Early referral of Type 2 diabetic patients: are we ready for the assault?

Giorgina Barbara Piccoli1,, Giorgio Grassi2, Elisabetta Mezza1, Massimo Gai1, Candida Iacuzzo1, Francesca Bechis1, Luigi Biancone1, Alberto Jeantet, Franco Dani2, Paolo Cavallo Perin3 and Giuseppe Paolo Segoloni1

1 Cattedra di Nefrologia, Department of Internal Medicine, University of Torino, Italy, Azienda Ospedaliera San Giovanni Battista della città di Torino, U.O.A.D.U. Nefrologia, Dialisi e Trapianto, 2 U.O.A. of Diabetology, Department of Internal Medicine, University of Torino, Italy and 3 Department of Internal Medicine, University of Torino, Italy



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 References
 
Background. Elderly diabetics on dialysis are dramatically increasing in number. Their late referral reduces efficacy of therapeutic interventions; early referral is fundamental for their survival on dialysis. However, need for nephrological follow-up in case of early referral is not assessed. The objective was to define the need for follow-up in the nephrology setting of Type 2 diabetics, according to the early referral criteria of serum creatinine >=1.5 mg/dl or macroproteinuria.

Methods. The setting of the study was an outpatient diabetic care unit (University of Torino), where ~25% of the Type 2 diabetics of a 900 000-inhabitant city (Torino, Northern Italy) were followed. At the time of the study (1998–1999) the unit followed 5182 Type 2 diabetics whose serum creatinine and proteinuria were tested at least yearly. A total of 3826 prevalent and 478 incident patients with one or more analyses in the same laboratory were included in the study. Demographic data were not statistically different between selected and excluded patients. We calculated the stepwise need for nephrological follow-ups calculated according to our usual policy (4–12 evaluations/ year, on serum creatinine and proteinuria, and 30 min/evaluation).

Results. The prevalence of increased serum creatinine and macroproteinuria was high (in the prevalent cohort: serum creatinine >=>=1.5 mg/dl, 8.1%; proteinuria 0.3 g/day, 25.2%; serum creatinine >=3 mg/dl, 1.2%; nephrotic proteinuria 3.4%). Projecting data to the entire unit, with adherence to our evaluation protocol, early nephrological follow-up of Type 2 diabetics requires ~1300 h/year (one full-time nephrologist); five nephrologists are needed for our city, and 24 for the region (4350 000 inhabitants).

Conclusions. Early nephrological referral and follow-up of Type 2 diabetics is time consuming and expensive. Meeting the outpatient care needs of this critical cohort requires considerable resources.

Keywords: end-stage renal disease; proteinuria; serum creatinine; Type 2 diabetes



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 References
 
Early referral to a nephrologist has been identified as crucial not only for slowing the progression of renal disease but also for improving survival and morbidity on renal replacement therapy [1,2].

In view of the high costs of dialysis, pre-end-stage renal disease (ESRD) care may be a sound investment. Along with contributing to the long-term goal of reducing the number of new dialysis patients, careful pre-dialysis evaluation and follow-up also may increase survival and decrease morbidity in the short term, thus reducing some expenses strictly related to late or emergency referrals such as the duration of hospitalization at start of dialysis or the need for temporary vascular access. Furthermore, patients who are referred early to the nephrologist are reported to have a higher reliance on self-dialysis [35].

These general rules may apply with even higher advantages to elderly and frail patients with comorbid conditions. Type 2 diabetics can be seen as the prototype of these critical cases. Moreover, their case value is enhanced by the great increase in the last two decades of their dependence on dialysis and by their grim prognosis in the event of late referral [6,7].

A close cooperation between nephrology and diabetology units has been identified as a crucial factor in improving outcomes for the elderly [8,9]. The course of comorbid conditions, such as diffuse vascular disease, retinopathy, or neuropathy usually is well established by the time dialysis starts, and sometimes even before the patient is referred to a nephrologist [15,79]. Various elements account for late referrals to the nephrologist; their weight may differ between settings: non-compliance, sanitary systems, the attitude of diabetologists, economic aspects, etc., all may play varied but important roles [1013].

Quantifying the need for nephrological care in the early phases of renal disease in diabetics is not simple. Because of the lack of data, the prevalence of diabetes and of its long-term complications is only partially known and in clinical practice definitions given to renal diseases may differ from diabetological and nephrological settings.

As is common in communities where acceptance to dialysis has no exclusion criteria, in the region where this study was performed (Piemonte, Northern Italy, about 4 350 000 inhabitants) the incidence of new diabetic patients on dialysis is steadily rising [14]. Against this background, this study was derived to assess the need for nephrological pre-dialysis evaluation and follow-up of Type 2 diabetic patients, the most critical subset of the dialysis population and also the one showing the sharpest rate of increase.

The study consists of two parts. The first evaluates the prevalence of the main signs of renal disease (increase in serum creatinine and macroproteinuria) in a cohort of Type 2 diabetics followed in the largest outpatient diabetic care unit (University of Torino) of a city with 900 000 inhabitants (Torino, Northern Italy). As the prevalence of diabetes mellitus in our region was recently estimated at ~2.4% (90% Type 2 diabetes) the unit follows ~25% of Type 2 diabetic patients of the city [15].

The second part of the study calculates the follow-up needs of the Type 2 diabetic patients in the entire region (Piemonte, about 4 350 000 inhabitants) according to early referral criteria. The first, based on the Canadian recommendations, which integrate an earlier consensus statement, triggers referral upon detection of the first signs of renal functional impairment [16]. Serum creatinine >=1.5 mg/dl was considered as the cut-off point in that study. The second is based upon different levels of macroproteinuria (>=0.3 g/24 h; >=1 g/24 h) [16,17]. This part of the study applies either the same follow-up patterns that we are now employing in our centre (30 min/clinical visit) or, alternatively, the policy of the Diabetic Care Unit (15 min/visit). In addition, we compared the costs of chronic dialysis and the costs of health care staffing between the two follow-up protocols and between early and late referral.



   Subjects and methods
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 References
 
Setting of study
The setting of the study was the Diabetes Care Unit of the University Hospital of Torino. The unit regularly follows about 5200 Type 2 diabetic patients (at time of the study, according to the unit archives, 5182 patients were evaluated at least once in 1998–1999: 2472 females and 2710 males; mean age 66.7±10.6 years; mean of diabetes duration 12.8±9.4 years). As in the region, the prevalence of diabetes mellitus was reported to be 2.2–3% (90% Type 2), we assumed an average prevalence of 2.4% of Type 2 diabetes, and estimated that the centre follows 25% of the Type 2 diabetics of the city [15].

In the unit, serum creatinine and 24-h proteinuria are routinely assessed at least once per year per patient.

In-patient load of the unit (prevalent patients) ranged from 5000 to 5500 during the last 5 years; the incidence of new entries (incident patients) was, therefore, considered as equivalent to the number lost to follow-up (drop-out, death, or transfer). Analysis was performed separately on prevalent and incident cases.

Selection of patients
To ensure the comparability of the blood and urinary tests, selection criteria included patients with serum creatinine >=1 mg/dl (Jaffé spectrophotometric method) and 24-h proteinuria (Coomassie spectrophotometric method) performed in the same setting (laboratory of the Outpatient Diabetic Care Unit of the University of Torino Hospital). We studied the following: prevalent patients, 3826 Type 2 diabetics (2011 males and 1817 females; M/F 1.1; mean age 66.4±10.4 years; mean diabetes follow-up 12.8±9.6 years; mean serum creatinine 1.1±0.5 mg/dl). Incident patients: 478 patients (251 males and 227 females; M/F 1.1; mean age 63.8±10.8 years; mean diabetes follow-up 7.5±8.2 years; mean serum creatinine 1.0±0.3 mg/dl). A total of 1356 prevalent patients and 72 incident patients were not included in the study because of lack of complete laboratory data in the same setting (either not performed or performed in other settings). Demographic data for the excluded patients were statistically superimposable to the data of patients included in the study with respect to age (mean 67.2±11.3 years in prevalent; 64±10.3 years in incident patients), male/female ratio (697 males and 659 females, M/F 1.05 in prevalent patients; 42 males and 30 females, M/F 1.4 in incident patients), and diabetes follow-up (12.9±9.0 years in prevalent patients; 6.2±7.0 years in incident patients).

Assessment of need for nephrological follow-up
Frequency and duration of clinical evaluations was calculated according to the policy developed in our nephrology outpatient care unit dedicated to diabetics, which follows at present about 450 patients, 80% referred from the diabetology unit where the current study was performed.

The subjects were classified as follows: stable patient, initial functional impairment (serum creatinine >=1.5 to <2 mg/dl and/or proteinuria >=0.3 to <3 g/24 h)—4 visits/ year; moderate functional impairment (serum creatinine >=2 to 3 mg/dl and proteinuria >=0.3 to <3 g/24 h or proteinuria >=3 g/24 h at lower levels of functional impairment)—6 visits/year; severe functional impairment (serum creatinine >=3 mg/dl and/or nephrotic syndrome)—10–12 visits/year. The time needed for each clinical evaluation was taken to be either as 30 min, as usual in the nephrology outpatient care units in our area and in private consultancies, or 15 min as performed in the diabetic care units of our region. In the first instance (30 min), the standard clinical evaluation consists of: detailed clinical history since the previous visit; reading and recording results of biochemical and other tests in the clinical chart; physical examination of the patient; taking blood pressure, standing, sitting, and lying; review of therapy, with attention to signs of non-compliance, recording of therapeutic modifications; planning of new tests; consultation with caregiver/diabetologist or other expert for special problems; writing of a detailed report for the diabetologist and family doctor; discussion with the patient of specific aspects of their situation. This last part becomes increasingly important as renal failure progresses. Education for the choice of dialysis, with specific regard to self-care dialysis, takes place in this phase.

A 15-min evaluation consists of: history of major problems since the previous visit; reading laboratory data; physical examination; taking blood pressure sitting; review of therapy; recording of therapeutic modifications; planning of new tests; discussion with caregiver/nephrologist or other experts for severe problems; writing of a short report for the nephrologist and family doctor; short discussion with the patient of specific aspects of diabetes care.

Costs of treatment
Data on costs of dialysis and on the salaries of the nephrologists were obtained from the databases of the Chair of Nephrology of the University of Torino; dialysis costs are calculated with the logic bottom-up technique [17]. The nephrologist's salary was calculated as an average of the salaries of the nephrologists working in the University Centre (56 534.40 Euros/year; 39.26 Euros/h, 1440 working h/year). Hospitalization costs were calculated using the charges of the University Hospital (average of the two most frequently used reimbursement fees per day, recorded for dialysis patients: D-DRG 392.50 Euros, C-DRG 516.45 Euros). Data on median survival and hospitalization of diabetic patients on dialysis in our region were obtained from the Regional Registry of Dialysis and Transplantation of Piemonte [18].

Statistical analysis
The archives of the Outpatient Diabetic Care Unit are regularly updated in ORACLE. Laboratory data are automatically transferred. Analysis was performed using Microsoft Access; when additional data became available, the most recent analysis was selected. ANOVA test was employed when appropriate.



   Results
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 References
 
Prevalence of renal functional impairment
In the prevalent patients, the distribution of different levels of serum creatinine and of proteinuria is reported in Table 1Go. Prevalence of macroprotenuria was high, being present in 25.2% of the cases; 3.4% of the patients had nephrotic range proteinuria (>=3 g/24 h).


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Table 1.  Prevalence of different levels of serum creatinine and 24 h proteinuria in 3826 prevalent Type 2 diabetic patients followed in the centre

 
Prevalence of renal function impairment (broadly defined as serum creatinine >=1.5 mg/dl) was lower, 8.1%; however, over half of the cases fell in a ‘grey zone’ (>=1 to <1.5 mg/dl).

A similar distribution was observed in the group of 478 incident patients (Table 2Go). A total of 23.4% displayed macroalbuminuria (1.9% nephrotic range proteinuria) and serum creatinine levels were >=1.5 mg/dl in 5.3%. Overall duration of diabetes and the mean age of the subjects at study were high (7.5±8.2 and 63.8±10.8 years, respectively) and in keeping with a negative selection bias, as it is usually reported in large university centres.


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Table 2.  Prevalence of different levels of serum creatinine and 24 h proteinuria in 478 incident Type 2 diabetic patients followed in the centre

 
A direct relationship between serum creatinine and proteinuria is observed; a direct relationship links also the duration of diabetes, increasing age, and signs of renal impairment.

It may be worth underlining that age is lower in cases with nephrotic syndrome or severe functional impairment; however, the relatively low number of cases does not allow specific conclusions. Overall, these trends confirm the well-known relationship between the signs of renal impairment in diabetic nephropathy, presumably the most important cause of renal failure in this subset. This observation may be considered as an index of the internal coherence of the data.

Resources needed for nephrological follow-up
On the basis of the data recorded in prevalent patients, the resources needed for nephrological follow-up were calculated for the entire cohort of Type 2 diabetic patients followed by the unit (rounded to 5500 patients) according to a stepwise hypothesis. The first step was to address the needs of patients with moderate to severe signs of renal impairment. Two separate hypotheses were tested: the first one based upon creatinine levels (>=1.5 mg/dl), the second one upon 24-h proteinuria, focusing on follow-up patients with proteinuria >=1 g/24 h (Table 3Go).


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Table 3.  Need for nephrological follow-up according to serum creatinine or 24 h proteinuria (data are calculated as for population of 5500 patients)

 
According to both hypotheses, to implement our existing procedures in the Outpatient Care Unit, i.e. allocating an average of 30 min to each clinic visit, a minimum of 1300 h/year is needed for regularly following this subset of Type 2 diabetic patients. Such a workload corresponds to one full-time nephrologist, working in the Outpatient Care Unit. This calculation takes into account the usual policy of allowing some time for ‘common’ activities (being on call; weekends; congresses; time out, etc.).

On a second level, if nephrological follow-up is started earlier, in the presence of macroproteinuria (>=0.3 to <1 g/24 h), 847 further patients are added. If these patients are included in a 3 visits/year nephrological follow-up schedule, 2541 clinic visits (1270.5 h) are added, corresponding to a second full-time nephrologist.

Projecting the data to the city of Torino (900000 inhabitants), we calculate a need for five full-time nephrologists for the first step and 10 for both the first and second step. Extrapolating data to the region, we may calculate a need for 24–46 nephrologists (Table 4Go)—on average, one nephrologist for each step of pre-dialysis care of Type 2 diabetic patients in each of the 22 nephrology and dialysis centres of the region [14].


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Table 4.  Health care staff requirement for early referral and follow-up of Type 2 diabetic patients, according to two different patterns or hypotheses of clinical evaluation

 
The time requirement and the need for health care staff is halved if a different policy, such as the one followed by the diabetic care units in our area, is chosen (Table 4Go). However, even following this option, an appreciable increase in the nephrology staff requires 11 nephrologists for the region.

The costs of dialysis and the average salary of a nephrologist working in our centre are shown in Table 5Go. Roughly, 2 years of ‘spared’ dialysis are needed yearly to compensate for 1 year of salary for one nephrologist. In the framework of a median survival of 36.7 months in diabetic patients (age >50 years at start of dialysis), each patient who avoids dialysis could ‘pay’ for ~2 years of a nephrologist's salary (Table 5Go).


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Table 5.  Costs of dialysis in diabetic patients: comparison with nephrologists' salaries (yearly nephrologist salary: 56534.40 Euros)

 



   Discussion
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 References
 
In our area, Piemonte (Northern Italy), as elsewhere in the world where acceptance to dialysis has no exclusion criteria, we are facing almost an epidemic of elderly and diabetic patients requiring dialysis [6,89,14]. From 1981 to 1998, when the Regional Registry of Dialysis and Transplantation started regular activity, the diabetic cohort underwent a 328% increase. Incidence in the younger diabetics has been stable, and it was Type 2 elderly patients [14] who contributed to the increase. The data are in keeping with other European reports [6,89]. Consensus is widespread on the importance of the impact of pre-dialysis follow-up and of early referral on subsequent results [24,68,16,1920]. Therefore, our study, aimed to assess the resource needs for early pre-dialysis care and to design nephrological interventions, was focused on Type 2 diabetic patients.

The unit where the study was performed follows a relevant sample (~25%) of Type 2 diabetic patients of Torino (900 000 inhabitants), the main city of Piemonte (4 350 000 inhabitants) [14,15]. In this unit, in 1987, was started the first cooperative Diabetological and Nephrological Outpatient Care Project, with an itinerary spanning from the diabetologist, through a shared attendance and discussion with the nephrologist, to care for the patient regularly in a dedicated Nephrology Outpatient Unit. The Nephrology Outpatient Care Unit follows at present about 450 diabetic patients—~90% Type 2, ~80% referred from the main Diabetic Care Unit. This study was designed to demonstrate the need to increase our activity and to plan a regional network of care.

Data from the Diabetic Care Unit show a high prevalence of signs of renal disease in Type 2 diabetic patients (8.1% of prevalent patients with creatinine levels >=1.5 mg/dl, 25.2% with macroalbuminuria, 9.8% with proteinuria >=1 g/24 h). Our prevalence of macroalbuminuria is higher than the 5–15% range reported by most authors [2124]. However, as it usually occurs in large university centres, referral bias may be present. Indeed, a >30% prevalence of macroproteinuria at stick urinalysis was reported in hospitalized patients and in patients followed in university centres [25,26]. The hypothesis of a referral bias may be supported by the relatively higher mean age and longer follow-up of the prevalent and of the incident cases considered in this study.

It may, however, be worth mentioning that a high prevalence of renal function impairment has also been reported in large unselected populations. For example, a recent analysis performed in the overall population of New Mexico found a 3.9–13.7% prevalence of creatinine >=1.5 mg/dl in elderly individuals belonging to different ethnic groups and an overall 1.78 and 9.74% prevalence of creatinine >=1.5 mg/dl was reported in females and males in a large USA survey in 1988–1994 [27,28]. These high figures are not far from the 8% prevalence of patients with increased creatinine levels in our study (Table 1Go) and may suggest a lower referral bias in our data.

In any case, according to our study, at least in settings of strict cooperation, the bottleneck for early referral of Type 2 diabetic patients may be at the level of the nephrological care units that are, unable to manage the heavy burden of regular follow-up in such a large population.

In fact, if we follow our present policy of a relatively strict follow-up and of a careful and time consuming clinical evaluation (on the average 30 min/visit, 3–12 visits/year, tailored to clinical needs), we would need at least one full-time nephrologist for filling the first needs of our centre (referral in the presence of creatinine >=1.5 mg/dl or of proteinuria >=1 g/24 h), and two nephrologists in case referrals are for macroalbuminuria. Taking into account the average creatinine level of this last subset (proteinuria range >=0.3 to <1: median creatinine 1.1 mg/dl), we would certainly include in the follow-up group several cases with functional impairment, since in elderly diabetics significant renal function impairment may be present at creatinine levels <1.5 mg/dl [29].

Projecting data to the city and to the region, we calculated the need for at least one full-time nephrologist dedicated to the pre-dialysis care of Type 2 diabetics for each of the 22 nephrology and dialysis centres of the region, for referrals for creatinine >=1.5 mg/dl and proteinuria >1 g/24 h. These numbers are to be doubled if follow-up is started at lower levels of renal disease (macroalbuminuria).

These are very high figures, but early referral and follow-up of Type 2 diabetic patients remains a challenge even if a less time-intensive schedule is chosen, such as the one commonly employed in our Diabetic Care Unit (15 min/patient): a minimum of one part-time nephrologist per centre would be needed (11 full-time jobs for the region).

Taking into account the high costs of dialysis, however, on an individual basis, even following the first model of organization, the overall time expenditure reduces itself to a reasonable 1.5 h dedicated yearly by a nephrologist to a Type 2 diabetic macroalbuminuric patient, and 2–6 h/year to a diabetic with severe functional impairment or nephrotic syndrome (58.89 and 78.52–235.56 Euros of a nephrologist's salary).

Regardless of the model of care chosen, an increase in the health care staff may become a cost effective investment if we consider that the salary for one nephrologist in full-time is equivalent to 0.52 years of in-hospital bicarbonate haemodialysis; avoiding dialysis in one single case corresponds to a full-time nephrologist's salary for ~2 years.

These analyses may, of course, yield different results in other European and non-European areas, due to, among other factors, considerable differences in physicians' salaries. Different models of care may be proposed, with higher involvement of nursing staff or of family physicians. That discussion, however, would go beyond the scope of the present paper.



   Conclusions
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 References
 
In conclusion, early referral of Type 2 diabetic patients is a major challenge for most nephrological care systems since, at least in Italy, outpatient care often is considered as economically unrewarding, and investments in dedicated structures for nephrological pre-dialysis care have been, so far, minor.

Even if alternative policies, for example a stricter co-operation with family physicians, could partly decrease the burden of care on the nephrologist, it should be stressed that even the organization of a network of care is a time consuming operation, itself needing ample resources. On the other hand, timely referral may help understand the evolution of ESRD in Type 2 diabetic patients and increase compliance, changing the patients with chronic renal failure from passive receivers of care into active participants in self-care, a goal to be pursued with even greater force in patients who have to manage several complex, life-long therapies.



   Notes
 
Correspondence and offprint requests to: Giorgina Barbara Piccoli, ASO San Giovanni Battista della città di Torino, U.O.A.D.U. Nefrologia, Dialisi e Trapianto, Corso Bramante 88, I-10126 Torino, Italy. Email: gbpiccoli{at}yahoo.it or gbpiccoli{at}hotmail.com Back



   References
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 References
 

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Received for publication: 21. 6.01
Accepted in revised form: 26.12.01