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1.
Predictors and significance of kidney dysfunction in patients with chronic graft-versus-host disease
Beshensky, D., Pirsl, F., Holtzman, N. G., Steinberg, S. M., Mays, J. W., Cowen, E. W., Comis, L. E., Joe, G. O., Magone, M. T., Schulz, E., et al
Bone marrow transplantation. 2023
Abstract
Kidney complications have been studied in allogeneic hematopoietic stem cell transplant patients but not specifically among chronic graft-versus-host disease (cGVHD) patients. Participants (n = 365) enrolled in the cross-sectional cGVHD natural history study (NCT00092235) were assessed for kidney dysfunction and overall survival. Kidney dysfunction was analyzed for associations in univariate and multivariable analyses. Kidney dysfunction (eGFR < 60) was found in 64 patients, and 29 patients had moderate-severe kidney dysfunction (eGFR < 45). Patients with kidney dysfunction were more likely treated with cyclosporine at evaluation or to have received it for GVHD prophylaxis, or prior treatment of GVHD. Patients with kidney dysfunction were less severely affected by cGVHD of skin, mouth, and joints/fascia. In multivariable modeling, history of cyclosporine use (OR = 2.19, 95% CI 1.13-4.25), angiotensin receptor blocker use (OR = 5.57, 95% CI 1.49-20.84), proteinuria (OR = 2.39, 95% CI 1.19-4.79), lower CRP (OR = 0.95, 95% CI 0.91-0.99), lower C3 (OR = 0.98, 95% CI 0.97-0.99), and lower hemoglobin (OR = 0.70, 95% CI 0.58-0.84) were jointly associated with kidney dysfunction. Overall survival was lower in those with moderate-severe kidney dysfunction (p = 0.015), demonstrating the importance of addressing kidney dysfunction in this population. The association of kidney dysfunction with less severe cGVHD suggests an etiology unrelated to cGVHD but potentially a consequence of drug-related toxicities.
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2.
The prevalence of anemia in people with chronic kidney disease after hematopoietic stem cell transplantation
Kępska-Dzilińska, M., Karakulska-Prystupiuk, E., Kaszyńska, A., Basak, G. W., Małyszko, J.
Renal failure. 2023;45(2):2263581
Abstract
The hematopoietic stem cell transplantation (HSCT) is performed for various hematological diseases. Chronic kidney disease (CKD) occurs relatively often after HSCT. Anemia after HSCT may be due to CKD and/or other reasons. The aim of this study is to assess the prevalence of anemia and its possible relationship to the presence of CKD in patients at least 3 months after HSCT. The study included 156 patients who underwent allogeneic HSCT treatment in our center in the years 1998 to 2021 due to different hematologic pathologies (acute myeloid leukemia, acute lymphoblastic leukemia, lymphoma, and others). Anemia was diagnosed in 13% of women and 35% of men. Anemia was most common in people after HSCT due to a history of acute myeloid leukemia (55% women, 30% men). In 56% of women and 17% of men, anemia was associated with chronic kidney disease. In patients with anemia, age was related to the eGFR (r = -0.39, p < 0.001), in patients without anemia age was negatively related to eGFR (r = -0.56, p < 0.001), and hemoglobin was positively related to platelet count (r = 0.62, p < 0.001). Concluding, anemia, was relatively common in CKD after HSCT. In CKD, in particular with coexistent anemia, nephrology referral is to be taken into account to optimize therapy, including nephroprotection.
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3.
Chronic kidney disease, survival and graft-versus-host-disease-free/relapse-free survival in recipients of allogeneic hematopoietic stem cell transplant
Pelletier, K., Côté, G., Madsen, K., Chen, S., Kim, S. J., Chan, C. T., Mattsson, J., Pasic, I., Kitchlu, A.
Clinical kidney journal. 2022;15(8):1583-1592
Abstract
BACKGROUND Advances in allogeneic hematopoietic stem cell transplant (HSCT) have increased patient survival, although substantial treatment-related toxicity remains, including chronic kidney disease (CKD). We assessed the association between CKD and survival and transplant-specific outcomes in HSCT recipients. METHODS We conducted a retrospective study of all 408 adult patients with allogenic HSCT at Princess Margaret Cancer Centre (Toronto, Canada, 2015-18). We used logistic regression to identify risk factors for CKD at 1 year post-transplant. Associations between CKD at 1 year and overall survival, relapse-free survival, graft-versus-host-disease (GVHD)-free/relapse-free survival, relapse and transplant-related mortality were examined using extended time-varying Cox models. In a sensitivity analysis, we restricted the cohort to survivors at 1 year, using standard Cox proportional hazard models to examine associations between CKD and overall survival, relapse-free survival and GVHD-free/relapse-free survival, and Fine and Gray's competing risk models to determine associations between CKD and relapse/transplant-related mortality. RESULTS The prevalence of CKD at 1 year was 19% (46 patients) with median follow-up of 23 months. Multivariable regression identified age at transplant [adjusted OR (aOR) 1.09, 95% confidence interval (95% CI) = 1.05-1.14; P < 0.0001), female gender (aOR 2.83, 95% CI = 1.34-5.97; P = 0.006) and acute kidney injury during the first 100 days (aOR 3.86, 95% CI = 1.70-8.73; P = 0.001) as risk factors for CKD at 1 year. Patients with CKD at 1 year had significantly poorer overall survival than those without CKD, when adjusted for relevant covariates [adjusted HR (aHR) 1.93, 95% CI = 1.02-3.66; P = 0.04 in the time-varying Cox model, and aHR 2.06, 95% CI = 1.04-4.07; P = 0.04 using the standard Cox model]. CKD at 1 year was also associated with worse GVHD-free/relapse-free survival (aHR 1.65, 95% CI = 1.04-2.61; P = 0.03). CONCLUSIONS CKD adversely affects the long-term prognosis for allogeneic HSCT recipients, with increased mortality risk and worse GVHD-free/relapse-free survival.
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4.
BK viremia and changes in eGFR in children and young adults after hematopoietic cell transplantation
Wychera, C., Imlay, H. N., Duke, E. R., Faino, A., Li-Huang, M., Stevens-Ayers, T., Davis, C., Lange-Sperandio, B., Mallhi, K. K., Hill, J. A., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND AND OBJECTIVES Kidney disease in allogeneic hematopoietic cell transplant (HCT) recipients is associated with increased mortality rates. BK virus (BKV) viremia has been associated with kidney dysfunction in pediatric HCT recipients, however, few studies have investigated longer-term kidney outcomes in association with BKV in this population. We assessed the relationship between BK viremia and changes in estimated glomerular filtration rate (eGFR) in children in the first year post-HCT. STUDY DESIGN We selected 136 patients ≤26 years old who underwent HCT from 2007-2018 at a single center and had plasma BK viral load data available at two time points: weeks 4-7 post-HCT and weeks 10-13 post-HCT from prospectively collected, stored plasma samples. Altogether, 272 samples were analyzed for BKV using quantitative PCR. We used multivariate linear models to determine the association of BK viremia and change in eGFR by one-year post-HCT. RESULTS Forty percent of patients (54/136) had BKV detection in weeks 4-7, 13% of whom (7/54) had BK viral loads of ≥10,000 copies/mL, and 46% (62/136) had BKV detection in weeks 10-13, 34% (21/62) of whom had BK viral loads of ≥10,000 copies/mL. The mean decline in eGFR was 25.73 mL/min/1.73m(2) by one-year post-HCT. In multivariate models, BK viral loads of ≥10,000 copies/mL during weeks 4-7 were associated with a mean decline in eGFR of 30.6 mL/min/1.73m(2) (95% CI: -55.94, -5.17; p=0.019) when compared to BK viral loads <10,000 copies/mL. CONCLUSIONS In adjusted analyses, high BK viral loads in the blood (≥10,000 copies/mL) were associated with a significant decline in eGFR by one-year post-HCT.
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5.
Kidney Disease After Allogeneic Hematopoietic Stem Cell Transplantation Is Associated With Decreased Physical Function
Hirano, Y., Hanajima, W., Yamauchi, K.
Transplantation proceedings. 2022
Abstract
OBJECTIVE/BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved outcomes and prognosis, but it has many complications and is associated with impaired physical function. To solve this problem, it is necessary to further analyze the factors that cause the decline in physical function. In the present study, we hypothesized that kidney disease following allo-HSCT would be associated with impaired physical function, in addition to conventional factors, and tested this hypothesis retrospectively. METHODS Thirty-one patients who underwent allo-HSCT at the Department of Hematology in our hospital from January 2016 to October 2021 were included in the analysis. Correlation analysis and stepwise multiple regression analysis with change in 30-second sit to stand test (Δ30-s STS) as the dependent variable were performed to identify predictors of physical function decline from pretransplant to discharge. RESULTS The mean age of participants was 43.9 years (SD = 11.8), the mean time from transplant to discharge was 103.1 days (SD = 35.0), and approximately 30% of patients had kidney disease following allo-HSCT. All patients were ambulatory and independent at discharge, but 30-s STS was significantly reduced (P < .001). Among various factors, age (β = -0.464, P < .05), total corticosteroid dose (β = -0.380, P < .05), and kidney disease after allo-HSCT (β = -0.307, P < .05) were the independent predictors of Δ30-s STS (R(2) = 0.592, adjusted R(2) = 0.547, F = 13.072, P < .01). CONCLUSION Kidney disease after allo-HSCT is one of the factors that may contribute to poor physical function, and patients who experience this condition may require additional follow-up to improve physical function.
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6.
Chronic Kidney Disease in Patients After Allogeneic Hematopoietic Cell Transplant
Kępska-Dzilińska, M., Chomicka, I., Karakulska-Prystupiuk, E., Tomaszewska, A., Basak, G. W., Malyszko, J.
Transplantation proceedings. 2022
Abstract
Hematopoietic stem cell transplant (HSCT) is used in advanced hematologic diseases to restart the immune system. Kidney damage remains significant complication of hematopoietic cell transplant (HCT) affecting the mortality of transplant recipients. The aim of the study was to assess the advancement of chronic kidney disease (CKD) in patients after HSCT. We studied 150 patients who underwent allo-HSCT treatment in our center in years 1995 to 2020 because of acute myeloid leukemia in 47% of patients, acute lymphoblastic leukemia in 19%, and lymphoma in 32%. The mean age of patients with acute leukemia is 48 years (including acute myeloid leukemia it is 47 years, and including acute lymphoblastic leukemia it is 32 years). The mean age of lymphoma patients is 34 years. We studied the prevalence and stages of CKD. CKD stage 3a and 3b was found in 24.6%. None of the patients studied had CKD stage 4 or 5. In patients after HSCT because of both acute myeloid leukemia and acute lymphoblastic leukemia, CKD stage 3a was found in 19% and stage 3b in 7.3%. Estimated glomerular filtration rate (eGFR) >90 mL/min/1.73 m(2), was found in 36.8% of this population, whereas eGFR between 90 and 60 mL/min/1.73 m(2) was observed in 36.8%. In patients with lymphoma who underwent HSCT, CKD stage 3a was found in 18%, while CKD stage 3b was diagnosed in 27% of the patients. An eGFR >90 mL/min/1.73 m(2), was found in 27% of this population, whereas eGFR between 90 and 60 mL/min/1.73 m(2) was observed in 27% of patients. The categorization of patients according to the underlying disease is important because other drugs are used in therapy of conditioning before HCT. CKD in patients after allogeneic HSCT is common, although advanced stages were not observed, probably because the age of the population studied was not advanced. CKD in these vulnerable patients may be because of prior chemotherapy, conditioning regimen, post-HSCT calcineurin therapy, and other possible nephrotoxic drugs.
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7.
Increase Urinary Biomarkers of Kidney Injury in Patients After Allogenic Hematopoietic Stem Cell Transplant Reflect Kidney Damage Even in Normal Kidney Function
Kępska-Dzilińska, M., Chomicka, I., Karakulska-Prystupiuk, E., Tomaszewska, A., Basak, G. W., Żórawski, M., Małyszko, J.
Transplantation proceedings. 2022
Abstract
Kidney function in patients undergoing hematopoietic stem cell transplant (HSCT) is frequently worsened by previous chemotherapy and exposure to a variety of nephrotoxic drugs. The aim of the study was to assess biomarkers of kidney injury in patients at least 3 months after HSCT under ambulatory care of the Hematology, Oncology and Internal Medicine Department. We studied 80 prevalent patients after allogeneic HSCT and 32 healthy volunteers to obtain normal ranges for biomarkers. In this cross-sectional study, the following biomarkers of kidney injury in urine were evaluated using commercially available assays: IGFBP7 and TIMP2, netrin-1, and semaphorin A2. All of the biomarkers studied were significantly higher in patients after HSCT compared with the healthy volunteers. When we divided patients according to kidney function (below and over 60 mL/min/1.73m2), we found that only concentration of IGFBP7 was significantly higher in 23 patients with chronic kidney disease (CKD) stage 3 relative to patients with an estimated glomerular filtration rate (eGFR) over 60 mL/min/1.73m2. All biomarkers in both subgroups of patients with eGFRs below and over 60 mL/min/1.73m2 were significantly higher relative to healthy volunteers. In univariate correlations, semaphorin A2 was related to netrin-1 (r = 0.47, P < .001), IGFBP7 (r = 0.35, P < .01), and TIMP2 (r = 0.32, P < .01), whereas IGFBP7 was positively related to serum creatinine (r = 0.38, P < .001) and inversely to eGFR (r = -0.36, P < .001). Patients after allogeneic HSCT, despite normal or near normal kidney function, show evidence of kidney injury.
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8.
Teenagers and young adults with a past of allogenic hematopoietic stem cell transplantation are at significant risk of chronic kidney disease
da Silva Selistre, L., Renard, C., Bacchetta, J., Goutagny, M. P., Hu, J., Carla de Souza, V., Bertrand, Y., Dubourg, L., Domenech, C.
Pediatric nephrology (Berlin, Germany). 2021
Abstract
BACKGROUND Allogenic hematopoietic stem cell transplantation (aHSCT) remains the treatment of choice for some malignant hemopathies in children, albeit with the risk of long-term consequences, including chronic kidney disease (CKD). METHODS In our single tertiary referral center, we retrospectively assessed the long-term renal outcome in a cohort of children and adolescents who had undergone aHSCT for malignant hemopathies between 2003 and 2017. We distinguished glomerular and tubular dysfunctions and assessed the accuracy of the most common formula(s) to estimate glomerular filtration rate (GFR) during standard clinical follow-up. RESULTS Among the 166 patients who had received aHSCT, 61 underwent kidney functional assessment 1 to 10 years post-transplantation. Twenty-seven patients (44.3%) had a CKD with glomerular impairment, including 20 patients with a GFR?90 mL/min/1.73 m(2), and among these, 5 patients?60 mL/min/1.73 m(2). Patients with tubular signs had a significantly higher baseline GFR: 112 mL/min/1.73 m(2) [100; 120] versus 102 [99.0; 112.5] for patients without kidney involvement, and 76 [61; 86] for patients with CKD (p?0.01). Schwartz, CKiDU25, and EKFC formulas significantly overestimated mGFR, with a P30%?=?30%, which could lead to overlooking CKD diagnosis in this population. No patient reached kidney failure. CONCLUSIONS In conclusion, our study shows that CKD represents an important long-term sequela for children and adolescents who undergo aHSCT for malignant hemopathies, either with glomerular dysfunction or with the more insidious tubular dysfunction which could potentially impact growth. These patients could benefit from specialized long-term nephrology follow-up. A higher resolution version of the Graphical abstract is available as Supplementary information.
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9.
Significance of BK Polyomavirus in Long-Term Survivors after Adult Allogeneic Stem Cell Transplantation
Neumann, T., Peters, N., Kranz, J., Dräger, D. L., Heidel, F. H., Krüger, W., Schneidewind, L.
Biology. 2021;10(6)
Abstract
BACKGROUND Allogeneic stem cell transplantation (aSCT) is a common treatment for a variety of hematological diseases. Advances in transplantation practices have led to an increasing number of long-term aSCT survivors, but data about health status and late complications are sparse. This analysis focusses on kidney function and urological complications in this population. METHODS This study is a prospective unicentric non-interventional trial. Before starting the study, we obtained the approval of the local ethics review board. Furthermore, the study was registered at WHO Clinical Trial Registry. The study protocol is available via UTN. RESULTS We were able to include 33 patients with a mean age of 60.5 years (SD 11.1). The median survival time following allogeneic stem cell transplantation was 9.0 years (IQR 8.5-13.0). Five patients (15.2%) had BKPyV viruria with mean 218.3 (SD 674.2) copies/mL. BKPyV viruria was significantly linked to pre-existing chronic kidney failure (p = 0.019), creatine > 100 µmol/L (p < 0.001), and cystatin c > 1.11 mg/L (p = 0.021), respectively. We were not able to identify a single risk factor for BKPyV viruria in univariate or multivariate Cox regression. CONCLUSIONS BKPyV-associated nephropathy might be one reason for impaired kidney function in long-term survivors of aSCT.
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10.
Changes in Glomerular Filtration Rate and Impact on Long-Term Survival among Adults after Hematopoietic Cell Transplantation: A Prospective Cohort Study
Hingorani, S., Pao, E., Stevenson, P., Schoch, G., Laskin, B. L., Gooley, T., McDonald, G. B.
Clinical journal of the American Society of Nephrology : CJASN. 2018
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Abstract
BACKGROUND AND OBJECTIVES Kidney injury is a significant complication for patients undergoing hematopoietic cell transplantation (HCT), but few studies have prospectively examined changes in GFR in long-term survivors of HCT. We described the association between changes in GFR and all-cause mortality in patients up to 10 years after HCT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted a prospective, observational cohort study of adult patients undergoing HCT at the Fred Hutchinson Cancer Center in Seattle, Washington from 2003 to 2015. Patients were followed from baseline, before conditioning therapy, until a maximum of 10 years after transplant. We used Cox proportional hazard models to examine the association between creatinine eGFR and all-cause mortality. We used time-dependent generalized estimating equations to examine risk factors for decreases in eGFR. RESULTS A total of 434 patients (median age, 52 years; range, 18-76 years; 64% were men; 87% were white) were followed for a median 5.3 years after HCT. The largest decreases in eGFR occurred within the first year post-transplant, with the eGFR decreasing from a median of 98 ml/min per 1.73 m(2) at baseline to 78 ml/min per 1.73 m(2) by 1 year post-HCT. Two thirds of patients had an eGFR<90 ml/min per 1.73 m(2) at 1 year after transplant. When modeled as a continuous variable, as eGFR declined from approximately 60 ml/min per 1.73 m(2), the hazard of mortality progressively increased relative to a normal eGFR of 90 ml/min per 1.73 m(2) (P<0.001). For example, when compared with an eGFR of 90 ml/min per 1.73 m(2), the hazard ratios for eGFR of 60, 50, and 40 ml/min per 1.73 m(2) are 1.15 (95% confidence interval, 0.87 to 1.53), 1.68 (95% confidence interval, 1.26 to 2.24), and 2.67 (95% confidence interval, 1.99 to 3.60), respectively. Diabetes, hypertension, acute graft versus host disease, and cytomegalovirus infection were independently associated with a decline in GFR, whereas calcineurin inhibitor levels, chronic graft versus host disease, and albuminuria were not. CONCLUSIONS Adult HCT recipients have a high risk of decreased eGFR by 1 year after HCT. Although eGFR remains fairly stable thereafter, a decreased eGFR is significantly associated with higher risk of mortality, with a progressively increased risk as eGFR declines.