The model of functional disorders in rats with kidney nephrectomy ¾ in comparison with a high-salt diet

M. Khasun, A. S. Rumyantsev, O. Beresneva, G. Ivanova, M. Parastaeva, V. Sipovskii
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Abstract

BACKGROUND. Modeling of chronic kidney disease using nephrectomy of 5/6 kidney parenchyma is actively used in experimental nephrology. However, the remaining 17 % of the organ parenchyma is associated with severe renal fibrosis in humans. A high-salt diet has traditionally been considered as a systemic hemodynamic model for the development of chronic kidney disease.THE AIM: to compare the functional disorders that occur in rats with nephrectomy of ¾ of the kidneys and when using only a high-salt diet.MATERIAL AND METHODS. The study was performed on 30 male Wistar rats. The animals were randomly divided into 3 equal groups: control (falsely operated, L), high-salt diet (falsely operated, LVD), nephrectomy ¾ renal parenchyma (NE). The rats received a balanced laboratory feed daily, differing only in the content of sodium chloride (NaCl). In the L and NE groups, rats received a feed containing 0.34 % NaCl, and in the VD group – 4 % NaCl. The duration of follow-up was 16 weeks. Systolic blood pressure (SBP) was measured on the tail by the cuff method. The serum and urine concentrations of creatinine, urea, potassium, sodium, chlorine, as well as the degree of proteinuria and albuminuria were determined.RESULTS. During the observation, the SBP in group L did not change. In the LVD group, SBP increased from 120 [120; 125] mmHg to 130.0 [125.0; 140.0] mmHg, p=0.011. In the NE group, SBP also increased from 120 [120; 125] mmHg to 135.0 [132.5; 137.5] mmHg, p=0.011. In the LVD group, there was an increase in serum creatinine concentration compared to the control to 52.5 [50.0; 56.0] mmol/l, p=0.0001; urea to 6.0 [5.6; 6.6] mmol/l, p=0.0001; potassium to 5.6 [5.3; 5.8] mmol/l, p=0.0001; chlorine up to 87.5 [86.6; 87.9] mmol/l, p= 0.0001. At the same time, creatinine clearance decreased from 187.5 [160.0; 205.0] ml/min in the L group to 92.0 [81.2; 99.0] ml/min, p=0.0003 in the LVD group and to 83.9 [65.7; 85.9] ml/min p=0.0001 in the NE group. The value of albuminuria before the end of the experiment was statistically significantly higher compared to the control in both the LVD group of 12.12 [6.36;18.41] mg/g creatinine, p= 0.0001, and in the NE group of 72.5 [61.6; 92.9] mg/g creatinine, p= 0.0001. When conducting a nonparametric correlation analysis (all three observation groups were combined), a statistically significant relationship was noted between the level of SBP after 1 month from the start of the experiment and the amount of albuminuria at its completion (Rs=0.583 p=0.001). A statistically significant relationship between the value of SBP and creatinine clearance was revealed before the end of the experiment (Rs=-0.700 p=0.005). Also, before the end of the experiment, a statistically significant relationship between albuminuria and creatinine clearance was revealed (Rs=-0.671 p=0.006).CONCLUSION. The NE model of the renal parenchyma is expected to be accompanied by the development of less severe functional changes compared to NE 5/6 of the renal parenchyma. In this regard, we assume that its use may be useful in studying the effectiveness of nephroprotective measures at the initial stages of CKD development. The negative effects of a high-salt diet are comparable in a number of indicators to nephrectomy of the renal parenchyma. Traditionally, an increase in salt intake is associated with an increase in blood pressure, which could result in an increase in albuminuria. However, we could not identify any relationships between albuminuria and the value of SAD. We assume that the model of a high-salt diet can be considered as a variant of a local, rather than a systemic hemodynamic model of the development of chronic kidney disease. In the future, we will present the results of nephrobiopsy in the experimental groups described above.
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肾切除大鼠功能紊乱模型 ¾ 与高盐饮食的比较
背景。采用5/6肾实质切除术建立慢性肾脏疾病模型在实验肾脏病学中得到了广泛应用。然而,剩下的17%的器官实质与人类严重的肾纤维化有关。高盐饮食传统上被认为是慢性肾脏疾病发展的全身血流动力学模型。目的:比较切除三分之二肾脏的大鼠和只吃高盐饮食的大鼠的功能障碍。材料和方法。研究对象为30只雄性Wistar大鼠。随机分为3组:对照组(假手术组,L)、高盐饮食组(假手术组,LVD)、肾切除/肾实质组(NE)。这些大鼠每天接受均衡的实验室饲料,只有氯化钠(NaCl)的含量不同。L组和NE组的饲料中NaCl含量为0.34%,VD组的饲料中NaCl含量为4%。随访16周。用袖带法测量尾部收缩压(SBP)。测定血清和尿肌酐、尿素、钾、钠、氯浓度,以及蛋白尿和蛋白尿程度。观察期间,L组收缩压无变化。LVD组收缩压从120升高[120;125] mmHg至130.0 [125.0];140.0] mmHg, p=0.011。在NE组,收缩压也从120升高[120;125] mmHg至135.0 [132.5;137.5] mmHg, p=0.011。与对照组相比,LVD组血清肌酐浓度升高至52.5 [50.0;56.0] mmol/l, p=0.0001;尿素至6.0 [5.6;6.6] mmol/l, p=0.0001;钾:5.6 [5.3];5.8] mmol/l, p=0.0001;氯高达87.5 [86.6;87.9] mmol/l, p= 0.0001。同时肌酐清除率从187.5[160.0]下降;L组205.0 ~ 92.0 [81.2]ml/min;99.0 ml/min, LVD组p=0.0003, LVD组p= 65.7;85.9] ml/min, NE组p=0.0001。实验结束前蛋白尿,LVD组为12.12 [6.36;18.41]mg/g肌酐,p= 0.0001, NE组为72.5 [61.6;[92.9] mg/g肌酐,p= 0.0001。当进行非参数相关分析时(所有三个观察组合并),从实验开始1个月后收缩压水平与实验结束时蛋白尿量之间存在统计学意义(Rs=0.583 p=0.001)。实验结束前收缩压值与肌酐清除率有统计学意义(Rs=-0.700 p=0.005)。实验结束前,尿白蛋白与肌酐清除率有统计学意义(Rs=-0.671 p=0.006)。与肾实质NE 5/6相比,肾实质NE模型预计会伴随较轻的功能改变。在这方面,我们认为它的使用可能有助于研究CKD发展初期肾脏保护措施的有效性。在许多指标上,高盐饮食的负面影响与肾实质切除术相当。传统上,盐摄入量的增加与血压升高有关,这可能导致蛋白尿的增加。然而,我们不能确定蛋白尿和SAD值之间的任何关系。我们假设高盐饮食模型可以被认为是慢性肾脏疾病发展的局部血流动力学模型的变体,而不是全身血流动力学模型。在未来,我们将介绍上述实验组的肾活检结果。
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