| BackgroundMalignant hypertension, MHT is a clinical syndrome associated with severely elevated blood pressure and bilateral retinal haemorrhages or exudates, or both, with or without papiloedema. MHT has relatively poor prognosis and usually significant renal involvement. However, only a few clinicopathlogic studies have evaluated the correlations between pathologic lesions and prognosis of essential MHT. Peritubular Capillary, PTC is part of renal microvasculature distributed diffusely in kidney, which is vulnerable to hemodynamic challenge caused by hypertension. Several studies have demonstrated the correlation between PTC loss and renal injury in different disease models but MHT. It has been known for long that Renin-Angiotensin-Aldosterone System, RAAS activation has a pivotal role in the development and progression of MHT. Renin, mostly secreted from the juxtaglomerular apparatus, is the first rate-limiting enzyme in RAAS. However, little is known about the mechanisms of intrarenal renin activation. Both the PTC loss and RAAS activation contribute to the development of renal hypoxia which will lead to the stabilization and activation of Hypoxia-Inducible Factor, HIF, which is thought to be helpful in hypoxic environment. Accumulating evidence suggest that HIF activation might cause renal fibrosis and PTC loss. Therefore, this study retrospectively analyzed the clinical and pathological characteristics of52essential MHT patients confirmed by renal biopsy. The PTC losses, the patterns of renin-secreting cells as well as HIF-la expressions were also evaluated, aiming to provide possible clues for the understanding and management of MHT.Purpose1. Analyze the clinical and pathological characteristics of essential MHT patients, and identify the factors correlated with prognosis preliminarily.2. Evaluate the PTC loss and its associations with clinical manifestations and prognosis in essential MHT patients.3. Observe the patterns of renin secreting cells and its potential recruitment in kidney. Assess the expression of HIF-1α and its possible associations with PTC loss as well as clinical manifestations.MethodThe clinical records and follow-up data of52patients with essential MHT confirmed by renal biopsy in Peking Union Medical College Hospital from January2003to March2012were reviewed. The pathological findings including ischemic glomerular sclerosis, tubulointerstitial injury and arteriolar lesions are evaluated semi-quantitatively. The PTC was evaluated (n=35) by immunohistochemical staining of CD34, a specific marker of arteriolar endothelium and compared with control groups (17patients with benign hypertensive nephrosclerosis, BHN and19patients with glomerular minimal lesions, GML). The immunohistochemical staining of renin and HIF-la were also performed to evaluate the pattern of renin secreting cells and the expression of HIF-la. The renin secreting cell recruitment was assessed by immunofluorescence double-staining of a-SMA and renin. Continuous variables are displayed as mean±standard deviation and compared using student’s t-test, one-way analysis of variance or Pearson’s correlation coefficients. Categorical variables are expressed as percentage and compared with chi-square test. Kaplan-Meier analysis and Cox proportional hazard model were also used. A P-value of<0.05was considered significant. Statistical analysis was performed with the SPSS software (version19.0for Windows).Results1. The clinical and pathological characteristics of52essential MHT patientsThe enrolled patients were mostly male (48M:4F) and relatively young (age34.0±8.2), with the maximum blood pressure of230.4±25.0mmHg over156.4±20.6mmHg. The serum creatinine (Scr) was486.8±375.7μmol/L and the24h urine protein (24hUpro) was1.87±1.50g/24h.21.1%(11/52) of the patients required dialysis. The mean glomerular sclerosis index was2.50±1.39and the mean percentage of tubular atrophy/interstitial fibrosis (TA/IF) were56±20%. Lumen occlusion (24.3%), mucoid changes (22.4%) and intimal hyperplasia (22.1%) were common in arterioles. TA/IF correlated positively with the proportion of arteriolar lesion, lumen occlusion in arterioles and Scr. Lumen occlusion in arterioles correlated positively with Scr, too. After adequate anti-hypertension therapy, the blood pressure and renal function improved significantly (P<0.001). The mean follow-up time of39patients eligible for survival analysis were29.1±30.1months and the renal survival rate at1,3and5year was65%、55%and50%, respectively.2. The PTC loss in primary MHT patientsThe PTC proportion in essential MHT patients was2.27±0.74%, which was significantly less than that of GML patients (3.75±0.79%, P<0.001) and BHN patients (2.85±0.51%, P<0.025). PTC proportion correlated negatively with Scr and the need for dialysis. Cox proportional hazard model identified PTC loss as an independent risk factor for renal outcome (RR=13.21,95%CI (1.50,116.69), P=0.020). 3. The evaluation of Renin and HIF-1α expression in MHT patientsThe renin expression level in essential MHT patients was elevated compared with BHN patients and GML patients. Such elevation in HIF-la expression was not observed. The renin secreting cell recruitment exists in essential MHT patients which might be a potential mechanism for local RAAS activation.Conclusion1. The renal involvement in essential MHT is severe both clinically and pathologically. The correlation of lesions in arterioles and small arteries with renal function and prognosis is not good enough.2. PTC loss in essential MHT patients correlated with renal function well and might predict the long time renal outcome.3. The elevation of renin expression in kidney may be related to renin secreting cell recruitment. Elevation of HIF-1α was not observed. |
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