Does pre-stenting influence outcomes of shockwave lithotripsy? A systematic review and meta-analysis.

OBJECTIVE: To determine whether preoperative use of JJ stents in patients undergoing shockwave lithotripsy (SWL) impacts on stone clearance and the rate of postoperative complications. PATIENTS AND METHODS: We screened multiple databases from inception to January 2021, using the relevant search terms for SWL in patients with a preoperative stent. Inclusion criteria were randomised controlled trials of ≥20 patients aged >18 years who had had SWL with a JJ stent. This review has been registered in the International Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42023443195). Statistical analysis was performed using 'meta' in R. RESULTS: There were seven eligible studies (403 patients receiving JJ stents and 394 controls). There was no significant difference in the stone-free rate (SFR) following SWL with a JJ stent compared to SWL alone. When considering the complication rates, there was a significantly reduced risk of steinstrasse in patients with a JJ stent. However, there was no significant difference in the risk of other complications including pain, fever, and haematuria, and no significant difference in the likelihood of requiring auxiliary procedures or re-treatment. CONCLUSIONS: There was a reduced risk of steinstrasse in patients undergoing SWL with a JJ stent compared to SWL alone. However, there was no significant difference in the risk of other postoperative complications. Use of a JJ stent had no effect on the efficacy of SWL, with no significant difference in the SFR.

Outcomes of alpha-blockers as medical expulsive therapy following shockwave lithotripsy: a systematic review and meta-analysis.

OBJECTIVES: To determine stone-free rate following shockwave lithotripsy (SWL) with/without alpha-blockers as well as complication rates (individual and classified using the Clavien-Dindo system). MATERIALS AND METHODS: We performed a systematic review of all randomized controlled trials that included more than 20 patients (age > 18 years) and examined the use of alpha-blockers after SWL. Meta-analysis was performed using 'metafor' in R. We report risk ratios (RRs) with 95% confidence intervals (95% CIs). The PROSPERO ID for the trial was: CRD42021248108. RESULTS: We assessed 158 full-text articles and included a total of 21 studies in our review. There were 1445 patients receiving alpha-blockers and 1478 control patients. Those receiving alpha-blockers were significantly more likely to be stone-free (RR 1.12, 95% CI 1.07-1.16; P < 0.001). This effect was robust to 'trim-and-fill' adjustment. In those taking alpha-blockers there was a significant reduction in Clavien III-V complications and, on trim-and-fill adjustment, a significant reduction in Clavien I-II complications. There were also significant reduction in rates of steinstrasse, pain and requirement for auxiliary procedures. There was no significant difference in retreatment rates. These effects were robust to trim-and-fill adjustment. CONCLUSIONS: There is a modest increase in stone-free rates in those receiving alpha-blockers following SWL, with a reciprocal modest risk reduction for steinstrasse, pain and auxiliary procedures. However, alpha-blockers do not reduce the risk of requiring retreatment.

Natural history of small asymptomatic kidney and residual stones over a long-term follow-up: systematic review over 25 years.

OBJECTIVE: To systematically review the natural history of small asymptomatic kidney and residual stones, as the incidental identification of small, asymptomatic renal calculi has risen with increasing use of high-resolution imaging. MATERIALS AND METHODS: We reviewed the natural history of small asymptomatic kidney and residual stones using the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. We searched MEDLINE, Scopus, EMBASE, EBSCO, Cochrane library and Clinicaltrials.gov using themes of 'asymptomatic', 'nephrolithiasis', 'observation', 'symptoms', 'admission', 'intervention' and similar allied terms for all English language articles from 1996 to 2020 (25 years). Inclusion criteria were studies with ≥50 patients, stones ≤10 mm, and a mean follow-up of ≥24 months. Primary outcomes were occurrence of symptoms, emergency admission, and interventions. RESULTS: Our literature search returned 2247 results of which 10 papers were included in the final review. Risk of symptomatic episodes ranged from 0% to 59.4%. Meta-analysis did not identify any significant difference in the likelihood of developing symptoms when comparing stones <5 mm to those >5 mm, nor those <10 mm to those >10 mm. Risk of admission varied from 14% to 19% and the risk of intervention from 12% to 35%. Meta-analysis showed a significantly decreased likelihood of intervention for stones <5 vs >5 mm and <10 vs >10 mm. Studies had variable risk of bias due to heterogeneous reporting of outcome measures with significant likelihood that observed differences in results were compatible with chance alone (Symptoms: I2 =0%, Cochran's Q = 3.09, P = 0.69; Intervention: I2 =0%, Cochran's Q = 1.76, P = 0.88). CONCLUSIONS: The present systematic review indicates that stone size is not a reliable predictor of symptoms; however, risk of intervention is greater for stones >5mm vs <5 mm and >10 vs <10 mm. This review will inform urologists as they discuss management strategies with patients who have asymptomatic renal stones and offer insight to committees during the development of evidence-based guidelines.

Natural History of Post-Treatment Kidney Stone Fragments: A Systematic Review and Meta-Analysis.

PURPOSE: We assessed the literature around post-treatment asymptomatic residual stone fragments and performed a meta-analysis. The main outcomes were intervention rate and disease progression. MATERIALS AND METHODS: We searched Ovid®, MEDLINE®, Embase™, the Cochrane Library and ClinicalTrials.gov using search terms: "asymptomatic", "nephrolithiasis", "ESWL", "PCNL", "URS" and "intervention." Inclusion criteria were all studies with residual renal fragments following treatment (shock wave lithotripsy, ureteroscopy or percutaneous nephrolithotomy). Analysis was performed using 'metafor' in R and bias determined using Newcastle-Ottawa scale. RESULTS: From 273 articles, 18 papers (2,096 patients) had details of intervention rate for residual fragments. Aggregate intervention rates for ≤4 mm fragments rose from 19% (20 months) to 22% (50 months), while >4 mm fragments rose from 22% to 47%. Aggregate disease progression rates for ≤4 mm rose from 25% to 47% and >4 mm rose from 26% to 88%. However, there was substantial difference in definition of "disease progression." Meta-analysis comparing >4 mm against ≤4 mm fragments: intervention rate for >4 mm (vs ≤4 mm): OR=1.50 (95% CI 0.70-2.30), p <0.001, I2=67.6%, tau2=0.48, Cochran's Q=11.4 (p=0.02) and Egger's regression: z=3.11, p=0.002. Disease progression rate for >4 mm: OR=0.06 (95% CI -0.98-1.10), p=0.91, I2=53.0%, tau2=0.57, Cochran's Q=7.11 (p=0.07) and Egger's regression: z=-0.75, p=0.45. Bias analysis demonstrated a moderate risk. CONCLUSIONS: Larger post-treatment residual fragments are significantly more likely to require further intervention especially in the long term. Smaller fragments, although less likely to require further intervention, still carry that risk. Notably, there is no significant difference in disease progression between fragment sizes. Patients with residual fragments should be appropriately counselled and informed decision-making regarding further management should be done.

Risk of UTI in kidney stone formers: a matched-cohort study over a median follow-up of 19 years.

PURPOSE: To describe risk of UTI in Stone formers comparing to non-stone formers. METHODS: Retrospective cohort study using electronic records for patients across southern England. Stone formers referred to a tertiary referral centre in Southern England, comparator patients were age and sex matched with 3:1 ratio from same database. Those with no documentation were excluded. UTI defined using ICD-10 codes. Risk of UTI presented as hazard ratio with 95% confidence interval, generated using cox regression. Sample size calculated using 80% power and significance set at 0.05. RESULTS: Eight hundred and nineteen stone formers were included after 1000 records were screened for inclusion, with 2477 age and sex matched non-stone formers extracted from the same database. Sample size was calculated at 287 per group. Stone formers were at significantly increased risk of developing a UTI (HR 5.67; 95% CI 4.52-7.18, p < 0.001). Median follow-up was 19 years (IQR: 15-22). CONCLUSIONS: Kidney stone formers are at increased risk of developing urinary tract infections.

The effects of caloric restriction on adipose tissue and metabolic health are sex- and age-dependent.

Caloric restriction (CR) reduces the risk of age-related diseases in numerous species, including humans. CR's metabolic effects, including decreased adiposity and improved insulin sensitivity, are important for its broader health benefits; however, the extent and basis of sex differences in CR's health benefits are unknown. We found that 30% CR in young (3-month-old) male mice decreased fat mass and improved glucose tolerance and insulin sensitivity, whereas these effects were blunted or absent in young females. Females' resistance to fat loss was associated with decreased lipolysis, energy expenditure and fatty acid oxidation, and increased postprandial lipogenesis, compared to males. The sex differences in glucose homeostasis were not associated with differential glucose uptake but with altered hepatic ceramide content and substrate metabolism: compared to CR males, CR females had lower TCA cycle activity and higher blood ketone concentrations, a marker of hepatic acetyl-CoA content. This suggests that males use hepatic acetyl-CoA for the TCA cycle whereas in females it accumulates, stimulating gluconeogenesis and limiting hypoglycaemia during CR. In aged mice (18-months old), when females are anoestrus, CR decreased fat mass and improved glucose homeostasis similarly in both sexes. Finally, in a cohort of overweight and obese humans, CR-induced fat loss was also sex- and age-dependent: younger females (<45 years) resisted fat loss compared to younger males while in older subjects (>45 years) this sex difference was absent. Collectively, these studies identify age-dependent sex differences in the metabolic effects of CR and highlight adipose tissue, the liver and oestrogen as key determinants of CR's metabolic benefits. These findings have important implications for understanding the interplay between diet and health, and for maximising the benefits of CR in humans.