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NDT Advance Access published online on July 25, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn413
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Diabetics on dialysis in Italy: a nationwide epidemiological study

Giovanni Panzetta1, Carlo Basile2, Antonio Santoro3, Enzo Ancarani4, Stefano Costantini4, Francesco Guarnieri5 and Giuseppe Verzetti6

1 Unità Operativa Complessa di Nefrologia e Dialisi, Azienda Ospedaliero-Universitaria "Ospedali Riuniti di Trieste", Trieste 2 Unità Operativa Complessa di Nefrologia, Ospedale Generale Regionale ‘F. Miulli’, Acquaviva delle Fonti 3 Unità Operativa Complessa di Nefrologia, Dialisi e Ipertensione, Azienda Ospedaliero-Universitaria Policlinico S.Orsola-Malpighi, Bologna 4 Centro di Riferimento Regionale di Nefrologia e Dialisi, Ospedale ‘Belcolle’, Viterbo 5 Hospal S.p.A, Bologna 6 Divisione di Nefrologia Dialisi e Trapianto, Ospedale Maggiore, Novara, Italy

Correspondence and offprint requests to: Carlo Basile, Via C. Battisti 192, 74100 Taranto, Italy. Tel: +39-80-3054205; Fax: +39-80-762165; E-mail: basile.miulli{at}libero.it



   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Discussion
 References
 
Background. Diabetes mellitus is a common disease, comprising 4–8% of the general population and up to 45% of new dialysis patients in industrialized countries.

Methods. We performed a nationwide study with the aim of analysing the approach of various centres to diabetic patients and to gather data on the epidemiology, clinical characteristics and complications of type 1 and type 2 diabetics.

Results. We acquired the data from 513 dialysis centres, 3665 prevalent diabetic patients and 4337 diabetic patients who started dialysis in the previous 10 years. Patient education and dialysis initiation: Sixty percent of the centres educate the patient regarding diet, pharmacological therapy and prevention of diabetic complications; in 245 centres (48%), this task belonged exclusively to the nephrologist and not to a multidisciplinary team. Seventy percent of the centres reported planning the initiation of dialysis and preparing the fistula between 1 and 3 months (78.5%) before the initiation of dialysis. Epidemiological and clinical data: Diabetic patients (56.9% males) represented 12.5% of the total dialysis population in Italy. The ratio between diabetes type 2 and type 1 was 5.3. The initial treatment was haemodialysis (HD) in 2533 patients (bicarbonate HD 88.8%) and peritoneal dialysis (PD) in 405 patients (CAPD 82.2%). During their dialytic life, 383 patients (226 from HD and 157 from PD) changed treatment modality, mainly because of cardiocirculatory instability (158 cases) or infection of the catheter tunnel/peritoneum (89 cases). The changes were mainly directed from bicarbonate HD and CAPD towards diffusive–convective extracorporeal techniques. Blood glucose (mean 154 ± 56.8 mg/dl) exceeded 200 mg/dl in 15.2% of patients; serum cholesterol was >200 mg/dl in 39.3% of patients; serum triglycerides exceeded 200 mg/dl in 39.2% of patients and mean values for glycosylated haemoglobin was 7.2 ± 1.8%. The nutritional state was judged to be normal in 59.6% of patients, 16.2% appeared to be mildly malnourished and 3% severely malnourished; 21.1% of subjects were obese. Echocardiography showed left ventricular hypertrophy in 90% of patients and echocolordoppler examination of the great vessels showed pathological findings (plaques and stenoses) in 73%. Pharmacological therapy. Sixty-nine percent of patients were treated with antihypertensive drugs, mainly calcium antagonists (50%) and ACE inhibitors (27%). Nitrates were prescribed for 33% of patients; antiplatelet or anticoagulant drugs were prescribed for 37% of patients.

Conclusions. The present study demonstrates that the prevalence of diabetics in dialysis continues to increase in Italy, but remains less than that in Northern European countries. Type 2 diabetes is as dangerous as type 1 in terms of serious complications. There appears to be a greater awareness on the part of nephrologists of the serious problems associated with the care of diabetic patients in dialysis. The ideal dialytic modality has not been determined, dialysis is often not initiated in a timely manner and optimal drug therapy is not always prescribed. The aspirations to treat the diabetic dialysis patient according to currently accepted best practice guidelines still need to be fully realized.

Keywords: diabetes mellitus; dialysis treatment; epidemiology; pharmacological therapy; survey



   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Discussion
 References
 
Diabetes mellitus is a common disease, comprising 4–8% of the general population of industrialized countries. In the United States, ~45% of dialysis patients are diabetics [1], and also in Northern Europe diabetic nephropathy constitutes one of the most frequent causes of end-stage renal disease [2]. Recently, the increased presence of diabetes in dialysis has been shown to be composed predominantly of type 2 diabetics [3], probably as a consequence of the ageing of the population in industrialized countries and, particularly, of the reduction of fatal cardiovascular events [3]. The clinical outcomes of dialyzed diabetic patients, although improved in recent years, are worse than those of non-diabetic patients [1,3,4]. Diabetes increases the risk of cardiovascular complications several fold and, proportionately, the death risk [5,6]. Other complications, such as malnutrition and sepsis, are more frequent in diabetics [7,8] and may increase the risk of death. Thus, the nephrologist is challenged both to control the underlying diabetic disease and to provide adequate renal replacement therapy.

Large epidemiological studies in recent years have demonstrated that cardiovascular morbidity and mortality can be reduced with strict glycaemic and blood pressure control and with the use of anti-angiotensin and lipid-lowering agents [9–13]. The concept of the ideal treatment of the diabetic dialysis patient has undergone a revision; currently, it is deemed very important that the doctor and patient form a partnership to confront the disease and its complications. Patient education is indispensable to obtain adherence to the very complex dietetic, pharmacological and behavioural regimens. In addition, an interdisciplinary approach in which diverse specialists collaborate is necessary to obtain the optimal outcome [3,14–16].

In recent years, factors have been identified that correlate with the survival of non-diabetic patients in dialysis [17,18], and these assume even greater importance in diabetics. Biocompatible membranes, ultrapure dialysis fluid and diffusive–convective techniques have also been promoted to reduce cardiovascular instability [19–23] and to minimize the injury of excessive oxidative stress inherent in uraemia and the dialysis treatment [24–30].

Thus, guidelines for optimal management of the diabetic patient in dialysis should include early referral to the nephrologist, a multidisciplinary approach, an effective correction of principal metabolic alterations, the choice of the most efficient and well-tolerated dialytic modality that does not provoke an acceleration of micro- and macrovascular diabetic complications and the use of pharmacological agents that counteract diabetes-induced cardiovascular morbidity and mortality.

The realization of the goals cited above in dialyzed diabetic patients—a population notoriously difficult to manage—is unknown in epidemiological terms. Large population studies have provided little more than the incidence and/or prevalence of diabetics in dialysis and annual crude mortality rates.

Given the dearth of large epidemiological studies designed to evaluate specifically diabetic patients in dialysis, we performed a nationwide study with the aim of defining the prevalence of these patients in Italy, determining the standard of care in diabetics in terms of the methodological approach, dialysis and drug treatment and analysing the clinical state of these patients in dialysis.



   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Discussion
 References
 
We utilized a summary questionnaire (centre questionnaire) devoted to the characteristics of the centres and to the methodological approach of centres to diabetics and a separate analytic questionnaire (patient questionnaire) dedicated to the treatment modalities and clinical evaluation of each diabetic patient (Figure 1), which were compiled in 2000.


Figure 1
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  		Fig. 1 Cellulosic (panel A), high flux (panel B) and low flux (panel C) synthetic dialysis membranes (CA = cellulose acetate; Cu = cuprophan; He = haemophan; SMC = synthetically modified cellulose; TCA = cellulose triacetate; AN69 = acrylonitrile and sodium methallyl sulphonate copolymer; PA = polyamyde; PAN = polyacrylonitrile; PMMA = polymethylmetacrylate; PS = polysulphone).

 
Centre questionnaire
This questionnaire consisted of 36 multiple-choice questions that provided data for the following fields of interest: epidemiology (questions 1–7), patient education and planning of access formation and of renal replacement therapy (questions 8–13), dialytic techniques available in the centre (questions 16–28), dialysis hypotension and treatment modalities (questions 29–32), number of kidney or kidney–pancreas transplants and mortality of patients who began dialysis within the previous 10 years (questions 33–36).

Patient questionnaire
This questionnaire, consisting of 87 questions, defined the demographic characteristics of each individual patient (questions 1–9), the dialytic technique used and changes of technique in these patients (questions 10–12 and 14–26), the frequency of hypotensive episodes (question 13), metabolic and nutritional status (questions 27–39), cardiovascular status (questions 40–51 and 63–75) and ophthalmological and neurological abnormalities (questions 52–62).

The questionnaires were developed to determine characteristics of current dialysis patients with diabetes mellitus; they did not differentiate patients who entered dialysis because of diabetic nephropathy.

Monitoring and data analysis
Each centre was allowed to use its usual laboratory procedures. Strict attention, however, was directed towards the reliability of data collection. Whenever necessary, questionable data were returned to the centres for verification and correction; this occurred in ~20% of cases.

We deliberately did not provide criteria for classifying the type of diabetes mellitus, which was left to the discretion of the local nephrologist. Nevertheless, specific questions within the questionnaire, such as the age of onset of the diabetes, presence of diabetic retinopathy, body mass index (BMI) and C-peptide levels, were used to evaluate the reliability of the local assessment [31].

Nutrition was assessed by the local nephrologists using anthropometric, laboratory and clinical data (including BMI, serum albumin levels and muscle mass examination); patients were subdivided according to a scale of four degrees: obesity, normality, mild malnutrition and severe malnutrition. Cardiologic status was evaluated by clinical symptoms, the electrocardiogram and echocardiography. Central and peripheral vascular disease was assessed with clinical symptoms [stroke, transient ischaemic attacks (TIA), claudication and gangrene] and by ultrasound of the great vessels of the ascending aorta and of the abdominal aorta.

The results are reported as percentages or as mean ± standard deviation. Statistical comparisons among groups were performed with unpaired Student's t-test or the chi-square test. A result was considered statistically significant when the P-value was < 0.05.



   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Discussion
 References
 
The questionnaires were delivered to all 622 Italian dialysis centres; responses were obtained from 513 centres (82.5%), which were distributed homogeneously throughout the country.

Individual data were gathered from the patient questionnaire for 3665 diabetics (demographic data for all patients, demographic and clinical data for 2938); cumulative data were gathered from the centre questionnaire for 4337 patients who entered the dialysis program in the previous 10 years.

Patient questionnaire
Epidemiology
The subjects consisted of 2085 males (56.9%) and 1580 females (43.1%) with mean ages of 64.1 ± 11 years and 66.5 ± 11 years, respectively (Table 1); the mean dialytic age was 34.5 ± 36.9 months (calculated from the first dialysis treatment to the moment of the survey, excluding any time without dialysis, for example, with a functioning renal allograft) without any differences according to gender. Since the total number of dialysis patients in responding centres was 30149, the prevalence of diabetes was 12.15%. The prevalence varied among the different centres (from a minimum of 3% to a maximum of 23%) and among the different regions of the country (from 8.8% in Emilia Romagna to 18.4% in Val d’Aosta), but significant differences disappeared when the great geographic areas of the nation were considered: north 11.5%, central 11.3%, south 13.2%. Critical analysis of the clinical data showed that 443 patients had type 1 diabetes (283 males and 160 females) and 2402 had type 2 diabetes (1335 males and 1066 females). Thus, the ratio between type 2 and type 1 diabetics was 5.3.


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  		Table 1 Data from 2938 patients resulting from the patient questionnaire

 
Dialytic therapy
The initial dialytic technique was extracorporeal in 2533 patients (86.2%) and peritoneal dialysis in 405 patients (13.8%). During their dialytic life, 226 patients in extracorporeal treatment and 157 patients in peritoneal dialysis (PD) changed treatment modality because of cardiocirculatory instability (158 cases), excessive interdialytic weight gain (33 cases), vascular access loss (16 cases) or infection of the catheter tunnel or of the peritoneum (89 cases). These changes were mainly directed from bicarbonate haemodialysis (BD) and continuous ambulatory peritoneal dialysis (CAPD) towards diffusive–convective extracorporeal techniques. Following the treatment changes, extracorporeal techniques increased from 86.2% to 89.8% [haemodiafiltration (HDF) from 4.7% to 7.0%, acetate-free biofiltration (AFB) from 6.0% to 10.9%] and peritoneal techniques decreased from 13.8% to 11.1% (CAPD from 82.2% to 75.0%; automated PD + intermittent PD increased from 17.8% to 25%). The distribution of treatment modalities is summarized in Table 2.


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  		Table 2 Initial and current (date of the survey) modality of treatment

 
Among patients in extracorporeal dialysis the first vascular access was a native arteriovenous fistula (AVF) in 1905 cases (75.2%), a prosthetic AVF in 84 cases (3.3%), a permanent central venous catheter in 126 cases (5%) and a temporary venous catheter in 418 cases (16.5%); at the date of the survey, vascular accesses were found to include native AVF 2295 cases (87%), prosthetic AVF 132 cases (5%) and permanent central venous catheters 211 (8%).

Dialysis filters included those that consisted of cellulose membranes or derivatives of cellulose in 1336 cases (52%), low-flux synthetic membranes in 606 cases (22.4%) and high-flux synthetic membranes in 648 cases (26.6%). Mean dialytic efficiency, expressed as Kt/V urea, was equal to 1.2 ± 0.2 for BD and 1.3 ± 0.2 for both HDF and AFB. Kt/V urea was <1.0 for 365 patients (14.4%) and <0.8 for 25 patients.

For PD, lactate buffer was the most commonly used (91%). Insulin was administered via the peritoneum in only 30 of 300 patients examined (10%).

Metabolic alterations and nutritional state
Table 3 shows the mean concentrations of blood glucose, serum lipids, glycosylated haemoglobin, serum albumin and transferrin. Blood glucose was >200 mg/dl in 15.2% of patients and >300 mg/dl in 3%; serum cholesterol was >200 mg/dl in 39.3% of patients and >300 mg/dl in 3%; serum triglycerides exceeded 200 mg/dl in 39.2% of patients and 300 mg/dl in 15.7%. Mean glycosylated haemoglobin was equal to 7.2 ± 1.8% and was >9% in 12.8% of patients. Mean serum albumin was 3.6 ± 0.4 g/dl and was <3 g/dl in 5.2% of patients.


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  		Table 3 Metabolic and nutritional data

 
Mean body weight was 67.7 ± 13.8 kg, and BMI was 25.1 ± 4.5 kg/m2. BMI values <20 were found in 10.5% of patients and >27 in 26.7%. The nutritional state was judged to be normal in 59.6% of patients; 16.2% appeared to be mildly malnourished (461 cases) and 3% severely malnourished (86 cases); 21.1% of subjects were obese (601 cases).

Clinical complications
Cardiovascular
Hypertension, defined as the assumption of antihypertensive drugs, or in the absence of drugs a predialytic value >140/90 mmHg, was present in 72.2% of patients. At the same time orthostatic hypotension was observed in 43.6% of patients. During the dialysis sessions hypotensive episodes were very frequent, appearing in 1–3/12 runs in 10.7% of patients, 4–6/12 runs in 27.2% and in more than 6/12 runs in 12.9% of patients (Table 4). The electrocardiogram demonstrated cardiac arrhythmias in 20.5% of patients (12.8% in type 1 diabetes and 22.2% in type 2), ischaemic lesions in 29.5%, infarcts in 14.4% and signs of left ventricular overload in 42.9%. Echocardiography showed left ventricular hypertrophy in 90% of patients (513 of 571 studied) and left ventricular dilatation in 76.2%; left ventricular ejection fraction was equal to 54.3 ± 11.8%, with a value <40% and 30% in 16.3% and 4.3% of patients, respectively.


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  		Table 4 Monthly hypotensive episodes: values are stratified according to 4 groups and expressed as % for each type of dialysis technique

 
Cerebrovascular disease was present in 20.2% of patients (TIA 12%, stroke 7%), whereas peripheral vascular disease, defined as claudication, was present in 49.6% of patients, with distal necrosis present in 17.6%. Echocolordoppler of the great vessels of the ascending aorta was normal in only 32.5% of patients (286 of 880 studied); 72.7% of patients presented plaques in one or more vessels, 42.8% stenoses of one or more vessels, and seven patients presented aneurysms. Calcifications of the plaques were seen in 33.7% of cases (196 patients).

Ocular
Ophthalmologic abnormalities were reported in 2210 patients (75.2%); diabetic retinopathy was present in 84.8%, hypertensive retinopathy in 38.2% and cataracts in 43.8%; blindness was described in 248 patients (11.2%). The proportion of patients affected by diabetic retinopathy may not have reached the 100% expected theoretically, since not all patients initiated dialysis therapy for diabetic nephropathy.

Neurological
Data were available from 1899 patients. Clinical signs of sensory or motor neuropathy were present in 94% of patients, whereas autonomic disturbances were reported as follows: 28.4% cardiovascular, 22.9% gastrointestinal and 27.4% genitourinary (bladder dysfunction in 104 patients and sexual dysfunction in 415).

Pharmacological therapy
Sixty-nine percent of all diabetic patients were treated with antihypertensive drugs: one drug in 1078 cases (37.6%), two drugs in 688 cases (24%) or three or more drugs in 175 cases (6%). The number of drugs per patient was 1.06 ± 0.94 for those in HD versus 1.39 ± 0.95 for those in PD (P < 0.01), with no differences between the two types of diabetes. The pharmacological agents used included calcium antagonists (50%), ACE inhibitors (27%) and alpha and beta blockers (12% and 6%, respectively).

Nitrates were prescribed for 33% of patients, digoxin for 14% and anti-arrhythmic drugs for 4%; antiplatelet or anticoagulant drugs were prescribed for 37% of patients; only 1.3% of patients were treated with lipid-lowering agents. There were no differences for these drugs according to the type of diabetes or treatment technique. The proportion of patients treated with erythropoietin, on the other hand, was higher among those undergoing extracorporeal techniques (78.9%) compared with those in PD (62.1%) although the target haemoglobin level was set at 11–12 g/dl for both groups.

Centre questionnaire
Patient education and dialysis initiation
Sixty percent of the centres reported dedicating time and attention to educating the patient regarding glycaemic control, diet, pharmacological therapy and prevention of diabetic complications. However, in 245 centres (48%), this task belonged exclusively to the nephrologists; a team approach including diabetologists (25 centres), dieticians (27 centres), psychologists (15 centres) and social workers (15 centres) in various permutations was practiced in the remaining 53 centres.

Seventy percent of the centres reported planning the initiation of dialysis and preparing the fistula between 1 and 3 months prior to the initiation of dialysis (78.5%), while 119 of 147 centres (81%) reported timely insertion of the peritoneal catheter. Although most of the centres stated that they paid particular attention to the planning of dialysis initiation, analysis of individual data revealed that only 9% of patients began dialysis with a serum creatinine of <6 mg/dl, whereas 41% began with a serum creatinine between 6 mg/dl and 8 mg/dl and 50% began with a serum creatinine >8 mg/dl.

Survival and causes of mortality
Information was provided by the centres on 4337 patients who began dialysis within the previous 10 years. One-year survival was 88%, while 44% of the patient population was still alive at the date of the survey. Causes of death of the 2337 deceased patients included myocardial infarction (23%), other cardiological causes (17%), stroke (10%) and sudden death in 15% of the patients. Since sudden death often results from an acute cardiovascular event (arrhythmia, severe hypotension), mortality due to a cardiac origin occurred in 60% of this diabetic population. Infection represented another significant cause of death at 9%.

Transplantation was performed in 185 patients (4%): 79 kidney alone and 106 kidney–pancreas. At the time of the survey, 279 patients (9.5%) were on the waiting list.

Type 1 versus type 2 diabetes
The local nephrologists identified 369 patients affected by type 1 diabetes and 2569 patients affected by type 2 diabetes. After controlling these data, diabetes classification was questionable in 293 cases. We reclassified 201 of these patients as type 1 in 74 cases and as type 2 in 127 cases, while we were unable to identify the type of diabetes of remaining 92 patients, which were excluded from the analyses comparing the two types of diabetes. Therefore, we determined that 443 patients were affected by type 1 diabetes and 2402 by type 2 and, as previously mentioned, the ratio between type 2 and type 1 was 5.3.

As expected, type 2 diabetics were older (67.6 ± 9.2 years versus 52.1 ± 11.4 years, P < 0.001), but type 1 diabetics had a longer dialytic age (41.3 ± 41.3 months versus 33.0 ± 35.6 months, P < 0.001). The proportion of patients treated with extracorporeal dialysis or peritoneal dialysis was similar between the two types of diabetes. Insulin therapy was used by 97.6% of type 1 and by 72% of type 2 diabetics, a proportion similar to that found by Williams et al. [32] (insulin dose/day: 36.8 ± 18.1 U versus 19.3 ± 18.3 U, P < 0.001). Blood glucose and glycosylated haemoglobin were higher in type 1 diabetics (167.9 ± 71.8 mg/dl versus 151 ± 53 mg/dl, P < 0.001; 7.8 ± 2% versus 7.0 ± 1.8%, P < 0.001), whereas serum lipid and albumin concentrations were equal (Table 3).

Cardiac and vascular status, whether determined by clinical symptoms or laboratory data, did not differ between the two groups. As previously mentioned, there were no differences in pharmacological therapy according to the type of diabetes.



   Discussion
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
References
 
The annual incidence of patients who initiate dialysis is constantly increasing in all industrialized countries, and a significant part of this increase is explained by the influx of diabetic patients. The prevalence of patients with diabetic nephropathy increased from 32.9% in 1989 to the current 45% in the United States (1) and from 13.7% to at least 20% in many Northern European countries (2).

As compared to the 1993 Italian study by Catalano and colleagues [33], the present survey demonstrated a conspicuous increase in the prevalence of diabetic dialysis patients also in Italy (from 6% to 12.15%) although the rate remains significantly lower than that of Northern European countries [34]. The low prevalence in Italy may be due to a number of genetic, environmental and nutritional factors. However, it is unlikely that a selection bias affected the present results for diabetes mellitus, given the elevated frequency of other comorbidities—higher than similar cross-sectional studies—and the proportion of elderly in the population (18.6% of patients were >75 years of age). In this regard, it should be emphasized that we included all diabetic patients in dialysis without differentiating patients who entered dialysis because of diabetic nephropathy from those diabetics who entered dialysis with other renal pathology. In addition, the low number of transplanted diabetic patients would tend to increase the prevalence of diabetes in dialysis.

The development of terminal uraemia in the diabetic constitutes a devastating clinical event, since these patients present an extraordinary acceleration of the clinical complications and benefit less often from renal transplantation [3,4,16,35,36]. Consequently, the survival of diabetics in dialysis is significantly curtailed and the quality of life impaired [1,3–5,16]. Today we know that the clinical results in this population depend both on the severity of the complications present at the initiation of dialysis and on our capacity to slow the evolution of the same complications during dialytic therapy [3–5,15,16,37,38–40]. Ideally, to treat uraemic diabetics successfully we should adhere to a large series of recommendations, but the epidemiological basis that supports these recommendations is not yet sufficient. Thus, the state of the art in the treatment of diabetics in dialysis still remains imprecise. We concluded that only a national survey would provide adequate numbers to define diabetological practices, dialysis therapy and clinical status.

Although 70% of nephrologists claimed to be aware of the importance of timely initiation of dialysis for diabetic patients, at least 50% of patients began dialysis with a serum creatinine >8 mg/dl and 20% with a central vein catheter as the initial vascular access. These data suggest that uraemic diabetics are still referred to the nephrologist late in the course of renal insufficiency, although at least part of the responsibility for the delayed initiation of dialysis may belong to the nephrologist, despite the avowed propensity for timely initiation.

PD has long been considered the treatment of choice in diabetics [41]. However, studies comparing PD and HD have shown that a clear superiority of one technique over the other does not exist for the survival or rehabilitation of the patient [11,41–44]. Our data confirm that in Italy the prevalence of PD in diabetics is similar to that of non-diabetics, clearly demonstrating that Italian nephrologists no longer consider PD as the treatment of choice. Only 10% of patients were treated with insulin in the dialysate, suggesting that also this option is no longer considered consequential [32,45].

The present study showed that many patients were undergoing treatment techniques different from the one with which they started dialysis, in particular changing from peritoneal to extracorporeal dialysis and from conventional HD to diffusive–convective techniques (AFB, mainly). Since the motivation for these changes was to improve treatment tolerability and to correct some typical diabetic pathophysiological alterations such as cardiocirculatory instability, it is plausible that the nephrologists perceived alternative extracorporeal techniques as more appropriate than conventional dialysis for the diabetic patient. The percentage of patients who utilized alternative techniques nearly doubled between the time dialysis was initiated and the moment of the survey, and the use of convective techniques was higher among diabetics than for dialysis patients at large (18.4% and 14.7%, respectively).

About 40% of type 1 diabetics develop chronic renal insufficiency during a 30- to 40-year period and are invariably destined to require renal replacement therapy. However, most diabetics in dialysis are type 2 patients probably because of the high prevalence of this disease among the general population. According to the literature, very large differences exist in the ratio of type 2 to type 1 diabetics in various European countries and among different regions of the same country [3]. Recent studies suggest that type 2 diabetics comprise ~90–95% of all diabetic patients [39,46]. In the present study, the ratio of type 2 to type 1 diabetics was 5.3, indicating that the relatively low prevalence of diabetic dialysis patients in Italy is due to a low number of type 2 diabetics.

The identification of diabetes type is probably an underestimated problem in dialysis. Often the patients reach the attention of the nephrologist several years after the onset of the disease; thus, patient's age, nutritional state and need for insulin therapy at this stage can be very different from the onset and may prevent the correct identification of diabetes. In the present study, the local nephrologist indicated the diagnosis; however, we re-analysed the diabetes type on the basis of certain key elements [31] and determined that ~20% of the diagnoses were questionable.

As expected, patients with type 2 diabetes were older, had higher body weights and BMI and had a higher frequency of obesity, equal to 22.6% as compared to 14.8% in type 1. Clinical complications were present in equally dramatic proportions, showing that type 2 diabetics are affected with as severe disease as type 1 diabetics.

Epidemiological studies have also shown that cardiovascular morbidity and mortality can be reduced with pharmacological therapy that normalizes blood pressure values and controls hyperlipidaemia, platelet aggregation and hypercoagulability [9–12]. In agreement with other studies [3,4,14,16], the proportion of our patients treated with ACE inhibitors, beta blockers and antiplatelet drugs was still quite low, and the number of patients treated with lipid-lowering agents was negligible, despite their proven efficacy in reducing cardiovascular complications in diabetics [11,12] and the absence of government-imposed restrictions for the use of these drugs (particularly of ACE inhibitors).

The present study did not evaluate the effect of current therapies on the incidence of complications or on mortality. It is important to remember that the survival of this large patient population was 88% at 1 year and that 44% of all diabetic patients who began dialysis during the previous 10 years were alive at the moment of the survey (roughly after a mean of 5 years). These results are better than those described in previous studies in which 1-year survival was <80% and 5-year survival <40% [1,3,4]. Thus, in agreement with more recent studies [13,32,34,46], we are probably witnessing a progressive improvement in the outcome of diabetics in dialysis due to modern pharmacological prevention of fatal complications and also our ability to provide efficient dialysis to these difficult patients.

The selection of patients in our cross-sectional survey may have been biased in the sense that in this type of study only living prevalent patients are observed and thus patients with serious complications who have died will be underestimated. Also, the fraction of diabetic patients who were on the transplantation waiting list or those in equally good condition who had not been transplanted may have improved the outcome. Thus, the results of our study may appear better than those of a longitudinal cohort study utilizing the same patient population. Our study included all diabetics in dialysis and did not differentiate those with diabetic nephropathy from those with other renal pathology; it is possible that outcomes may differ between the two groups. Given the large scope of our study, we were unable to standardize the criteria for the execution and interpretation of the clinical examinations although we requested clarification for questionable data. Finally, regarding patients with missing data, for each parameter we reported the mean value and the percentage of patients from which the value was derived. We documented that the principal characteristics of the patients with the missing values did not differ from the study population in which the values were available; thus, we are confident that there was no significant bias in the selection or interpretation of the data.

In conclusion, the present study suggests a greater awareness on the part of nephrologists of the serious problems associated with the care of diabetic patients in dialysis. Although dialyzed diabetics still represent a high-risk category, the results related to the grave clinical condition of the patients are probably improving. However, too many patients arrive late to the attention of the nephrologist, and greater efforts should be made to begin timely dialysis and to impede the development of the most severe complications. Dialytic treatment remains problematic, and the increased use of alternative dialytic techniques suggests that there is an ongoing effort to determine the best technique to treat diabetics. Additional improvements in the clinical outcomes might result from the increased utilization of these techniques. Finally, as stated in other studies [3,4,14,16], a more attentive pharmacological approach appears necessary to impede the most severe manifestations of vascular disease in these patients.



   Acknowledgments
 
The authors would like to thank all the Italian Dialysis Centers that have participated in this nationwide survey and particularly the Regional and Interregional coordinators of the survey: R. Bonofiglio (Cosenza), M. Borghi (Treviglio), M. Buemi (Messina), R. Ferrara (Cagliari), B. Memoli (Napoli) and P. Rindi (Pisa).

Conflict of interest statement. Dr Francesco Guarnieri is an employee of Gambro-Hospal Company.



   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

  1. US Renal Data System: 2005 Report. Am J Kidney Dis (2006) 47(Suppl_1):S65–S80.[CrossRef][Web of Science][Medline]
  2. ERA-EDTA Registry. (2007) 2005 Annual Report. Academic Medical Center, Department of Medical Informatics, Amsterdam, The Netherlands.
  3. Ritz E, Rychlik I, Locatelli F, et al. End-stage renal failure in type 2 diabetes: a medical catastrophe of worldwide dimensions. Am J Kidney Dis (1999) 34:795–808.[Web of Science][Medline]
  4. Locatelli F, Canaud B, Eckardt KU. The importance of diabetic nephropathy in current nephrological practice. Nephrol Dial Transplant (2003) 18:1716–1725.[Abstract/Free Full Text]
  5. Stack AG, Bloembergen WE. Prevalence and clinical correlates of coronary artery disease among new dialysis patients in the United States: a cross-sectional study. J Am Soc Nephrol (2001) 12:1516–1523.[Abstract/Free Full Text]
  6. Johnson JG, Gore SM, Firth J. The effect of age, diabetes, and other comorbidity on the survival of patients on dialysis: a systematic quantitative overview of the literature. Nephrol Dial Transplant (1999) 14:2156–2164.[Abstract/Free Full Text]
  7. Okuno S, Ishimura E, Kim M, et al. Changes in body fat mass in male hemodialysis patients: a comparison between diabetics and nondiabetics. Am J Kidney Dis (2001) 38(Suppl 1):S208–S211.[CrossRef][Web of Science][Medline]
  8. Brunner FP, Brynger H, Challah S, et al. Renal replacement therapy in patients with diabetic nephropathy, 1980–1985 Registry Report. Nephrol Dial Transplant (1988) 3:585–595.[Abstract/Free Full Text]
  9. Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial. Lancet (1998) 351:1755–1762.[CrossRef][Web of Science][Medline]
  10. Gaede P, Vedel P, Parving HH, et al. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the steno type 2 randomized study. Lancet (1999) 353:617–622.[CrossRef][Web of Science][Medline]
  11. Gaede P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med (2003) 348:383–393.[Abstract/Free Full Text]
  12. Nissen SE, Tuzcu EM, Schoenhagen P, et al. Effect of intensive compared to moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA (2004) 291:1071–1080.[Abstract/Free Full Text]
  13. Hayashino Y, Fukuhara S, Akiba T, et al. Diabetes, glycemic control and mortality risk in patients on hemodialysis: the Japan Dialysis Outcomes and Practice Pattern Study. Diabetologia (2007) 50:1170–1177.[CrossRef][Web of Science][Medline]
  14. McMurray SD, Johnson G, Davis S, et al. Diabetes education and care management significantly improve patient outcomes in the dialysis unit. Am J Kidney Dis (2002) 40:566–575.[CrossRef][Web of Science][Medline]
  15. Flauto RP, Leon JB, Sehgal AR. The provision and outcomes of diabetic care of hemodialysis patients. Am J Kidney Dis (2003) 41:125–131.[CrossRef][Web of Science][Medline]
  16. Sorensen VR, Mathiesen ER, Watt T, et al. Diabetic patients treated with dialysis: complications and quality of life. Diabetologia (2007) 50:2254–2262.[CrossRef][Web of Science][Medline]
  17. NKF-K/DOQI. Clinical practice guidelines for hemodialysis adequacy. Am J Kidney Dis (2006) 48(Suppl 1):S2–S90.[CrossRef][Medline]
  18. European Best Practice Guidelines for Haemodialysis. Available at http://ndt.oxfordjournals.org/content/vol17_7/index.dtl.
  19. Verzetti G, Navino G, Bolzani R, et al. Acetate-free biofiltration versus bicarbonate haemodialysis in the treatment of patients with diabetic nephropathy: a cross-over multicentric study. Nephrol Dial Transplant (1998) 13:955–961.[Abstract/Free Full Text]
  20. Movilli E, Camerini C, Zein H, et al. A prospective comparison of bicarbonate dialysis, hemodiafiltration, and acetate-free biofiltration in the elderly. Am J Kidney Dis (1995) 27:541–547.[Web of Science]
  21. Todeschini M, Macconi D, Fernàndez NG, et al. Effect of acetate-free biofiltration and bicarbonate hemodialysis on neutrophil activation. Am J Kidney Dis (2002) 40:783–793.[CrossRef][Web of Science][Medline]
  22. Rabindranath KS, Strippoli GFM, Roderick P, et al. Comparison of hemodialysis, hemofiltration, and acetate-free biofiltration for ESRD: systematic review. Am J Kidney Dis (2005) 45:437–447.[CrossRef][Web of Science][Medline]
  23. Lederer SR, Schiffl H. Ultrapure dialysis fluid lowers the cardiovascular morbidity in patients on maintenance hemodialysis by reducing continuous microinflammation. Nephron (2002) 91:452–455.[CrossRef][Web of Science][Medline]
  24. Panichi V, Migliori M, De Pietro S, et al. The link of biocompatibility to cytokine production. Kidney Int (2000) 58(Suppl 76):S96–S103.[CrossRef][Web of Science]
  25. Caglar C, Peng Y, Pupim LB, et al. Inflammatory signals associated with hemodialysis. Kidney Int (2002) 62:1408–1416.[CrossRef][Web of Science][Medline]
  26. Carracedo J, Ramirez R, Madueño JA, et al. Cell apoptosis and hemodialysis-induced inflammation. Kidney Int (2002) 61:89–93.[CrossRef]
  27. Bouré T, Vanholder R. Which dialyser membrane to choose? Nephrol Dial Transplant (2004) 19:293–296.[Free Full Text]
  28. Wanner C, Bahner U, Mattern R, et al. Effect of dialysis flux and membrane material on dyslipidaemia and inflammation in hemodialysis patients. Nephrol Dial Transplant (2004) 19:2570–2575.[Abstract/Free Full Text]
  29. Chauveau P, Nguyen H, Combe C, et al. Dialyzer membrane permeability and survival in hemodialysis patients. Am J Kidney Dis (2005) 45:565–571.[CrossRef][Web of Science][Medline]
  30. Carracedo J, Merino A, Nogueras S, et al. On line hemodiafiltration reduces the proinflammatory CD14 and CD16 monocyte-derived dendritic cells: a prospective, crossover study. J Am Soc Nephrol Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (from the American Diabetes Association). Diabetes Care (2003) 26(Suppl 1):S5–S20.[CrossRef][Medline]
  31. Gavin TR, Alberti KG, Davison MB, et al. Report of the Expert Commitee on the Diagnosis and Classification of Diabetes Mellitus (from the American Diabetes Association). Diabetes Care (2003) 26(Suppl 1):S5–S20.[CrossRef][Medline]
  32. Williams ME, Lacson E Jr, Teng M, et al. Hemodialyzed type I and type II diabetic patients in the US: characteristics, glycemic control, and survival. Kidney Int (2006) 70:1503–1509.[CrossRef][Web of Science][Medline]
  33. Catalano C, Postorino M, Kelly PJ, et al. Diabetes mellitus and renal replacement therapy in Italy: prevalence, main characteristics and complications. Nephrol Dial Transplant (1990) 5:788–796.[Abstract/Free Full Text]
  34. Van Dijk PC, Jager KJ, Stengel B, et al. Renal replacement therapy for diabetic end-stage renal disease: data from 10 registries in Europe (1991–2000). Kidney Int (2005) 67:1489–1499.[CrossRef][Web of Science][Medline]
  35. Sorensen VR, Mathiesen ER, Heaf J, et al. Improved survival rate in patients with diabetes and end-stage renal disease in Denmark. Diabetologia (2007) 50:922–929.[CrossRef][Web of Science][Medline]
  36. Stel VS, van Dijk PC, van Manen JG, et al. Prevalence of co-morbidity in different European RRT populations and its effect on access to renal transplantation. Nephrol Dial Transplant (2005) 20:2803–2811.[Abstract/Free Full Text]
  37. Ritz E, Stefanski A. Diabetic nephropathy in type II diabetes. Am J Kidney Dis (1996) 27:167–194.[Web of Science][Medline]
  38. Schrier RW. Treating high-risk diabetic hypertensive patients with comorbid conditions. Am J Kidney Dis (2000) 36(Suppl 1):S10–S17.[Web of Science][Medline]
  39. Canaud B, Chènine L, Formet C, et al. Hemodialysis as renal replacement therapy of choice for diabetic patients. Nephrol Dial Transplant (2006) 21(Suppl 1):S86–S93.
  40. Nolph KD. Clinical results with peritoneal dialysis—registry experiences. In: Contemporary Issues in Nephrology. Peritoneal Dialysis—Twardowski ZJ, Nolph KD, Khanna R, eds. (1990) New York: Churchill Livingstone. 127–144.
  41. Fenton SS, Schaubel DE, Desmeules M, et al. Hemodialysis versus peritoneal dialysis: a comparison of adjusted mortality rates. Am J Kidney Dis (1997) 30:334–342.[Web of Science][Medline]
  42. Lee HB, Chung SH, Chu WS, et al. Peritoneal dialysis in diabetic patients. Am J Kidney Dis (2001) 38(Suppl 1):S200–S203.[CrossRef][Web of Science][Medline]
  43. Issad B, Deray G. Peritoneal dialysis as prime treatment for diabetic patients with ESRD. Nephrol Ther (2006) 2(Suppl 1):S94–S102.[Medline]
  44. Quellhorst E. Insulin therapy during peritoneal dialysis: pros and cons of various forms of administration. J Am Soc Nephrol (2003) 13:93–96.
  45. Johnson CA, Amidon G, Reicher JE, et al. Absorption of insulin to the surface of peritoneal dialysis solutions containers. Am J Kidney Dis (1983) 3:224–228.[Web of Science][Medline]
  46. Icks A, Rathmann W, Haaster B, et al. KORA Studiengruppe. Dtsch Med Wochenschr (2006) 131:73–78.[CrossRef][Medline]
Received for publication: 2. 2.07
Accepted in revised form: 30. 6.08


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