关键词: 非奈利酮 , 达格列净,  2 型糖尿病肾病, 肾脏保护

Abstract:  Objective:To study the efficacy and safety of finerenone combined with dapagliflozin to improve kidney injury  in  patients  with  type  2  diabetic  nephropathy  （ DN ）   on  the  basis  of  angiotensin⁃converting  enzyme  inhibitor / angiotensin  receptor  blocker  （ ACEI / ARB）  therapy.      Methodology: DN  patients  diagnosed  at  the  National  Clinical Medical Research Center for  Kidney  Diseases  from  August  2016  to  October  2022  and  prospectively  from  August  2023  to December 2023 were retrospectively collected as the control group of ACEI / ARB monotherapy and the observation group of combination therapy with ACEI / ARB， dapagliflozin， and finerenone， respectively.  The general data of patients in the two groups were  collected，  and  kidney  injury⁃related  indexes，  efficacy  and  adverse  reactions  were  observed  at  baseline，  6 months of  treatment  and  12  months  of  treatment，  and  the  factors  affecting  the  efficacy  were  analyzed.  The  primary observation efficacy index was that  urine  microalbumin / creatinine  ratio（ UACR）  decreased≥15%  from baseline， and  the secondary observation efficacy index was that  renal  function  remained  stable  [ estimated  glomerular  filtration  rate（ eGFR） decreased <15%  from  baseline].     Results: There  were  50  cases  in  the  control  group  and  100  cases  in  the  observation group， and there was no difference in baseline data between the two groups. （ 1） Compared with baseline， after 6 months of treatment the UACR of the control group decreased from baseline; in the observation group， 24h urine protein quantification and UACR decreased from baseline， and albumin increased from baseline （ P<0.05）. After 12 months of treatment， UACR further decreased， and eGFR  decreased  from  baseline  in  the  control  group;  in  the  observation  group，  24h  urine  protein quantification and UACR further decreased， hemoglobin  （ Hb），  eGFR  and  albumin  increased  from  baseline  （ P< 0.05）. Compared with the control group， the  change  rates  of 24h  urine  protein  quantification， UACR， and  albumin  at 6  and 12 months of treatment were statistically significant in the observation group; the change rate of Hb was statistically significant after 12 months of treatment （ P< 0.01）. （ 2）  Compared  with  the  control  group，  patients  in  the  observation  group  had  a higher incidence of UACR decline rate≥15%  overall， especially in patients with stage 3 versus stage 4 （ P<0.05）; there was no difference between the  two  groups  in  the  incidence  of  eGFR  decline  rate  < 15%，  the  incidence  of  adverse  events overall and after staging （ P>0.05）.（ 3） Multifactorial binary logistic regression analysis suggested that combination therapy （ OR = 4.782，95%CI 2.172~ 10.529）  promoted the occurrence of UACR decline rate≥15%; high Hb （ OR = 0.981，95% CI 0.964~ 0.999）  was a protective factor for the rate of decline of eGFR≥15%; the combination of other antihypertensive drug treatments （ OR = 3.684，95%CI 1.596 ~ 8.507）， and high triglycerides （ OR = 1.287，95% CI 1.016 ~ 1.630）  were risk factors for eGFR decline rate≥15%.    Conclusion:Compared to ACEI / ARB monotherapy for reducing proteinuria， the combined  treatment  of  ACEI / ARB，  finerenone，  and  dapagliflozin  achieves  a  more   significant   reduction   in   UACR （ particularly in mid⁃to⁃late⁃stage  patients）  and  improves  albumin  levels  in  DN  patients，  while  maintaining  stable  eGFR. Refractory hypertension， anemia， and high triglyceride levels are risk factors for rapid eGFR decline. The combined therapy did not increase the incidence of adverse reactions.

Key words: finerenone, dapagliflozin, type 2 diabetic kidney disease, kidney protection