Urolithiasis

Role of ‘dusting and pop-dusting’ using a high-powered (100 W) laser machine in the treatment of large stones (≥ 15 mm): prospective outcomes over 16 months Abstract Ureteroscopy and laser stone fragmentation (URSL) has had recent advancements with the more powerful laser systems with the ability to ‘dust’ and ‘pop-dust’ the stone. We wanted to look at the outcomes of this method for large stones (≥ 15 mm) using our new 100 W holmium laser. Over a period of 16 months (January 2017–April 2018), 50 patients underwent URSL for minimum cumulative stone size of ≥ 15 mm. Data were collected prospectively on patient and stone demographics and outcomes of URSL. The laser setting used was a power of 0.3–0.6 J and a frequency of 20–50 Hz using a long-pulse setting with a 272-µm fiber. Fifty patients underwent 55 URSL procedures (5 bilateral procedures) using dusting and pop-dusting settings. The mean age was 58 years (range 2–88 years) with a male:female ratio of 35:15. The mean single and overall stone size were 10.3 mm (3–23 mm) and 21 mm (range 15–52 mm) with two-thirds of all patients (65%) having multiple stones. The stone location was in the kidney (n = 65, 78%), in the ureter (n = 19, 22%) and 5 patients had bilateral renal stones. With a mean operating time of 51 min, the initial and final SFR were 93 and 98%, respectively. A pre-operative stent, access sheath and a post-operative stent were present in 29 (53%), 34 (62%) and 51 (93%) procedures, respectively. Over a mean hospital stay of 0.6 days (74% day-case procedures), there was one Clavien IV complication related to urosepsis but without any other major or minor complications. Dusting and pop-dusting techniques achieve an excellent SFR with low risk of complications even for large stones. This might set a new benchmark for treating large stones, bilateral or multiple stones in a single setting, without the need for secondary procedures in most cases.

Development of a two-stage model system to investigate the mineralization mechanisms involved in idiopathic stone formation: stage 2 in vivo studies of stone growth on biomimetic Randall’s plaque Abstract Idiopathic stone formers often form calcium oxalate (CaOx) stones that are attached to calcium phosphate (CaP) deposits in the renal tissue, known as Randall’s plaques (RP). Plaques are suggested to originate in the renal tubular basement membrane and spread into the interstitial regions where collagen fibrils and vesicles become mineralized; if the epithelium is breached, the RP becomes overgrown with CaOx upon exposure to urine. We have developed a two-stage model system of CaP–CaOx composite stones, consisting of Stage (1) CaP mineralized plaque, followed by Stage (2) CaOx overgrowth into a stone. In our first paper in this series (Stage 1), osteopontin (and polyaspartate) were found to induce a non-classical mineralization of porcine kidney tissues, producing features that resemble RP. For the Stage 2 studies presented here, biomimetic RPs from Stage 1 were implanted into the bladders of rats. Hyperoxaluria was induced with ethylene glycol for comparison to controls (water). After 4 weeks, rats were sacrificed and the implants were analyzed using electron microscopy and X-ray microanalyses. Differences in crystal phase and morphologies based upon the macromolecules present in the biomimetic plaques suggest that the plaques have the capacity to modulate the crystallization reactions. As expected, mineral overgrowths on the implants switched from CaP (water) to CaOx (hyperoxaluric). The CaOx crystals were aggregated and mixed with organic material from the biomimetic RP, along with some amorphous and spherulitic CaOx near the “stone” surfaces, which seemed to have become compact and organized towards the periphery. This system was successful at inducing “stones” more similar to human idiopathic kidney stones than other published models.

Combined antegrade and retrograde access to difficult ureters: revisiting the rendezvous technique Abstract Introduction Complex ureteric strictures present a significant challenge to the endourologist and uro-radiologist. Multiple separate interventions to try to cross the stricture are often attempted. We describe our experience managing a heterogenous patient group using the ‘rendezvous’ procedure. Methods and materials 16 patients and 18 ureters (one bilateral procedure, and two separate procedures in one patient) underwent rendezvous procedures. Seven patients had coexisting ureteric calculi treated. Each case was followed up for between 3 months and 5 years. Results In 16/18 ureters there was technical success at time of surgery; successfully crossing the stricture, allowing ureteroscopic access to the ureter, dilating and/or stenting the ureter. 2/18 were unsuccessful; one secondary to advanced malignancy resulting in a uretero-vaginal fistula and the second a failure to remove a retained, displaced ureteric stent. Of the 18 ureteric procedures; 7/18 were stent free at 3 months, improving to 8/18 stent free at 6 months. 4/18 remained nephrostomy dependent (failure of drainage despite stent or failure to stent) at 3 months, increasing to 6/18 being nephrostomy dependent at 6 months. 1/16 remained dialysis dependent with a nephrostomy tube. For those procedures involving ureteric calculi, 6/7 were stone free and 1/5 had a persistent stone fragment requiring further intervention. Conclusions A combined approach may decrease the number of separate interventions required, with the aim of removing the need for a long-term nephrostomy, as well as providing opportunity to treat ureteric calculi in the context of stricture disease. Our experience has been that where the rendezvous has been required to treat strictures caused by malignant extrinsic compression, stenting has not been successful; this information is key to informed consent in a group of patients who may have a limited life expectancy.

Long-term effects of anatrophic nephrolithotomy on selective renal function Abstract To evaluate the long-term changes of selective renal function after anatrophic nephrolithotomy (ANL). A retrospective study was conducted for patients who underwent ANL between January 1995 and December 2016. Inclusion criteria were availability of preoperative and follow-up (1 year or more) radio-isotopic renal scans. Stone-free status was evaluated after 1 month with KUB and ultrasonography or NCCT. Renal isotope scans using 99mTc MAG3 were performed to measure the changes in selective function of the affected kidney (GFR%). Eligible patients were classified into two groups, group 1 patients with stable or improved function and group 2 patients with deteriorated function (> 5% decrease in GFR%). Univariate and multivariate analyses were performed to determine risk factors for deterioration of renal function. The cutoff value for any significant variable was determined using ROC curve. The study included 50 patients with mean age 43.8 + 13.9 years. Complications developed in 26 patients (52%), and stone-free status was documented in 42 patients (84%). After a median follow-up of 2.7 years (range 1–11), mean GFR% of all cases significantly decreased from preoperative value of 52.7% + SD 20 to 45.4% + SD 25% during follow-up (P < 0.001). Deterioration of GFR% was documented in 21 kidneys (42%). Cold ischemia time with a cutoff value 50 min was the independent risk factor (RR 3.986, 95% CI 1.069–14.869, P 0.039). The results of this study support limiting ANL to a selected group of patients and taking all the possible efforts to minimize cold ischemia time below 50 min.

Hypertension and renal impairment in patients with cystinuria: findings from a specialist cystinuria centre Abstract Higher blood pressures (mean systolic difference 16.8 mmHg) when compared to matched individuals are already reported in patients with calcium urolithiasis. We present the prevalence of hypertension and renal impairment in patients with cystinuria from our specialist single centre. We analysed our prospective database of adult patients with cystinuria who attend our cystinuria service. This included details of the medical and operative management of their disease. Descriptive statistics were used to analyse and present the data. 120 patients were included with a median age of 40 (19–76) years, 66 were male (55%) and 54 were female (45%). 54/120 patients (45%) were taking medications to prevent stone formation. 78% (94/120) patients reported having undergone one or more stone-related procedure. 59% (55/94) of these having required at least one PCNL or open procedure during their lifetime. Prevalence of hypertension was 50.8% (61/120), and double in males compared to females (62.1% vs. 37.0%, P = 0.0063). Mean baseline creatinine was 88.2 (49–153) µmol/l and eGFR was 77.6 (32–127) ml/min/1.73 m2. When categorized by CKD stage, only 24.6% (27% vs. 21%, M vs. F) patients had normal renal function (being an eGFR > 89 ml/min/1.73 m2). 57.6% patients were CKD stage 2 and 17.8% CKD stage 3. Females had a slightly greater incidence of renal impairment. All patients who have previously undergone a nephrectomy (n = 10) or have a poorly functioning kidney (n = 19) have renal impairment (CKD stage 2 or 3). Incidence of hypertension in patients with cystinuria is 51%, with a male preponderance. Only 25% of patients with cystinuria have normal renal function. This highlights the long-term cardiovascular and renal risks that the metabolic effects of cystinuria pose, in addition to the challenges of managing recurrent urolithiasis in a young population.

Hydroxycitrate: a potential new therapy for calcium urolithiasis Abstract Alkali supplements are used to treat calcium kidney stones owing to their ability to increase urine citrate excretion which lowers stone risk by inhibiting crystallization and complexing calcium. However, alkali increases urine pH, which may reduce effectiveness for patients with calcium phosphate stones and alkaline urine. Hydroxycitrate is a structural analog of citrate, widely available as an over-the-counter supplement for weight reduction. In vitro studies show hydroxycitrate has the capacity to complex calcium equivalent to that of citrate and that it is an effective inhibitor of calcium oxalate monohydrate crystallization. In fact, hydroxycitrate was shown to dissolve calcium oxalate crystals in supersaturated solution in vitro. Hydroxycitrate is not known to be metabolized by humans, so it would not be expected to alter urine pH, as opposed to citrate therapy. Preliminary studies have shown orally ingested hydroxycitrate is excreted in urine, making it an excellent candidate as a stone therapeutic. In this article, we detail the crystal inhibition activity of hydroxycitrate, review the current knowledge of hydroxycitrate use in humans, and identify gaps in knowledge that require appropriate research studies before hydroxycitrate can be recommended as a therapy for kidney stones.

Does leaving residual fragments after percutaneous nephrolithotomy in patients with positive stone culture and/or renal pelvic urine culture increase the risk of infectious complications? Abstract The residual fragments in patients with preoperative and intraoperative culture positivity may serve as an infection focus. The aim of this study was to assess the importance of residual fragments for developing SIRS in patients with stone culture and/or RPUC positivity. After obtaining institutional review board approval, a total of 729 patients who undergone PCNL for renal stones were included in this study. Residual fragments accepted to be positive if any fragment was detected irrespective of size. All patients were followed-up postoperatively for SIRS criteria. The patients were then followed-up for residual stone-related events and infectious complications. 94 of the 729 patients have developed SIRS postoperatively. SIRS positivity was more common among males and found to be associated with higher stone burden and presence of staghorn stone. Patients with residual fragments after PCNL also had higher rates of SIRS. In the subgroup analysis of 203 patients who had post-PCNL residual fragments, the peroperative stone and/or RPUC positivity was not found to be associated with the development of the SIRS. Although presence of residual fragments after PCNL is associated with SIRS development, stone culture and/or RPUC positivity has no additional risk for development of post-PCNL infectious complications in patients with residual fragments.

Is oxidized low-density lipoprotein the connection between atherosclerosis, cardiovascular risk and nephrolithiasis? Abstract Nephrolithiasis is considered a systemic disease. A link has been established between nephrolithiasis, cardiovascular disease (CVD), the metabolic syndrome and atherosclerosis. A significant correlation has been found between the high levels of oxidized low-density lipoprotein (oxLDL) and CVD and atherosclerosis, including coronary and femoral artery disease. To the best of our knowledge, oxLDL has not been evaluated in patients with nephrolithiasis. This study aimed to evaluate serum levels of oxLDL, anti-oxLDL antibodies (oxLDL-ab) and other markers of atherosclerosis in patients with nephrolithiasis, according to the severity of the disease. The population sample consisted of 94 patients of 30–70 years of age with no symptoms of CVD who presented with renal calculi documented by ultrasonography, abdominal X-ray or computed tomography. The patients were divided into two groups: Group 1 (≥ 3 stones) and Group 2 (1–2 stones). A comparison control group was formed with 21 healthy individuals. Enzyme-linked immunosorbent assays were used to assess oxLDL and oxLDL-ab. Lipid peroxidation indexes were also analyzed. Median serum oxLDL values were higher in Groups 1 and 2 compared to the control group (≥ 3 stones, p = 0.02; 1–2 stones, p = 0.03). Median serum anti-oxLDL antibody levels were lower in the patients in Group 1 compared to the controls (p = 0.03). There was no significant difference in the oxLDL/oxLDL-ab ratio between patients and controls. These findings suggest that this may be the link between nephrolithiasis and the greater incidence of atherosclerosis and cardiovascular disease in patients with kidney stones.

An in vitro evaluation of laser settings and location in the efficiency of the popcorn effect Abstract To examine different locations and laser settings’ effects on the efficiency of the “popcorn” method of laser lithotripsy, which consists of placing the laser in a group of small stones and firing continuously to break them into smaller particles. Pre-fragmented BegoStones were created between 2 and 4 mm to mimic typical popcorning conditions. A 0.5 g collection of fragments was placed into 3D-printed models (a spherical calyx and ellipsoid pelvis model) and a 200-µm laser fiber was positioned above the stones. The laser was fired for 2 min with irrigation, with 5 trials at each setting: 0.2 J/50 Hz, 0.5 J/20 Hz, 0.5 J/40 Hz, 1 J/20 Hz, 0.2 J/80 Hz, 0.5 J/80 Hz. After drying, fragmentation efficiency was determined by calculating the mass of stones reduced to sub-2 mm particles. Statistical analysis was performed with ANOVA and Student’s t test. The trials within the calyx model were significantly more efficient compared to the pelvis (0.19 vs 0.15 g, p = 0.01). When comparing laser settings, there was a difference between groups by one-way ANOVA [F(5,54) = 8.503, p = 5.47 × 10−6]. Post hoc tests showed a power setting of 0.5 J/80 Hz was significantly more efficient than low-power settings 0.2 J/50 Hz and 0.5 J/20 Hz (p < 0.05). Additionally, 0.2 J/50 Hz was significantly less efficient than 0.5 J/40 Hz, 1 J/20 Hz, and 0.2 J/80 Hz. Popcorning is most efficient in smaller spaces; we recommend displacement of stones into a calyx before popcorning. No difference was seen between high-power settings, although 0.5 J/40 Hz and 0.5 J/80 Hz performed best, suggesting that moderate energy popcorning methods with at least 0.5 J per pulse are most efficient.

Development of a two-stage in vitro model system to investigate the mineralization mechanisms involved in idiopathic stone formation: stage 1—biomimetic Randall’s plaque using decellularized porcine kidneys Abstract Idiopathic calcium oxalate (CaOx) stone formers form stones that are commonly attached to calcium phosphate (CaP) deposits in the renal tissue, known as Randall’s plaques (RP). Plaques are suggested to originate in the renal tubular basement membrane, where they exhibit a morphology of concentrically laminated apatitic spherules, while in the interstitial regions, the collagen fibrils and vesicles become mineralized. We hypothesize that these minerals might form by non-classical crystallization mechanisms, such as via amorphous precursors, some of which might originate from a polymer-induced liquid-precursor (PILP) process. Thus, our goal is to identify mineralogical ‘signatures’ of various stone formation mechanisms. To do this for idiopathic CaOx stones, we are developing a two-stage model system of CaP–CaOx composite stones, consisting of stage (1) CaP mineralized plaque, followed by stage (2) CaOx overgrowth into a stone. For the studies presented here, decellularized porcine kidneys were mineralized with CaP using polyaspartic acid or the protein osteopontin (OPN) to induce the PILP process and create biomimetic RP. Analysis of the PILP-mineralized tissues shows features that resemble the native plaques, including mineral spherules and collagen with intrafibrillar mineral. In contrast, the classical crystallization produced large apatitic spherulites, which is a very different morphology, but one which is also found in some stones. An alternative hypothesis regarding Randall’s plaque, and if or when it becomes pathological, is discussed.