*Article* **Totally X-ray-Free Ultrasound-Guided Mini-Percutaneous Nephrolithotomy in Galdakao-Modified Supine Valdivia Position: A Novel Combined Surgery**

**Yi-Yang Liu 1,2, Yen-Ta Chen 1, Hao-Lun Luo 1, Yuan-Chi Shen 1, Chien-Hsu Chen 1, Yao-Chi Chuang 1, Ko-Wei Huang <sup>2</sup> and Hung-Jen Wang 1,\***


**Abstract:** We introduced a novel surgery that combines ultrasound guidance, miniaturization and Galdakao-modified supine Valdivia (GMSV) position in percutaneous nephrolithotomy (PCNL) and evaluated the safety and efficacy. This retrospective, single-center study retrospectively reviewed 150 patients who underwent ultrasound-guided mini-PCNL in the GMSV position from November 2019 to March 2022. All perioperative parameters were collected. Stone-free status was defined as no residual stones or clinically insignificant residual fragments (CIRF) <0.4 cm on postoperative day one. Among the 150 patients, the mean age was 56.96 years. The mean stone size was 3.19 cm (427 mm2). The mean S.T.O.N.E. score was 7.61, including 36 patients (24%) with scores ≥9. The mean operative time was 66.22 min, and the success rate of renal access creation in the first attempt was 88.7%. One hundred and forty (93.3%) patients were stone free. The mean decrease in Hemoglobin was 1.04 g/dL, and no patient needed a blood transfusion. Complications included transient hematuria (*n* = 13, 8.7%), bladder blood clot retention (*n* = 2, 1.3%), fever (*n* = 15, 10%) and sepsis (*n* = 2, 1.3%). Totally X-ray-free ultrasound-guided mini-PCNL in the GMSV position is feasible, safe and effective for patients with upper urinary tract stones, indicating the synergistic and complementary effects of the three novel techniques.

**Keywords:** mini-PCNL; ultrasound guidance; GMSV position

#### **1. Introduction**

Percutaneous nephrolithotomy (PCNL) was first introduced in 1976 [1], and over the years, it has become the gold standard of surgical treatment for renal stones larger than 2 cm [2]. Conventionally, PCNL was performed via a larger percutaneous nephrostomy (PCN) tract (≥22 French) [3], under fluoroscopic guidance, with patients in the prone position. Gradually, three novel techniques have been developed and widely accepted. First, ultrasound-guided PCNL reduces or even eliminates radiation exposure by fluoroscopy [4]. Moreover, mini-PCNL with miniaturization of the PCN tract (<22 French) [3] decreases renal trauma compared to standard PCNL [5]. Moreover, mini-PCNL demonstrated non-inferior surgical outcomes to standard PCNL for 2- to 4-cm-sized renal stones [6]. Finally, the Galdakao-modified supine Valdivia (GMSV) position facilitates simultaneous bidirectional endourological procedures rather than using the prone position [7].

Nevertheless, each of these three techniques also has its own weak points. First, it is not easy to monitor the process of PCN tract dilation using ultrasound guidance [8]. In addition, mini-PCNL is associated with lower lithotripsy efficiency and longer operative time [9]. Finally, the GMSV position may lead to renal displacement during PCN tract dilation and a narrow operating space during lithotripsy [10]. Fortunately, these three techniques have

**Citation:** Liu, Y.-Y.; Chen, Y.-T.; Luo, H.-L.; Shen, Y.-C.; Chen, C.-H.; Chuang, Y.-C.; Huang, K.-W.; Wang, H.-J. Totally X-ray-Free Ultrasound-Guided Mini-Percutaneous Nephrolithotomy in Galdakao-Modified Supine Valdivia Position: A Novel Combined Surgery. *J. Clin. Med.* **2022**, *11*, 6644. https://doi.org/10.3390/ jcm11226644

Academic Editor: Bhaskar K Somani

Received: 16 October 2022 Accepted: 8 November 2022 Published: 9 November 2022

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

complementary advantages when they are combined. In the GMSV position, retrograde semi-rigid ureteroscopic assistance can be used to increase the safety of the puncture and dilation process [11]. In addition, the GMSV position improves the efficiency of mini-PCNL lithotripsy by the horizontal or downward axis of the Amplatz-type renal sheath [10]. Moreover, the GMSV position avoids repositioning from the lithotomy position to the prone position and, therefore, decreases the total operative time [12]. Mini-PCNL makes up for the insufficient operating space in the GMSV position [13]. Finally, ultrasound guidance facilitates PCNL in the supine position, including in the GMSV position [8].

Based on these complementary properties, we combined these three techniques for PCNL. To the best of our knowledge, studies of PCNL using the three combined techniques are limited. Therefore, we conducted a retrospective, single-center study to evaluate the outcomes of patients undergoing totally X-ray-free ultrasound-guided mini-PCNL in the GMSV position.

#### **2. Materials and Methods**

#### *2.1. Study Design and Sample*

This retrospective cohort study retrospectively reviewed the data of consecutive patients with upper urinary tract stone disease who had undergone one-step totally X-ray-free ultrasound-guided single-tract mini-PCNL in the GMSV position from November 2019 to March 2022 at Kaohsiung Chang Gung Memorial Hospital. Patients with age <18 years old, pregnancy, radiolucent stone, abnormal upper urinary tract anatomy (including horseshoe kidney, renal duplication, ureteropelvic junction obstruction, or ureteral stricture), preoperative severe urinary tract infection such as acute pyelonephritis or urosepsis, bleeding tendency, concurrent malignancy, multiple-tract PCNL, concurrent bilateral urinary tract endoscopic stone surgery, incomplete perioperative data or loss of follow-up were excluded. Finally, a total of 150 patients were included in the study.

#### *2.2. Ethical Considerations*

The protocol of the present study was approved by the Institutional Review Board of Kaohsiung Chang Gung Memorial Hospital (No. 202201106B0). Due to the retrospective study design, the IRB waived informed consent of the included patients.

#### *2.3. Surgical Procedure and Statistical Analysis*

All PCNL operations were performed by the same urologist (Dr. Yi Yang Liu). All included patients received basic preoperative examination, including non-contrast computed tomography (NCCT) of abdomen for image survey. The S.T.O.N.E. nephrolithotomy score (a graded system to predict patients' stone-free status) was calculated according to NCCT findings [14]. Moreover, preoperative urinary culture was collected. If the result was positive, we would use intravenous antibiotics for the pathogen during the perioperative period. Otherwise, prophylactic antibiotics would be administered to the patients 30 min before the operation and kept for 24 h after the operation.

The patient was placed in the GMSV position under general anesthesia [7]. Ipsilateral 4 or 5 French ureteral catheterization was performed initially to create artificial hydronephrosis by manual ureteral catheter injection of 0.9% sodium chloride solution. Then, an ultrasound-guided (BK5000, BK Medical, Herlev, Denmark) 18-gauge needle transpapillary puncture toward the target renal calyx was performed with the assistance of a puncture frame. The needle tip in the renal collecting system was confirmed by the urine efflux from the puncture needle sheath, and the puncture depth was then measured. Subsequently, a 0.035-inch J-tip guidewire was indwelled into the puncture needle sheath, and a 0.6 cm skin incision was made. Sequentially, both 8 and 10 French fascial dilators were followed by the puncture depth. Finally, an 18 French UltraxxTM Nephrostomy Balloon Catheter (Cook Medical, Bloomington, IN, USA) was indwelled and inflated with 0.9% sodium chloride solution under the pressure of 20 atm for 3 min, and an 18 French Amplatztype renal sheath was introduced to create the renal access. The dilation procedures were monitored by real-time ultrasound in as much detail as possible [15].

After creating the renal access, a 12 French Miniature Nephroscope (Richard Wolf, Knittlingen, Germany) and Holmium laser (Auriga XL 50 Watt, Boston Scientific, Boston, MA, USA) were used for stone fragmentation. The broken stone chips were washed out by low-pressure irrigation with 0.9% sodium chloride solution continuous irrigation from the mere height of 70 cm above the operating table. No irrigation pump or negative pressure suction device was used. Residual stones were checked by the nephroscope and ultrasound. Finally, a 4.7 or 6 French Double J stent was indwelled by the nephroscope. Either no catheter or a 14 French percutaneous nephrostomy balloon catheter was installed with 1 to 3 cc distilled water, depending on the surgeon's decision. Simultaneously, retrograde semi-rigid ureteroscopy may be performed if indicated (e.g., failed artificial hydronephrosis creation by ureteral catheterization, confirmation of the guidewire or puncture needle tip in collecting system, residual stone in upper ureter or upper calyx, or failed antegrade Double J stenting). Operative time was defined as the time from ureteral catheterization to removal of the Amplatz sheath or the placement of the percutaneous nephrostomy balloon catheter.

Stone fragments were sent for analysis postoperatively. Blood examination and kidney ureter bladder (KUB) plain X-ray were performed on postoperative day one. Stone-free status was defined as no residual stone or clinically insignificant residual fragment (CIRF) <0.4 cm in KUB on postoperative day one. All perioperative data and events associated with postoperative surgical complications within one month were recorded. All descriptive statistics were analyzed using IBM SPSS version 21.0 Software (IBM, Armonk, NY, USA).

#### **3. Results**

The patients' characteristics are listed in Table 1. Among the 150 patients, the mean age was 56.96 years, including 90 male patients and 60 female patients. Ninety-two patients underwent left-side PCNL. The mean body mass index (BMI) was 26 kg/m2, and 16.7% of the patients were obese (BMI > 30 kg/m2). The mean stone size and burden were 3.19 cm and 427 mm2, respectively. Twenty-two patients (14.7%) had staghorn stones, and 38 patients (25.3%) had both renal and upper ureteral stones. Mean stone density was 1199 Hounsfield units. Seventy percent of the patients have moderate to severe hydronephrosis. Twelve patients (8%) have history of percutaneous nephrolithotomy or open nephrolithotomy. High stone complexity (S.T.O.N.E. score -9) was noted in 36 patients (24%). The majority of patients (75.3%) belong to American Society of Anesthesiologists (ASA) classification 1 or 2. Preoperative mean hemoglobin (14.05 g/dL), mean creatinine (1.04 mg/dL), mean estimated glomerular filtration rate (eGFR) (74.3 mL/min/1.73 m2) and mean visual analog scale (VAS) for pain (0.35) were basically normal. In addition, 44 patients (29.3%) had positive urine cultures and underwent specific antibiotics treatment during the all-perioperative period.

Table 2 demonstrates the intraoperative parameters. The mean operative time was 66.22 min. Subcostal (93.3%) and middle calyceal (56.7%) punctures were used most frequently. The mean puncture depth was 8.84 cm. Thirty patients (20%) underwent nonhydronephrotic calyceal puncture with difficulty. However, the success rate of renal access creation on the first attempt was 88.7%. Retrograde semi-rigid ureteroscopic assistance was performed in 49 patients (32.7%). Tubeless procedures were performed in 21 patients (14%).


SD = standard deviation; ESWL = extracorporeal shock wave lithotripsy; URSM = ureteroscopic stone manipulation; RIRS = retrograde intrarenal surgery; PCNL = percutaneous nephrolithotomy; ASA = American Society of Anesthesiologists; eGFR = estimated glomerular filtration rate; MDRD = modification of diet in renal disease.

**Table 2.** Intraoperative parameters.


SD = standard deviation.

Postoperative outcomes are shown in Table 3. The mean hospital stay was 3.73 days, and immediate stone-free rate was 93.3% (140 patients). The mean reduction in hemoglobin was 1.04 g/dL. Compared to preoperative status, the mean postoperative eGFR was increased by 10.63 mL/min/1.73 m2. The mean postoperative VAS for pain was 2.99. Only 30 patients (20%) had postoperative VAS for pain ≥4 and needed postoperative intravenous analgesic agents for pain control. For stone analysis, 109 patients (72.7%) had calcium oxalate as the predominant stone. Regarding postoperative infection, 15 patients (10%) experienced fever >38 ◦C postoperatively. The fever was transient and subsided after antipyretic treatment in most patients. Only two patients (1.3%) had urosepsis but recovered soon without septic shock after broad-spectrum antibiotics treatment. In terms of hemorrhagic complications, 13 patients (8.7%) had transient gross hematuria that subsided spontaneously. Bladder blood clot retention was noted in two patients (1.3%) who underwent cystoscopic blood clot evacuation under general anesthesia. No blood transfusions, radiological interventions or nephrectomy for bleeding control were needed. Moreover, no intensive care unit transferation, chest or abdominal organ injury or mortality was noted. To sum up, the majority of the complications were classified as Clavien–Dindo Grade I. The incidence of Clavien–Dindo grade II and grade IIIb complications were only 1.3% and 1.3%, respectively.

**Table 3.** Postoperative outcomes.


SD = standard deviation; eGFR = estimated glomerular filtration rate; MDRD = modification of diet in renal disease.

#### **4. Discussion**

The results have revealed that totally X-ray-free ultrasound-guided mini-PCNL in the GMSV position is feasible with safety and efficacy. The mean operative time was about one hour, and the majority of cases had successful renal access creation on the first attempt. Postoperative outcomes showed that the majority of patients were stone free, and no major complication was noted. In the following discussion, we will analyze the detailed advantages through the whole process of PCNL. Figure 1 summarizes the three core techniques we used in the study and their effects on surgical outcomes.

**Figure 1.** Three core techniques and their effects on surgical outcomes.

The GMSV position, which is the combination of the oblique supine position and lithotomy position, simultaneously facilitates bidirectional endourological procedures without repositioning and saves significant operative time [7]. There is also no chest or abdominal compression in the GMSV position, which enables anesthesiologists to easily monitor and control each patient's condition intraoperatively. Moreover, urologists can be seated with better ergonomics during the surgery [10]. Therefore, we can use the GMSV position throughout the procedures of PCNL with safety and efficacy.

In percutaneous renal calyceal puncture, ultrasound guidance requires no radiation exposure and provides easy identification of the posterior calyx and perirenal adjacent organs. In the present case series, no patient experienced pleura or perirenal organ injury. In addition, arterial puncture can be avoided under doppler mode ultrasound [8]. Hence, the risk of hemorrhagic complications is also decreased. The GMSV position also aids the puncture procedure because it allows retrograde semi-rigid ureteroscopic assistance to enhance retrograde ureteral irrigation when artificial hydronephrosis cannot be created by the ureteral catheter. Surgeons may also see the puncture needle tip or guidewire directly in the renal pelvis or ureter using the retrograde semi-rigid ureteroscope to ensure a successful renal puncture.

The rest part of renal access creation, including PCN tract dilation and Amplatz-type renal sheath setup, is a critical step before lithotripsy. Under the GMSV position, renal mobility is typically obvious because of the absence of abdominal compression, and it may lead to a shorter dilation or guidewire slippage and then failure of renal access creation [10]. To reduce renal mobility, we used skills such as coordinated abdominal counterpressure and brief apnea in maximal inspiration. Additionally, the use of the balloon dilator reduces the number of times of repetitive and sequential PCN tract dilation. Moreover, balloon dilation can be monitored under ultrasound during inflation [15]. Moreover, retrograde semi-rigid ureteroscopic assistance has been used for difficult cases by setting up a throughand-through guidewire to secure the subsequent renal access creation procedures [11]. In the present study, 20% of patients underwent non-hydronephrotic calyceal puncture. Even so, the success rate of renal access creation in the first attempt was still 88.7%. This result is comparable with that of another study in terms of ultrasound-guided conventional PCNL with balloon dilation in the prone position performed by very experienced urologists (88.4%) [15]. In other words, renal access creation by ultrasound-guided mini-PCNL in the GMSV position is shown to be feasible with a high success rate in the first attempt.

The vacuum cleaner effect of lithotripsy during mini-PCNL is the basic mechanism for stone fragment removal [16]. Conventionally, mini-PCNL often needs an irrigation pump with high irrigation pressure (150 to 250 mmHg) to effectively remove stone fragments [17]. In the GMSV position, the axis of the Amplatz-type renal sheath is horizontal or slightly inclined downward toward the ground. There is no doubt that this will enhance the vacuum cleaner effect compared to the prone position [10]. In the present study, just gravity irrigation with low irrigation pressure (70 cm H2O) was used for stone fragment removal, and there was no need for the irrigation pump. Additionally, compared to the standard PCNL, the mini-PCNL allows greater exploration from the single calyx to most of the desired locations in the renal collecting system without placing excessive torque on the renal parenchyma [13]. This advantage of the mini-PCNL compensates for the restricted working space and limited instrument movement through the longer PCN tract in the GMSV position [10]. Moreover, if residual fragments are found in the upper ureter or upper calyx, retrograde semi-rigid ureteroscopy is also readily available for lithotripsy. Although 24% of patients in the present study had complex renal stones with S.T.O.N.E. nephrolithotomy scores ≥9, the overall stone-free rate was still 93.3%, which was comparable with other studies of mini-PCNL (ranging from 75.0% to 95.1%) [18] or the pooled data from the latest meta-analysis (85.1%) [19].

In the literature review, Clavien–Dindo grade I to V complication rates of mini-PCNL were 2.7–20.8%, 1.4–17.3%, 0–10.3%, 0–0.05% and 0–0.02%, respectively [20]. The results of the current study were within the range and may prove the safety of our technique.

In addition to precise transpapillary renal puncture by ultrasound guidance, the miniaturization of the PCN tract is also associated with less renal trauma and lower bleeding risk and will lead to lower pain scale scores and fewer hemorrhagic complications [9,21]. In the present study, the mean decrease in hemoglobin is 1.04 g/dL. In addition, only two patients experienced bladder blood clot retention and underwent further cystoscopic blood clot evacuation. No patient needed a blood transfusion or radiological intervention for hemorrhage. Contemporary reports of mini-PCNL also showed a very low incidence of blood transfusion (<2%) [20]. Moreover, only 20% of the patients needed postoperative intravenous analgesics. These results indicated the minimal invasiveness of the procedure.

The incidence and severity of postoperative infection were low and acceptable in the present series. It is well known that mini-PCNL with a smaller Amplatz-type renal sheath wall causes higher intrarenal pressure, which leads to pyelovenous backflow [22] and has been identified as a risk factor for sepsis after PCNL [23]. However, the horizontal or downward axis of the Amplatz-type renal sheath in the GMSV position and low irrigation pressure by gravity rather than by irrigation pump decreases the intrarenal pressure significantly and helps to avoid postoperative infection [10]. In addition, the longer operative time is another risk factor for postoperative sepsis after PCNL [23]. However, in the GMSV position, the operative time was reduced not only by a single position throughout the whole procedure but also enhancement of the vacuum cleaner effect associated with the Amplatztype renal sheath axis. Given the lower intrarenal pressure and shorter operative time in the present study, although 44 patients (29.3%) had positive preoperative urine cultures, only 15 patients (10%) experienced postoperative fever >38 ◦C, which was transient in most patients. Only two patients (1.3%) developed urosepsis, which was controlled by antibiotics administration. No patients developed septic shock. In the latest meta-analysis, the pooled incidence of fever after mini-PCNL is also about 10% [19]. Additionally, postoperative sepsis developed in 0.9–4.7% of patients after PCNL [20]. The results of current study were similar and acceptable.

The present study has several limitations. First, it was a retrospective, single-center study with the inherent limitations of these design factors. Moreover, it lacked a control group for comparison. The stone-free status was measured by KUB but not by computed tomography, which may lead to the under-detection of residual stone fragments. However, all surgeries were performed by the same urologist (Dr. Yi Yang Liu), which eliminates intersurgeon bias. To the best of our knowledge, only a few studies have investigated PCNL in combination with the three novel techniques. Therefore, this study is a pioneer in exploring the combined PCNL techniques. Further prospective, multi-institutional comparative studies are still needed to confirm the safety and efficacy of this novel procedure compared

to the conventional PCNL. Moreover, this combined technique may be suitable for some special situations, such as urolithiasis in solitary kidneys or transplant kidneys, to avoid severe intraoperative complications [24].

#### **5. Conclusions**

In this study, we found that ultrasound guidance, GMSV position and mini-PCNL are mutually complementary. Additionally, balloon dilation of the PCN tract and retrograde semi-rigid ureteroscopic assistance is helpful for renal access creation when performing ultrasound-guided PCNL under the GMSV position. Moreover, low-pressure gravity irrigation under the GMSV position ensures low intrarenal pressure and intraoperative safety. In conclusion, totally X-ray-free ultrasound-guided mini-PCNL in the GMSV position is feasible, safe and effective for patients with renal or upper ureteral stones, indicating the synergistic effects of the three novel techniques.

**Author Contributions:** Study conception and design: Y.-T.C.; provision of study patients: H.-L.L., Y.-C.S., C.-H.C. and Y.-C.C.; data acquisition: H.-L.L., Y.-C.S., C.-H.C. and Y.-C.C.; data analysis: K.-W.H.; data interpretation: Y.-Y.L. and H.-J.W.; manuscript writing: Y.-Y.L.; manuscript revision: H.-J.W. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Kaohsiung Chang Gung Memorial Hospital (No. 202201106B0, approved on 28 July 2022).

**Informed Consent Statement:** Due to the retrospective review design of this study, the IRB waived informed consent of the included patients.

**Data Availability Statement:** The datasets generated during the current study are available from the corresponding author upon reasonable request.

**Acknowledgments:** We thank all the patients and staff at the Department of Urology of the Kaohsiung Chang Gung Memorial Hospital for their valuable support of this study.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**


## *Article* **Variation in Tap Water Mineral Content in the United Kingdom: Is It Relevant for Kidney Stone Disease?**

**Kirolos G. F. T. Michael <sup>1</sup> and Bhaskar K. Somani 2,\***


**Abstract:** Introduction: The dissolved mineral content of drinking water can modify a number of excreted urinary parameters, with potential implications for kidney stone disease (KSD). The aim of this study is to investigate the variation in the mineral content of tap drinking water in the United Kingdom and discuss its implications for KSD. Methods: The mineral composition of tap water from cities across the United Kingdom was ascertained from publicly available water quality reports issued by local water supply companies using civic centre postcodes during 2021. Water variables, reported as 12-monthly average values, included total water hardness and concentrations of calcium, magnesium, sodium and sulphate. An unpaired t-test was undertaken to assess for regional differences in water composition across the United Kingdom. Results: Water composition data were available for 66 out of 76 cities in the United Kingdom: 45 in England, 8 in Scotland, 7 in Wales and 6 in Northern Ireland. The median water hardness in the United Kingdom was 120.59 mg/L CaCO3 equivalent (range 16.02–331.50), while the median concentrations of calcium, magnesium, sodium and sulphate were 30.46 mg/L (range 5.35–128.0), 3.62 mg/L (range 0.59–31.80), 14.72 mg/L (range 2.98–57.80) and 25.36 mg/L (range 2.86–112.43), respectively. Tap water in England was markedly harder than in Scotland (192.90 mg/L vs. 32.87 mg/L as CaCO3 equivalent; *p* < 0.001), which overall had the softest tap water with the lowest mineral content in the United Kingdom. Within England, the North West had the softest tap water, while the South East had the hardest water (70.00 mg/L vs. 285.75 mg/L as CaCO3 equivalent). Conclusions: Tap water mineral content varies significantly across the United Kingdom. Depending on where one lives, drinking 2–3 L of tap water can contribute over one-third of recommended daily calcium and magnesium requirements, with possible implications for KSD incidence and recurrence.

**Keywords:** urolithiasis; kidney calculi; tap water; mineral composition; kidney stones

#### **1. Introduction**

The aetiology of kidney stone disease (KSD) is complex and is the product of the intricate interplay between dietary, lifestyle, environmental and genetic factors which predispose individuals to disease [1]. In the United Kingdom, the prevalence of KSD is rising, with an estimated 1 in 7 individuals requiring intervention during their lifetime, posing a substantial burden to health services [2,3]. There is therefore great impetus for investigating factors implicated in KSD, which may lead to more specific preventative strategies.

At present, the mainstay of KSD prevention is to advise patients to increase their daily fluid intake [4,5]. Nevertheless, whether or not the type of fluid matters is still debatable. Amongst studies conducted to investigate whether any type of water is superior for patients with KSD, there is a weak consensus that mineral-rich water may result in favourable changes to urine composition, which may reduce the risk of calcium stone formation [6]. For this reason, a number of studies have sought to compare the mineral composition of drinking water, whether bottled or supplied through taps, to further study the association between water composition and KSD [7–9].

**Citation:** Michael, K.G.F.T.; Somani, B.K. Variation in Tap Water Mineral Content in the United Kingdom: Is It Relevant for Kidney Stone Disease? *J. Clin. Med.* **2022**, *11*, 5118. https:// doi.org/10.3390/jcm11175118

Academic Editors: Francisco Guillen-Grima and Ersilia Lucenteforte

Received: 2 August 2022 Accepted: 28 August 2022 Published: 30 August 2022

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Drinking water supplied through taps is derived from different sources depending on the region, leading to variations in its dissolved mineral content. [10] The "hardness" of tap water reflects the quantity of dissolved metal ions, principally calcium and magnesium [11]. Given the recognised implications of drinking water on human health, most countries monitor and tightly regulate tap water quality and composition, though recommended ranges and maximum values are largely not based on research [12]. In the United Kingdom, governmental studies have revealed that up to 97% of adults drink tap water, with the average adult consuming 1.3 L of tap water per day, accounting for nearly two-thirds of daily fluid consumption in England and Wales [13]. Given these findings, the aim of this study is to investigate the variation in tap water composition across the United Kingdom and describe potential implications for KSD.

#### **2. Materials and Methods**

The mineral composition of tap water during 2021 across all officially designated cities in the United Kingdom was investigated from online, publicly available water quality reports obtained from the local water supply company using the postcode of the city hall or civic centre, as a representative of the area. Where reports were not available online, water supply companies were contacted directly to request these. Cities that did not have water quality reports covering 2021 were excluded. Water variables collected included total water hardness, in addition to the concentrations of calcium, magnesium, sodium and sulphate where available. Values obtained represent an average value over a 12-month period for a given area. Potassium and bicarbonate concentrations were not included due to insufficient data across the regions to enable comparison.

To determine whether tap water mineral composition varies significantly between regions of the United Kingdom, a pairwise comparison of mean water variables was undertaken between constituent countries in the United Kingdom. Statistical analysis was undertaken using SPSS Statistics for Windows, version 25 (IBM Corp., Armonk, NY, USA), and statistical significance was determined at the ≤0.05 level.

#### **3. Results**

#### *3.1. Comparison of Water Composition across Constituent Countries in the United Kingdom*

In total, 66 out of 76 cities in the United Kingdom were included in this study: 45 in England, 8 in Scotland, 7 in Wales and 6 in Northern Ireland. Tap water was supplied to these by 17 different water supply companies across the United Kingdom.

The median water hardness in the United Kingdom was 120.59 mg/L CaCO3 equivalent (range: 16.02–331.50). The median concentrations of calcium, magnesium, sodium and sulphate were 30.46 mg/L (range: 5.35–128.0), 3.62 mg/L (range: 0.59–31.80), 14.72 mg/L (range: 2.98–57.80) and 25.36 mg/L (range: 2.86–112.43), respectively.

A comparison of the median values and ranges of water composition variables of interest between countries in the United Kingdom is presented in Table 1 and Figure 1. Compared to Scotland, which had the lowest mineral content, tap water in England was significantly harder (192.90 mg/L vs. 32.87 mg/L as CaCO3 equivalent) and had a higher concentration of calcium (77.56 mg/L vs. 10.69 mg/L), magnesium (4.65 mg/L vs. 1.59 mg/L), sodium (17.90 mg/L vs. 6.39 mg/L) and sulphate (37.00 mg/L vs. 9.07 mg/L) when comparing median values. A pairwise comparison of mean water variables revealed statistically significant differences between water composition values across the United Kingdom (Table 2).


N.D. denotes no data available.

**Table 1.** Comparison of water composition by country in the United Kingdom.

**Figure 1.** Distribution of the mineral composition of tap water across the United Kingdom. Mineral composition of tap water by country (mg/L). (**a**) Total water hardness as CaCO3 equivalent (**b**) Calcium concentration (**c**) Magnesium concentration (**d**) Sodium concentration (**e**) Sulphate concentration. -Outlier (value > 1.5 IQR); Extreme outlier (value > 3 IQR). N.D. denotes no data available.


**Table 2.** Pairwise t-test significance values for differences in mean water variables by country in the United Kingdom.

N.D. denotes no data available; *p* values in bold are statistically significant at the 0.05 level.

#### *3.2. Regional Variation in Tap Water Composition across England*

Given the wide range of water variables in England, a comparison of tap water composition across the different regions of England was undertaken. Cities in eight out of the nine regions in England had freely available water quality reports from 2021, with no cities in the Yorkshire and the Humber region reporting water composition beyond 2020 at the time of the investigation. The differences in water composition across the eight regions are presented in Table 3 and Figure 2. Even within England, there was a four-fold difference between the region with the hardest tap water (South East) and the region with the softest water (North West). Similarly, there was approximately a six-fold difference between the region with the highest calcium concentration (East) and the North West, as well as a near the 13-fold difference between the region with the highest magnesium concentration (East Midlands) and the North West.


N.D. denotes no data available.

**Table 3.** Comparison of water composition by region in England.

**Figure 2.** Distribution of the mineral composition of tap water across England Mineral composition of tap water by region (mg/L). (**a**) Total water hardness as CaCO3 equivalent (**b**) Calcium concentration (**c**) Magnesium concentration (**d**) Sodium concentration (**e**) Sulphate concentration. - Outlier (value > 1.5 IQR); Extreme outlier (value > 3 IQR).

#### *3.3. Comparison of Bottled Water and Tap Water*

Tap water mineral content in the United Kingdom was compared to that of commonly available bottled water brands comprising 11 brands of still water and 6 of sparkling water, as previously described by Stoots et al. (Table 4) [8]. Compared to bottled still and sparkling water from popular brands in the United Kingdom, tap water had a lower median calcium and magnesium concentration but a greater range in these values overall. By contrast, tap water had a higher sodium and sulphate content compared to bottled water.


**Table 4.** Comparison of bottled and tap water in the United Kingdom.

#### **4. Discussion**

#### *4.1. Findings from Our Study*

Our study described the variation in the mineral composition of drinking water supplied through taps across the United Kingdom. We found significant regional variation in tap water hardness and calcium, magnesium, sodium and sulphate concentrations of tap water. Notably, we report a 24-fold and 54-fold difference between the maximum and minimum tap water calcium and magnesium concentrations across regions of the United Kingdom. Interestingly, whilst bottled water, on average, had higher concentrations of most minerals of interest, the ranges of these values for tap water were larger. As far as the authors are aware, this study is the first to compare tap water mineral content across the different cities and regions of the United Kingdom.

#### *4.2. Mineral Content and Pathogenesis of KSD*

A number of minerals present in drinking water likely play a role in the pathogenesis of KSD, particularly calcium, magnesium and sodium. At present, the literature is in agreement that moderate calcium intake is protective against KSD, though supplemental calcium may not be beneficial and could, on the contrary, increase the risk of calcium nephrolithiasis, especially if taken separately from meals [14]. Likewise, the role of magnesium in protecting against KSD is widely recognised, while sulphate may be protective against calcium nephrolithiasis by reducing ionised urinary calcium and supersaturation of calcium salts [6,15–17]. Conversely, sodium in the form of salt (sodium chloride) is a well-established risk factor for calcium nephrolithiasis, and it is a routine clinical practice to counsel patients at risk of KSD to reduce their salt intake [18].

#### *4.3. Comparison with Previous Studies*

Several studies investigating tap water mineral variation have been undertaken, with comparable findings. In the Flanders region of Belgium, tap water mineral content was found to vary significantly, with a 10-fold and 12-fold difference between the highest and lowest calcium and magnesium concentrations with similar maximum values reported compared to the United Kingdom [9]. Similarly, in Australia, tap water calcium was found to vary regionally by a factor of 15.6, while magnesium varied by a factor of 10.7, though unlike in Flanders, the mineral content of tap water overall was significantly lower compared to the United Kingdom, with the maximum calcium and magnesium concentrations being approximately 6-times and 3-times lower [19]. In North America, one study found a 42-fold difference in tap water calcium concentration, while there was a 48-fold difference in magnesium concentration between regions with the highest and lowest concentrations [20]. It should be noted that these comparisons are, in most cases, between regions with the highest and lowest 12-monthly average figures; thus, differences are likely to be even larger if day-to-day variations are considered.

#### *4.4. Implications for Clinical Practice*

For adults living in the United Kingdom, the recommended daily intake for calcium is 700 mg/d, while for magnesium, it is 300 mg/d (males) or 270 mg (females); for sodium, it is 2400 mg/d [21]. Our study found that depending on where one lives, drinking 2 L of tap water can contribute 1.5–36.6% of recommended daily calcium intake and 0.4–23.6% of daily magnesium intake, making tap water a significant but often overlooked source of these minerals. By contrast, tap water contributes 0.2–4.7% of daily sodium intake, which is relatively insignificant compared to other dietary sources. Furthermore, the proportion of calcium and magnesium derived from tap water is likely to be even higher for KSD patients, who will often be advised to drink up to 3 L of fluid per day. The British Association of Urological Surgeons (BAUS) includes advice on calcium intake in its "dietary advice for stone formers" patient information leaflet, highlighting that daily intake of up to 1,000 mg of calcium is safe whilst also detailing the calcium content of a number of dairy products for reference [22]. Our finding that tap water in the United Kingdom can be a significant contributor to daily calcium intake raises an interesting question: should clinicians routinely advise KSD patients to be mindful of the mineral content of their tap water? Similarly, should such advice be included on patient information leaflets?

Having recognised that significant variations in the mineral content of tap water exist regionally and globally and that tap water can be a significant contributor to daily calcium and magnesium intake, the question then becomes whether these regional variations are of clinical significance when it comes to KSD incidence and recurrence. A number of interventional studies have demonstrated that consumption of drinking water with different mineral compositions can result in changes to excreted urinary calcium, magnesium and citrate levels as well as urinary pH, with a weak consensus in the literature favouring hard, mineral-rich water for patients at risk of KSD [6]. When compared to tap water in our study, the mineral content of different types of water included in these study protocols was, for the most part, within the ranges of total hardness, calcium and magnesium levels in tap water in the United Kingdom, although the maximum calcium concentrations in some of the studies were significantly higher, being derived from bottled mineral water [23–25]. It can therefore be hypothesised that variation in the mineral content of tap water in the United Kingdom may translate into variations in excreted urinary parameters of key promoting and inhibitory lithogenic factors. This is supported by a large North American study which found that 24-h urine calcium, magnesium and citrate increased with tap water hardness [26]. Nevertheless, the same study did not find large differences in the number of lifetime KSD episodes between those living in regions with soft versus hard water, though dietary, metabolic and other environmental risk factors for urolithiasis were not controlled for. Moreover, in Iran, a weak inverse correlation was demonstrated between tap water magnesium concentration and KSD incidence, further raising the possibility that tap water variations may be implicated in KSD incidence [27].

#### *4.5. Limitations and Future Direction*

A number of limitations are present in our study. Since water composition data were derived from 19 different water supply companies providing for the 66 cities included in our study, there was a degree of heterogeneity in how tap water quality and composition were reported between companies. Though all values were reported as a 12-monthly average, with most companies reporting mean values, for others, it was not clear what kind of average was reported. Furthermore, a number of water supply companies did not report all variables of interest in this study, though every company reported total water hardness, and the vast majority reported calcium and magnesium levels. Few reports included pH, bicarbonate and potassium levels and hence were not included in our study since meaningful comparisons between regions could not be undertaken. While our study described variations in tap water mineral composition, it did not relate this to KSD incidence or recurrence. Finally, we considered the mineral content of tap water in light of KSD; however, there are a number of other conditions, including mineral bone disease, that may be impacted by drinking water mineral composition, which should not be neglected when advising patients on the optimal type of water [28]. To further investigate the association between tap water and KSD, future studies should explore whether variation in tap water mineral content correlates with KSD incidence. Additionally, it would be interesting to determine whether there are significant regional variations in urinary calculus composition and, if so, whether these correlate with any tap water variable since different types of calculi may be impacted in different ways by different types of water. In the future, it would also be interesting to perform additional epidemiological studies, in particular ecological studies related to water composition and incidence of KSD.

#### **5. Conclusions**

The mineral content of tap water varies significantly between different regions in the United Kingdom. Depending on where one lives, drinking 2–3 L of tap water per day can contribute over one-third of recommended daily calcium and magnesium intake, making tap water a significant but often overlooked source of these minerals. Whilst the exact relationship between drinking water mineral content and KSD incidence and recurrence has yet to be fully elucidated, clinicians should be mindful that in some regions, tap water can be a significant source of important minerals such as calcium, especially when counselling patients already on supplementation for other medical conditions. Future studies should focus on tailoring preventative strategies related to fluid consumption to the type of drinking water available to patients, 24-h urine chemistries and calculus composition to deliver more effective, personalised preventative strategies for patients at risk of recurrence.

**Author Contributions:** K.G.F.T.M.: Methodology, investigation, visualisation, writing—original draft preparation; B.K.S.: conceptualisation, supervision, writing—review and editing. All authors have read and agreed to the published version of the manuscript.

**Funding:** No funds: grants or other support was received for conducting this study.

**Institutional Review Board Statement:** This study does not describe research on patients or human subjects and hence did not require ethical approval.

**Informed Consent Statement:** Informed consent was not required, as it is a review article.

**Data Availability Statement:** Data generated and analysed are included in this study. Further enquiries can be directed to the corresponding author regarding acquisition of water quality reports used in this investigation.

**Conflicts of Interest:** The authors have no conflict of interest, financial or otherwise, to declare.

#### **References**

