Malaria associated pathogenesis of chronic kidney disease (MAP-CKD): a prospective study of children hospitalized with severe malaria
Abstract Background Severe malaria (SM) remains a leading cause of child mortality and an important global contributor to acute kidney injury (AKI), which can progress to chronic kidney disease (CKD) in some survivors. Notably, 80% of AKI deaths occur in low- and middle-income countries (LMIC). Desp...
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2025-07-01
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| Series: | BMC Nephrology |
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| Online Access: | https://doi.org/10.1186/s12882-025-04333-7 |
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| author | Anthony Batte Violah Nakulima Ruth Namazzi Judith Caroline Aujo Michelle C. Starr Andrew L. Schwaderer Michael Lintner-Rivera Avias Ahumwire Daniel Ogwal Emmanuel Tenywa William Oyang John M. Ssenkusu Paul Bangirana Richard Idro Robert Kalyesubula Gavin Dreyer Mignon McCulloch Quique Bassat Chandy C. John Stuart L. Goldstein Andrea L. Conroy |
| author_facet | Anthony Batte Violah Nakulima Ruth Namazzi Judith Caroline Aujo Michelle C. Starr Andrew L. Schwaderer Michael Lintner-Rivera Avias Ahumwire Daniel Ogwal Emmanuel Tenywa William Oyang John M. Ssenkusu Paul Bangirana Richard Idro Robert Kalyesubula Gavin Dreyer Mignon McCulloch Quique Bassat Chandy C. John Stuart L. Goldstein Andrea L. Conroy |
| author_sort | Anthony Batte |
| collection | DOAJ |
| description | Abstract Background Severe malaria (SM) remains a leading cause of child mortality and an important global contributor to acute kidney injury (AKI), which can progress to chronic kidney disease (CKD) in some survivors. Notably, 80% of AKI deaths occur in low- and middle-income countries (LMIC). Despite this burden, the mechanisms and recovery trajectory of SM associated AKI remain poorly understood. There is a critical need to define the etiology and pathophysiology of SM-AKI, uncover pathways of maladaptive repair, identify risk factors for CKD, and evaluate long-term health and development. Methods This prospective multi-site cohort study will enroll children at three sites in Uganda: Mulago National Referral and Teaching Hospital, Jinja Regional Referral Hospital, and Lira Regional Referral Hospital. We aim to recruit 750 children with severe malaria and 375 community controls between 3 months of age and < 16 years. Participants will be followed for two years. Children with severe malaria will be assessed at 1-, 2-, and 4-months to evaluate short-term kidney recovery and 12- and 24-months to assess kidney function and health-related quality of life. The study will investigate short-term and long-term kidney disease risk factors following severe malaria. We will characterize host pathways involved in maladaptive kidney repair, focusing on mechanisms related to cell stress, angiogenesis, and tubulointerstitial injury. Additionally, we will assess the impact of AKI and persistent kidney disease on morbidity, mortality, and health-related quality of life. Cognitive and behavioral assessments, along with brain magnetic resonance imaging (MRI), will be used to evaluate the effects of AKI on brain injury and edema. Discussion This study will generate key insights into the prevalence of persistent kidney disease following SM-AKI and identify risk factors for CKD to inform clinical follow-up. Defining specific pathways involved with maladaptive repair in severe malaria will provide the foundation for targeted interventions to promote adaptive recovery. The research has the potential to transform long-term health outcomes following SM-AKI. Trial registration ISRCTN10885288. |
| format | Article |
| id | doaj-art-e4ffd831e0ac4a0d914a55303685b43d |
| institution | Kabale University |
| issn | 1471-2369 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj-art-e4ffd831e0ac4a0d914a55303685b43d2025-08-20T03:42:30ZengBMCBMC Nephrology1471-23692025-07-0126111410.1186/s12882-025-04333-7Malaria associated pathogenesis of chronic kidney disease (MAP-CKD): a prospective study of children hospitalized with severe malariaAnthony Batte0Violah Nakulima1Ruth Namazzi2Judith Caroline Aujo3Michelle C. Starr4Andrew L. Schwaderer5Michael Lintner-Rivera6Avias Ahumwire7Daniel Ogwal8Emmanuel Tenywa9William Oyang10John M. Ssenkusu11Paul Bangirana12Richard Idro13Robert Kalyesubula14Gavin Dreyer15Mignon McCulloch16Quique Bassat17Chandy C. John18Stuart L. Goldstein19Andrea L. Conroy20Child Health and Development Centre, Makerere University College of Health SciencesGlobal Health UgandaGlobal Health UgandaDepartment of Paediatrics, Mulago National Referral and Teaching HospitalDepartment of Pediatric Nephrology, Indiana University School of MedicineDepartment of Pediatric Nephrology, Indiana University School of MedicineRyan White Center for Pediatric Infectious Disease and Global Health, Indiana University School of MedicineGlobal Health UgandaGlobal Health UgandaJinja Regional Referral HospitalLira Regional Referral HospitalGlobal Health UgandaGlobal Health UgandaGlobal Health UgandaDepartment of Physiology, Makerere University College of Health SciencesDepartment of Nephrology, Barts Health NHS TrustRed Cross War Memorial Children’s Hospital, University of Cape TownISGlobal, Hospital Clínic - Universitat de BarcelonaRyan White Center for Pediatric Infectious Disease and Global Health, Indiana University School of MedicineDivision of Nephrology, Department of Pediatrics, Center for Acute Care Nephrology, Cincinnati Children’s Hospital Medical CenterGlobal Health UgandaAbstract Background Severe malaria (SM) remains a leading cause of child mortality and an important global contributor to acute kidney injury (AKI), which can progress to chronic kidney disease (CKD) in some survivors. Notably, 80% of AKI deaths occur in low- and middle-income countries (LMIC). Despite this burden, the mechanisms and recovery trajectory of SM associated AKI remain poorly understood. There is a critical need to define the etiology and pathophysiology of SM-AKI, uncover pathways of maladaptive repair, identify risk factors for CKD, and evaluate long-term health and development. Methods This prospective multi-site cohort study will enroll children at three sites in Uganda: Mulago National Referral and Teaching Hospital, Jinja Regional Referral Hospital, and Lira Regional Referral Hospital. We aim to recruit 750 children with severe malaria and 375 community controls between 3 months of age and < 16 years. Participants will be followed for two years. Children with severe malaria will be assessed at 1-, 2-, and 4-months to evaluate short-term kidney recovery and 12- and 24-months to assess kidney function and health-related quality of life. The study will investigate short-term and long-term kidney disease risk factors following severe malaria. We will characterize host pathways involved in maladaptive kidney repair, focusing on mechanisms related to cell stress, angiogenesis, and tubulointerstitial injury. Additionally, we will assess the impact of AKI and persistent kidney disease on morbidity, mortality, and health-related quality of life. Cognitive and behavioral assessments, along with brain magnetic resonance imaging (MRI), will be used to evaluate the effects of AKI on brain injury and edema. Discussion This study will generate key insights into the prevalence of persistent kidney disease following SM-AKI and identify risk factors for CKD to inform clinical follow-up. Defining specific pathways involved with maladaptive repair in severe malaria will provide the foundation for targeted interventions to promote adaptive recovery. The research has the potential to transform long-term health outcomes following SM-AKI. Trial registration ISRCTN10885288.https://doi.org/10.1186/s12882-025-04333-7Acute kidney injurySevere malariaPediatricsMaladaptive repairChronic kidney diseaseHealth-related quality of life |
| spellingShingle | Anthony Batte Violah Nakulima Ruth Namazzi Judith Caroline Aujo Michelle C. Starr Andrew L. Schwaderer Michael Lintner-Rivera Avias Ahumwire Daniel Ogwal Emmanuel Tenywa William Oyang John M. Ssenkusu Paul Bangirana Richard Idro Robert Kalyesubula Gavin Dreyer Mignon McCulloch Quique Bassat Chandy C. John Stuart L. Goldstein Andrea L. Conroy Malaria associated pathogenesis of chronic kidney disease (MAP-CKD): a prospective study of children hospitalized with severe malaria BMC Nephrology Acute kidney injury Severe malaria Pediatrics Maladaptive repair Chronic kidney disease Health-related quality of life |
| title | Malaria associated pathogenesis of chronic kidney disease (MAP-CKD): a prospective study of children hospitalized with severe malaria |
| title_full | Malaria associated pathogenesis of chronic kidney disease (MAP-CKD): a prospective study of children hospitalized with severe malaria |
| title_fullStr | Malaria associated pathogenesis of chronic kidney disease (MAP-CKD): a prospective study of children hospitalized with severe malaria |
| title_full_unstemmed | Malaria associated pathogenesis of chronic kidney disease (MAP-CKD): a prospective study of children hospitalized with severe malaria |
| title_short | Malaria associated pathogenesis of chronic kidney disease (MAP-CKD): a prospective study of children hospitalized with severe malaria |
| title_sort | malaria associated pathogenesis of chronic kidney disease map ckd a prospective study of children hospitalized with severe malaria |
| topic | Acute kidney injury Severe malaria Pediatrics Maladaptive repair Chronic kidney disease Health-related quality of life |
| url | https://doi.org/10.1186/s12882-025-04333-7 |
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