nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical Universitynefr-138Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ. КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES. CLINICAL INVESTIGATIONSДИНАМИКА БИОМАРКЕРОВ ПОВРЕЖДЕНИЯ ПОЧЕК ПОСЛЕ ТРАНСПЛАНТАЦИИ ГЕМОПОЭТИЧЕСКИХ СТВОЛОВЫХ КЛЕТОК (ПИЛОТНОЕ ИССЛЕДОВАНИЕ)DYNAMICS OF KIDNEY INJURY BIOMARKERS FOLLOWING HEMATOPOIETIC STEM CELL TRANSPLANTATION (PILOT STUDY)СмирновК. А.SmirnovK. A.smimoff2610@mail.ruДобронравовВ. А.DobronravovV. A.noemail@neicon.ruАфанасьевБ. В.AfanasievB. V.noemail@neicon.ruГалкинаО. В.GalkinaO. V.noemail@neicon.ruЗубинаИ. М.ZubinaI. M.noemail@neicon.ruБогдановаЕ. О.BogdanovaE. O.noemail@neicon.ruБлиноваТ. В.BlinovaT. V.noemail@neicon.ruБархатовИ. М.BarhatovI. M.noemail@neicon.ruСмирновА. В.SmirnovA. V.noemail@neicon.ruПервый Санкт-Петербургский государственный медицинский университет им. акад. И.П.Павлова; Научно-исследовательский институт нефрологииРоссияNephrology Research Institute, Pavlov First Saint-Petersburg State Medical UniversityRussian FederationНаучно-исследовательский институт детской онкологии, гематологии и трансплантологии им. Р.М. ГорбачёвойРоссияRaisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and TransplantationRussian FederationНаучно-исследовательский институт нефрологии Первого Санкт-Петербургского государственного медицинского университета им. акад. И.П.ПавловаРоссияNephrology Research Institute, Pavlov First Saint-Petersburg State Medical UniversityRussian FederationНаучно-исследовательский институт нефрологии Первого Санкт-Петербургского государственного медицинского университета им.акад.И.П.ПавловаРоссияNephrology Research Institute, Pavlov First Saint-Petersburg State Medical UniversityRussian Federation2015011120151962833Copyright © Смирнов К.А., Добронравов В.А., Афанасьев Б.В., Галкина О.В., Зубина И.М., Богданова Е.О., Блинова Т.В., Бархатов И.М., Смирнов А.В., 20152015Смирнов К.А., Добронравов В.А., Афанасьев Б.В., Галкина О.В., Зубина И.М., Богданова Е.О., Блинова Т.В., Бархатов И.М., Смирнов А.В.Smirnov K.A., Dobronravov V.A., Afanasiev B.V., Galkina O.V., Zubina I.M., Bogdanova E.O., Blinova T.V., Barhatov I.M., Smirnov A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/138

ЦЕЛЬ ИССЛЕДОВАНИЯ: оценка динамики биомаркеров тубулярного повреждения (БМ) и частоты развития острого повреждения почек (ОПП) по данным рутинной диагностики после трансплантации гемопоэтических стволовых клеток (ТГСК). ПАЦИЕНТЫ И МЕТОДЫ. Обследовано 30 пациентов после аллогенной ТГСК. В образцах мочи за 7 дней до ТГСК (неделя 0), на неделях 1-4 после ТГСК измерены концентрации БМ (кальбиндин, кластерин, интерлейкин-18, IL-18), молекула повреждения почек-1 (KIM-1), глутатион-S-трансфераза (p-класс) (GST-п), протеин хемотаксиса моноцитов-1 (MCP-1). В указанные временные периоды определён креатинин (Cr). Клиническое ОПП диагностировали согласно классификациям AKIN/KDIGO. РЕЗУЛЬТАТЫ. Диагностика ОПП(AKIN/KDIGO): доля случаев с ОПП(AKIN/KDIGO) в 1-ю и 2-ю недели после ТГСК - 7%, на 3-й неделе -17%, на 4-й неделе - 54% (р<0,05). Частота выявления случаев повышения концентраций 1 и более БМ на неделе 1 после ТГСК составила 78%, на неделе 2 - 85%, на неделе 3 - 90%. Доля случаев одновременного повышения концентраций 4 и более БМ после ТГСК прогрессивно увеличивалась: 6% - до ТГСК и 38% - на неделе 4 после ТГСК. К 4-й неделе только в 6% случаев не было зарегистрировано повышение БМ, а кумулятивная доля случаев без клинических критериев ОПП(AKIN/KDIGO) была значительно больше и составила 40%. Частота развития ОПП(AKIN/KDIGO) возрастала при увеличении числа одновременно повышенных БМ. Выявлены достоверные прямые связи между БМ проксимальных канальцев; дистальных канальцев, а также между БМ, характеризующими как проксимальное, так и дистальное повреждение. ROC-анализ показал, что число БМ обладает достаточной чувствительностью в отношении прогноза развития ОПП (AKIN/KDIGO) (SAUC=0,69, р=0,006). ЗАКЛЮЧЕНИЕ. Повышение концентраций БМ, указывающих на повреждение канальцев, после ТГСК выявляется у большинства пациентов (90%) и предшествует развитию клинического ОПП (AKIN/KDIGO). БМ могут быть использованы для оценки субклинического структурного тубулярного повреждения и прогнозирования развития глобальной дисфункции органа - ОПП.

THE AIM. To evaluate dynamics of tubular damage biomarkers (BMs) and to determine frequency of acute kidney injury (AKI) according to routine diagnostics following hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS. The study involved 30 patients after allogeneic hematopoietic stem cell transplantation (HSCT). The urine samples were taken 7 days prior to HSCT (week 0), on the weeks 1, 2, 3 and 4. BMs concentrations (calbindin, clusterin, IL-18, KIM-1, GST-п, MCP-1) were estimated. Serum creatinine was measured at the same time periods. Clinical AKI was diagnosed according to AKIN/ KDIGO (acute kidney injury network/kidney disease improving global outcomes) classification systems. RESULTS. Clinical AKI (AKIN/KDIGO) diagnostics: the proportion of AKI (AKШN/KDIGO) cases on the weeks 1 and 2 after HSCT was 7%, on the week 3 - 17%, on the week 4- 54% (p <0.05). The frequency of cases with increase of 1 and more BMs concentrations on the week 1 following HSCT was 78%, on the week 2 - 85% and thereafter on the week 3 - 90%. The proportion of cases with simultaneous elevation of 4 and more BMs after HSCT had been progressively increasing: from 6% before HSCT to 38% on the week 4 after it. By week 4 only in 6% of cases no increase in BMs concentration was found, while the cumulative proportion of cases without clinical AKI criteria (AKIN/KDIGO) was much more higher and reached 40%. The frequency of AKI (AkIN/KDIGO) development increased in relation to the number of simultaneously increased BMs. Statistically significant direct correlations were found between BMs of proximal and distal tubules, as well as between BMs simultaneously showing the damage of both proximal and distal tubule. ROC analysis showed that BMs number has sufficient sensitivity in terms of prognosis of clinical AKI (AKIN/KDIGO) development (SAUC=0,69; p=0.006). CONCLUSION. The BMs concentration increase, showing the tubular damage following HSCT, was found in majority of patients (90%) and preceded the development of clinical AKI (AKIN/KDIGO). The evaluation of BMs concentration may be used for the assessment of subclinical tubular structural damage and prognosis of AKI.

острое повреждение почектрансплантация гемопоэтических стволовых клетокбиомаркеры острого повреждения почекacute kidney injuryhematopoietic stem cell transplantationacute kidney injury biomarkersReferencesChertow G.M, Burdick E, Honour M. et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 2005;16(11): 3365-3370Chertow G.M, Burdick E, Honour M. et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 2005;16(11): 3365-3370Wang H.E, Muntner P, Chertow G.M. et al. Acute kidney injury and mortality in hospitalized patients. Am J Nephrol 2012; 35(4): 349-355Wang H.E, Muntner P, Chertow G.M. et al. Acute kidney injury and mortality in hospitalized patients. Am J Nephrol 2012; 35(4): 349-355Uchino S, Bellomo R, Goldsmith D. et al. An assesment of the RIFLE criteria for acute kidney failure in hospitalized patients. Crit Care Med 2006; 34(7): 1913-1917Uchino S, Bellomo R, Goldsmith D. et al. An assesment of the RIFLE criteria for acute kidney failure in hospitalized patients. Crit Care Med 2006; 34(7): 1913-1917Mandelbaum T, Scott D.J, Lee J. et al. Outcome of critically ill patients with acute kidney injury using the Acute kidney injury network criteria. Crit Care Med 2011; 39(12): 2659-2664Mandelbaum T, Scott D.J, Lee J. et al. Outcome of critically ill patients with acute kidney injury using the Acute kidney injury network criteria. Crit Care Med 2011; 39(12): 2659-2664Nin N, Lombardi R, Frutos-Vivar F et al. VENTILA Group: Early and small changes in serum creatinine concentrations are associated with mortality in mechanically ventilated patients. Shock 2010; 34(2): 109-116Nin N, Lombardi R, Frutos-Vivar F et al. VENTILA Group: Early and small changes in serum creatinine concentrations are associated with mortality in mechanically ventilated patients. Shock 2010; 34(2): 109-116Zeng X, Mcmahon G.M, Brunelli S.M. et al. Incidence, Outcomes, and Comparisons across Definitions of AKI in Hospitalized Individuals. Clin J Am Soc Nephrol 2014;9(1): 12-20Zeng X, Mcmahon G.M, Brunelli S.M. et al. Incidence, Outcomes, and Comparisons across Definitions of AKI in Hospitalized Individuals. Clin J Am Soc Nephrol 2014;9(1): 12-20Hahn T, Rondeau C, Shaukat A. et al. Acute renal failure requiring dialysis after allogeneic blood and marrow transplantation identifies very poor prognosis patients. Bone Marrow Transplant 2003; 32(4): 405-410Hahn T, Rondeau C, Shaukat A. et al. Acute renal failure requiring dialysis after allogeneic blood and marrow transplantation identifies very poor prognosis patients. Bone Marrow Transplant 2003; 32(4): 405-410Bucaloiu I.D, Kirchner H.L, Norfolk E.R. et al. Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury. Kidney Int 2012;81(5): 477-485Bucaloiu I.D, Kirchner H.L, Norfolk E.R. et al. Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury. Kidney Int 2012;81(5): 477-485Wu V.C, Huang T.M, Lai C.F. et al. Acute on chronic kidney injury at hospital discharge is associated with long-term dialysis and mortality. Kidney Int 2011;80(11): 1222-1230Wu V.C, Huang T.M, Lai C.F. et al. Acute on chronic kidney injury at hospital discharge is associated with long-term dialysis and mortality. Kidney Int 2011;80(11): 1222-1230Chawla L.S, Amdur R.L, Amodeo S. et al. The severity of acute kidney injury predicts progression to chronic kidney disease. Kidney Int 2011;79(12): 1361-1369Chawla L.S, Amdur R.L, Amodeo S. et al. The severity of acute kidney injury predicts progression to chronic kidney disease. Kidney Int 2011;79(12): 1361-1369Lafrance J.P, Djurdjev O, Levin A. Incidence and outcomes of acute kidney injury in a referred chronic kidney disease cohort. Nephrol Dial Transplant 2010;25(7): 2203-2209Lafrance J.P, Djurdjev O, Levin A. Incidence and outcomes of acute kidney injury in a referred chronic kidney disease cohort. Nephrol Dial Transplant 2010;25(7): 2203-2209Lopes J.A, Jorge S. Acute kidney injury following HCT: incidence, risk factors and outcome. Bone Marrow transplantation 2011;46(11): 1399-1408Lopes J.A, Jorge S. Acute kidney injury following HCT: incidence, risk factors and outcome. Bone Marrow transplantation 2011;46(11): 1399-1408Weiss A.S, Sandmaier B.M, Storer B. et al. Chronic kidney disease following non-myeloablative hematopoietic cell transplantation. Am J Transplant 2006;6(1): 89-94Weiss A.S, Sandmaier B.M, Storer B. et al. Chronic kidney disease following non-myeloablative hematopoietic cell transplantation. Am J Transplant 2006;6(1): 89-94Ellis M.J, Parikh C.R, Inriq J.K. et al. Chronic kidney disease after hematopoietic cell transplantation: a systematic review. Am J Transplant 2008;8(11): 2378-2390Ellis M.J, Parikh C.R, Inriq J.K. et al. Chronic kidney disease after hematopoietic cell transplantation: a systematic review. Am J Transplant 2008;8(11): 2378-2390Kogon A, Hingorani S. Acute kidney injury in hematopoietic cell transplantation. Semin Nephrol 2010;30(6): 615-626Kogon A, Hingorani S. Acute kidney injury in hematopoietic cell transplantation. Semin Nephrol 2010;30(6): 615-626Bellomo R, Kellum J.A, Ronco C. Defining acute renal failure: physiological principles. Intensive Care Med 2004;30(1): 33-37Bellomo R, Kellum J.A, Ronco C. Defining acute renal failure: physiological principles. Intensive Care Med 2004;30(1): 33-37Coca S.G, Parikh C.R. Urinary biomarkers for acute kidney injury: perspectives on translation. Clin J Am Soc Nephrol 2008;3(2): 481-490Coca S.G, Parikh C.R. Urinary biomarkers for acute kidney injury: perspectives on translation. Clin J Am Soc Nephrol 2008;3(2): 481-490Moore E, Bellomo R. Novel biomarkers of acute kidney injury: ready for clinical application? Curr Opin Crit Care 2010;16(6): 523-525Moore E, Bellomo R. Novel biomarkers of acute kidney injury: ready for clinical application? Curr Opin Crit Care 2010;16(6): 523-525Nguyen M.T, Devarajan P Biomarkers for the early detection of acute kidney injury 2008;23(12): 2151-2157Nguyen M.T, Devarajan P Biomarkers for the early detection of acute kidney injury 2008;23(12): 2151-2157Doi K, Yuen P.S, Eisner C. Reduced production of creatinine limits its use as marker of kidney injury in sepsis. J Am Soc Nephrol 2009;20(6): 1217-1221Doi K, Yuen P.S, Eisner C. Reduced production of creatinine limits its use as marker of kidney injury in sepsis. J Am Soc Nephrol 2009;20(6): 1217-1221Soni S.S, Cruz D, Bobek I. NGAL: a biomarker of acute kidney injury and other systemic conditions. Int Urol Nephrol 2010; 42(1): 141-150Soni S.S, Cruz D, Bobek I. NGAL: a biomarker of acute kidney injury and other systemic conditions. Int Urol Nephrol 2010; 42(1): 141-150Ghatanatti R, Teli A, Tirkey S.S. et al. Role of renal biomarkers as predictors of acute kidney injury in cardiac surgery. Asian Cardiovasc Thorac Ann 2014;22(2): 234-241Ghatanatti R, Teli A, Tirkey S.S. et al. Role of renal biomarkers as predictors of acute kidney injury in cardiac surgery. Asian Cardiovasc Thorac Ann 2014;22(2): 234-241Добронравов В.А. Обзор патофизиологии острого повреждения почек. В: Смирнов А.В, Добронравов В.А, Румянцев А.Ш, Каюков И.Г. Острое повреждение почек. МИА, 2015, 3076Добронравов В.А. Обзор патофизиологии острого повреждения почек. В: Смирнов А.В, Добронравов В.А, Румянцев А.Ш, Каюков И.Г. Острое повреждение почек. МИА, 2015, 3076Field M, Dronovalli V, Mistry P. et al. Urinary biomarkers of acute kidney injury in diceased organ donors-kidney injury molecule-1 as an adjunct to predicting outcome. Clin Transplant 2014;28(7): 808-815Field M, Dronovalli V, Mistry P. et al. Urinary biomarkers of acute kidney injury in diceased organ donors-kidney injury molecule-1 as an adjunct to predicting outcome. Clin Transplant 2014;28(7): 808-815Han W.K, Wagener G, Zhu Y. at al. Urinary biomarkers in the early detection of acute kidney injury after cardiac surgery. Clin J Am Soc Nephrol 2009 4(5): 873-882Han W.K, Wagener G, Zhu Y. at al. Urinary biomarkers in the early detection of acute kidney injury after cardiac surgery. Clin J Am Soc Nephrol 2009 4(5): 873-882Levi T.M, de Souza S.P, de Magalhaes J.G. et al. Comparison of the RIFLE, AKIN and KDIGO criteria to predict mortality in critically ill patients. Rev Bras Ter Intensiva 2013;25(4): 290-296Levi T.M, de Souza S.P, de Magalhaes J.G. et al. Comparison of the RIFLE, AKIN and KDIGO criteria to predict mortality in critically ill patients. Rev Bras Ter Intensiva 2013;25(4): 290-296

The authors declare that there are no conflicts of interest present.