Role of Medical Approach in the Management of Stone Disease

In the management of stone disease, the medical approach concerned with the prevention of stone recurrence is equally as important as the surgical removal of stones. The application of medical approach requires an understanding of the pathophysiology of stone formation. A wide variety of physiological or environmental disturbances have been identified in stone–forming patients. They include hypercalciuria, hypocitraturia, undue urinary acidity and hyperuricosuria. Reliable diagnostic protocols have been developed which are based on the presence of above derangements. The prophylactic treatment programs are directed at the correction or amelioration of underlying environmental disturbances. Conservative measures include a high fluid intake, dietary sodium and oxalate restriction, dietary calcium restriction (in absorptive hypercalciuria and primary hyperparathyroidism), and moderate animal protein restriction. Specific medical treatments chosen for discussion are thiazide, slow–release neutral potassium phosphate, potassium citrate and potassium magnesium citrate.     

某大型水面舰艇部队肾结石和肾结晶流行病学调查分析

【摘要】目的 分析某大型水面舰艇官兵尿石症流行病学特点及其危险因素。 方法 收集2021年某大型水面舰艇部队官兵体检报告原始数据,包括一般信息、内外科体检结果、超声、血尿检验结果等,并行作训环境及生活习惯调查,分析官兵肾结石和肾结晶患病情况及影响因素。 结果 1315名官兵中,肾结石/结晶总患病率6.92%。肾结石和肾结晶患病率均随着年龄、军龄和上舰龄的增长而增加。肾结石/结晶患者中合并超重者占32.97%,显著高于无肾结石/结晶者（17.04%）。肾结石/结晶患者饮水量大于2000ml/d的比例（20.45% vs. 30.24%）及饮用牛奶的比例（82.95% vs. 90.64%）显著低于无肾结石/结晶者。与不伴有肾结石/结晶的官兵相比,患有肾结石/结晶官兵的作训环境、水源、饮料摄入、血尿酸水平、尿渗透压均无显著差异。Logistic多因素回归分析显示年龄增加和超重是舰艇官兵肾结石/结晶患病的独立危险因素,而多饮水和牛奶是保护性因素。 结论 舰艇官兵肾结石和肾结晶患病率较高,其发生与年龄增加、超重、少饮水和少饮牛奶等因素相关。     

Lead (Pb2+)-induced calcium oxalate crystallization ex vivo is ameliorated via inositol 1,4,5-trisphosphate receptor (InsP3R) knockdown in a Drosophila melanogaster model of nephrolithiasis

Nephrolithiasis causes severe pain and is a highly recurrent pathophysiological state. Calcium-containing stones, specifically calcium oxalate (CaOx), is the most common type accounting for approximately 75 % of stone composition. Genetic predisposition, gender, geographic region, diet, and low fluid intake all contribute to disease pathogenesis. However, exposure to environmental pollutants as a contribution to kidney stone formation remains insufficiently studied. Lead (Pb2+) is of particular interest as epidemiological data indicate that low-level exposure (BLL = 0.48–3.85 μM) confers a 35 % increased risk of developing CaOx nephrolithiasis. However, mechanisms underlying this association have yet to be elucidated. Drosophila melanogaster provide a useful genetic model where major molecular pathophysiological pathways can be efficiently studied. Malpighian tubules (MT) were isolated from either Wild-Type or InsP₃R knockdown flies and treated with oxalate (5 mM) ± Pb²⁺ (2μM) for 1 h. Following exposure, MTs were imaged and crystals quantified. CaOx crystal number and total area were significantly increased (˜5-fold) in Pb²⁺(pre-treatment) + oxalate-exposed MTs when compared to oxalate alone controls. However, CaOx crystal number and total crystal area in Pb²⁺ + oxalate-exposed InsP₃R knockdown MTs were significantly decreased (˜3-fold) indicating the role for principal cell-specific InsP₃R-mediated Ca²⁺ mobilization as a mechanism for Pb²⁺-induced increases in CaOx crystallization inset model of nephrolithiasis.     

经乙二醇诱导的改良型草酸钙肾结石果蝇模型

目的:通过一种改良方法构建果蝇草酸钙肾结石模型。方法:配制标准培养基和造模用培养基，空白对照组果蝇仅予标准培养基，而传统模型组和改良模型组分别从成虫期和幼虫期开始摄入含 0.5%乙二醇( EG)的造模用培养基。于偏光显微镜下观察并评估各组果蝇马氏管内成石情况，分别记录模型组成石率达 100%所花时间，并对成石率 100%时模型组间“ ++”和“ +++”所占比率进行比较；用傅立叶变换拉曼光谱仪鉴定模型组果蝇马氏管内结石成分。绘制各组果蝇生存曲线，并比较生存周期差异。结果:改良模型组和传统模型组分别在果蝇成虫日龄 14 d和 22 d，马氏管内成石率达到 100%。当改良模型组和传统模型组成石率均达到 100%时，两组“ ++”与“+++”所占比率分别为(40.5±4.4)%和(39.0±4.2)%，差异无统计学意义(P＞ 0.05)；拉曼位移的主峰主要集中在 1 462 cm-1、1 463 cm-1和 1 473 cm-1，说明模型组果蝇马氏管内结石成分均为草酸钙。空白对照组、传统模型组和改良模型组的最高寿命分别为 76 d、70 d和 68 d，中位生存时间分别为 35 d、30.5 d和 30 d，与空白对照组相比，模型组生存周期均显著缩短(P均＜ 0.01)，但传统模型组与改良模型组间差异无统计学意义( P＞ 0.05)。结论:改良型造模方法使果蝇在其幼虫期即摄入 0.5% EG，缩短了模型构建周期且具有可重复性，值得进一步研究推广。     

Significant association between RGS14 rs12654812 and nephrolithiasis risk among Guangxi population in China

Background

Nephrolithiasis is a worldwide health problem that affects almost all populations. This study aimed to evaluate the association between rs12654812 of regulator of G protein signaling 14 (RGS14) gene and nephrolithiasis in the Chinese population.

Methods

A total of 1541 participators including 830 cases and 711 controls were included from Guangxi area in China. Age, sex, BMI, smoking status, drinking status, creatinine, uric acid, and urea nitrogen were analyzed between the case group and control group.

Results

We found that the G/A+A/A genotypes of rs12654812 had a significantly increased nephrolithiasis risk after adjusting age, sex, BMI, smoking, drinking, and hypertension, compared with G/G genotype (OR = 1.361, 95% CI = 1.033‐1.794, P = .029). This hazardous effect was more pronounced in subgroup of age < 50, ever smoking, ever drinking, creatinine normal, and high uric acid. The G/A genotype of rs12654812 also had a significantly increased nephrolithiasis risk compared with G/G genotype. The A allele of rs12654812 significantly increased the risk of nephrolithiasis compared with the G allele after adjusting for age, sex, BMI, smoking, drinking and hypertension (OR = 1.277, 95% CI = 1.013‐1.609, P = .038).

Conclusions

Our results suggest that the RGS14 polymorphism is involved in the etiology of nephrolithiasis and thus may be a genetic marker for nephrolithiasis.

     

Approach to the patient with recurrent neprolithiasis

Although recurring nephrolithiasis may not be as common as single-episode disease, it poses greater problems to the patient's daily lifestyle and general future health status. The general need for an adequate history, examination, and radiological assessment is acknowledged, but a more intensive investigative and management approach is required. Investigations for secondary causes are paramount and may lead to identification of unusual metabolic abnormalities and specific therapies. Such medical approaches entail consideration of dietary adjustments to lower the urinary excretion of components of the renal stones, pharmacological therapies to modulate urinary constituents and limit renal stone risk, and monitoring efficacy of the therapy over time. This approach will prevent significant deterioration of renal function and other serious metabolic consequences.