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Effectiveness of multidisciplinary care for chronic kidney disease in Taiwan: a 3-year prospective cohort study

Effectiveness of multidisciplinary care for chronic kidney disease in Taiwan: a 3-year... Abstract Background Previous studies have demonstrated that multidisciplinary pre-dialysis education and team care may slow the decline in renal function for chronic kidney disease (CKD). Our study compared clinical outcomes of CKD patients between multidisciplinary care (MDC) and usual care in Taiwan. Methods In this 3-year prospective cohort study from 2008 to 2010, we recruited 1056 CKD subjects, aged 20–80 years, from five hospitals, who received either MDC or usual care, had an estimated glomerular filtration rate (eGFR) <60 mL/min, were matched one to one with the propensity score including gender, age, eGFR and co-morbidity diseases. The MDC team was under-cared based on NKF K/DOQI clinical practice guidelines and the Taiwanese pre-end-stage renal disease (ESRD) care program. The incidence of progression to ESRD (initiation of dialysis) and mortality was compared between two groups. We also monitored blood pressure control, the rate of renal function decline, lipid profile, hematocrit and mineral bone disease control. Results Participants were prone to be male (64.8%) with a mean age of 65.1 years and 33.1 months of mean follow-up. The MDC group had higher prescription rates of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), phosphate binder, vitamin D3, uric acid lower agents and erythropoietin-stimulating therapy and better control in secondary hyperparathyroidism. The decline of renal function in advanced stage CKD IV and V was also slower in the MDC group (−5.1 versus −7.3 mL/min, P = 0.01). The use of temporary dialysis catheter was higher in the usual care group, and CKD patients under MDC intervention exhibited a greater willingness to choose peritoneal dialysis modality. A Cox regression revealed that the MDC group was associated with a 40% reduction in the risk of hospitalization due to infection, and a 51% reduction in patient mortality, but a 68% increase in the risk of initiation dialysis when compared with the usual care group. Conclusions MDC patients were found to have more effective medication prescription according to K/DOQI guidelines and slower renal function declines in advanced/late-stage CKD. After MDC intervention, CKD patients had a better survival rate and were more likely to initiate renal replacement therapy (RRT) instead of mortality. chronic kidney disease, hospitalization, multidisciplinary care, mortality, renal replacement therapy INTRODUCTION The rapid increased incidence and prevalence of chronic kidney disease (CKD) has been recognized as a global public health problem that consumes a large proportion of health-care budgets. In the USA, CKD affects >16 million adults with stage 3 or higher stage CKD [1]. Approximately 500 000 people were treated by means of renal replacement therapy (RRT) (dialysis or transplantation) for end-stage renal disease (ESRD) in the USA in 2007, and the number of ESRD patients is projected to increase to 700 000 by 2015 and potentially to more than two million by 2030 [2]. In Taiwan, the national prevalence of CKD is high, but awareness of CKD is inadequate. Only 3.5% of patients are able to report their stage of the disease [3]. Notably, subjects with a low socio-economic and educational status have a low awareness of CKD and have a high CKD prevalence [4]. As one of the rapidly aging countries with an increasing prevalence of diabetes, hypertension and subsequently CKDs, Taiwan has the highest prevalence and incidence of ESRD in the world [5]. According to the Bureau of National Health Insurance (BNHI) annual report in 2007, ESRD patients in Taiwan accounted for 0.23% of the local population, but cost 7.2% of the health-care resources. The unbalanced allocation of resources not only creates a financial burden, but may also endanger the welfare of other insured population. Comorbidity such as cardiovascular disease is the major cause of mortality among CKD patients [6–10]. Optimal management of CKD and comorbidity may improve clinical outcome and decrease mortality. In 2002, the US National Kidney Foundation launched the promotion of clinical practice guidelines for the diagnosis, evaluation and monitoring of CKD within the Kidney Disease Outcomes Quality Initiative (NKF K/DOQI) in an effort to increase the awareness of optimal CKD care [11]. It recommends co-management with a nephrologist at stage 3 CKD [estimated glomerular filtration rate (eGFR) 30–59 mL/min/1.73 m2] and a referral no later than stage 4 of CKD (eGFR <30 mL/min/1.73 m2). CKD patients are complex and at high-medical risk. However, some CKD patients cared for by primary care physicians (PCPs) or other specialists may not be configured to provide optimal care. Israni et al. [12] have recently found that PCPs are unaware of either applying estimating equations to measure GFR or suboptimal management of CKD. Several research articles have highlighted the risks of late referrals to nephrologists, associated with poor outcome, increased mortality and morbidity [13–16]. Early referral and nephrology care allow for more adequate pre-dialysis education, which can delay the initiation of dialysis and decrease mortality [17–19]. Although pre-dialysis nephrology care improves the clinical outcomes for patients with CKD, it is still insufficient to minimize the social and psychological impact of CKD [20]. Owing to complications, comorbidities and the complexity of care for CKD patients, more co-operative intervention with multidisciplinary care (MDC) is required to optimize the care of CKD and related comorbidity. Recent studies have found that integrated comprehensive nephrology-based MDC affirmed their substantial benefits [21–25]. A study by Curtis et al. [25] revealed a survival advantage with better laboratory parameters independent of the GFR for CKD patients under MDC care when compared with standard nephrology care. The medical system in Taiwan has established a unique protocol to standardize and regulate pre-ESRD care, with all the medical expenditures covered by the National Health Insurance (NHI). This nationwide CKD Preventive program in Taiwan has been evaluated to be effective in reducing the incident ESRD, mortality and medical costs in pilot studies with relatively small samples [23, 26]. Using a larger sample with multi-hospital collaboration, the present study compared the treatment effectiveness for CKD patients between MDC care and usual care in Taiwan. MATERIALS AND METHODS Subjects and methods This was a 3-year prospective cohort study. From five co-operative hospitals in the northern, central and southern areas of Taiwan, we recruited pre-dialysis CKD patients aged 20–80 years with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 [determined using simplified Modification of Diet in Renal Disease (MDRD) equation] [27] from multi-specialists and MDC nephrologists during the 33.1-month period from 2008 to 2010. We then staged the severity of CKD based on the NKF K/DOQI clinical practice guideline [11]. We excluded patients with severe comorbid diseases such as cerebrovascular disease, mental retardation and psychiatric disorder, malignancy or acquired immunodeficiency disorder or those who were in poor compliance and who had difficulty adhering to the study visit to minimize dropouts (Figure 1). FIGURE 1: View largeDownload slide Enrollment flowchart. CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HD, haemodialysis; PD, peritoneal dialysis. FIGURE 1: View largeDownload slide Enrollment flowchart. CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HD, haemodialysis; PD, peritoneal dialysis. We categorized our subjects into the MDC group and the usual care group, and they were matched one to one on the basis of their propensity score including gender, age, eGFR and comorbid diseases. Finally, 1056 study subjects (528 pairs) were included in our study. The Institutional Review Boards at each of the five collaboration hospitals reviewed and approved this study. Definition of MDC and usual care (non-MDC) group, patient management Usual care (non-MDC) group Usual care of CKD consisted of care under a PCP, general internal medicine and specialists including endocrinologists, cardiologists, rheumatologists, orthopedics and nephrologists without referring to the MDC team for instruction. Patients of the usual care group were managed according to the PCP's knowledge and sub-specialist guidelines. MDC Group The MDC consisted of a nephrologist, nephrology nurse educator, renal dietitian, social worker, pharmacy specialist, and surgeon for vascular access placement, tenchoff catheter implantation and transplantation. For standardized intervention of CKD in the MDC group, the management and education was dependent upon the different stages of CKD and, according to the NKF K/DOQI guidelines, Taiwan pre-ESRD care program and reimbursement policy of NHI. CKD management in the MDC group is focused both on medical management and lifestyle modification. Stage III or IV CKD patients were followed up every 3 months, and stage V CKD patients were followed up at least every month. As renal function declines and uremia symptoms progress in pre-ESRD, CKD patients increased the frequency of visits to every 2 weeks or every week. For stage III CKD patients, MDC was focused on renal function introduction, clinical presentations of CKD and uremia symptoms, risk and deterioration factors and related complications. For stage IV patients, MDC focused on the management of CKD and related complications, introduction and creation of the dialysis access and indications of RRT initiation. For stage V patients, MDC focused on monitoring renal function and uremia symptoms, evaluation of timing initiation of RRTs, and care of dialysis access. The case-management nephrology nurse contacted patients to ensure regular follow-ups. The members of the MDC team met and followed up on patients regularly to review and discuss the patient's individualized therapy and management, medical recommendations for the comorbid condition (such as cardiovascular risk reduction), metabolic abnormality (such as renal anemia, mineral bone disease) and regular diet assessment and recommendations. Data collection All laboratory analysis in our study was collected and analyzed under the standard protocols. All patients completed a structured questionnaire providing information on socio-demographic characteristics and lifestyle. Patient information obtained from chart reviewers included anthropometric index, blood pressure (BP), biochemical measurements, comorbidity history and medication prescription (including antihypertensive drugs, diuretics, cholesterol lower agents, phosphate binder, antihyperuricemic agents, non-steroid anti-inflammatory drugs, antihyperglycemic agents and erythropoietin), hospitalization utilization (hospitalization rate, hospitalization day and the frequency of hospitalization), permanent vascular access preparation, transfer to dialysis and mortality from the five co-operating hospitals. If medications were prescribed >6 months during the follow-up period, it was recorded and defined. Clinical and laboratory data were also collected at the beginning and the end of the study including BP and creatinine, albumin, cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), hematocrit (Hct), calcium, phosphate, calcium–phosphate product, HbA1c, intact parathyroid hormone (iPTH), and urine albumin–creatinine ratio and protein–creatinine ratio. The eGFR was estimated using the MDRD equation. For mortality subjects, the last outpatient visit or in-hospital serum creatinine was used to define mortality eGFR. Definition of comorbid diseases Based on the definition of Dartmouth-Manitoba's Charlson comorbidity index [28], we used the International Classification of Diseases 9 code on the in-hospital database to identify comorbidities at the baseline including type 2 diabetes mellitus, hypertension, hyperlipidemia, CVD, polycystic kidney disease, renal stone diseases, hyperuricemia, chronic liver diseases and autoimmune diseases. Outcome assessment Subjects were followed up until 15 March 2011. The primary outcome of our study was the presence of ESRD warranting initiation of RRT or patient mortality. The secondary outcomes were hospitalization rate, rate of renal function declines, BP control and the change of laboratory measurements. Statistical analyses We compared the baseline mean age, matched GFR, comorbidity number, BP, biochemical measurements, hospitalization days and the frequency of hospitalization by means and standard deviation between the MDC group and the usual care group. Number (n) and percentage (%) were used to describe gender, comorbidity diseases, medication therapy, hospitalization rate, transfer to dialysis and patient death. The differences in continuous and categorical variables between the usual care and MDC groups were examined, respectively by Student's t-test (or Mann–Whitney U test) and the Chi-squared test (or Fisher's exact test). The Kaplan–Meier model and log-rank statistic were used to describe hospitalization risk, dialysis risk, patient survival and days of hospital stay on CKD. A multivariate Cox regression model was performed to predict hospitalization risk, dialysis risk, and patient mortality and drop out after adjusting for gender, age, GFR and comorbid diseases. A two-tailed P-value <0.05 was considered statistically significant. All statistical analyses were conducted using the statistical package SAS 8.2 (SAS institute, Inc., Cary, NC, USA) and SPSS 16.0 (SPSS, Chicago, IL, USA). RESULTS In total, 1056 subjects (528 pairs, men 64.5%) with a mean age of 65.2 years were included in our study (Table 1). Both the MDC group and the usual care group had similar characteristics in baseline CKD stage (∼60% for stage III CKD), baseline mean eGFR (∼33 mL/min), and the prevalence of comorbidities such as hypertension (76.9 versus 76.5) and diabetes (49.4 versus 49.1%). Table 1. General characteristics with propensity matched between the MDC group and the usual care group   MDC (n = 528)   Usual care (n = 528)   P-value  n  %  n  %  Gender, male  339  64.2  342  64.8  0.85  CKD stage          0.054  Stage III  311  58.9  282  58.4    Stage IV  163  30.9  200  37.9    Stage V  54  10.2  46  8.7    Matched eGFR(mL/min)  (32.7 ± 12.6)  (32.9 ± 13.1)  0.84  Comorbid disease   Cardiovascular diseases  157  29.7  148  28.0  0.54   Cerebral vascular diseases  34  6.4  35  6.6  0.90   Polycystic kidney diseasesa  3  0.6  3  0.6  1.00   Renal stone diseases  14  2.7  14  2.7  1.00   Gout  102  19.3  110  20.8  0.54   Diabetes mellitus  261  49.4  259  49.1  0.90   Hypertension  406  76.9  404  76.5  0.88   Hyperlipidemia  150  28.4  161  30.5  0.46   Autoimmune diseases  16  3.0  14  2.7  0.71  Receiving other interventionb  92  17.4  101  19.1  0.47  Age (year)  (65.2 ± 10.5)  (65.1 ± 11.0)  0.87  Number of morbidities  (2.2 ± 1.3)  (2.2 ± 1.3)  0.91    MDC (n = 528)   Usual care (n = 528)   P-value  n  %  n  %  Gender, male  339  64.2  342  64.8  0.85  CKD stage          0.054  Stage III  311  58.9  282  58.4    Stage IV  163  30.9  200  37.9    Stage V  54  10.2  46  8.7    Matched eGFR(mL/min)  (32.7 ± 12.6)  (32.9 ± 13.1)  0.84  Comorbid disease   Cardiovascular diseases  157  29.7  148  28.0  0.54   Cerebral vascular diseases  34  6.4  35  6.6  0.90   Polycystic kidney diseasesa  3  0.6  3  0.6  1.00   Renal stone diseases  14  2.7  14  2.7  1.00   Gout  102  19.3  110  20.8  0.54   Diabetes mellitus  261  49.4  259  49.1  0.90   Hypertension  406  76.9  404  76.5  0.88   Hyperlipidemia  150  28.4  161  30.5  0.46   Autoimmune diseases  16  3.0  14  2.7  0.71  Receiving other interventionb  92  17.4  101  19.1  0.47  Age (year)  (65.2 ± 10.5)  (65.1 ± 11.0)  0.87  Number of morbidities  (2.2 ± 1.3)  (2.2 ± 1.3)  0.91  Note: values are expressed as (mean ± SD). aFisher's exact test. bExpect CKD intervention, diabetic, hypertension or metabolic syndrome intervention. View Large The prescription rates of medication therapy between the usual care group and the MDC group are shown in Table 2. Compared with the usual care group, the MDC group had a lower prescription rate of NSAIDs, and a higher prescription rate of ACEI/ARB, Vit D3, phosphate binders, uric acid control agents and erythropoietin (P < 0.05). Table 2. Prescription rate of medication therapy between the MDC group and the usual care group   MDC (n = 528)   Usual care (n = 528)   P-value  n  %  n  %  ACEI  80  15.2  63  11.9  0.13  ARB  367  69.5  305  57.8  <0.001  ACEI or ARB  406  76.9  343  65.0  <0.001  Ca channel blocker  294  55.7  299  56.6  0.76  α-Blocker  136  25.8  116  22.0  0.15  β-Blocker  166  31.4  175  33.1  0.55  NSAIDs  15  2.8  34  6.4  0.01  Vit D3  19  3.6  4  0.8  0.002  Statin  254  48.1  236  44.7  0.27  Phosphate binders  180  34.1  46  8.7  <0.001  Diuretics  211  40.0  190  36.0  0.18  Uric acid control agents  212  40.2  147  27.8  <0.001  EPO  73  13.8  25  4.7  <0.001  Blood sugar-lowering agents  213  40.3  211  40.0  0.90  Insulin  96  18.2  85  16.1  0.37    MDC (n = 528)   Usual care (n = 528)   P-value  n  %  n  %  ACEI  80  15.2  63  11.9  0.13  ARB  367  69.5  305  57.8  <0.001  ACEI or ARB  406  76.9  343  65.0  <0.001  Ca channel blocker  294  55.7  299  56.6  0.76  α-Blocker  136  25.8  116  22.0  0.15  β-Blocker  166  31.4  175  33.1  0.55  NSAIDs  15  2.8  34  6.4  0.01  Vit D3  19  3.6  4  0.8  0.002  Statin  254  48.1  236  44.7  0.27  Phosphate binders  180  34.1  46  8.7  <0.001  Diuretics  211  40.0  190  36.0  0.18  Uric acid control agents  212  40.2  147  27.8  <0.001  EPO  73  13.8  25  4.7  <0.001  Blood sugar-lowering agents  213  40.3  211  40.0  0.90  Insulin  96  18.2  85  16.1  0.37  ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; Ca channel blocker, calcium channel blocker; NSAIDs, non-steroid anti-inflammatory drugs; EPO, erythropoietin. View Large Decline of renal function and other laboratory measurements Table 3 illustrates the baseline parameters, the difference (Δ) per year of renal function and other laboratory measurements between the usual care and MDC groups. There were no significant differences in the secondary outcomes of BP control, albumin, lipid profile, Hct level and HbA1c between the MDC and usual care groups. However, iPTH was controlled better in the MDC group (20.9 versus −66.3, P = 0.02). The decline of renal function (eGFR) at an advanced stage of CKD (stages 4 and 5) was slower in the MDC group compared with the usual care group (−5.1 versus −7.3, P = 0.01). Table 3. Baseline characteristics and mean changes (Δ) per year in renal function and other laboratory measurements compared between the MDC group and the usual care group   MDC (n = 528)   Usual care (n = 528)   P-value  Baseline   Difference   Baseline   Difference   Mean  SD  ΔMean  ΔSD  Mean  SD  ΔMean  ΔSD  SBP (mmHg)  137.96  19.88  1.2  20.5  138.45  21.15  0.4  37.3  0.70  DBP (mmHg)  78.43  12.53  −1.0  13.5  79.81  13.53  −0.8  22.0  0.85  eGFR (mL/min)  32.7  12.6  −5.8  6.2  32.9  13.2  −6.7  8.7  0.18  Early stage (stage 3)  41.6  7.4  −6.4  7.1  43.2  8.0  −5.8  7.4  0.49  Late stage (stage 4 and 5)  20.0  5.7  −5.1  4.9  21.0  5.8  −7.3  9.4  0.01  Albumin (g/dL)  4.0  0.5  −0.2  1.4  3.8  0.7  −0.3  1.3  0.52  Cholesterol (mg/dL)  191.2  43.0  −7.0  50.8  187.2  47.1  −13.0  66.9  0.16  TG (mg/dL)  162.0  90.6  −13.5  97.0  163.8  102.1  −8.9  104.7  0.53  HDL-C (mg/dL)  49.0  16.4  −2.2  26.6  45.7  13.7  −2.3  17.6  0.98  LDL-C(mg/dL)  112.5  37.6  −10.0  51.5  108.6  47.2  −7.1  46.0  0.53  Hct (mg/dL)  35.2  6.4  −1.1  6.8  34.9  7.0  −0.9  7.6  0.79  Ca*P  35.0  7.7  0.6  11.0  34.9  7.8  3.1  30.2  0.58  HbA1C (%)  6.9  1.6  −0.3  3.7  7.6  1.9  −0.3  2.5  0.98  iPTH (pg/mL)a  67.2  91.4  20.9  59.0  216.0  186.6  −66.3  46.4  0.02  ACR (‰)a  767.5  1836.4  81.4  1079.0  1424.2  3285.4  832.1  6145.8  0.87  PCR (mg/g)a  1481.4  2135.3  66.6  1672.4  4362.3  15 983.3  1079.0  1589.3  0.30    MDC (n = 528)   Usual care (n = 528)   P-value  Baseline   Difference   Baseline   Difference   Mean  SD  ΔMean  ΔSD  Mean  SD  ΔMean  ΔSD  SBP (mmHg)  137.96  19.88  1.2  20.5  138.45  21.15  0.4  37.3  0.70  DBP (mmHg)  78.43  12.53  −1.0  13.5  79.81  13.53  −0.8  22.0  0.85  eGFR (mL/min)  32.7  12.6  −5.8  6.2  32.9  13.2  −6.7  8.7  0.18  Early stage (stage 3)  41.6  7.4  −6.4  7.1  43.2  8.0  −5.8  7.4  0.49  Late stage (stage 4 and 5)  20.0  5.7  −5.1  4.9  21.0  5.8  −7.3  9.4  0.01  Albumin (g/dL)  4.0  0.5  −0.2  1.4  3.8  0.7  −0.3  1.3  0.52  Cholesterol (mg/dL)  191.2  43.0  −7.0  50.8  187.2  47.1  −13.0  66.9  0.16  TG (mg/dL)  162.0  90.6  −13.5  97.0  163.8  102.1  −8.9  104.7  0.53  HDL-C (mg/dL)  49.0  16.4  −2.2  26.6  45.7  13.7  −2.3  17.6  0.98  LDL-C(mg/dL)  112.5  37.6  −10.0  51.5  108.6  47.2  −7.1  46.0  0.53  Hct (mg/dL)  35.2  6.4  −1.1  6.8  34.9  7.0  −0.9  7.6  0.79  Ca*P  35.0  7.7  0.6  11.0  34.9  7.8  3.1  30.2  0.58  HbA1C (%)  6.9  1.6  −0.3  3.7  7.6  1.9  −0.3  2.5  0.98  iPTH (pg/mL)a  67.2  91.4  20.9  59.0  216.0  186.6  −66.3  46.4  0.02  ACR (‰)a  767.5  1836.4  81.4  1079.0  1424.2  3285.4  832.1  6145.8  0.87  PCR (mg/g)a  1481.4  2135.3  66.6  1672.4  4362.3  15 983.3  1079.0  1589.3  0.30  SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; Hct, hematocrit; iPTH, intact parathyroid hormone; ACR, albumin creatinine ratio; PCR, plasma creatinine ratio aMann–Whitney U test. View Large Hospitalization risk A total of 183 (34.7%) subjects in the MDC group and 171 (32.4%) subjects in the usual care group had been hospitalized at least once during the study period. The mean frequency of hospitalization (0.6 ± 1.2 versus 0.6 ± 1.2) and days of hospital stays (6.7 ± 17.1 versus 5.9 ± 13.3 days) were not different between the MDC group and the usual care group (Table 4). The hospitalization rate (73.9% versus 85.7%) and days of hospital stays (11.4 ± 12.5 versus 19.1 ± 21.9 days) at dialysis initiation also showed significant difference between the MDC group and the usual care group (data not shown). Kaplan–Meier analysis showed that all-cause hospitalization risk and the probability of hospitalization for cardiovascular disease were not different between the two groups (data not shown), but the MDC group had a 40% reduction in the risk of hospitalization due to infection (log-rank test, P = 0.02) (HR: 0.60; 95% CI: 0.37–0.94) (Figure 2). In the adjusted Cox regression analysis, there was still no significant difference in the probability of all-cause hospitalization between the two groups [hazard ratio (HR: 0.91; 95% CI: 0.74–1.12) (Table 5). Table 4. Clinical outcomes between the MDC group and the usual care group   MDC (n = 528)   Usual care (n = 528)   P-value  n  %  n  %  Hospitalization rate  183  34.7  171  32.4  0.43  The frequency of hospitalization  (0.6 ± 1.2)  (0.6 ± 1.2)  0.57  Hospital days  (6.7 ± 17.1)  (5.9 ± 13.3)  0.42  eGFR at dialysis initiation  5.8 ± 1.7  5.5 ± 2.0  0.60  Transfer to dialysis  46  8.7  21  4.0  0.002   Temporary catheter at dialysis initiation  21  45.6  14  66.7     Peritoneal dialysis  14  30.4  3  14.3     Hemodialysis  32  69.6  18  85.7      Mature functional vascular access  15  32.6  6  28.6    Mortality  17  3.2  30  5.7  0.05  eGFR at mortality  16.3 ± 14.2  20.0 ± 12.7  0.26    MDC (n = 528)   Usual care (n = 528)   P-value  n  %  n  %  Hospitalization rate  183  34.7  171  32.4  0.43  The frequency of hospitalization  (0.6 ± 1.2)  (0.6 ± 1.2)  0.57  Hospital days  (6.7 ± 17.1)  (5.9 ± 13.3)  0.42  eGFR at dialysis initiation  5.8 ± 1.7  5.5 ± 2.0  0.60  Transfer to dialysis  46  8.7  21  4.0  0.002   Temporary catheter at dialysis initiation  21  45.6  14  66.7     Peritoneal dialysis  14  30.4  3  14.3     Hemodialysis  32  69.6  18  85.7      Mature functional vascular access  15  32.6  6  28.6    Mortality  17  3.2  30  5.7  0.05  eGFR at mortality  16.3 ± 14.2  20.0 ± 12.7  0.26  Note: values are expressed as (mean ± SD); mature functional vascular access in the MDC group composed of four subjects with perm catheter and 11 subjects with fistula; usual care composed of two subjects with perm catheter and four subjects with fistula. View Large Table 5. Cox regression model   Crude   P-value  Adjusted   P-value  HR  95% CI  HR  95% CI  Hospitalization risk  0.94  0.76–1.15  0.53  0.91  0.74–1.12  0.37  Dialysis risk  1.90  1.13–3.18  0.02  1.68  1.00–2.86  0.05  Patient mortality  0.50  0.28–0.92  0.03  0.49  0.27–0.88  0.02  Drop out  1.09  0.75–1.59  0.65  1.02  0.70–1.50  0.91    Crude   P-value  Adjusted   P-value  HR  95% CI  HR  95% CI  Hospitalization risk  0.94  0.76–1.15  0.53  0.91  0.74–1.12  0.37  Dialysis risk  1.90  1.13–3.18  0.02  1.68  1.00–2.86  0.05  Patient mortality  0.50  0.28–0.92  0.03  0.49  0.27–0.88  0.02  Drop out  1.09  0.75–1.59  0.65  1.02  0.70–1.50  0.91  View Large FIGURE 2: View largeDownload slide The Kaplan–Meier curve for time to first hospitalization for infection between the MDC group and usual care group. FIGURE 2: View largeDownload slide The Kaplan–Meier curve for time to first hospitalization for infection between the MDC group and usual care group. Dialysis risk and modality selection There were 21 (4.0%) subjects in the usual care group and 46 (8.7%) subjects in the MDC group who progressed to ESRD and initiation of dialysis (P = 0.002). The mean eGFR at dialysis initiation was not significantly different between two groups (5.8 versus 5.5 mL/min, P = 0.60) (Table 4). For patients who initiated dialysis (n = 67), the MDC group had a higher prevalence in peritoneal dialysis (PD) (30.4 versus 14.3%) and less temporary catheter use (45.6 versus 66.7%) (Table 4). Of the patients initiating hemodialysis, 46.9% (15 of 32) subjects in the MDC group had mature functional vascular access (including perm catheter and fistula) and the usual care group had only 33.3% (6 of 18 subjects) (Table 4). The result of Kaplan–Meier analysis showed that the MDC group was more likely to initiate dialysis than the usual care group (log-rank test, P = 0.01) (Figure 3). The unadjusted Cox regression analysis revealed that the MDC group was associated with a 90% increase in the risk of initiating of dialysis compared with the usual care group (HR: 1.90; 95% CI: 1.13–3.18) (Table 5). The HR changed slightly to 1.68 (95% CI: 1.00–2.86) after adjusting for gender, age, eGFR and comorbidity. (Table 5) FIGURE 3: View largeDownload slide The Kaplan–Meier curve for the probability of dialysis between the MDC group and the usual care group. FIGURE 3: View largeDownload slide The Kaplan–Meier curve for the probability of dialysis between the MDC group and the usual care group. Patient mortality During an average follow-up time of 33.1 months, a total of 30 (5.7%) patients in the usual care group and 17 (3.2%) patients in the MDC group died (P = 0.05). The MDC group had better patient survival compared with the usual care group in the Kaplan–Meier analysis (Figure 4, log-rank test P = 0.02). The adjusted Cox regression analysis showed that MDC was associated with 51% reduction in patient mortality compared with the usual care group (HR: 0.49; 95% CI: 0.27–0.88) (Table 5). Furthermore, we estimated ‘drop out CKD’ (either as the initiation of RRT or patient mortality) and found that there was no significant difference between the two groups (Table 5). FIGURE 4: View largeDownload slide The Kaplan–Meier curve of patient survival between the MDC group and the usual care group. FIGURE 4: View largeDownload slide The Kaplan–Meier curve of patient survival between the MDC group and the usual care group. DISCUSSION This 3-year prospective cohort study demonstrated that the integrated, comprehensive, team-based, MDC care for patients with CKD significantly slowed the decline of renal function in the late stage of CKD and improved mineral bone disease control. The risk of mortality was also lower in the MDC group than in the usual care group. Although all-cause hospitalization and cardiovascular-related hospitalization were not significantly different between the two groups. In addition, the MDC group had fewer instances of temporary vascular catheter use at the initiation of dialysis and had a greater willingness to select PD as the initial modality of the RRT. Lifestyle modification and medical utilization The MDC treatment provides CKD patients with enhanced disease knowledge and awareness for the disease care. Patients had a more positive attitude toward the disease and a greater improvement of medication and treatment compliance, as well as self-management, such as the adoption of nutritional counseling, lifestyle behavior change and avoidance of taking NSAIDS and nephrotoxins [29]. The rate of NSAID prescription in our study was lower compared with previous studies [29]. Consensus guidelines for CKD management emphasize the administration of nephroprotective agents [renin–angiotensin system (RAAS) blockade], reduction in cardiovascular risk, management of BP, screening and intervention for CKD-MBD and anemia. Medications for the blockade of the renin–angiotensin system (RAAS) have been considered as the first line of antihypertensive therapy for CKD patients to slow renal function decline, and to reduce proteinuria and cardiovascular events. Despite the JNC7 and the NKF K/DOQI guidelines, target BP control is achieved in less than 50% of CKD patients [30–32] and the overall prescription of the RAAS blockade was insufficient. Physicians may be reluctant to prescribe due to side effects including hyperkalemia or hemodynamic-mediated increase in serum creatinine. In our study, CKD participants in the MDC group were generally more likely to be prescribed ACEI/ARB medications (76.9 versus 65.0%, P < 0.001), and MDC members also supported additional effort to monitor side-effects and to conduct follow-up such as hyperkalemia. Lack of awareness and recognition of K/DOQI guidelines may explain why there are fewer tests for parameters of CKD-MBD and less attention paid to phosphate control and secondary hyperparathyroidism (SHPT) [33]. Hyperphosphatemia and a high FGF-23 level are associated with more rapid declines in renal function, increased risk of vascular calcifications and cardiovascular events [34–36]. In the present study, a higher prescription rate of phosphate binders and vitamin D3 therapy in the MDC group has led to better SHPT control. Moreover, awareness and treatment of dyslipidemia and hyperuricemia are generally poor in CKD patients, which not only contribute to CKD progression, but is also associated with higher cardiovascular events [30]. Consequences of a combination of lifestyle modifications and more effective medication prescription according to K/DOQI guidelines under MDC intervention may contribute to slower renal function declines and may reduce all-causes mortality in our study. Reduction in temporary vascular catheter and dialysis modality selection Early referral to nephrologists increased the initiation of dialysis outside of the hospital by the CKD patients with more mature functional vascular access [37, 38]. Previous studies have shown that reduction in temporary vascular catheter is associated with a lower systemic infection rate, avoidance of emergency dialysis and suboptimal initiation of dialysis [39–41]. Complications related to temporary vascular access are also important causes of excessive morbidity and mortality, longer hospitalization and also account for high health-care costs. Timing referral and pre-dialysis education play an important role for CKD patients in choice of RRT modality and their compliance with therapy prescription [42–45]. According to the United States Renal Data System (USRDS) report, only 6.5% of the dialysis patients in the USA preferred PD. In Taiwan, the proportion of dialysis patients undergoing PD increased from 6.1% in 2001 to 7.8% in 2005, but the proportion of dialysis patients opting for PD remains low [46]. Our study demonstrated that under MDC, there was less temporary catheter use (45.6 versus 66.7%) at the initiation of dialysis. Patients in the MDC group are more likely to select PD (30.45 versus 14.3%) as the initial dialysis modality and more mature functional vascular access at hemodialysis initiation (46.9 versus 33.3%). MDC may help CKD patients to receive well-balanced presentations of all RRT options. Educational intervention could increase patient self-care ability and the provision of adequate and good quality information of dialysis, making patients willing to undergo PD and self-care dialysis. MDC places emphasis on dialysis modality introduction, early preparation of RRT and timing initiation of RRT, does not force patients to receive dialysis when they encounter uremia. Initiation of RRT rather than mortality MDC plays an important role in managing CKD and related complications, reducing cardiovascular risk and also ensuring the smooth transition from the pre-dialysis stage to RRT. Studies have made an effort to define suboptimal and non-elective dialysis when patients initiate dialysis as (i) in-patients, (ii) with a central venous catheter and (iii) without dialysis modality selection [47–49]. CKD patients with sub-optimal dialysis initiation have worse biochemical parameters, clinical status and vascular access. They are less likely to utilize self-care dialysis modalities and thus have longer hospitalization rates and a higher mortality rate than well-prepared patients. As renal function declines, MDC would promote patient awareness of clinical conditions to initiate dialysis electively [23]. There was no earlier initiation of dialysis in the MDC group and the mean eGFR at mortality was not significantly different (16.3 versus 20.0 mL/min, P = 0.26) between two groups. We proposed several possible explanations for higher dialysis initiation rather than mortality in the MDC group.There are several limitations in our study. Patient compliance, attitudes and adherence to disease education intervention could not be evaluated. Laboratory data were collected and measured at different medical institutions, at different period intervals and assayed with different laboratory equipment. It is possible that systemic bias in laboratory measures exists. The fixed reimbursement policy of the NHI restrained laboratory parameter measurement and medical utilization. These limitations may result difficulty to achieve adequate BP and MBD control, reduction in the lipid profile and maintenance of hemocrit levels by consensus guidelines. To eliminate such bias, our study used the propensity score with one to one matching of MDC and usual care patients for further analysis and evaluation. Less frequent CKD parameters and laboratory measurement were noted in the usual care group, thus resulting in incomplete data collection and hampering further evaluation of the impact of intervention between two groups. This finding may be related to the primary physician's lack of awareness and recognition of consensus CKD management guidelines. Indeed, nephrologists of the MDC group appear more attentive to CKD management guidelines and CKD patients in the MDC group have optimal care delivery. This study was the first multi-hospital-collaborated research on the CKD Prevention and Care Plan in Taiwan with a large sample size, which was supported by the Bureau of Health Promotion, Department of Health, ROC (Taiwan) for the construction and evaluation of the effectiveness of MDC intervention for CKD patients during a 3-year follow-up (2008–10) and it showed the true phase of MDC in CKD in Taiwan. The five hospitals in our study included community hospitals to tertiary referral medical centers, and were located in the northern, middle and southern areas of Taiwan. All five hospitals in our study are pioneer organizations with ample experience in the pre-ESRD care program and in promotion performance for CKD prevention in Taiwan. There was a robust association between renal function, cardiovascular outcome and all-cause mortality. Keith et al. has revealed that patients with stage IV CKD were more likely to die rather than progress to ESRD, and death was far more common than dialysis at all stages of CKD [9]. Owing to slower renal function declines in the MDC group, we proposed CKD patients could receive more effective intervention in treatment of CKD and reduction of cardiovascular risk. A longer pre-dialysis educational period and a prolonged mean time to dialysis in the MDC group, CKD patients could receive more adequate intervention, adequately communicate with nephrologists and MDC members about treatment of CKD and related complications, indication and preparation of RRT. MDC education could encourage patients with a positive attitude and increasing motivation to accept RRT. MDC makes CKD patients initiate timely RRT and have smooth transition from pre-ESRD to dialysis rather than reaching mortality. In conclusion, we have demonstrated that CKD patients participate in the integrated, comprehensive, and team-based, MDC are benefited from slower renal function declines in advanced stage CKD and achieving greater improvement of clinical outcomes, timing initiation of dialysis with functional vascular access and reduced mortality. Patients in the MDC intervention are also more willing to choose PD as dialysis modality. FUNDING This study was supported by the Bureau of Health Promotion, Department of Health of Taiwan, grant numbers DOH 101-TD-B-111–004. CONFLICT OF INTEREST STATEMENT None declared. ACKNOWLEDGMENTS We thank the co-operation of the hospital for the help in data collection, including Shih-Te Tu, Kwo-Chuan Lin, Pei-Yung Liao, Su-Lan Lin, Li-Ching Chen, Chih-Ying Huang, Shu-Ya Chen, Su-Mei Sun, Li-Fang Lai, Pen-Lin Lin and Hui-Chu Lee for Changhua Christian Hospital; Jui-Hsin Chen and Chiu-Yueh Chen for Kaohsiung Municipal Hsiaokang Hospital; Shu-Chi Lu for Taipei Medical University Hospital; Jay-Jen Lin for Cathay General Hospital; Ya-Hsueh Shih for Chiayi Chang Gung Memorial Hospital. We thank Professor Fung-Chang Sung for his revision of this paper. REFERENCES 1 Coresh J,  Selvin E,  Stevens LA, et al.  Prevalence of chronic kidney disease in the United States,  JAMA ,  2007, vol.  298 (pg.  2038- 2047) https://doi.org/10.1001/jama.298.17.2038 Google Scholar CrossRef Search ADS PubMed  2 Gilbertson DT,  Liu J,  Xue JL, et al.  Projecting the number of patients with end-stage renal disease in the United States to the year 2015. 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Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nephrology Dialysis Transplantation Oxford University Press

Effectiveness of multidisciplinary care for chronic kidney disease in Taiwan: a 3-year prospective cohort study

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Oxford University Press
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© The Author 2012. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
Subject
CLINICAL SCIENCE
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0931-0509
eISSN
1460-2385
DOI
10.1093/ndt/gfs469
pmid
23223224
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Abstract Background Previous studies have demonstrated that multidisciplinary pre-dialysis education and team care may slow the decline in renal function for chronic kidney disease (CKD). Our study compared clinical outcomes of CKD patients between multidisciplinary care (MDC) and usual care in Taiwan. Methods In this 3-year prospective cohort study from 2008 to 2010, we recruited 1056 CKD subjects, aged 20–80 years, from five hospitals, who received either MDC or usual care, had an estimated glomerular filtration rate (eGFR) <60 mL/min, were matched one to one with the propensity score including gender, age, eGFR and co-morbidity diseases. The MDC team was under-cared based on NKF K/DOQI clinical practice guidelines and the Taiwanese pre-end-stage renal disease (ESRD) care program. The incidence of progression to ESRD (initiation of dialysis) and mortality was compared between two groups. We also monitored blood pressure control, the rate of renal function decline, lipid profile, hematocrit and mineral bone disease control. Results Participants were prone to be male (64.8%) with a mean age of 65.1 years and 33.1 months of mean follow-up. The MDC group had higher prescription rates of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), phosphate binder, vitamin D3, uric acid lower agents and erythropoietin-stimulating therapy and better control in secondary hyperparathyroidism. The decline of renal function in advanced stage CKD IV and V was also slower in the MDC group (−5.1 versus −7.3 mL/min, P = 0.01). The use of temporary dialysis catheter was higher in the usual care group, and CKD patients under MDC intervention exhibited a greater willingness to choose peritoneal dialysis modality. A Cox regression revealed that the MDC group was associated with a 40% reduction in the risk of hospitalization due to infection, and a 51% reduction in patient mortality, but a 68% increase in the risk of initiation dialysis when compared with the usual care group. Conclusions MDC patients were found to have more effective medication prescription according to K/DOQI guidelines and slower renal function declines in advanced/late-stage CKD. After MDC intervention, CKD patients had a better survival rate and were more likely to initiate renal replacement therapy (RRT) instead of mortality. chronic kidney disease, hospitalization, multidisciplinary care, mortality, renal replacement therapy INTRODUCTION The rapid increased incidence and prevalence of chronic kidney disease (CKD) has been recognized as a global public health problem that consumes a large proportion of health-care budgets. In the USA, CKD affects >16 million adults with stage 3 or higher stage CKD [1]. Approximately 500 000 people were treated by means of renal replacement therapy (RRT) (dialysis or transplantation) for end-stage renal disease (ESRD) in the USA in 2007, and the number of ESRD patients is projected to increase to 700 000 by 2015 and potentially to more than two million by 2030 [2]. In Taiwan, the national prevalence of CKD is high, but awareness of CKD is inadequate. Only 3.5% of patients are able to report their stage of the disease [3]. Notably, subjects with a low socio-economic and educational status have a low awareness of CKD and have a high CKD prevalence [4]. As one of the rapidly aging countries with an increasing prevalence of diabetes, hypertension and subsequently CKDs, Taiwan has the highest prevalence and incidence of ESRD in the world [5]. According to the Bureau of National Health Insurance (BNHI) annual report in 2007, ESRD patients in Taiwan accounted for 0.23% of the local population, but cost 7.2% of the health-care resources. The unbalanced allocation of resources not only creates a financial burden, but may also endanger the welfare of other insured population. Comorbidity such as cardiovascular disease is the major cause of mortality among CKD patients [6–10]. Optimal management of CKD and comorbidity may improve clinical outcome and decrease mortality. In 2002, the US National Kidney Foundation launched the promotion of clinical practice guidelines for the diagnosis, evaluation and monitoring of CKD within the Kidney Disease Outcomes Quality Initiative (NKF K/DOQI) in an effort to increase the awareness of optimal CKD care [11]. It recommends co-management with a nephrologist at stage 3 CKD [estimated glomerular filtration rate (eGFR) 30–59 mL/min/1.73 m2] and a referral no later than stage 4 of CKD (eGFR <30 mL/min/1.73 m2). CKD patients are complex and at high-medical risk. However, some CKD patients cared for by primary care physicians (PCPs) or other specialists may not be configured to provide optimal care. Israni et al. [12] have recently found that PCPs are unaware of either applying estimating equations to measure GFR or suboptimal management of CKD. Several research articles have highlighted the risks of late referrals to nephrologists, associated with poor outcome, increased mortality and morbidity [13–16]. Early referral and nephrology care allow for more adequate pre-dialysis education, which can delay the initiation of dialysis and decrease mortality [17–19]. Although pre-dialysis nephrology care improves the clinical outcomes for patients with CKD, it is still insufficient to minimize the social and psychological impact of CKD [20]. Owing to complications, comorbidities and the complexity of care for CKD patients, more co-operative intervention with multidisciplinary care (MDC) is required to optimize the care of CKD and related comorbidity. Recent studies have found that integrated comprehensive nephrology-based MDC affirmed their substantial benefits [21–25]. A study by Curtis et al. [25] revealed a survival advantage with better laboratory parameters independent of the GFR for CKD patients under MDC care when compared with standard nephrology care. The medical system in Taiwan has established a unique protocol to standardize and regulate pre-ESRD care, with all the medical expenditures covered by the National Health Insurance (NHI). This nationwide CKD Preventive program in Taiwan has been evaluated to be effective in reducing the incident ESRD, mortality and medical costs in pilot studies with relatively small samples [23, 26]. Using a larger sample with multi-hospital collaboration, the present study compared the treatment effectiveness for CKD patients between MDC care and usual care in Taiwan. MATERIALS AND METHODS Subjects and methods This was a 3-year prospective cohort study. From five co-operative hospitals in the northern, central and southern areas of Taiwan, we recruited pre-dialysis CKD patients aged 20–80 years with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 [determined using simplified Modification of Diet in Renal Disease (MDRD) equation] [27] from multi-specialists and MDC nephrologists during the 33.1-month period from 2008 to 2010. We then staged the severity of CKD based on the NKF K/DOQI clinical practice guideline [11]. We excluded patients with severe comorbid diseases such as cerebrovascular disease, mental retardation and psychiatric disorder, malignancy or acquired immunodeficiency disorder or those who were in poor compliance and who had difficulty adhering to the study visit to minimize dropouts (Figure 1). FIGURE 1: View largeDownload slide Enrollment flowchart. CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HD, haemodialysis; PD, peritoneal dialysis. FIGURE 1: View largeDownload slide Enrollment flowchart. CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HD, haemodialysis; PD, peritoneal dialysis. We categorized our subjects into the MDC group and the usual care group, and they were matched one to one on the basis of their propensity score including gender, age, eGFR and comorbid diseases. Finally, 1056 study subjects (528 pairs) were included in our study. The Institutional Review Boards at each of the five collaboration hospitals reviewed and approved this study. Definition of MDC and usual care (non-MDC) group, patient management Usual care (non-MDC) group Usual care of CKD consisted of care under a PCP, general internal medicine and specialists including endocrinologists, cardiologists, rheumatologists, orthopedics and nephrologists without referring to the MDC team for instruction. Patients of the usual care group were managed according to the PCP's knowledge and sub-specialist guidelines. MDC Group The MDC consisted of a nephrologist, nephrology nurse educator, renal dietitian, social worker, pharmacy specialist, and surgeon for vascular access placement, tenchoff catheter implantation and transplantation. For standardized intervention of CKD in the MDC group, the management and education was dependent upon the different stages of CKD and, according to the NKF K/DOQI guidelines, Taiwan pre-ESRD care program and reimbursement policy of NHI. CKD management in the MDC group is focused both on medical management and lifestyle modification. Stage III or IV CKD patients were followed up every 3 months, and stage V CKD patients were followed up at least every month. As renal function declines and uremia symptoms progress in pre-ESRD, CKD patients increased the frequency of visits to every 2 weeks or every week. For stage III CKD patients, MDC was focused on renal function introduction, clinical presentations of CKD and uremia symptoms, risk and deterioration factors and related complications. For stage IV patients, MDC focused on the management of CKD and related complications, introduction and creation of the dialysis access and indications of RRT initiation. For stage V patients, MDC focused on monitoring renal function and uremia symptoms, evaluation of timing initiation of RRTs, and care of dialysis access. The case-management nephrology nurse contacted patients to ensure regular follow-ups. The members of the MDC team met and followed up on patients regularly to review and discuss the patient's individualized therapy and management, medical recommendations for the comorbid condition (such as cardiovascular risk reduction), metabolic abnormality (such as renal anemia, mineral bone disease) and regular diet assessment and recommendations. Data collection All laboratory analysis in our study was collected and analyzed under the standard protocols. All patients completed a structured questionnaire providing information on socio-demographic characteristics and lifestyle. Patient information obtained from chart reviewers included anthropometric index, blood pressure (BP), biochemical measurements, comorbidity history and medication prescription (including antihypertensive drugs, diuretics, cholesterol lower agents, phosphate binder, antihyperuricemic agents, non-steroid anti-inflammatory drugs, antihyperglycemic agents and erythropoietin), hospitalization utilization (hospitalization rate, hospitalization day and the frequency of hospitalization), permanent vascular access preparation, transfer to dialysis and mortality from the five co-operating hospitals. If medications were prescribed >6 months during the follow-up period, it was recorded and defined. Clinical and laboratory data were also collected at the beginning and the end of the study including BP and creatinine, albumin, cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), hematocrit (Hct), calcium, phosphate, calcium–phosphate product, HbA1c, intact parathyroid hormone (iPTH), and urine albumin–creatinine ratio and protein–creatinine ratio. The eGFR was estimated using the MDRD equation. For mortality subjects, the last outpatient visit or in-hospital serum creatinine was used to define mortality eGFR. Definition of comorbid diseases Based on the definition of Dartmouth-Manitoba's Charlson comorbidity index [28], we used the International Classification of Diseases 9 code on the in-hospital database to identify comorbidities at the baseline including type 2 diabetes mellitus, hypertension, hyperlipidemia, CVD, polycystic kidney disease, renal stone diseases, hyperuricemia, chronic liver diseases and autoimmune diseases. Outcome assessment Subjects were followed up until 15 March 2011. The primary outcome of our study was the presence of ESRD warranting initiation of RRT or patient mortality. The secondary outcomes were hospitalization rate, rate of renal function declines, BP control and the change of laboratory measurements. Statistical analyses We compared the baseline mean age, matched GFR, comorbidity number, BP, biochemical measurements, hospitalization days and the frequency of hospitalization by means and standard deviation between the MDC group and the usual care group. Number (n) and percentage (%) were used to describe gender, comorbidity diseases, medication therapy, hospitalization rate, transfer to dialysis and patient death. The differences in continuous and categorical variables between the usual care and MDC groups were examined, respectively by Student's t-test (or Mann–Whitney U test) and the Chi-squared test (or Fisher's exact test). The Kaplan–Meier model and log-rank statistic were used to describe hospitalization risk, dialysis risk, patient survival and days of hospital stay on CKD. A multivariate Cox regression model was performed to predict hospitalization risk, dialysis risk, and patient mortality and drop out after adjusting for gender, age, GFR and comorbid diseases. A two-tailed P-value <0.05 was considered statistically significant. All statistical analyses were conducted using the statistical package SAS 8.2 (SAS institute, Inc., Cary, NC, USA) and SPSS 16.0 (SPSS, Chicago, IL, USA). RESULTS In total, 1056 subjects (528 pairs, men 64.5%) with a mean age of 65.2 years were included in our study (Table 1). Both the MDC group and the usual care group had similar characteristics in baseline CKD stage (∼60% for stage III CKD), baseline mean eGFR (∼33 mL/min), and the prevalence of comorbidities such as hypertension (76.9 versus 76.5) and diabetes (49.4 versus 49.1%). Table 1. General characteristics with propensity matched between the MDC group and the usual care group   MDC (n = 528)   Usual care (n = 528)   P-value  n  %  n  %  Gender, male  339  64.2  342  64.8  0.85  CKD stage          0.054  Stage III  311  58.9  282  58.4    Stage IV  163  30.9  200  37.9    Stage V  54  10.2  46  8.7    Matched eGFR(mL/min)  (32.7 ± 12.6)  (32.9 ± 13.1)  0.84  Comorbid disease   Cardiovascular diseases  157  29.7  148  28.0  0.54   Cerebral vascular diseases  34  6.4  35  6.6  0.90   Polycystic kidney diseasesa  3  0.6  3  0.6  1.00   Renal stone diseases  14  2.7  14  2.7  1.00   Gout  102  19.3  110  20.8  0.54   Diabetes mellitus  261  49.4  259  49.1  0.90   Hypertension  406  76.9  404  76.5  0.88   Hyperlipidemia  150  28.4  161  30.5  0.46   Autoimmune diseases  16  3.0  14  2.7  0.71  Receiving other interventionb  92  17.4  101  19.1  0.47  Age (year)  (65.2 ± 10.5)  (65.1 ± 11.0)  0.87  Number of morbidities  (2.2 ± 1.3)  (2.2 ± 1.3)  0.91    MDC (n = 528)   Usual care (n = 528)   P-value  n  %  n  %  Gender, male  339  64.2  342  64.8  0.85  CKD stage          0.054  Stage III  311  58.9  282  58.4    Stage IV  163  30.9  200  37.9    Stage V  54  10.2  46  8.7    Matched eGFR(mL/min)  (32.7 ± 12.6)  (32.9 ± 13.1)  0.84  Comorbid disease   Cardiovascular diseases  157  29.7  148  28.0  0.54   Cerebral vascular diseases  34  6.4  35  6.6  0.90   Polycystic kidney diseasesa  3  0.6  3  0.6  1.00   Renal stone diseases  14  2.7  14  2.7  1.00   Gout  102  19.3  110  20.8  0.54   Diabetes mellitus  261  49.4  259  49.1  0.90   Hypertension  406  76.9  404  76.5  0.88   Hyperlipidemia  150  28.4  161  30.5  0.46   Autoimmune diseases  16  3.0  14  2.7  0.71  Receiving other interventionb  92  17.4  101  19.1  0.47  Age (year)  (65.2 ± 10.5)  (65.1 ± 11.0)  0.87  Number of morbidities  (2.2 ± 1.3)  (2.2 ± 1.3)  0.91  Note: values are expressed as (mean ± SD). aFisher's exact test. bExpect CKD intervention, diabetic, hypertension or metabolic syndrome intervention. View Large The prescription rates of medication therapy between the usual care group and the MDC group are shown in Table 2. Compared with the usual care group, the MDC group had a lower prescription rate of NSAIDs, and a higher prescription rate of ACEI/ARB, Vit D3, phosphate binders, uric acid control agents and erythropoietin (P < 0.05). Table 2. Prescription rate of medication therapy between the MDC group and the usual care group   MDC (n = 528)   Usual care (n = 528)   P-value  n  %  n  %  ACEI  80  15.2  63  11.9  0.13  ARB  367  69.5  305  57.8  <0.001  ACEI or ARB  406  76.9  343  65.0  <0.001  Ca channel blocker  294  55.7  299  56.6  0.76  α-Blocker  136  25.8  116  22.0  0.15  β-Blocker  166  31.4  175  33.1  0.55  NSAIDs  15  2.8  34  6.4  0.01  Vit D3  19  3.6  4  0.8  0.002  Statin  254  48.1  236  44.7  0.27  Phosphate binders  180  34.1  46  8.7  <0.001  Diuretics  211  40.0  190  36.0  0.18  Uric acid control agents  212  40.2  147  27.8  <0.001  EPO  73  13.8  25  4.7  <0.001  Blood sugar-lowering agents  213  40.3  211  40.0  0.90  Insulin  96  18.2  85  16.1  0.37    MDC (n = 528)   Usual care (n = 528)   P-value  n  %  n  %  ACEI  80  15.2  63  11.9  0.13  ARB  367  69.5  305  57.8  <0.001  ACEI or ARB  406  76.9  343  65.0  <0.001  Ca channel blocker  294  55.7  299  56.6  0.76  α-Blocker  136  25.8  116  22.0  0.15  β-Blocker  166  31.4  175  33.1  0.55  NSAIDs  15  2.8  34  6.4  0.01  Vit D3  19  3.6  4  0.8  0.002  Statin  254  48.1  236  44.7  0.27  Phosphate binders  180  34.1  46  8.7  <0.001  Diuretics  211  40.0  190  36.0  0.18  Uric acid control agents  212  40.2  147  27.8  <0.001  EPO  73  13.8  25  4.7  <0.001  Blood sugar-lowering agents  213  40.3  211  40.0  0.90  Insulin  96  18.2  85  16.1  0.37  ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; Ca channel blocker, calcium channel blocker; NSAIDs, non-steroid anti-inflammatory drugs; EPO, erythropoietin. View Large Decline of renal function and other laboratory measurements Table 3 illustrates the baseline parameters, the difference (Δ) per year of renal function and other laboratory measurements between the usual care and MDC groups. There were no significant differences in the secondary outcomes of BP control, albumin, lipid profile, Hct level and HbA1c between the MDC and usual care groups. However, iPTH was controlled better in the MDC group (20.9 versus −66.3, P = 0.02). The decline of renal function (eGFR) at an advanced stage of CKD (stages 4 and 5) was slower in the MDC group compared with the usual care group (−5.1 versus −7.3, P = 0.01). Table 3. Baseline characteristics and mean changes (Δ) per year in renal function and other laboratory measurements compared between the MDC group and the usual care group   MDC (n = 528)   Usual care (n = 528)   P-value  Baseline   Difference   Baseline   Difference   Mean  SD  ΔMean  ΔSD  Mean  SD  ΔMean  ΔSD  SBP (mmHg)  137.96  19.88  1.2  20.5  138.45  21.15  0.4  37.3  0.70  DBP (mmHg)  78.43  12.53  −1.0  13.5  79.81  13.53  −0.8  22.0  0.85  eGFR (mL/min)  32.7  12.6  −5.8  6.2  32.9  13.2  −6.7  8.7  0.18  Early stage (stage 3)  41.6  7.4  −6.4  7.1  43.2  8.0  −5.8  7.4  0.49  Late stage (stage 4 and 5)  20.0  5.7  −5.1  4.9  21.0  5.8  −7.3  9.4  0.01  Albumin (g/dL)  4.0  0.5  −0.2  1.4  3.8  0.7  −0.3  1.3  0.52  Cholesterol (mg/dL)  191.2  43.0  −7.0  50.8  187.2  47.1  −13.0  66.9  0.16  TG (mg/dL)  162.0  90.6  −13.5  97.0  163.8  102.1  −8.9  104.7  0.53  HDL-C (mg/dL)  49.0  16.4  −2.2  26.6  45.7  13.7  −2.3  17.6  0.98  LDL-C(mg/dL)  112.5  37.6  −10.0  51.5  108.6  47.2  −7.1  46.0  0.53  Hct (mg/dL)  35.2  6.4  −1.1  6.8  34.9  7.0  −0.9  7.6  0.79  Ca*P  35.0  7.7  0.6  11.0  34.9  7.8  3.1  30.2  0.58  HbA1C (%)  6.9  1.6  −0.3  3.7  7.6  1.9  −0.3  2.5  0.98  iPTH (pg/mL)a  67.2  91.4  20.9  59.0  216.0  186.6  −66.3  46.4  0.02  ACR (‰)a  767.5  1836.4  81.4  1079.0  1424.2  3285.4  832.1  6145.8  0.87  PCR (mg/g)a  1481.4  2135.3  66.6  1672.4  4362.3  15 983.3  1079.0  1589.3  0.30    MDC (n = 528)   Usual care (n = 528)   P-value  Baseline   Difference   Baseline   Difference   Mean  SD  ΔMean  ΔSD  Mean  SD  ΔMean  ΔSD  SBP (mmHg)  137.96  19.88  1.2  20.5  138.45  21.15  0.4  37.3  0.70  DBP (mmHg)  78.43  12.53  −1.0  13.5  79.81  13.53  −0.8  22.0  0.85  eGFR (mL/min)  32.7  12.6  −5.8  6.2  32.9  13.2  −6.7  8.7  0.18  Early stage (stage 3)  41.6  7.4  −6.4  7.1  43.2  8.0  −5.8  7.4  0.49  Late stage (stage 4 and 5)  20.0  5.7  −5.1  4.9  21.0  5.8  −7.3  9.4  0.01  Albumin (g/dL)  4.0  0.5  −0.2  1.4  3.8  0.7  −0.3  1.3  0.52  Cholesterol (mg/dL)  191.2  43.0  −7.0  50.8  187.2  47.1  −13.0  66.9  0.16  TG (mg/dL)  162.0  90.6  −13.5  97.0  163.8  102.1  −8.9  104.7  0.53  HDL-C (mg/dL)  49.0  16.4  −2.2  26.6  45.7  13.7  −2.3  17.6  0.98  LDL-C(mg/dL)  112.5  37.6  −10.0  51.5  108.6  47.2  −7.1  46.0  0.53  Hct (mg/dL)  35.2  6.4  −1.1  6.8  34.9  7.0  −0.9  7.6  0.79  Ca*P  35.0  7.7  0.6  11.0  34.9  7.8  3.1  30.2  0.58  HbA1C (%)  6.9  1.6  −0.3  3.7  7.6  1.9  −0.3  2.5  0.98  iPTH (pg/mL)a  67.2  91.4  20.9  59.0  216.0  186.6  −66.3  46.4  0.02  ACR (‰)a  767.5  1836.4  81.4  1079.0  1424.2  3285.4  832.1  6145.8  0.87  PCR (mg/g)a  1481.4  2135.3  66.6  1672.4  4362.3  15 983.3  1079.0  1589.3  0.30  SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; Hct, hematocrit; iPTH, intact parathyroid hormone; ACR, albumin creatinine ratio; PCR, plasma creatinine ratio aMann–Whitney U test. View Large Hospitalization risk A total of 183 (34.7%) subjects in the MDC group and 171 (32.4%) subjects in the usual care group had been hospitalized at least once during the study period. The mean frequency of hospitalization (0.6 ± 1.2 versus 0.6 ± 1.2) and days of hospital stays (6.7 ± 17.1 versus 5.9 ± 13.3 days) were not different between the MDC group and the usual care group (Table 4). The hospitalization rate (73.9% versus 85.7%) and days of hospital stays (11.4 ± 12.5 versus 19.1 ± 21.9 days) at dialysis initiation also showed significant difference between the MDC group and the usual care group (data not shown). Kaplan–Meier analysis showed that all-cause hospitalization risk and the probability of hospitalization for cardiovascular disease were not different between the two groups (data not shown), but the MDC group had a 40% reduction in the risk of hospitalization due to infection (log-rank test, P = 0.02) (HR: 0.60; 95% CI: 0.37–0.94) (Figure 2). In the adjusted Cox regression analysis, there was still no significant difference in the probability of all-cause hospitalization between the two groups [hazard ratio (HR: 0.91; 95% CI: 0.74–1.12) (Table 5). Table 4. Clinical outcomes between the MDC group and the usual care group   MDC (n = 528)   Usual care (n = 528)   P-value  n  %  n  %  Hospitalization rate  183  34.7  171  32.4  0.43  The frequency of hospitalization  (0.6 ± 1.2)  (0.6 ± 1.2)  0.57  Hospital days  (6.7 ± 17.1)  (5.9 ± 13.3)  0.42  eGFR at dialysis initiation  5.8 ± 1.7  5.5 ± 2.0  0.60  Transfer to dialysis  46  8.7  21  4.0  0.002   Temporary catheter at dialysis initiation  21  45.6  14  66.7     Peritoneal dialysis  14  30.4  3  14.3     Hemodialysis  32  69.6  18  85.7      Mature functional vascular access  15  32.6  6  28.6    Mortality  17  3.2  30  5.7  0.05  eGFR at mortality  16.3 ± 14.2  20.0 ± 12.7  0.26    MDC (n = 528)   Usual care (n = 528)   P-value  n  %  n  %  Hospitalization rate  183  34.7  171  32.4  0.43  The frequency of hospitalization  (0.6 ± 1.2)  (0.6 ± 1.2)  0.57  Hospital days  (6.7 ± 17.1)  (5.9 ± 13.3)  0.42  eGFR at dialysis initiation  5.8 ± 1.7  5.5 ± 2.0  0.60  Transfer to dialysis  46  8.7  21  4.0  0.002   Temporary catheter at dialysis initiation  21  45.6  14  66.7     Peritoneal dialysis  14  30.4  3  14.3     Hemodialysis  32  69.6  18  85.7      Mature functional vascular access  15  32.6  6  28.6    Mortality  17  3.2  30  5.7  0.05  eGFR at mortality  16.3 ± 14.2  20.0 ± 12.7  0.26  Note: values are expressed as (mean ± SD); mature functional vascular access in the MDC group composed of four subjects with perm catheter and 11 subjects with fistula; usual care composed of two subjects with perm catheter and four subjects with fistula. View Large Table 5. Cox regression model   Crude   P-value  Adjusted   P-value  HR  95% CI  HR  95% CI  Hospitalization risk  0.94  0.76–1.15  0.53  0.91  0.74–1.12  0.37  Dialysis risk  1.90  1.13–3.18  0.02  1.68  1.00–2.86  0.05  Patient mortality  0.50  0.28–0.92  0.03  0.49  0.27–0.88  0.02  Drop out  1.09  0.75–1.59  0.65  1.02  0.70–1.50  0.91    Crude   P-value  Adjusted   P-value  HR  95% CI  HR  95% CI  Hospitalization risk  0.94  0.76–1.15  0.53  0.91  0.74–1.12  0.37  Dialysis risk  1.90  1.13–3.18  0.02  1.68  1.00–2.86  0.05  Patient mortality  0.50  0.28–0.92  0.03  0.49  0.27–0.88  0.02  Drop out  1.09  0.75–1.59  0.65  1.02  0.70–1.50  0.91  View Large FIGURE 2: View largeDownload slide The Kaplan–Meier curve for time to first hospitalization for infection between the MDC group and usual care group. FIGURE 2: View largeDownload slide The Kaplan–Meier curve for time to first hospitalization for infection between the MDC group and usual care group. Dialysis risk and modality selection There were 21 (4.0%) subjects in the usual care group and 46 (8.7%) subjects in the MDC group who progressed to ESRD and initiation of dialysis (P = 0.002). The mean eGFR at dialysis initiation was not significantly different between two groups (5.8 versus 5.5 mL/min, P = 0.60) (Table 4). For patients who initiated dialysis (n = 67), the MDC group had a higher prevalence in peritoneal dialysis (PD) (30.4 versus 14.3%) and less temporary catheter use (45.6 versus 66.7%) (Table 4). Of the patients initiating hemodialysis, 46.9% (15 of 32) subjects in the MDC group had mature functional vascular access (including perm catheter and fistula) and the usual care group had only 33.3% (6 of 18 subjects) (Table 4). The result of Kaplan–Meier analysis showed that the MDC group was more likely to initiate dialysis than the usual care group (log-rank test, P = 0.01) (Figure 3). The unadjusted Cox regression analysis revealed that the MDC group was associated with a 90% increase in the risk of initiating of dialysis compared with the usual care group (HR: 1.90; 95% CI: 1.13–3.18) (Table 5). The HR changed slightly to 1.68 (95% CI: 1.00–2.86) after adjusting for gender, age, eGFR and comorbidity. (Table 5) FIGURE 3: View largeDownload slide The Kaplan–Meier curve for the probability of dialysis between the MDC group and the usual care group. FIGURE 3: View largeDownload slide The Kaplan–Meier curve for the probability of dialysis between the MDC group and the usual care group. Patient mortality During an average follow-up time of 33.1 months, a total of 30 (5.7%) patients in the usual care group and 17 (3.2%) patients in the MDC group died (P = 0.05). The MDC group had better patient survival compared with the usual care group in the Kaplan–Meier analysis (Figure 4, log-rank test P = 0.02). The adjusted Cox regression analysis showed that MDC was associated with 51% reduction in patient mortality compared with the usual care group (HR: 0.49; 95% CI: 0.27–0.88) (Table 5). Furthermore, we estimated ‘drop out CKD’ (either as the initiation of RRT or patient mortality) and found that there was no significant difference between the two groups (Table 5). FIGURE 4: View largeDownload slide The Kaplan–Meier curve of patient survival between the MDC group and the usual care group. FIGURE 4: View largeDownload slide The Kaplan–Meier curve of patient survival between the MDC group and the usual care group. DISCUSSION This 3-year prospective cohort study demonstrated that the integrated, comprehensive, team-based, MDC care for patients with CKD significantly slowed the decline of renal function in the late stage of CKD and improved mineral bone disease control. The risk of mortality was also lower in the MDC group than in the usual care group. Although all-cause hospitalization and cardiovascular-related hospitalization were not significantly different between the two groups. In addition, the MDC group had fewer instances of temporary vascular catheter use at the initiation of dialysis and had a greater willingness to select PD as the initial modality of the RRT. Lifestyle modification and medical utilization The MDC treatment provides CKD patients with enhanced disease knowledge and awareness for the disease care. Patients had a more positive attitude toward the disease and a greater improvement of medication and treatment compliance, as well as self-management, such as the adoption of nutritional counseling, lifestyle behavior change and avoidance of taking NSAIDS and nephrotoxins [29]. The rate of NSAID prescription in our study was lower compared with previous studies [29]. Consensus guidelines for CKD management emphasize the administration of nephroprotective agents [renin–angiotensin system (RAAS) blockade], reduction in cardiovascular risk, management of BP, screening and intervention for CKD-MBD and anemia. Medications for the blockade of the renin–angiotensin system (RAAS) have been considered as the first line of antihypertensive therapy for CKD patients to slow renal function decline, and to reduce proteinuria and cardiovascular events. Despite the JNC7 and the NKF K/DOQI guidelines, target BP control is achieved in less than 50% of CKD patients [30–32] and the overall prescription of the RAAS blockade was insufficient. Physicians may be reluctant to prescribe due to side effects including hyperkalemia or hemodynamic-mediated increase in serum creatinine. In our study, CKD participants in the MDC group were generally more likely to be prescribed ACEI/ARB medications (76.9 versus 65.0%, P < 0.001), and MDC members also supported additional effort to monitor side-effects and to conduct follow-up such as hyperkalemia. Lack of awareness and recognition of K/DOQI guidelines may explain why there are fewer tests for parameters of CKD-MBD and less attention paid to phosphate control and secondary hyperparathyroidism (SHPT) [33]. Hyperphosphatemia and a high FGF-23 level are associated with more rapid declines in renal function, increased risk of vascular calcifications and cardiovascular events [34–36]. In the present study, a higher prescription rate of phosphate binders and vitamin D3 therapy in the MDC group has led to better SHPT control. Moreover, awareness and treatment of dyslipidemia and hyperuricemia are generally poor in CKD patients, which not only contribute to CKD progression, but is also associated with higher cardiovascular events [30]. Consequences of a combination of lifestyle modifications and more effective medication prescription according to K/DOQI guidelines under MDC intervention may contribute to slower renal function declines and may reduce all-causes mortality in our study. Reduction in temporary vascular catheter and dialysis modality selection Early referral to nephrologists increased the initiation of dialysis outside of the hospital by the CKD patients with more mature functional vascular access [37, 38]. Previous studies have shown that reduction in temporary vascular catheter is associated with a lower systemic infection rate, avoidance of emergency dialysis and suboptimal initiation of dialysis [39–41]. Complications related to temporary vascular access are also important causes of excessive morbidity and mortality, longer hospitalization and also account for high health-care costs. Timing referral and pre-dialysis education play an important role for CKD patients in choice of RRT modality and their compliance with therapy prescription [42–45]. According to the United States Renal Data System (USRDS) report, only 6.5% of the dialysis patients in the USA preferred PD. In Taiwan, the proportion of dialysis patients undergoing PD increased from 6.1% in 2001 to 7.8% in 2005, but the proportion of dialysis patients opting for PD remains low [46]. Our study demonstrated that under MDC, there was less temporary catheter use (45.6 versus 66.7%) at the initiation of dialysis. Patients in the MDC group are more likely to select PD (30.45 versus 14.3%) as the initial dialysis modality and more mature functional vascular access at hemodialysis initiation (46.9 versus 33.3%). MDC may help CKD patients to receive well-balanced presentations of all RRT options. Educational intervention could increase patient self-care ability and the provision of adequate and good quality information of dialysis, making patients willing to undergo PD and self-care dialysis. MDC places emphasis on dialysis modality introduction, early preparation of RRT and timing initiation of RRT, does not force patients to receive dialysis when they encounter uremia. Initiation of RRT rather than mortality MDC plays an important role in managing CKD and related complications, reducing cardiovascular risk and also ensuring the smooth transition from the pre-dialysis stage to RRT. Studies have made an effort to define suboptimal and non-elective dialysis when patients initiate dialysis as (i) in-patients, (ii) with a central venous catheter and (iii) without dialysis modality selection [47–49]. CKD patients with sub-optimal dialysis initiation have worse biochemical parameters, clinical status and vascular access. They are less likely to utilize self-care dialysis modalities and thus have longer hospitalization rates and a higher mortality rate than well-prepared patients. As renal function declines, MDC would promote patient awareness of clinical conditions to initiate dialysis electively [23]. There was no earlier initiation of dialysis in the MDC group and the mean eGFR at mortality was not significantly different (16.3 versus 20.0 mL/min, P = 0.26) between two groups. We proposed several possible explanations for higher dialysis initiation rather than mortality in the MDC group.There are several limitations in our study. Patient compliance, attitudes and adherence to disease education intervention could not be evaluated. Laboratory data were collected and measured at different medical institutions, at different period intervals and assayed with different laboratory equipment. It is possible that systemic bias in laboratory measures exists. The fixed reimbursement policy of the NHI restrained laboratory parameter measurement and medical utilization. These limitations may result difficulty to achieve adequate BP and MBD control, reduction in the lipid profile and maintenance of hemocrit levels by consensus guidelines. To eliminate such bias, our study used the propensity score with one to one matching of MDC and usual care patients for further analysis and evaluation. Less frequent CKD parameters and laboratory measurement were noted in the usual care group, thus resulting in incomplete data collection and hampering further evaluation of the impact of intervention between two groups. This finding may be related to the primary physician's lack of awareness and recognition of consensus CKD management guidelines. Indeed, nephrologists of the MDC group appear more attentive to CKD management guidelines and CKD patients in the MDC group have optimal care delivery. This study was the first multi-hospital-collaborated research on the CKD Prevention and Care Plan in Taiwan with a large sample size, which was supported by the Bureau of Health Promotion, Department of Health, ROC (Taiwan) for the construction and evaluation of the effectiveness of MDC intervention for CKD patients during a 3-year follow-up (2008–10) and it showed the true phase of MDC in CKD in Taiwan. The five hospitals in our study included community hospitals to tertiary referral medical centers, and were located in the northern, middle and southern areas of Taiwan. All five hospitals in our study are pioneer organizations with ample experience in the pre-ESRD care program and in promotion performance for CKD prevention in Taiwan. There was a robust association between renal function, cardiovascular outcome and all-cause mortality. Keith et al. has revealed that patients with stage IV CKD were more likely to die rather than progress to ESRD, and death was far more common than dialysis at all stages of CKD [9]. Owing to slower renal function declines in the MDC group, we proposed CKD patients could receive more effective intervention in treatment of CKD and reduction of cardiovascular risk. A longer pre-dialysis educational period and a prolonged mean time to dialysis in the MDC group, CKD patients could receive more adequate intervention, adequately communicate with nephrologists and MDC members about treatment of CKD and related complications, indication and preparation of RRT. MDC education could encourage patients with a positive attitude and increasing motivation to accept RRT. MDC makes CKD patients initiate timely RRT and have smooth transition from pre-ESRD to dialysis rather than reaching mortality. In conclusion, we have demonstrated that CKD patients participate in the integrated, comprehensive, and team-based, MDC are benefited from slower renal function declines in advanced stage CKD and achieving greater improvement of clinical outcomes, timing initiation of dialysis with functional vascular access and reduced mortality. Patients in the MDC intervention are also more willing to choose PD as dialysis modality. FUNDING This study was supported by the Bureau of Health Promotion, Department of Health of Taiwan, grant numbers DOH 101-TD-B-111–004. CONFLICT OF INTEREST STATEMENT None declared. ACKNOWLEDGMENTS We thank the co-operation of the hospital for the help in data collection, including Shih-Te Tu, Kwo-Chuan Lin, Pei-Yung Liao, Su-Lan Lin, Li-Ching Chen, Chih-Ying Huang, Shu-Ya Chen, Su-Mei Sun, Li-Fang Lai, Pen-Lin Lin and Hui-Chu Lee for Changhua Christian Hospital; Jui-Hsin Chen and Chiu-Yueh Chen for Kaohsiung Municipal Hsiaokang Hospital; Shu-Chi Lu for Taipei Medical University Hospital; Jay-Jen Lin for Cathay General Hospital; Ya-Hsueh Shih for Chiayi Chang Gung Memorial Hospital. We thank Professor Fung-Chang Sung for his revision of this paper. REFERENCES 1 Coresh J,  Selvin E,  Stevens LA, et al.  Prevalence of chronic kidney disease in the United States,  JAMA ,  2007, vol.  298 (pg.  2038- 2047) https://doi.org/10.1001/jama.298.17.2038 Google Scholar CrossRef Search ADS PubMed  2 Gilbertson DT,  Liu J,  Xue JL, et al.  Projecting the number of patients with end-stage renal disease in the United States to the year 2015. 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Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Journal

Nephrology Dialysis Transplantation – Oxford University Press

Published: Dec 6, 2012

Keywords: chronic kidney disease hospitalization, multidisciplinary care mortality renal replacement therapy

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