Determinants of Obesity-Related Kidney Dysfunction Remission after Bariatric Surgery

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Pereira, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6415243/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction : Bariatric surgery was demonstrated to improve obesity-related kidney dysfunction (ORKD). However, the mechanisms underlying ORKD remittance or persistence remain unclear. This study aimed to explore the factors associated with proteinuria remission after bariatric surgery. Methods : A cohort of 39 patients with obesity and proteinuria was followed up for an average of 21.3 ± 4.6 months after bariatric surgery. Pre- and post-surgical assessments included the evaluation of weight-related and kidney-related outcomes. Results : After bariatric surgery, there was a significant reduction in body mass index (BMI) (41.0 ± 9.5 to 26.5 ± 4.6 kg/m², p < 0.05) with a total weight loss (TWL) of 38.5 ± 11.8%. Significant reductions in proteinuria (Δ43.0 ± 35.6%; 352.1 ± 761.5 to 144.2 ± 142.9 mg/24h, p < 0.05) and albuminuria (Δ14.3 ± 81.8%; 137.4 ± 485.9 to 43.7 ± 106.1 mg/24h; p < 0.01) were also observed. Higher pre-operative percentage of albuminuria predicted a greater post-operative reduction in albuminuria (HR: 1.979; 95% CI: 0.686 to 3.272; p < 0.05). Patients with persistent proteinuria (25.6%; n = 10) despite weight loss were predominantly males (79.3% vs 40.0%, p = 0.004) with lower serum creatinine levels (0.62 ± 0.07 mg/dL vs. 0.72 ± 0.13 mg/dL, p < 0.05) and greater CKD-EPI eGFR (117.4 ± 8.8 vs. 104.8 ± 12.4 mL/min/1.73m², p = 0.005). Conclusion : Bariatric surgery in patients with ORKD resulted in kidney dysfunction remission or significant reductions in proteinuria and albuminuria. Despite weight loss, persistent proteinuria can still be observed suggesting the presence of underlying kidney structural damage that limits kidney dysfunction full recovery. obesity-related kidney dysfunction albuminuria proteinuria hyperfiltration fatty kidney Figures Figure 1 Key Learning Points Bariatric surgery in patients with obesity-related kidney dysfunction results in kidney dysfunction remission, with significant reductions in proteinuria and albuminuria. Persistent proteinuria can still be observed in a subset of patients, occurring predominantly in males and patients with higher pre-surgery eGFR. These findings suggest that the presence of underlying kidney structural damage may limit kidney dysfunction full recovery in some patients. Introduction Obesity is a well-established risk factor for chronic kidney disease (CKD) [ 1 , 2 ] and is associated with increased risk of proteinuria and albuminuria [ 3 , 4 ], which are key biomarkers of kidney dysfunction. The mechanisms underlying obesity-related kidney disease (ORKD) are multifactorial and involve glomerular hyperfiltration, altered sodium handling, activation of the renin-angiotensin-aldosterone system (RAAS), and ectopic lipid accumulation within the kidneys[ 5 ]. These mechanisms are known to contribute to kidney injury, ultimately leading to CKD in a significant proportion of affected individuals [ 4 , 6 ]. Bariatric surgery has been shown to improve kidney function outcomes by decreasing proteinuria or even inducing its resolution, while contributing to normalization of glomerular filtration rate (GFR) and renal plasma flow (RPF) in patients with glomerular hyperfiltration [ 7 – 10 ]. Data from the Swedish Obesity Study (SOS) study, which included individuals with diabetes, showed that weight loss achieved through bariatric surgery was associated with a lower incidence of albuminuria [ 11 ] and long-term protection against stage 4 CKD and end stage kidney disease (ESKD) in this patient population [ 12 ]. However, the specific drivers underlying the nephroprotective effects associated with bariatric surgery, particularly in individuals with pre-existing proteinuria who do not have other identified causes for kidney dysfunction, such as diabetes or inflammatory diseases, remain incompletely understood. In order to gain further insights into potential mechanisms involved in ORKD recovery, it would be necessary to eliminate confounding factors such as hyperglycemia-related nephropathy. Therefore, in this study we aimed to evaluate the impact of bariatric surgery in a cohort of individuals with obesity and pre-existing proteinuria, while isolating the effects of weight loss from other sources of bias, such as diabetes or inflammatory conditions. Additionally, we sought to identify the factors associated with kidney function recovery, with the ultimate goal of improving the management and clinical outcomes of patients with ORKD undergoing bariatric surgery. Methods Patients This study included 242 patients who sought surgical treatment for obesity at a single public bariatric center between 2019 and 2022. Eligibility for bariatric surgery was determined by a body mass index (BMI) of > 40 kg/m² or a BMI > 35 kg/m² in the presence of obesity-related comorbidities. Figure 1 illustrates the patient selection process, detailing inclusion, exclusion criteria, and the final study cohort. Exclusion criteria included the presence of diabetes mellitus (HbA1c > 6.5% or treatment with anti-diabetic medications regardless of HbA1c value; n = 25), prediabetes treated with metformin (HbA1c between 5.7% and 6.5%, n = 14), neoplastic diseases (n = 0), inflammatory conditions (n = 0), and low 24-hour urine volume ( 150 mg/day before undergoing bariatric surgery and therefore underwent kidney function reassessment at follow-up. Over the 2-year postoperative period, 4 patients were lost to follow-up (10.3%), resulting in a final number of 39 patients. The study protocol received prior approval from the Institutional Independent Ethical Review Board (CA-014/20-Ot_MP/CC). Data acquisition Comprehensive patient data were retrieved from electronic clinical records, including age, gender, weight, type of bariatric surgery, BMI, hypertension status, dyslipidemia status, serum creatinine, uric acid levels, total serum proteins levels, and lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and non-LDL cholesterol). Anthropometric data were used to calculate BMI [weight(kg) ÷ height 2 (m 2 )], percentage of excess body mass index loss (%EBMIL) [(preoperative BMI − postoperative BMI) ÷ (preoperative BMI − 25) ×100] and percentage of total weight loss (%TWL) [(preoperative weight − post-operative weight) ÷ preoperative weight × 100]. Additional assessments included 24-hour urine urinalysis for albuminuria and proteinuria measurement. The 2021 CKD-EPI Creatinine equation was used to estimate the GFR in this cohort[ 13 ]. Patients were instructed to perform 24-hour urine collections on two consecutive days prior to blood sampling. Detailed oral and written instructions were provided to ensure proper collection technique. Urinary albumin, protein, and creatinine concentrations were measured from each collection, and the percentage of albuminuria (%Albuminuria) was calculated by dividing the 24-hour urine concentrations of albumin and protein for each patient and multiplying by 100. Pre and post-surgery proteinuria measurements were used to calculate the percentage of proteinuria reduction [[(pre-surgical proteinuria - post-surgical proteinuria) ÷ pre-surgical proteinuria] × 100); pre and post-surgery albuminuria measurements were used to calculate the percentage of albuminuria reduction [[(pre-surgical albuminuria - post-surgical albuminuria) ÷ pre-surgical albuminuria] × 100); pre and post-surgery calculations of CKD-EPI were used to calculate the percentage of CKD-EPI reduction [[(pre-surgical CKD-EPI - post-surgical CKD-EPI) ÷ pre-surgical CKD-EPI] × 100); pre and post-surgery measurements of the percentage of albuminuria were used to calculate the reduction in the percentage of albuminuria (pre-surgical percentage of albuminuria – post-surgery percentage of albuminuria). Statistical analysis Data are expressed as mean ± standard deviation (SD), unless otherwise stated. The Shapiro-Wilk test was employed to assess the normality of data distribution. For the comparison of the multiple variables before and after surgery, a paired analysis was conducted using unpaired T-test or Wilcoxon test, depending on the normality of the data. For the comparison of independent groups, either unpaired t-test or Mann-Whitney U test, depending on the normality of the data. Nominal variables were analyzed using the χ² test. To evaluate relative risk increases and adjusted odds ratios, linear or binary logistic regression models were applied based on the type of variable. Statistical analyses were performed using GraphPad Prism (version 8.0.1) and IBM SPSS (version 28.0) for Windows. Results The study cohort consisted of 39 patients, including 27 females (69.2%) and 12 males (30.8%), with a mean age of 43.5 ± 12.1 years at the time of surgery. The average follow-up duration was 21.3 ± 4.6 months. The clinical and biochemical characteristics of the participants, both before and after bariatric surgery, are summarized in Table 1. The types of bariatric surgery performed were Roux-en-Y gastric bypass (RYGB), n= 26 (66.7%); single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADIS-S), n = 10 (25.6%); gastric sleeve: n= 2 (5.1%); biliopancreatic diversion with duodenal switch (BPD-DS): n = 1 (2.6%). The total number of patients with the diagnosis of hypertension before surgery was 14 (35.9%) and the total number of patients with diagnosis of dyslipidemia was 13 (33.3%). After bariatric surgery, significant reductions were observed in BMI, with mean BMI decreasing from 41.0 ± 9.5 kg/m² to 26.5 ± 4.6 kg/m² (p<0.0001), while average %TWL was 38.5% and average %EBMIL was 99.5%. Lipid profile parameters experienced significant reductions including the total cholesterol (193.4 ± 34.6 to 161.5 ± 35.6 mg/dL, p=0.002), LDL cholesterol (133.1 ± 34.5 to 93.5±31.3, p<0.0001) and triglycerides (133.0 ± 59.6 to 74.3 ± 32.8 mg/dL, p<0.0001), while a non-significant increase in HDL was observed. Uric acid levels were also significantly decreased (5.8 ± 1.2 to 4.3 ± 0.9 mg/dL; p<0.0001). Table 1. Clinical and Biochemical Parameters Before and After Bariatric Surgery. Before (Mean ± SD) After (Mean ± SD) p-value Weight (kg) 113.7 ± 24.3 71.7 ± 16.8 <0.0001 BMI (kg/m²) 40.9 ± 9.5 26.5 ± 4.6 <0.0001 Hypertension, n (%) 15 (38.5) 5 (12.8) 0.01 Dyslipidemia, n (%) 13 (33.3) 1 (2.6) <0.001 Creatinine (mg/dL) 0.8 ± 0.2 0.7 ± 0.1 0.004 CKD-EPI (mL/min/1.73m²) 105.9 ± 16.0 108.8 ± 14.4 0.40 Urea (mg/dL) 31.3 ± 8.7 29.9 ± 7.5 0.20 Uric Acid (mg/dL) 5.9 ± 1.1 4.3 ± 0.9 <0.0001 Fasting glucose (mg/dL) 99.1 ± 27.5 83.8 ± 13.4 <0.0001 HbA1C (%) 5.6 ± 0.9 # - Total Cholesterol (mg/dL) 190.9 ± 41.2 161.5 ± 36.6 0.002 HDL Cholesterol (mg/dL) 43.1 ± 9.9 53.2 ± 14.8 0.057 LDL Cholesterol (mg/dL) 133.1 ± 34.5 93.5±31.3 <0.0001 Triglycerides (mg/dL) 138.8 ± 50.4 74.3 ± 33.7 <0.0001 Total Bilirubin (mg/dL) 0.6 ± 0.3 0.7 ± 0.3 0.006 Total Proteins (g/dL) 7.2 ± 0.4 6.9 ± 0.5 0.004 Albuminuria (mg/24h) 137.4 ± 485.9 43.7 ± 106.1 0.01 Proteinuria (mg/24h) 352.1 ± 771.5 144.2 ± 144.8 <0.0001 %Albuminuria (%) 24.0 ± 19.7 21.4 ± 14.0 0.96 %EBMIL (%) - 97.8 ± 19.9 - TWL (%) - 38.5± 11.8 - Note: # Only assessed before surgery to evaluate diabetes and pre-diabetes status as exclusion criteria. Abbreviations: BMI, Body Mass Index; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration Equation; HbA1C, Glycated Hemoglobin; HDL, High-Density Lipoprotein; LDL, Low-Density Lipoprotein; VLDL, Very Low-Density Lipoprotein; AST, Aspartate Aminotransferase; Gamma-GT, Gamma-Glutamyl Transferase; %EBMIL, Percentage of Excess BMI Lost; TWI, Total Weight Loss. After surgery, there was no significant change in kidney function as assessed by CKD-EPI (105.9 ± 16.0 to 108.8 ± 14.4 mL/min/1.73m², p=0.40), despite the significant decrease of creatinine levels (0.8 ± 0.2 to 0.7 ± 0.1 mg/dL, p=0.004) although within the interval of normality. Additionally, significant reductions in proteinuria (Δ43.0 ± 35.6%; 352.1 ± 761.5 to 144.2 ± 142.9 mg/24h, p<0.0001) and microalbuminuria (Δ14.3 ± 81.8%; 136.8 ± 456.0 to 43.7 ± 104.6 mg/24h, p=0.01) were observed. There were no significant differences in the percentage of albuminuria before and after surgery (24.0 ± 19.7 to 21.4 ± 14.0%; p=0.96). Table 2 summarizes the key findings on pre-surgery factors associated with variations in proteinuria, albuminuria, %Albuminuria and CKD-EPI. Full results dataset is available as Supplementary Materials (Supplementary Tables 1-4). Table 2. Summary of key findings of Pre-Surgical Clinical and Biochemical Parameters Significantly Associated with Percentage of Reduction in Proteinuria, Albuminuria, CKD-EPI and Reduction in the Rate of Albuminuria Univariate Multivariate Variable HR (CI) p-value HR (CI) p-value Factors Associated with Percentage of Reduction in Proteinuria Total Bilirubin (mg/dL) -7.580 (-53.596-38.436) 0.002 - - Factors Associated with Percentage of Reduction in Albuminuria %Albuminuria (%) 1.979 (0.686-3.272) 0.002 - - Factors Associated with Reduction in the %Albuminuria CKD-EPI (mL/min/1.73 m²) -0.338 (-0.674 - -0.001) 0.049 -0.126 (-0.478-0.226) 0.470 Uric Acid (mg/dL) -4.888 (-9.567 - -0.209) 0.041 -3.440 (-7.902-1.021) 0.126 Total Cholesterol (mg/dL) -0.177 (-0.332 - -0.022) 0.026 0.135 (-0.276-0.546) 0.507 LDL Cholesterol (LDL, mg/dL) -0.217 (-0.362 - -0.072) 0.005 -0.298 (-0.720-0.124) 0.160 Note: The expanded version of this analysis, including detailed regression tables and additional variables, can be found in the Supplemental Data. Abbreviations: CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration Equation; LDL, Low-Density Lipoprotein. Among the pre-operative variables analyzed as being associated with kidney function parameters improvement, higher total bilirubin levels were associated with a lower reduction in the percentage of proteinuria (HR: -7.580; 95% CI: -53.596 to -38.436; p=0.002), while a higher %Albuminuria predicted greater post-operative reductions in albuminuria (HR: 1.979; 95% CI: 0.686 to 3.272; p=0.002). Univariate analysis showed that CKD-EPI, Uric Acid, Total Cholesterol and LDL Cholesterol were significantly associated with the reduction in percentage of albuminuria, although this was not confirmed by the multivariate analysis. Despite a significant weight loss, at the end of follow up, 25.6% of patients (n=10) still exhibited proteinuria levels above 150 mg/day, with an average proteinuria of 290.6 ± 232.0 mg/24h (Table 3). Patients with persistent proteinuria were predominantly males (79.3% vs 40.0%, p =0.004), had lower serum creatinine levels (0.62 ± 0.07 mg/dL vs. 0.72 ± 0.13 mg/dL, p <0.05), greater CKD-EPI eGFR (117.4 ± 8.8 vs. 104.8 ± 12.4 mL/min/1.73m², p =0.005) and higher levels of microalbuminuria (132.1 ± 206.3 vs. 17.5 ± 11.9 mg/24h, p =0.0006). The analysis of clinical and biochemical variables potentially influencing persistent proteinuria above 150 mg/day did not identify any statistically significant associations (Supplementary Table 5). Table 3. Pre-operative Clinical and Biochemical Parameters according to proteinuria higher or lower than 150 mg/day. Variable Proteinuria 150 (Mean ± SD) p-value Number of patients, n (%) 29 (74.4) 10 (25.6) - Age (years) 44.3 ± 13.0 41.20 ± 9.1 0.49 Female gender, n (%) 23 (79.3) 4 (40.0) 0.004 Hypertension, n (%) 9 (31.0) 5 (50.0) 0.281 Dyslipidemia, n (%) 11 (37.9) 2 (20.0) 0.3 BMI (kg/m²) 26.6 ± 4.4 26.2 ± 5.6 0.43 Fasting Glucose (mg/dL) 85.0 ± 14.9 80.2 ± 6.1 0.22 Serum Creatinine (mg/dL) 0.7 ± 0.1 0.6 ± 01 0.03 CKD-EPI (mL/min/1.73m²) 104.8 ± 12.4 117.4 ± 8.8 0.005 Blood Urea (mg/dL) 29.6 ± 7.6 30.7 ± 7.4 0.72 Uric Acid (mg/dL) 4.4 ± 0.9 4.0 ± 0.9 0.41 Total Cholesterol (mg/dL) 162.6 ± 38.3 155.7 ± 31.8 0.77 HDL (mg/dL) 52.0 ± 11.5 59.3 ± 30.0 0.44 LDL (mg/dL) 95.2 ± 33.7 84.3 ± 25.5 0.60 Triglycerides (mg/dL) 76.9 ± 35.4 60.3 ± 12.7 0.62 Total Bilirubin (mg/dL) 0.7 ± 0.4 0.8 ± 0.2 0.15 Total Serum Proteins (g/dL) 6.9 ± 0.4 6.7 ± 0.7 0.23 Serum Albumin (g/dL) 4.3 ± 0.3 4.14 ± 0.60 0.38 Proteinuria (mg/24h) 93.7 ± 29.3 290.6 ± 232.0 <0.0001 Albuminuria (mg/24h) 17.5 ± 11.9 132.1 ± 206.3 0.0006 %Albuminuria (%) 22.4 ± 19.9 31.8 ± 19.3 0.02 %EBMIL (%) 96.4 ± 19.5 114.6 ± 44.2 0.08 TWL (%) 36.2 ± 6.9 45.1 ± 19.5 0.054 Note: Values in bold indicate statistically significant results (p-value < 0.05). Abbreviations: BMI, Body Mass Index; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration Equation; HbA1C, Glycated Hemoglobin; HDL, High-Density Lipoprotein; LDL, Low-Density Lipoprotein; VLDL, Very Low-Density Lipoprotein; AST, Aspartate Aminotransferase; Gamma-GT, Gamma-Glutamyl Transferase; %EBMIL, Percentage of Excess BMI Lost; TWI, Total Weight Loss. Discussion The mechanisms underlying the nephroprotective effects of bariatric surgery induced weight loss and in particular the factors influencing ORKD remission, along with the remittance of proteinuria and albuminuria, remain incompletely understood. In this study, we focused on a population of patients with ORKD—presenting obesity and proteinuria, but no other common confounders, such as diabetes or inflammatory diseases, which allowed us to isolate the effects of weight loss on ORKD. By analyzing 24-hour urine collections instead of spot urine samples a more precise assessment of proteinuria changes was enabled. In this study we observed that the significant weight loss achieved through bariatric surgery was accompanied by substantial reduction in albuminuria and proteinuria, while the corresponding eGFR (CKD-EPI 2021 equation) remained stable, despite the decrease observed in creatinine levels. Additionally, we identified an association between albuminuria reduction and pre-surgical percentage of albuminuria, offering new insights into the mechanisms underlying renal improvements after bariatric surgery. Bariatric surgery, as an effective intervention to attain sustained weight-loss [14], has been shown to significantly reduce proteinuria and support GFR normalization in patients with obesity-related kidney dysfunction [7-10]. As a risk factor for CKD progression, proteinuria reduction highlights the potential nephroprotective role of bariatric surgery, even in patients without diabetes. In a study by Fathy et al. [15], 137 patients without diabetes or hypertension submitted to bariatric surgery evaluated using 24-hour urine collections at baseline and 6 months after surgery, albuminuria remission occurred in 83% of patients. Obesity is associated with glomerular hyperfiltration that is the end result of several factors, including an increased transcapillary hydraulic pressure [16], altered tubular sodium and water handling [17, 18], and activation of RAAS [19, 20], which contribute to proteinuria and hyperfiltration even at initial stages. Modulation of these factors, which is known to occur along with weight loss after surgery, may play a role in the observed improvements. None the less, our herein study findings bring novel data to this equation, since it revealed that patients with higher pre-surgical percentage of albuminuria were the ones who experienced greater albuminuria reductions postoperatively. Indeed, albuminuria often reflects glomerular barrier dysfunction, while non-albuminuric proteinuria may be more indicative of tubular protein excretion due to tubulointerstitial inflammation or injury[21-23]. Therefore, this finding suggests that following significant weight loss, a marked improvement in glomerular hemodynamic dysfunction that was associated with obesity is likely to have occurred. This finding further reinforces the findings of previous studies conducted in populations including patients with diabetes, which suggested that nephroprotective benefits of bariatric surgery may be even greater in patients with higher pre-surgical levels of albuminuria[12]. Moreover, a negative correlation between pre-surgical serum total bilirubin levels and proteinuria reduction was also observed, a finding for which we do not have any plausible hypothesis since bilirubin levels were within the normal range and did not correlate with any other kidney function parameter evaluated in our study. Although eGFR, calculated using the CKD-EPI 2021 equation, remained stable, we noted a slight reduction of serum creatinine levels. This finding is expected following bariatric surgery due to the reduction in muscle mass that typically accompanies significant weight loss [24], leading to decreased creatinine production. However, these modest changes, within the physiological limits and normal reference ranges, do not substantially influence eGFR values. Interestingly, no associations were found between lipid metabolism variables and kidney function outcomes. This is a somehow surprising finding, as previous studies have shown that dyslipidemia negatively impacts glomerular filtration rate (GFR) [25, 26] and is linked to an increased incidence of albuminuria[27]. Indeed, obesity has been associated with fat accumulation in the kidney cortex, particularly within proximal tubule and glomerular cells ("fatty kidney"), as well as in perirenal adipose tissue. This accumulation leads to increased deposition of triglycerides and cholesterol esters, which may further contribute to kidney function impairment [28-30]. Ectopic lipid accumulation is known to compromise glomerular integrity, contributing to albuminuria [31] and fibrosis [5], mesangial cell alterations [32, 33] and podocyte dysfunction [34]. In obesity-related glomerulopathy (ORG), dysregulated lipid metabolism has been shown to promote triglyceride and cholesterol ester deposition in renal tissue, leading to maladaptive changes in renal cells that further exacerbate kidney dysfunction [35, 36]. However, lipid profile improvements observed after surgery could have contributed to mitigate the negative impact of lipids on kidney function and particularly on proteinuria. Importantly, while significant reductions in body weight and proteinuria were observed, proteinuria levels above the 150 mg/day threshold persisted in 25.6% of patients even 2 years after surgery, suggesting that ongoing kidney dysfunction can be observed in some individuals, suggesting the presence of underlying disorders or structural kidney damage that limits full recovery. One pre-surgical factor associated with persistent proteinuria was male sex. Prior studies have examined sex-based disparities in obesity-related kidney function, but the findings have been inconsistent [37, 38]. In our cohort, the observed variations may partly stem from the imbalanced gender representation among individuals undergoing bariatric surgery as men with obesity often delay seeking medical intervention or are less likely to pursue surgical options compared to women, which may contribute to these differences [39]. Another contributing factor was the combination of lower serum creatinine and higher estimated GFR (CKD-EPI), which may indicate a state of preoperative hyperfiltration which associates with elevated glomerular capillary pressure, podocyte loss, albuminuria, and proximal tubular overload, mechanisms that can accelerate CKD progression and lead to persistent kidney injury[40]. For this particular group of patients with persistent proteinuria, referral to nephrology for a more detailed work-up of kidney function and long -term management of weight-independent risk factors of kidney dysfunction is warranted. In summary, this study provides valuable insights into the putative determinants of kidney dysfunction improvement two-years after bariatric surgery in patients with ORKD, excluding concomitant medical conditions which could have acted as confounding factors, and using precise methods of proteinuria assessment in 24-hour urine collections. However, this study has also limitations that ought to be acknowledged, including the small sample size and observational design, which restrict causality assessment and generalizability. Additionally, there are other potential confounders which were not accounted for, such as lifestyle and dietary factors, as well as type of bariatric surgery procedure, which may have influenced outcomes. Lastly, while the two-year follow-up period captured early renal changes, longer term studies are needed to assess the real impact of bariatric surgery on kidney function. In conclusion, bariatric surgery leads to significant reductions in proteinuria and albuminuria, highlighting its potential nephroprotective role and its ability to potentially induce ORKD remission. The association between higher percentage of pre-operative albuminuria and reduction of albuminuria after surgery suggests that the subset of patients with significant glomerular barrier dysfunction may have additional benefits from surgery. However, persistent proteinuria in some patients suggests factors other than obesity might be affecting kidney function including established structural kidney damage. Declarations Conflict of Interest Statement The authors have no conflicts of interest to declare. All authors have seen and agree with the contents of the manuscript and there is no financial interest to report. Author Contribution Author Contributions: PRP, AR and MPM planned and designed the study. PRP, JP, MG, JM, MN conducted data acquisition. PRP, PB and SSP performed the statistical analysis. PRP, SP, AR and MPM participated in data analysis and interpretation. PRP wrote the manuscript. PRP, MPM, PB, SSP, and AR reviewed the manuscript. All the authors approved the submitted version. References Ejerblad E, Fored CM, Lindblad P, Fryzek J, McLaughlin JK, Nyrén O: Obesity and risk for chronic renal failure . J Am Soc Nephrol 2006, 17 (6):1695-1702. Hsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS: Body mass index and risk for end-stage renal disease . Ann Intern Med 2006, 144 (1):21-28. Chen HM, Li SJ, Chen HP, Wang QW, Li LS, Liu ZH: Obesity-related glomerulopathy in China: a case series of 90 patients . Am J Kidney Dis 2008, 52 (1):58-65. 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Pereira PR, Pereira J, Braga PC, Pereira SS, Nora M, Guimarães M, Monteiro MP, Rodrigues A: Renal Dysfunction Phenotypes in Patients Undergoing Obesity Surgery . Biomolecules 2023, 13 (5):790. Nuijten MAH, Eijsvogels TMH, Monpellier VM, Janssen IMC, Hazebroek EJ, Hopman MTE: The magnitude and progress of lean body mass, fat-free mass, and skeletal muscle mass loss following bariatric surgery: A systematic review and meta-analysis . Obes Rev 2022, 23 (1):e13370. Liang X, Ye M, Tao M, Zheng D, Cai R, Zhu Y, Jin J, He Q: The association between dyslipidemia and the incidence of chronic kidney disease in the general Zhejiang population: a retrospective study . BMC Nephrology 2020, 21 (1):252. Suh SH, Kim SW: Dyslipidemia in Patients with Chronic Kidney Disease: An Updated Overview . Diabetes Metab J 2023, 47 (5):612-629. Yamagata K, Ishida K, Sairenchi T, Takahashi H, Ohba S, Shiigai T, Narita M, Koyama A: Risk factors for chronic kidney disease in a community-based population: a 10-year follow-up study . Kidney International 2007, 71 (2):159-166. Bobulescu IA, Lotan Y, Zhang J, Rosenthal TR, Rogers JT, Adams-Huet B, Sakhaee K, Moe OW: Triglycerides in the human kidney cortex: relationship with body size . PLoS One 2014, 9 (8):e101285. Li H, Li M, Liu P, Wang Y, Zhang H, Li H, Yang S, Song Y, Yin Y, Gao L et al : Telmisartan Ameliorates Nephropathy in Metabolic Syndrome by Reducing Leptin Release From Perirenal Adipose Tissue . Hypertension 2016, 68 (2):478-490. Ma S, Zhu XY, Eirin A, Woollard JR, Jordan KL, Tang H, Lerman A, Lerman LO: Perirenal Fat Promotes Renal Arterial Endothelial Dysfunction in Obese Swine through Tumor Necrosis Factor-α . J Urol 2016, 195 (4 Pt 1):1152-1159. Ruan XZ, Varghese Z, Moorhead JF: An update on the lipid nephrotoxicity hypothesis . Nat Rev Nephrol 2009, 5 (12):713-721. de Vries AP, Ruggenenti P, Ruan XZ, Praga M, Cruzado JM, Bajema IM, D'Agati VD, Lamb HJ, Pongrac Barlovic D, Hojs R et al : Fatty kidney: emerging role of ectopic lipid in obesity-related renal disease . Lancet Diabetes Endocrinol 2014, 2 (5):417-426. Berfield AK, Andress DL, Abrass CK: IGF-1-induced lipid accumulation impairs mesangial cell migration and contractile function . Kidney Int 2002, 62 (4):1229-1237. Chung JJ, Huber TB, Gödel M, Jarad G, Hartleben B, Kwoh C, Keil A, Karpitskiy A, Hu J, Huh CJ et al : Albumin-associated free fatty acids induce macropinocytosis in podocytes . J Clin Invest 2015, 125 (6):2307-2316. Wickman C, Kramer H: Obesity and kidney disease: potential mechanisms . Semin Nephrol 2013, 33 (1):14-22. Guebre-Egziabher F, Alix PM, Koppe L, Pelletier CC, Kalbacher E, Fouque D, Soulage CO: Ectopic lipid accumulation: A potential cause for metabolic disturbances and a contributor to the alteration of kidney function . Biochimie 2013, 95 (11):1971-1979. Pehlivan E, Ozen G, Taskapan H, Gunes G, Sahin I, Colak C: Identifying the determinants of microalbuminuria in obese patients in primary care units: the effects of blood pressure, random plasma glucose and other risk factors . J Endocrinol Invest 2016, 39 (1):73-82. Jafar TH, Qadri Z, Hashmi S: Prevalence of microalbuminuria and associated electrocardiographic abnormalities in an Indo-Asian population . Nephrol Dial Transplant 2009, 24 (7):2111-2116. Fuchs HF, Broderick RC, Harnsberger CR, Chang DC, Sandler BJ, Jacobsen GR, Horgan S: Benefits of bariatric surgery do not reach obese men . J Laparoendosc Adv Surg Tech A 2015, 25 (3):196-201. Kanbay M, Copur S, Bakir CN, Covic A, Ortiz A, Tuttle KR: Glomerular hyperfiltration as a therapeutic target for CKD . Nephrology Dialysis Transplantation 2024, 39 (8):1228-1238. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6415243","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":450755853,"identity":"2eeb2c4f-da36-470a-8f07-618beaaa6284","order_by":0,"name":"Pedro Reis Pereira","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7UlEQVRIiWNgGAWjYHACAxDBA2Z+AGI2dlK0MM4AaWEmUgsYMIM1EtJizt687cPHPTYy8rObj322+bVNno+ZgfHDxxzcWix7jhXPnPEsjcfgzrHk2bl9tw3bmBmYJWduw+OqGznGzDwHDvMYSAAZuT23GYFa2Jh58Wm5/wak5T+P/Iz8z8yWPbftCWu5wQPScoCH4UYOMzPDj9uJBLVY9qQVM844kAzyizFjb8Pt5DZmxma8fjFnP7yZ4cMBO3tgiD1m+PHntu389uaDHz7icxicJQHEjG0gFmMDbvUYWhj+4FU8CkbBKBgFIxQAAMQmTKwANt6UAAAAAElFTkSuQmCC","orcid":"","institution":"University of Porto","correspondingAuthor":true,"prefix":"","firstName":"Pedro","middleName":"Reis","lastName":"Pereira","suffix":""},{"id":450755854,"identity":"de83b202-3449-4af3-bf9e-089ca0b9bce3","order_by":1,"name":"Patricia Braga","email":"","orcid":"","institution":"University of Porto","correspondingAuthor":false,"prefix":"","firstName":"Patricia","middleName":"","lastName":"Braga","suffix":""},{"id":450755855,"identity":"57b4851b-703e-4464-874d-ff0155e27265","order_by":2,"name":"João Pereira","email":"","orcid":"","institution":"University of Porto","correspondingAuthor":false,"prefix":"","firstName":"João","middleName":"","lastName":"Pereira","suffix":""},{"id":450755856,"identity":"a2481b7c-4d23-4c7b-b849-a66db8f27803","order_by":3,"name":"Sofia S. Pereira","email":"","orcid":"","institution":"University of Porto","correspondingAuthor":false,"prefix":"","firstName":"Sofia","middleName":"S.","lastName":"Pereira","suffix":""},{"id":450755857,"identity":"8ee80d32-c9db-4cf4-91e2-0a18bb021c93","order_by":4,"name":"Mário Nora","email":"","orcid":"","institution":"Hospital de São Sebastião","correspondingAuthor":false,"prefix":"","firstName":"Mário","middleName":"","lastName":"Nora","suffix":""},{"id":450755858,"identity":"defc4024-8215-4152-869b-015aaead9a7d","order_by":5,"name":"Marta Guimarães","email":"","orcid":"","institution":"Hospital de São Sebastião","correspondingAuthor":false,"prefix":"","firstName":"Marta","middleName":"","lastName":"Guimarães","suffix":""},{"id":450755859,"identity":"3ad31396-a700-4ac4-9385-64c45bd809da","order_by":6,"name":"Anabela Rodrigues","email":"","orcid":"","institution":"University of Porto","correspondingAuthor":false,"prefix":"","firstName":"Anabela","middleName":"","lastName":"Rodrigues","suffix":""},{"id":450755860,"identity":"091e4296-e46d-434c-842b-e58e255472ff","order_by":7,"name":"Mariana P. Monteiro","email":"","orcid":"","institution":"University of Porto","correspondingAuthor":false,"prefix":"","firstName":"Mariana","middleName":"P.","lastName":"Monteiro","suffix":""}],"badges":[],"createdAt":"2025-04-10 00:53:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6415243/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6415243/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82175974,"identity":"392d9902-864a-4be5-b87d-75cc6e44e974","added_by":"auto","created_at":"2025-05-07 11:12:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":65376,"visible":true,"origin":"","legend":"\u003cp\u003ePatient Selection Process.\u003c/p\u003e\n\u003cp\u003eLegend: Flowchart depicting patient inclusion and exclusion criteria. Of 242 patients assessed, 50 were excluded, leaving 192 eligible. Among them, 43 had baseline proteinuria \u0026gt;150 mg/day, with 4 lost to follow-up, resulting in a final number of 39 patients.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6415243/v1/71fea0ab3cc8f12b82f143a3.png"},{"id":85424445,"identity":"a4ee8c2b-b352-45f5-9d2a-3cd7fdc0171e","added_by":"auto","created_at":"2025-06-25 16:23:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2549844,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6415243/v1/6cab8902-ee7b-4864-a645-acf9ae2de08a.pdf"},{"id":82175975,"identity":"2922973b-6094-47b9-8e26-d4745dd28e15","added_by":"auto","created_at":"2025-05-07 11:12:13","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":26479,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryData.docx","url":"https://assets-eu.researchsquare.com/files/rs-6415243/v1/92d3e448ca190ae535acbcb7.docx"},{"id":82177251,"identity":"78c1dde2-5130-454e-833b-56c2c99380ef","added_by":"auto","created_at":"2025-05-07 11:20:14","extension":"pptx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1931880,"visible":true,"origin":"","legend":"","description":"","filename":"GraphicalAbstract.pptx","url":"https://assets-eu.researchsquare.com/files/rs-6415243/v1/040754e1e0e3753d8af94cba.pptx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Determinants of Obesity-Related Kidney Dysfunction Remission after Bariatric Surgery","fulltext":[{"header":"Key Learning Points","content":"\u003cul\u003e\n \u003cli\u003eBariatric surgery in patients with obesity-related kidney dysfunction results in kidney dysfunction remission, with significant reductions in proteinuria and albuminuria.\u003c/li\u003e\n \u003cli\u003ePersistent proteinuria\u0026nbsp;can still be observed\u0026nbsp;in a subset of patients, occurring predominantly in males and patients with higher pre-surgery eGFR.\u003c/li\u003e\n \u003cli\u003eThese findings suggest that the presence of underlying kidney structural damage may limit kidney dysfunction full recovery in some patients.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eObesity is a well-established risk factor for chronic kidney disease (CKD) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] and is associated with increased risk of proteinuria and albuminuria [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], which are key biomarkers of kidney dysfunction. The mechanisms underlying obesity-related kidney disease (ORKD) are multifactorial and involve glomerular hyperfiltration, altered sodium handling, activation of the renin-angiotensin-aldosterone system (RAAS), and ectopic lipid accumulation within the kidneys[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. These mechanisms are known to contribute to kidney injury, ultimately leading to CKD in a significant proportion of affected individuals [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBariatric surgery has been shown to improve kidney function outcomes by decreasing proteinuria or even inducing its resolution, while contributing to normalization of glomerular filtration rate (GFR) and renal plasma flow (RPF) in patients with glomerular hyperfiltration [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Data from the Swedish Obesity Study (SOS) study, which included individuals with diabetes, showed that weight loss achieved through bariatric surgery was associated with a lower incidence of albuminuria [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] and long-term protection against stage 4 CKD and end stage kidney disease (ESKD) in this patient population [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, the specific drivers underlying the nephroprotective effects associated with bariatric surgery, particularly in individuals with pre-existing proteinuria who do not have other identified causes for kidney dysfunction, such as diabetes or inflammatory diseases, remain incompletely understood. In order to gain further insights into potential mechanisms involved in ORKD recovery, it would be necessary to eliminate confounding factors such as hyperglycemia-related nephropathy.\u003c/p\u003e \u003cp\u003eTherefore, in this study we aimed to evaluate the impact of bariatric surgery in a cohort of individuals with obesity and pre-existing proteinuria, while isolating the effects of weight loss from other sources of bias, such as diabetes or inflammatory conditions. Additionally, we sought to identify the factors associated with kidney function recovery, with the ultimate goal of improving the management and clinical outcomes of patients with ORKD undergoing bariatric surgery.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eThis study included 242 patients who sought surgical treatment for obesity at a single public bariatric center between 2019 and 2022. Eligibility for bariatric surgery was determined by a body mass index (BMI) of \u0026gt;\u0026thinsp;40 kg/m\u0026sup2; or a BMI\u0026thinsp;\u0026gt;\u0026thinsp;35 kg/m\u0026sup2; in the presence of obesity-related comorbidities. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e illustrates the patient selection process, detailing inclusion, exclusion criteria, and the final study cohort. Exclusion criteria included the presence of diabetes mellitus (HbA1c\u0026thinsp;\u0026gt;\u0026thinsp;6.5% or treatment with anti-diabetic medications regardless of HbA1c value; n\u0026thinsp;=\u0026thinsp;25), prediabetes treated with metformin (HbA1c between 5.7% and 6.5%, n\u0026thinsp;=\u0026thinsp;14), neoplastic diseases (n\u0026thinsp;=\u0026thinsp;0), inflammatory conditions (n\u0026thinsp;=\u0026thinsp;0), and low 24-hour urine volume (\u0026lt;\u0026thinsp;800 mL, n\u0026thinsp;=\u0026thinsp;11) to ensure accurate creatinine clearance and proteinuria measurements. After exclusions, 192 patients remained eligible. From this cohort, 43 patients (22.4%) had proteinuria levels\u0026thinsp;\u0026gt;\u0026thinsp;150 mg/day before undergoing bariatric surgery and therefore underwent kidney function reassessment at follow-up. Over the 2-year postoperative period, 4 patients were lost to follow-up (10.3%), resulting in a final number of 39 patients.\u003c/p\u003e \u003cp\u003e The study protocol received prior approval from the Institutional Independent Ethical Review Board (CA-014/20-Ot_MP/CC).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData acquisition\u003c/h3\u003e\n\u003cp\u003eComprehensive patient data were retrieved from electronic clinical records, including age, gender, weight, type of bariatric surgery, BMI, hypertension status, dyslipidemia status, serum creatinine, uric acid levels, total serum proteins levels, and lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and non-LDL cholesterol). Anthropometric data were used to calculate BMI [weight(kg)\u0026thinsp;\u0026divide;\u0026thinsp;height\u003csup\u003e2\u003c/sup\u003e (m\u003csup\u003e2\u003c/sup\u003e)], percentage of excess body mass index loss (%EBMIL) [(preoperative BMI\u0026thinsp;\u0026minus;\u0026thinsp;postoperative BMI) \u0026divide; (preoperative BMI\u0026thinsp;\u0026minus;\u0026thinsp;25) \u0026times;100] and percentage of total weight loss (%TWL) [(preoperative weight\u0026thinsp;\u0026minus;\u0026thinsp;post-operative weight)\u0026thinsp;\u0026divide;\u0026thinsp;preoperative weight \u0026times; 100]. Additional assessments included 24-hour urine urinalysis for albuminuria and proteinuria measurement. The 2021 CKD-EPI Creatinine equation was used to estimate the GFR in this cohort[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePatients were instructed to perform 24-hour urine collections on two consecutive days prior to blood sampling. Detailed oral and written instructions were provided to ensure proper collection technique. Urinary albumin, protein, and creatinine concentrations were measured from each collection, and the percentage of albuminuria (%Albuminuria) was calculated by dividing the 24-hour urine concentrations of albumin and protein for each patient and multiplying by 100. Pre and post-surgery proteinuria measurements were used to calculate the percentage of proteinuria reduction [[(pre-surgical proteinuria - post-surgical proteinuria)\u0026thinsp;\u0026divide;\u0026thinsp;pre-surgical proteinuria] \u0026times; 100); pre and post-surgery albuminuria measurements were used to calculate the percentage of albuminuria reduction [[(pre-surgical albuminuria - post-surgical albuminuria)\u0026thinsp;\u0026divide;\u0026thinsp;pre-surgical albuminuria] \u0026times; 100); pre and post-surgery calculations of CKD-EPI were used to calculate the percentage of CKD-EPI reduction [[(pre-surgical CKD-EPI - post-surgical CKD-EPI)\u0026thinsp;\u0026divide;\u0026thinsp;pre-surgical CKD-EPI] \u0026times; 100); pre and post-surgery measurements of the percentage of albuminuria were used to calculate the reduction in the percentage of albuminuria (pre-surgical percentage of albuminuria \u0026ndash; post-surgery percentage of albuminuria).\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD), unless otherwise stated. The Shapiro-Wilk test was employed to assess the normality of data distribution. For the comparison of the multiple variables before and after surgery, a paired analysis was conducted using unpaired T-test or Wilcoxon test, depending on the normality of the data. For the comparison of independent groups, either unpaired t-test or Mann-Whitney U test, depending on the normality of the data. Nominal variables were analyzed using the χ\u0026sup2; test. To evaluate relative risk increases and adjusted odds ratios, linear or binary logistic regression models were applied based on the type of variable. Statistical analyses were performed using GraphPad Prism (version 8.0.1) and IBM SPSS (version 28.0) for Windows.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe study cohort consisted of 39 patients, including 27 females (69.2%) and 12 males (30.8%), with a mean age of 43.5 \u0026plusmn; 12.1 years at the time of surgery. The average follow-up duration was 21.3 \u0026plusmn; 4.6 months. The clinical and biochemical characteristics of the participants, both before and after bariatric surgery, are summarized in Table 1. The types of bariatric surgery performed were Roux-en-Y gastric bypass (RYGB), n= 26 (66.7%); single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADIS-S), n = 10 (25.6%); gastric sleeve: n= 2 (5.1%); biliopancreatic diversion with duodenal switch (BPD-DS): n = 1 (2.6%). The total number of patients with the diagnosis of hypertension before surgery was 14 (35.9%) and the total number of patients with diagnosis of dyslipidemia was 13 (33.3%). After bariatric surgery, significant reductions were observed in BMI, with mean BMI decreasing from 41.0 \u0026plusmn; 9.5 kg/m\u0026sup2; to 26.5 \u0026plusmn; 4.6 kg/m\u0026sup2; (p\u0026lt;0.0001), while average %TWL was 38.5% and average %EBMIL was 99.5%. Lipid profile parameters experienced significant reductions including the total cholesterol (193.4 \u0026plusmn; 34.6 to 161.5 \u0026plusmn; 35.6 mg/dL, p=0.002), LDL cholesterol (133.1 \u0026plusmn; 34.5 to 93.5\u0026plusmn;31.3, p\u0026lt;0.0001) and triglycerides (133.0 \u0026plusmn; 59.6 to 74.3 \u0026plusmn; 32.8 mg/dL, p\u0026lt;0.0001), while a non-significant increase in HDL was observed. Uric acid levels were also significantly decreased (5.8 \u0026plusmn; 1.2 to 4.3 \u0026plusmn; 0.9 mg/dL; p\u0026lt;0.0001).\u003c/p\u003e\n\u003cp\u003eTable 1. Clinical and Biochemical Parameters Before and After Bariatric Surgery.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBefore (Mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAfter (Mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWeight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e113.7 \u0026plusmn; 24.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e71.7 \u0026plusmn; 16.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBMI (kg/m\u0026sup2;)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e40.9 \u0026plusmn; 9.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e26.5 \u0026plusmn; 4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHypertension, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15 (38.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5 (12.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDyslipidemia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCreatinine (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.8 \u0026plusmn; 0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.7 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCKD-EPI (mL/min/1.73m\u0026sup2;)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e105.9 \u0026plusmn; 16.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e108.8 \u0026plusmn; 14.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUrea (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e31.3 \u0026plusmn; 8.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e29.9 \u0026plusmn; 7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUric Acid (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.9 \u0026plusmn; 1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.3 \u0026plusmn; 0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFasting glucose (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e99.1 \u0026plusmn; 27.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e83.8 \u0026plusmn; 13.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHbA1C (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.6 \u0026plusmn; 0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTotal Cholesterol (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e190.9 \u0026plusmn; 41.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e161.5 \u0026plusmn; 36.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHDL Cholesterol (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e43.1 \u0026plusmn; 9.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e53.2 \u0026plusmn; 14.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLDL Cholesterol (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e133.1 \u0026plusmn; 34.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e93.5\u0026plusmn;31.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTriglycerides (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e138.8 \u0026plusmn; 50.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e74.3 \u0026plusmn; 33.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTotal Bilirubin (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.6 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.7 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTotal Proteins (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7.2 \u0026plusmn; 0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.9 \u0026plusmn; 0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAlbuminuria (mg/24h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e137.4 \u0026plusmn; 485.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e43.7 \u0026plusmn; 106.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eProteinuria (mg/24h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e352.1 \u0026plusmn; 771.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e144.2 \u0026plusmn; 144.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e%Albuminuria (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e24.0 \u0026plusmn; 19.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e21.4 \u0026plusmn; 14.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e%EBMIL (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e97.8 \u0026plusmn; 19.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTWL (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e38.5\u0026plusmn; 11.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u003c/strong\u003e # Only assessed before surgery to evaluate diabetes and pre-diabetes status as exclusion criteria.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e BMI, Body Mass Index; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration Equation; HbA1C, Glycated Hemoglobin; HDL, High-Density Lipoprotein; LDL, Low-Density Lipoprotein; VLDL, Very Low-Density Lipoprotein; AST, Aspartate Aminotransferase; Gamma-GT, Gamma-Glutamyl Transferase; %EBMIL, Percentage of Excess BMI Lost; TWI, Total Weight Loss.\u003c/p\u003e\n\u003cp\u003eAfter surgery, there was no significant change in kidney function as assessed by CKD-EPI (105.9 \u0026plusmn; 16.0 to 108.8 \u0026plusmn; 14.4 mL/min/1.73m\u0026sup2;, p=0.40), despite the significant decrease of creatinine levels (0.8 \u0026plusmn; 0.2 to 0.7 \u0026plusmn; 0.1 mg/dL, p=0.004) although within the interval of normality. Additionally, significant reductions in proteinuria (\u0026Delta;43.0 \u0026plusmn; 35.6%; 352.1 \u0026plusmn; 761.5 to 144.2 \u0026plusmn; 142.9 mg/24h, p\u0026lt;0.0001) and microalbuminuria (\u0026Delta;14.3 \u0026plusmn; 81.8%; 136.8 \u0026plusmn; 456.0 to 43.7 \u0026plusmn; 104.6 mg/24h, p=0.01) were observed. There were no significant differences in the percentage of albuminuria before and after surgery (24.0 \u0026plusmn; 19.7 to 21.4 \u0026plusmn; 14.0%; p=0.96).\u003c/p\u003e\n\u003cp\u003eTable 2 summarizes the key findings on pre-surgery factors associated with variations in proteinuria, albuminuria, %Albuminuria and CKD-EPI. Full results dataset is available as Supplementary Materials (Supplementary Tables 1-4).\u003c/p\u003e\n\u003cp\u003eTable 2. Summary of key findings of Pre-Surgical Clinical and Biochemical Parameters Significantly Associated with Percentage of Reduction in Proteinuria, Albuminuria, CKD-EPI and Reduction in the Rate of Albuminuria\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR (CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR (CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 592px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFactors Associated with Percentage of Reduction in Proteinuria\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTotal Bilirubin (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-7.580 (-53.596-38.436)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 592px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFactors Associated with Percentage of Reduction in Albuminuria\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e%Albuminuria (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.979 (0.686-3.272)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 592px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFactors Associated with Reduction in the %Albuminuria\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCKD-EPI (mL/min/1.73 m\u0026sup2;)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0.338 (-0.674 - -0.001)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.049\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.126 (-0.478-0.226)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.470\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUric Acid (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e-4.888 (-9.567 - -0.209)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.041\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-3.440 (-7.902-1.021)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.126\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTotal Cholesterol (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0.177 (-0.332 - -0.022)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.026\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.135 (-0.276-0.546)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.507\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLDL Cholesterol (LDL, mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0.217 (-0.362 - -0.072)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.005\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.298 (-0.720-0.124)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.160\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u003c/strong\u003e The expanded version of this analysis, including detailed regression tables and additional variables, can be found in the Supplemental Data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration Equation; LDL, Low-Density Lipoprotein.\u003c/p\u003e\n\u003cp\u003eAmong the pre-operative variables analyzed as being associated with kidney function parameters improvement, higher total bilirubin levels were associated with a lower reduction in the percentage of proteinuria (HR: -7.580; 95% CI: -53.596 to -38.436; p=0.002), while a higher %Albuminuria predicted greater post-operative reductions in albuminuria (HR: 1.979; 95% CI: 0.686 to 3.272; p=0.002).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUnivariate analysis showed that CKD-EPI, Uric Acid, Total Cholesterol and LDL Cholesterol were significantly associated with the reduction in percentage of albuminuria, although this was not confirmed by the multivariate analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDespite a significant weight loss, at the end of follow up, 25.6% of patients (n=10) still exhibited proteinuria levels above 150 mg/day, with an average proteinuria of 290.6 \u0026plusmn; 232.0 mg/24h (Table 3). \u0026nbsp;Patients with persistent proteinuria were predominantly males (79.3% vs 40.0%, \u003cem\u003ep\u003c/em\u003e=0.004), had lower serum creatinine levels (0.62 \u0026plusmn; 0.07 mg/dL vs. 0.72 \u0026plusmn; 0.13 mg/dL, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.05), greater CKD-EPI eGFR (117.4 \u0026plusmn; 8.8 vs. 104.8 \u0026plusmn; 12.4 mL/min/1.73m\u0026sup2;, \u003cem\u003ep\u003c/em\u003e=0.005) and higher levels of microalbuminuria (132.1 \u0026plusmn; 206.3 vs. 17.5 \u0026plusmn; 11.9 mg/24h, \u003cem\u003ep\u003c/em\u003e=0.0006). The analysis of clinical and biochemical variables potentially influencing persistent proteinuria above 150 mg/day did not identify any statistically significant associations (Supplementary Table 5).\u003c/p\u003e\n\u003cp\u003eTable 3. Pre-operative Clinical and Biochemical Parameters\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eaccording to proteinuria higher or lower than 150 mg/day.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eProteinuria \u0026lt;150 (Mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eProteinuria \u0026gt;150 (Mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of patients, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e29 (74.4)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e10 (25.6)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e44.3\u0026nbsp;\u0026plusmn; 13.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e41.20 \u0026plusmn; 9.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale gender, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23 (79.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypertension, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9 (31.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.281\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDyslipidemia, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e11 (37.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI (kg/m\u0026sup2;)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e26.6 \u0026plusmn; 4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e26.2 \u0026plusmn; 5.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFasting Glucose (mg/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e85.0 \u0026plusmn; 14.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e80.2 \u0026plusmn; 6.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerum Creatinine (mg/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.7 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.6 \u0026plusmn; 01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.03\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCKD-EPI (mL/min/1.73m\u0026sup2;)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e104.8 \u0026plusmn; 12.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e117.4 \u0026plusmn; 8.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.005\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood Urea (mg/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e29.6 \u0026plusmn; 7.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e30.7 \u0026plusmn; 7.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eUric Acid (mg/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.4 \u0026plusmn; 0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.0 \u0026plusmn; 0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Cholesterol (mg/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e162.6 \u0026plusmn; 38.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e155.7 \u0026plusmn; 31.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHDL (mg/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e52.0 \u0026plusmn; 11.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e59.3 \u0026plusmn; 30.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLDL (mg/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e95.2 \u0026plusmn; 33.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e84.3 \u0026plusmn; 25.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTriglycerides (mg/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e76.9 \u0026plusmn; 35.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e60.3 \u0026plusmn; 12.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Bilirubin (mg/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.7 \u0026plusmn; 0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.8 \u0026plusmn; 0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Serum Proteins (g/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.9 \u0026plusmn; 0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.7 \u0026plusmn; 0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerum Albumin (g/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.3 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.14 \u0026plusmn; 0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eProteinuria (mg/24h)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e93.7 \u0026plusmn; 29.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e290.6 \u0026plusmn; 232.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlbuminuria (mg/24h)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e17.5 \u0026plusmn; 11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e132.1 \u0026plusmn; 206.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.0006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e%Albuminuria (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e22.4 \u0026plusmn; 19.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e31.8 \u0026plusmn; 19.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e%EBMIL (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e96.4 \u0026plusmn; 19.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e114.6 \u0026plusmn; 44.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.08\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTWL (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e36.2 \u0026plusmn; 6.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e45.1 \u0026plusmn; 19.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u003c/strong\u003e Values in bold indicate statistically significant results (p-value \u0026lt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e BMI, Body Mass Index; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration Equation; HbA1C, Glycated Hemoglobin; HDL, High-Density Lipoprotein; LDL, Low-Density Lipoprotein; VLDL, Very Low-Density Lipoprotein; AST, Aspartate Aminotransferase; Gamma-GT, Gamma-Glutamyl Transferase; %EBMIL, Percentage of Excess BMI Lost; TWI, Total Weight Loss.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe mechanisms underlying the nephroprotective effects of bariatric surgery induced weight loss and in particular the factors influencing ORKD remission, along with the remittance of proteinuria and albuminuria, remain incompletely understood. In this study, we focused on a population of patients with ORKD\u0026mdash;presenting obesity and proteinuria, but no other common confounders, such as diabetes or inflammatory diseases, which allowed us to isolate the effects of weight loss on ORKD. By analyzing 24-hour urine collections instead of spot urine samples a more precise assessment of proteinuria changes was enabled.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn this study we observed that the significant weight loss achieved through bariatric surgery was accompanied by substantial reduction in albuminuria and proteinuria, while the corresponding eGFR (CKD-EPI 2021 equation) remained stable, despite the decrease observed in creatinine levels. Additionally, we identified an association between albuminuria reduction and pre-surgical percentage of albuminuria, offering new insights into the mechanisms underlying renal improvements after bariatric surgery.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBariatric surgery, as an effective intervention to attain sustained weight-loss [14], has been shown to significantly reduce proteinuria and support GFR normalization in patients with obesity-related kidney dysfunction [7-10]. As a risk factor for CKD progression, proteinuria reduction highlights the potential nephroprotective role of bariatric surgery, even in patients without diabetes.\u0026nbsp;In a study by Fathy et al.\u0026nbsp;[15], 137 patients without diabetes or hypertension submitted to bariatric surgery evaluated using 24-hour urine collections at baseline and 6 months after surgery, albuminuria remission occurred in 83% of patients.\u0026nbsp;Obesity is associated with glomerular hyperfiltration that is the end result of several factors, including an increased transcapillary hydraulic pressure\u0026nbsp;[16], altered tubular sodium and water handling\u0026nbsp;[17, 18], and activation of RAAS\u0026nbsp;[19, 20], which contribute to proteinuria and hyperfiltration even at initial stages. Modulation of these factors, which is known to occur along with weight loss after surgery, may play a role in the observed improvements. None the less,\u0026nbsp;our herein study findings bring novel data to this equation, since it revealed that patients with higher pre-surgical percentage of albuminuria were the ones who experienced greater albuminuria reductions postoperatively. Indeed, albuminuria often reflects glomerular barrier dysfunction, while non-albuminuric proteinuria may be more indicative of tubular protein excretion due to tubulointerstitial inflammation or injury[21-23]. Therefore, this finding suggests that following significant weight loss, a marked improvement in glomerular hemodynamic dysfunction that was associated with obesity is likely to have occurred. This finding further reinforces the findings of previous studies conducted in populations including patients with diabetes, which suggested that nephroprotective benefits of bariatric surgery may be even greater in patients with higher pre-surgical levels of albuminuria[12]. Moreover, a negative correlation between pre-surgical serum total bilirubin levels and proteinuria reduction was also observed, a finding for which we do not have any plausible hypothesis since bilirubin levels were within the normal range and did not correlate with any other kidney function parameter evaluated in our study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough eGFR, calculated using the CKD-EPI 2021 equation, remained stable, we noted a slight reduction of serum creatinine levels. This finding is expected following bariatric surgery due to the reduction in muscle mass that typically accompanies significant weight loss [24], leading to decreased creatinine production. However, these modest changes, within the physiological limits and normal reference ranges, do not substantially influence eGFR values.\u003c/p\u003e\n\u003cp\u003eInterestingly, no associations were found between lipid metabolism variables and kidney function outcomes. This is a somehow surprising finding, as previous studies have shown that dyslipidemia negatively impacts glomerular filtration rate (GFR) [25, 26] and is linked to an increased incidence of albuminuria[27]. Indeed, obesity has been associated with fat accumulation in the kidney cortex, particularly within proximal tubule and glomerular cells (\u0026quot;fatty kidney\u0026quot;), as well as in perirenal adipose tissue. This accumulation leads to increased deposition of triglycerides and cholesterol esters, which may further contribute to kidney function impairment [28-30]. Ectopic lipid accumulation is known to compromise glomerular integrity, contributing to albuminuria\u0026nbsp;[31]\u0026nbsp;and fibrosis\u0026nbsp;[5], mesangial cell alterations\u0026nbsp;[32, 33]\u0026nbsp;and podocyte dysfunction\u0026nbsp;[34]. In obesity-related glomerulopathy (ORG), dysregulated lipid metabolism has been shown to promote triglyceride and cholesterol ester deposition in renal tissue, leading to maladaptive changes in renal cells that further exacerbate kidney dysfunction\u0026nbsp;[35, 36]. \u0026nbsp;However, lipid profile improvements observed after surgery could have contributed to mitigate the negative impact of lipids on kidney function and particularly on proteinuria.\u003c/p\u003e\n\u003cp\u003eImportantly, while significant reductions in body weight and proteinuria were observed, proteinuria levels above the 150 mg/day threshold persisted in 25.6% of patients even 2 years after surgery, suggesting that ongoing kidney dysfunction can be observed in some individuals, suggesting the presence of underlying disorders or structural kidney damage that limits full recovery. One pre-surgical factor associated with persistent proteinuria was male sex. Prior studies have examined sex-based disparities in obesity-related kidney function, but the findings have been inconsistent [37, 38]. In our cohort, the observed variations may partly stem from the imbalanced gender representation among individuals undergoing bariatric surgery as men with obesity often delay seeking medical intervention or are less likely to pursue surgical options compared to women, which may contribute to these differences [39]. Another contributing factor was the combination of lower serum creatinine and higher estimated GFR (CKD-EPI), which may indicate a state of preoperative hyperfiltration which associates with elevated glomerular capillary pressure, podocyte loss, albuminuria, and proximal tubular overload, mechanisms that can accelerate CKD progression and lead to persistent kidney injury[40].\u0026nbsp;For this particular group of patients with\u0026nbsp;persistent proteinuria, referral to nephrology for a more detailed work-up of kidney function and\u0026nbsp;long -term management of\u0026nbsp;weight-independent\u0026nbsp;risk\u0026nbsp;factors of kidney dysfunction is warranted.\u003c/p\u003e\n\u003cp\u003eIn summary, this study provides valuable insights into the putative determinants of kidney dysfunction improvement two-years after bariatric surgery in patients with ORKD, excluding concomitant medical conditions which could have acted as confounding factors, and using precise methods of proteinuria assessment in 24-hour urine collections. However, this study has also limitations that ought to be acknowledged, including the small sample size and observational design, which restrict causality assessment and generalizability. Additionally, there are other potential confounders which were not accounted for, such as lifestyle and dietary factors, as well as type of bariatric surgery procedure, which may have influenced outcomes. Lastly, while the two-year follow-up period captured early renal changes, longer term studies are needed to assess the real impact of bariatric surgery on kidney function.\u003c/p\u003e\n\u003cp\u003eIn conclusion, bariatric surgery leads to significant reductions in proteinuria and albuminuria, highlighting its potential nephroprotective role and its ability to potentially induce ORKD remission. The association between higher percentage of pre-operative albuminuria and reduction of albuminuria after surgery suggests that the subset of patients with significant glomerular barrier dysfunction may have additional benefits from surgery. However, persistent proteinuria in some patients suggests factors other than obesity might be affecting kidney function including established structural kidney damage.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare. All authors have seen and agree with the contents of the manuscript and there is no financial interest to report.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAuthor Contributions: PRP, AR and MPM planned and designed the study. PRP, JP, MG, JM, MN conducted data acquisition. PRP, PB and SSP performed the statistical analysis. PRP, SP, AR and MPM participated in data analysis and interpretation. PRP wrote the manuscript. PRP, MPM, PB, SSP, and AR reviewed the manuscript. All the authors approved the submitted version.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eEjerblad E, Fored CM, Lindblad P, Fryzek J, McLaughlin JK, Nyr\u0026eacute;n O: \u003cstrong\u003eObesity and risk for chronic renal failure\u003c/strong\u003e. \u003cem\u003eJ Am Soc Nephrol \u003c/em\u003e2006, \u003cstrong\u003e17\u003c/strong\u003e(6):1695-1702.\u003c/li\u003e\n\u003cli\u003eHsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS: \u003cstrong\u003eBody mass index and risk for end-stage renal disease\u003c/strong\u003e. \u003cem\u003eAnn Intern Med \u003c/em\u003e2006, \u003cstrong\u003e144\u003c/strong\u003e(1):21-28.\u003c/li\u003e\n\u003cli\u003eChen HM, Li SJ, Chen HP, Wang QW, Li LS, Liu ZH: \u003cstrong\u003eObesity-related glomerulopathy in China: a case series of 90 patients\u003c/strong\u003e. \u003cem\u003eAm J Kidney Dis \u003c/em\u003e2008, \u003cstrong\u003e52\u003c/strong\u003e(1):58-65.\u003c/li\u003e\n\u003cli\u003eTsuboi N, 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\u003cstrong\u003e39\u003c/strong\u003e(8):1228-1238.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"obesity-related kidney dysfunction, albuminuria, proteinuria, hyperfiltration, fatty kidney","lastPublishedDoi":"10.21203/rs.3.rs-6415243/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6415243/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e: Bariatric surgery was demonstrated to improve obesity-related kidney dysfunction (ORKD). However, the mechanisms underlying ORKD remittance or persistence remain unclear. This study aimed to explore the factors associated with proteinuria remission after bariatric surgery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: A cohort of 39 patients with obesity and proteinuria was followed up for an average of 21.3 ± 4.6 months after bariatric surgery. Pre- and post-surgical assessments included the evaluation of weight-related and kidney-related outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: After bariatric surgery, there was a significant reduction in body mass index (BMI) (41.0 ± 9.5 to 26.5 ± 4.6 kg/m², p \u0026lt; 0.05) with a total weight loss (TWL) of 38.5 ± 11.8%. Significant reductions in proteinuria (Δ43.0 ± 35.6%; 352.1 ± 761.5 to 144.2 ± 142.9 mg/24h, p \u0026lt; 0.05) and albuminuria (Δ14.3 ± 81.8%; 137.4 ± 485.9 to 43.7 ± 106.1 mg/24h; p \u0026lt; 0.01) were also observed. Higher pre-operative percentage of albuminuria predicted a greater post-operative reduction in albuminuria (HR: 1.979; 95% CI: 0.686 to 3.272; p \u0026lt; 0.05). Patients with persistent proteinuria (25.6%; \u003cem\u003en\u003c/em\u003e = 10) despite weight loss were predominantly males (79.3% vs 40.0%, \u003cem\u003ep\u003c/em\u003e = 0.004) with lower serum creatinine levels (0.62 ± 0.07 mg/dL vs. 0.72 ± 0.13 mg/dL, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05) and greater CKD-EPI eGFR (117.4 ± 8.8 vs. 104.8 ± 12.4 mL/min/1.73m², \u003cem\u003ep\u003c/em\u003e = 0.005).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Bariatric surgery in patients with ORKD resulted in kidney dysfunction remission or significant reductions in proteinuria and albuminuria. Despite weight loss, persistent proteinuria can still be observed suggesting the presence of underlying kidney structural damage that limits kidney dysfunction full recovery.\u003c/p\u003e","manuscriptTitle":"Determinants of Obesity-Related Kidney Dysfunction Remission after Bariatric Surgery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 11:12:09","doi":"10.21203/rs.3.rs-6415243/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b3943ea5-df28-4eb7-b410-87513af8bbf2","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-25T16:23:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-07 11:12:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6415243","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6415243","identity":"rs-6415243","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}