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1.
Patterns of Renal Dysfunction and Profile of Kidney Biopsies in Hematopoietic Stem Cell Transplant Recipients
John, E. E., Roy, S., Devasia, A. J., Karuppusami, R., Jose, N., Mani, S. S. R., Eapen, J. J., Yusuf, S., Thomas, A., Valson, A. T., et al
Glomerular diseases. 2023;3(1):98-115
Abstract
INTRODUCTION Post hematopoietic stem cell transplant (HSCT), kidney can be subjected to injury by various causes. Of these, graft versus host disease (GvHD) affecting the kidney is an under-recognized entity with no clear guidelines on its diagnosis, clinicopathological manifestations, and outcomes. MATERIAL AND METHODS Out of 2,930 patients who underwent HSCT at our center between 2005 and 2020, kidney biopsy was performed in 19 allogenic and 5 autologous recipients. RESULTS The mean age of the cohort at transplant was 33.2 ± 7 years, and 15 (62%) were males. Median time to kidney biopsy from HSCT was 14 (IQR, 9-30) months. Aplastic anemia was the most common underlying hematological disease (54.2%). All 19 allogenic recipients were classified based on clinicopathological manifestations into either thrombotic microangiopathy (TMA, 12/19 [63%]) or nephrotic syndrome (NS, 7/19 [37%]) pattern. Glomerular tuft "mesangiolysis" was the dominant pattern of injury noted in 9/12 cases of TMA pattern. There was a predominance of acute microangiopathic changes restricted primarily to the glomerular compartment. Of the 7 patients with NS pattern, membranous nephropathy was seen in 4 (57%) and minimal change disease in 3 (43%) patients. Thirty-nine percent (7/18) stained positive for C4d which was predominantly glomerular. Allogenic recipients who did not receive immunosuppression (IS) for renal disease had a lower eGFR at biopsy, a longer latency between withdrawal of GvHD prophylaxis and biopsy, and were significantly at a higher risk of kidney failure (IS: 2/11, 18.1% vs. no IS: 2/6, 33.3%, p = 0.04). "Associated extra-renal GvHD" occurred in 11/19 (57.9%) allogenic recipients. Patients with "associated extra-renal GvHD" had significantly more deaths (6/11, 60% vs. 0, p = 0.02) but comparable renal outcomes. CONCLUSION Renal GvHD can present with or without "associated extra-renal GvHD" after a prolonged period of withdrawal of GvHD prophylaxis, requiring careful diagnostic vigilance and consideration of IS.
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2.
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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3.
Comparison of clinical features of nephrotic syndrome after haploidentical and matched donor hematopoietic stem cell transplantation
Sun, W., Zhang, Y., Chen, Y., Sun, Y., Cheng, Y., Wang, F., Chen, H., Chen, Y., Yan, C., Mo, X., et al
Chinese medical journal. 2023
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4.
Clinico-pathological correlations and outcomes of de novo glomerular diseases in patients after haematopoietic stem cell transplantation
Yap, D. Y. H., Lie, D., Lau, T., Tang, A., Chan, G., Chan, T. S. Y., Sim, J., Lie, A. K. W., Chan, T. M.
Clinical kidney journal. 2023;16(6):976-984
Abstract
BACKGROUND Various glomerular pathologies have been reported in patients who have undergone haematopoietic stem cell transplantation (HSCT), but the data on clinico-pathological correlations and clinical outcome remain limited. METHODS We analysed the clinical and histopathological data of patients who had biopsy-proven de novo glomerular diseases after HSCT since 1999. RESULTS A total of 2204 patients underwent HSCT during the period 1999-2021, and 31 patients (1.4%) developed de novo glomerular diseases after a mean duration of 2.8 ± 2.7 years after HSCT. Fifteen of these patients (48.4%) had graft-versus-host-disease prior to or concomitant with renal abnormalities. Proteinuria and eGFR at the time of kidney biopsy were 4.1 ± 5.3 g/day and 50.8 ± 25.4 mL/min/1.73 m(2), respectively. Kidney histopathologic diagnoses included thrombotic microangiopathy (TMA) (38.7%), membranous nephropathy (MN) (25.8%), mesangial proliferative glomerulonephritis (12.9%), minimal change disease (9.7%), focal segmental glomerulosclerosis (9.7%) and membranoproliferative glomerulonephritis (3.2%). Immunosuppressive treatment was given to patients who presented with nephrotic-range proteinuria and/or acute kidney injury, while renin-angiotensin-aldosterone blockade was given to all patients with proteinuria ≥1 g/day, with complete and partial response rates of 54.8% and 19.4%, respectively. One patient with TMA progressed to end-stage kidney disease after 24 weeks, and two patients, one with TMA and one with MN, (6.4%) progressed to chronic kidney disease (CKD) Stage ≥3. Kidney and patient survival rates were 96.6% and 83.5%, respectively, at 5 years. CONCLUSION De novo glomerular diseases with diverse histopathologic manifestations affect 1.4% of patients after HSCT, and approximately 10% develop progressive CKD.
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5.
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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6.
Acute kidney injury and chronic kidney disease in umbilical cord blood transplant recipients
Lopedote, P., Xue, E., Chotivatanapong, J., Pao, E. C., Wychera, C., Dahlberg, A. E., Thur, L., Roberts, L., Baker, K., Gooley, T. A., et al
Frontiers in oncology. 2023;13:1186503
Abstract
INTRODUCTION Acute kidney injury (AKI) is a frequent early complication post hematopoietic stem cell transplant (HSCT), associated with high morbidity and mortality. Cord blood transplant (CBT) recipients are potentially exposed to more nephrotoxic insults, compared to patients undergoing HSCT from other donor sources. We aimed to identify risk factors for AKI in patients undergoing CBT. We also aimed to identify the impact of AKI on chronic kidney disease (CKD) and survival outcomes by one-year post-CBT. METHODS Adults and children who underwent a first CBT at our Institution were retrospectively evaluated. AKI was staged according to Kidney Disease Improving Global Outcomes (KDIGO) definitions. Cox regression models were used to estimate the association of demographic factors and post-CBT parameters with the cause-specific hazard of AKI. RESULTS We identified 276 patients. Median age was 32 years, 28% (77/276) were children (<18 years) and 129 (47%) were white. A myeloablative conditioning regimen was administered to 243 patients (88%) and 248 (90%) received cyclosporine for GVHD prophylaxis. One-hundred and eighty-six patients (67%) developed AKI by day 60 post-transplant, with 72 (26%) developing severe AKI (stage 2 and 3). In a multivariable analysis, each increase in bilirubin level of 1 mg/dL was associated with a 23% increase in the risk of severe AKI (adjusted HR 1.23, 95% CI 1.13 - 1.34, p<.0001). Conversely, systemic steroid administration appeared to be protective of severe AKI (unadjusted HR 0.36, 95% CI 0.18 - 0.72, p=.004) in a univariate model . Two-hundred-forty-seven patients were evaluable at the one-year time point. Among those, 100 patients (40%) developed CKD one-year post-CBT. Severe AKI was associated with a higher hazard of non-relapse mortality (adjusted HR=3.26, 95% CI 1.65-6.45, p=.001) and overall mortality (adjusted HR=2.28, 95% CI 1.22-4.27, p=.01). DISCUSSION AKI is a frequent complication after CBT and is associated with worse outcomes. Questions remain as to the mechanism of the protective role of steroids on kidney function in the setting of CBT.
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7.
Long-term kidney outcomes in children after allogeneic hematopoietic stem cell transplantation assessed with estimated glomerular filtration rate equations, creatinine levels, and cystatin C levels
Gadashova, A., Tunçay, S. C., Özek, G., Hakverdi, G., Kansoy, S., Kabasakal, C., Aksoylar, S.
Jornal brasileiro de nefrologia : 'orgao oficial de Sociedades Brasileira e Latino-Americana de Nefrologia. 2022
Abstract
BACKGROUND AND OBJECTIVE With the widespread use of allogeneic hematopoietic stem cell transplantation (allo-HSCT), long-term complications have come to the fore. The aim of this study was to determine the prevalence and risk factors of chronic kidney disease (CKD) developing in the long term in patients who underwent allo-HSCT in childhood and also to investigate the superiority of eGFR formulas. METHODS The present study evaluated CKD in patients who underwent allo-HSCT. We analyzed the 94 children who received allo-HSCT at the Ege University in İzmir between August and November, 2019. The patients were evaluated at 2 years after transplantation. CKD was defined as a glomerular filtration rate (GFR) <90 mL/min/1.73 m2 using eGFR equations based on serum creatinine (SCr), cystatin C (CysC), and SCr plus CysC. RESULTS In our study, 9 (9.4%), according to Bedside Schwartz, 59 (76.6%), according to CKiD-eGFR-CysC, and 20 (26%) patients, according to CKiD-eGFR-SCr-CysC equations were identified with CKD. In cases identifies as CKD according to CysC, early development of acute kidney injury (AKI), post-transplant cytomegalovirus (CMV) reactivation and being >120 months during transplantation were found to be associated with the development of CKD. CONCLUSION We may be delayed in detecting CKD by calculating SCr-based formulas in allo-HSCT cases, which is a patient group where early diagnosis and treatment of CKD is very important.
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8.
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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9.
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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10.
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.