| Objective:Renal failure is the main cause of death in patients with malignant hypertension(MHT).The kidney is the target organ often involved by MHT(60-70%).Its renal pathological changes can appear segmental cellulose like necrosis of arterioles in the acute stage,and ischemic wrinkling and ischemic sclerosis of glomerular basement membrane,"onion skin-like thickening"of small arterial intima,and severe luminal narrowing in the chronic stage,progressing to end-stage renal failure,which affects the prognosis.This study compared the effects of different treatment methods on renal prognosis,and explored the best treatment for MHT patients,so as to maximize the improvement of renal function.We also investigated the pathogenesis of patients with MHT from the perspective of renal pathology,clarified the RAAS activation and infiltration of T and B lymphocytes in the kidney tissue of MHT,explored the possible connection between RAAS and immune system,provided theoretical basis for existing treatment options and explored new ideas for future MHT treatment.Methods:Through the Medu Cloud database of the Affiliated Hospital of Qingdao University and the HIS and LIS medical records and test retrieval systems of the hospital,182 patients with MHT diagnosed from June1 2010 to June1 2021 were collected and divided into the drug-only group and the RASI combined with dialysis group according to the treatment mode,in which the drug-only patients were grouped according to whether they used RASI or not.RASI combined with dialysis included peritoneal dialysis combined with RASI and hemodialysis combined with RASI.The clinical information of the patients was summarized,then,the general clinical information of the patients in the two groups of drug treatment alone and the two groups of RASI combined with dialysis were compared by SPSS 21.0 and Graphpad Prism 8.0 software.After that,the activation of each index of renin angiotensin aldosterone system(RAAS)in each group was clarified.Immediately afterwards,independent sample t-tests based onΔe GFR as an indicator was used to assess changes in renal function during the follow-up period in the group with and without RASI for equal follow-up times.Then,we separately analyzed the patients whose serum creatinine rose sharply in a short time and needed to start emergency dialysis.Taking the real-time creatinine value as the evaluation standard,we first analyzed the treatment effect of each group by using the paired t-test in the group,and then compared the treatment effect between the two groups by Fisher’s accurate test.Next,Kaplan-Meier curves were used to reveal the value of attainment of blood pressure control in renal prognosis.Subsequently,immunohistochemistry was used to further verify the infiltration levels of RAAS,CD20 and CD3 in the renal tissues of MHT patients.MHT Patients who showed renal damage by renal biopsy were divided into a poor renal prognosis group(group B)and a better renal prognosis group(group G)according to their renal function prognosis,and the rank sum test was used to compare the pathological changes in two groups.Next,Cox regression analysis was made full use of to find the influencing factors affecting the prognosis of renal function.Results:1.Patients in the MHT group treated with RASI showed a significant improvement in eGFR levels after 6 months of continuous treatment compared to the previous level,and the longer the treatment period,the more pronounced the improvement was.At six months of follow-up,blood e GFR increased by 9.65±10.79 ml/(min·1.73m~2),and at 3 years of follow-up,blood e GFR increased by 18.26±16.84 ml/(min·1.73m~2);Patients in the MHT group not treated with RASI showed significant deterioration in renal function over time,with a further reduction in e GFR of 2.62±5.11ml/(min·1.73m~2)at 6 months and 6.73±17.38 ml/(min·1.73m~2)at 3 years.2.10 patients whose serum creatinine increased sharply in a short period of time requiring initiation of acute dialysis.6 patients who received peritoneal dialysis showed significant improvement in serum creatinine after treatment,from 1018.62±429.47 umol/L to 193.82±81.92 umol/L,and all were withdrawn from peritoneal dialysis within two years.Only 2 of the 4 hemodialysis patients were withdrawn from dialysis and 1 entered long-term maintenance hemodialysis,and one case died after 1 year of dialysis.Peritoneal dialysis was superior to hemodialysis in improving prognosis,but due to the small number of cases,there was no significant difference in treatment outcome between the two groups by corrected chi-square test(P=0.133).3.Renal survival analysis confirmed the best renal prognosis in those using RASI with concomitant blood pressure control(Log-rank test,X~2=50.45,P<0.0001).4.Renin and aldosterone receptors were only highly expressed in MHT renal tissues,while renin,aldosterone receptors,CD20 and CD3 were not significantly highly expressed in normal tissues.B lymphocyte(CD20 marker)and T lymphocyte(CD3 marker)were highly expressed in MHT and benign hypertensive kidney.5.Severe tubular atrophy/interstitial fibrosis is a predictor of poor prognosis of renal function in MHT patients.(OR=16.039,P=0.013).Conclusions:1.RASI is the drug of choice for the treatment of patients with MHT,at the same time,blood pressure is controlled below 130/80 mm Hg,the longer the treatment time,the better the efficacy.2.For patients with rapid deterioration of renal function requiring initiation of dialysis treatment,peritoneal dialysis combined with RASI treatment can better improve renal function and have a greater likelihood of leaving dialysis than hemodialysis.3.The clear high expression of renin and aldosterone receptors in the renal tissues of patients with MHT represents a clear activation of the local RAS in the kidney,providing a clear theoretical basis for the effectiveness of active long-term treatment of RASI,and the finding of high expression of T and B lymphocytes in the renal tissues of patients with MHT represents a possible simultaneous involvement of immune inflammatory system activation in renal pathogenesis.4.The long-term prognosis of renal function in MHT patients with severe tubular atrophy/interstitial fibrosis is poor. |
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