Long-Term Normal Renal Function after Drastic Weight Reduction in Patients with Obesity-Related Glomerulopathy

No long-term studies of renal function evolution in morbidly obese (MO) patients after weight loss are available. The aim of our work was to ascertain the long-term influence of drastic weight reduction on renal function in MO patients with obesity-related glomerular lesions. 92 MO patients with normal renal function and biopsy evidence of mild obesity-related glomerulopathy underwent bariatric surgery (BS) and subsequent drastic weight loss. A long-term prospective follow-up (mean duration: 76 ± 42 months) was carried out. Basal renal biopsies and basal and long-term metabolic and renal function studies were performed in all cases. Linear mixed models were applied. Blood pressure dropped early after BS and remained stable thereafter. Creatinine clearance and BMI fell in the first 2 years, rose slightly after 5 years and then remained stable. Serum creatinine and albuminuria decreased throughout the follow-up period. Renal function and albuminuria evolution showed non-significant differences in relation to the number of glomerular lesions. Drastic weight loss in BS-treated MO patients with pre-surgical normal renal function and mild obesity-related glomerular lesions is associated with short- and long-term maintenance of normal renal function and improvement in both arterial hypertension and albuminuria

Ambrisentan use in a HIV-1 infected patient with end-stage renal disease and pulmonary hypertension : minimal removal by hemodialysis - a case report

Ambrisentan is a selective endothelin receptor antagonist used for the treatment of pulmonary arterial hypertension (PAH). Little is known about ambrisentan removal by hemodialysis in patients with end-stage renal disease (ESRD). A 53-year-old woman with HIV/hepatitis C virus (HCV) co-infection, PAH and ESRD on regular hemodialyis was admitted in our hospital due to refractory heart failure while on treatment with bosentan (125 mg twice daily) and tadalafil (20 mg once daily) for PAH and antiretroviral treatment (cART) including darunavir/cobicistat (800/150 mg once daily). Excessive exposure to bosentan due to drug interactions between bosentan and darunavir/cobicistat was suspected. Bosentan was replaced by ambrisentan, with progressive improvement in her clinical condition. Pre- and postdialyzer cocentrations of ambrisentan in plasma were determined and hemodialysis extraction ratio for ambrisentan was 2%. Our results suggest that hemodialysis results in minimal ambrisentan removal, and therefore no specific ambrisentan dosage adjustment seems to be required in ESRD patients undergoing hemodialysis

Gut microbiome in hemodialysis patients treated with calcium acetate or treated with sucroferric oxyhydroxide : a pilot study

It has been proved that the gut microbiome is altered in patients with chronic kidney disease. This contributes to chronic inflammation and increases cardiovascular risk and mortality, especially in those undergoing hemodialysis. Phosphate binders may potentially induce changes in their microbiome. This trial aimed to compare the changes in the gut microbiome of hemodialysis patients treated with calcium acetate to those treated with sucroferric oxyhydroxide. Twelve hemodialysis patients were distributed to receive calcium acetate or sucroferric oxyhydroxide for 5 months. Blood samples (for biochemical analysis) and stool samples (for microbiome analysis) were collected at baseline, 4, 12, and 20 weeks after treatment initiation. Fecal DNA was extracted and a 16S rRNA sequencing library was constructed targeting the V3 and V4 hypervariable regions. Regarding clinical variables and laboratory parameters, no statistically significant differences were observed between calcium acetate or sucroferric oxyhydroxide groups. When analyzing stool samples, we found that all patients were different (p = 0.001) among themselves and these differences were kept along the 20 weeks of treatment. The clustering analysis in microbial profiles grouped the samples of the same patient independently of the treatment followed and the stage of the treatment. These results suggest that a 5-month treatment with either calcium acetate or sucroferric oxyhydroxide did not modify baseline diversity or baseline bacterial composition in hemodialysis patients, also about the high-variability profiles of the gut microbiome found among these patients

Long-Term Normal Renal Function after Drastic Weight Reduction in Patients with Obesity-Related Glomerulopathy

Aims: No long-term studies of renal function evolution in morbidly obese (MO) patients after weight loss are available. The aim of our work was to ascertain the long-term influence of drastic weight reduction on renal function in MO patients with obesity-related glomerular lesions. Methods: 92 MO patients with normal renal function and biopsy evidence of mild obesity-related glomerulopathy underwent bariatric surgery (BS) and subsequent drastic weight loss. A long-term prospective follow-up (mean duration: 76 ± 42 months) was carried out. Basal renal biopsies and basal and long-term metabolic and renal function studies were performed in all cases. Linear mixed models were applied. Results: Blood pressure dropped early after BS and remained stable thereafter. Creatinine clearance and BMI fell in the first 2 years, rose slightly after 5 years and then remained stable. Serum creatinine and albuminuria decreased throughout the follow-up period. Renal function and albuminuria evolution showed non-significant differences in relation to the number of glomerular lesions. Conclusions: Drastic weight loss in BS-treated MO patients with pre-surgical normal renal function and mild obesity-related glomerular lesions is associated with short- and long-term maintenance of normal renal function and improvement in both arterial hypertension and albuminuria

Vesículas extracelulares en orina como fuente no invasiva de material biológico para la monitorización de pacientes trasplantados /

Departament responsable de la tesi: Departament de Medicina.El trasplante renal es el tratamiento de elección para los pacientes con enfermedad renal crónica avanzada. Aunque la tasa de supervivencia del injerto renal al año supera el 90%, se ha estimado que a los 5 años una cuarta parte de los pacientes trasplantados no tendrán un injerto renal funcionante. En la práctica clínica habitual, para valorar el injerto renal se están utilizando parámetros de laboratorio como la creatinina sérica, el filtrado glomerular y la proteinuria. Sin embargo, su alteración en muchas ocasiones es tardía y no permite discernir entre diferentes patologías. La biopsia renal sigue siendo el gold standard de diagnóstico en la patología del riñón trasplantado. No obstante, es una técnica invasiva, no exenta de complicaciones y con una repetibilidad limitada. Por lo tanto, existe una necesidad de desarrollar métodos de diagnóstico alternativos. El objetivo de este trabajo fue el de evaluar el uso de las vesículas extracelulares en orina como fuente no invasiva de miRNAs, que permita un diagnóstico precoz, así como una monitorización frecuente y precisa del paciente trasplantado. La orina de los pacientes trasplantados contiene vesículas extracelulares cuyo perfil transcriptómico, en particular su contenido de miRNAs, refleja el estado fisiopatológico del riñón. En el trabajo actual, tras obtener el RNA de las vesículas extracelulares de orina, detectamos 12 miRNAs diferencialmente expresados en el grupo de pacientes con disfunción del injerto y el grupo control de pacientes trasplantados con función renal normal. Se objetivó que la combinación de 5 de los miRNAs estudiados podría representar un buen test diagnóstico para detectar una alteración de la función renal en el paciente trasplantado renal.Exploramos la capacidad de cada uno de los miRNAs de discernir entre los distintos diagnósticos histológicos que presentaron los pacientes incluidos en el estudio (rechazo agudo celular, fibrosis intersticial/ atrofia tubular, toxicidad crónica por anticalcineurínicos). Dos de los miRNAs analizados mostraron utilidad en discriminar entre los pacientes con rechazo agudo celular y el grupo control, así como entre los pacientes con rechazo agudo celular y los pacientes que presentaban las otras dos patologías analizadas. Otros dos miRNAs analizados permitieron discriminar pacientes con fibrosis intersticial/ atrofia tubular.La utilidad de nuestros hallazgos reside en la posibilidad de detectar mediante un método completamente no invasivo la presencia de alteraciones en el riñón trasplantado. Nuestros resultados, aún preliminares, deberían ser validados en estudios futuros.Kidney transplantation is the treatment of choice for patients with advanced chronic kidney disease. Although the renal graft survival at one year exceeds 90%, it has been estimated that at 5 years a quarter of the transplanted patients will not have a functioning renal graft. In routine clinical practice, laboratory parameters such as serum creatinine, glomerular filtration rate and proteinuria are being used to evaluate the renal graft. However, the alteration of these parameters is often late and they cannot distinguish between different pathologies. Renal biopsy is an invasive technique and its consequently associated with and increased risk of complications; in addition, it is a method of limited repeatability. Still, it remains the gold standard of diagnosis in the pathology of the transplanted kidney. Therefore, there is a need for developing alternative diagnostic methods. The aim of this study was to evaluate the use of urine microvesicles as a non-invasive source of miRNAs that could allow an early diagnosis, as well as a frequent and accurate monitoring of the transplanted patients. The urine of the transplanted patients contains extracellular vesicles whose transcriptomic profile, in particular its miRNA content, reflects the physiopathological state of the kidney. In the present work, we detected 12 miRNAs that were differentially expressed in the group of patients with graft dysfunction and the control group of transplanted patients with normal renal function. We observed that the combination of 5 of the miRNAs could represent a good diagnostic test to detect alterations of the renal function in the kidney transplanted patient. Next, we explored the ability of each of the miRNAs to distinguish between three different histological diagnoses found in patients included in the study (acute rejection, interstitial fibrosis/ tubular atrophy and chronic anti-calcineurin toxicity). Two of the analysed miRNAs showed utility in discriminating between patients with acute cellular rejection and the control group, as well as between patients with acute cellular rejection and patients who presented another pathology. Two of the analysed miRNAs discriminated patients with interstitial fibrosis / tubular atrophy. The usefulness of our findings lies in the possibility of detecting alterations in the transplanted kidney by a completely non-invasive method. Our results, yet preliminary, should be validated in future studie

Low Insulin-Like Growth Factor-1 Level in Obesity Nephropathy: A New Risk Factor?

INTRODUCTION: IGF-1 (insulin-like growth factor-1) is a hormone involved in cell growth and other important processes. In the kidney, IGF-1 has a stimulating effect, increasing the blood flow and glomerular filtration rate. Although many experimental animal studies regarding the role of IGF-1 in the kidney have been conducted, few human studies are available in the literature. Obesity is a cause of renal failure, and several glomerular lesions associated with obesity have been described. However, no studies regarding the levels of IGF-1 in morbidly obese patients with renal injury associated with obesity have been conducted. AIM: To determine the serum IGF-1 concentrations in morbidly obese patients with normal renal function but with different types of early obesity-related glomerular lesions and to evaluate the possible relationship between IGF-1 and the presence of renal lesions. METHODS: Eighty morbidly obese patients with renal biopsy, including 11 patients with no evidence of renal lesion, 17 patients with single glomerulomegaly, 21 patients with single podocyte hypertrophy, 10 patients with glomerulomegaly and podocyte hypertrophy, 5 patients with focal segmental hyalinosis, and 16 patients with increased mesangial matrix and/or mesangial proliferation, participated in this study. Biological parameters, including serum IGF-1 concentrations with the standard deviation score for age (SDS-IGF-1), were determined for all patients. RESULTS: Eighty patients (50 women and 30 men) with a mean BMI of 52.63 ± 8.71 and a mean age of 42.40 ± 9.45 years were included in this study. IGF-1, IGF-1 SDS and IGF-1BP3 levels according to the renal injury were compared (normal glomeruli: IGF-1 = 190.17 ± 72.46; glomerulomegaly: IGF-1 = 122.3 ± 50.05; podocyte hypertrophy: IGF-1 = 119.81 ± 60.34; focal segmental hyalinosis: IGF-1 170.98 ± 100.83, increased mesangial matrix and/or mesangial proliferation: IGF-1 117.73 ± 63.87). Statistically significant differences were observed between serum levels of IGF-1 and between the levels of SDS-IGF-1 by comparing the group without glomerular lesion with the group formed by patients with any type of glomerular injury. Logistic regression analysis was performed, with the dependent variable defined as the glomerular injury. In the multivariate analysis, only SDS-IGF-1 was associated with glomerular injury, and low levels of IGF-1 SDS were a risk factor for kidney injury. CONCLUSIONS: Our study demonstrates that low IGF-1 serum levels are associated with renal lesions in morbidly obese patients without overt clinical renal manifestation

Traumatic Intralenticular Neovascularization in a HLA B27+ Pediatric Patient

(1) Background: Intralenticular tumors are an entity akin to Schrodinger’s cat since, although the human crystalline cells themselves are not known to malignly proliferate, various entities can take the appearance and clinical presentation of a tumor originating in the lens. We present the peculiar case of an 11-year-old male patient of African descent, HLA B27+, with a previous history of minor ocular trauma and unilateral anterior uveitis a year before which was admitted to our department with total opacification of the crystalline lens in the right eye and lens neovascularization. During surgery, a vascular, white fibrotic mass measuring 0.1–0.2 cm was discovered inside the lens bag and was excised. (2) Methods: Retrospective case review. (3) Results: The histopathological exam of the excised mass revealed an abundant infiltrate consisting of CD68+ foamy macrophages and lymphoplasmacytic elements. CD68 is a pan-macrophage marker associated with an active inflammatory mechanism soliciting macrophages, and tissue activated macrophages are correlated to increased stromal and serum levels of vascular endothelial growth factor, providing an explanation for lens angiogenesis. (4) Conclusions: The diagnosis is of a “masquerade tumor” resulted from an abnormal inflammatory process in connection with previous ocular trauma and possibly the patient’s HLA B27+ status

Frail Patient in Hemodialysis: A New Challenge in Nephrology—Incidence in Our Area, Barcelonès Nord and Maresme

Introduction. Labeling a patient as “frail” may be useful in assessing the prognosis and therapeutic approach. Objective. The aim of the study is to define a pattern of frailty among our dialysis population, to analyse the incidence and clinical evolution of these patients. Materials and Methods. We analysed a total of 320 patients with stage V chronic kidney disease (CKD) who were on hemodialysis between September 2014 and September 2015. To define a patient as frail we used the Fried phenotype model, and we added a new criteria-dialysis session length longer than 12 hours/week. Results. 5.6% of the 320 patients were frail. We found statistically significant differences regarding body mass index (BMI), hemoglobin (Hgb), and serum albumin, as well as the ability to perform the basic activities of daily living (p<0.005), ability to ambulate (p=0.01) and perform transfers (p<0.005). We found statistically significant differences between the two groups in terms of hospital admissions (p=0.005) and mortality (p<0.005). Conclusion. 5.6% of the study population were frail, with lower BMI, serum albumin and hemoglobin, lower capacity for basic activities of daily living, ambulation, and transference, as well as higher morbidity and mortality