Abstract

Chronic kidney disease (CKD) is an important sequela of hematopoietic stem cell transplantation (HSCT), but data regarding CKD after pediatric HSCT are limited. In this single center cohort study, we evaluated the estimated glomerular filtration rate (eGFR) dynamics, proteinuria and hypertension in the first decade after HSCT and assessed risk factors for CKD in 216 pediatric HSCT survivors, transplanted 2002-2012. The eGFR decreased from a median of 148 to 116 ml/min/1.73 m2 between pre-HSCT to ten years post-HSCT. CKD (KDIGO stages G2 or A2 or more; eGFR under 90 ml/min/1.73m2 and/or albuminuria) occurred in 17% of patients. In multivariate analysis, severe prolonged stage 2 or more acute kidney injury (AKI), with an eGFR under 60ml/min/1.73m2 and duration of 28 days or more, was the main risk factor for CKD (hazard ratio 9.5, 95% confidence interval 3.4-27). Stage 2 or more AKI with an eGFR of 60ml/min/1.73m2 or more and KDIGO stage 2 or more AKI with eGFR under 60ml/min/1.73m2 but recovery within 28 days were not associated with CKD. Furthermore, hematological malignancy as HSCT indication was an independent risk factor for CKD. One third of patients had both CKD criteria, one third had isolated eGFR reduction and one third only had albuminuria. Hypertension occurred in 27% of patients with CKD compared to 4.4% of patients without. Tubular proteinuria was present in 7% of a subgroup of 71 patients with available β2-microglobulinuria. Thus, a significant proportion of pediatric HSCT recipients developed CKD within ten years. Our data stress the importance of structural long-term monitoring of eGFR, urine and blood pressure after HSCT to identify patients with incipient CKD who can benefit from nephroprotective interventions.

Highlights

  • A llogeneic hematopoietic stem cell transplantation (HSCT) is applied as a curative treatment for patients with hematological malignancies, bone marrow failure syndromes, hemoglobinopathies, inborn errors of immunity, and inborn errors of metablism.[1]

  • Nephrotoxic conditioning regimens before HSCT, as well as various nephrotoxic drugs that are frequently used in the period after HSCT, bear the risk of both acute kidney injury (AKI) and chronic kidney disease (CKD).[3]

  • CKD is reported in 5% to 30% of long-term HSCT survivors, and frequently reported risk factors are the occurrence of AKI, older age, cyclosporine A use, total body irradiation (TBI), and chronic graft-versus-host disease.[4,5,6,7,8,9,10,11]

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Summary

Introduction

A llogeneic hematopoietic stem cell transplantation (HSCT) is applied as a curative treatment for patients with hematological malignancies, bone marrow failure syndromes, hemoglobinopathies, inborn errors of immunity, and inborn errors of metablism.[1]. In many HSCT recipients, preexistent subclinical kidney damage is present because of medication, chemotherapy, or complications of primary disease.[2,3] Nephrotoxic conditioning regimens before HSCT, as well as various nephrotoxic drugs that are frequently used in the period after HSCT, bear the risk of both acute kidney injury (AKI) and chronic kidney disease (CKD).[3] In adults, CKD is reported in 5% to 30% of long-term HSCT survivors, and frequently reported risk factors are the occurrence of AKI, older age, cyclosporine A use, total body irradiation (TBI), and chronic graft-versus-host disease.[4,5,6,7,8,9,10,11] The reported incidence of CKD after pediatric HSCT varies between 0% and 44%.12–29. We evaluated risk factors for CKD and assessed estimated glomerular filtration rate (eGFR) dynamics, albuminuria, b2-microglobulinuria, and hypertension in a large single-center cohort of pediatric HSCT recipients during 10 years of follow-up

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