1 Health Care Research Unit, University of Southampton, Southampton General Hospital, Southampton, 2 Renal Unit, St Mary's Hospital, Portsmouth, 3 Health Services Research Unit, University of Oxford, Oxford and 4 Richard Bright Renal Unit, Southmead Hospital, Bristol, UK
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Abstract |
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Methods. Three hundred and sixty-one (88%) out of 411 patients accepted for RRT in six renal units in the South and West Region of the UK between 1 June 1996 and 31 May 1997 were studied retrospectively. We examined the history of chronic renal failure, referral path to nephrologist, management of chronic renal failure (CRF) and patient outcomes. Patients were categorized as late if they were referred to the renal unit either within 4 months or within 1 month of requiring RRT.
Results. One hundred and twenty-four (35%) patients were referred within 4 months of RRT, and 84 (23%) within 1 month. The main differences between patients referred later and other patients was seen for those referred within 1 month. These patients were older and had more co-morbidity, significantly worse laboratory parameters at the start of RRT, were less likely to have received standard treatments for CRF, had less permanent dialysis access in place at the start of RRT (18% vs 47%, P=0.001), and had a significantly longer hospital stay (18 vs 10 days, P=0.001). Seventy-four (19%) patients died in the first 6 months: 27 (32%) in the 1-month group, 46 (16%) in all others (P=0.002). We found no evidence that patients referred late had defaulted from nephrology follow-up or had an excess of rapidly progressive disease. Though data were incomplete, there was evidence of prior CRF of over 1 year in all late referral groups.
Conclusion. Nearly a quarter of patients are referred for specialist nephrology treatment at a very late stage, within 1 month of RRT. They are less likely to receive interventions that could alter the progression of CRF or reduce its associated co-morbidity, have a worse clinical state at the start of RRT, longer hospitalization and poorer survival. These differences were much less marked for those referred within 14 months of starting RRT, although this is an insufficient time to prepare for RRT. Further research is needed to determine the missed opportunities for more proactive diagnosis and management of CRF.
Keywords: chronic renal failure; early intervention; end-stage renal disease; late referral; renal replacement therapy
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Introduction |
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Whilst chronic renal failure (CRF) can be difficult to detect unless actively searched for, opportunities for detection exist. Hypertension, urine and blood tests are all useful in detecting renal disease, especially in those from groups at increased risk of impairment such as diabetic and hypertensive patients. Timely referral of patients with CRF is essential, since for some individuals the progression of CRF to end stage can be delayed, halted or even reversed [3], and intervention may also ameliorate the morbidity associated with CRF. Timely referral also allows more time to inform patients of the RRT options and to establish dialysis access. The UK Renal Association has recommended referral of all patients to a nephrologist once serum creatinine is repeatedly above 150 µmol/l [4].
Several studies have shown that late referral (variably defined as starting dialysis within 1 month, or 34 months from first referral to a dialysing nephrologist) occurs in approximately 2348% [58] and 2251% [911] of patients respectively. The consequences are worse biochemical parameters [11] and patient co-morbidity prior to starting RRT [7], higher rates of emergency dialysis [8], longer hospitalization [9], increased early mortality [9] and reduced chances of receiving a kidney transplant [8]. Health care costs are consequently increased [6]. Most studies of late referral have been in single centres and have focused on the size of the problem and its consequences. We present here the results of a large retrospective analysis of patients accepted for RRT in six renal dialysis units in the South and West Region of England, an area with a largely Caucasian population of approximately 6.6 million. We investigated the scale of the problem of late referral, dividing our sample by the two definitions used in previous studies (starting dialysis within 1 month or 4 months of referral). We compared the prior care, referral patterns, patient characteristics and outcomes of patients referred.
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Subjects and methods |
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A retrospective analysis of ESRD patients clinical history was carried out using renal unit records, both clinical notes and computerized records. Data were collected using a standard questionnaire and short outcome profile devised by an expert panel including a geriatrician, a general practitioner, a diabetologist, two nephrologists involved in dialysis, and one physician with a special interest in nephrology. This included details on prior history of CRF (serum creatinine and urinalysis), referral history, the use of anti-hypertensive drugs including angiotensin-converting enzyme (ACE) inhibitors to delay progression of CRF, biochemical measures of CRF severity (e.g. creatinine), the use of measures to treat renal co-morbidity (e.g. phosphate binders), start of RRT, and outcomes including hospitalization and survival up to 6 months after the start of RRT. The risk index used by Khan et al. [12] was also used to classify patients into high-, medium- and low-risk groups using age, and presence of vascular disease, diabetes, myeloma or other organ diseases. The prescription of low-protein diets was not collected because dietary information was poorly recorded.
The participating renal units provided a list of all patients starting renal replacement therapy in the study period. Forty-one (9%) of 452 patients initially identified were excluded: 27 patients had moved units and were already on dialysis, five had recovered renal function, five had restarted dialysis following a failed transplant, and four had acute renal failure, which recovered. Of the remaining 411,361 (88%) had medical records available and, following questionnaire completion, were entered into the analysis. The definition of CRF used in the study was persistently raised serum creatinine above 150 µmol/l and/or recorded diagnosis in the medical notes. The initial definition of late referral used was that described previously [911], namely patient starting RRT within 4 months of referral to a nephrologist. Patients were then sub-divided into periods from referral to RRT of less than 1 month, 14 months, 412 months, and greater than 12 months. This allowed comparison with other late referral studies that used dialysis within 1 month of referral as their definition and investigation of how late referral has changed over time.
As well as the six renal units, the South and West Region also has some physicians with a special interest in nephrology based at District General Hospitals. Whilst these physicians have expertise in the management of renal disease, they do not have access to RRT programmes or dialysis access facilities.
Statistics
Statistical analysis included the comparison of patient group characteristics (here presented as referral under or over 1 month to the start of RRT) using tests appropriate to their data and distribution (2 test, t-test, MannWhitney). Regression analysis was used to identify factors predictive of death. P values of <0.05 were accepted as significant. All data were analysed using SPSS for Windows version 8.0.
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Results |
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One hundred and twenty-four (35%) patients were referred within 4 months of RRT, 84 (23%) within 1 month. In all units except the smallest, over 28% of patients were referred within 4 months.
The characteristics of the sample at first dialysis are shown in Table 1. Whilst there was little difference between those patients referred 14 months prior to RRT and early referrals in age, gender, or co-morbidity, those referred within 1 month of starting RRT were significantly older (68 vs 59 years, P=0.002) and had a greater degree of co-morbidity (26 (31%) vs 53 (19%), P=0.237) than those referred more than 1 month before RRT. The final referral of the patient to a nephrologist based in the dialysing renal unit differed between these two groups, with referrals within 1 month more likely to be referred by a hospital physician, including a proportion directly from a physician with a special interest in nephrology, whilst GPs were the main referral source for those referred more than 1 month before RRT (P=0.034). The cause of ESRD did not differ significantly between any of the groups, with tests positive for vasculitis (ANCA) and rapidly progressive glomerulonephritis found for small, similar numbers in all groups. The characteristics of those late referral patients referred by a physician with a special interest in nephrology (n=22) and those from all other doctors (n=102) were compared. There was no difference between the two groups in gender, co-morbidity index, and biochemical values; patients in the special interest in nephrology group were younger (median age 51 vs 67 years) and were more likely to have permanent access (68 vs 51%), to start dialysis as an outpatient (19 vs 13%), and to be discharged on peritoneal dialysis (26 vs 18%) rather than haemodialysis (68 vs 82%).
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Overall, at referral, 22% of patients had a SBP <140 mmHg and 28% had a DBP <80 mmHg; this improved to 33 and 43% respectively at dialysis.
Those referred within 1 month of RRT were more likely to be on haemodialysis (Table 4) and to have temporary vascular access than all others. This included tunnelled catheters whose use was limited in all groups (5%). They were also less likely to have received a transplant at 6 months (0 vs 4%, P=0.001), less likely to have had a significantly longer initial hospital stay (18 vs 10 days, P=0.001), less likely to start dialysis as an outpatient (11 vs 28%, P=0.001), and had more hospitalization episodes within the first 6 months (mean 2.6 vs 1.7, P=0.001).
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Independent factors affecting survival at 6 months were found using regression analysis. Compared with being referred more than 1 month prior to RRT, referrals within 1 month were less likely to survive at 6 months, once age, co-morbidity and serum albumin levels were taken into account (OR, 1.5; 95% CI, 0.732.89), although this did not reach significance (P=0.293).
Having a high degree of co-morbidity was also related to poorer survival (OR, 1.8; 95% CI, 0.903.69), although again this was not significant (P=0.098). Increasing age by 1 year reduced 6-monthly survival by approximately 4% (P=0.005; 95% CI, 0.930.98) and increasing albumin levels by 1 g/l increased survival by 10% (P=0.001; 95% CI, 1.051.16).
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Discussion |
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Figure 2 shows the previous late referral studies characterized by year of study and definition of late referral, and this suggests that despite an increasingly elderly and more co-morbid population, when similar study definitions are used, the incidence of late referral may be falling [58,10,11,13,14]. The markedly small number of late referrals found by Arora et al. [11] may be due to their excluding patients with unrecovered acute renal failure.
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Albumin levels were significantly lower in those referred within 1 month; hypo-albuminaemia is a good marker of chronic illness and inflammation and is predictive of early death on dialysis [15]. Referrals within 1 month were more likely to have biochemical signs of renal bone disease such as higher phosphate and alkaline phosphatase [11,16]. They were also less likely to receive treatment for such complications. Haemoglobin levels were much lower in the late-referred group and they were less likely to receive erythropoietin treatment for anaemia. The control of anaemia is important in the reduction of left ventricular hypertrophy, itself a predictor of mortality, and is present long before patients reach ESRD [17].
Whilst we found no difference between the two groups for SBP or DBP, at referral only 22% of SBP and 28% of DBP measurements for the sample as a whole met the guidelines of the day (SBP <140 mmHg and DBP <80 mmHg), recommended in the second report of the British Hypertension Society [18].
We showed that those referred within 1 month of RRT had a poorer outcome, were more likely to start dialysis in an emergency, using temporary access [16], and required more access procedures [5,7,12]. This group also had increased hospital length of stay, poorer survival and less chance of early transplantation [7,14,19]. Despite their increasing popularity, we found the use of tunnelled catheters for vascular access was limited in this population.
We found a greater degree of co-morbid illness in those referred within 1 month of RRT, but this did not reach significance. This supports another study [12], which suggests that this may be one of the factors associated with late referral, as physicians are less likely to refer those with a complicated medical history. Logistic regression showed that, once age, co-morbidity and albumin levels were taken into account, referral within 1 month of RRT was associated with poorer survival at 6 months, but was not significant. This suggests that it is the condition of the patient at the start of RRT rather than the referral time that is important in predicting survival, a finding similar to that found in some [9,6,13] but not all [5,7,8] previous late referral studies.
Patients referred late may be subdivided into those for whom late referral is unavoidable (i.e. patients with rapidly progressive renal failure or late presenters who are asymptomatic until a late stage), and those involving avoidable factors. Most studies have not investigated these factors. One that did [7], found that of 65 patients referred within 1 month, 12 (18%) had been virtually asymptomatic until late in the disease, 27 (42%) had been referred to the renal unit but had discontinued follow-up, and 26 (40%) had been diagnosed with renal disease 211 years earlier and were not referred to a renal unit despite receiving family physician care. We were unable to find any confirmed cases of loss to follow-up from nephrology care, nor an excess of rapidly progressive renal failure, though this may have been under-ascertained due to the retrospective design of the study. We did find that over one-half of all patients for whom data were available had evidence of CRF over 1 year before referral, suggesting that there may be avoidable factors in late referral.
An important question then is under whose care late-referred patients are, prior to referral, as this might indicate where educational initiatives, shared care, or joint policies are required. However, retrospective data only gives the final referral. This period may be short-lived once advanced CRF is diagnosed, and therefore may not reflect the setting in which opportunities are missed. We found that 14% of late referrals were from a general practitioner, a similar proportion to others [10], and this suggests that these are not simply patients being held in the community. A large proportion of late-referred patients were referred by physicians with a special interest in nephrology. Although these physicians are able to provide expert advice on the management of renal failure, they do not have access to dialysis access facilities or pre-dialysis counsellors, important factors in preparing the patient for RRT. However, they do appear to prepare the patient better for dialysis, but due to the retrospective nature of the study we were unable to assess the likelihood of these physicians receiving patients in a very poor state and having to refer them immediately. An important point is that even if such patients are removed as a special case, that still leaves 29% of RRT patients being referred within 4 months of RRT.
Some might argue that a degree of late referral is understandable as clinicians may be more concerned with the competing risks, e.g. fatal cardiovascular disease. When this does not occur and renal function deteriorates the need for dialysis then becomes overriding and late referral ensues. This assumes that there are many more patients who would have developed ESRD had they not died of competing causes. The impact on pre-dialysis services of referring them all earlier is hard to quantify. We would argue that earlier nephrology referral would be beneficial in the treatment of CRF and its associated co-morbidity, and probably in cardiovascular management too, but the cost-effectiveness of earlier referral requires future research.
The strengths of the study are the large sample size with comprehensive population coverage and its attempt to investigate patient history. The major limitation was the retrospective design and its reliance on one source of data, renal unit records. All retrospective studies are unavoidably limited by the amount and accuracy of data available, particularly the medical notes. In our study, important information regarding referral patterns, duration of known renal failure, and patient history prior to referral was incomplete. This has limited our ability to assess the level of renal function at the start of RRT, an important factor, as it appears that even our early referrals commence RRT more uraemic than current DOQI guidelines recommend [20]. It is with this in mind that a prospective follow-up study has been undertaken to collect data from multiple sources (referring hospitals, general practitioners, renal units, and patients themselves) to allow a more accurate assessment of the scale and nature of missed opportunities for management of CRFfor example whether raised serum creatinine results are acted upon.
The region studied has a generally healthy, predominantly Caucasian population and, as such, findings may not be applicable to a largely urban area or one with a significant proportion of ethnic minorities. Whilst the acceptance rate for this region has traditionally been lower than UK or English rates it is probably commensurate for the level of need for RRT.
In summary, late referral remains a feature of patients starting RRT, with adverse consequences especially if less than 1 month. Further work is ongoing to characterize the scale and nature of the missed opportunities. This should inform effective policies on the identification and diagnosis, and appropriate referral and treatment of patients with chronic renal failure, and ultimately may reduce the incidence of late referral and/or improve the cost-effectiveness of renal replacement therapy.
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Acknowledgments |
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Notes |
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References |
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