (ICU). It constitutes an independent risk factor for mortality, especially when renal replacement therapy (RRT) is required.
Due to limited evidence pertaining to timing, choice of RRT modality and lack of studies investigating AKI in Polish ICUs, we sought to analyse outcomes of adult AKI-RRT ICU patients in the Silesian Voivodeship.
Material and methods
We analysed data regarding 1,380 patients with AKI who required RRT (AKI-RRT) (9.2% of all subjects in the registry) hospitalized between October 2011 and December 2014 in Silesian ICUs. The primary outcome was crude ICU mortality. Length of ICU stay (LOS) was considered the secondary outcome.
Of 15,030 patients 1,380 (9.2%) individuals developed AKI requiring RRT. The overall mortality in the registry was 43.9%, but it was significantly higher (69.1%) in AKI-RRT patients (p < 0.01). Mortality with regard to timing of institution of RRT was 67.1% in the group with RRT instituted prior to ICU admission (RRT-prior-ICU) and 69.4% in patients with RRT instituted during ICU hospitalization (RRT-in-ICU) (p = 0.58).
Multiple patient- and hospitalization-related factors determine mortality in this specific cohort. There are no differences in mortality with regard to RRT being initiated before or during hospitalization in the ICU. Due to multiple confounders, differences in mortality in terms of modality of RRT should be interpreted with caution.
PMCID: PMC4971266  PMID: 27516784
acute kidney injury; renal replacement therapy
10.  A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: a systematic review and meta-analysis 
Critical Care  2011;15(1):R72.
Our aim was to investigate the impact of early versus late initiation of renal replacement therapy (RRT) on clinical outcomes in critically ill patients with acute kidney injury (AKI).
Systematic review and meta-analysis were used in this study. PUBMED, EMBASE, SCOPUS, Web of Science and Cochrane Central Registry of Controlled Clinical Trials, and other sources were searched in July 2010. Eligible studies selected were cohort and randomised trials that assessed timing of initiation of RRT in critically ill adults with AKI.
We identified 15 unique studies (2 randomised, 4 prospective cohort, 9 retrospective cohort) out of 1,494 citations. The overall methodological quality was low. Early, compared with late therapy, was associated with a significant improvement in 28-day mortality (odds ratio (OR) 0.45; 95% confidence interval (CI), 0.28 to 0.72). There was significant heterogeneity among the 15 pooled studies (I2 = 78%). In subgroup analyses, stratifying by patient population (surgical, n = 8 vs. mixed, n = 7) or study design (prospective, n = 10 vs. retrospective, n = 5), there was no impact on the overall summary estimate for mortality. Meta-regression controlling for illness severity (Acute Physiology And Chronic Health Evaluation II (APACHE II)), baseline creatinine and urea did not impact the overall summary estimate for mortality. Of studies reporting secondary outcomes, five studies (out of seven) reported greater renal recovery, seven (out of eight) studies showed decreased duration of RRT and five (out of six) studies showed decreased ICU length of stay in the early, compared with late, RRT group. Early RRT did not; however, significantly affect the odds of dialysis dependence beyond hospitalization (OR 0.62 0.34 to 1.13, I2 = 69.6%).
Earlier institution of RRT in critically ill patients with AKI may have a beneficial impact on survival. However, this conclusion is based on heterogeneous studies of variable quality and only two randomised trials. In the absence of new evidence from suitably-designed randomised trials, a definitive treatment recommendation cannot be made.
PMCID: PMC3222005  PMID: 21352532
11.  ‘Reality and desire’ in the care of advanced chronic kidney disease 
NDT Plus  2010;3(5):431-435.
There is a long distance between the actual worldwide reality in advanced chronic kidney disease care and the desire of how these patients should be managed to decrease cardiovascular and general morbidity and mortality. Implementation of adequate infrastructures may improve clinical outcomes and increase the use of home renal replacement therapies (RRT). Current pitfalls should be addressed to optimise care: inadequate medical training for nephrological referral and RRT selection, late referral to nephrologists, inadequate patient education for choice of RRT modality, lack of multidisciplinary advanced kidney disease clinics and lack of programmed RRT initiation. These deficiencies generate unintended consequences, such as inequality of care and limitations in patient education and selection-choice for RRT technique with limited use of peritoneal dialysis. Multidisciplinary advanced kidney disease clinics may have a direct impact on patient survival, morbidity and quality of life. There is a common need to reduce health care costs and scenarios increasing PD incidence show better efficiency. The following proposals may help to improve the current situation: defining the scope of the problem, disseminating guidelines with specific targets and quality indicators, optimising medical speciality training, providing adequate patient education, specially through the use of general decision making tools that will allow patients to choose the best possible RRT in accordance with their values, preferences and medical advice, increasing planned dialysis starts and involving all stakeholders in the process.
PMCID: PMC4421705  PMID: 25984045
advanced chronic kidney disease care units; multidisciplinary care; planned dialysis start; quality indicators
12.  Impact of timing of renal replacement therapy initiation on outcome of septic acute kidney injury 
Critical Care  2011;15(3):R134.
Sepsis is the leading cause of acute kidney injury (AKI) in critical patients. The optimal timing of initiating renal replacement therapy (RRT) in septic AKI patients remains controversial. The objective of this study is to determine the impact of early or late initiation of RRT, as defined using the simplified RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification (sRIFLE), on hospital mortality among septic AKI patients.
Patient with sepsis and AKI requiring RRT in surgical intensive care units were enrolled between January 2002 and October 2009. The patients were divided into early (sRIFLE-0 or -Risk) or late (sRIFLE-Injury or -Failure) initiation of RRT by sRIFLE criteria. Cox proportional hazard ratios for in hospital mortality were determined to assess the impact of timing of RRT.
Among the 370 patients, 192 (51.9%) underwent early RRT and 259 (70.0%) died during hospitalization. The mortality rate in early and late RRT groups were 70.8% and 69.7% respectively (P > 0.05). Early dialysis did not relate to hospital mortality by Cox proportional hazard model (P > 0.05). Patients with heart failure, male gender, higher admission creatinine, and operation were more likely to be in the late RRT group. Cox proportional hazard model, after adjustment with propensity score including all patients based on the probability of late RRT, showed early dialysis was not related to hospital mortality. Further model matched patients by 1:1 fashion according to each patient's propensity to late RRT showed no differences in hospital mortality according to head-to-head comparison of demographic data (P > 0.05).
Use of sRIFLE classification as a marker poorly predicted the benefits of early or late RRT in the context of septic AKI. In the future, more physiologically meaningful markers with which to determine the optimal timing of RRT initiation should be identified.
PMCID: PMC3219003  PMID: 21645350
13.  Renal replacement therapy in Latin American end-stage renal disease 
Clinical Kidney Journal  2014;7(4):431-436.
The Latin American Dialysis and Renal Transplant Registry (RLADTR) was founded in 1991; it collects data from 20 countries which are members of Sociedad Latinoamericana de Nefrología e Hipertension. This paper presents the results corresponding to the year 2010. This study is an annual survey requesting data on incident and prevalent patients undergoing renal replacement treatment (RRT) in all modalities: hemodialysis (HD), peritoneal dialysis (PD) and living with a functioning graft (LFG), etc. Prevalence and incidence were compared with previous years. The type of renal replacement therapy was analyzed, with special emphasis on PD and transplant (Tx). These variables were correlated with the gross national income (GNI) and the life expectancy at birth. Twenty countries participed in the surveys, covering 99% of the Latin American. The prevalence of end stage renal disease (ESRD) under RRT in Latin America (LA) increased from 119 patients per million population (pmp) in 1991 to 660 pmp in 2010 (HD 413 pmp, PD 135 pmp and LFG 111 pmp). HD proportionally increased more than PD, and Tx HD continues to be the treatment of choice in the region (75%). The kidney Tx rate increased from 3.7 pmp in 1987 to 6.9 pmp in 1991 and to 19.1 in 2010. The total number of Tx's in 2010 was 10 397, with 58% deceased donors. The total RRT prevalence correlated positively with GNI (r2 0.86; P < 0.05) and life expectancy at birth (r2 0.58; P < 0.05). The HD prevalence and the kidney Tx rate correlated significantly with the same indexes, whereas the PD rate showed no correlation with these variables. A tendency to rate stabilization/little growth was reported in the most regional countries. As in previous reports, the global incidence rate correlated significantly only with GNI (r2 0.63; P < 0.05). Diabetes remained the leading cause of ESRD. The most frequent causes of death were cardiovascular (45%) and infections (22%). Neoplasms accounted for 10% of the causes of death. The prevalence of RRT continues to increase, particularly in countries with 100% public health or insurance coverage for RRT, where it approaches rates comparable to those displayed by developed countries with a better GNI. The incidence also continues to increase in both countries that have not yet extended its coverage to 100% of the population as well as in those that have an adequate program for timely detection and treatment of chronic kidney disease (CKD) and its associated risk factors. PD is still an underutilized strategy for RRT in the region. Even though renal Tx is feasible, its growth rate is still not as fast as it should be in order to compensate for the increased prevalence of patients on waiting lists. Diagnostic and prevention programs for hypertension and diabetes, appropriate policies promoting the expansion of PD and organ procurement as well as transplantation as cost-effective forms of RRT are needed in the region. Regional cooperation among Latin American countries, allowing the more developed to guide and train others in starting registries and CKD programs, may be one of the key initiatives to address this deficit.
PMCID: PMC4208784  PMID: 25349696
peritoneal dialysis; hemodialysis; kidney transplantation; chronic renal failure; Latin America
14.  Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery 
Critical Care  2009;13(5):R171.
Abdominal surgery is probably associated with more likelihood to cause acute kidney injury (AKI). The aim of this study was to evaluate whether early or late start of renal replacement therapy (RRT) defined by simplified RIFLE (sRIFLE) classification in AKI patients after major abdominal surgery will affect outcome.
A multicenter prospective observational study based on the NSARF (National Taiwan University Surgical ICU Associated Renal Failure) Study Group database. 98 patients (41 female, mean age 66.4 ± 13.9 years) who underwent acute RRT according to local indications for post-major abdominal surgery AKI between 1 January, 2002 and 31 December, 2005 were enrolled The demographic data, comorbid diseases, types of surgery and RRT, as well as the indications for RRT were documented. The patients were divided into early dialysis (sRIFLE-0 or Risk) and late dialysis (LD, sRIFLE -Injury or Failure) groups. Then we measured and recorded patients' outcome including in-hospital mortality and RRT wean-off until 30 June, 2006.
The in-hospital mortality was compared as endpoint. Fifty-seven patients (58.2%) died during hospitalization. LD (hazard ratio (HR) 1.846; P = 0.027), old age (HR 2.090; P = 0.010), cardiac failure (HR 4.620; P < 0.001), pre-RRT SOFA score (HR 1.152; P < 0.001) were independent indicators for in-hospital mortality.
The findings of this study support earlier initiation of acute RRT, and also underscore the importance of predicting prognoses of major abdominal surgical patients with AKI by using RIFLE classification.
PMCID: PMC2784403  PMID: 19878554
15.  Cancer risk in patients receiving renal replacement therapy: A meta-analysis of cohort studies 
Molecular and Clinical Oncology  2016;5(3):315-325.
It has been reported that patients receiving renal replacement therapy (RRT), including dialysis and kidney transplantation, tend to have an increased risk of cancer; however, studies on the degree of this risk have remained inconclusive. The present meta-analysis was therefore performed to quantify the cancer risk in patients with RRT. Cohort studies assessing overall cancer risk in RRT patients published before May 29, 2015 were included following systematic searches with of PubMed, EMBASE and the reference lists of the studies retrieved. Random-effects meta-analyses were used to pool standardized incidence rates (SIRs) with 95% confidence intervals (CIs). Heterogeneity tests, sensitivity analyses and publication bias assessment were performed. A total of 18 studies including 22 cohort studies were eventually identified, which comprised a total of 1,528,719 patients. In comparison with the general population, the pooled SIR for patients with dialysis including non-melanoma skin cancer (NMSC), dialysis excluding NMSC, transplantation including NMSC, transplantation excluding NMSC and RRT were 1.40 (95% CI, 1.36–1.45), 1.35 (95% CI, 1.23–1.50), 3.26 (95% CI, 2.29–4.63), 2.08 (95% CI, 1.73–2.50) and 2.01 (95% CI, 1.70–2.38), respectively. The cancer risk was particularly high in subgroups of large sample size trials, female patients, younger patients (age at first dialysis, 0–34 years; age at transplantation, 0–20 years), the first year of RRT and non-Asian transplant patients. A significant association was also found between RRT and the majority of organ-specific cancers. However, neither dialysis nor transplantation was associated with breast, body of uterus, colorectal or prostate cancer. Significant heterogeneity was found regarding the association between RRT and overall cancer as well as the majority of site-specific cancer types. However, this heterogeneity had no substantial influence on the pooled SIR for overall cancer in RRT according to the sensitivity analysis. Compared with the general population, RRT patients have a significantly increased risk of overall cancer and the majority of specific cancer types, particularly Kaposi sarcoma (KS), lip cancer and NMSC in patients subjected to kidney transplantation and cancer of the thyroid gland and kidney as well as myeloma in dialysis patients. Considering the high heterogeneity encountered, further high-quality studies are required.
PMCID: PMC4998351  PMID: 27602224
cancer; dialysis; hemodialysis; transplantation; transplant; standardised incidence ratio
16.  Reduction in hospital-wide mortality after implementation of a rapidresponse team: a long-term cohort study 
Critical Care  2011;15(6):R269.
Rapid response teams (RRTs) have been shown to reduce cardiopulmonary arrests outside the intensive care unit (ICU). Yet the utility of RRTs remains in question, as most large studies have failed to demonstrate a significant reduction in hospital-wide mortality after RRT implementation.
A cohort design with historical controls was used to determine the effect on hospital-wide mortality of an RRT in which clinical judgment, in addition to vital-signs criteria, was widely promoted as a key trigger for activation. All nonprisoner patients admitted to a tertiary referral public teaching hospital from 2003 through 2008 were included. In total, 77, 021 admissions before RRT implementation (2003 through 2005) and 79, 013 admissions after RRT implementation (2006 through 2008) were evaluated. The a priori primary outcome was unadjusted hospital-wide mortality. A Poisson regression model was then used to adjust for hospital-wide mortality trends over time. Secondary outcomes defined a priori were unadjusted out-of-ICU mortality and out-of-ICU cardiopulmonary-arrest codes.
In total, 855 inpatient RRTs (10.8 per 1, 000 hospital-wide discharges) were activated during the 3-year postintervention period. Forty-seven percent of RRTs were activated for reasons of clinical judgment. Hospital-wide mortality decreased from 15.50 to 13.74 deaths per 1, 000 discharges after RRT implementation (relative risk, 0.887; 95% confidence interval (CI), 0.817 to 0.963; P = 0.004). After adjusting for inpatient mortality trends over time, the reduction in hospital-wide mortality remained statistically significant (relative risk, 0.825; 95% CI, 0.694 to 0.981; P = 0.029). Out-of-ICU mortality decreased from 7.08 to 4.61 deaths per 1, 000 discharges (relative risk, 0.651; 95% CI, 0.570 to 0.743; P < 0.001). Out-of-ICU cardiopulmonary-arrest codes decreased from 3.28 to 1.62 codes per 1, 000 discharges (relative risk, 0.493; 95% CI, 0.399 to 0.610; P < 0.001).
Implementation of an RRT in which clinical judgment, in addition to vital-signs criteria, was widely cited as a rationale for activation, was associated with a significant reduction in hospital-wide mortality, out-of-ICU mortality, and out-of-ICU cardiopulmonary-arrest codes. The frequent use of clinical judgment as a criterion for RRT activation was associated with high RRT utilization.
PMCID: PMC3388666  PMID: 22085785
17.  Impact of renal dysfunction on weaning from prolonged mechanical ventilation 
Critical Care  1998;1(3):101-104.
In the intensive care unit (ICU) setting, the combination of mechanical ventilation and renal replacement therapy (RRT) has been associated with prolonged length of hospital stay, high cost of care and poor outcome. We gathered outcome data on patients who had severe renal dysfunction on transfer to our regional weaning center (RWC) for attempted weaning from prolonged mechanical ventilation (PMV). We screened the admission laboratory values of 1077 patients transferred to our RWC over an 8-year period. We reviewed the medical records of patients with serum creatinine > 2.5 mg/dl.
Sixty-three patients met screening criteria and 40 patients were on RRT at the time of transfer. Eighteen patients had begun chronic RRT at least 2 months prior to admission to the transferring hospital for their current illness. Twenty-two patients had RRT initiated at the transferring hospital. Ten patients had RRT initiated at the RWC; eight patients had improvement or resolution of azotemia at our facility. RRT was withheld at patient/family request in five patients with progressive renal failure. None of the 50 patients who received RRT recovered renal function during treatment at our RWC. Intermittent hemodialysis was the standard RRT at the RWC. Duration of mechanical ventilation prior to transfer to the RWC was 49.7 ± 33.5 days (mean ± SD).
Outcome of weaning attempts in the 63 patients was as follows: 13% weaned, 3% failed to wean and 84% died. These outcomes were significantly worse (P<0.001) than those in the 1014 patients whose admission serum creatinine was ≤ 2.5 mg/dl (58% weaned, 15% failed to wean, 27% died). The five patients in whom RRT was withheld were predominantly in progressive multisystem organ failure, and were unlikely to have survived regardless of RRT. From the study cohort, only one of the 10 patients discharged alive returned home, in contrast to 42% of the control group. No patient with severe renal dysfunction survived to 1 year post-discharge, compared to a 1-year survival of 38% in the control group (P = 0.029). Only four of the 10 patients survived more than 1 month, with the longest survival being 122 days.
Patients who require PMV and RRT have a very poor prognosis. The small number of patients with renal insufficiency not requiring RRT had a more favorable hospital outcome and mortality, but long-term survival remained poor.
PMCID: PMC28994  PMID: 11056702
hemodialysis; patient outcome; prolonged mechanical ventilation; renal failure; renal replacement therapy; respiratory failure; ventilator weaning
18.  Survival prognosis after the start of a renal replacement therapy in the Netherlands: a retrospective cohort study 
BMC Nephrology  2013;14:258.
There is no single model available to predict the long term survival for patients starting renal replacement therapy (RRT). The available models either predict survival on dialysis until transplantation, survival on the transplant waiting list, or survival after transplantation. The aim of this study was to develop a model that includes dialysis survival and survival after an eventual transplantation.
From the Dutch renal replacement registry, patients of 16 years of age or older were included if they started RRT between 1995 and 2005, still underwent RRT at baseline (90 days after the start of RRT) and were not registered at a non-renal organ transplant waiting list (N = 13868). A prediction model of 10-year patient survival after baseline was developed through multivariate Cox regression analysis, in one half of the research group. Age at start, sex, primary renal disease (PRD) and therapy at baseline were included as possible predictors. A sensitivity analysis has been performed to determine whether listing on the transplant waiting list should be added. The predictive performance of the model was internally validated. Calibration and discrimination were computed in the other half of the research group. Another sensitivity analysis was to assess whether the outcomes differed if the model was developed and tested in two geographical regions, which were less similar than the original development and validation group. No external validation has been performed.
Survival probabilities were influenced by age, sex, PRD and therapy at baseline (p < 0.001). The calibration and discrimination both showed very reasonable results for the prediction model (C-index = 0.720 and calibration slope for the prognostic index = 1.025, for the 10 year survival). Adding registration on the waiting list for renal transplantation as a predictor did not improve the discriminative power of the model and was therefore not included in the model.
With the presented prediction model, it is possible to give a reasonably accurate estimation on the survival chances of patients who start with RRT, using a limited set of easily available data.
PMCID: PMC4225578  PMID: 24256551
19.  Opinion of French nephrologists on renal replacement therapy: survey on their personal choice 
Clinical Kidney Journal  2015;8(6):785-788.
In France, like in most developed countries, peritoneal dialysis (PD) is less used than haemodialysis (HD). This is not based on medical evidence supporting HD superiority. As the practitioner's opinion is important to patients and may influence their treatment choice, we conducted a survey among French nephrologists to determine which renal replacement therapy (RRT) they would choose if they had end-stage renal disease (ESRD).
We e-mailed a self-administered questionnaire to all members of the French-speaking Nephrology Society between 19 October 2008 and 12 January 2009. We then selected from the French Renal Epidemiology and Information Network (REIN) registry a reference population of 20- to 64-year-old patients with ESRD who began RRT [HD, PD or pre-emptive transplantation, (PT)] in 2008.
The survey response rate was 17.8%. Results showed that 59.6% of respondents chose early inscription on the transplantation waiting list in view of PT, 20.2% selected HD and 20.2% selected PD. When dialysis was the only choice, 50.2% chose HD and 49.8% chose PD. Younger nephrologists (≤44 years old) selected PD more frequently than older nephrologists (≥45 years old) (58.9 versus 40.5%; P < 0.01). Similarly, PD was chosen more often by nephrologists from regions with ‘more PD’ than from regions with ‘less PD’ (79.0 versus 48.8%; P < 0.05). The nephrologists' choices were different from the RTT distribution among the reference population: 81.7% HD, 10.1% PD and 8.2% PT.
Our survey on the theoretical choice of RTT suggests that the low PD rate in France cannot be explained by a negative opinion of PD among French nephrologists.
PMCID: PMC4655798  PMID: 26613040
haemodialysis; opinion survey; peritoneal dialysis; therapeutic education
20.  Association of blood pressure with decline in renal function and time until the start of renal replacement therapy in pre-dialysis patients: a cohort study 
BMC Nephrology  2011;12:38.
To investigate whether high blood pressure accelerates renal function decline in patients with advanced chronic kidney disease (CKD), we studied the association of systolic (SBP) and diastolic blood pressure (DBP) with decline in renal function and time until the start of renal replacement therapy (RRT) in patients with CKD stages IV-V on pre-dialysis care.
In the PREPARE-1 cohort 547 incident pre-dialysis patients, referred as part of the usual care to outpatient clinics of eight Dutch hospitals, were included between 1999 and 2001 and followed until the start of RRT, mortality, or end of follow-up (January 1st 2008). Main outcomes were rate of decline in renal function, estimated as the slope of available eGFR measurements, and time until the start of RRT.
A total of 508 patients, 57% men and median (IQR) age of 63 (50-73) years, were available for analyses. Mean (SD) decline in renal function was 0.35 (0.75) ml/min/1.73 m2/month. Every 10 mmHg increase in SBP or DBP resulted in an accelerated decline in renal function (adjusted additional decline 0.04 (0.02;0.07) and 0.05 (0.00;0.11) ml/min/1.73 m2/month respectively) and an earlier start of RRT (adjusted HR 1.09 (1.04;1.14) and 1.16 (1.05;1.28) respectively). Furthermore, patients with SBP and DBP above the BP target goal of < 130/80 mmHg experienced a faster decline in renal function (adjusted additional decline 0.31 (0.08;0.53) ml/min/1.73 m2/month) and an earlier start of RRT (adjusted HR 2.08 (1.25;3.44)), compared to patients who achieved the target goal (11%). Comparing the decline in renal function and risk of starting RRT between patients with only SBP above the target (≥ 130 mmHg) and patients with both SBP and DBP below the target (< 130/80 mmHg), showed that the results were almost similar as compared to patients with both SBP and DBP above the target (adjusted additional decline 0.31 (0.04;0.58) ml/min/1.73 m2/month and adjusted HR 2.24 (1.26;3.97)). Therefore, it seems that especially having SBP above the target is harmful.
In pre-dialysis patients with CKD stages IV-V, having blood pressure (especially SBP) above the target goal for CKD patients (< 130/80 mmHg) was associated with a faster decline in renal function and a later start of RRT.
PMCID: PMC3171298  PMID: 21835038
blood pressure; chronic kidney disease stages IV-V; estimated glomerular filtration rate; pre-dialysis care; renal replacement therapy
21.  The effect of gender, age, and geographical location on the incidence and prevalence of renal replacement therapy in Wales 
BMC Nephrology  2007;8:1.
This study used a cross sectional survey to examine the effect of gender, age, and geographical location on the population prevalence of renal replacement therapy (RRT) provision in Wales.
Physicians in renal centres in Wales and in adjacent areas of England were asked to undertake a census of patients on renal replacement therapy on 30 June 2004 using an agreed protocol. Data were collated and analysed in anonymous form.
2434 patients were on RRT in Wales at the census date. Median age of patients on RRT was 56 years, peritoneal dialysis 58 years, haemodialysis 66 years and transplantation 50 years. The three treatment modalities had significantly different age-specific peak prevalence rates and distributions. RRT age-specific prevalence rates peaked at around 70 years (1790 pmp), transplantation at around 60 years (924 pmp), haemodialysis at around 80 years (1080 pmp) and peritoneal dialysis did not have a clear peak prevalence rate. Age-specific incidence of RRT peaked at a rate of 488 pmp at 79 years, as did incidence rates for haemodialysis, which peaked at the same age. Age had less effect on the initiation of peritoneal dialysis, which had a broad plateau between the early fifties and late seventies. Kidney transplantation rates were highest in the early fifties but were markedly absent in old age.
Differences in the provision of RRT are evident, particularly in the very elderly, where the gender difference for haemodialysis is particularly marked. The study illustrates that grouping patients over 75 years into a single age-band may mask significant diversity within this age group. Significant numbers of very elderly patients who are currently not receiving RRT may wish to receive RRT as the elderly population increases, and as technology improves survival and quality of life on RRT.
The study suggests that if technologies that are more effective were developed, and which had a lower impact on quality of life, there might be up to a 17% increase in demand for RRT in those aged over 75 years; around 90% of this increased demand would be for haemodialysis.
PMCID: PMC1781434  PMID: 17217542
22.  The increase in renal replacement therapy (RRT) incidence has come to an end in Sweden—analysis of variations by region over the period 1991–2010 
Clinical Kidney Journal  2013;6(3):352-357.
Renal replacement therapy (RRT) incidence has increased significantly in Sweden during the past decades. This study analyses variations in time and regional trends in RRT incidence in Sweden, adjusted for age and gender, focusing on the impact change in incidence during the last decade.
Using data from the Swedish Renal Registry (SRR) (21 counties in Sweden, total population 9 million), we identified all incident subjects starting RRT from 1991 through 2010. Only individuals alive following 90 days of RRT start were included. Gender- and age-specific standardized RRT incidences on an annual and regional basis were calculated, and differences between counties and variations over time were examined. We compared the overall age and gender-adjusted RRT incidence rates for Sweden by calendar year. Furthermore, we also calculated the age and gender-adjusted RRT incidence in each county during two time periods (1991–1999 versus 2000–2010).
There were 20 172 new subjects treated with RRT between January 1991 and December 2010. The most common cause of end-stage renal disease (ESRD) was diabetes (24%) and hypertension/renal vascular disease (19%), followed by glomerulonephritis (16%). Sixty-four percent of new patients were male; the median age when commencing RRT was 66 years (10–90 percentiles; 39–80). The overall standardized RRT incidence reached its peak in 2000, and slowly decreased thereafter. A decrease in RRT incidence was observed over the study period in eight regions. The standardized RRT incidence varied between the different counties, from 0.82 to 1.19.
Adjusted for demographic changes in the population, an overall decrease in RRT incidence was observed from the year 2000 onwards—suggesting that the previously reported steady increase in RRT incidence is coming to an end in Sweden. Noteworthy differences were found between counties and in 8 out of 21 counties, a decreased incidence of RRT was found. Further studies need to identify the factors that contribute to this decrease.
PMCID: PMC4400478  PMID: 26064505
dialysis; geography; kidney disease; survival
23.  Fluid balance, intradialytic hypotension, and outcomes in critically ill patients undergoing renal replacement therapy: a cohort study 
Critical Care  2014;18(6):624.
In this cohort study, we explored the relationship between fluid balance, intradialytic hypotension and outcomes in critically ill patients with acute kidney injury (AKI) who received renal replacement therapy (RRT).
We analysed prospectively collected registry data on patients older than 16 years who received RRT for at least two days in an intensive care unit at two university-affiliated hospitals. We used multivariable logistic regression to determine the relationship between mean daily fluid balance and intradialytic hypotension, both over seven days following RRT initiation, and the outcomes of hospital mortality and RRT dependence in survivors.
In total, 492 patients were included (299 male (60.8%), mean (standard deviation (SD)) age 62.9 (16.3) years); 251 (51.0%) died in hospital. Independent risk factors for mortality were mean daily fluid balance (odds ratio (OR) 1.36 per 1000 mL positive (95% confidence interval (CI) 1.18 to 1.57), intradialytic hypotension (OR 1.14 per 10% increase in days with intradialytic hypotension (95% CI 1.06 to 1.23)), age (OR 1.15 per five-year increase (95% CI 1.07 to 1.25)), maximum sequential organ failure assessment score on days 1 to 7 (OR 1.21 (95% CI 1.13 to 1.29)), and Charlson comorbidity index (OR 1.28 (95% CI 1.14 to 1.44)); higher baseline creatinine (OR 0.98 per 10 μmol/L (95% CI 0.97 to 0.996)) was associated with lower risk of death. Of 241 hospital survivors, 61 (25.3%) were RRT dependent at discharge. The only independent risk factor for RRT dependence was pre-existing heart failure (OR 3.13 (95% CI 1.46 to 6.74)). Neither mean daily fluid balance nor intradialytic hypotension was associated with RRT dependence in survivors. Associations between these exposures and mortality were similar in sensitivity analyses accounting for immortal time bias and dichotomising mean daily fluid balance as positive or negative. In the subgroup of patients with data on pre-RRT fluid balance, fluid overload at RRT initiation did not modify the association of mean daily fluid balance with mortality.
In this cohort of patients with AKI requiring RRT, a more positive mean daily fluid balance and intradialytic hypotension were associated with hospital mortality but not with RRT dependence at hospital discharge in survivors.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-014-0624-8) contains supplementary material, which is available to authorized users.
PMCID: PMC4255668  PMID: 25407408
24.  Variation in the use of renal replacement therapy in patients with septic shock: a substudy of the prospective multicenter observational FINNAKI study 
Critical Care  2014;18(1):R26.
Indications for renal replacement therapy (RRT) have not been generally standardized and vary among intensive care units (ICUs). We aimed to assess the proportion, indications, and modality of RRT, as well as the association between the proportion of RRT use and 90-day mortality in patients with septic shock in Finnish adult ICUs.
We identified patients with septic shock from the prospective observational multicenter FINNAKI study conducted between 1 September 2011 and 1 February 2012. We divided the ICUs into high-RRT and low-RRT ICUs according to the median of the proportion of RRT-treated patients with septic shock. Differences in indications, and modality of RRT between ICU groups were assessed. Finally, we performed an adjusted logistic regression analysis to evaluate the possible association of the ICU group (high vs. low-RRT) with 90-day mortality.
Of the 726 patients with septic shock, 131 (18.0%, 95% CI 15.2 to 20.9%) were treated with RRT. The proportion of RRT-treated patients varied from 3% up to 36% (median 19%) among ICUs. High-RRT ICUs included nine ICUs (354 patients) and low-RRT ICUs eight ICUs (372 patients). In the high-RRT ICUs patients with septic shock were older (P = 0.04), had more cardiovascular (P <0.001) and renal failures (P = 0.003) on the first day in the ICU, were more often mechanically ventilated, and received higher maximum doses of norepinephrine (0.25 μg/kg/min vs. 0.18 μg/kg/min, P <0.001) than in the low-RRT ICUs. No significant differences in indications for or modality of RRT existed between the ICU groups. The crude 90-day mortality rate for patients with septic shock was 36.2% (95% CI 31.1 to 41.3%) in the high-RRT ICUs compared to 33.9% (95% CI 29.0 to 38.8%) in the low-RRT ICUs, P = 0.5. In an adjusted logistic regression analysis the ICU group (high-RRT or low-RRT ICUs) was not associated with 90-day mortality.
Patients with septic shock in ICUs with a high proportion of RRT had more severe organ dysfunctions and received more organ-supportive treatments. Importantly, the ICU group (high-RRT or low-RRT group) was not associated with 90-day mortality.
PMCID: PMC4056326  PMID: 24499547
25.  Smoking and renal function in people living with human immunodeficiency virus: a Danish nationwide cohort study 
Clinical Epidemiology  2015;7:391-399.
Smoking is a main risk factor for morbidity and mortality in people living with human immunodeficiency virus (PLHIV), but its potential association with renal impairment remains to be established.
We did a nationwide population-based cohort study in Danish PLHIV to evaluate the association between smoking status and 1) overall renal function and risk of chronic kidney disease (CKD), 2) risk of any renal replacement therapy (aRRT), and 3) mortality following aRRT. We calculated estimated creatinine clearance using the Cockcroft–Gault equation (CG-CrCl), and evaluated renal function graphically. We calculated cumulative incidence of CKD (defined as two consecutive CG-CrCls of ≤60 mL/min, ≥3 months apart) and aRRT and used Cox regression models to calculate incidence rate ratios (IRRs) for risk of CKD, aRRT, and mortality rate ratios (MRRs) following aRRT.
From the Danish HIV Cohort Study, we identified 1,475 never smokers, 768 previous smokers, and 2,272 current smokers. During study period, we observed no association of smoking status with overall renal function. Previous and current smoking was not associated with increased risk of CKD (adjusted IRR: 1.1, 95% confidence interval [CI]: 0.7–1.7; adjusted IRR: 1.3, 95% CI: 0.9–1.8) or aRRT (adjusted IRR: 0.8, 95% CI: 0.4–1.7; adjusted IRR: 0.9, 95% CI: 0.5–1.7). Mortality following aRRT was high in PLHIV and increased in smokers vs never smokers (adjusted MRR: 3.8, 95% CI: 1.3–11.2).
In Danish PLHIV, we observed no strong association between smoking status and renal function, risk of CKD, or risk of aRRT, but mortality was increased in smokers following aRRT.
PMCID: PMC4559253  PMID: 26357490
chronic kidney disease; renal replacement therapy; mortality; creatinine clearance; incidence rate ratio; mortality rate ratio

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