Biology of Blood and Marrow Transplantation
Volume 14, Issue 4 , Pages 403-408, April 2008

Chronic Kidney Disease after Nonmyeloablative Stem Cell Transplantation in Adults

  • Sabina Kersting

      Affiliations

    • Corresponding Author InformationCorrespondence and reprint requests: Sabina Kersting, MD, Department of Hematology, B02.226, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
    • ,
  • Leo F. Verdonck

Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands

Received 18 December 2007; accepted 26 December 2007.

Article Outline

Abstract 

Chronic kidney disease (CKD) after myeloablative stem cell transplantation (SCT) is a well-established problem. Little is known about CKD after nonmyeloablative SCT. We performed a retrospective cohort study of 108 adults who received nonmyeloablative SCT with fludarabine and/or total-body irradiation (TBT) conditioning. Renal function was assessed by estimating glomerular filtration rate (GFR) with the MDRD equation. CKD was defined as GFR <60 mL/min/1.73 m2. CKD developed in 15% of patients after a median of 15 months. None of the patients required dialysis. Cumulative incidence of CKD was 7% at 12 months, 14% at 24 months, and 22% at 48 months. Risk factors for CKD were female sex (P = .021), older age (P = .040), and lower GFR pretransplant (P < .001). Complications after SCT were not associated with CKD. SCT nephropathy, a cause of CKD after myeloablative SCT, did not occur. Overall survival (OS) was 66%. There was no difference in survival between patients with or without CKD. In conclusion, CKD is a frequent complication after nonmyeloablative SCT and is not related to SCT nephropathy. Women, patients above 50 years of age, and patients with slightly decreased kidney function pretransplant have the greatest risk of development of CKD.

Key Words: Chronic kidney disease, Hematopoietic stem cell transplantation, Stem cell transplantation nephropathy, Survival

 

Back to Article Outline

Introduction 

Because treatment-related morbidity and mortality (TRM) limit the success of myeloablative stem cell transplantation (SCT), a nonmyeloablative SCT regimen was developed. This regimen would be suitable for patients of older age and also for patients with comorbid conditions who were not eligible for myeloablative SCT [1]. Differences between myeloablative and nonmyeloablative conditioning are a reduction in intensities of both chemotherapy and total-body irradiation (TBI) in the nonmyeloablative approach. Because patients' characteristics and transplant procedures are different in the 2 regimens, it is likely that transplant-related organ dysfunction after transplantation will be different also.

Chronic kidney disease (CKD) after myeloablative SCT is a well-established problem. Incidence of CKD after myeloablative SCT ranges between 7% and 66%, dependent on different definitions that were used 2, 3, 4, 5, 6, 7, 8, 9. Two recent large studies showed an incidence of CKD (defined according to Kidney Disease Outcomes Quality Initiative [K/DOQI] as an estimated glomerular filtration rate [GFR] of <60 mL/min/1.73 m2 for more than 3 months) [10] after myeloablative SCT of 22.3% and 23%, respectively 11, 12. Detection of patients with CKD is important, because these patients have adverse outcomes, such as kidney failure, cardiovascular disease, and premature death, which can be prevented or delayed by interventions [10]. A subset of patients with CKD after myeloablative SCT has a thrombotic microangiopathic syndrome known as SCT nephropathy, radiation nephritis, or conditioning-associated homolytic uremic syndrome, wherein TBI is the most probable cause 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24. These patients have a higher risk for development of end-stage renal disease with increased mortality 3, 12. Because TBI dose is lower in nonmyeloablative SCT, the development of CKD might be less. However, patients receiving nonmyeloablative transplants are usually older, and renal function declines with age [25], which may increase the incidence of CKD after nonmyeloablative SCT.

Until now, only 1 study describes chronic renal dysfunction after nonmyeloablative SCT, with an incidence of 66% defined by reduction of GFR of at least 25% from baseline [26]. How many of these patients have a GFR <60 mL/min/1.73 m2 (K/DOQI definition of CKD) is not clear from this study. This particular cutoff is important because of the increased prevalence of hypertension, anemia, derangements in calcium-phosphorous metabolism, reduction in serum albumin, and reductions in functional status that occur below this cutoff [10].

The aim of the present study was to evaluate the prevalence of CKD (defined as a GFR <60 mL/min/173 m2) and to analyze risk factors of CKD in a large cohort. Moreover, we wanted to study whether CKD influenced survival.

Back to Article Outline

Patients and Methods 

Patients 

Between September 1, 2001, and October 1, 2005, nonmyeloablative SCT was performed in 150 adults aged 20-69 years, at the Department of Hematology of the University Medical Center Utrecht. Because the primary outcome of this study was CKD, we excluded patients with a survival of <6 months (n = 24) or with a GFR ≤60 mL/min/1.73 m2 (n = 18) within 1 month prior to transplantation. Patients gave informed consent and were treated according to clinical protocols approved by the local ethics review board.

Methods 

Of the 108 remaining patients, data were collected and analyzed retrospectively using a database and patient records through December 1, 2006. The following baseline variables were noted: sex, age, history of autologous transplantation, history of hypertension (defined as a blood pressure ≥140/80 mmHg or receiving antihypertensive medication), history of vascular disease (angina pectoris, myocardial infarction, cerebrovascular event, and diabetes mellitus), diagnosis of hematologic disease, malignancy risk (low risk malignancy: patients with acute leukemia in the first complete remission, chronic myelogenous leukemia (CML) in the first chronic phase, and untreated severe aplastic anemia (AA); high-risk malignancy: all other hematologic diseases), type of transplant (matched related donor, partially matched-related donor, matched-unrelated donor), and conditioning regimen.

Serum creatinine was noted at 6 months, 8 months, 12 months, 18 months, and 24 months, and thereafter annually. Renal function was assessed by estimating GFR with the simplified Modification of Diet in Renal Disease Study prediction equation: GFR = 186.3 × (serum creatinine)−1.154 × age−0.203 × (0.742 for women) [10]. CKD was defined according to the K/DOQI definition of kidney disease. Stage 3 CKD was an estimated GFR <60 mL/min/1.73 m2, stage 4 CKD was a GFR <30 mL/min/1.73 m2, and stage 5 CKD was a GFR <15 mL/min/1.73 m2 or need for dialysis [10]. Only if low GFR persisted until death or last follow-up was the patients defined as having CKD.

Acute renal failure was defined as occurrence of renal dysfunction within 100 days after transplantation. Acute renal failure was categorized as follows: grade 0 (or normal renal function) was equivalent to a decrease in estimated GFR of <25% of the value at time of transplantation. Grade 1 corresponded to a <2-fold rise in serum creatinine concentration, with a decrease in estimated GFR of >25% of the value at time of transplantation. Grade 2 corresponded to a >2-fold rise in serum creatinine, without indication for dialysis. Grade 3 corresponded to patients with grade 2 parameters but requiring dialysis. This classification of grades of acute renal failure is similar to other studies on acute renal failure after SCT 26, 27, 28.

Nephrotic syndrome was defined as a urinary protein excretion >3.5 g/24 hours and hypoalbuminemia with plasma levels <3 g/dL.

The following variables posttransplantation were registered until last follow-up or death: acute and chronic graft-versus-host disease (aGVHD, cGVHD), cytomegalovirus (CMV) reactivation, admission to intensive care unit (ICU), hypertension (defined as a blood pressure ≥140/80 mmHg or receiving antihypertensive medication), and cyclosporine trough levels.

SCT Procedure 

The nonmyeloablative conditioning regimen consisted of fludarabine (30 mg/m2/day for 3 days) followed by TBI of 200 cGy (n = 76) or TBI alone (n = 32). The graft was infused after TBI on day 0. In recipients of a histocompatibility leukocyte antigen (HLA)-matched unrelated donor or a single HLA-antigen mismatched family donor, antithymocyte globulin (Rabbit ATG, Thymoglobulin™, Genzyme, Cambridge, MA) was given before fludarabine was infused, at a dose of 2 mg/kg/day for 4 days (n = 41). All patients received GVHD prophylaxis orally with cyclosporine and mycophenolate mofetil (MMF). Cyclosporine was started on day −3 at 4.5 mg/kg twice daily and continued until day +84 (n = 66) or +120 (n = 42), followed by tapering if no GVHD was present. Dose adjustments were made to keep cyclosporine trough levels between 200 ng/mL and 400 ng/mL. Moreover, cyclosporine dose was lowered when creatinine rise was caused by cyclosporine, at the discretion of the physician. MMF was started 5 hours after graft infusion at 15 mg/kg/day, with a maximum dose of 3 g/day until day +28 (n = 66) or +84 (n = 42), followed by tapering if no GVHD was present. GVHD was diagnosed according to the Seattle criteria [29]. aGVHD grade I was treated with topical corticosteroids. aGVHD grade II or higher was treated with high-dose systemic corticosteroids. Limited cGVHD was not treated and extensive cGVHD was treated with cyclosporine, systemic or topical corticosteroids, MMF, or a combination of these drugs.

Infection prevention consisted of ciprofloxacin and fluconazole, given orally, until granulocyte counts exceeded 500 cell/μL. Co-trimoxazol 480 mg twice daily was given for 15 months and valacyclovir 500 mg twice daily was given for 12 months, both orally.

Statistical Analysis 

Continuous variables are displayed as the median, with the range in parentheses. For dichotomous variables, the frequency of occurrence is given along with the corresponding percentage. For comparison of characteristics between groups, a chi-square test was used to compare proportions, and 2-sided Student's t-test to compare continuous outcomes.

Those parameters reaching a univariable significance level of P ≤ .1 were assessed for significance using multiple logistic regressions. Kaplan-Meier survival curves were made for overall survival (OS). Curves were compared with a log-rank test. All P-values were 2 sided, and a value of <.05 was considered statistically significant. Analysis was performed using SPSS version 12.0 (SPSS Inc., Chicago, IL).

Competing risk data were used to make a cumulative incidence for CKD, wherein outcome is CKD, competing risk is death without CKD, and time variable is time to CKD, death, or last follow-up, whichever was first. This analysis was performed using a R-library for multistate models and SPSS version 15.0 [30].

Back to Article Outline

Results 

CKD stage 3 (GFR <60 mL/min/1.73 m2) developed in 14 patients (13%) and CKD stage 4 (GFR <30 mL/min/1.73 m2) developed in 2 patients (2%) after a median of 15 months (range: 1-48 months). None of the patients required dialysis. Median follow-up for surviving patients was 29 months (range: 15-61). Cumulative incidence of CKD was 7% at 12 months, 14% at 24 months, 16% at 36 months, and 22% at 48 months (Figure 1). OS was 66% at 48 months. There was no difference in survival between patients with and without CKD.

Pretransplant risk factors for CKD stage 3 and 4 were female sex (P = .021), older age (P = .040), and lower GFR 1 month prior to SCT (P < .001) (Table 1). Patients older than 60 years (n = 30), patients between 50 and 59 years (n = 48), and patients between 40 and 49 years (n = 20) developed CKD in 17%, 21%, and 5%, respectively. None of the patients younger than 40 years (n = 10) developed CKD. Patients with GFR <90 mL/min/1.73 m2 (n = 47) progressed to CKD in 23% of cases, patients with GFR between 90 and 120 mL/min/1.73 m2 (n = 43) progressed to CKD in 12% of cases. None of the patients with GFR >120 mL/min/1.73 m2 developed CKD. In multivariate analysis only lower GFR 1 month prior to SCT was associated with CKD stage 3 and 4 (P = .027, odds ratio 0.96, 95% confidence interval 0.924-0.995). Diagnosis, high-risk malignancy, type of transplant, conditioning regimen and a history of hypertension, autologous transplantation, or vascular disease did not differ between patients with or without CKD stage 3 and 4.

Table 1. Risk Factors and Outcome of Patients with and without Chronic Kidney Disease (CKD)
All Patients (%)CKD Grade 3 or 4no CKDPMultivariate OR (95% CI)
Sex .021
Male70 (64.8)6 (37.5)64 (69.6)
Female38 (35.2)10 (62.5)28 (30.4)
Age55 (20-66)55.5 (44-65)55 (20-66).04
History
Autologous46 (42.6)8 (50.0)38 (41.3)ns
Hypertension (>140/90 mmHg)43 (39.8)10 (62.5)33 (35.9)ns
Vascular disease10 (9.3)2 (12.5)8 (8.7)
Diagnosis ns
Acute myelogenous leukemia17 (15.7)0 (0)17 (18.5)
Acute lymphoblastic leukemia4 (2.7)1 (6.3)3 (3.3)
Chronic myelogenous leukemia4 (2.7)1 (6.3)3 (3.3)
Severe aplastic anemia4 (3.7)0 (0)4 (4.3)
Multiple myeloma48 (44.4)9 (56.3)39 (42.4)
Other31 (28.7)5 (31.3)26 (28.3)
Malignancy risk ns
High risk87 (80.6)14 (87.5)73 (79.3)
Low risk21 (19.4)2 (12.5)19 (20.7)
Type of transplant ns
Matched related donor70 (64.8)8 (50.0)62 (67.4)
Partially matched related donor7 (6.5)2 (12.5)5 (5.4)
Matched unrelated donor31 (28.7)6 (37.5)25 (27.2)
Mismatch15 (13.9)4 (25.0)11 (12.0)
Conditioning ns
Fludarabine/TBI35 (32.4)2 (12.5)33 (35.9)
Fludarabine/TBI/ATG41 (38.0)8 (50.0)33 (35.9)
TBI32 (29.6)6 (37.5)26 (28.3)
Renal function
Estimated GFR -1 month94 (62-156)81.5 (62-102)99 (63-156)<.0010.96 (0.924-0.995)
Estimated GFR baseline87 (61-187)76 (66-120)88.5 (61-187)ns
Creatinine -1month73 (48-129)77 (58-112)72.5 (48-129)ns
Creatinine baseline77 (47-112)77 (57-101)77 (47-112)ns
Immune suppression ns
Cyclosporine until + 84 days66 (61.1)9 (56.3)57 (62.0)
Cyclosporine until + 120 days42 (38.9)7 (43.8)35 (38.0)
Complications
Acute renal failure32 (29.6)6 (37.5)26 (28.3)ns
Nephrotic syndrome3 (2.8)0 (0)3 (3.3)ns
Hypertension within 100 days30 (27.8)5 (31.3)25 (27.2)ns
Chronic hypertension30 (27.8)5 (31.3)25 (27.2)ns
CMV reactivation11 (10.2)2 (12.5)9 (9.8)ns
ICU admission5 (4.6)1 (6.3)4 (4.3)ns
Acute GVHD grade 0-I63 (58.3)8 (50.0)55 (59.8)ns
Acute GVHD grade II33 (30.6)6 (37.5)27 (29.3)ns
Acute GVHD III-IV12 (11.1)2 (12.5)10 (10.9)ns
Chronic GVHD limited10 (10.9)0 (0)10 (9.3)ns
Chronic GVHD extensive49 (45.4)7 (43.8)42 (45.7)ns
Hb at 12 months8.3 (5.0-10.5)8.0 (5.0-10.4)8.6 (5.8-10.5).036
Cyclosporine trough level >400 ng/mL54 (50.9)8 (50.0)46 (51.1)ns
Outcome ns
Alive86 (79.6)14 (87.5)72 (73.3)
Deceased22 (20.4)2 (12.5)20 (21.7)

TBI indicates total-body irradiation; ATG, antithymocyte globulin; GFR-1month, glomerular filtration rate 1 month prior to SCT in mL/min/1.73 m2. Median (range); Creatinine-1 months, creatinine 1 month prior to SCT in μmmol/L. Median (range); CMV, cytomegalovirus; ICU, intensive care unit; GVHD, graft-versus-host disease; Hb, hemoglobin in mmol/L. Median (range).

None of the complications after SCT was associated with CKD (Table 1). Moreover, immune suppression regimen (cyclosporine until day +84 and MMF until day +28 or cyclosporine until day +120 and MMF until day +84), cyclosporine trough levels, or long-term cyclosporine use in the case of cGVHD did not differ between the groups with or without CKD. Three patients developed nephrotic syndrome, but none of them developed CKD. No patient developed thrombotic thrombocytopenic purpura, sinusoidal occlusion syndrome, or SCT nephropathy. Patients who developed CKD had significantly lower hemoglobin (Hb) at 12 months than patients who did not (Hb 8.0 mmol/L, range: 5.0-10.4 versus Hb 8.6 mmol/L, range: 5.8-10.5, P = .036).

Back to Article Outline

Discussion 

In this large single-center cohort of recipients of nonmyeloablative SCT, 15% of patients developed CKD after a median follow-up of 29 months. This is higher compared to the general population of the same age, where CKD is present in <10% [31]. The cumulative incidence of CKD was 22% at 48 months, which is slightly higher than a cumulative incidence of CKD of 20% at 5 years seen after myeloablative SCT at the same institution [12]. The most likely rationale for this is that patients who develop CKD despite nonmyeloablative conditioning regimen are of older age and/or have more comorbidities.

The strongest risk factor for the development of CKD was lower estimated GFR 1 month prior to SCT in multivariate analysis. This was similar to our previous study regarding CKD after myeloablative SCT [12]. Also, in community-based population studies, mildly reduced GFR is a predictor for the development of kidney disease [32]. Suboptimal kidney function therefore seems to predispose for CKD. Critical evaluation of kidney function before SCT and adequate treatment of risk factors for CKD (eg, hypertension and diabetes) seems a logical approach for these vulnerable patients.

A second risk factor for CKD was older age in univariate analysis. This was also found in studies on CKD after myeloablative SCT 5, 12. Cross-sectional community studies showed progressive decline in renal function with aging 25, 32. Renal aging is a natural phenomenon with a course that is dependent on a combination of genetic and environmental factors [33]. The nonmyeloablative conditioning before transplantation, and the immune suppression regimen or infection prophylaxis used posttransplantation, are candidate factors that progress the renal aging process.

A third risk factor for CKD was female sex in univariate analysis. This was also found in our earlier study on CKD after myeloablative SCT [12]. Also, studies in the general population showed a higher incidence of CKD for women than for men 31, 32, a reason to modify the cutoff value for CKD for women in 1 study [32]. Awareness of CKD in women is lower, which might be caused by overlooking CKD in older women, who often have a serum creatinine that is in the normal range for younger individuals [34].

Acute renal failure after nonmyeloablative SCT was not associated with increased risk for CKD, in contrast to previous studies 11, 26. Our system of frequent monitoring of serum creatinine and performing dose reductions of nephrotoxic medication in the case of an acute rise in creatinine might prevent irreversible renal damage in those patients. Cyclosporine use did not influence the occurrence of CKD. It is known that chronic cyclosporine use contributes to CKD in patients after heart and lung transplantation [35]. Acute cyclosporine injury is usually reversible [36], but there is also evidence that chronic cyclosporine nephrotoxicity has reversible components [37]. Using cyclosporine only for restricted periods and monitoring of trough levels seems to be a safe method to prevent cyclosporine nephrotoxicity in patients after SCT. Also, cGVHD was not a risk factor for CKD, in contrast to other studies 4, 11, 26. The postulated independent role in development of CKD for cGVHD with chronic inflammation and cyclosporine use therefore could not be confirmed by our study [17].

No patient developed SCT nephropathy, which is in line with results of a previous study after nonmyeloablative SCT [26]. The low dose of TBI in nonmyeloablative SCT in comparison with myeloablative SCT may account for this.

The mechanisms by which CKD is caused after nonmyeloablative SCT are still unknown, but a thrombotic microangiopathic syndrome caused by radiation is very unlikely. A combination of factors (eg, chemotherapy, TBI, nephrotoxic medication, and GVHD) might cause CKD in susceptible patients because they are of older age, have female sex, or, most important, have decreased kidney function.

Patients with CKD had slightly lower hb levels compared to patients without CKD. This is as expected, and underscores the importance of identifying patients with GFR <60 mL/min/1.73m2 because of increased morbidity under this cutoff value [10].

Finally, survival was not influenced by CKD in this cohort. The reason for this might be that follow-up was still too short for development of late complications of CKD.

In conclusion, CKD is a frequent complication after nonmyeloablative SCT. Women, patients above 50 years of age, and patients with slightly decreased kidney function pretransplant have the greatest risk of development of CKD. Multiple factors are thought to influence the development of CKD, but the exact mechanism needs further study.

Back to Article Outline

Acknowledgments 

We thank Dr. R. Brand, PhD, of the Department of Medical Statistics in Leiden, for assistance with statistical analysis. We are also grateful to M.I. Gerrits, J. vd Giessen, and Suzanne v Dorp, MD (Department of Hematology, University Medical Centre, Utrecht) for providing data.

Back to Article Outline

References 

  1. Niederwieser D, Maris M, Shizuru JA, et al. Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood. 2003;101:1620–1629
  2. Borg M, Hughes T, Horvath , et al. Renal toxicity after total body irradiation. Int J Radiat Oncol Biol Phys. 2002;54:1165–1173
  3. Cohen EP, Piering WF, Kabler-Babbitt C, Moulder JE. End-stage renal disease (ESRD) after bone marrow transplantation: poor survival compared to other causes of ESRD. Nephron. 1998;79:408–412
  4. Deconinck E, Kribs M, Rebibou JM, et al. Cytomegalovirus infection and chronic graft-versus-host disease are significant predictors of renal failure after allogeneic hematopoietic stem cell transplantation. Haematologica. 2005;90:569–570
  5. Delgado J, Cooper N, Thomson K, et al. The importance of age, fludarabine, and total body irradiation in the incidence and severity of chronic renal failure after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2006;12:75–83
  6. Imai H, Oyama Y, Miura AB, et al. Hematopoietic cell transplantation-related nephropathy in Japan. Am J Kidney Dis. 2000;36:474–480
  7. Leblond V, Sutton L, Jacquiaud C, et al. Evaluation of renal function in 60 long-term survivors of bone marrow transplantation. J Am Soc Nephrol. 1995;6:1661–1665
  8. Miralbell R, Bieri S, Mermillod B, et al. Renal toxicity after allogeneic bone marrow transplantation: the combined effects of total-body irradiation and graft-versus-host disease. J Clin Oncol. 1996;14:579–585
  9. Miralbell R, Sancho G, Bieri S, et al. Renal insufficiency in patients with hematologic malignancies undergoing total body irradiation and bone marrow transplantation: a prospective assessment. Int J Radiat Oncol Biol Phys. 2004;58:809–816
  10. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39:S1–S266
  11. Hingorani S, Guthrie KA, Schoch G, et al. Chronic kidney disease in long-term survivors of hematopoietic cell transplant. Bone Marrow Transplant. 2007;39:223–229
  12. Kersting S, Hené RJ, Koomans HA, Verdonck LF. Chronic kidney disease after myeloablative allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2007;13:1169–1175
  13. Chappell ME, Keeling DM, Prentice HG, Sweny P. Haemolytic uraemic syndrome after bone marrow transplantation: an adverse effect of total body irradiation?. Bone Marrow Transplant. 1988;3:339–347
  14. Cohen EP, Lawton CA, Moulder JE, et al. Clinical course of late-onset bone marrow transplant nephropathy. Nephron. 1993;64:626–635
  15. Cohen EP, Lawton CA, Moulder JE. Bone marrow transplant nephropathy: radiation nephritis revisited. Nephron. 1995;70:217–222
  16. Cohen EP. Radiation nephropathy after bone marrow transplantation. Kidney Int. 2000;58:903–918
  17. Hingorani S. Chronic kidney disease in long-term survivors of hematopoietic cell transplantation: epidemiology, pathogenesis, and treatment. J Am Soc Nephrol. 2006;17:1995–2005
  18. Juckett M, Perry EH, Daniels BS, Weisdorf DJ. Hemolytic uremic syndrome following bone marrow transplantation. Bone Marrow Transplant. 1991;7:405–409
  19. Kersting S, Verdonck LF. Stem cell transplantation nephropathy: a report of six cases. Biol Blood Marrow Transplant. 2007;13:638–643
  20. Lawton CA, Cohen EP, Barber-Derus SW, et al. Late renal dysfunction in adult survivors of bone marrow transplantation. Cancer. 1991;67:2795–2800
  21. Lawton CA, Barber-Derus SW, Murray KJ, et al. Influence of renal shielding on the incidence of late renal dysfunction associated with T-lymphocyte deplete bone marrow transplantation in adult patients. Int J Radiat Oncol Biol Phys. 1992;23:681–686
  22. Lawton CA, Cohen EP, Murray KJ, et al. Long-term results of selective renal shielding in patients undergoing total body irradiation in preparation for bone marrow transplantation. Bone Marrow Transplant. 1997;20:1069–1074
  23. Rabinowe SN, Soiffer RJ, Tarbell NJ, et al. Hemolytic-uremic syndrome following bone marrow transplantation in adults for hematologic malignancies. Blood. 1991;77:1837–1844
  24. Zenz T, Schlenk RF, Glatting G, et al. Bone marrow transplantation nephropathy after an intensified conditioning regimen with radioimmunotherapy and allogeneic stem cell transplantation. J Nucl Med. 2006;47:278–286
  25. Culleton BF, Larson MG, Evans JC, et al. Prevalence and correlates of elevated serum creatinine levels—the Framingham heart study. Arch Int Med. 1999;159:1785–1790
  26. Weiss AS, Sandmaier BM, Storer B, et al. Chronic kidney disease following non-myeloablative hematopoietic cell transplantation. Am J Transplant. 2006;6:89–94
  27. Parikh CR, McSweeney PA, Korular D, et al. Renal dysfunction in allogeneic hematopoietic cell transplantation. Kidney Int. 2002;62:566–573
  28. Parikh CR, McSweeney P, Schrier RW. Acute renal failure independently predicts mortality after myeloablative allogeneic hematopoietic cell transplant. Kidney Int. 2005;67:1999–2005
  29. Thomas ED, Storb R, Clift RA, et al. Bone-marrow transplantation (second of two parts). N Engl J Med. 1975;292:895–902
  30. Putter H, Fiocco M, Geskus RB. Tutorial in biostatistics: competing risks and multi-state models. Stat Med. 2007;26:2389–2430
  31. Coresh J, Astor BC, Greene T, et al. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: third National Health and Nutrition Examination Survey. Am J Kidney Dis. 2003;41:1–12
  32. Fox CS, Larson MG, Leip EP, et al. Predictors of new-onset kidney disease in a community-based population. JAMA. 2004;291:844–850
  33. Buemi M, Nostro L, Aloisi C, et al. Kidney aging: from phenotype to genetics. Rejuvenat Res. 2005;8:101–109
  34. Coresh J, Byrd-Holt D, Astor BC, et al. Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000. J Am Soc Nephrol. 2005;16:180–188
  35. Bloom RD, Doyle AM. Kidney disease after heart and lung transplantation. Am J Transplant. 2006;6:671–679
  36. Gruss E, Bernis C, Tomas JF, et al. Acute renal failure in patients following bone marrow transplantation: prevalence, risk factors and outcome. Am J Nephrol. 1995;15:473–479
  37. Tedoriya T, Keogh AM, Kusano K, et al. Reversal of chronic cyclosporine nephrotoxicity after heart transplantation-potential role of mycophenolate mofetil. J Heart Lung Transplant. 2002;21:976–982

PII: S1083-8791(08)00005-0

doi:10.1016/j.bbmt.2007.12.495

Biology of Blood and Marrow Transplantation
Volume 14, Issue 4 , Pages 403-408, April 2008

Article Tools

* Image Usage & Resolution