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Journal: Urolithiasis


Prevention of recurrent calcium stone disease includes treatment with thiazide and thiazide-type diuretics to reduce urinary calcium (UCa) levels, with the reduction in UCa correlating with risk of stone recurrence. There has been a recent trend of using lower doses of these medications and change from chlorthalidone (CTL) use to hydrochlorothiazide (HCTZ) use. It is unknown whether low doses of HCTZ are effective in lowering UCa levels to target levels. We hypothesize that HCTZ is associated with less reduction in UCa than is CTL when comparing currently used doses. Retrospective observational study of stone-formers was seen in metabolic stone clinic during a 3 years period. Data included patient demographics, co-morbidities, and 24 h urine electrolyte composition. Primary outcome was the change in 24 h UCa. 322 patients were identified with 112 meeting criteria and used in analysis. The majority were placed on HCTZ (n = 42) or CTL (n = 47) 25 mg QD. Patients on CTL 25 mg had a greater reduction in UCa (164 mg; 41 %) than those on HCTZ (85 mg; 21 %), p = 0.01. Neither CTL nor HCTZ at 12.5 mg QD significantly lowered UCa. There was a decrease in serum [K] of 0.5 Meq/L (p = 0.001) in patients on CTL 25 mg daily, but no significant difference in severe hypokalemia or arrhythmia compared to HCTZ. Our data show that CTL is associated with greater reduction in 24 h UCa compared to similarly dosed HCTZ.

Concepts: Kidney, Observational study, Urinary bladder, Urethra, Gout, Diuretic, Hydrochlorothiazide, Hypokalemia


Herbal remedies are increasingly being considered as suitable long-term treatments for renal dysfunction. The objective of the present study was to investigate the effect of some herbal extracts, all previously identified in published studies as influencing kidney stone formation, on the crystallization characteristics of calcium oxalate (CaOx) in synthetic urine (SU). Five herbal extracts were selected for the study: Folium pyrrosiae, Desmodium styracifolium, Phyllanthus niruri, Orthosiphon stamineus and Cystone(®). Concentrated stock solutions of each herbal extract were prepared and were tested at their recommended dosages in in vitro crystallization studies in SU. CaOx crystallization experiments were performed in which the metastable limit (MSL), average particle size, and nucleation and growth rates were determined. The CaOx MSL of SU was unaltered by the five herbal extracts. Three of the herbs (Desmodium styracifolium, Orthosiphon stamineus and Cystone(®)) significantly reduced the average particle size of precipitated crystals relative to undosed SU. All of the extracts increased the rate of nucleation and decreased the rate of growth significantly in SU. Cystone(®) showed the greatest effect on the measured risk factors. It is concluded that all of the herbs have the potential to serve as inhibitors of calcium oxalate stone formation and warrant investigation in clinical trials.

Concepts: Kidney, Crystallization, Herbalism, Kidney stone, Nucleation, Calcium oxalate, Phyllanthus, Phyllanthus niruri


Stone disease is a unique condition that requires appropriate management in a timely manner as it can result in both emergent conditions and long term effects on kidney functions. In this study it is aimed to identify the up-to-date practice patterns related to preoperative evaluation and anesthesia for stone disease interventions during COVID-19 pandemic. The data of 473 patients from 11 centers in 5 different countries underwent interventions for urinary stones during the Covid-19 pandemic was collected and analyzed retrospectively. Information on the type of the stone related conditions, management strategies, anesthesiologic evaluation, anesthesia methods, and any alterations related to COVID-19 pandemic was collected. During the preoperative anesthesia evaluation thorax CT was performed in 268 (56.7%) and PCR from nasopharyngeal swab was performed in 31 (6.6%) patients. General anesthesia was applied in 337 (71.2%) patients and alteration in the method of anesthesia was recorded in 45 (9.5%) patients. A cut-off value of 21 days was detected for the hospitals to adapt changes related to COVID-19. Rate of preoperative testing, emergency procedures, conservative approaches and topical/regional anesthesia increased after 21 days. The preoperative evaluation for management of urinary stone disease is significantly affected by COVID-19 pandemic. There is significant alteration in anesthesia methods and interventions. The optimal methods for preoperative evaluation are still unknown and there is discordance between different centers. It takes 21 days for hospitals and surgeons to adapt and develop new strategies for preoperative evaluation and management of stones.


This study aimed at comparing the success rates of silodosin to the most commonly used for medical expulsive therapy (MET) tamsulosin for the management of ureteral stones. A systematic review using the search string: “silodosin AND (ston* OR calcu* OR expul*)” was conducted on Pubmed, SCOPUS, Web of Science, Cochrane Central Register. The Primary endpoint was the stone expulsion rate. Secondary endpoint was the time to stone expulsion. Two authors independently screened the studies depending on inclusion and exclusion criteria. Meta-analysis and forest-plot figures were calculated with the software Review Manager (RevMan 5.3.5). Variations were evaluated with the χ (2) statistical method and heterogeneity with I (2) index. After screening of 39 publications obtained by the initial search, three randomized controlled trials were eligible to be included in the meta-analysis. 407 patients were pooled. Favorable results were observed for silodosin in terms of stone expulsion rates with a risk ratio of 1.33 (95 % CI 1.17-1.50) (I (2) = 0 %). Similarly, faster stone expulsion times were observed with silodosin when compared with tamsulosin. Mean difference -2.49 (95 % CI -3.40 to 1.58) (I (2) = 89 %). This meta-analysis showed significantly higher stone expulsion rates and faster expulsion times in favor of silodosin when compared to tamsulosin.

Concepts: Epidemiology, Statistics, Evidence-based medicine, Systematic review, Randomized controlled trial, Stone


Primary hyperoxaluria (PH) patients overproduce oxalate because of rare genetic errors in glyoxylate metabolism. Recurrent urolithiasis and/or progressive nephrocalcinosis are PH hallmarks and can lead to kidney damage, systemic oxalosis and death. Based on previous studies, we hypothesised that treatment with the oxalate-metabolizing bacterium Oxalobacter formigenes would mediate active elimination of oxalate from the plasma to the intestine of PH patients, thereby reducing urinary oxalate excretion (Uox). The efficacy and safety of O. formigenes (Oxabact™ OC3) were evaluated for 24 weeks in a randomised, placebo-controlled, double-blind study. The primary endpoint was reduction in Uox. Secondary endpoints included change in plasma oxalate (Pox) concentration, frequency of stone events, number of responders, and Uox in several subgroups. Additional post hoc analyses were conducted. Thirty-six patients were randomised; two patients withdrew from placebo treatment. Both OC3 and placebo groups demonstrated a decrease in Uox/urinary creatinine ratio, but the difference was not statistically significant. No differences were observed with respect to change in Pox concentration, stone events, responders' number or safety measures. In patients with estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m(2), Pox increased by 3.25 µmol/L in the placebo group and decreased by -1.7 µmol/L in the OC3 group (p = 0.13). After 24 weeks, eGFR had declined to a greater degree in the placebo than in the OC3 group: -8.00 ± 2.16 versus -2.71 ± 2.50; p = 0.01. OC3 treatment did not reduce urinary oxalate over 24 weeks of treatment compared with placebo in patients with PH. The treatment was well tolerated.

Concepts: Kidney, Nephrology, Statistics, Blood, Renal physiology, Blood urea nitrogen, Placebo, Oxalobacter formigenes


Nephrolithiasis is a common urological disease with high prevalence and recurrence rates. Characterizing gut microbiome profiles of nephrolithiasis patients may provide valuable insights and potential biomarkers for the disease. Therefore, we explored the relation between gut microbiome and nephrolithiasis using 16S ribosomal RNA (rRNA) gene sequencing. 13 patients with multiple kidney stones and 13 matched healthy controls were recruited. A decreasing trend in number of observed species in nephrolithiasis patients was detected, although statistical significance was not reached (p = 0.086). The inter-group variability in community structure by beta diversity analysis showed a clear separation between nephrolithiasis patients and healthy controls. Twenty genera differentiated significantly in relative abundance between nephrolithiasis patients and healthy controls (all p < 0.05). Among the 20 genera, Phascolarctobacterium, Parasutterella, Ruminiclostridium_5, Erysipelatoclostridium, Fusicatenibacter and Dorea were correlated with the concentration of the trace elements in blood, including potassium, sodium, calcium and chlorinum. Characteristic microbiome in nephrolithiasis patients was also identified by linear discriminant analysis effect size (LEfSe). These findings may provide novel and non-invasive potential diagnostic biomarkers for nephrolithiasis, and contribute to prevention and treatment of nephrolithiasis from the perspective of maintaining micro-ecological equilibrium in gut.

Concepts: Archaea, RNA, Ribosomal RNA, Ribosome, Statistical significance, 16S ribosomal RNA, 30S, Effect size


The aim of our study is to explore the relationship between genotype and phenotype in Chinese PH1 patients and determine the putative mutation hotspot regions. This was a retrospective study regarding 13 Chinese PH1 patients. And all sporadic published researches of Chinese PH1 populations were searched and enrolled based on the inclusive standard. All patients presented with multiple urolithiasis or nephrolithiasis. Urinary oxalate values demonstrated an obvious and extensive variability, ranging from 1.01 to 3.85 mmol/1.73 m2. Molecular diagnosis showed that 13 mutant types were detected. Infantile form patient (pt.) 10 and five patients (pts. 5, 7, 8, 9, 12) carrying c.815_816insGA or c.33_34insC demonstrated a worse prognosis, of whom pt. 5 progressed into ESRD 4 years later and died of chronic kidney failure. Based on the integrated Chinese mutation data, two variants (c.815_816insGA and c.33_34insC) were determined as the most common mutations. Besides, c.1049G>A was initially identified in a Chinese patient. Conclusions: heterogeneity between genotype and phenotype was observed and described in Chinese PH1 patients. c.815_816insGA and c.33_34insC which were recognized as AGXT mutation hotspot regions in China implied a poor prognosis. And c.1049G>A was not determined as the race-specific mutation of Pakistani.


The authors aimed to evaluate the factors affecting clinical outcomes of cystine stone disease in children and to understand the change in disease management over time. Between January 1991 and September 2017, the demographic and clinical data of pediatric patients with documented cystine stone disease were retrospectively analyzed. Patients with at least 12-month follow-up were included. Disease management and clinical outcomes were compared between the first and second 35 patients managed during the study’s time frame. A total of 70 patients were included. The female to male ratio was 30/40. The mean age and follow-up period was 29.8 ± 40.1 months and 106.5 ± 56 months, respectively. The mean initial procedure number to treat the first stone episode was 2.4 ± 1.6. Single stone and single affected site were significant predictors for stone clearance. Overall, patients underwent a mean of 5.5 procedure during their follow-up. Recurrence was detected in 71.4% (50/70) of patients. Residual fragments and non-compliance to medical treatment after the initial intervention were significant predictors for recurrence within shorter interval period. 31.4% (22/70) of patients had renal atrophy during follow-up. They were older at the initial diagnosis and had average urine pH lower than 7.5. The first 35 patients had more open procedures. Still, they had more recurrence rate and tend to have more renal atrophy. As a conclusion, cystine stone disease has a recurrent course in children. Stone and fragments entirely removed (SaFER) concept with all minimally invasive methods available and strict follow-up should be the basis for any management plan.


Among 208 kidney stone patients referred within 2 years, 75 patients (66 men, nine women) with truly idiopathic calcium oxalate stones (ICSF) were recruited. Dietary advice (DA) aimed at (1) urine dilution, (2) reduced crystallization promotion (lowering oxalate), and (3) increased crystallization inhibition (increasing citrate). We recommended higher intakes of fluid and calcium with meals/snacks (reducing intestinal oxalate absorption) as well as increased alkali and reduced meat protein (acid) for increasing urinary citrate. The intended effects of DA were elevations in urine volume, calcium (U-Ca) and citrate (U-Cit) as well as reductions in oxalate (U-Ox) and uric acid (U-UA). We retrospectively calculated an adherence score (AS), awarding + 1 point for parameters altered in the intended direction and - 1 point for opposite changes. Calcium oxalate supersaturation (CaOx-SS) was calculated using Tiselius' AP(CaOx) index EQ. DA induced changes (all p < 0.0001) in urine volume (2057 ± 79 vs. 2573 ± 71 ml/day) and U-Ca (5.49 ± 0.24 vs. 7.98 ± 0.38 mmol/day) as well as in U-Ox (0.34 ± 0.01 vs. 0.26 ± 0.01 mmol/day) and U-UA (3.48 ± 0.12 vs. 3.13 ± 0.10 mmol/day). U-Cit only tendentially increased (3.07 ± 0.17 vs. 3.36 ± 0.23 mmol/day, p = 0.06). DA induced a 21.5% drop in AP(CaOx) index, from 0.93 ± 0.05 to 0.73 ± 0.05 (p = 0.0005). Decreases in CaOx-SS correlated with AS (R = 0.448, p < 0.0005), and highest AS (+ 5) always indicated lowering of CaOx-SS. Thus, simple DA can reduce CaOx-SS which may be monitored by AS.


Measurement of oxalate in the blood is essential for monitoring primary hyperoxaluria patients with progressive renal impairment and on dialysis prior to transplantation. As no external quality assurance scheme is available for this analyte, we conducted a sample exchange scheme between six laboratories specifically involved with the investigation of primary hyperoxaluria to compare results. The methodologies compared were gas chromatography/mass spectrometry (GCMS), ion chromatography with mass spectrometry (ICMS), and enzymatic methods using oxalate oxidase and spectrophotometry. Although individual laboratories performed well in terms of reproducibility and linearity, there was poor agreement (absolute values) between centres as illustrated by a longer-term comparison of patient results from two of the participating laboratories. This situation was only partly related to differences in calibration and mainly reflected the lower recoveries seen with the ultrafiltration of samples. These findings lead us to conclude that longitudinal monitoring of primary hyperoxaluria patients with deteriorating kidney function should be performed by a single consistent laboratory and the methodology used should always be defined. In addition, plasma oxalate concentrations reported in registry studies and those associated with the risk of systemic oxalosis in published studies need to be interpreted in light of the methodology used. A reference method and external quality assurance scheme for plasma oxalate analysis would be beneficial.