nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical Universitynefr-192Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESKlotho, фактор роста фибробластов 23 и неорганический фосфат на ранних стадиях хронической болезни почекKlotho, fibroblast growth factor 23 and inorganic phosphate in early stages of cronic kidney diseaseБогдановаЕвдокия ОлеговнаBogdanovaE. O.evdokia.bogdanova@gmail.comГалкинаОльга ВладимировнаGalkinaO. V.ovgalkina@mail.ruЗубинаИрина МихайловнаZubinaI. M.zubina@list.ruДобронравовВладимир АлександровичDobronravovV. A.dobronravov@nepbrolog.ruПервый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова, Научно-исследовательский институт нефрологииРоссияPavlov First Saint Petersburg State Medical University Institute of NephrologyRussian Federation2016010720162045461Copyright © Богданова Е.О., Галкина О.В., Зубина И.М., Добронравов В.А., 20162016Богданова Е.О., Галкина О.В., Зубина И.М., Добронравов В.А.Bogdanova E.O., Galkina O.V., Zubina I.M., Dobronravov V.A.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/192

ЦЕЛЬ: уточнить, связана ли система αKlotho/FGF23 с изменениями мочевой экскреции неорганического фосфата (Pi) почками на ранних стадиях хронической болезни почек (ХБП). ПАЦИЕНТЫ И МЕТОДЫ: в исследование включены 80 пациентов (возраст 40,3±16,1 года) с первичной иммунной гломерулопатией и расчетной скоростью клубочковой фильтрации (рСКФ) от 140 до 30 мл/мин на 1,73 м2. Анализировали концентрации Pi, интактного FGF23, интактного PTH и белка aKlotho (sKlotho) в крови, концентрацию αKlotho в моче, стандартизированную по креатинину мочи (uKlotho/uCr). Уровень экспрессии белка aKlotho в тубулоинтерстиции (rKlotho) оценивали методом морфометрии. Рассчитывали фракционную (FEPi) и суточную (uPi24) экскрецию Pi почками. РЕЗУЛЬТАТЫ: в группах больных с рСКФ 140-100, 99-70, 69-50 и 49-30 мл/мин на 1,73 м2 достоверных различий sPi и uPi24 выявлено не было. Уровень FEPi достоверно возрастал по мере снижения рСКФ (р<0,001). Экспрессия rKlotho в тубулярном эпителии была достоверно ниже при рСКФ 99-70 мл/мин на 1,73 м2, а концентрация sKlotho - при рСКФ 69-50 мл/мин на 1,73 м2 в сравнении с рСКФ 140-100 мл/мин на 1,73 м2. Последняя имела достоверные связи с рСКФ (r=0,35, p=0,002), выраженностью интерстициального фиброза (r=-0,43, p=0,025) и гломерулосклероза (r=-0,45, p=0,015). По мере снижения рСКФ было выявлено достоверное увеличение PTH, начиная с рСКФ 99-70 мл/мин на 1,73 м2 в сравнении с рСКФ 140-100 мл/мин на 1,73 м2. Значения FGF23 были достоверно выше только в группе пациентов с рСКФ 49-30 мл/мин на 1,73 м2. При корреляционном анализе не выявлено достоверных взаимосвязей показателей обмена Pi, aKlotho и FGF23 в подгруппе больных с рСКФ > 50 мл/мин на 1,73 м2; при рСКФ < 50 мл/мин на 1,73 м2 FGF23 коррелировал с sPi. В этих же подгруппах FEPi имела достоверную корреляционную связь с уровнем PTH. Ни αKlotho, ни FGF23 не вошли в число независимых факторов, связанных с индексами мочевой экскреции Pi, при мультивариантном регрессионом анализе; sPi был независимо связан с FGF23 (ß=0,50; р=0,007), a FEPi - с PTH (ß=0,43; р=0,003). ЗАКЛЮЧЕНИЕ: снижение уровня αKlotho в почке и циркуляции происходит на ранних стадиях ХБП, предшествует росту концентрации FGF23 и, предположительно, связано с повреждением тубулоинтерстиция. На ранних стадиях ХБП изменение тубулярной реабсорбции и почечной экскреции Pi как важного фактора поддержания нейтрального баланса данного аниона происходит независимо от FGF23, циркулирующего и ренального αKlotho.

THE AIM: to ascertain whether aKlotho and FGF23 are associated with inorganic phosphate urinary excretion in early stages of chronic kidney disease (CKD). PATIENTS AND METHODS. The cross-sectional study included 80 patients (age 40.3±16.1) with primary immune glomerulopathies and estimated glomerular filtration rate (eGFR) range 30-140 ml/min/1.73 m2. Serum levels of Pi (sPi), intact FGF23, intact PTH, serum αKlotho (sKlotho), urinary αKlotho creatinine ratio (uKlotho/uCr) were analyzed. Renal expression of αKlotho protein (rKlotho) was estimated by morphometric method. Evaluated parameters of renal Pi exchange including fractional excretion of Pi (FEPi) and 24h urinary Pi excretion (uPi24). RESULTS. There are no significant differences of sPi and uPi24 in groups of patients with eGFR 140-100, 99-70, 69-50 и 49-30 ml/min/1.73 m2. The level of FEPi increased gradually along with fall of eGFR of 99-70 ml/min/1.73 m2 (р<0.001). FEPi level significantly increased during decrease of eGFR (р<0,001). Compared to eGFR 140-100 ml/min/1.73 m2 rKlotho expression in tubular epithelium was significantly lower at eGFR 99-70 ml/min/1.73 m2, while sKlotho concentration decreased at eGFR 69-50 ml/min/1.73 m2. sKlotho concentration was significantly associated with eGFR, interstitial fibrosis, and glomerular sclerosis. During eGFR decrease the level of PTH increased significantly at eGFR 99-70 ml/min/1.73 m2 compared to eGFR 140-100 ml/min/1.73 m2. The level of FGF23 was significantly higher in patients with eGFR 49-30 ml/min/1.73 m2. In patients with eGFR > 50 ml/min/1.73 m2 no correlations were found between aKlotho/FGF23 and indices of Pi metabolism. FGF23 was associated with sPi in patients with eGFR < 50 ml/min/1.73 m2. In the same groups FEPi was associated with PTH level. Neither Klotho nor FGF23 were associated with indices of urinary Pi excretion in multivariable regression analysis. sPi was independently associated with FGF23 (ß=0.50; р=0.007), while FEPi with PTH (ß=0.43; р=0.003). CONCLUSION. The decline of αKlotho in serum and kidneys occurs on early stages of CKD and apparently associates with tubulointerstitial injury preceding the increase of FGF23. In early stages of CKD the alterations in tubular reabsorption and renal excretion of Pi as important factor of this anion neutral balance support occur independently of circulating FGF23 and renal αKlotho.

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