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Risk of urogenital infections in non-diabetic patients treated with sodium glucose transporter 2 (SGLT2) inhibitors. Systematic review and meta-analysis.
Bapir, R, Bhatti, KH, Eliwa, A, García-Perdomo, HA, Gherabi, N, Hennessey, D, Magri, V, Mourmouris, P, Ouattara, A, Perletti, G, et al
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2023;(2):11509
Abstract
UNLABELLED Although SGLT2 inhibitors have been initially employed in the treatment of type 2 diabetes, their clinical use was later extended to the treatment of other conditions such as heart failure, chronic kidney disease and obesity. In patients with type 2 diabetes, the administration of SGLT2 inhibitors has been associated with an increased incidence of urogenital infections, which may be linked to high glucose levels in the urine. The rate of urogenital side effects may be different in non-diabetic patients. The aim of this study was to review the risk of urogenital infections in non-diabetic patients taking SGLT2 inhibitors. MATERIALS AND METHODS We conducted a systematic review and meta-analysis by searching PubMed and EMBASE for randomized controlled trials (RCTs) reporting urogenital adverse effects in non-diabetic patients treated with SGLT2 inhibitors. Odds ratios for urogenital infections were calculated using random effect Mantel-Haenszel statistics. RESULTS Out of 387 citations retrieved, 12 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared to placebo, SGLT2 inhibitors were associated with increased odds of genital infections (OR 3.01, 95% CI: 1.93- 4.68, 9 series, 7326 participants, Z = 5.74, p < 0.0001, I2 = 0%) as well as urinary tract infections (OR 1.33, 95% CI: 1.13-1.57, 9 series, 7326 participants, Z = 4.05, p < 0.0001, I2 = 0%). When four trials investigating the effects of SGLT2 inhibitors in populations including both diabetic and non-diabetic patients were considered, administration of SGLT2 inhibitors in diabetic patients was associated with significantly higher odds of genital infections but not urinary tract infections compared to patients without type 2 diabetes. In patients taking placebo, the odds for urinary tract infections were significantly increased in diabetic patients compared to non-diabetic patients. CONCLUSIONS The risk of genital infections is increased also in non-diabetic patients taking SGLT2 inhibitors although at a lesser extent that in diabetics. A careful assessment of the local anatomical conditions and of the history of previous urogenital infections is desirable to select those patients who need more intense follow-up, possibly combined with prophylactic measures of infections during treatment with SGLT2 inhibitors.
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Treatment of urge incontinence in postmenopausal women: A systematic review.
Bapir, R, Bhatti, KH, Eliwa, A, García-Perdomo, HA, Gherabi, N, Hennessey, D, Magri, V, Mourmouris, P, Ouattara, A, Perletti, G, et al
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2023;(3):11718
Abstract
BACKGROUND Urinary incontinence and other urinary symptoms tend to be frequent at menopause because of hormonal modifications and aging. Urinary symptoms are associated with the genitourinary syndrome of menopause which is characterized by physical changes of the vulva, vagina and lower urinary tract. The treatment strategies for postmenopausal urinary incontinence are various and may include estrogens, anticholinergics, and pelvic floor muscle training. A comparison of these treatments is difficult due to the heterogeneity of adopted protocols. We systematically reviewed the evidence from randomized controlled trials (RCTs) focusing on treatment of postmenopausal women with urge incontinence. METHODS We conducted a systematic review and meta-analysis by searching PubMed and EMBASE databases for randomized controlled trials (RCTs) reporting results of treatments for postmenopausal urinary urge incontinence. Odds ratios for improvement of urinary incontinence were calculated using random effect Mantel-Haenszel statistics. RESULTS Out of 248 records retrieved, 35 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared with placebo, systemic estrogens were associated with decreased odds of improving urinary incontinence in postmenopausal women (OR = 0.74, 95% CI: 0.61-0.91, 7 series, 17132 participants, Z = 2.89, P = 0.004, I2 = 72%). In most studies, no significant improvement in urinary symptoms was observed in patients treated with local estrogens, although they showed to be helpful in improving vaginal symptoms. Vitamin D, phytoestrogens and estrogen modulators were not effective in improving symptoms of incontinence and other symptoms of genitourinary menopause syndrome or yielded contradictory results. A randomized controlled trial demonstrated that oxybutynin was significantly better than placebo at improving postmenopausal urgency and urge incontinence. The combination of anticholinergics with local estrogens has not been shown to be more effective than anticholinergics alone in improving urinary incontinence symptoms in postmenopausal women. Physical therapy showed an overall positive outcome on postmenopausal urinary incontinence symptoms, although such evidence should be further validated in the frame of quality RCTs. CONCLUSIONS The evidence for effective treatment of postmenopausal urinary incontinence is still lacking. Welldesigned large studies having subjective and objective improvement primary endpoints in postmenopausal urinary incontinence are needed. At present, a combination of different treatments tailored to the characteristics of the individual patient can be suggested.
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Risk of urinary stone formation associated to proton pump inhibitors: A systematic review and metanalysis.
Bapir, R, Bhatti, KH, Eliwa, A, García-Perdomo, HA, Gherabi, N, Hennessey, D, Magri, V, Mourmouris, P, Ouattara, A, Perletti, G, et al
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2022;(4):507-514
Abstract
OBJECTIVE Proton pump inhibitors are widely used as treatment of acid-related disorders. They are considered safe although their long-term use has been associated with some adverse effects including an increased propensity for urinary calculi formation. The aim of this study was to systematically review available data from studies evaluating the association of PPIs and nephrolithiasis. MATERIALS AND METHODS We searched two electronic databases (PubMed and EMBASE) for cohort studies or case-control studies evaluating the relationship between treatment with proton pump inhibitors and the risk of stone formation published up to 31 October 2022. The overall association of PPIs and urinary calculi was analyzed using a random effects model (RevMan5). The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS A total of 550 studies were retrieved; 7 were selected by title and abstract screening; after removal of duplicates, 4 records were evaluated by full-text examination. An additional study was retrieved by handsearching the references included in screened studies. In the unadjusted analysis, the odds of urinary calculi were greater in subjects taking PPIs compared to controls (unadjusted OR = 2.10, 95% CI 1.74-2.52, p < 0.00001). The pooled odds ratio of two case-control studies confirmed that use of PPIs increased the odds of urinary calculi compared with non-use (OR 2.44, 95% CI 2.29 to 2.61). Pooled analysis of three cohort studies evaluating incident nephrolithiasis showed an overall hazard ratio estimate of 1.34 (95% CI = 1.28-1.40). One study found lower urinary citrate and urinary magnesium levels in subjects exposed to PPIs. The Newcastle-Ottawa Quality Assessment Scale scores ranged between 6 and 8. CONCLUSIONS PPIs showed an association with urinary calculi in patients included in the studies included in this review. If these data will be confirmed in adequately powered randomized trials, clinicians may consider limiting the long-term use of PPIs, to avoid unnecessary prolongation of treatment. Urinary magnesium and citrate should be evaluated in renal stone forming patients taking PPIs to supplement their intake when requested.
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Urine and stone analysis for the investigation of the renal stone former: a consensus conference.
Williams, JC, Gambaro, G, Rodgers, A, Asplin, J, Bonny, O, Costa-Bauzá, A, Ferraro, PM, Fogazzi, G, Fuster, DG, Goldfarb, DS, et al
Urolithiasis. 2021;(1):1-16
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Abstract
The Consensus Group deliberated on a number of questions concerning urine and stone analysis over a period of months, and then met to develop consensus. The Group concluded that analyses of urine and stones should be routine in the diagnosis and treatment of urinary stone diseases. At present, the 24-h urine is the most useful type of urine collection, and accepted methods for analysis are described. Patient education is also important for obtaining a proper urine sample. Graphical methods for reporting urine analysis results can be helpful both for the physician and for educating the patient as to proper dietary changes that could be beneficial. Proper analysis of stones is also essential for diagnosis and management of patients. The Consensus Group also agreed that research has shown that evaluation of urinary crystals could be very valuable, but the Group also recognizes that existing methods for assessment of crystalluria do not allow this to be part of stone treatment in many places.
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The impact of nutrition and lifestyle on male fertility.
Benatta, M, Kettache, R, Buchholz, N, Trinchieri, A
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2020;92(2)
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The impact of environmental, lifestyle and nutritional factors on unexplained male fertility has long been acknowledged. Yet, little research had been dedicated to the topic, despite declining semen quality having become a worldwide phenomena. Available studies have yielded limited, and at times conflicting, evidence. Hence this literature review sought to capture the current knowledge around unexplained male infertility and environmental, lifestyle, diet and nutrients factors. Summarized is the evidence from 69 studies, including population observations and clinical trials. The collected outcomes showed that a Western-type diet, rich in red and processed meats, refined grains, high-energy drinks and sweets, trans and saturated fats was associated with poor semen quality. Whereby higher intakes of fruits and vegetables, whole grains, omega-3 and poultry showed beneficial effects. However, as only selected groups were examined, more research is needed to project such findings onto the wider population. The reviewed evidence also included alcohol consumption, which showed high alcohol intake closely correlated to declining sperm concentrations. Whilst the verdict on caffeine consumption and the impact on sperm quality was inconclusive. In addition, several interventional studies evaluated the effect of dietary supplementation on various parameters of semen, where coenzyme Q10, L-carnitine, vitamin E, antioxidants, combined nutrient formulations and herbal blends all had positive outcomes. The review on zinc and folic acid supplementation yielded mixed results. This brief recap of the current evidence on environmental, lifestyle and nutritional influences on male infertility summarises the dietary foundations for the support of unexplained male infertility.
Abstract
BACKGROUND AND AIMS Male unexplained infertility has long been suspected to result from environmental, lifestyle and nutritional factors. However, the literature on the subject is still scarce, and clinical studies providing robust evidence are even scarcer. In addition, some similar studies come to different conclusions. Dietary pattern can influence spermatogenesis by its content of fatty acids and antioxidants. Yet, in an age of industrialized mass food production, human bodies become more exposed to the ingestion of xenobiotics, as well as chemicals used for production, preservation, transportation and taste enhancement of foods. We attempted in this paper to collect the available evidence to date on the effect of nutritional components on male fertility. MATERIAL AND METHODS A systematic search of the relevant literature published in PubMed, ScienceDirect and Cochrane Central Register of Controlled Trials Database was conducted. Literature was evaluated according to the Newcastle-Ottawa- Scale. RESULTS Epidemiological observations are concordant in demonstrating an association of low-quality sperm parameters with higher intake of red meat, processed and organ meat and fullfat dairy. On the contrary, better semen parameters were observed in subjects consuming a healthy diet, rich in fruit, vegetables, whole grains and fish. Evidences of the negative impact on male fertility of by-products of water disinfection, accumulation in food chain of persistent organochlorine pollutants, pesticides, phthalates from food and water containers and hormones used in breeding cattle have been reported. Clinical trials of the effects of micronutrients on semen parameters and outcomes of assisted fertilization are encouraging, although optimal modality of treatment should be established. CONCLUSIONS Although quality of evidence should be ameliorated, it emerges that environmental factors can influence male fertility. Some nutrients may enhance fertility whereas others will worsen it. With diagnostic analysis on a molecular or even sub-molecular level, new interactions with micronutrients or molecular components of our daily ingested foods and leisure drugs may lead to a better understanding of so far suspected but as yet unexplained effects on male spermatogenesis and fertility.
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[A diagnostic-therapeutic pathway for patients with kidney stone disease: 2020 update].
Cupisti, A, Trinchieri, A, Lombardi, M, Agostini, S, Arcidiacono, T, Beltrami, P, Berri, E, Bevilacqua, L, Campo, S, Cannavò, R, et al
Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia. 2020;(Suppl 75)
Abstract
The natural history of urinary kidney stone disease includes the risk of relapses and can be associated with the risk of chronic kidney disease, bone and cardiovascular disease. For this reason, a wide clinical-metabolic assessment of the kidney stone patient is of great importance since the first presentation of the stone, to set an appropriate preventive treatment. The proposed diagnostic-therapeutic pathway includes a careful medical history, in order to highlight a secondary kidney stone disease and the main risk factors for kidney stones, chronic renal disease, or cardiovascular and bone disease; a metabolic evaluation on multiple levels, according to the severity of the disease, and the presence or absence of risk factors, and appropriate instrumental investigations. Thus, the information collected makes it possible to set a preventive treatment consisting of general rules and, if necessary, specific pharmacological or nutritional interventions. This paper has been prepared by the Italian Multidisciplinary Study Group for Kidney Stone Disease, and it is addressed to the several professional figures involved in the management of patients suffering from nephrolithiasis, from the emergency doctor to the general practitioner, urologist, nephrologist, radiologist, and dietician. A diagnostic-therapeutic pathway for patients with kidney stone disease was first published on this Journal in 2010. The present contribution aims at amending and updating the article published exactly ten years ago, to serve as an easy-to-use reference and to guide good clinical practice in this field.
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Nutrients, vitamins, probiotics and herbal products: an update of their role in urolithogenesis.
Pedro, RN, Aslam, AU, Bello, JO, Bhatti, KH, Philipraj, J, Sissoko, I, Vasconcellos, GS, Trinchieri, A, Buchholz, N
Urolithiasis. 2020;(4):285-301
Abstract
Nutrients, vitamins, probiotics, and herbal products may be risk factors, or alternately, protect against the formation of urinary stones. The purpose of this review was to update knowledge of the role of nutraceuticals in renal stone formation. A systematic search of the relevant literature published in PubMed in the last ten years was conducted and a narrative review of the data from the included studies was done. Search screened 513 studies that were reduced to 34 after evaluation by title and abstract; other 38 studies were retrieved by references of the selected studies. Beverages high fluid intake confirmed protective effect; orange juice protective effect; apple or grapefruit juice not confirmed as risk factors; sugar-sweetened soda and punch increased risk of stone formation. Energy intake: very high energy intake increased risk factor for women (especially after menopause); dietary acid load increased risk at equal levels of energy intake. Macronutrients confirmed increased risk of high protein intake. Calcium and Oxalate: calcium intake protective effect; oxalate intake only modest increase of risk in men and older women. Metal cations zinc and iron intake no clear impact on the risk of stone formation, dietary copper increased risk; manganese intake reduced risk of stone formation. Fruits and Vegetables decreased risk. Vitamins B6 intake not associated to risk of stone formation; vitamin C intake increased risk in men; vitamin D or supplemental vitamin D intake not associated to increased risk in men and younger women, suggestion of a higher risk in older women; Probiotics Gut colonization with Oxalobacter formigenes associated to lower risk of stone formation, effect of oxalate-degraders probiotics on urinary oxalate equivocal. Herbal products efficacy of some herbal products demonstrated in some trials, more investigations needed to confirm their efficacy and safety.
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Influence of dietary energy intake on nephrolithiasis - A meta-analysis of observational studies.
Perletti, G, Magri, V, Ferraro, PM, Montanari, E, Trinchieri, A
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2020;(1):30-33
Abstract
OBJECTIVE Obesity has been associated with an increased risk of kidney stone formation. The presence of obesity is due to an imbalance between energy intake and energy consumption resulting from physical activity and resting metabolic rate. The purpose of this meta-analysis was to assess the differences in dietary energy intake levels between patients developing urinary stones versus healthy individuals. MATERIALS AND METHODS Medline/PubMed and EMBASE databases search was performed using the terms "urolithiasis", "kidney stones*", "calcul*", "energy", "calor*", "intake", "food", "kilojoule/kjoule", "Kilocal*/kcal" from January 1st, 2000, and were assessed as up to date on September 30th, 2019. RESULTS After having screened 1.782 records, four studies were included in the meta-analysis. The total population was 467.063, including 453.078 healthy men and/or women and 13.985 men and/or women affected by nephrolithiasis. When energy intake data were pooled irrespective of the sex of participants, mean calory intake values were significantly higher in nephrolithiasis patients, compared to healthy individuals. The mean difference (MD) was 39.16 kcal (95% CI 18.53 to 59.78, p = 0.0002, random-effects model, inverse-variance weighing). The odds ratio for this comparison - calculated from the standardized mean difference - is significant (OR = 1.946; 95% CI: 1.869 to 5.561). CONCLUSIONS Patients affected by urolithiasis show a significantly higher energy intake in various patient populations (USA, China and Korea) including subjects of both sexes. The relevance of this finding should be confirmed by studies in populations showing different and diverse dietary patterns, and by evaluating energy consumption linked to physical activity and metabolic rate in renal stone formers.
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Green tea catechins for chemoprevention of prostate cancer in patients with histologically-proven HG-PIN or ASAP. Concise review and meta-analysis.
Perletti, G, Magri, V, Vral, A, Stamatiou, K, Trinchieri, A
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2019;(3)
Abstract
A focused, single outcome meta-analysis on the protective role of extracts of green tea catechins against prostate cancer. Randomized, placebo-controlled studies enrolling patients with a histologically confirmed diagnosis of high-grade Prostate Intraepithelial Neoplasia or Atypical Small Acinar proliferation but no prostate cancer were included. Meta-analysis for binary data was performed using Mantel-Haenszel statistics, using a random-effects model. Heterogeneity was investigated by calculating the I2. Four studies matched the inclusion criteria for the review. The pooled population was 223 patients; 114 and 109 patients were randomized to catechin and placebo groups, respectively. Nine cases of prstate cancer occurred in the catechin arm (7.9%), and 24 cases were reported in the placebo arm (22%). Pooled analysis resulted in a significant reduction of cancer risk in favor of the catechin arm (risk-ratio = 0.41; 95% CI: 0.19- 0.86; I2 = 0). In conclusion, our data suggest that the intake of concentrated green tea catechin preparations may confer a significant protective effect to carriers of early neoplastic lesions in the prostate. The quality of the evidence is moderate, and additional, largescale studies are warranted to substantiate these preliminary findings.
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Impact of food quantity and quality on the biochemical risk of renal stone formation.
Esperto, F, Miano, R, Marangella, M, Trinchieri, A
Scandinavian journal of urology. 2018;(3):225-229
Abstract
OBJECTIVE This study evaluated the role of body mass index (BMI) and dietary potential renal acid load (PRAL) with urinary saturation for calcium oxalate (US-CaOx), calcium phosphate (US-CaP) and uric acid (US-UA) in renal stone formers. MATERIALS AND METHODS A retrospective analysis was conducted of laboratory data collected on 442 renal stone-forming patients. Demographic information, BMI and 24 h urinary samples were collected from patients on their regular diets. PRAL was calculated as the Load of Acid to Kidney Evaluation (LAKE) score through a short questionnaire. RESULTS Urinary risk factors, but also inhibitors of calcium stone formation such as magnesium, tended to increase in relation to BMI (p = .000). Urinary pH (p = .002) and ammonium/sulfate ratio (p = .000) were negatively related to BMI. This resulted in a positive correlation between BMI and US-UA (p = .000), whereas US-CaOx and US-CaP were not influenced by BMI. LAKE score was positively correlated with US-CaOx (p = .022) and US-CaP (p = .000) as a consequence of the inverse relationship between LAKE score and citrate (p = .000). Multiple linear regression analysis identified BMI (p = .009) and male gender (p = .002) as independent predictors of US-UA, and LAKE score (p = .004) and age (p = .001) as independent predictors of US-CaP. CONCLUSIONS BMI, which depends on excessive intake of energy from food, is not related to an increased biochemical risk of calcium stone formation, which is more dependent on the renal acid load of the diet. In contrast, obesity is associated with an increased risk of uric acid stone formation due to insulin resistance, impaired ammoniagenesis and low urinary pH.