Maruja Navarro

Renal injury in the extremely obese patients with normal renal function

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.

Uromodulin and α1-Antitrypsin Urinary Peptide Analysis to Differentiate Glomerular Kidney Diseases

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.

Urinary Peptide Profiling to Differentiate between Minimal Change Disease and Focal Segmental Glomerulosclerosis

Background Minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS) are the main causes of primary idiopathic nephrotic syndrome in children and adults, with diagnosis being essential for the appropriate choice of therapy and requiring renal biopsy. However, the presence of only normal glomeruli on renal biopsy of FSGS patients may lead to the misclassification of these patients as having MCD. The aim of this study was to (i) compare the peptide profile of MCD and FSGS patients with that of a group of healthy subjects, (ii) generate and validate a class prediction model to classify MCD and FSGS patients and (ii) identify candidate biomarkers of these glomerular entities by analysis of the urinary peptidome. Methods The urinary peptide profile was analyzed by magnetic bead-based technology combined with MALDI-TOF mass spectrometry in 44 patients diagnosed of MCD (n = 22) and FSGS (n = 22). The resulting spectra were compiled and analyzed using ClinProTools software. Results A class prediction model was developed to differentiate MCD and FSGS patients. The validation of this model correctly classified 81.8% (9/11) of MCD patients and 72.7% (8/11) of FSGS patients. Moreover, the signal with m/z 1913.60, identified as a fragment of uromodulin, and the signal with m/z 2392.54, identified as a fragment of alpha-1-antitrypsin, showed higher and lower peak areas, respectively, in FSGS patients compared with MCD patients. Conclusions The simple, non-invasive technique described in the present study may be a useful tool to help clinicians by confirming diagnoses achieved by renal biopsy, thereby reducing misdiagnoses and avoiding the implementation of inappropriate therapies.

IGF1 modifications after bariatric surgery in morbidly obese patients: potential implications of nutritional status according to specific surgical technique.

OBJECTIVES IGF1 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. DESIGN Retrospective follow-up study at the University Medical Center. METHODS One hundred and nine MO patients (age 44.19.3, BMI 51.748.75KG/M(2)) 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. RESULTS Baseline prevalence of low IGF1 (defined by s.d. IGF1<-2) was 22%, and %WL 1 year after surgery was 34.9±8.9%. There was a significant decrease in IGFBP3 in all the procedures, an increase in IGF1:IGFBP3 ratio in rRYGBP and SG, but total IGF1 only increased significantly in SG. Albumin concentrations decreased in mRYGBP, did not change in rRYGBP, but increased in SG after surgery. Total ghrelin concentrations increased after both RYGBPs and decreased after SG (P<0.05 in all cases). The prevalence of low IGF1 decreased in SG (28.6 vs 10.1%, P=0.03) and did not change in RYGPBP techniques. The %albumin change was the only dependent variable associated with the % total IGF1 change. CONCLUSIONS Recovery of low IGF1 after bariatric surgery was specifically related to the albumin modifications induced by surgery and was not related to ghrelin modifications.

Postinfectious glomerulonephritis secondary to Erythrovirus B19 (Parvovirus B19): case report and review of the literature.

A previously healthy 32-yearold woman developed arterial hypertension, proteinuria, and hematuria (nephritic syndrome) with normal renal function and was diagnosed with post-infectious glomerulonephritis secondary to parvovirus B19 infection. The renal biopsy showed endocapillary glomerulonephritis, with positive IgG, C3, and C1q immunoreactivity in the capillary walls and ultrastructural evidence of subendothelial deposits. The diagnosis of parvovirus B19 infection was confirmed by IgG/IgM serological positivity and parvovirus DNA demonstration in both peripheral blood and kidney tissue. Glomerular involvement improved spontaneously. To be noted are the atypical signs and symptoms of our patient who, unlike previously reported cases, failed to show fever, skin rash, or affected relatives.

Neumonía eosinófila crónica: a propósito de una observación

Objetivo La enfermedad pulmonar eosinofila constituye un grupo variado de patologia pulmonar que tiene en comun un aumento en los eosinofilos circulantes o titulares acompanado de sintomas pulmonares o de alteraciones en la radiografia de torax. Nuestro objetivo es presentar el caso clinico de una bronconeumopatia cronica con eosinofilia, patologia muy poco frecuente en edad pediatrica. Material y metodo Nino de 13 anos de edad diagnosticado de asma bronquial extrinseca con sensibilizacion a olivo, gramineas y alternaria, con evolucion torpida a pesar de tratamiento con broncodilatadores y corticoides orales en fase aguda y mantenimiento con montelukast, broncodilatadores de larga duracion y corticoides inhalados, por lo que es derivado a nuestro servicio. En la anamnesis refiere tos persistente de 8 meses de evolucion asociada a episodios de fiebre, dificultad respiratoria y astenia generalizada recidivantes. Antecedentes personales y familiares sin interes. A la exploracion presenta tos productiva con esputos espesos con forma de moldes, de color marron claro, auscultandose estertores crepitantes y sibilancias aisladas. Asocia marcada eosinofilia (30,9 %) e infiltrados alveolares bilaterales de predominio en lobulos superiores en radiografia de torax. Se completo el estudio de este proceso de bronconeumopatia cronica con eosinofilia con una espirometria basal forzada de patron restrictivo y test de broncodilatacion negativo. Pletismografia que confirmaba el aumento de gas intratoracico. TACAR con patron en mosaico e impactaciones mucosas junto a dilataciones bronquiales de predominio en lobulos superiores y nodulos centrolobulillares de aspecto “arbol en brotes”. La gammagrafia de perfusion pulmonar presentaba defectos de perfusion no segmentarios en ambos campos pulmonares. IgE 200 U/ml, rast a Aspergillus, serologia a parasitos y Mantoux negativo. Fibrobroncoscopia que visualizo autenticos moldes de moco, y lavado broncoalveolar que demostro que estaban compuestos por un 95 % de eosinofilos, siendo todo ello concordante con neumonia eosinofila cronica (NEC). Resultados Se inicio tratamiento con corticoides orales a 1 mg/kg/dia durante 4 meses siguiendo pauta descendente (5 mg de dosis total cada 14 dias), hasta realizar un total de 8 meses. Se observo mejoria clinica, analitica, radiologica y de funcion pulmonar durante el tratamiento presentando recidiva en pauta de descenso, antes de la suspension. Conclusiones La NEC es una entidad de baja frecuencia en pediatria, que debemos sospechar ante una historia clinica y una exploracion compatibles asi como infiltrados pulmonares bilaterales persistentes de predominio el lobulos superiores y eosinofilia periferica, siendo de gran utilidad para el diagnostico la fibrobroncoscopia con lavado broncoalveolar. Aunque la respuesta al tratamiento es precoz y efectiva se han descrito recidivas hasta en el 80 % de los casos.