Late Nephrological Co-Management and Chronic Kidney Disease
Late Nephrological Co-Management and Chronic Kidney Disease
Aims: To assess the impact of late referral (LR) for nephrological co-management compared with early referral (ER) on morbidity and mortality in chronic kidney disease (CKD) and to identify individual factors associated with higher mortality in LR, correcting for lead-time and immortal time bias.
Patients and methods: Retrospective observational study comparing 46 LR patients with 103 ER patients. The quality of CKD management was assessed by measures to prevent CKD progression and to modify CKD complications and cardiovascular risk factors according to current guidelines. One-year mortality of LR and ER was compared and factors associated with mortality were identified. Analysis was performed with equivalent GFR (glomerular filtration rate) of ER and LR at baseline to correct for lead-time and immortal time bias.
Results: Late referral was associated with inferior control of most risk factors for CKD progression, CKD complications and cardiovascular risk factors. In particular, glycaemic control, the use of angiotensin converting enzyme inhibitors and angiotensin-2-receptor blockers in diabetic nephropathy or proteinuria, the control of nutritional and volume status were inferior in LR. One-year mortality was significantly higher in LR (RR 5.9 (95% CI 1.5–19.6); p < 0.01). Inadequate control of blood pressure, anaemia, volume status, malnutrition and emergency initial dialysis, but not LR itself were independently associated with mortality.
Conclusions: Late referral was associated with a substantially lower survival after correction for lead-time and immortal time bias and with inferior control of most risk factors for CKD progression, complications and cardiovascular risk factors. CKD patients may particularly profit from adequate control of blood pressure, anaemia, nutritional and volume status, and avoidance of emergency initial dialysis as these factors may predominately contribute to survival.
The high incidence and prevalence of chronic kidney disease (CKD) are an enormous and increasing worldwide public health problem. CKD and associated complications, especially cardiovascular disease (CVD) have been identified as major causes of morbidity and mortality. Cardiovascular morbidity and mortality are particularly high in advanced CKD. Furthermore, CKD may progress to end-stage renal disease (ESRD), which aggravates CVD. There are effective interventions to reduce the morbidity and mortality associated with CKD by delaying CKD progression, ameliorating comorbidity and correcting cardiovascular risk factors. These interventions should be initiated as early as possible in the course of CKD to be most effective. In contrast, late and irregular referral (LR) to nephrologists for co-management was demonstrated to be deleterious in CKD and to increase morbidity and mortality compared with early referral (ER). Currently, LR is still common in 30–40% of all advanced CKD patients worldwide (11,13–17).
In contrast to the wealth of studies demonstrating the contribution of ER on outcome in CKD, there are limited data on which components of LR actually exert its deleterious effects and impact mortality. Focusing on these individual deleterious factors in the complexity of LR may be more efficient to improve care and outcomes in CKD. Of note, virtually all previous studies reporting a disadvantage of LR have not addressed the effects of lead-time and immortal time bias. Lead-time is the interval between the start and the end-point of a study. Conclusions from a study may be incorrect if patients are entered at different stages of the disease. Any perceived higher end-point rate may simply be resulting from later inclusion time points of patients, that is, by recording a shorter lead-time. In the context of this study, lead-time bias refers to the perceived differences in mortality and morbidity over time when comparing cohorts at different CKD stages instead of investigating outcome in all cohorts from a similar GFR. Immortal time again is the time a patient is guaranteed to be alive between the patient's study entry and exposure to a treatment. Immortal time bias is called the perceived survival benefit originating from the time between study entry and treatment in patients who received ER. The objectives of this study were, while correcting for lead-time and immortal time bias, (i) to assess further the impact of LR in comparison to ER on morbidity and mortality in patients with advanced CKD and (ii) to identify individual factors associated with LR and its higher mortality.
Abstract and Introduction
Abstract
Aims: To assess the impact of late referral (LR) for nephrological co-management compared with early referral (ER) on morbidity and mortality in chronic kidney disease (CKD) and to identify individual factors associated with higher mortality in LR, correcting for lead-time and immortal time bias.
Patients and methods: Retrospective observational study comparing 46 LR patients with 103 ER patients. The quality of CKD management was assessed by measures to prevent CKD progression and to modify CKD complications and cardiovascular risk factors according to current guidelines. One-year mortality of LR and ER was compared and factors associated with mortality were identified. Analysis was performed with equivalent GFR (glomerular filtration rate) of ER and LR at baseline to correct for lead-time and immortal time bias.
Results: Late referral was associated with inferior control of most risk factors for CKD progression, CKD complications and cardiovascular risk factors. In particular, glycaemic control, the use of angiotensin converting enzyme inhibitors and angiotensin-2-receptor blockers in diabetic nephropathy or proteinuria, the control of nutritional and volume status were inferior in LR. One-year mortality was significantly higher in LR (RR 5.9 (95% CI 1.5–19.6); p < 0.01). Inadequate control of blood pressure, anaemia, volume status, malnutrition and emergency initial dialysis, but not LR itself were independently associated with mortality.
Conclusions: Late referral was associated with a substantially lower survival after correction for lead-time and immortal time bias and with inferior control of most risk factors for CKD progression, complications and cardiovascular risk factors. CKD patients may particularly profit from adequate control of blood pressure, anaemia, nutritional and volume status, and avoidance of emergency initial dialysis as these factors may predominately contribute to survival.
Introduction
The high incidence and prevalence of chronic kidney disease (CKD) are an enormous and increasing worldwide public health problem. CKD and associated complications, especially cardiovascular disease (CVD) have been identified as major causes of morbidity and mortality. Cardiovascular morbidity and mortality are particularly high in advanced CKD. Furthermore, CKD may progress to end-stage renal disease (ESRD), which aggravates CVD. There are effective interventions to reduce the morbidity and mortality associated with CKD by delaying CKD progression, ameliorating comorbidity and correcting cardiovascular risk factors. These interventions should be initiated as early as possible in the course of CKD to be most effective. In contrast, late and irregular referral (LR) to nephrologists for co-management was demonstrated to be deleterious in CKD and to increase morbidity and mortality compared with early referral (ER). Currently, LR is still common in 30–40% of all advanced CKD patients worldwide (11,13–17).
In contrast to the wealth of studies demonstrating the contribution of ER on outcome in CKD, there are limited data on which components of LR actually exert its deleterious effects and impact mortality. Focusing on these individual deleterious factors in the complexity of LR may be more efficient to improve care and outcomes in CKD. Of note, virtually all previous studies reporting a disadvantage of LR have not addressed the effects of lead-time and immortal time bias. Lead-time is the interval between the start and the end-point of a study. Conclusions from a study may be incorrect if patients are entered at different stages of the disease. Any perceived higher end-point rate may simply be resulting from later inclusion time points of patients, that is, by recording a shorter lead-time. In the context of this study, lead-time bias refers to the perceived differences in mortality and morbidity over time when comparing cohorts at different CKD stages instead of investigating outcome in all cohorts from a similar GFR. Immortal time again is the time a patient is guaranteed to be alive between the patient's study entry and exposure to a treatment. Immortal time bias is called the perceived survival benefit originating from the time between study entry and treatment in patients who received ER. The objectives of this study were, while correcting for lead-time and immortal time bias, (i) to assess further the impact of LR in comparison to ER on morbidity and mortality in patients with advanced CKD and (ii) to identify individual factors associated with LR and its higher mortality.
Source...