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ObjectivesIGF1 is decreased in morbidly obese (MO) patients and its changes after bariatric surgery weight loss (WL) are not well known. The aim of this study was to analyse IGF1 modifications in MO patients after WL and its relationship to ghrelin and to different types of surgeries.DesignRetrospective follow-up study at the University Medical Center.MethodsOne hundred and nine MO patients (age 44.1±9.3, BMI 51.74±8.75 kg/m2) were evaluated at baseline and 1 year after surgery: 28 sleeve gastrectomy (SG), 31 distal modified (m), and 50 ringed (r) Roux-en-Y gastric bypass (RYGBP) surgery. Changes in IGF1, IGFBP3, ratio IGF1:IGFBP3, and ghrelin were evaluated 1 year after surgery.ResultsBaseline prevalence of low IGF1 (defined bys.d.IGF1PP=0.03) and did not change in RYGPBP techniques. The %albumin change was the only dependent variable associated with the % total IGF1 change.ConclusionsRecovery of low IGF1 after bariatric surgery was specifically related to the albumin modifications induced by surgery and was not related to ghrelin modifications.

Background/Aims: Glomerular kidney disease (GKD) is suspected in patients based on proteinuria, but its diagnosis relies primarily on renal biopsy. We used urine peptide profiling as a noninvasive means to link GKD-associated changes to each glomerular entity. Methods: Urinary peptide profiles of 60 biopsy-proven glomerular patients and 14 controls were analyzed by combining magnetic bead peptide enrichment, MALDI-TOF MS analysis, and ClinProTools v2.0 to select differential peptides. Tentative identification of the differential peptides was carried out by HPLC-MS/MS. Results: The HPLC-MS/MS results suggest that uromodulin (UMOD; m/z: 1682, 1898 and 1913) and α1-antitrypsin (A1AT; m/z: 1945, 2392 and 2505) are differentially expressed urinary peptides that distinguish between GKD patients and healthy subjects. Low UMOD and high A1AT peptide abundance was observed in 80–92% of patients with GKD. Proliferative forms of GKD were distinguished from nonproliferative forms, based on a combination of UMOD and A1AT peptides. Nonproliferative forms correlated with higher A1AT peptide levels – focal segmental glomerulosclerosis was linked more closely to high levels of the m/z 1945 peptide than minimal change disease. Conclusion: We describe a workflow – urinary peptide profiling coupled with histological findings – that can be used to distinguish GKD accurately and noninvasively, particularly its nonproliferative forms.

Canas L, Bayes B, Granada ML, Ibernon M, Porrini E, Benitez R, Diaz JM, Lauzurica R, Moreso F, Torres A, Lampreabe I, Serra A, Romero R. Is adiponectin a marker of preclinical atherosclerosis in kidney transplantation? Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01490.x. © 2011 John Wiley & Sons A/S. Abstract: The aim of this study was to analyze the relationship between pre-transplant adiponectin (pre-ADP), abnormalities in glucose homeostasis (AGH) at three months post-transplantation, and preclinical atherosclerosis in non-diabetic patients prior to kidney transplantation (KT). Methods: We carried out a multicenter study in 157 non-diabetic KT patients (66.5% men; age: 50 ± 13 yr). Pre-ADP levels were analyzed using radioimmunoassay. Carotid ultrasound was performed to determine carotid intima-media thickness (c-IMT). Oral glucose tolerance test was carried out to classify patients according ADA criteria. Results: Of the patients, 52.8% had AGH. Median pre-ADP was 19.5 (14–27) μg/mL. An inverse correlation was found between ADP and HOMA index (r = −0.432; p 0.6 mm had more AGH (p = 0.012) and lower ADP levels (p = 0.02). We performed a logistic regression analysis using preclinical atherosclerosis (c-IMT ≥0.6 mm) as dependent variable and sex, age, BMI, ADP, AGH, and HOMA index as independent variables of altered c-IMT. Age, pre-ADP, and AGH were independent risk factors for elevated c-IMT. Conclusions: Patients with AGH have a greater presence of preclinical atherosclerosis. ADP has an inverse relationship with AGH and is an independent marker of preclinical atherosclerosis.

Obesity and extreme obesity are associated with a wide range of well known comorbidities (cardiovascular disease, dyslipidemia, hypertension, diabetes mellitus, metabolic syndrome). Recently, the association between obesity and renal involvement has been accepted since several epidemiological and pathological studies support this relationship. However, the physiopathological mechanism of this association is not completely understood. Different mechanisms have been implicated in the production of these renal lesions. Between them, metabolic alterations and inflammatory adipocytokines have been suggested. This paper is a review of the association between inflammatory adipocytokines or metabolic syndrome with renal involvement. We also briefly report our experience in a cohort of extremely obese patients.

We studied the glomerular architecture in renal biopsies of 95 patients undergoing bariatric surgery for extreme obesity but whose renal function was normal. The comparison group was 40 control patients having protocol biopsies. These latter patients had normal weight and renal function, were non-diabetic, non-hypertensive, and were undergoing nephrectomy or donating a kidney. Logistic regression models determined associations between the clinical and biochemical variables and glomerular lesions. Arterial hypertension, sleep apnea syndrome (SAS), and microalbuminuria were prevalent in the obese patients, as was hyperglycemia to a lesser extent. Focal and segmental glomerulosclerosis was present in only five extremely obese (EO) patients but absent in controls. Increased mesangial matrix, podocyte hypertrophy, mesangial cell proliferation, and glomerulomegaly were more frequent in the obese cohort than in the control group. Body mass index was a significant independent risk factor associated with glomerular lesions in all 135 patients and in the 95 EO patients, whereas SAS was associated with glomerulomegaly only in the EO. Our study shows that EO patients who lack overt clinical renal symptoms have a variety of glomerular abnormalities that correlate with body mass.

Background New-onset diabetes mellitus after transplantation (NODAT) is a severe complication of kidney transplantation (KTx) with negative effects upon patient and graft survival. Several risk factors for NODAT have been described; however, the search for an early predictive marker is ongoing. It has recently been demonstrated that high concentrations of adiponectin (APN), which is an adipocyte-derived peptide with antiinflammatory and insulin-sensitizing properties, protect against future development of type 2 diabetes in healthy individuals. The purpose of this report was to study pretransplant insulin resistance and analyze pretransplant serum leptin and APN levels as independent risk factors for the development of NODAT. Methods A total of 68 KTx patients were studied [mean age, 48 +/- 11 years; 70% males; body mass index (BMI), 25 +/- 3 kg/m]; 31 KTx patients with NODAT and 37 KTx patients without NODAT (non-NODAT) with similar age, sex, BMI, immunosuppression, and posttransplant time were studied. All patients received prednisone and calcineurin inhibitors (75% tacrolimus and 25% cyclosporine A), and 76% of patients received mycophenolate mofetil. Family history of diabetes mellitus was recorded. Pretransplant homeostasis model assessment for insulin resistance (HOMA-IR) index was calculated from fasting plasma glucose and insulin. Pretransplant serum leptin and APN levels were determined by radioimmunoassay. Results NODAT patients showed higher pretransplant plasma insulin concentrations [NODAT, 13.4 (11-22.7) microIU/mL; non-NODAT, 10.05 (7.45-18.4) microIU/mL; P=0.049], HOMA-IR index [NODAT, 4.18 (2.49-5.75); non-NODAT, 2.63 (1.52-4.68); P=0.043], and lower pretransplant serum APN concentration [NODAT, 8.78 (7.2-11.38) microg/mL; non-NODAT, 11.4 (8.56-15.27) microg/mL, P=0.012]. Inverse correlations between APN and BMI (r=-0.33; P=0.014) and APN and HOMA-IR index (r=-0.39; P=0.002) and between APN and NODAT (r=-0.31; P=0.011) were observed. Multiple logistic regression analysis showed the patients with lower pretransplant APN concentrations to be those at greater risk of developing NODAT [Odds Ratio=0.832 (0.71-0.96); P=0.01]. Conclusion Pretransplant serum APN concentration is an independent predictive factor for NODAT development in kidney-transplanted patients.

The aim of this study was to analyze the relationship between pre-transplant adiponectin (pre-ADP), abnormalities in glucose homeostasis (AGH) at three months post-transplantation, and preclinical atherosclerosis in non-diabetic patients prior to kidney transplantation (KT).We carried out a multicenter study in 157 non-diabetic KT patients (66.5% men; age: 50±13 yr). Pre-ADP levels were analyzed using radioimmunoassay. Carotid ultrasound was performed to determine carotid intima-media thickness (c-IMT). Oral glucose tolerance test was carried out to classify patients according ADA criteria.Of the patients, 52.8% had AGH. Median pre-ADP was 19.5 (14-27) μg/mL. An inverse correlation was found between ADP and HOMA index (r=-0.432; p0.001). Median c-IMT was 0.6 (0.48-0.71) mm. Significant inverse correlation existed between ADP and c-IMT on both sides (p0.05). Patients with c-IMT0.6 mm had more AGH (p=0.012) and lower ADP levels (p=0.02). We performed a logistic regression analysis using preclinical atherosclerosis (c-IMT ≥0.6 mm) as dependent variable and sex, age, BMI, ADP, AGH, and HOMA index as independent variables of altered c-IMT. Age, pre-ADP, and AGH were independent risk factors for elevated c-IMT.Patients with AGH have a greater presence of preclinical atherosclerosis. ADP has an inverse relationship with AGH and is an independent marker of preclinical atherosclerosis.

Glomerular kidney disease (GKD) is suspected in patients based on proteinuria, but its diagnosis relies primarily on renal biopsy. We used urine peptide profiling as a noninvasive means to link GKD-associated changes to each glomerular entity.Urinary peptide profiles of 60 biopsy-proven glomerular patients and 14 controls were analyzed by combining magnetic bead peptide enrichment, MALDI-TOF MS analysis, and ClinProTools v2.0 to select differential peptides. Tentative identification of the differential peptides was carried out by HPLC-MS/MS.The HPLC-MS/MS results suggest that uromodulin (UMOD; m/z: 1682, 1898 and 1913) and α(1)-antitrypsin (A1AT; m/z: 1945, 2392 and 2505) are differentially expressed urinary peptides that distinguish between GKD patients and healthy subjects. Low UMOD and high A1AT peptide abundance was observed in 80-92% of patients with GKD. Proliferative forms of GKD were distinguished from nonproliferative forms, based on a combination of UMOD and A1AT peptides. Nonproliferative forms correlated with higher A1AT peptide levels - focal segmental glomerulosclerosis was linked more closely to high levels of the m/z 1945 peptide than minimal change disease.We describe a workflow - urinary peptide profiling coupled with histological findings - that can be used to distinguish GKD accurately and noninvasively, particularly its nonproliferative forms.

Statins are prescribed to reduce posttransplant dyslipidemia, which is frequent among kidney graft recipients. Their efficacy to reduce cholesterol levels has been accompanied by pleiotropic effects. Proteomics is the study of the expressed complement of proteins in tissues or biological fluids. It includes the identification of changes in proteins that occur in various states, eg, after drug administration. Our study objectives were: (1) to analyze the effect of atorvastatin (10 mg/d) on lipid profile, renal function, proteinuria, and inflammation parameters, such as C-reactive protein (CRP), and (2) to use proteomics to ascertain whether this treatment modified the patients' urinary peptide profiles seeking to understand the molecular actions of the drug. Urinary peptide profiles, lipids, renal function parameters (creatinine clearance), proteinuria, and CRP were determined in 39 patients at baseline and at 12 weeks after atorvastatin treatment (10 mg/d). The peptide fraction of each sample acquired using magnetic beads was analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Our results showed that treatment with atorvastatin produced a significant reduction in lipid profile, but did not modify renal function (creatinine clearance), proteinuria, or CRP. The proteomic study showed that statin treatment did not produce significant changes in the urinary peptidome, although there was a tendency for some peptides to increase or decrease after the treatment.

To study the effects of two variants of Roux-en-Y gastric bypass (RYGBP) on plasma ghrelin concentrations according to different exposure of gastric fundus to the nutrient pathway. A prospective longitudinal 2-year follow-up study was conducted. Ninety-six morbidly obese (MO) patients (age range: 41.6 ± 9.6 years, body mass index: 53 ± 9.5 kg/m2) were assigned to two bariatric surgical (BS) procedures: one that preserves food contact with gastric fundus (ringed RYGBP, n = 50) and the other that avoids it (modified RYGBP, n = 46). Different anthropometric and biochemical parameters were studied, focusing on ghrelin concentrations at baseline and 6, 12, and 24 months post-BS. At 24 months post-BS, all metabolic parameters studied had improved in all patients compared with those at 1-year follow-up and baseline (p

The high incidence of new-onset diabetes mellitus after transplantation (NODAT) suggests the need to find new factors to explain the pathogenesis. Our objectives were (1) to confirm that low levels of pre-transplant adiponectin are an independent risk factor for the development of NODAT in a larger transplanted population; (2) to analyze whether adiponectin is a better predictor of NODAT than other inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and pregnancy-associated plasma protein A (PAPP-A)) and (3) to assess the relationship between obesity, inflammatory markers and NODAT. One hundred ninety-nine non-diabetic patients (128 men; age: 53 +/- 11 years; body mass index (BMI) 24.98 +/- 3.76 kg/m2) were included. Pre-transplant plasma glucose, insulin, adiponectin, CRP, TNF-alpha, IL-6 and PAPP-A were measured. Forty-five patients developed NODAT. Patients with NODAT had a greater BMI (p = 0.005). Adiponectin was lower (p0.001) and CRP higher (p = 0.032) in patients with NODAT. Multivariate logistic regression and Cox analysis showed that the calcineurin inhibitor used, pre-transplant BMI and adiponectin were predictors of NODAT. ROC analysis showed that an adiponectin concentration of 11.4 microg/mL had a significant negative prediction for NODAT risk (sensitivity: 81% and specificity: 70%). Of the inflammatory markers studied, adiponectin proved to be an independent predictor of NODAT.

Obesity is a health problem that is reaching epidemic proportions. Extreme obesity (body mass index [BMI] > or =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.

Summary Aims To evaluate the effect of weight loss after bariatric surgery (BS) on peripheral adipocytokines, renal parameters and other cardiovascular risk factors (CVRFs). Methods A total of 70 (41 women) extremely obese adults were prospectively studied before and 12 months after surgery. Controls: 24 (15 women) normal-weight adults. Anthropometric, biochemical and renal parameters were recorded. Results Presurgery, adiponectin (ADPN) was lower, whereas leptin, insulin resistance, C-reactive protein, creatinine clearance and albuminuria were higher in patients than controls ( P 0.001 ). All parameters improved postsurgery. Changes in ADPN correlated negatively with leptin, insulin resistance, albumin, C-reactive protein, and creatinine clearance. Multiple regression analysis: using changes in ADPN as the dependent variable, only changes in insulin resistance ( P = 0.005 ) and albumin ( P = 0.019 ) were significant independent determinants for changes in ADPN. No statistical differences were found in relation to the degree of obesity. Conclusion Patients changed to obesity type I after surgery. This implies a substantial improvement of CVRFs including ADPN, creatinine clearance and albuminuria. Changes in plasma ADPN correlated negatively with insulin resistance and with albuminemia but not with renal parameters. The lack of differences between different degrees of obesity suggests that the relationship between weight and CVRFs no longer exists when obesity becomes very extreme.

Criteria for renal biopsy in proteinuric type 2 diabetes mellitus (T2DM) patients have been not defined. Usually criteria for renal biopsy in type 1 diabetes mellitus (T1DM) are used (microhaematuria, absence of diabetic retinopathy (DR), uncharacteristic change in renal function or immunological abnormalities). The aim of this study was to reconsider the indications for renal biopsy in T2DM using T1DM criteria, to determine whether they are useful in identifying patients with potentially treatable lesions. We studied 127 proteinuric patients with T2DM. Renal biopsy was performed in 35 who met the criteria for biopsy. Biopsy revealed diabetic glomerulopathy (DG) in 29 (83%) (in three associated with nondiabetic renal disease), immunoglobulin A (IgA) glomerulonephritis in three, focal glomerulosclerosis in one and normal glomeruli in two. DG was diagnosed in 17 (74%) of the patients without DR, in 18 (78%) of the patients with microhaematuria and in 10 (67%) of the patients with microhaematuria and without DR. All patients with DR had DG alone, except three with sudden unexpected changes in renal function. We conclude that DG is the most commonly found renal lesion in T2DM patients with proteinuria biopsied according to T1DM criteria, even in patients with microhaematuria or without retinopathy. Thus, these biopsy criteria are not useful in identifying patients with potentially treatable other renal diseases.

Publisher Summary This chapter discusses the issue of renal vasculitis in the aged. The subject of renal vasculitis in the elderly comprises: (1) its incidence above 60 years of age, (2) the clinical features of the vasculitides in the elderly compared with those of patients under 60 years of age, (3) identification of the types of vasculitis that are specially prevalent in this period of life and, conversely, that forms are seldom seen in this population. The chapter discusses the problems in the definition, nomenclature, and the pathology and pathogenesis of renal vasculitis. The survival of those with this disease aged over 60 is poorer than younger patients, partly because of less aggressive treatment. Immunosuppressive agents have improved on the results obtained with corticosteroids, and plasma exchange seems likely to improve these still further. Even so, up to half of the patients with renal vasculitis die, the majority within the first year.

We appreciate the comments of Dr Bomback and Dr Klemmer on the possible relationship between aldosterone and obesity-related renal lesions.1