Metabolic syndrome and nephrolithiasis

Problem

This review focuses on the association between the metabolic syndrome (MS) and nephrolithiasis.

Findings

Associations between nephrolithiasis and systemic diseases are recognized, including atherosclerosis, cardiovascular (CV) disease, hypertension (HNT), diabetes mellitus (DM)—composite risk factors grouped as the MS. Kidney stones incidence is increasing in this particularly high risk group. Those with stones are prone to the disease and those with the systemic disease are at risk for stone formation, with the highest incidence in persons with multiple traits of the MS. Pathophysiologic explanations for the increased stone risk related to MS are likely complex and dynamic.

Conclusions

Kidney stones disproportionately affect persons with some or all traits of MS. One unifying theory may be of a common systemic malfunction of inflammation and tissue damage as an underlying mechanism, but it is unlikely to be the only mechanistic explanation. Further research is needed to investigate this and other hypotheses that go beyond population based and urine physiochemical studies in order to elucidate the mechanisms behind the individual disease states themselves.     

Metabolic syndrome and uric acid nephrolithiasis

The metabolic syndrome describes a cluster of metabolic features that increases the risk for type 2 diabetes mellitus and cardiovascular disease. The prevalence of uric acid nephrolithiasis is higher among stone-forming patients with features of the metabolic syndrome such as obesity and/or type 2 diabetes mellitus. The major determinant in the development of idiopathic uric acid stones is an abnormally low urinary pH. The unduly urinary acidity in uric acid stone formers increasingly is recognized to be one of the features observed in the metabolic syndrome. Two major abnormalities have been implicated to explain this overly acidic urine: (1) increased net acid excretion, and (2) impaired buffering caused by defective urinary ammonium excretion, with the combination resulting in abnormally acidic urine. New information is emerging linking these defects to changes in insulin signaling in the kidney. This article reviews the epidemiologic and metabolic studies linking uric acid nephrolithiasis with the metabolic syndrome, and examines the potential mechanisms underlying the unduly acidic urine in these conditions.     

Metabolic evaluation of patients with recurrent idiopathic calcium nephrolithiasis

BACKGROUND: Metabolic evaluation in recurrent idiopathic calcium renal stone-formers (RCSF) was analysed with respect to the following questions: (1) do three 24-h urines provide more diagnostic accuracy in the metabolic evaluation of RCSF than 1 or 2 urines?; (2) does time after stone event influence the diagnostic yield?; (3) is urine composition at weekends different from that at mid-week?; (4) what are the prevalences of the most important risk factors (RF) of idiopathic calcium nephrolithiasis, i.e. low volume (LV), hypercalciuria (HC), hyperoxaluria (HO), hyperuricosuria (HU), hypocitraturia (Hypo-Cit), and hypomagnesiuria (Hypo-Mg)?; and (5) do male RCSF differ from females with respect to urinary RFs? METHODS: Seventy-five RCSF (59 men, 16 women) collected three 24-h urines (U1-3) while on free-choice diet. To account for possible variations in lifestyle and diet, U1 and U3 had to be collected midweek and U2 at a weekend. RESULTS: When considering all three urines together (U1 + U2 + U3), the number of RF abnormalities/patient was 2.8 +/- 0.1, higher than numbers of any combination of two urines or of any single urine (P = 0.0001 for all comparisons). The number of RF abnormalities also rose with time after stone event, from 0.8 +/- 0.1 (range 0-4) in U1 to 1.1 +/- 0.1 (range 0- 4) in U3 (P = 0.011 vs U1). Whereas all other RF did not change between collections, urine volume was lower in U2 (1793 +/- 90 ml) than in U1 (2071 +/- 97 ml, P = 0.0001 vs U2) and U3 (1946 +/- 97 ml, P = 0.046 vs U2). At least 1 abnormality was found in 85.3% of all RCSF, and multiple abnormalities occurred in 47%. The most frequent RF was HC (39%), followed by HO and LV (32% each), Hypo-Cit (29%), HU (23%) and Hypo-Mg (19%). Males more often had Hypo-Cit (P < 0.001) and Hypo-Mg (P < 0.01) than females, whereas HO was more frequent in female RCSF (P < 0.025 vs males). CONCLUSIONS: Diagnostic accuracy of metabolic evaluation in RCSF increases both with the number of urines collected and the time passing after a stone event. Urines collected at weekends differ from those of the week only by their lower volumes. Abnormalities of RF for calcium nephrolithiasis can be detected in 85.3% of RCSF, and HC is the most common RF both in male and female RCSF.      

Metabolic investigation of recurrent nephrolithiasis: compliance with recommendations

Objectives. Nephrolithiasis is a recurrent condition with significant associated morbidity and economic impact. Although urologic intervention addresses symptomatic stone episodes, prevention of recurrences with proven medical therapy is indicated.Methods. This retrospective study examined 97 patients who presented in 1997 and 1998 with recurrent nephrolithiasis in a large tertiary care center for the presence of an appropriate metabolic investigation as recommended by the National Institutes of Health Consensus Conference. Complete data were abstracted from the hospital and private clinic charts.Results. The average patient age was 50.5 years; 61.9% of patients were men. The mean number of stones per patient was 5.6 (range 2 to 62), with stone analysis performed for 78 patients. Fifty-eight stones (74.4%) were calcium oxalate and/or phosphate, 14 (17.9%) urate, 8 (10.3%) struvite, and 3 (3.8%) cystine. Five patients had two stone types on different occasions. Either lithotripsy or a urologic procedure was required for at least one stone presentation in 89 patients (91.8%). An investigation for stone disease was pending in 54 patients (55.7%). A complete evaluation, satisfying the preset criteria, was performed in 34 patients (35.1%). Six patients who did not undergo evaluation were lost to follow-up. Univariate analysis revealed that referral to a nephrologist (P = 0.001), treatment with medications used for stone disease (P = 0.008), and urate stones (P = 0.005) were associated with a complete investigation. Similarly, these were independently associated with a complete evaluation in regression analysis of 77 complete data sets, with odds ratios of 24.4 (nephrology referral), 4.9 (medication use), and 5.6 (urate stones).Conclusions. The results of this study demonstrate that a significant proportion of patients with recurrent nephrolithiasis do not undergo appropriate metabolic investigations. Efforts should be made to improve the evaluation of these patients.     

Metabolic syndrome

About 20 years ago, Reaven presented the concept that a series of related factors such as hyperinsulinemia, hypertension, low high-density lipoprotein (HDL)-cholesterol levels, and hypertriglyceridemia tended to co-occur in the same individual and that this risk-factor clustering and its association with insulin resistance might be of critical importance in the underlying cause of cardiovascular disease. This risk-factor clustering called as "syndrome X" has now become "metabolic syndrome" (METS). Nowadays, METS is becoming well known as a condition of high-risk for the subsequent development of ischemic cardiovascular disease in Western population as well as Japanese population and it is proved that the prevalence of METS is very common. There are several different diagnostic definitions for METS. In Japanese definition, waist circumference is essential for criterion of METS because visceral fat accumulation is believed to be associated with METS more closely than the body mass index (BMI) itself or the amount of subcutaneous fat. Therefore treatment strategy to reduce visceral fat seems to be crucial for management of patients with METS. Adipose tissue is not simply an energy storage organ, but also a secretary organ, producing a variety of bioactive substances, including adiponectin. Adiponectin is paradoxically reduced in obesity and elevated adiponectin concentration is associated with greater insulin sensitivity. Therefore hypoadiponectinemia can be considered a key factor of the development of METS. We believe that detection, prevention and treatment of METS are important clinical and public health challenges.     

Recurrent nephrolithiasis in renal tubular acidosis. Metabolic profiles,therapy and course

13 patients with recurrent urolithiasis and distal renal tubular acidosis (RTA I) were investigated for lithogenic metabolic disorders. Treatment was given and the patients observed for periods of up to 10 years.     

代谢综合征与糖尿病肾病

众所周知，代谢综合征（metabolic syndrome，MS）是心血管疾病发生的危险因素。近年的研究显示，MS与糖尿病肾病（diabetic nephropathy，DN）的发生与进展亦关系密切：合并MS的糖尿病患者DN发病率明显增高，MS组中除高血糖、高血压外，胰岛素抵抗与肥胖、血脂异常均可能与DN有关。胰岛素增敏剂、他汀类等药物除改善代谢紊乱外，亦可能对糖尿病肾脏具有保护作用。     

Metabolic syndrome and robustness tradeoffs

The metabolic syndrome is a highly complex breakdown of normal physiology characterized by obesity, insulin resistance, hyperlipidemia, and hypertension. Type 2 diabetes is a major manifestation of this syndrome, although increased risk for cardiovascular disease (CVD) often precedes the onset of frank clinical diabetes. Prevention and cure for this disease constellation is of major importance to world health. Because the metabolic syndrome affects multiple interacting organ systems (i.e., it is a systemic disease), a systems-level analysis of disease evolution is essential for both complete elucidation of its pathophysiology and improved approaches to therapy. The goal of this review is to provide a perspective on systems-level approaches to metabolic syndrome, with particular emphasis on type 2 diabetes. We consider that metabolic syndromes take over inherent dynamics of our body that ensure robustness against unstable food supply and pathogenic infections, and lead to chronic inflammation that ultimately results in CVD. This exemplifies how trade-offs between robustness against common perturbations (unstable food and infections) and fragility against unusual perturbations (high-energy content foods and low-energy utilization lifestyle) is exploited to form chronic diseases. Possible therapeutic approaches that target fragility of emergent robustness of the disease state have been discussed. A detailed molecular interaction map for adipocyte, hepatocyte, skeletal muscle cell, and pancreatic beta-cell cross-talk in the metabolic syndrome can be viewed at http://www.systems-biology.org/001/003.html.     

代谢综合征与前列腺增生症

前列腺增生症（benign prostatic hyperplasia，BPH）是老年男性的常见病。随着肥胖症及糖尿病病人的增多、社会老龄化的加速，BPH已成为颇受社会关注的健康问题。其发病受遗传、营养、内分泌等多因素影响。近来流行病学研究发现BPH与代谢综合征有密切关系。     

Metabolic risk factors and the impact of medical therapy on the management of nephrolithiasis in obese patients

PURPOSE: Previous studies have demonstrated that obesity can increase the risk of stone formation as well as recurrence rates of stone disease. Yet appropriate medical management can significantly decrease the risk of recurrent stone disease. Therefore, we analyzed our obese patient population, assessing the risk factors for stone formation and the impact of selective medical therapy on recurrent stone formation. MATERIALS AND METHODS: A retrospective chart review was performed to identify obese patients with stone disease from our Stone Center. Metabolic risk factors for stones were identified as well as patient response to medical therapy. A similar analysis was performed on a group of age and sex matched nonobese stone formers. RESULTS: Of 1,021 patients 140 (14%) were identified as obese (body mass index greater than 30). Of these patients complete metabolic evaluations were available in 83 with an average followup of 2.3 years. The most common presenting metabolic abnormalities among these obese patients included gouty diathesis (54%), hypocitraturia (54%) and hyperuricosuria (43%), which presented at levels that were significantly higher than those of the nonobese stone formers (p <0.05). Stone analysis was available in 32 obese patients with 63% having uric acid calculi. After initiating treatment with selective medical therapy obese and nonobese patients demonstrated normalization of metabolic abnormalities, resulting in an average decrease in new stone formation from 1.75 to 0.15 new stones formed per patient per year in both groups. CONCLUSIONS: Obesity, as a result of dietary indiscretion, probable purine gluttony and possible type II diabetes, appears to have a significant role in recurrent stone formation. Appropriate metabolic evaluation, institution of medical therapy and dietary recommendations to decrease animal protein intake can significantly improve the risk of recurrent stone formation in these often difficult to treat patients.     

Cystine nephrolithiasis

Our understanding of the molecular basis of cystinuria has deepened as the result of the causative genes, SLC3A1 and SLC7A9, being identified. The proteins coded for by these genes form a heterodimer responsible for reabsorption of filtered cystine in the proximal tubule. Failure of this transport system to be targeted to the apical membrane, as in the case of SLC3A1 mutations, or failure of the transport system to function, as in the case of SLC7A9 mutations, leads to abnormal urinary excretion of the relatively insoluble amino acid cystine. Stones and plugs of tubules result, with chronic kidney disease a frequent complication. Here we review the genetics, pathophysiology, pathology, clinical manifestations and clinical management. Increased fluid intake, restriction of sodium and animal protein ingestion, and urinary alkalinization are the standard therapies. Cystine binding thiol drugs tiopronin and D-penicillamine are reserved for patients for whom the conservative therapies are insufficient. New studies of cystine crystal inhibition are highlighted.