Medical management of urolithiasis: Great efforts and limited progress

Objective:To provide a comprehensive review on the existing literature on medical management of urolithiasis.Methods:A thorough literature review was performed using Medline,PubMed/PMC,Embase,and the Cochrane Database of Systematic Reviews up to December 2022 to identify publications on the medical management of urolithiasis.Studies that assessed dietary and pharmacologic management of urolithiasis were reviewed;studies on medical expulsive therapy were not included in this review.Results:Medical management of urolithiasis ranges from the prophylactic management of kidney stone disease to dissolution therapies.While most treatment concepts have been long established,large randomized controlled trials are scarce.Dietary modification and increased fluid intake remain cornerstones in the conservative management of urolithiasis.A major limitation for medical management of urolithiasis is poor patient compliance.Conclusion:Medical management of urolithiasis is more important in patients with recurrent urolithiasis and patients with metabolic abnormalities putting them at higher risk of developing stones.Although medical management can be effective in limiting stone recurrence,medical interventions often fail due to poor compliance.

Percutaneous nephrostomy versus ureteral stent in hydronephrosis secondary to obstructive urolithiasis:A systematic review and meta-analysis

Objective: To assess if there is a preferable intervention between retrograde ureteral stent (RUS) and percutaneous nephrostomy (PCN) tube, in cases of upper urinary tract stone obstruction with complications requiring urgent drainage, by evaluating outcomes regarding urinary symptoms, quality of life (QoL), spontaneous stone passage, and length of hospital stays, since there is no literature stating the superiority of one modality over the other.Methods: We searched MEDLINE and other sources for relevant articles in June 2019 without any date restrictions or filters applied. The selection was done first by the title and abstract screening and then by full-text assessment for eligibility. Only randomized controlled trials or cohort studies in patients with hydronephrosis secondary to obstructive urolithiasis that presented comparative data between PCN and RUS placement concerning at least one of the defined outcome measures were included. Lastly, MEDLINE database and PubMed platform were screened again using the same terms, from June 2019 until November 2022.Results: Of 556 initial articles, seven were included in this review. Most works were considered of moderate-to-high quality. Three studies regarding QoL showed a tendency against stenting, even though only one demonstrated statistically significant negative impact on overall health state. Two works reported significantly more post-intervention urinary symptoms in stenting patients. One article found that PCN is a significant predictor of spontaneous stone passage, when adjusted for stone size and location. Findings on length of hospital stays were not consistent among articles.Conclusion: PCN appears to be the intervention better tolerated, with less impact on the patient’s perceived QoL and less post-operative urinary symptoms, in comparison with RUS. Nevertheless, further studies with larger samples and a randomized controlled design are suggested.

Monogenic features of urolithiasis: A comprehensive review

Objective: Urolithiasis formation has been attributed to environmental and dietary factors. However, evidence is accumulating that genetic background can contribute to urolithiasis formation. Advancements in the identification of monogenic causes using high-throughput sequencing technologies have shown that urolithiasis has a strong heritable component.Methods: This review describes monogenic factors implicated in a genetic predisposition to urolithiasis. Peer-reviewed journals were evaluated by a PubMed search until July 2023 to summarize disorders associated with monogenic traits, and discuss clinical implications of identification of patients genetically susceptible to urolithiasis formation.Results: Given that more than 80% of urolithiases cases are associated with calcium accumulation, studies have focused mainly on monogenetic contributors to hypercalciuric urolithiases, leading to the identification of receptors, channels, and transporters involved in the regulation of calcium renal tubular reabsorption. Nevertheless, available candidate genes and linkage methods have a low resolution for evaluation of the effects of genetic components versus those of environmental, dietary, and hormonal factors, and genotypes remain undetermined in the majority of urolithiasis formers.Conclusion: The pathophysiology underlying urolithiasis formation is complex and multifactorial, but evidence strongly suggests the existence of numerous monogenic causes of urolithiasis in humans.

The Deleterious Effect of Inappropriate Calcium and Vitamin D Supplementation during Pregnancy in Women Predisposed to Calcium Oxalate Urolithiasis

Background: Gestational formation of new urolithiasis is rare yet the impact of inappropriate gestational calcium and vitamin D supplementation (Ca/DS) is underestimated. Patients and Methods: we retrospectively evaluated 75 pregnant women with history of UL, yet were stable for >2 years on dietary restrictions, for new UL after Ca/DS. Results: During the past 5 years 21 (48%) of those who had received Ca/DS had developed UL and all had high Vitamin D with hypercalcemia while the remaining 31 patients, without Ca/DS, did not have UL and maintained normal vitamin D urinary calcium without need for supplementation. Overt UL was evident by 30th weeks of gestations and most were diagnosed by ultrasonography and managed by medical expulsive therapy. Conclusion: in patients with history of UL, prudent use of Ca/DS is indicated to avoid new UL.

Ureteric Stone Containing Gas: First Case Report with Review of Cases of Urolithiasis with Gas within the Stone and Its Clinical Implications

We report the first case of a ureteric stone containing gas. This rare stone with gas within it was found during the management of a diabetic patient with urosepsis as the initial presentation. Literature review of cases of renal stone containing gas, mechanisms of gas within the stone, and clinical implications of stone containing gas are discussed. Also, a new terminology is proposed to describe this phenomenon.

Epidemiology of urolithiasis in Asia

In Asia,about 1%-19.1% of the population suffer fromurolithiasis.However,due to variations in socio-economic status and geographic locations,the prevalence and incidence have changed in different countries or regions over the years.The research for risk factors of urinary tract stones is of predominant importance.In this review,we find the prevalence of urolithiasis is 5%-19.1% in West Asia,Southeast Asia,South Asia,aswellas somedevelopedcountries(SouthKorea and Japan),whereas,it is only 1%e8%inmost part of East Asia and North Asia.The recurrence rate ranges from 21% to 53% after 3e5 years.Calciumoxalate(75%-90%)is themost frequent component of calculi,followed by uric acid(5%-20%),calciumphosphate(6%-13%),struvite(2%-15%),apatite(1%)and cystine(0.5%-1%).The incidence of urolithiasis reaches its peak in population agedover 30 years.Males aremore likely to suffer fromurinary calculi.Because of different dietary habits or genetic background,differences of prevalence among races or nationalities also exist.Geneticmutation of specific locus may contribute to the formation of different kinds of calculi.Dietary habits(westernized dietary habits and less fluid intake),as well as climatic factors(hot temperature andmany hours of exposure to sunshine)play a crucial role in the development of stones.Other diseases,especially metabolic syndrome,may also contribute to urinary tract stones.

Ureteral stents in urolithiasis

Ever since the ureteral stent design was fitted with a curl on both sides to prevent it from migrating up or down the ureter some 40 years ago,its use has gained tremendous momentum,aiding in the rise and evolution of endourology and has confidently kept its place in modern time urology.Over the past four decades,several designs,coating and biomaterials have been developed,trying to reduce infection,encrustation and other stent related symptoms.As the ideal stent has not yet been discovered,different ways of helping patients with their complaints have been researched.This review will cover these aspects of stent use in urolithiasis.

Flexible ureteroscopy:Technological advancements,current indications and outcomes in the treatment of urolithiasis

The last 3 decades have witnessed great improvements in the technology and clinical applications of many minimally invasive procedures in the urological field.Flexible ureteroscopy(fURS)has advanced considerably to become a widely utilized diagnostic and therapeutic tool for multiple upper urinary tract pathologies.The most common indication for fURS is the treatment of upper urinary tract stones with the aid of Holmium:Yttrium Aluminium Garnet(YAG)laser lithotripsy.Advancements in endoscope technologies and operative techniques have lead to a broader application of fURS in the management of urolithiasis to include larger and more complex stones.fURS has proved to be an effective and safe procedure with few contraindications.Continued progression in fURS may increase its clinical applicability and supplant other procedures as the first line treatment option for urolithiasis.

Epidemiological trends of urinary tract infections,urolithiasis and benign prostatic hyperplasia in 203 countries and territories from 1990 to 2019

Background:Urinary tract infections(UTI),urolithiasis,and benign prostatic hyperplasia(BPH)are three of the most common nonmalignant conditions in urology.However,there is still a lack of comprehensive and updated epidemiological data.This study aimed to investigate the disease burden of UTI,urolithiasis,and BPH in 203 countries and territories from 1990 to 2019.Methods:Data were extracted from the Global Burden of Disease 2019,including incident cases,deaths,disabilityadjusted life-years(DALYs)and corresponding age-standardized rate(ASR)from 1990 to 2019.Estimated annual percentage changes(EAPC)were calculated to evaluate the trends of ASR.The associations between disease burden and social development degrees were analyzed using a sociodemographic index(SDI).Results:Compared with 1990,the incident cases of UTI,urolithiasis,and BPH increased by 60.40%,48.57%,and 105.70%in 2019,respectively.The age-standardized incidence rate(ASIR)of UTI increased(EAPC=0.08),while urolithiasis(EAPC=–0.83)and BPH(EAPC=–0.03)decreased from 1990 to 2019.In 2019,the age-standardized mortality rate(ASMR)of UTI and urolithiasis were 3.13/100,000 and 0.17/100,000,respectively.BPH had the largest increase(110.56%)in DALYs in the past three decades,followed by UTI(68.89%)and urolithiasis(16.95%).The burden of UTI was mainly concentrated in South Asia and Tropical Latin America,while the burden of urolithiasis and BPH was recorded in Asia and Eastern Europe.Moreover,the ASIR and SDI of urolithiasis in high-SDI regions from 1990to 2019 were negatively correlated,while the opposite trend was seen in low-SDI regions.In 2019,the ASIR of UTI in females was 3.59 times that of males,while the ASIR of urolithiasis in males was 1.96 times higher than that in females.The incidence was highest in the 30–34,55–59,and 65–69 age groups among the UTI,urolithiasis,and BPH groups,respectively.Conclusions:Over the past three decades,the disease burden has increased for UTI but decreased for urolithiasis and BPH.The allocation of medical resources should be based more on the epidemiological characteristics and geographical distribution of diseases.

Retrograde intrarenal surgery:An expanding role in treatment of urolithiasis

During the past 3 decades,the surgical management of kidney stones has undergone many technological advances and one is the development of the flexible ureteroscopy.The development of this instrument as well as ancillary equipment such as baskets,graspers,and others,and improvements in lithotripsy with Holmium:YAG laser have led to expand its indications with diagnostic and therapeutic management of medical issues of the upper urinary tract such as urolithiasis and urothelial tumors.The objective of this review is to describe its indications and results in the different scenarios for the treatment of urinary stones.

Urolithiasis in inflammatory bowel disease and bariatric surgery

AIM To analyse current literature focusing on pathogenesis and therapeutic aspects of urolithiasis with inflammatory bowel disease(IBD) and following bariatric surgery. METHODS A systematic literature search was performed using PubMed, supplemented with additional references. Studies assessing the association of IBD or bariatric surgery with renal stones in both paediatric and adulthood were included. RESULTS Certain types of stones are seen more frequently with IBD. Hyperoxaluria and hypocitraturia are the main metabolic changes responsible for urolithiasis. The incidence of renal stones in malabsorptive types of bariatric surgery such as gastric bypass is high; this is not as common in modern restrictive surgical methods. Preventative methods and urine alkalinisation have been shown to be beneficial.CONCLUSION Both conditions are associated with renal stones. Patients' counselling and prevention strategies are the mainstay of urolithiasis management in these patients.

Progress on the Causes and Current Status of Canine Urolithiasis

Canine urolithiasis is a common disease of the urinary system, referring to the hemorrhage, inflammation and stagnation of the urinary tract caused by the mineral congelation centered with the dediduous epithelial cel s and other foreign matters surrounded by the salt crystal ization from the urine when the in the case of mineral metabolism disorder of canine. ln this paper, the causes, classification, treatment and prevention of canine urolithiasis were reviewed.

Pediatric primary urolithiasis: Symptoms, medical management and prevention strategies

In the past few decades pediatric urolithiasis has become more frequent. The reason for this increase is not completely clear but has been attributed to changes in climate, nutritional habits and possibly other environ-mental factors. Although less frequent than adult stone disease, urolithiasis in the pediatric age group is also related to significant morbidity, particularly since stones tend to recur, and, thus, should not be underestimated. Most children with idiopathic stone disease have an underlying metabolic abnormality substantiating the importance of metabolic evaluation already following initial diagnosis of urolithiasis. Identification of the metabolic abnormality allows for more specifc prescription of non pharmacological and pharmacological interventions aimed at preventing recurrent stone formation. A better understanding of the causes of kidney stone disease will provide better strategies for stone prevention in children.

Decreased Expression of Vitamin K Epoxide Reductase Complex Subunit 1 in Kidney of Patients with Calcium Oxalate Urolithiasis

Urinary prothrombin fragment 1 （UPTFl） is a potent inhibitor of urinary stone formation. UPTF1 exerts such inhibitory effect by effective 7-carboxylation in which vitamin K epoxide reductase complex subunit 1 （VKORC1）, the rate-limiting enzyme, is involved. This study examined the correlation between VKORC1 expression and calcium oxalate urolithiasis. The renal cortex samples were obtained from patients undergoing nephrectomy and then divided into 3 groups： urolithiasis group, control group A [hydronephrosis-without-stone （HWS） group], control group B （normal control group）, The localization and expression of VKORC1 in renal tissues were determined by using immunohistochemistry, immunofluorescence microscopy, Western blotting and SYBR Green I real-time reverse-transcription PCR. The rapid amplification of cDNA ends （RACE） were conducted to obtain the 3＇- and 5＇-untranslated region （UTR） of VKORC1. The results showed that VKORC1 was located in the cytoplasm of renal tubular epithelial cells. The expression of VKORC1 in the uro- lithiasis group was significantly lower than that in the other two control groups （P〈0.05）. Moreover, the 3＇- and 5＇-UTR sequence of the VKORC1 gene was successfully cloned. No insertion or deletion was found in the 3＇- and 5＇-UTR. However, a 171-bp new base sequence was discovered in the up- stream of 5＇-UTR end in the urolithiasis group. It was concluded that the decreased expression of VKORC 1 may contribute to the development of calcium oxalate urolithiasis in the kidney.

Whole Leea macrophylla ethanolic extract normalizes kidney deposits and recovers renal impairments in an ethylene glycol-induced urolithiasis model of rats

Objective:To investigate the antilithiatic effect of the whole Leea macrophylla(L macrophylla) Roxb(Leeaeeae) ethanol extract in ediylene glycol-induced urolithiasis model of rats.Methods: Forty two seven weeks old male wistar albino rats were randomly divided into two major groups namely:preventive(n=18) and therapeutic(n=24).Preventive group was further subdivided into 3 groups of 6 rats namely:preventive control(PC),preventive lithiatic control(PLC) and preventive lithiatic L.macrophylla(PLLM).Similarly,therapeutic group was also subdivided into 4 groups of 6 rats namely:therapeutic control(TC),therapeutic lithiatic control(TLC).therapeutic lithitatic L macrophylla(TLLM) and therapeutic lithiatic cystone(TLCYS).The lithiasis was induced by 0.75%(v/v) ethylene glycol in the drinking water of all groups except the PC and TC groups.The urinary ionic parameters such as calcium,inorganic phosphate,oxalate,magnesium & creatinine and renal morphology were altered by ediylene glycol,which were partially recovered by 14 d preventive and almost fully recovered by 28 d therapeutic intervention trials with L macrophylla extract(500 mg/kg BW daily).Results:Significant difference on recovery was observed between preventive and dierapeutic interventional trials.Anti-urolithiatic effect of cystone was significantly(P【0.001) higher than extracts.L macrophylla extract was found nontoxic in the acute toxicity test.Conclusions:The results of this study demonstrated very promising antiurolithiatic effect of L.macrophylla extract with preventive and therapeutic treatments in this experimental condition.

A Survey of Urolithiasis in Young Children Fed Infant Formula Contaminated with Melamine in Two Townships of Gansu,China

Objective To determine the prevalence of urolithiasis in young children fed infant formula（IF） contaminated with melamine,and the association between IF consumption and urolithiasis.Design A total of 2 733 children ≤3 years of age on September 1,2008 in two townships of Gansu Province,China were studied.Cases of urolithiasis were diagnosed by ultrasonography.Milk product consumption was determined by their caregivers.Remaining IF samples were tested for melamine and cyanuric acid.Results Of 2 733 eligible children in the two townships,2 186（80%） were enrolled in our study.Overall,16.6%（362） of 2 186 children had urolithiasis.The prevalence was 24.6% in children exclusively fed Sanlu brand IF,9.7% in those fed other IF,and 8.5% in those fed exclusively on other milk products.For children exclusively breast-fed,no urolithiasis was found（P0.05）.The prevalence of urolithiasis was 11.4% in children fed 400 g of Sanlu IF,rising to 37.5% in children fed over 25 600 g.Of 48 Sanlu IF samples,91.7% contained melamine（median=1 800 ppm;range=45-4 700） and 66.7% contained cyanuric acid（median=1.2 ppm;range=0.4-6.3）.Melamine was also detected in 22.2% of 36 other brand IF（median=27.5 ppm,range=4-50）.Conclusions Urolithiasis was associated with melamine-contaminated IF.Although one product caused most morbidity,other milk products may have also contributed to the outbreak.

CLINICAL STUDY ON THE TREATMENT OF UROLITHIASIS WITH ACUPUNCTURE

120 cases of urolithlasis were randomly divided into 3 groups of 40 persons each.The first group was solely treated with an improved acupuncture method,the second group was treatedwith Chinese herbal medicine,and the third group was treated with both of the above methods.Results showed that the improved acupuncture method possessed better stone-removing effect thanthe herbal medicine method and no much difference occurred between the patients treated withacupuncture and those treated with both above methods.Besides,the authors also experienced the excellentanalgesic and stone-dissolving effect of acupuncture in this study.

Urolithiasis in Pregnancy: Survey in Clinical Epidemiology

This study examined the association of pregnancy with urolithiasis and provided new insights into urolithiasis in pregnancy. A total of 462 subjects were studied from January 2004 to December 2009 in Foshan Maternal and Child Health Hospital, China. Among the 462 subjects, 162 cases of urolithiasis during pregnancy （UPG） were selected as the observation group, 150 cases of no urolithiasis during pregnancy （NUPG） served as pregnancy control group, and 150 cases of no pregnancy （NPG） at reproductive age who took part in physical examination were randomly assigned into non-pregnant control group. At the same time, the patients in observation group were divided into the following sub-groups： no symptomatic urinary calculus （NSUC） and symptomatic urinary calculus （SUC） groups; SUC group was further divided into surgical intervention （SI） and conservative management （CM） groups. The general information and the data of blood and urine were collected and compared among the groups. The results showed that the incidence of urinary calculi in pregnant women was lower than that in non-pregnant women, the formation of urinary stone was associated with the change of metabolism of protein and sugar in pregnant women, and the surgical intervention was a practicable alternative to treat the clinical intractable symptomatic urinary calculi in pregnancy.

Simultaneous vs staged treatment of urolithiasis in patients undergoing radical prostatectomy

AIM: To assess the outcomes of men treated for urolithiasis at the time of radical prostatectomy.METHODS: From 1991 to 2010, 22 patients were retrospectively identified who were treated simultaneously(n = 10) at radical prostatectomy, or(n = 12) within 120 d prior to prostatectomy, for urolithiasis. Clinical characteristics were reviewed including: type of prostatectomy and stone surgery, location and amount of stone burden, perioperative change in hemoglobin and creatinine, stent frequency, total hospital d, stone-free rates, additional stone procedures and complications. Long-term functional outcomes including stress urinary incontinence and bladder neck contracture were reported. Differences between cohorts(simultaneous vs staged treatment) were assessed. RESULTS: Among men undergoing radical prostatectomy, primary stone procedures included 12 ureteroscopy, 6 shock wave lithotripsy, 2 open nephrolithotomyand 2 percutaneous nephrolithotomy. In staged shock wave lithotripsy there were 4 complications and 3 additional procedures vs 1(P = 0.5) and 0(P = 0.2) in the simultaneous cohort. Meanwhile in staged ureteroscopy there were 5 complications and 1 additional procedure vs 1(P = 0.2) and 1(P = 0.9) in the simultaneous cohort. Additional procedures for residual stones was greater among patients with asymptomatic upper tract calculi 3(60%) relative to patients with symptomatic stones 2(13%; P = 0.02). Likewise, patients with proximal or multiple calculi had a greater total hospital days 5.5 vs 4.1(P = 0.04), additional procedures 6 vs 0(P = 0.04) and lower stone-free rates 39% vs 89%(P = 0.02) relative to men with distal stones. Finally, there was no difference in the incidence of bladder neck contracture(P = 0.4) or stress urinary incontinence(P = 0.7) between cohorts.CONCLUSION: Ureteroscopic treatment of symptomatic distal urolithiasis at radical prostatectomy appears to be safe and efficacious with a low rate of adverse postoperative outcomes.

Associations between IL-1RN variable number of tandem repeat, IL-1β (-511) and IL-1β (+3954) gene polymorphisms and urolithiasis in Uighur children of China

Objective:Interleukin-1(IL-1)is a pro-inflammatory cytokine which may be related to urolithiasis.Genetic polymorphisms of the interleukin-1beta(IL-1β)have been proposed as markers for urolithiasis in some areas.Due to the high incidence of urolithiasis in Uighur children(Xinjiang,China)and existence of ethnic difference,our aim is to explore the potential of IL-1 gene polymorphisms and urolithiasis among these children.Methods:Genomic DNA extracted from peripheral blood of 115 patients and 98 controls were used for genotype polymorphisms analyses.IL-1 receptor antagonist(IL-1RN)gene variable number of tandem repeat(VNTR)gene polymorphisms were analyzed by PCR method.PCR-based restriction analysis was done for the IL-1β(-511)and IL-1β(+3954)gene polymorphisms by endonucleases Ava I and Taq I,respectively.The genotype distribution,allele frequencies,carriage rate,and haplotype frequencies were statistically analyzed.Results:No significant differences were observed in genotypic frequencies between pediatric urolithiasis patients and control group for IL-1RN gene(χ^(2)=1.906,p=0.605),IL-1β(-511)gene(χ^(2)=0.105,p=0.949),or IL-1β(+3954)gene(χ^(2)=3.635,p=0.169).There were yet no significant differences of the allele frequencies of IL-1RN VNTR gene(p=0.779),IL-1β(-511)gene(p=0.941),and IL-1β(+3954)gene(p=0.418)in the case and control groups,as well as the carriage rate and haplotype of them(all p>0.05).Conclusions:The associations between IL-1RN VNTR,IL-1β(-511)and IL-1β(+3954)genes polymorphisms and urolithiasis were not significant in Uighur children.The results need to be confirmed in studies with larger population sample size,as well as in other ethnic groups.