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Survival After Dialysis Initiation: A Comparison of Transplant Patients After Graft Loss Versus Nontransplant Patients
Survival After Dialysis Initiation: A Comparison of Transplant Patients After Graft Loss Versus Nontransplant Patients G. Fernández Fresnedo, J.C. Ruiz, C. Gómez Alamillo, A.L.M. de Francisco, and M. Arias ABSTRACT Background. A substantial number of patients return to dialysis therapy after a renal transplant fails. It is not clear whether mortality increases among patients with graft failure relative to those who initiate dialysis but who have not yet received a kidney transplant. Patients and Methods. We compared the outcomes of an incident cohort of patients (n ⫽ 194) with a cohort of renal transplant patients who returned to dialysis after graft loss (n ⫽ 74). We analyzed the morbidity and mortality after dialysis initiation and the parameters during the year beforehand. Results. Mortality among post-graft loss dialysis patients was higher than transplant-naive patients (relative risk [RR]: 2.05; 95% confidence interval [CI]: 1.26 –3.35). Additionally, complications, such as the number of hospitalizations during the first year after dialysis initiation, were higher (29% vs 57%; P ⬎ .001). At dialysis initiation no differences were found in glomerular filtration rate, although hemoglobin and albumin levels were lower and C-reactive protein was higher in post-graft loss dialysis patients. Conclusions. Mortality among patients on dialysis therapy after graft loss increased significantly compared with mortality among patients who initiated dialysis for the first time, despite specialty physicians being aware of them. Additional studies are urgently needed to define the mechanisms of the increased risk and strategies to decrease mortality.
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URVIVAL PROBABILITY following kidney transplantation has improved steadily over the last few years; however, chronic allograft nephropathy with subsequent graft loss remains a vexing problem and these patients must return to dialysis. This situation, together with the progressive increase in the number of renal transplant patients, means that the population of transplant patients readmitted to a dialysis program will be progressively greater. Therefore, it is necessary to consider this group of patients as a specific subgroup among the predialysis patients given their specific characteristics. A limited number of studies have evaluated patients returning to dialysis after graft failure.1 The majority have been single-center studies with relatively small sample sizes, involved various groups of patients (patients on the waiting list or patients with a functioning graft), and are therefore of limited generalizability.2,3 No large-scale study has addressed the question of whether patients on dialysis following a failed kidney transplant are at increased risk for death relative to patients who have not yet received a transplant. The aim of this study was to compare mortality risk between post-graft loss patients
and patients who initiated dialysis but who had not yet received a kidney transplant. PATIENTS AND METHODS We analyzed 268 patients who started substitutive therapy between 2000 and 2006. This group included 2 subgroups of patients: 74 patients with chronic allograft nephropathy (CAN; group A) and 194 patients initiating dialysis for the first time (NoCAN; group B). The whole group corresponded to all the patients entering dialysis with clinical and analytical data available for at least 1 year before the initiation of dialysis. Serum chemistry and complete blood cell counts were performed in all patients at each evaluation: creatinine, urea, calculated MDRD-4, hemoglobin level, calcium, phosphorous, albumin, C-reactive protein, and calculated erythropoietin resistance index.4 To analyze patient morbidity, the number of hospital admissions was computed during the first year after From the Nephrology Service, University Hospital Marqués de Valdecilla, Santander, Spain. Address reprint requests to Gema Fernández Fresnedo, Servicio de Nefrologı´a, Hospital Marqués de Valdecilla, Avda de Valdecilla, 39008 Santander, Spain. E-mail: [email protected]
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.08.094
Transplantation Proceedings, 40, 2889 –2890 (2008)
2889
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initiating dialysis. The mortality rate was analyzed by actuarial survival curves (Kaplan-Meier).
Table 2. Analytical Data in Both Groups at the Moment of Initiating Dialysis Group A (CAN)
RESULTS
Table 1 shows the demographic characteristics of the 2 groups, and Table 2 the analytical data for both groups at the start of dialysis. With regard to morbidity, the group A patients underwent more hospital admissions than group B (49% vs 34%; P ⬍ .05). Also, the average number of admissions per patient was significantly higher in group A. The patient survivals after return to dialysis (group A) were 80% and 62% at 1 and 5 years, respectively. In group B, the patient survivals were significantly better: 93% and 78% at 1 and 5 years (log-rank; P ⫽ .003). The relative risk of total mortality with a Cox regression model was 2.05 (95% confidence interval: 1.26 –3.35; P ⫽ .001). DISCUSSION
This study demonstrated that patients with a failed kidney transplant initiate dialysis at a mean estimated glomerular filtration rate, calcium, and phosphorous levels that are inadequate and similar to mean levels in the incident end-stage renal disease population.3 The data suggested that even among patients who are presumed to be under the care of transplant physicians, chronic kidney disease care is suboptimal. However, this population presents its own characteristics leading to excess mortality. The causes of Table 1. Demographic Characteristics of Both Groups Group A (CAN)
Age Male/female (%) Diabetes (%) CVD (%) No. of transplantations (%) 1 ⱖ2 Follow-up after dialysis initiation (y)
Group B (NoCAN)
P
48 ⫾ 10 64/36 7 26
50 ⫾ 10 70/30 20 20
NS NS NS NS
68 32 3.02 ⫾ 1.8
NA NA 2.5 ⫾ 1.9
NS
CVD, cardiovascular disease; NA, not applicable; NS, not significant.
Creatinine (mg/dL) Urea (mg/dL) Calcium (mg/dL) Phosphorous (mg/dL) GFR (MDRD-4) (mL/min/ 1.73 m2) Hemoglobin (g/dL) Albumin (g/dL) CRP (mg/dL) ERI (U/kg/week per g/dL)
Group B (NoCAN)
P
6.9 ⫾ 2.8 218 ⫾ 66 8.7 ⫾ 0.8 6.3 ⫾ 2.4 9.4 ⫾ 3.6
7.1 ⫾ 2.1 216 ⫾ 59 8.7 ⫾ 1.1 6.7 ⫾ 1.9 8.7 ⫾ 3.1
NS NS NS NS NS
10.1 ⫾ 2 3.2 ⫾ 0.5 3.4 ⫾ 2.3 9.3 ⫾ 5.8
10.9 ⫾ 1.3 4.3 ⫾ 0.5 1.9 ⫾ 2.3 5.4 ⫾ 3.9
⬍.05 ⬍.05 ⬍.05 ⬍.05
GFR, glomerular filtration rate; CRP, C-reactive protein; ERI, erythropoietin resistance index; NS, not significant.
these high rates of morbidity and mortality are not very well known. However, poor control of chronic kidney disease complications, the persistence of a chronic inflammatory state due to the failed graft, and the lack of a protective effect of the functioning graft may play important roles.5 Clinical markers of inflammation may help us predict a poor outcome. Our findings demonstrated that there are many opportunities to improve the care of patients with kidney failure who return to dialysis. REFERENCES 1. Arias M, Escallada R, de Francisco AL, et al: Return to dialysis after renal transplantation. Which would be the best way? Kidney Int Suppl 61:85, 2002 2. Gill JS, Abichandani R, Kausz AT, et al: Mortality after kidney transplant failure: the impact of non-immunologic factors. Kidney Int 62:1875, 2002 3. Gill JS, Abichandani R, Khan S, et al: Opportunities to improve the care of patients with kidney transplant failure. Kidney Int 61:2193, 2002 4. López-Gómez JM, Pérez-Flores I, Jofré R, et al: Presence of a failed kidney transplant in patients who are on hemodialysis is associated with chronic inflammatory state and erythropoietin resistance. J Am Soc Nephrol 15:2494, 2004 5. Marcen R, Teruel JL: Patient outcomes after kidney allograft loss. Transplantation Rev 22:62, 2008
S
URVIVAL PROBABILITY following kidney transplantation has improved steadily over the last few years; however, chronic allograft nephropathy with subsequent graft loss remains a vexing problem and these patients must return to dialysis. This situation, together with the progressive increase in the number of renal transplant patients, means that the population of transplant patients readmitted to a dialysis program will be progressively greater. Therefore, it is necessary to consider this group of patients as a specific subgroup among the predialysis patients given their specific characteristics. A limited number of studies have evaluated patients returning to dialysis after graft failure.1 The majority have been single-center studies with relatively small sample sizes, involved various groups of patients (patients on the waiting list or patients with a functioning graft), and are therefore of limited generalizability.2,3 No large-scale study has addressed the question of whether patients on dialysis following a failed kidney transplant are at increased risk for death relative to patients who have not yet received a transplant. The aim of this study was to compare mortality risk between post-graft loss patients
and patients who initiated dialysis but who had not yet received a kidney transplant. PATIENTS AND METHODS We analyzed 268 patients who started substitutive therapy between 2000 and 2006. This group included 2 subgroups of patients: 74 patients with chronic allograft nephropathy (CAN; group A) and 194 patients initiating dialysis for the first time (NoCAN; group B). The whole group corresponded to all the patients entering dialysis with clinical and analytical data available for at least 1 year before the initiation of dialysis. Serum chemistry and complete blood cell counts were performed in all patients at each evaluation: creatinine, urea, calculated MDRD-4, hemoglobin level, calcium, phosphorous, albumin, C-reactive protein, and calculated erythropoietin resistance index.4 To analyze patient morbidity, the number of hospital admissions was computed during the first year after From the Nephrology Service, University Hospital Marqués de Valdecilla, Santander, Spain. Address reprint requests to Gema Fernández Fresnedo, Servicio de Nefrologı´a, Hospital Marqués de Valdecilla, Avda de Valdecilla, 39008 Santander, Spain. E-mail: [email protected]
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.08.094
Transplantation Proceedings, 40, 2889 –2890 (2008)
2889
2890
FERNÁNDEZ FRESNEDO, RUIZ, GÓMEZ ALAMILLO ET AL
initiating dialysis. The mortality rate was analyzed by actuarial survival curves (Kaplan-Meier).
Table 2. Analytical Data in Both Groups at the Moment of Initiating Dialysis Group A (CAN)
RESULTS
Table 1 shows the demographic characteristics of the 2 groups, and Table 2 the analytical data for both groups at the start of dialysis. With regard to morbidity, the group A patients underwent more hospital admissions than group B (49% vs 34%; P ⬍ .05). Also, the average number of admissions per patient was significantly higher in group A. The patient survivals after return to dialysis (group A) were 80% and 62% at 1 and 5 years, respectively. In group B, the patient survivals were significantly better: 93% and 78% at 1 and 5 years (log-rank; P ⫽ .003). The relative risk of total mortality with a Cox regression model was 2.05 (95% confidence interval: 1.26 –3.35; P ⫽ .001). DISCUSSION
This study demonstrated that patients with a failed kidney transplant initiate dialysis at a mean estimated glomerular filtration rate, calcium, and phosphorous levels that are inadequate and similar to mean levels in the incident end-stage renal disease population.3 The data suggested that even among patients who are presumed to be under the care of transplant physicians, chronic kidney disease care is suboptimal. However, this population presents its own characteristics leading to excess mortality. The causes of Table 1. Demographic Characteristics of Both Groups Group A (CAN)
Age Male/female (%) Diabetes (%) CVD (%) No. of transplantations (%) 1 ⱖ2 Follow-up after dialysis initiation (y)
Group B (NoCAN)
P
48 ⫾ 10 64/36 7 26
50 ⫾ 10 70/30 20 20
NS NS NS NS
68 32 3.02 ⫾ 1.8
NA NA 2.5 ⫾ 1.9
NS
CVD, cardiovascular disease; NA, not applicable; NS, not significant.
Creatinine (mg/dL) Urea (mg/dL) Calcium (mg/dL) Phosphorous (mg/dL) GFR (MDRD-4) (mL/min/ 1.73 m2) Hemoglobin (g/dL) Albumin (g/dL) CRP (mg/dL) ERI (U/kg/week per g/dL)
Group B (NoCAN)
P
6.9 ⫾ 2.8 218 ⫾ 66 8.7 ⫾ 0.8 6.3 ⫾ 2.4 9.4 ⫾ 3.6
7.1 ⫾ 2.1 216 ⫾ 59 8.7 ⫾ 1.1 6.7 ⫾ 1.9 8.7 ⫾ 3.1
NS NS NS NS NS
10.1 ⫾ 2 3.2 ⫾ 0.5 3.4 ⫾ 2.3 9.3 ⫾ 5.8
10.9 ⫾ 1.3 4.3 ⫾ 0.5 1.9 ⫾ 2.3 5.4 ⫾ 3.9
⬍.05 ⬍.05 ⬍.05 ⬍.05
GFR, glomerular filtration rate; CRP, C-reactive protein; ERI, erythropoietin resistance index; NS, not significant.
these high rates of morbidity and mortality are not very well known. However, poor control of chronic kidney disease complications, the persistence of a chronic inflammatory state due to the failed graft, and the lack of a protective effect of the functioning graft may play important roles.5 Clinical markers of inflammation may help us predict a poor outcome. Our findings demonstrated that there are many opportunities to improve the care of patients with kidney failure who return to dialysis. REFERENCES 1. Arias M, Escallada R, de Francisco AL, et al: Return to dialysis after renal transplantation. Which would be the best way? Kidney Int Suppl 61:85, 2002 2. Gill JS, Abichandani R, Kausz AT, et al: Mortality after kidney transplant failure: the impact of non-immunologic factors. Kidney Int 62:1875, 2002 3. Gill JS, Abichandani R, Khan S, et al: Opportunities to improve the care of patients with kidney transplant failure. Kidney Int 61:2193, 2002 4. López-Gómez JM, Pérez-Flores I, Jofré R, et al: Presence of a failed kidney transplant in patients who are on hemodialysis is associated with chronic inflammatory state and erythropoietin resistance. J Am Soc Nephrol 15:2494, 2004 5. Marcen R, Teruel JL: Patient outcomes after kidney allograft loss. Transplantation Rev 22:62, 2008