Kidney Stones In Adults Research Articles

The Durability of Active Surveillance in Patients with Asymptomatic Kidney Stones: A Systematic Review.

Introduction: The natural progression of asymptomatic kidney stones remains unclear. Such knowledge may promote value-aligned care for patients and reduce potentially unnecessary procedures. We sought to evaluate the natural history of asymptomatic kidney stones in adults undergoing active surveillance. Materials and Methods: Using themes of "Kidney Stone" and "Active Surveillance," we performed a systematic review by searching for studies in MEDLINE, all Cochrane libraries, EMBASE, Cumulative Index to Nursing and Allied Health Literature, BIOSIS, Scopus, and Web of Science from inception through October 2017-in addition to ClinicalTrials.gov, American Urological Association Annual Meeting abstracts (2014-2017), Google Scholar, and references of included studies and prior reviews. Two blinded reviewers independently extracted data and assessed methodological quality. We qualitatively summarized rates of surgical intervention (primary outcome), spontaneous stone passage, symptom development, and stone growth. We assessed the relationship between surveillance duration and rate of surgical intervention with Pearson's correlation coefficient. Results: Of 7034 unique records, 13 studies met final eligibility criteria. There was substantial variation in reported rates of surgical intervention from 6/85 (7.1%) to 80/301 (26.6%), spontaneous stone passage from 1/32 (3.1%) to 101/347 (29.1%), symptom development from 7/96 (7.3%) to 231/300 (77.0%), and stone growth from 5/96 (5.2%) to 33/50 (66.0%). Mean surveillance duration spanned from 11.3 to 80 months (range 2-180 months). Longer mean duration of surveillance did not correlate with an increase in surgical intervention rate across studies (n = 13, r = 0.01, p = 0.98), and this finding persisted when restricting analysis to observational studies (n = 9, r = 0.12, p = 0.76). Conclusions: Active surveillance appears to be a durable strategy for a majority of patients with asymptomatic kidney stones, as there was no increase in failure of watchful waiting despite increasing duration of surveillance. Higher quality studies are needed to ascertain which patients may benefit most from active surveillance.

Evaluating pathogenicity of SLC34A3-Ser192Leu, a frequent European missense variant in disorders of renal phosphate wasting

Loss-of-function mutations of SLC34A3 represent an established cause of a distinct renal phosphate wasting disorder termed hereditary hypophosphatemic rickets with hypercalciuria (HHRH). SLC34A3 encodes the renal phosphate transporter NaPi2c expressed at the apical brush border of proximal renal tubules. Substitution of p.Ser192Leu is one of the most frequent genetic changes among HHRH patients in Europe, but has never been systematically evaluated, clinically or on a cellular level. Identification of a 32-year-old female with a homozgyous c.575C>T, p.Ser192Leu substitution enabled a more comprehensive assessment of the impact of this missense variant. Clinically, the patient showed renal phosphate wasting and nephrocalcinosis without any bone abnormalities. Heterozygous carriers of deleterious SLC34A3 variants were previously described to harbor an increased risk of kidney stone formation and renal calcification. We hence examined the frequency of p.Ser192Leu variants in our adult kidney stone cohort and compared the results to clinical findings of previously published cases of both mono- and biallelic p.Ser192Leu changes. On a cellular level, p.Ser192Leu-mutated transporters localize to the plasma membrane in different cellular systems, but lead to significantly reduced transport activity of inorganic phosphate upon overexpression in Xenopus oocytes. Despite the reduced function in ectopic cellular systems, the clinical consequences of p.Ser192Leu may appear relatively mild, at least in our index patient, and can potentially be missed in clinical practice.

A rapid screening of a recurrent CYP24A1 pathogenic variant opens the way to molecular testing for Idiopathic Infantile Hypercalcemia (IIH)

IntroductionLoss-of-function mutations in cytochrome P450 family 24 subfamily A member 1 (CYP24A1) gene are associated with Idiopathic Infantile Hypercalcemia (IIH) and adult kidney stone disease. The enzyme deficiency leads to an impaired vitamin D catabolism pathway, resulting in a syndrome characterized by recurrent hypercalcemia, hypercalciuria and suppressed parathyroid hormone (PTH) levels. In these patients, the genetic evaluation of CYP24A1 is an important diagnostic tool, allowing the definitive diagnosis of IIH. MethodsA rapid CYP24A1 gene testing based on High Resolution Melting Analysis (HRMA) was designed in order to detect the CYP24A1 c.428_430delAAG (p.Glu143del), a recurrent IIH-associated variant. ResultsHRMA method was able to identify c.428_430delAAG genotypes evaluating melting curve shape and melting temperature (Tm). Heterozygous samples exhibited a typical melting profile while homozygous samples showed a specific Tm shift. ConclusionsWe provide evidence about application of HRMA in unambiguous genotyping of the CYP24A1 c.428_430delAAG variant, making this method useful in clinical molecular diagnostics. This approach opens the way to a helpful molecular analysis of CYP24A1 gene in IIH diagnosis, to an improved pharmacological treatment strategy and to a reduced risk of recurrent stones and worsening nephrocalcinosis.

Incidence and characteristics of kidney stones in patients with horseshoe kidney: A systematic review and meta-analysis.

Introduction:The horseshoe kidney (HSK) is the most common type of renal fusion anomaly. The incidence and characteristics of kidney stones in patients with HSK are not well studied. The aim of this meta-analysis was to evaluate the incidence and types of kidney stones in patients with HSK.Methods:A systematic literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from the databases' inception through November 2016. Studies assessing the incidence and types of kidney stones in patients with HSK were included. We applied a random-effects model to estimate the incidence of kidney stones. The study protocol was registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42016052037).Results:A total of 14 observational studies with 943 patients (522 adults and 421 pediatric) with HSK were enrolled. The estimated pooled incidence of kidney stones was 36% (95% confidence interval [CI], 15%–59%) in adults with the HSK. Kidney stones were less common in pediatric patients with HSK with an estimated pooled incidence of 3% (95% CI, 2%–5%). The mean age of adult stone formers with HSK was 44.9 ± 6.2 years, and 75% were males. Within reported studies, 89.2% of kidney stones were calcium-based stones (64.2% calcium oxalate [CaOx], 18.8% calcium phosphate [CaP], and 6.2% mixed CaOx/CaP), followed by struvite stones (4.2%), uric acid stones (3.8%), and others (2.8%).Conclusions:Kidney stones are very common in adult patients with HSK with an estimated incidence of 36%. Calcium-based stones are the most prevalent kidney stones in adults with HSKs. These findings may impact the prevention and clinical management of kidney stones in patients with HSK.

Efficacy and Safety of Alpha-Blockers for Kidney Stones in Adults.

Objective: To review the literature for α-blocker treatment of kidney stones. Data Sources: PubMed search performed November 15, 2017, using the following search terms: alpha-blocker, alfuzosin, silodosin, or tamsulosin AND kidney or ureteral stones. Additional studies found through references of primary and tertiary literature. Inclusion criteria included English language, randomized controlled trials (not included in meta-analyses), and meta-analyses evaluating US available alpha-blockers as medical expulsive therapy with or without lithotripsy in adults with renal or ureteral stones, and no date limits. Study Selection and Data Extraction: Seven randomized controlled trials (RCTs), 1 case-control trial, and 6 meta-analyses were found and included in this review. Two RCTs and 4 meta-analyses evaluated alpha-blockers without lithotripsy. Five RCTs, 1 case-control trial, and 2 meta-analyses evaluated their use post-lithotripsy. The primary endpoint was stone clearance rate in most studies. Data Synthesis: For ureteral stones ≤10 mm treated without lithotripsy, alpha-blockers increased clearance in all meta-analyses and one RCT versus control. For ureteral or renal stones treated with lithotripsy, 4 RCTs and all meta-analyses found benefit with alpha-blockers compared with control. When results were stratified by stone size, alpha-blockers performed better for stones 10 to 20 mm, while there was no difference for stones <10 mm. Conclusion: Alpha-blockers are beneficial without lithotripsy for ureteral stones 5 to 10 mm. They are beneficial post-lithotripsy for renal or ureteral stones >10 mm. They can be considered post-lithotripsy for stones 5 to 10 mm, but little benefit may be seen. Although all uroselective alpha-blockers have been found to be effective, most data are with tamsulosin 0.4 mg daily.

Citrate salts for preventing and treating calcium containing kidney stones in adults.

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. 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. 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. 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. 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. 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). 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.

Summaries for patients. Prevention of repeated episodes of kidney stones in adults: a clinical practice guideline from the American College of Physicians.

Summaries for patients. Prevention of repeated episodes of kidney stones in adults: a clinical practice guideline from the American College of Physicians.

Is Medical Nutrition Therapy Appropriate for Kidney Stones?

Is Medical Nutrition Therapy Appropriate for Kidney Stones?

The ROKS nomogram for predicting a second symptomatic stone episode.

Most patients with first-time kidney stones undergo limited evaluations, and few receive preventive therapy. A prediction tool for the risk of a second kidney stone episode is needed to optimize treatment strategies. We identified adult first-time symptomatic stone formers residing in Olmsted County, Minnesota, from 1984 to 2003 and manually reviewed their linked comprehensive medical records through the Rochester Epidemiology Project. Clinical characteristics in the medical record before or up to 90 days after the first stone episode were evaluated as predictors for symptomatic recurrence. A nomogram was developed from a multivariable model based on these characteristics. There were 2239 first-time adult kidney stone formers with evidence of a passed, obstructing, or infected stone causing pain or gross hematuria. Symptomatic recurrence occurred in 707 of these stone formers through 2012 (recurrence rates at 2, 5, 10, and 15 years were 11%, 20%, 31%, and 39%, respectively). A parsimonious model had the following risk factors for recurrence: younger age, male sex, white race, family history of stones, prior asymptomatic stone on imaging, prior suspected stone episode, gross hematuria, nonobstructing (asymptomatic) stone on imaging, symptomatic renal pelvic or lower-pole stone on imaging, no ureterovesicular junction stone on imaging, and uric acid stone composition. Ten-year recurrence rates varied from 12% to 56% between the first and fifth quintiles of nomogram score. The Recurrence of Kidney Stone nomogram identifies kidney stone formers at greatest risk for a second symptomatic episode. Such individuals may benefit from medical intervention and be good candidates for prevention trials.

Analysis of Urinary Parameters as Risk Factors for Nephrolithiasis in Children with Celiac Disease

Intestinal malabsorption can cause urinary stone disease via enteric hyperoxaluria. It has been shown that celiac disease, a common malabsorption disorder, is associated with an increased risk of calcium oxalate kidney stones in adults. Since no published data are available in the pediatric population, we analyzed urinary excretion of electrolytes in children with celiac disease to assess the risk of nephrolithiasis. The study population consisted of 115 children 1 to 16 years old (mean 5 years) with positive serological tests for celiac disease (anti-endomysium and anti-tissue transglutaminase antibodies) referred to us for jejunal biopsy to confirm the diagnosis. Assessment was requested because patients presented with poor growth, anemia, gastrointestinal disorders or a family history of celiac disease. After obtaining informed consent we performed urine tests to measure urinary variables and blood tests to exclude metabolic disorders and evaluate renal function. All patients had a biopsy confirmed diagnosis of celiac disease. Oxaluria was normal in all children studied. However, levels of urinary calcium were decreased in patients with celiac disease and were inversely associated with disease severity (p = 0.0004). In contrast to adults, increased urinary excretion of oxalate was not detectable in children presenting with celiac disease. Therefore, the risk of nephrolithiasis appears not to be increased compared to healthy children. The observed hypocalciuria probably further decreases the tendency to form kidney stones.

Approach to the Adult Kidney Stone Former

Nephrolithiasis is a prevalent and costly condition with high recurrence rate. A medical evaluation to identify abnormalities responsible for nephrolithiasis and guide subsequent therapy has been advocated to reduce the risk of stone recurrence. The evaluation of kidney stone formers generally comprises an extensive medical history to identify metabolic, environmental, dietary and/or genetic factors contributing to stone formation. Imaging studies are utilized to evaluate and follow stone burden. Laboratory studies including stone composition analysis and serum and urinary chemistries are commonly obtained to further assess for any underlying systemic disorders, to detect environmental and metabolic processes contributing to stone disease, and to guide initial and follow-up dietary and pharmacological therapy. The nature and extent of such an evaluation is discussed in this review article.

Epidemiologic insights into pediatric kidney stone disease

The epidemiology of pediatric kidney stone has not yet been as rigorously defined as that of adult kidney stone disease. Herein, we review our recent epidemiologic works characterizing pediatric stone disease using the Kids' Inpatient Database (KID). Specifically we investigated the age and gender distribution of pediatric kidney stone disease, changes in disease prevalence over time, and medical comorbidities associated with this disorder. We identified patients by International Classification of Disease 9th Edition (ICD-9) codes for renal and ureteral calculi as the primary diagnosis. Medical comorbidities were identified using specific comorbidity software. Statistical comparisons between children with and without stone disease were performed. In the first decade of life, stone disease was more prevalent among males than females; however, in the second decade of life females were more commonly affected. Of note, there was a significant increase in treated stone disease across both genders between 1997 and 2003. We also found that the risk of kidney stone diagnosis in children younger than 6 years of age was significantly associated with hypertension and diabetes mellitus. The gender distribution among pediatric stone formers varies significantly by age, although overall females have a greater prevalence than males. There is also a strong association of stone disease and both diabetes and hypertension, although this was only observed in children less than 6 years of age. Taken all together, these findings suggest that urolithiasis in the young child is a complex systemic disease process.

Urolithiasis in Pediatric Patients: A Single Center Study of Incidence, Clinical Presentation and Outcome

The incidence of kidney stones in adults has increased in the last 30 years. This retrospective, single site review was done to test the hypotheses that the incidence of urolithiasis in pediatric patients increased from 1994 to 2005, and that metabolic abnormalities were more common in patients with renal stones in the final 3 years of the study period. Charts from 2 time periods were reviewed, 1994 to 1996 (period 1) and 2003 to 2005 (period 2). Clinical and laboratory data, including demographics, presenting complaints, laboratory assessment, treatment and outcome, were tabulated in patients with confirmed urolithiasis. The number of patients with urolithiasis increased from 7 in period 1 to 61 in period 2. When expressed as cases per 100 new patients the incidence increased 4.6 times (p = 0.014). Focusing on period 2, 28% of patients were younger than 10 years. While blood tests were generally normal, 76% of patients had at least 1 abnormality in the 24-hour urine collection. Hypocitraturia, which was the most common metabolic abnormality, was noted in 52% of patients. The small number of patients in period 1 precluded determination as to whether metabolic abnormalities were more common in period 2. Surgery and/or lithotripsy was required in 12 children. Stone disease recurred in 39% of the patients. The incidence of urolithiasis in the pediatric population increased nearly 5-fold at our institution during the last decade. We recommend that the primary diagnostic test be a 24-hour urine collection. The most common metabolic abnormality was hypocitraturia, followed by hypercalciuria. Recurrence of stones is common (approximately 40% rate) and followup is advised.

Circadian variation in urine pH and uric acid nephrolithiasis risk

The proportion of uric acid stones in paediatric stone formers is estimated at 3–4% in the United States [1], although reports from Armenia and Turkey indicate higher proportions of 7 and 15%, respectively [2,3]. Risk factors for uric acid stones include hyperuricosuria, low urinary volume and unduly acidic UpH (<5.5) [4]. Acidic UpH is a recognized risk factor in children consuming a ketogenic diet [5], or those with chronic diarrhoea. In adults, an acidic urine pH is the most common abnormality that predisposes to idiopathic uric acid nephrolithiasis [4]. Urinary alkalinization with potassium citrate is an effective treatment for uric acid kidney stones in adults [6]. We report the case of a 13-year-old boy who presented with recurrent uric acid stones that did not respond to a conventional regimen of potassium citrate therapy.

Chronic renal insufficiency (CRI) in urolithiasis.

In 80 adult kidney stone formers (52 with reversible and 28 with irreversible renal impairment) laboratory and clinical data were evaluated to estimate the share of abnormalities in the metabolism of stone forming substances in the development of renal impairment, and to search for the causes of the irreversibility of renal impairment. The study confirmed the previous results from this laboratory suggesting a causal relationship between renal impairment and metabolic disorders. No significant differences in the incidence of metabolic disorders or in therapy have been found in patients with irreversible renal impairment as compared to those with progressive deterioration of renal function. Irreversible renal impairment developed in relationship with bilateral kidney stone formation and recurrent urinary infection.