BACKGROUND: Accurate prediction of patient survival from the time of starting renal replacement therapy (RRT) is desirable, but previously published predictive models have low accuracy. We have attempted to overcome limitations of previous studies by conducting an ambidirectional inception cohort study in patients on RRT from centres throughout Europe. A conventional multivariate regression (MVR) model, a self-learning rule-based model (RBM) and a simple co-morbidity score [the Charlson score modified for renal disease (MCS)] were compared. METHODS: In 1996, all 3640 dialysis centres registered with the ERA-EDTA were invited to identify all patients on RRT for end-stage renal failure (ESRF) who died during the 28 days of February 1997 (training cohort) and all patients who started RRT in the same period (validation cohort). Fifty-four clinical and laboratory variables from the time of starting RRT were collected in both cohorts using a two-page questionnaire. The data from the training cohort were given to statisticians at the Amsterdam Academic Medical Centre to create the MVR model and to engineers in Strathclyde University to create the RBM. They were then given the baseline data from patients in the validation cohort to predict how long each patient would survive. Follow-up questionnaires were sent to the centre of each patient in the validation cohort to determine actual survival. RESULTS: A total of 2310 patients from 793 centres in 37 countries in the ERA-EDTA area were used to construct and validate the models. For predicting 1-year survival, the RBM had the highest positive predictive value (PPV) (84.2%), the MVR model had the highest negative predictive value (NPV) (47%) and the RBM had the highest likelihood ratio (1.59). For predicting 5-year survival, the MCS had the highest PPV (79.4%), the RBM had the highest NPV (74.3%) and the MCS had the highest likelihood ratio (7.0). The proportion of explained variance in survival for MCS, MVR and RBM was 14.6, 12.9 and 3.95%, respectively. CONCLUSION: Using the ambidirectional inception cohort design of this ERA-EDTA Registry survey, we have been able to create and validate two novel instruments to predict survival in patients starting RRT and compare them with a simple scoring model. The models tended to predict 5-year survival with more accuracy than 1-year survival. Examples of potential applications include informing clinical decision making about the likely benefit of starting RRT and listing for transplantation, adjusting for baseline risk in comparative studies and identifying specific risk groups to participate in clinical trials.

Comorbidity↗

PubMed2005

Allocation of deceased donor kidneys for transplantation: opinions of patients with CKD.

BACKGROUND: Deceased donor kidney allocation schemes are designed to balance optimal utility with equity of access. The aim of this single-center survey is to seek patient opinion about the relative importance of factors used to determine the optimal transplant recipient in kidney allocation schemes. METHODS: In each of 8 scenarios, participants were invited to select which 1 of 2 hypothetical patients should receive a kidney. RESULTS: Two hundred thirty-two of 295 invited patients (78.6%) completed the questionnaire: 104 of 153 invited hemodialysis patients (68.0%) and 128 of 142 invited patients with functioning transplants (90.1%). Only 6.0% of participants agreed with current UK Transplant (UKT) and United Network for Organ Sharing (UNOS) allocation to a patient not yet on dialysis therapy who had been on the transplant waiting list longer than a patient already on dialysis therapy. Only 24.6% of participants agreed with the UKT and UNOS schemes that the transplant survival advantage associated with HLA matching warranted allocation of a kidney to a patient who had been waiting 2 years in preference to a patient waiting 7 years. Participants also were opposed to the use of recipient age and balance of exchange agreements (that reward centers with high rates of organ retrieval). The majority agreed with UKT and UNOS that recipient sex should not be used to allocate kidneys and allocation should favor recipients who have waited longer. CONCLUSION: Patients disagreed with several aspects of current allocation systems. Analysis of patient opinion should be taken into consideration when attempting to optimize the use of this scarce health resource.

Adolescent↗

PubMed2004

Restless legs syndrome in patients on dialysis.

The past decade has seen an explosion of interest in both idiopathic and secondary restless legs syndrome (RLS). Secondary RLS occurs in patients with uremia, pregnancy, and iron deficiency. Patients experience an irresistible urge to move the legs that is worse during inactivity and at night. RLS affects 6.6% to 62% of patients on long-term dialysis therapy and is associated with a greater mortality risk. The wide range of reported prevalence is explained in part by variations in methods of diagnosis. The International Restless Legs Syndrome Study Group defined diagnostic criteria that have improved the quality of RLS research. Advanced neurological imaging techniques suggest the pathophysiological state of idiopathic RLS involves dysfunction of subcortical areas of the brain. Dopaminergic pathways and neuronal iron handling have been implicated. Limited studies of patients with uremic RLS suggested similar mechanisms, but anemia, hyperphosphatemia, and psychological factors also may have a role. The few clinical trials in uremic RLS suggest that treatment should involve the reduction of potential exacerbating agents (tricyclic antidepressants, selective serotonin uptake inhibitors, lithium, and dopamine antagonists), correction of anemia (with erythropoietin and iron), and use of levodopa or dopamine agonists. Other agents shown to be of benefit in idiopathic RLS can be tried, but may be limited by side effects in patients with uremia (benzodiazepines, opioids, gabapentin, carbamazepine, and clonidine). Symptoms of uremic RLS will disappear within a few weeks of successful renal transplantation. The progress made to date in unraveling the pathophysiological state of uremic RLS should stimulate additional research toward targeted therapy.

Dopamine Agents↗

PubMed2004

Early initiation of dialysis fails to prolong survival in patients with end-stage renal failure.

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Humans↗

PubMed2004

Persistent dipstick haematuria following renal transplantation.

Despite widespread testing for dipstick haematuria following renal transplantation, there are no published series describing the prevalence and possible causes of this complication in an adult population. A cross-sectional study of 640 renal transplant recipients under review at our follow-up clinic was performed. Persistent haematuria was defined as a minimum of 1+ of blood on urinalysis stick testing detected at not fewer than 75% of clinic visits since its onset, or since the start of routine testing, present over a period of at least 4 weeks. The prevalence of persistent dipstick haematuria was 13.3%. Median serum creatinine was higher in patients with persistent haematuria but age, gender and length of time since transplantation were not significantly different. Potential explanations for persistent haematuria in 21 of 85 affected patients were chronic infection, ureteric stent without chronic infection, regular or intermittent self-catheterization, persistent menstrual bleeding, anticoagulant therapy, graft calculus, and allograft renal cell carcinoma. Recurrent or de novo glomerular disease was confirmed by graft biopsy in 10 of 85 patients. Among the 41 recipients whose original cause of renal failure was IgA nephropathy (IgAN), the prevalence of persistent haematuria was 31.7% compared with 12% in the remaining patients (relative risk 2.6, 95% CI: 1.6-4.3). Persistent haematuria in IgAN patients was not associated with gender, age or time since transplantation. After 29 months of follow-up, 20% of patients with haematuria had progressed to graft failure or death compared with 11.6% of the unaffected group (p = 0.029). However, despite the association with earlier graft failure, haematuria did not predict this endpoint independently of renal function.

Adolescent↗

PubMed2003

Excess interdialytic sodium intake is not always dietary.

Explore the source record for details and available documents.

Aged↗

PubMed2003

Once weekly administration of erythropoietin.

Explore the source record for details and available documents.

Dose-Response Relationship, Drug↗

PubMed2003

A tricontinental view of IgA nephropathy.

BACKGROUND: The purpose of this retrospective study was to analyse patients from four centres in three continents to determine if differences in long-term outcome of IgA nephropathy (IgAN) are explained by clinical and laboratory features at presentation. METHODS: The study included 711 adults with biopsy-proven IgAN from Glasgow, UK (n = 112), Helsinki, Finland (n = 204), Sydney, Australia (n = 121) and Toronto, Canada (n = 274). Data collected from time of presentation to a nephrologist were age, gender, 24-h urine protein excretion (UP(0)), mean arterial pressure (MAP(0)) and creatinine clearance (CrCl(0)). Outcomes were slope of creatinine clearance (CrCl) and renal survival. RESULTS: At presentation there was significant vari-ability in baseline clinical features with patients from Helsinki having the lowest median UP(0), lowest MAP(0) and highest CrCl(0), all suggesting milder disease. There was significant variability in renal survival between centres with 10-year actuarial survival of 95.7, 87.0, 63.9 and 61.6% in Helsinki, Sydney, Glasgow and Toronto, respectively (P < 0.0001; log rank). Cox proportional hazards model revealed lower age(0) and lower CrCl(0) were significant independent predictors of reduced renal survival. In addition, patients from Helsinki and Sydney but not Glasgow had significantly longer renal survival than patients from Toronto. Median slope of CrCl varied by region from -1.24 ml/min/year in Helsinki, to -3.99 ml/min/year in Toronto (Kruskal-Wallis H test P < 0.0001). By multivariate analysis older age(0), higher CrCl(0) and lower UP(0) were independently associated with slower progression. Subjects from Helsinki had a significantly slower deterioration independent of the other clinical parameters at presentation. When the 269 patients presenting with CrCl(0) <75 ml/min were analysed separately there was no independent centre effect. CONCLUSIONS: The findings are consistent with the hypothesis that geographical variability in long-term outcome of IgAN is explained by lead-time bias and inclusion of milder cases in centres with apparent good outcome, but do not exclude the possibility that some of the variability is due to other factors such as genetics, diet or treatment.

Australia↗

PubMed2003

Management of cytomegalovirus infection by weekly surveillance after renal transplant: analysis of cost, rejection and renal function.

BACKGROUND: Recently published guidelines recommend anti-viral prophylaxis as the best method of preventing cytomegalovirus (CMV) disease in the post-transplant period, but some authors have suggested that surveillance strategies may be as effective and less costly. The aim of the present study was to analyse the effectiveness and cost of a deferred treatment strategy using weekly CMV polymerase chain reaction (PCR) surveillance in high risk renal transplant recipients. METHODS: We used weekly surveillance for plasma CMV PCR positivity for the first 3 months in consecutive renal transplants between CMV seropositive donors and seronegative recipients, and analysed incidence of CMV infection, timing of infection, acute rejection and renal function at 1 year. RESULTS: There was evidence of CMV infection in 27/41 (65.9%) patients and of CMV disease in 20/41 (48.8%). Only 8/20 (40%) patients were PCR positive before disease onset. Patients were treated on the basis of clinical evidence of CMV disease (deferred strategy), but we used the data to compare the potential costs of a pre-emptive strategy (all patients PCR positive before the onset of clinical features of disease treated with intravenous ganciclovir) and prophylaxis (oral ganciclovir for 3 months in all patients). The deferred strategy cost pound 1159 per patient (excluding the cost of hospitalization) while a pre-emptive strategy would cost pound 1381 per patient. Prophylaxis costs pound 1500- pound 2213 per patient depending on published estimates of relative risk reduction. Mean estimated creatinine clearance at 1 year was 70.0 ml/min in patients who experienced no infection, 47.7 ml/min in patients who experienced infection but no disease, and 39.6 ml/min in patients who experienced CMV disease (P < 0.001). The incidence of acute rejection in these groups was 7.1, 14.3 and 35%, respectively (P = 0.13). CONCLUSIONS: CMV surveillance strategies may cost slightly less but may have a deleterious effect on long-term outcome compared with prophylaxis.

Adult↗

PubMed2002

Predicting 30-minute postdialysis blood urea concentrations using the stop dialysate flow method.

The stop dialysate flow (SDF) method has been the recommended method of postdialysis urea sampling by the Scottish Renal Association since November 1998. However, this method does not lend itself to calculation of Kt/V using currently favored formulas, which require either a 30-minute postdialysis sample or a 20-second "slow flow" sample. We, therefore, derived a formula that uses a 5-minute postdialysis urea sample using the SDF method to estimate the urea concentration at 30 minutes. Blood samples were obtained from 70 hemodialysis patients immediately before dialysis and at 0, 5, and 30 minutes postdialysis. Half of the patients from each unit were randomly selected to form the linear regression equation: Estimated 30-minute urea concentration = 1.06 x (5-minute urea concentration) + 0.22. This equation was validated using the data from the remaining 35 patients. This showed a very close correlation between measured and estimated urea concentration at 30 minutes (R2 = 0.97), and a Bland-Altman plot confirmed this close relationship. The sensitivity, specificity, positive, and negative predictive values of this equation were high when used to estimate 30-minute urea reduction ratio (URR) greater than 65% (100%, 85.7%, 97%, and 100%, respectively) and 30-minute Kt/V greater than 1. 2 (96.7%, 100%, 100%, and 80%, respectively). The coupling of the SDF method with the above formula combines the advantages of simple and reproducible postdialysis blood sampling with an accurate estimation of the 30-minute postdialysis blood urea concentration, URR, and Kt/V. This method should be a useful tool for comparative audit of hemodialysis adequacy.

Adult↗

PubMed2002

Early initiation of dialysis fails to prolong survival in patients with end-stage renal failure.

There is a trend to start dialysis earlier in patients with chronic renal failure. Studies that suggest improved survival from earlier initiation of dialysis are flawed in that they have measured survival from start of dialysis rather than from a time point before dialysis, when patients have the same renal function. This flaw is termed lead-time bias. Using the electronic patient record at the renal unit of Glasgow Royal Infirmary, all patients were identified who had received dialysis for chronic renal failure and who had sufficient data to calculate the time point at which they reached an estimated creatinine clearance (eC(Cr)) of 20 ml/min (n = 275). This date was used to time survival. The patients were divided into early and late start groups by the median eC(Cr) for all patients at initiation of dialysis, which was 8.3 ml/min. There was no significant benefit in patient survival from earlier initiation of dialysis. A Cox proportional hazards model demonstrated a significant inverse relationship between eC(Cr) at start of dialysis and survival (hazard ratio, 1.1; P = 0.02), i.e., patients who started dialysis with a lower eC(Cr) tended to survive longer. This relationship retained significance when gender, age, weight, presence of diabetes, mode of first dialysis, initial dialysis access, hemoglobin, serum albumin, blood leukocyte count, Wright/Khan index, and eC(Cr) at the start of dialysis were taken into account. This study fails to support a policy of earlier initiation of dialysis for patients with end-stage renal failure.

Female↗

PubMedDate not supplied

The impact of delayed graft function on the long-term outcome of renal transplantation.

Recent studies provide conflicting conclusions regarding the impact of delayed graft function (DGF) on the long-term outcome of renal transplantation. Some centres report DGF as an independent risk factor for reduced long-term graft and patient survival, while others report no impact on long-term outcome. Further scrutiny of data from these studies reveals differences in the definition of DGF, definition of long-term outcome, and statistical methods that may partly explain the variability. The commonest definition of DGF is the need for dialysis in the first week post-transplant, but this may be less informative than definitions that consider DGF as a continuous variable such as time to achieving creatinine clearance > 10ml/min. Acute rejection (AR) occurs more commonly in patients with DGF and variability in the impact of DGF may also relate to strategies to detect and treat AR during DGF. Centres with a vigilant strategy are likely to note a lower impact of DGF because the associated long-term adverse impact of AR is minimised. Furthermore, many centres reduce the dose of calcineurin inhibiting drugs and/or use polyclonal antibody therapy during DGF but the long-term impact of this strategy is unclear. Newer agents such as humanised anti-IL2 monoclonal antibodies and rapamycin may have a role, but controlled studies are required to define the optimal immunosuppressive regimen for patients with DGF. In the meantime, measures to minimise ischaemic damage to the transplant kidney and intensive surveillance for AR with weekly renal biopsy in patients with DGF are recommended.

Graft Rejection↗