Departments of * Nephrology and General Surgery, "Germans Trias i Pujol" Hospital, Department of Medicine, Universidad Autónoma de Barcelona, Barcelona, Spain
Address correspondence to: Dr. Ramón Romero, Department of Nephrology, "Germans Trias y Pujol" Hospital, Carretera de Canyet, s/n Badalona, 08916 Barcelona, Spain. Phone: +34-93-497-8898; Fax: +34-93-497-8852; E-mail: r.romero{at}uab.es
Obesity is a health problem that is reaching epidemic proportions.Extreme obesity (body mass index [BMI] 40 kg/m2) is a type ofobesity that usually does not respond to medical treatment,with surgery being the current treatment of choice. Extremeobesity is associated with cardiovascular disease, type 2 diabetes,dyslipidemia, and hypertension. Recently, obesity has been relatedwith high rate of renal lesions, but renal function and renalparameters in extreme obesity scarcely are documented. The objectiveof this study was to evaluate the effect of weight loss afterbariatric surgery (BS) on BP, renal parameters, and renal functionin 61 extremely obese (EO) patients after 24 mo of follow-up.A total of 61 EO adults (37 women) were studied prospectivelybefore and 24 mo after surgery. Control subjects were 24 healthy,normal-weight adults (15 women). Anthropometric, BP, and renalparameters were determined. Presurgery weight, BMI, GFR, 24-hproteinuria, and 24-h albuminuria were higher in the EO patientsthan in control subjects (P < 0.001). All parameters improvedat 12 mo after BS. However, during the second year of follow-up,only 24-h albuminuria (P = 0.006) and BMI (P = 0.014) continuedto improve. At 24 mo after BS, obesity-related renal alterationsconsiderably improved. This improvement was observed mainlyin the first year after surgery, when the majority of weightloss occurred. However, 24-h albuminuria still improves duringthe second year of follow-up. It is possible that this decreasein 24-h albuminuria is not GFR related but rather is attributableto the persistence of the decrease in BMI and to the improvementof other weight-related metabolic factors.
Obesity is a worldwide health problem of epidemic proportions.Extreme obesity (body mass index [BMI] 40 kg/m2) is a type ofobesity that usually does not respond to medical treatment,with surgery being the current treatment of choice (1). Cardiovasculardisease, diabetes, dyslipidemia, hypertension (2–4), andimpaired renal parameters have been described as obesity-relatedcomorbidities, although obesity-related renal lesions scarcelyare documented (5,6). Both experimental and clinical data showthat obesity produces glomerular hyperfiltration, although thephysiopathologic mechanism still is unknown (7). Hyperlipidemia(8), hyperinsulinemia (9), and the implication of some adipocytokinessuch as leptin (10) may contribute to this state of hyperfiltration.Moreover, fat tissue may contribute to the increase of angiotensinII (AngII), which enhances tubular sodium reabsorption and activatestubuloglomerular feedback (11). These mechanisms lead to vasodilationof the afferent arterioles, with a consequent increase in renalblood flow, intraglomerular pressure, and GFR (7,12). Glomerularhyperfiltration favors the occurrence of microalbuminuria andproteinuria in obese patients with unknown renal disease (13)and, in addition, can increase the progression of preexistingrenal disease (8,14,15). Reducing glomerular hyperfiltration,therefore, could prevent or delay the incidence of obesity-associatedrenal damage. Some studies have shown that both weight losswith hypocaloric diets and treatment with angiotensin-convertingenzyme inhibitors (ACEI) and/or AngII type I receptor blockersare useful drugs for reducing obesity-related proteinuria (16,17).Bariatric surgery (BS) produces greater weight loss and is moreeffective in controlling hypertension, diabetes, dyslipidemia,and other cardiovascular risk factors (18,19). However, itseffect on renal parameters (e.g., changes in GFR, albuminuria,and proteinuria) scarcely are described in the literature (12,19–21),and, to our knowledge, there are no studies on the long-termevolution of these effects (2 yr follow-up). Therefore, theaim of this study was to evaluate the effect of weight lossafter BS on BP, renal parameters, and renal function in 61 extremelyobese (EO) patients after 24 mo of follow-up.
We carried out a prospective study of 102 EO patients who underwentBS in our hospital between December 2001 and January 2004. Patientsmet the surgical criteria according to NIH Consensus and SociedadEspañola para el Estudio de la Obesidad (SEEDO) SpanishConsensus (22,23). Of the 102 patients who underwent BS, only61 patients (24 men and 37 women) who had biochemical and clinicalstudies at both 12 and 24 mo after BS were included in our study.The mean age was 41 ± 9.07 yr, and the mean BMI was 53.62± 9.65 kg/m2 (range 40.32 to 93.98 kg/m2). The surgicaltechnique performed was gastric bypass according to the methoddescribed by Fobi et al. (24) (in 27 patients) and Salmon (25)(in 34 patients). Both interventions combined a permanent restrictionin the volume ingested (gastroplasty) with moderate to mildmalabsorption. This study was approved by the ethics committeeof our hospital, and all of our patients gave their informedconsent to participate in the study.
Twenty-one (35%) patients were smokers, and three (5%) had cardiovasculardisease (two who had angina and had a normal coronary catheterismstudy and one who had undergone aortic-coronary bypass). Noneof the patients selected was being treated with insulin, oralantidiabetic drugs, or lipid-lowering drugs. Twenty-two patientswere receiving treatment for hypertension (five with ACEI, fourwith AngII type I receptor blockers, three with diuretics, onewith blockers, and nine with ACEI in combination with otherdrugs). Medications were withdrawn 8 d before the analyses wereperformed. All patients in the study had normal levels of serumcreatinine (normal values in our laboratory 44 to 106 µmol/L),and none had a history of renal disease.
Twenty-four healthy, normal-weight adults (nine men and 15 women)were included as a control group (mean BMI 23.52 ± 2.59kg/m2; mean age 42.54 ± 11.39 yr). Only baseline studieswere available for the control subjects.
Preoperative and postoperative (at 12 and 24 mo after bariatricsurgery) blood samples were drawn between 8:00 and 9:00 a.m.after a minimum of 8 h of fasting. A 24-h urine sample alsowas collected from all patients. Plasma creatinine, urea, andurinary creatinine were determined using a routine clinicalchemistry laboratory analyzer. Creatinine clearance was calculatedas 24-h urine (ml) x urinary creatinine concentration x 1000/plasmacreatinine concentration x 1440 min. Twenty-four-hour proteinuriawas measured by a spectrophotometric method (Pyrogallol Red),and 24-h albuminuria was determined by nephelometry. Proteinuriavalues >0.15 g/24 h and albuminuria values 30 mg/24 h wereconsidered pathologic. Microalbuminuria was defined as albuminlevels in 24-h urine between 30 and 300 mg.
BMI was calculated as weight (kg)/height (m2). Waist circumference(cm) was measured with a soft tape measure in a horizontal planearound the abdomen at the level of the iliac crest. BP was measuredusing a standard mercury sphygmomanometer of appropriate cuffsize. High casual systolic BP (SBP) and high casual diastolicBP (DBP) were defined as SBP 140 mmHg and DBP 90 mmHg in twodifferent measurements. Glomerular hyperfiltration was consideredwhen the creatinine clearance was >140 ml/min (26) and microhematuriawhen there were four or more red blood cells per high-powerfield in the urinary sediment, according to routine values ofour laboratory.
Statistical Analyses
Data first were tested for normal distribution using the Kolmogorov-Smirnovtest. Variables with normal distribution were expressed as mean± SD. Nonparametric variables such as proteinuria andalbuminuria were expressed as median (25th and 75th percentiles).The significance of differences between the control group andthe obese patients was evaluated with unpaired t test or 2 test,as appropriate. Differences within the obese group before andafter BS were evaluated with paired t test or the McNemar test,as appropriate. The t test was applied to the nonparametricdata after log transformation.
All statistical analyses were made with the statistical softwarepackage SPSS (version 12.0; SPSS, Chicago, IL). Statisticalsignificance was considered at P < 0.05.
Study Population Table 1 shows the general characteristics of the 61 EO patientscompared with the 24 healthy normal-weight control subject,with no differences in the distribution for age or gender. Beforeundergoing BS, the EO patients presented with a statisticallysignificant elevation in BP (both SBP and DBP) compared withthe control group. Although there were no differences in ureaand blood creatinine between the two groups, the EO patientshad a greater creatinine clearance, 24-h proteinuria, and 24-halbuminuria and a greater percentage of microhematuria thanin the control group.
Table 1. General characteristics of the EO patients and control groupa
Changes Observed 12 Mo after BS
In comparing the group of obese patients before and 12 mo afterBS (Table 2), a mean weight loss of 56.3 kg and a mean decreasein BMI of 20 units was found. There also was a significant decreasein SBP and DBP. In regard to renal parameters, a decrease increatinine clearance, 24-h proteinuria, 24-h albuminuria, andmicrohematuria is shown.
Table 2. Anthropometric, BP, and renal parameter changes in EO patients observed 12 and 24 mo after BSa
Changes Observed 24 Mo after BS
At 24 mo after surgery (Table 2), the patients continued tolose weight, although in a smaller proportion than during thefirst year (weight loss was 37% during the first year and 3%during the second). However, there were no significant differencesin the decrease of SBP, DBP, creatinine clearance, 24-h proteinuria,and microhematuria in the second year compared with the firstyear. There was, however, a significant decrease in 24-h albuminuriaduring the 24th month of follow-up in relation to the firstyear. Table 3 illustrates the percentage of patients with glomerularhyperfiltration, systolic and diastolic arterial hypertension,high 24-h albuminuria, 24-h proteinuria, and microhematuriabefore and 24 mo after BS. A significant decrease in all ofthe variables studied is shown after 2 yr of weight loss, withthe exception of microhematuria, which showed a tendency towarddecreasing but without reaching statistical significance (P= 0.33).
Table 3. Percentage of EO patients with glomerular hyperfiltration, hypertension, high 24-h albuminuria, 24-h proteinuria, and microhematuria before and 24 mo after BS
In comparing the group of EO patients at 24 mo of follow-upwith the control group (Table 4), we found that there stillwere significant differences between the anthropometric parameters(weight, BMI, and waist circumference). SBP was significantlylower in the control group, whereas DBP did not show statisticallysignificant differences among the two groups, although it tendedto be lower in the control group. There were no differencesin urinary sediment or 24-h proteinuria between the two groups,although the postoperative EO patients continued to presenthigher 24-h albuminuria than the control group. Although EOpatients showed a decrease in creatinine clearance at 24 moafter BS, it still was significantly lower in the control group.
This study demonstrates that after BS, there is a significantimprovement in the renal alterations that are associated withextreme obesity (glomerular hyperfiltration, proteinuria, highalbuminuria, and microhematuria), as well as in the values ofSBP and DBP. This improvement occurred mainly in the first yearafter surgery, because this is when the majority of weight losstakes place. Furthermore, we demonstrate for the first timethat albuminuria continued to improve despite the discrete levelof weight loss observed in the second year after BS.
Obesity is associated with glomerular hyperfiltration, whichfavors the occurrence of microalbuminuria and/or proteinuriain patients without known renal disease (7,27,28). Brochneret al. (20) demonstrated for the first time in the 1980s thatGFR decreased in EO patients who had undergone intestinal bypasssurgery. Only two studies support these results after 12 moof follow-up (12,19), and there are no studies on GFR in patientswho undergo BS and are followed over a longer period of time.In our study, an important percentage of EO patients had glomerularhyperfiltration before undergoing BS. This percentage decreasedat 12 mo after BS in a similar way to patients in previous studies,including one from our group (12,19). However, this percentageof EO patients with high GFR did not improve significantly between12 and 24 mo, even though there was a discrete weight loss duringthis time. That a few patients still had glomerular hyperfiltrationat 24 mo after BS could be attributed to these patients’still having type 1 obesity. The value of GFR was estimatedusing creatinine clearance as measured by 24-h urine sample,without correcting for body surface area, because the correctionwould underestimate considerably the real value of the GFR (29).For the same reason, we did not use other types of formulasto estimate the GFR (Cockcroft-Gault and Modification of Dietin Renal Disease), because these formulas are designed for patientswith chronic renal failure and, if applied to our study population,also would underestimate the real value of GFR (30,31).
Almost half of the EO patients in our study presented with albuminuriaand/or proteinuria before undergoing BS. This improved significantlyat 12 mo after BS, although it did not disappear completely,which confirms previously published reports by other authors(12,19). During the second year of follow-up, albuminuria continuedto decrease even though GFR did not decrease. Other weight-relatedfactors, such as improvement of lipid alterations and hyperinsulinemiaor decrease in plasma leptin levels, may contribute to the persistenceof this improvement (our unpublished observations, 2005).
This is the first study to demonstrate that EO patients presentwith a greater percentage of microhematuria compared with thecontrol group and that these alterations in urinary sedimentimprove within 12 mo of drastic weight loss. To evaluate theseresults further, we would have had to carry out subsequent histologicstudies, which are difficult to justify for ethical reasons.
Although the cause-and-effect relationship of glomerular hyperfiltrationin obesity is not fully understood, we do know that in thesepatients, there is an increase in the tubular reabsorption ofsodium in the loop of Henle. As such, the macula densa receivesless salt, which leads to vasodilatation of the afferent arteriolesand a subsequent increase in GFR (3). This retention of sodiumcould be the physiopathologic mechanism of the arterial hypertensionthat is associated with obesity. This study shows that drasticweight loss and the subsequent decrease in glomerular filtrationleads to a decrease in SBP and DBP, as shown in previous studies(12,18,19,21). SBP and DBP did not decrease more between thefirst and the second years, probably because of the lack ofchange in the GFR.
After the drastic weight loss 24 months after BS, parametersof renal function and BP considerably improved, although a smallpercentage of patients still had glomerular hyperfiltration,proteinuria, and/or microalbuminuria, given that at 2 yr offollow-up the patients changed to type 1 obesity. The decreasein albuminuria that took place during the first year after BScould be attributed mainly to the drastic weight loss that tookplace during this time, whereas during the second year, othermetabolic factors may have played a more important role. Onlyweight loss decreases GFR and stops the cascade of events thatare caused by glomerular hyperfiltration, which could slow theevolution toward irreversible renal damage.
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Abstract
Introduction
40 kg/m2) is a type of obesity that usually does not respond to medical treatment, with surgery being the current treatment of choice. Extreme obesity is associated with cardiovascular disease, type 2 diabetes, dyslipidemia, and hypertension. Recently, obesity has been related with high rate of renal lesions, but renal function and renal parameters in extreme obesity scarcely are documented. The objective of this study was to evaluate the effect of weight loss after bariatric surgery (BS) on BP, renal parameters, and renal function in 61 extremely obese (EO) patients after 24 mo of follow-up. A total of 61 EO adults (37 women) were studied prospectively before and 24 mo after surgery. Control subjects were 24 healthy, normal-weight adults (15 women). Anthropometric, BP, and renal parameters were determined. Presurgery weight, BMI, GFR, 24-h proteinuria, and 24-h albuminuria were higher in the EO patients than in control subjects (P < 0.001). All parameters improved at 12 mo after BS. However, during the second year of follow-up, only 24-h albuminuria (P = 0.006) and BMI (P = 0.014) continued to improve. At 24 mo after BS, obesity-related renal alterations considerably improved. This improvement was observed mainly in the first year after surgery, when the majority of weight loss occurred. However, 24-h albuminuria still improves during the second year of follow-up. It is possible that this decrease in 24-h albuminuria is not GFR related but rather is attributable to the persistence of the decrease in BMI and to the improvement of other weight-related metabolic factors. 
blockers, and nine with ACEI in combination with other drugs). Medications were withdrawn 8 d before the analyses were performed. All patients in the study had normal levels of serum creatinine (normal values in our laboratory 44 to 106 µmol/L), and none had a history of renal disease. 
2 test, as appropriate. Differences within the obese group before and after BS were evaluated with paired t test or the McNemar test, as appropriate. The t test was applied to the nonparametric data after log transformation. 
