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Health Technology Assessment... Dec 2011Peripheral arterial disease (PAD) is a condition in which there is blockage or narrowing of the arteries that carry blood to the legs and arms. It is estimated to affect... (Review)
Review
A systematic review and economic evaluation of cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate for the treatment of intermittent claudication in people with peripheral arterial disease.
BACKGROUND
Peripheral arterial disease (PAD) is a condition in which there is blockage or narrowing of the arteries that carry blood to the legs and arms. It is estimated to affect around 4.5% of people aged between 55 and 74 years within the UK. The most common symptom of PAD is intermittent claudication (IC), characterised by pain in the legs on walking that is relieved with rest.
OBJECTIVE
To assess the effectiveness and cost-effectiveness of cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate, compared with no vasoactive drugs, for IC due to PAD in adults whose symptoms continue despite a period of conventional management.
DATA SOURCE
Electronic bibliographic databases were searched during April to June 2010 (MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Conference Proceedings Citation Index, BIOSIS Previews).
REVIEW METHODS
Effectiveness outcomes sought were maximal walking distance (MWD), pain-free walking distance (PFWD), ankle-brachial pressure index, cardiovascular events, mortality, adverse events (AEs) and health-related quality of life (HRQoL). A narrative synthesis was provided for all outcomes and a network meta-analysis was undertaken for the walking distance outcomes. A Markov model was developed to assess the relative cost-effectiveness of the interventions from a NHS perspective over a lifetime. The model has three states: vasoactive drug treatment, no vasoactive drug treatment and death. Each 1-week cycle, patients may continue with the drug, discontinue the drug or die. Regression analysis was undertaken to model the relationship between MWD and utility so that a cost per quality-adjusted life-year (QALY) outcome measure could be presented. Univariate and probabilistic sensitivity analyses were undertaken. All costs and outcomes were discounted at 3.5%.
RESULTS
Twenty-six randomised controlled trials were identified that met the inclusion criteria for the clinical effectiveness review. There was evidence that walking distance outcomes were significantly improved by both cilostazol and naftidrofuryl oxalate; the 95% credible intervals for the difference from placebo in the logarithm mean change MWD from baseline were 0.108 to 0.337 and 0.181 to 0.762, respectively. It was not possible to include inositol nicotinate within the meta-analysis of MWD and PFWD owing to the lack of 24-month data; however, the shorter-term data did not suggest a significant effect. AEs were minor for all drugs and included headaches and gastrointestinal difficulties. The incidence of serious adverse events (SAEs), including cardiovascular events and mortality, was not increased by the vasoactive drugs compared with placebo; however, most studies had a relatively short follow-up time to address this outcome. HRQoL data were limited. Two studies of limited quality were identified within the review of cost-effectiveness. The de novo model developed suggests that naftidrofuryl oxalate dominates cilostazol and pentoxifylline and has a cost per QALY gained of around £6070 compared with no vasoactive drug. This result is reasonably robust to changes within the key model assumptions. Inositol nicotinate was not included within the main analysis owing to lack of data. However, it is unlikely to be considered to be cost-effective due to its high acquisition cost (£900 vs £100-500 per year for the other drugs).
CONCLUSIONS
Naftidrofuryl oxalate and cilostazol both appear to be effective treatments for this patient population, with minimal SAEs. However, naftidrofuryl oxalate is the only treatment that is likely to be considered cost-effective. The long-term effectiveness is uncertain and hence a trial comparing cilostazol, naftidrofuryl oxalate and placebo beyond 24 weeks would be beneficial. Outcomes associated with naftidrofuryl oxalate could also be compared with those associated with supervised exercise programmes and angioplasty.
Topics: Cilostazol; Cost-Benefit Analysis; Humans; Intermittent Claudication; Nafronyl; Nicotinic Acids; Pentoxifylline; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Tetrazoles; United Kingdom; Vasodilator Agents
PubMed: 22142554
DOI: 10.3310/hta15400 -
International Braz J Urol : Official... 2023Several studies have explored the impact of BMI on size and composition of urinary stones. Because there were controversies, a meta-analysis was necessary to be carried... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several studies have explored the impact of BMI on size and composition of urinary stones. Because there were controversies, a meta-analysis was necessary to be carried out to provide some evidence of the relationship of BMI and urolithiasis.
MATERIALS AND METHODS
PubMed, Medline, Embase, Web of Science databases, and the Cochrane Library were searched up to August 12th 2022 for eligible studies. The urolithiasis patients were summarized into two groups: BMI < 25 and ≥ 25 kg/m2. Summary weighted mean difference (WMD), relative risk (RR) and 95% confidence intervals (CI) were calculated through random effects models in RevMan 5.4 software.
RESULTS
A total of fifteen studies involving 13,233 patients were enrolled in this meta-analysis. There was no significant correlation of BMI and size of urinary stone (WMD -0.13mm, 95% CI [-0.98, 0.73], p = 0.77). Overweight and obesity increased the risk of uric acid stones in both genders and in different regions (RR=0.87, [95% CI] = 0.83, 0.91, p<0.00001). There was a higher risk of calcium oxalate stones formation in overweight and obesity group in total patients (RR=0.95, [95% CI] = 0.91, 0.98, p = 0.006). The relationship of BMI and calcium phosphate was not observed in this meta-analysis (RR=1.12, [95% CI] = 0.98, 1.26, p = 0.09). Sensitivity analysis was performed and indicated similar results.
CONCLUSIONS
The current evidence suggests a positive association between BMI and uric acid and calcium oxalate stones. It would be of great guiding significance to consider losing weight when treating and preventing urinary stones.
Topics: Humans; Female; Male; Body Mass Index; Overweight; Calcium Oxalate; Uric Acid; Urolithiasis; Urinary Calculi; Obesity
PubMed: 37115175
DOI: 10.1590/S1677-5538.IBJU.2022.0587 -
Kidney International Reports Nov 2018Little is known of the clinical outcomes of secondary oxalate nephropathy. To inform clinical practice, we performed a systematic review of case reports and case series...
INTRODUCTION
Little is known of the clinical outcomes of secondary oxalate nephropathy. To inform clinical practice, we performed a systematic review of case reports and case series to examine the clinical characteristics and outcomes of patients with secondary oxalate nephropathy.
METHODS
Electronic databases were searched for case reports and case series of individual cases or cohorts of patients with biopsy-proven oxalate nephropathy in native or transplanted kidneys from 1950 until January 2018.
RESULTS
Fifty-seven case reports and 10 case series met the inclusion criteria, totaling 108 patients. The case series were meta-analyzed. Mean age was 56.4 years old, 59% were men, and 15% were kidney transplant recipients. Fat malabsorption (88%) was the most commonly attributed cause of oxalate nephropathy, followed by excessive dietary oxalate consumption (20%). The mean baseline serum creatinine was 1.3 mg/dl and peaked at 4.6 mg/dl. Proteinuria, hematuria, and urinary crystals was reported in 69%, 32%, and 26% of patients, respectively. Mean 24-hour urinary oxalate excretion was 85.4 mg/d. In addition to universal oxalate crystal deposition in tubules and/or interstitium, kidney biopsy findings included acute tubular injury (71%), tubular damage and atrophy (69%), and interstitial mononuclear cell infiltration (72%); 55% of patients required dialysis. None had complete recovery, 42% had partial recovery, and 58% remained dialysis-dependent. Thirty-three percent of patients died.
CONCLUSION
Secondary oxalate nephropathy is a rare but potentially devastating condition. Renal replacement therapy is required in >50% of patients, and most patients remain dialysis-dependent. Studies are needed for effective preventive and treatment strategies in high-risk patients with hyperoxaluria-enabling conditions.
PubMed: 30450463
DOI: 10.1016/j.ekir.2018.07.020 -
Journal of Experimental Pharmacology 2023The Urticaceae family contains 54 genera and more than 2000 species that can be found in tropical, subtropical, and temperate climates all over the world. This family... (Review)
Review
The Urticaceae family contains 54 genera and more than 2000 species that can be found in tropical, subtropical, and temperate climates all over the world. This family includes the largest genus in the world, , which is also known as stinging nettle. Stinging hairs are present on the lower surface of the leaves and beneath the stems of , also known as the stinging nettle, herbal nettle that is dioecious, upright, and unbranched. For the treatment of conditions like gastritis, heart disease, diabetes, gonorrhea, and malaria, people employ various portions of in a variety of ways in traditional medicine. The leaves are rich in variety of active secondary phytochemical constituents including terpenoids, saponins, tannins, flavonoids, steroids, alkaloids, polyphenols, sterols, oxalate, and ascorbic acid (vitamin C). According to different reports, it possesses a variety of pharmacological properties, including antioxidant, antiproliferative, antidiabetic, cardioprotective, antiulcer, antibacterial, and antifungal actions. The current review summarizes published and unpublished information about the ethnobotanical, phytochemical, ethnopharmacological, and toxicological reports of and summarizes all the research work carried out on this plant to provide updated information for future work.
PubMed: 37035014
DOI: 10.2147/JEP.S404506 -
Archivio Italiano Di Urologia,... Mar 2016To analyze the clinical evidence on the efficacy of phytotherapy in the treatment of calculi in the urinary tract. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To analyze the clinical evidence on the efficacy of phytotherapy in the treatment of calculi in the urinary tract.
METHODS
To be eligible, full-length articles should include the results of randomized controlled trials enrolling patients affected by urolithiasis, reporting any comparison between an experimental herbal agent versus placebo or any active comparator, aimed at preventing the formation or facilitating the dissolution of calculi in any portion of the urinary tract. Fifteen databases were searched for relevant references. The primary outcomes investigated were (i) the reduction of stone size and/or number and (ii) the urinary excretion rates of calcium, urate, or oxalate. The secondary outcome of the review was the adverse effects (AE) of treatment. Risk of bias (ROB) and quality of the evidence were assessed according to Cochrane and GRADE guidelines. We performed a random-effect meta-analysis.
RESULTS
541 articles were retrieved and 16 studies were finally confirmed as eligible. Multiple Cochrane ROB tool items were rated as having high risk of bias in each analyzed trial report. Pooled analysis of continuous data could be performed for three different comparisons: (i) phytotherapy versus citrate as single agent (ii) phytotherapy versus placebo, (iii) preparation of Didymocarpus pedicellata (DP)--combined with other herbal agents--versus placebo. Results showed that citrate is superior to phytotherapy in significantly decreasing both the size of urinary stones (mean difference: phytotherapy, 0.42 mm higher; 95% CI: 0.23 to 0.6; Z = 4.42, P < 0.0001; I2 = 30%) and the urinary excretion rate of urate (mean difference: 42.32 mg/24h higher, 95% CI: 19.44 to 65.19; Z = 3.63, P = 0.0003; I2 = 96%), assessed after 3 months on-therapy. No significant differences in the excretion rates of urinary calcium or oxalate were found. The DP preparation was superior to placebo in inducing total clearance (risk ratio: 6.19, 95% CI: 2.60 to 14.74; Z = 4.12, P < 0.0001; I2 = 0%) and size reduction (mean difference: DP preparation, 4.93 mm lower; 95% CI: -9.18 to -0.67; Z = 2.27, P = 0.02; I2 = 99%) of renal and ureteral stones after 3 months of therapy. No significant differences in the inter-arm variation of excretion rates of urinary calcium or urate were found as result of the pooled phytotherapy-placebo comparison. Herbal remedies were in general devoid of side effects and in few cases citrate appeared to induce GI disturbances in a higher fraction of patients. Most reports did not provide inferential data concerning AE, and meta-analysis was not feasible.
CONCLUSIONS
Citrate is more effective than phytotherapy in decreasing the size of existing calculi in the urinary tract and in decreasing the urinary excretion rate of uric acid. A preparation containing Didymocarpus pedicellata combined with other herbal agents induces stone size reduction and clearance significantly better than placebo. Mayor limitations in the applicability of these results are the low quality of the evidence and the multiple sources of bias assessed in the studies included in the present review.
Topics: Calcium; Citric Acid; Humans; Oxalic Acid; Phytotherapy; Plant Preparations; Plants, Medicinal; Randomized Controlled Trials as Topic; Uric Acid; Urinary Calculi
PubMed: 27072174
DOI: 10.4081/aiua.2016.1.38 -
The Cochrane Database of Systematic... Oct 2015Kidney stones affect people worldwide and have a high rate of recurrence even with treatment. Recurrences are particularly prevalent in people with low urinary citrate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Kidney stones affect people worldwide and have a high rate of recurrence even with treatment. Recurrences are particularly prevalent in people with low urinary citrate levels. These people have a higher incidence of calcium phosphate and calcium oxalate stones. Oral citrate therapy increases the urinary citrate levels, which in turn binds with calcium and inhibits the crystallisation thus reduces stone formation. Despite the widespread use of oral citrate therapy for prevention and treatment of calcium oxalate stones, the evidence to support its clinical efficacy remains uncertain.
OBJECTIVES
The objective of this review was to determine the efficacy and adverse events associated with citrate salts for the treatment and prevention of calcium containing kidney stones.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Specialised Register to 29 July 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that assessed the efficacy and adverse events associated with citrate salts for the treatment and prevention of calcium containing kidney stones in adults treated for a minimum of six months.
DATA COLLECTION AND ANALYSIS
Two authors assessed studies for inclusion in this review. Data were extracted according to predetermined criteria. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes.
MAIN RESULTS
We included seven studies that included a total of 477 participants, most of whom had oxalate stones. Of these, three studies (247 participants) compared potassium citrate with placebo or no intervention; three (166 participants) compared potassium-sodium citrate with no intervention; and one (64 participants) compared potassium-magnesium citrate with placebo. Overall, quality of the reporting of the included studies was considered moderate to poor, and there was a high risk of attrition bias in two studies.Compared with placebo or no intervention, citrate therapy significantly reduced the stone size (4 studies, 160 participants: RR 2.35, 95% CI 1.36 to 4.05). New stone formation was significantly lower with citrate therapy compared to control (7 studies, 324 participants: RR 0.26, 95% CI 0.10 to 0.68). The beneficial effect on stone size stability was also evident (4 studies, 160 participants: RR 1.97, 95% CI 1.19 to 3.26). Adverse events were reported in four studies, with the main side effects being upper gastrointestinal disturbance and one patient reported a rash. There were more gastrointestinal adverse events in the citrate group; however this was not significant (4 studies, 271 participants: RR 2.55, 95% CI 0.71 to 9.16). There were significantly more dropouts due to adverse events with citrate therapy compared to control (4 studies, 271 participants: RR 4.45, 95% CI 1.28 to 15.50). The need for retreatment was significantly less with citrate therapy compared to control (2 studies, 157 participants: RR 0.22, 95% CI 0.06 to 0.89).
AUTHORS' CONCLUSIONS
Citrate salts prevent new stone formation and reduce further stone growth in patients with residual stones that predominantly contain oxalate. The quality of reported literature remains moderate to poor; hence a well-designed statistically powered multi-centre RCT is needed in order to answer relevant questions concerning the efficacy of citrate salts.
Topics: Adult; Calcium Oxalate; Calcium Phosphates; Citrates; Drug Combinations; Humans; Kidney Calculi; Magnesium Compounds; Potassium Compounds; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention
PubMed: 26439475
DOI: 10.1002/14651858.CD010057.pub2 -
Nutrition (Burbank, Los Angeles County,... Jan 2024Vulvodynia is an emerging health problem, still insufficiently studied, that causes a significant reduction in quality of life in many women and individuals assigned... (Review)
Review
OBJECTIVES
Vulvodynia is an emerging health problem, still insufficiently studied, that causes a significant reduction in quality of life in many women and individuals assigned female sex at birth. Little is known about the effects of diet and metabolic disorders on this condition. The objective of this study was to review currently available evidence on the diet and the nutritional and metabolic status of patients affected by vulvodynia.
METHODS
Published articles were systematically searched in the PubMed, Scopus, and Web of Science databases.
RESULTS
The few available studies that reported data on patients' body mass index (BMI) described a BMI within the normal range in most patients affected by vulvodynia, showing no difference or a slightly lower BMI with respect to control individuals. Data on the relationship between metabolic diseases and vulvodynia are lacking. Regarding nutrition, the few available data do not support the prescription of a low-oxalate diet in women with vulvodynia. To date, studies on other dietary behaviors are also lacking.
CONCLUSIONS
This review emphasizes-for the first time, to our knowledge-the lack of data and the importance of conducting prospective studies investigating the nutritional and metabolic aspects related to the onset, maintenance, and therapy of vulvodynia.
Topics: Infant, Newborn; Female; Humans; Vulvodynia; Prospective Studies; Quality of Life; Diet; Research Design
PubMed: 37856898
DOI: 10.1016/j.nut.2023.112232 -
The Cochrane Database of Systematic... Feb 2014Idiopathic hypercalciuria is an inherited metabolic abnormality that is characterised by excessive amounts of calcium excreted in the urine by people whose calcium serum... (Review)
Review
BACKGROUND
Idiopathic hypercalciuria is an inherited metabolic abnormality that is characterised by excessive amounts of calcium excreted in the urine by people whose calcium serum levels are normal. Morbidity associated with idiopathic hypercalciuria is chiefly related to kidney stone disease and bone demineralisation leading to osteopenia and osteoporosis. Idiopathic hypercalciuria contributes to kidney stone disease at all life stages; people with the condition are prone to developing oxalate and calcium phosphate kidney stones. In some cases, crystallised calcium can be deposited in the renal interstitium, causing increased calcium levels in the kidneys. In children, idiopathic hypercalciuria can cause a range of comorbidities including recurrent macroscopic or microscopic haematuria, frequency dysuria syndrome, urinary tract infections and abdominal and lumbar pain. Various dietary interventions have been described that aim to decrease urinary calcium levels or urinary crystallisation.
OBJECTIVES
Our objectives were to assess the efficacy, effectiveness and safety of dietary interventions for preventing complications in idiopathic hypercalciuria (urolithiasis and osteopenia) in adults and children, and to assess the benefits of dietary interventions in decreasing urological symptomatology in children with idiopathic hypercalciuria.
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register (23 April 2013) through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) and quasi-RCTs that investigated dietary interventions aimed at preventing complications of idiopathic hypercalciuria, compared with placebo, no intervention, or other dietary interventions regardless of route of administration, dose or amount.
DATA COLLECTION AND ANALYSIS
Studies were assessed for inclusion and data extracted using a standardised data extraction form. We calculated risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, both with 95% confidence intervals (CI).
MAIN RESULTS
We included five studies (379 adult participants) that investigated a range of interventions. Lack of similarity among interventions investigated meant that data could not be pooled. Overall, study methodology was not adequately reported in any of the included studies. There was a high risk of bias associated with blinding (although it seems unlikely that outcomes measures were unduly influenced by lack of intervention blinding), random sequence generation and allocation methodologies were unclear in most studies, but selective reporting bias was assessed as low.One study (120 participants) compared a low calcium diet with a normal calcium, low protein, low salt diet for five years. There was a significant decrease in numbers of new stone recurrences in those treated with the normal calcium, low protein, low salt diet (RR 0.77, 95% CI 0.61 to 0.98). This diet also led to a significant decrease in oxaluria (MD 78.00 µmol/d, 95% CI 26.48 to 129.52) and the calcium oxalate relative supersaturation index (MD 1.20 95% CI 0.21 to 2.19).One study (210 participants) compared a low salt, normal calcium diet with a broad diet for three months. The low salt, normal calcium diet decreased urinary calcium (MD -45.00 mg/d, 95% CI -74.83 to -15.17) and oxalate excretion (MD -4.00 mg/d, 95% CI -6.44 to -1.56).A small study (17 participants) compared the effect of dietary fibre as part of a low calcium, low oxalate diet over three weeks, and found that although calciuria levels decreased, oxaluria increased. Phyllanthus niruri plant substrate intake was investigated in a small subgroup with hypercalciuria (20 participants); there was no significant effect on calciuria levels occurred after three months of treatment.A small cross-over study (12 participants) evaluating the changes in urinary supersaturation indices among patients who consumed calcium-fortified orange juice or milk for one month found no benefits for participants.None of the studies reported any significant adverse effects associated with the interventions.
AUTHORS' CONCLUSIONS
Long-term adherence (five years) to diets that feature normal levels of calcium, low protein and low salt may reduce numbers of stone recurrences, decrease oxaluria and calcium oxalate relative supersaturation indexes in people with idiopathic hypercalciuria who experience recurrent kidney stones. Adherence to a low salt, normal calcium level diet for some months can reduce calciuria and oxaluria. However, the other dietary interventions examined did not demonstrate evidence of significant beneficial effects.No studies were found investigating the effect of dietary recommendations on other clinical complications or asymptomatic idiopathic hypercalciuria.
Topics: Adult; Calcium, Dietary; Diet, Protein-Restricted; Diet, Sodium-Restricted; Humans; Hypercalciuria; Hyperoxaluria; Nephrolithiasis; Randomized Controlled Trials as Topic
PubMed: 24519664
DOI: 10.1002/14651858.CD006022.pub4 -
Cureus Sep 2023Kidney stone formation is an intricate process that involves a disruption in the interplay of the multiple organs and systems involved in regulating the concentration of... (Review)
Review
Kidney stone formation is an intricate process that involves a disruption in the interplay of the multiple organs and systems involved in regulating the concentration of specific ions in the body. Women who have gone through menopause are susceptible to kidney stone disease. This systematic review aims to investigate the potential influence of estrogen on kidney function and oxalate homeostasis, notably through the anion transporter SLC26A6 (also known as putative anion transporter 1 or PAT1) in females. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist, a systematic search of online databases included Pubmed, ScienceDirect Journals, and Ingenta Connect Journals. Predetermined criteria to include and exclude papers, gathering articles published between 2012 and 2022, were determined. After a thorough analysis, eight articles (three cohorts, one case-control, one in vivo, one in vitro, and two cross-sectional studies) were identified for the final quality assessment review. The eight selected and quality-assessed articles provided evidence of a directly proportional connection between estrogen and kidney function. A correlation between serum estrogen levels and the development of kidney stone disease was confirmed. Administration of β-estradiol was shown to effectively inhibit the function of the anion transporter PAT1 in a tissue-specific manner. In the case of the kidney, estrogen was observed to down-regulate PAT1, which led to a reduction in oxalate transporting activity and, consequently, a decrease in kidney stone formation. Consensus suggests that serum estrogen levels and optimal kidney functioning are interrelated. Furthermore, analysis of the quality-assessed articles and a comprehensive literature review revealed estrogen's tissue-specific regulation of the PAT1 anion transporter aids in maintaining kidney function and anion homeostasis. Additional research is needed to solidify estrogen's role in kidney stone disease to determine its therapeutic value in clinical practice.
PubMed: 37881392
DOI: 10.7759/cureus.45839 -
Frontiers in Immunology 2021The global prevalence and recurrence rate of kidney stones is very high. Recent studies of Randall plaques and urinary components , and including gene manipulation,...
BACKGROUND
The global prevalence and recurrence rate of kidney stones is very high. Recent studies of Randall plaques and urinary components , and including gene manipulation, have attempted to reveal the pathogenesis of kidney stones. However, the evidence remains insufficient to facilitate the development of novel curative therapies. The involvement of renal and peripheral macrophages in inflammatory processes offers promise that might lead to the development of therapeutic targets. The present systematic literature review aimed to determine current consensus about the functions of macrophages in renal crystal development and suppression, and to synthesize evidence to provide a basis for future immunotherapy.
METHODS
We systematically reviewed the literature during February 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles investigating the relationship between macrophages and urolithiasis, particularly calcium oxalate (CaOx) stones, were extracted from PubMed, MEDLINE, Embase, and Scopus. Study subjects, languages, and publication dates were unrestricted. Two authors searched and screened the publications.
RESULTS
Although several studies have applied mixed modalities, we selected 10, 12, and seven (total, n = 29) of 380 articles that respectively described cultured cells, animal models, and human samples.The investigative trend has shifted to macrophage phenotypes and signaling pathways, including micro (m)-RNAs since the discovery of macrophage involvement in kidney stones in 1999. Earlier studies of mice-associated macrophages with the acceleration and suppression of renal crystal formation. Later studies found that pro-inflammatory M1- and anti-inflammatory M2-macrophages are involved. Studies of human-derived and other macrophages and showed that M2-macrophages (stimulated by CSF-1, IL-4, and IL-13) can phagocytose CaOx crystals, which suppresses stone development. The signaling mechanisms that promote M2-like macrophage polarization toward CaOx nephrocalcinosis, include the NLRP3, PPARγ-miR-23-Irf1/Pknox1, miR-93-TLR4/IRF1, and miR-185-5p/CSF1 pathways.Proteomic findings have indicated that patients who form kidney stones mainly express M1-like macrophage-related proteins, which might be due to CaOx stimulation of the macrophage exosomal pathway.
CONCLUSIONS
This systematic review provides an update regarding the current status of macrophage involvement in CaOx nephrolithiasis. Targeting M2-like macrophage function might offer a therapeutic strategy with which to prevent stones crystal phagocytosis.
Topics: Animals; Calcium Oxalate; Humans; Kidney Calculi; Macrophages; Nephrolithiasis
PubMed: 34108970
DOI: 10.3389/fimmu.2021.673690