The Metabolomic Effects of Tripeptide Gut Hormone Infusion Compared to Roux-en-Y Gastric Bypass and Caloric Restriction.

CONTEXT: The gut-derived peptide hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY) are regulators of energy intake and glucose homeostasis and are thought to contribute to the glucose-lowering effects of bariatric surgery. OBJECTIVE: To establish the metabolomic effects of a combined infusion of GLP-1, OXM, and PYY (tripeptide GOP) in comparison to a placebo infusion, Roux-en-Y gastric bypass (RYGB) surgery, and a very low-calorie diet (VLCD). DESIGN AND SETTING: Subanalysis of a single-blind, randomized, placebo-controlled study of GOP infusion (ClinicalTrials.gov NCT01945840), including VLCD and RYGB comparator groups. PATIENTS AND INTERVENTIONS: Twenty-five obese patients with type 2 diabetes or prediabetes were randomly allocated to receive a 4-week subcutaneous infusion of GOP (n = 14) or 0.9% saline control (n = 11). An additional 22 patients followed a VLCD, and 21 underwent RYGB surgery. MAIN OUTCOME MEASURES: Plasma and urine samples collected at baseline and 4 weeks into each intervention were subjected to cross-platform metabolomic analysis, followed by unsupervised and supervised modeling approaches to identify similarities and differences between the effects of each intervention. RESULTS: Aside from glucose, very few metabolites were affected by GOP, contrasting with major metabolomic changes seen with VLCD and RYGB. CONCLUSIONS: Treatment with GOP provides a powerful glucose-lowering effect but does not replicate the broader metabolomic changes seen with VLCD and RYGB. The contribution of these metabolomic changes to the clinical benefits of RYGB remains to be elucidated.

Assessment of Kidney Function in Patients With Extreme Obesity: A Narrative Review.

OBJECTIVES: To discuss the evidence and caveats associated with estimated and measured creatinine clearance (eClCr and mClCr) and glomerular filtration rate (eGFR and mGFR) assessments of kidney function in patients with more extreme forms of obesity. DATA SOURCES: PubMed (1976 to mid-May 2020) was used, with bibliographies of retrieved articles searched for additional articles. STUDY SELECTION AND DATA EXTRACTION: Articles using gold standard mGFR to evaluate eClCr, mClCr, and eGFR assessments of kidney function in patients with more extreme forms of obesity were included. DATA SYNTHESIS: The overestimation of GFR by mClCr is well established, but mClCr is an alternative to mGFR assessments for determining medication dosing in patients with extremes of body size or muscle mass, or in patients receiving narrow therapeutic index medications when eGFR is likely to be inaccurate. The vast majority of studies comparing eGFR assessments with gold standard indicators of kidney function were attempts to validate eGFR equations for diagnosing and staging chronic kidney disease (CKD). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: For dosing medications in patients with stable kidney function and extreme obesity, a deindexed 4-variable Modification of Diet in Renal Disease or CKD Epidemiology Collaboration equation is an alternative to Cockcroft-Gault. Consistent use of the same equation by provider and between providers within any given setting is of paramount importance. CONCLUSIONS: In patients with extreme obesity and stable kidney function, eClCr or eGFR using deindexed values provides estimates of function for dosing adjustments of medications with elimination by the kidneys, but more research is needed with respect to the best size descriptor to use with estimating equations.

The Short-Term Effects of Roux-en-Y Gastric Bypass on Renal Excretion of Sodium and Its Association with Blood Pressure.

INTRODUCTION: Bariatric surgery has been shown to be effective in reducing weight and has benefits, such as lowering blood pressure. An increase in urinary sodium excretion has been suggested as a possible mechanism. This study explored changes in sodium excretion and their correlation with blood pressure after Roux-en-Y gastric bypass. MATERIALS AND METHODS: This study was conducted on 28 obese participants with body mass index (BMI) of 44.54 ± 7.81 kg/m2 who underwent gastric bypass. Before surgery and at the third and sixth months after gastric bypass, blood pressure, urinary sodium concentration, 24-hour (24-h) urinary sodium excretion, and fractional excretion of sodium were evaluated. In addition, serum sodium and potassium levels were determined. Nonparametric tests were used to analyze the data. RESULTS: Blood pressure decreased after surgery and remained at low levels over the 3- and 6-month periods. The urinary sodium concentration increased at 3 months after surgery; however, the 24-h urinary sodium excretion and urine volume decreased. Interestingly, although some associations between variables were observed, significant correlations between the 24-h urinary sodium excretion and the systolic, diastolic, and mean blood pressures were found. In addition, the urine volume was higher in the sixth month than in the third month following surgery. CONCLUSIONS: In the months immediately following surgery, a low-salt and low-volume diet favors decreases in urine volume and 24-h urinary sodium excretion. In addition, in the sixth month after surgery, an association between blood pressure and 24-h urinary sodium excretion was observed.

Effect of bariatric surgery on urinary sphingolipids in adolescents with severe obesity.

BACKGROUND: Untreated severe obesity of adolescents is associated with abnormal kidney function and development of chronic kidney disease. Lipotoxicity due to lipid accumulation in glomeruli might be an important mechanism in the progression of kidney disease in obesity. OBJECTIVE: To assess subclinical glomerular injury by measuring urinary sphingolipids in adolescents with severe obesity before and after weight loss surgery. We hypothesized that the levels of urinary sphingolipids would be elevated at baseline and improve after weight reduction. SETTING: Cincinnati Children's Hospital Medical Center, University of Cincinnati. METHODS: Ten adolescents undergoing bariatric surgery with no microalbuminuria and normal kidney function were selected. Urinary sphingolipids (ceramides, glycosphingolipids, and sphingomyelins) were quantified using ultra performance liquid chromatography electrospray ionization tandem mass spectrometry at baseline and 1 year postoperatively. The levels of sphingolipids were compared with lean and moderately obese controls. RESULTS: Participants with severe obesity had a mean baseline body mass index of 50 kg/m2 that decreased to 36 kg/m2 at 1 year postsurgery (28% reduction). Almost all urinary ceramides, glycosphingolipids, and sphingomyelin species were significantly elevated in participants with severe obesity compared with controls at baseline (P<.01). One year after weight loss surgery, levels of urinary sphingolipids improved but were still significantly elevated compared with controls. CONCLUSIONS: Our study indicates that severe obesity is associated with increased urinary excretion of sphingolipids despite the absence of microalbuminuria or decreased kidney function. Urinary sphingolipids may therefore represent a marker of early (subclinical) glomerular injury in adolescents with severe obesity.

Estimation of Urinary Creatinine Excretion and Prediction of Renal Function in Morbidly Obese Patients: New Tools from Body Composition Analysis.

BACKGROUND/AIMS: In obese subjects the accuracy of prediction of renal function is quite low. The aim of this study was to obtain a more accurate estimate of urinary creatinine excretion (UCr), creatinine clearance (CCr), and GFR from body cell mass (BCM). METHODS: Seventy-three adult morbidly obese patients (BMI 35.2-64.5 kg/m2) were examined. BCM was calculated from body impedance analysis. CCr was measured (mCCr) and was predicted from BCM and antropometric data (MR-BCMCCr), with Cockcroft and Gault (C&GCCr) and Salazar and Corcoran (S&CCCr) formulas. GFR was predicted from BCM (BCM GFR) and with MDRD and CKD-EPI formulas. RESULTS: Multiple regression (MR) indicated a strict linear correlation between UCr, BCM and anthropometric data. UCr predicted from MR equation (MR-BCMUCr) was very similar to measured UCr. MR-BCMCCr (168±46 mL/min) and mCCr (167±51 mL/min) were also similar, while significant differences were found between mCCr, C&GCCr and S&CCCr. The correlation and the agreement between MR-BCMCCr and mCCr were closer and prediction error was lower than the other formulas. BCM GFR (125±32 mL/min) had close correlations and agreements with MDRD GFR and CKD EPI formulas. CONCLUSIONS: In morbidly obese patients the measurement of BCM meliorates the prediction of UCr and CCr, and allows the prediction of GFR.

One-year follow-up of clinical, metabolic and oxidative stress profile of morbid obese patients after laparoscopic sleeve gastrectomy. 8-oxo-dG as a clinical marker.

Obesity has grown worldwide over the last few decades. In its different degrees, obesity is accompanied by many clinical and biochemical alterations reflecting the pathological condition of various body tissues. Among the mechanisms underlying the pathogenesis of obesity and associated complications, oxidative stress (OS) may be playing an important role. In the present study, we have characterized at systemic level the degree of OS status in a group of morbid obese patients (BMI>40kg/m2) at basal sate and its modulation during one year after bariatric surgery using the laparoscopic sleeve gastrectomy (LSG) technique. As compared with normal weight subjects matched in age, peripheral blood mononuclear cells (PBMc) of obese patients present a significant reduction of the antioxidant enzyme activities superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) as well as a significant increase of the oxidized/reduced glutathione ratio (GSSG/GSH) in these cells. Lipid peroxidation is significantly increased in the patient group as shown by the increased levels of malondialdehyde (MDA) in PBMc and the amount of F2-Isoprostanes (F2-IsoPs) released in urine. In addition, the DNA damage product 8-oxo-7,8-2'-deoxyguanosine (8-oxo-dG) was also observed to be increased in serum and urine of morbid obese patients as compared with the control group. After LSG, an improvement of their ponderal and metabolic profile was accompanied by a progressive recovery of antioxidant enzyme activities and the decline of oxidative byproducts both in PBMc and biological fluids. The observed changes of urinary 8-oxo-dG levels correlate positively with its serum concentration, the lipid peroxidation products MDA and F2-IsoPs, triglycerides, glucose, insulin, HOMA index and body weight and negatively with the percentage of weight and BMI loss and antioxidant activities. We conclude that the analysis of urinary 8-oxo-dG could be validated as a useful marker for the monitoring of ponderal and metabolic status of morbid obese patients.

The SURMetaGIT study: Design and rationale for a prospective pan-omics examination of the gastrointestinal response to Roux-en-Y gastric bypass surgery.

Objective To describe the protocol of the SURgically induced Metabolic effects on the Human GastroIntestinal Tract (SURMetaGIT) study, a clinical pan-omics study exploring the gastrointestinal tract as a central organ driving remission of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGB). The main points considered in the study's design and challenges faced in its application are detailed. Methods This observational, longitudinal, prospective study involved collection of gastrointestinal biopsy specimens, faeces, urine, and blood from 25 obese women with T2DM who were candidates for RYGB (20 patients for omics assessment and 5 for omics validation). These collections were performed preoperatively and 3 and 24 months postoperatively. Gastrointestinal transcriptomics; faecal metagenomics and metabolomics; plasma proteomics, lipidomics, and metabolomics; and biochemical, nutritional, and metabolic data were assessed to identify their short- and long-term correlations with T2DM remission. Results Data were collected from 20 patients before and 3 months after RYGB. These patients have nearly completed the 2-year follow-up assessments. The five additional patients are currently being selected for omics data validation. Conclusion The multi-integrated pan-omics approach of the SURMetaGIT study enables integrated analysis of data that will contribute to the understanding of molecular mechanisms involved in T2DM remission after RYGB.

Increased urine podocyte-associated messenger RNAs in severe obesity are evidence of podocyte injury.

OBJECTIVE: The aim of this study was to correlate different degrees of excess weight with the expression of podocyte-associated messenger RNAs (mRNAs) in urine. METHODS: The sample comprised 83 patients with overweight or obesity class I, II, or III and 18 healthy controls. The expression of nephrin, podocin, podocalyxin, α-actinin-4, α3ß1integrin, vascular endothelial growth factor, and transforming growth factor-beta (TGF-ß1 ) mRNA in urine was quantified with the real-time polymerase chain reaction. mRNA expression was correlated with body mass index, the metabolic syndrome, albuminuria, and inflammation. RESULTS: Adults with obesity class III had higher levels of serum lipids, glucose, HbA1C, insulin resistance, and C-reactive protein (P < 0.05), with 85% of the subjects meeting criteria for the metabolic syndrome (P < 0.001 vs. other groups). Urinary podocyte-associated mRNAs were higher in adults with obesity class III than in other groups (P < 0.05). Patients with overweight or obesity class I or II also had higher levels of podocyte mRNAs than controls: nephrin (P = 0.021), α-actinin-4 (P = 0.014), α3ß1integrin (P = 0.036), and TGF-ß1 (P = 0.005). Metabolic syndrome, hyperinsulinemia, and C-reactive protein were correlated with podocyturia, but only higher insulin levels were related regardless of obesity. CONCLUSIONS: Severe obesity and hyperinsulinemia were associated with higher urinary expression of podocyte-associated mRNAs, even at normal urinary albumin excretion rates.

Tissue specific regulation of glucocorticoids in severe obesity and the response to significant weight loss following bariatric surgery (BARICORT).

CONTEXT: Tissue cortisol exposure is under the control of the isozymes of 11ß-hydroxysteroid dehydrogenase (11ß-HSD). 11ß-HSD1 in vivo, acts as an oxoreductase converting inactive cortisone to active cortisol. We hypothesized that 11ß-HSD1 activity is dysregulated in obesity and alters following bariatric surgery induced weight loss in different tissues. METHODS: We recruited 21 patients prior to undergoing bariatric surgery and performed cortisol generation profiles (following oral cortisone administration), urinary corticosteroid metabolite analysis, adipose tissue microdialysis, and tissue gene expression before and after weight loss, following bariatric surgery. Archived tissue samples from 20 previous bariatric surgery patients were also used for tissue gene expression studies. RESULTS: Gene expression showed a positive correlation with 11ß-HSD1 and BMI in omental adipose tissue (OM) (r = +0.52, P = .0001) but not sc adipose tissue (r = +0.28, P = .17). 11ß-HSD1 expression in liver negatively correlated with body mass index (BMI) (r = -0.37, P = .04). 11ß-HSD1 expression in sc adipose tissue was significantly reduced after weight loss (0.41 ± 0.28 vs 0.17 ± 0.1 arbitrary units, P = .02). Following weight loss, serum cortisol generation increased during a cortisol generation profile (area under the curve 26 768 ± 16 880 vs 47 579 ± 16 086 nmol/L/minute, P ≤ .0001.) Urinary corticosteroid metabolites demonstrated a significant reduction in total cortisol metabolites after bariatric surgery (15 224 ± 6595 vs 8814 ± 4824 µg/24 h, P = .01). Microdialysis of sc adipose tissue showed a threefold reduction in cortisol/cortisone ratio after weight loss. CONCLUSIONS: This study highlights the differences in tissue specific regulation of cortisol metabolism in obesity and after weight loss. Following bariatric surgery hepatic 11ß-HSD1 activity increases, sc adipose tissue 11ß-HSD1 activity is reduced and total urinary cortisol metabolites are reduced indicating a possible reduction in hypothalamic pituitary adrenal axis drive. 11ß-HSD1 expression correlates positively with BMI in omental adipose tissue and negatively within hepatic tissue. 11ß-HSD1 expression is reduced in sc adipose tissue after weight loss.

Iodine deficiency is higher in morbid obesity in comparison with late after bariatric surgery and non-obese women.

BACKGROUND: Iodine deficiency and obesity are worldwide-occurring health problems. Our purpose was to investigate the relationship between morbid obesity and iodine status, including subjects who lost weight after bariatric surgery. METHODS: Ninety morbidly obese women, 90 women with at least 18 months follow-up after bariatric surgery, and 45 healthy non-obese women were recruited. Urinary iodine concentration (UIC) was measured in a spot urinary sample and expressed as the iodine-to-creatinine ratio. RESULTS: Obese women showed a significantly lower UIC in comparison with non-obese women (96.6 (25.8-267.3) vs. 173.3 (47.0-493.6) µg/g; p < 0.001), with a lesser proportion of subjects with adequate iodine status (46.6 vs. 83.3 %, p < 0.001). The mean UIC significantly increased among women who underwent bariatric surgery before the collection of the urinary sample (96.6 (25.8-267.3) vs. 131.9 (62.9-496.4) µg/g; p < 0.001). No difference in UIC was detected between laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy. Univariate analysis showed that UIC negatively correlated with body mass index (BMI) (r = -0.278, p < 0.001) and positively with age (r = 0.206, p = 0.002). Finally, multiple linear regression analyses showed that BMI was independently associated with UIC (beta = -0.312, p < 0.001; R (2) = 0.166). CONCLUSION: Obesity is an independent risk factor to iodine deficiency, almost in women. Whether more obese population needs to be considered as a vulnerable group and whether bariatric surgery can reverse iodine deficiency still remain to be elucidated.

The body composition and excretory burden of lean, obese, and severely obese individuals has implications for the assessment of chronic kidney disease.

Obesity could affect associations between creatinine generation, estimated body surface area, and excretory burden, with effects on chronic kidney disease assessment. We therefore examined the impact of obesity on the performances of estimated glomerular filtration rate (eGFR), the urine albumin:creatinine ratio (ACR), and excretory burden in 3611 participants of the Chronic Renal Insufficiency Cohort. Urine creatinine excretion significantly increased with body mass index (BMI) (34 and 31% greater at 40 kg/m(2) or more versus the normal of 18.5-25 kg/m(2)) in men and women, respectively, such that patients with a normal BMI and an ACR of 30 mg/g had the same 24-h albuminuria as severely obese patients with ACR 23 mg/g. The bias of eGFR (referenced to body surface area-indexed iothalamate (i-)GFR) had a U-shaped relationship to obesity in men but progressively increased in women. Nevertheless, obesity-associated body surface area increases were accompanied by a greater absolute (non-indexed) iGFR for a given eGFR, particularly in men. Two men with eGFRs of 45 ml/min per 1.73 m(2), height 1.76 m, and BMI 22 or 45 kg/m(2) had absolute iGFRs of 46 and 62 ml/min, respectively. The excretory burden, assessed as urine urea nitrogen and estimated dietary phosphorus, sodium, and potassium intakes, also increased in obesity. However, obese men had lower odds of anemia, hyperkalemia, and hyperphosphatemia. Thus, for a given ACR and eGFR, obese individuals have greater albuminuria, absolute GFR, and excretory burden. This has implications for chronic kidney disease management, screening, and research.

Changes in intestinal permeability after Roux-en-Y gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) interferes considerably with the anatomy and physiology of the gastrointestinal tract. The study of intestinal permeability can provide important information regarding changes in the structure and function of the mucosal barrier after the procedure. METHODS: The urinary excretion rates of lactulose and mannitol after oral intake of both substances were evaluated. We also evaluated the lactulose/mannitol excretion ratio. Tests were performed during the preoperative period (T0), at the first postoperative month (T1), and at the sixth postoperative month (T6). RESULTS: The study included 16 morbidly obese patients. The excretion rate of mannitol was significantly lower at T1 compared with T0 and T6 (p = 0.003). There was no significant difference in the excretion rates of lactulose or in the lactulose/mannitol ratio during the three periods. Six patients (37.5%) exhibited a considerable increase in the excretion rate of lactulose at T6 (4-73 times higher than the preoperative value), accompanied by proportional variations in the lactulose/mannitol ratio. CONCLUSIONS: The significant increase in mannitol excretion rate from T1 to T6 most likely reflects the occurrence of intestinal adaptation (mucosal hyperplasia), which would tend to minimize the malabsorption of macronutrients. A subgroup of patients who undergo RYGB exhibit pronounced increase in their intestinal permeability (assessed by the lactulose/mannitol ratio and the lactulose excretion rate) at T6.

Calcium oxalate supersaturation increases early after Roux-en-Y gastric bypass.

BACKGROUND: Calcium oxalate (CaOx) nephrolithiasis is an adverse effect of Roux-en-Y gastric bypass surgery (RYGB). It is unknown when the increased risk for CaOx stone formation occurs after surgery. METHODS: We studied 13 morbidly obese adults undergoing RYGB with 24-hour urine collections at 4 weeks before and 1, 2, 4, and 6 months after surgery and computed CaOx relative saturation ratio (RSR) by EQUIL2. RESULTS: Eleven patients were female, mean ± standard deviation age was 41.1 ± 7.2 years, and none had diabetes or chronic kidney disease. Median (interquartile range) urinary oxalate excretion increased linearly from 12.6 (10.9-37.9) mg/24 hr at baseline to 28.4 (14.4-44.0) mg/24 hr at 6 months (slope = .188; P = .005). CaOx RSR increased significantly at 2 months after RYGB (1.4 [1.2-2.4] to 4.9 [1.7-10.0]; P = .017) and rose throughout the study to 5.7 (3.7-12.2) at 6 months (P = .001) with a positive linear slope (.255; P = .001). One patient had critical CaOx supersaturation (RSR = 34.7) and severe hyperoxaluria (101.7 mg/24 hr) at 6 months after RYGB. Significant decreases over time were seen in urine volume and sodium and potassium excretion, but no changes were noted in urinary pH, calcium, magnesium, or citrate. CONCLUSIONS: Our data suggest that CaOx RSR, and thus risk for nephrolithiasis, rises as early as 2 months after RYGB and increases gradually in the first 6 months, largely because of reduced urine volume and increased urinary oxalate excretion. Interventions to reduce CaOx RSR, such as adequate fluid intake and agents to bind enteric oxalate, need to be evaluated in patients at risk for nephrolithiasis after RYGB.

Urinary evaluation after RYGBP: a lithogenic profile with early postoperative increase in the incidence of urolithiasis.

BACKGROUND: The objective of this study was to assess predictors for new-onset stone formers after Roux-en-Y gastric bypass (RYGBP). METHODS: One hundred and fifty-one obese patients underwent RYGBP and were followed for 1 year. The analysis comprised two study time points: preoperative (T0) and 1 year after surgery (T1). They were analyzed for urinary stones, blood tests, and 24-h urinary evaluation. Nonparametric tests, logistic regression, and multivariate analysis were conducted using SPSS 17. RESULTS: Median BMI decreased from 44.1 to 27.0 kg/m2 (p < 0.001) in the postoperative period. Urinary oxalate (24 versus 41 mg; p < 0.001) and urinary uric acid (545 versus 645 mg; p < 0.001) increased significantly postoperatively (preoperative versus postoperative, respectively). Urinary volume (1310 versus 930 ml; p < 0.001), pH (6.3 versus 6.2; p = 0.019), citrate (268 versus 170 mg; p < 0.001), calcium (195 versus 105 mg; p < 0.001), and magnesium (130 versus 95 mg; p = 0.004) decreased significantly postoperatively (preoperative versus postoperative, respectively). Stone formers increased from 16 (10.6 %) to 27 (17.8%) patients in the postoperative analysis (p = 0.001). Predictors for new stone formers after RYGBP were postoperative urinary oxalate (p = 0.015) and uric acid (p = 0.044). CONCLUSIONS: RYGBP determined profound changes in urinary composition which predisposed to a lithogenic profile. The prevalence of urinary lithiasis increased almost 70% in the postoperative period. Postoperative urinary oxalate and uric acid were the only predictors for new stone formers.

Weight loss independently predicts urinary albumin excretion normalization in morbidly obese type 2 diabetic patients undergoing bariatric surgery.

BACKGROUND: Despite obesity being closely associated with two common risk factors for albuminuria, namely type 2 diabetes mellitus (T2DM) and hypertension, information on the impact of weight loss on albumin excretion rate in morbidly obese (MO) subjects is scarce. OBJECTIVE: To evaluate the independent contribution of weight loss following bariatric surgery (BS) to the improvement of the albumin-to-creatinine ratio (ACR) in MO subjects with T2DM. SUBJECTS AND METHODS: Observational prospective study, including consecutive (n = 255) patients undergoing Roux-en-Y gastric bypass (GBP) or sleeve gastrectomy (SG) of whom 37.6 % (n = 96) presented with T2DM. Stepwise logistic regression analysis was used to assess the contribution of T2DM-related, hypertension-related, and weight loss-related variables, and type of surgery to normalization of ACR (<30 mg/g) at 12 and 24 months follow-up. RESULTS: In T2DM subjects, baseline ACR was 85.7 ± 171 mg/g with ACR ≥ 30 mg/g being present in 45.7 % of the cohort. At 12 months, the ACR significantly decreased in T2DM subjects (42.2 ± 142.8 mg/g; p < 0.005) with no further reduction at 24 months after surgery (44.4 ± 227.7; p = 0.862). Among T2DM subjects with ACR ≥ 30 mg/g at baseline, the ACR became <30 mg/g in 58.5 % and 76.9 % at 12 and 24 months, respectively (p < 0.001 relative to baseline). Body mass index (BMI) change from baseline was the only independent predictor of ACR normalization at 12 months [Exp(B) 1.373, 95 % confidence interval 1.075-1.703; p < 0.05]. None of the evaluated variables appeared as an independent predictor of ACR normalization at 24 months. CONCLUSIONS: Our data suggest that, in MO subjects with T2DM, interventions aiming at slowing the progression of nephropathy should not only focus on optimization of glucose and blood pressure control but also include effective weight loss strategies.

The longer-term effects of Roux-en-Y gastric bypass surgery on sodium excretion.

BACKGROUND: Obesity is an independent risk factor for hypertension and chronic kidney disease. During the first months after bariatric surgery, an improvement of sodium excretion has been described. The aim of this work was to study the influence of bariatric surgery on sodium excretion at more than a year after the intervention. METHODS: Patients who have undergone Roux-en-Y gastric bypass (RYGB) and who had collected a 24-h urine sample before surgery more than 12 months ago were asked to participate. A second 24-h urine sample was collected. Blood pressure and weight were measured. The difference in sodium excretion before and after surgery was calculated, and the relationship with blood pressure and weight loss was investigated. RESULTS: We included 33 patients; the median follow-up time was 21 months (range 14-41). Sodium excretion was high before surgery (median 195 mmol/day, IQR range 167-247) and decreased by 18 % after surgery (median 160 mmol/day, IQR range 118-205, p = 0.015), while there were significant improvements in body weight (% EWL 80.9 ± 21.8), systolic blood pressure (126 to 120 mmHg, p = 0.02), and diastolic blood pressure (84 to 77 mmHg, p = 0.002), even with a reduced number of antihypertensive drugs. CONCLUSIONS: After RYGB and considerable weight loss, sodium excretion remains high in the longer term. The profound improvement in blood pressure cannot be explained by reductions in sodium excretion after RYGB.

Response to dietary oxalate after bariatric surgery.

BACKGROUND AND OBJECTIVES: Bariatric surgery (BS) may be associated with increased oxalate excretion and a higher risk of nephrolithiasis. This study aimed to investigate urinary abnormalities and responses to an acute oxalate load as an indirect assessment of the intestinal absorption of oxalate in this population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Twenty-four-hour urine specimens were collected from 61 patients a median of 48 months after BS (post-BS) as well as from 30 morbidly obese (MO) participants; dietary information was obtained through 24-hour food recalls. An oral oxalate load test (OLT), consisting of 2-hour urine samples after overnight fasting and 2, 4, and 6 hours after consuming 375 mg of oxalate (spinach juice), was performed on 21 MO and 22 post-BS patients 12 months after BS. Ten post-BS patients also underwent OLT before surgery (pre-BS). RESULTS: There was a higher percentage of low urinary volume (<1.5 L/d) in post-BS versus MO (P<0.001). Hypocitraturia and hyperoxaluria (P=0.13 and P=0.36, respectively) were more frequent in BS versus MO patients. The OLT showed intragroup (P<0.001 for all periods versus baseline) and intergroup differences (P<0.001 for post-BS versus MO; P=0.03 for post-BS versus pre-BS). The total mean increment in oxaluria after 6 hours of load, expressed as area under the curve, was higher in both post-BS versus MO and in post-BS versus pre-BS participants (P<0.001 for both). CONCLUSIONS: The mean oxaluric response to an oxalate load is markedly elevated in post-bariatric surgery patients, suggesting that increased intestinal absorption of dietary oxalate is a predisposing mechanism for enteric hyperoxaluria.

Changes in renal function following Roux-en-Y gastric bypass: a prospective study.

BACKGROUND: Studies of the impact of Roux-en-Y gastric bypass (RYGB) on renal function have shown mixed results. We constructed this prospective repeated-measures controlled study to characterize this response and identify the best method of gauging renal function in this setting. METHODS: Clinical data, serum creatinine (SC), and 24-h urine were collected 1 week before and 6 months following RYGB. Glomerular filtration rate (GFR) was calculated utilizing the Modification of Diet in Renal Disease formula. Creatinine clearance (CCL) was measured as a 24-h collection (24 CCL) and calculated by the Cockcroft-Gault (CG) formula. RESULTS: The study population of 37 patients (81% women) had a mean age of 47 ± 11 years, had mean BMI of 47.6 ± 6.3 kg/m(2), and achieved a mean % excess weight loss (EWL) of 60.9 ± 17.1%. SC decreased from 0.83 ± 0.21 mg/dl to 0.72 ± 0.16 mg/dl (p < 0.001) and mean GFR improved from 91.6 ± 29.7 ml/min/1.73 m(2) to 104.9 ± 23.5 ml/min/1.73 m(2) (p < 0.01). Preoperatively, CG significantly overestimated CCL when compared with 24 CCL (197.1 ± 88.2 ml/min vs. 136.5 ± 53.0 ml/min, p < 0.001). In all patients, improvement in 24 CCL correlated with EWL (r = 0.32) and %EWL (r = 0.16), and significantly correlated with decrease in BMI (r = 0.51, p < 0.005). In hypertensive patients, improvement in 24 CCL significantly correlated with EWL (r = 0.43, p < 0.05), %EWL (r = 0.40, p < 0.05), and decrease in BMI (r = 0.60, p < 0.001) and was negatively correlated with age (r = -0.45, p < 0.05). CONCLUSIONS: This study demonstrates that renal function improves following RYGB and is best identified by change in GFR. Improvement in 24 CCL is correlated with the EWL success of the patient, especially hypertensive patients.

Oxalobacter colonization in the morbidly obese and correlation with urinary stone risk.

OBJECTIVE: To establish the baseline preoperative prevalence of Oxalobacter formigenes (OF) colonization in a cohort of obese patients scheduled for Roux-en-Y gastric bypass (RYGB) and determine the effect of OF colonization on urinary oxalate excretion. It has been proposed that loss of OF colonization after RYGB may contribute to the development of hyperoxaluria. METHODS: Adult patients scheduled to undergo RYGB were requested to provide a stool specimen and 24-hour urine collection before surgery. OF colonization status was determined by the calcium precipitation test. The 24-hour urine specimens were analyzed by the Litholink Corporation (Chicago, IL). RESULTS: Of the 51 patients submitting initial stool specimens, only 8 (16%) tested positive for OF, whereas 43 (84%) were negative. Patients colonized with OF were older than uncolonized subjects (52.9±6.8 vs 46.0±10.4 years, P=.03). Urinary oxalate was not significantly different between these groups (P=.14). CONCLUSION: OF colonization is uncommon in morbidly obese patients (16%) before surgery. Because hyperoxaluria develops in more than 50% of patients after RYGB, it is unlikely that loss of OF colonization is the primary cause.

Short-term carbohydrate-restricted diet for weight loss in severely obese women.

BACKGROUND: Weight loss in bariatric pre-surgery period reduces surgical complications, surgery time, blood loss, and length of hospital stay. Carbohydrate-restricted diets have been used as an alternative for weight loss. We tested the efficacy of a low-calorie carbohydrate-restricted diet (RD) for short-term weight loss in women with severe obesity and evaluate its metabolic effects in relation to a conventional low-calorie diet (CD). METHODS: The subjects received a 1,200-kcal diet with or without carbohydrate restriction for a period of 1 week in the hospital. Nineteen obesity class III women were distributed into two groups: experimental (n = 10) and control (n = 9). The following variables were assessed at the beginning and end of the study: anthropometric measurements, body composition, resting energy expenditure, substrate oxidation, and biochemical tests. RESULTS: Compared with CD, RD led to larger weight loss (2.6 and 4.4 kg, respectively; p = 0.01) and waist circumference reduction (p < 0.01). Among the assessed biochemical indicators, only plasma and urine acetone levels were different (p < 0.01); higher values were found in the experimental group with no symptoms and other diet-related complaints. There was also a significant decrease in triglycerides and carbohydrate oxidation, as well as a significant enhancement in lipid oxidation in the RD group. CONCLUSION: Short-term RD was more efficient than CD regarding quick weight loss and waist circumference reduction, which may favor gastroplasty. Also, RD did not lead adverse metabolic effects.