Are Tacrolimus Pharmacokinetics Affected by Nephrotic Stage?

BACKGROUND: Although tacrolimus therapy is not the first-line therapy for childhood nephrotic syndrome, it is often used instead of cyclosporine to ameliorate the side effects. The pharmacokinetics (PK) of tacrolimus (Tac) can be influenced by many conditions, and it has a high plasma protein binding. The Tac PK during relapse and remission of childhood nephrotic syndrome has not been well described. METHODS: We performed 14 PK profiles (with measurements before intake and 0.5, 1, 2, 4, and 12 hours postintake) in 7 children with steroid-resistant nephrotic syndrome at week 1 (all nephrotic) and week 16 after Tac therapy (all in remission). These data were compared with historical PK data of 161 PK profiles in 87 pediatric renal transplant recipients with measurements before intake and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postintake. Tac levels were measured using the Abbott Tacro II assay. We used descriptive statistics to generate percentiles and compared these with those of patients with steroid-resistant nephrotic syndrome. RESULTS: The median age of patients with nephrotic syndrome was 3.2 years (range 2.5, 17.2), male gender 71.4%, significantly younger than the control group. Median Tac dose was similar during both PK profiles (0.11 mg·kg·d at week 1 versus 0.13 mg·kg·d at week 16, P = 0.81). There were no statistically significant differences in median dose-normalized area-under-the-time-concentration profiles, peak concentration, time to reach peak concentration, and Tac trough levels. Individual dose-normalized Tac levels for each time point during the PK profile were also not different (P = 0.81). CONCLUSIONS: We conclude that Tac PK profiles are unaltered during relapse of nephrotic syndrome.

Post-renal transplant erythrocytosis: a case report.

PTE is defined as hematocrit >51% or hemoglobin >17 g/dL after renal transplantation. Risk factors include native kidneys with adequate erythropoiesis pretransplant, smoking, renal artery stenosis, and cyclosporine treatment. We report the case of a 14-yr-old female kidney transplant patient, with triple therapy immunosuppression and stable graft function who developed PTE at 12 months post-transplant with hemoglobin 17.3 g/dL, hematocrit 54.2%, stable graft function, and normotensive with normal cardiac echocardiogram and erythropoietin levels. The only risk factor found was tobacco use. As she had no spontaneous improvement, enalapril treatment was started at 19 months post-transplant with a hemoglobin level of 17.5 g/dL and hematocrit 53%; by 23 months post-transplant, hemoglobin lowered to 15 g/dL and hematocrit to 44.5% and continued to be in normal range thereafter. PTE is a rare condition in childhood and can be successfully treated with enalapril.

Urinary MCP-1/creatinine in Henoch-Schönlein purpura and its relationship with nephritis.

BACKGROUND: Monocyte chemotactic protein-1 (MCP-1) plays a direct role in the infiltration of macrophages and monocytes during the early stages of Henoch-Schönlein purpura (HSP) nephritis. The aim of this study was to compare the urinary MCP-1/creatinine levels in children with and without HSP nephritis and determine if they are associated with the severity of renal lesions. METHODS: We included 77 patients with HSP and 25 healthy control children. Levels of serum creatinine, urinalysis, and 12-h proteinuria assessments were performed. Urinary MCP-1 levels were determined by ELISA. RESULTS: Fifty-seven patients had nephritis (74 %). Urinary MCP-1/creatinine levels were significantly higher in patients with HSP nephritis (median, 653 pg/mg) compared to those with HSP without nephritis (median, 269 pg/mg) or healthy children (191 pg/mg). In addition, higher MCP-1/creatinine levels were observed in HSP patients who had renal biopsy (median, 1,412 pg/mg) in comparison to HSP patients without renal biopsy (median, 302 pg/mg). The urinary MCP-1 cut-off value of 530 pg/mg could be used to distinguish patients who undergo renal biopsy with a sensitivity of 81 % and specificity of 77 %. CONCLUSIONS: Urinary MCP-1/creatinine levels are elevated in the early stages of severe HSP nephritis and can be used as a biomarker for HSP nephritis.

Prevalence of metabolic syndrome and obesity in renal transplanted Mexican children.

The purpose of the study was to evaluate the prevalence of MS and obesity in Mexican children with more than one yr post-renal transplantation. Thirty-two children transplanted between January 2004 and February 2006 were included in the study. The weight and height at the time of renal transplant were obtained. A fasting blood sample was drawn for serum creatinine, adiponectin, and complete lipid profile, and a three-h glucose tolerance test was also taken. A complete nutritional evaluation was performed including anthropometry. There was a statistically significant increase in BMI at one yr post-transplant that was maintained at two yr post-transplant. Three patients exhibited obesity and were overweight. Seventeen patients had hypertension, 14 patients had low HDL, 12 patients had hypertriglyceridemia, all had normal fasting glucose, six of them had glucose intolerance, and two had waist circumference higher than 90%. Eight patients (25%) had MS. Patients with MS had higher proportion of deceased donor grafts, acute rejection episodes, and received more methylprednisolone pulses; also they had a statistically significant higher pretransplant BMI than patients without MS. There was a significant relationship between BMI at one yr post-renal transplant and creatinine clearance estimated by Schwartz formula.

[Focal segmental glomerulosclerosis related to BK virus in a child with nephrotic syndrome. A case report]. / Glomerulopatía colapsante asociada a virus BK en un niño con síndrome nefrótico idiopático. Informe de un caso.

BACKGROUND: focal segmental glomerulosclerosis (FSGS) is observed in about 10 % of children with idiopathic nephrotic syndrome; this disorder is usually resistant to corticoid therapy. In the last few years, five histological types of FSGS have been recognized; the collapsing nephropathy type is characterized by a rapid evolution to chronic renal failure. CLINICAL CASE: a four-year-old boy presented with an irrelevant past history; eight months before admission he developed idiopathic nephrotic syndrome. He was treated with steroids without improvement, and a renal biopsy was performed in which minimal glomerular changes were found. Despite combined immunosuppressive treatment, he developed renal failure, septic shock and death. Collapsing nephropathy was demonstrated by immunohistochemistry, light and electron microscopy; renal new human papovirus (BK) infection was also found in the postmortem study. CONCLUSIONS: collapsing nephropathy is an aggressive disorder resistant to immunosuppressive treatment, as occurred in our patient. Although some viral diseases have been associated with collapsing nephropathy, to our knowledge, BK infection has not been previously described in those patients.

Randomized Controlled Trial of Mineralocorticoid Receptor Blockade in Children with Chronic Kidney Allograft Nephropathy.

BACKGROUND AND OBJECTIVES: We showed that mineralocorticoid receptor blockade (MRB) prevented acute and chronic cyclosporine nephropathy (CsA-Nx) in the rat. The aim of this translational study was to investigate the effect of long-term eplerenone administration on renal allograft function in children with biopsy-proven chronic allograft nephropathy (CAN). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Renal transplant children <18 years, biopsy-proven CAN, and a GFR>40 ml/min per 1.73 m2 were included. Patients with BK virus active nephritis, recurrence of renal disease, GFR decline in previous 3 months, or treated with calcium antagonists or antifungal drugs were excluded. They were randomized to receive placebo (n=10) or eplerenone 25 mg/d for 24 months (n=13). Visits were scheduled at baseline, 6, 12, and 24 months. At each period, a complete clinical examination was performed and blood and urine samples were taken. Urine creatinine, 8-hydroxylated-guanosine, heat shock protein 72 (HSP72), and kidney injury molecule (KIM-1) levels were also assessed. In kidney biopsy samples, the tubulo-interstitial area affected by fibrosis (TIF) and glomerulosclerosis were measured at baseline and after 24 months. RESULTS: The baseline eGFR was 80±6 in the placebo and 86±6 ml/min per 1.73 m2 in the eplerenone group; at 24 months it was 66±8 and 81±7 ml/min per 1.73 m2, respectively (P=0.33; 95% confidence intervals, -18 to 33 at baseline, and -11 to 40 after 24 months). The albumin-to-creatinine ratio was 110±74 in the placebo, and 265±140 mg/g in the eplerenone group; and after 24 months it was 276±140 and 228±88 mg/g, respectively (P=0.15; 95% confidence intervals, -283 to 593, and -485 to 391, respectively). In addition, the placebo exhibited a greater TIF, glomerulosclerosis, and urinary HSP72 compared with the eplerenone group. CONCLUSIONS: Although this study was underpowered to provide definitive evidence that long-term eplerenone administration attenuates the progression of CAN in pediatric transplant patients, it encourages testing the potential benefit of MRB in this pediatric population.

[Long term follow up of a patient with type I vitamin D-dependent rickets]. / Seguimiento a largo plazo de un paciente con raquitismo dependiente de vitamina D tipo I.

BACKGROUND: Vitamin D dependent rickets type I is a rare hereditary disease due to a mutation in CYP27B1 encoding the 1α-hydroxylase gene. Clinically, the condition is characterized by hypocalcemic rickets in early infancy due to a deficit in the production of the vitamin D active metabolite 1,25-dihydroxy-vitamin D3. CASE REPORT: We report the case of a patient diagnosed at 11 months with follow-up until 9 years of age. CONCLUSIONS: The pathophysiology of the disease and the relevance of early diagnosis and management are discussed.

[Prevalence of kidney disease in asymptomatic children with family history of renal replacement therapy]. / Prevalencia de enfermedad renal en niños aparentemente sanos con antecedente familiar de terapia de reemplazo renal.

BACKGROUND: Having a first- or second-degree relative with chronic kidney disease (CKD) has been reported as a risk factor for CKD development. The aim of the study was to determine the prevalence of CKD in children with a first- or second-degree relative undergoing renal replacement therapy (hemodialysis or renal transplant). METHODS: A screening study was performed in asymptomatic children with a family history of CKD in a first- or second-degree relative undergoing renal replacement therapy. Informed consent was obtained in all cases. A clinical examination was performed. Blood and urine samples were obtained for serum creatinine, serum electrolytes, urinalysis, and microalbumin/creatinine ratio. RESULTS: There were 45 subjects included with a median age of 9.6 years; 24 (53%) were male. Urinary abnormality/CKD was observed in 11 subjects (24.4%). The most common urinary abnormalities were hematuria (6/11) and microalbuminuria (4/11). Stage 2 CKD was found in seven subjects and four subjects with stage 1 CKD. CONCLUSIONS: The study of families of patients undergoing renal replacement therapy is useful to identify children in early stages of kidney disease.

[Nephrogenic diabetes insipidus]. / Diabetes insípida nefrogénica.

The anti-diuretic hormone arginine-vasopressin (AVP) is released from the pituitary and regulates water reabsorption in the principal cells of the kidney collecting duct. Binding of AVP to the arginine-vasopressin receptor type-2 in the basolateral membrane leads to translocation of aquaporin-2 water channels to the apical membrane of the principal cells of the collecting duct, inducing water permeability of the membrane. This results in water reabsorption in the collecting duct of the nephron following an osmotic gradient. Nephrogenic diabetes insipidus is caused by partial or complete renal resistance to the effects of AVP. Congenital nephrogenic diabetes insipidus is a disorder associated with mutations in either the AVPR2 or AQP2 gene, causing the inability of patients to concentrate their urine. Acquired nephrogenic diabetes insipidus can be caused by electrolyte imbalances (e.g., hypercalcemia, hypokalemia), renal/extra-renal diseases and drugs (e.g., lithium toxicity). This article reviews the causes, clinical manifestations, diagnosis and treatment of patients with nephrogenic diabetes insipidus. Based on more in-depth mechanistic understanding, new therapeutic strategies are current being explored.

[Treatment of idiopathic nephrotic syndrome in children]. / Tratamiento del síndrome nefrótico idiopático en niños.

The annual incidence of the nephrotic syndrome has been estimated to be 1-3 per 100,000 children<16 year of age. In children, the most common cause of nephrotic syndrome is idiopathic nephrotic syndrome (INS). INS is defined by the presence of proteinuria and hypoalbuminemia and by definition is a primary disease. Renal biopsy study shows non-specific histological abnormalities of the kidney including minimal changes, focal and segmental glomerular sclerosis, and diffuse mesangial proliferation. Steroid therapy is applied in all cases of INS. Renal biopsy is usually not indicated before starting corticosteroid therapy. The majority of patients (80-90%) are steroid-responsive. Children with INS who do not achieve a complete remission with corticosteroid therapy commonly present focal and segmental glomerular sclerosis and require treatment with calcineurin inhibitors (cyclosporine or tacrolimus), mycophenolate mofetil or rituximab, plus renin-angiotensin system blockade. In this article we review the recent accepted recommendations for the treatment of children with INS.

[Nutcracker syndrome: Cause of non-glomerular hematuria and massive proteinuria]. / Síndrome de cascanueces: causa de hematuria y proteinuria masiva no glomerular.

BACKGROUND: Nutcracker syndrome caused by compression of the left renal vein between the aorta and superior mesenteric artery is a non-glomerular cause of left renal bleeding and left varicocele. It has also been recognized to be an important cause of orthostatic proteinuria. CASE REPORT: A 17-year-old male was evaluated due to recurrent macroscopic hematuria. Physical examination showed left varicocele. Body mass index 16.3 kg/m2. Urinalysis demonstrated hematuria and massive proteinuria. Renal biopsy showed mild mesangial glomerular proliferation. Cystoscopy showed hematuria originating from the left ureter. Doppler ultrasonography and contrast-enhanced computed angiotomography revealed a peak velocity of the left renal vein of 20cm/s, ratio of peak velocity of aortomesenteric and hilar portions of left renal vein of 7.7 and enlargement of the left renal vein in the hilar portion. With a diagnosis of nutcracker syndrome, the patient received conservative treatment. During follow-up, progressive remission of the recurrent episodes of hematuria and proteinuria was observed. The patient had no clinical symptoms or abnormal urinalysis. At 13 months of follow-up the body mass index was 19 kg/m2. CONCLUSIONS: This case shows the relationship between the increase in body mass index and remission of nutcracker syndrome, manifested as left varicocele, hematuria and massive proteinuria. All symptoms disappeared with the increase of body mass index, probably due to increase in retroperitoneal fat with improvement of the aortomesenteric angle of the left renal vein.

Seguimiento a largo plazo de un paciente con raquitismo dependiente de vitamina D tipo I / Long term follow up of a patient with type I vitamin D-dependent rickets

ResumenINTRODUCCIÓN: El raquitismo dependiente de vitamina D tipo I es una enfermedad hereditaria rara debida a una mutación en el gen CYP27B1 que codifica la enzima 1 α -hidroxilasa. Se caracteriza por la presentación de raquitismo hipocalcémico grave desde la edad de la lactancia debido al déficit de producción del metabolito activo de la vitamina D, la 1α,25-dihidroxivitamina D3.CASO CLÍNICO: Presentamos el caso de un paciente con raquitismo diagnosticado a los 11 meses de edad y el seguimiento hasta los 9 años.CONCLUSIONES: Se discute la fisiopatología de la enfermedad y la importancia del diagnóstico y tratamiento oportunos.

AbstractBACKGROUND: Vitamin D dependent rickets type I is a rare hereditary disease due to a mutation in CYP27B1 encoding the 1α-hydroxylase gene. Clinically, the condition is characterized by hypocalcemic rickets in early infancy due to a deficit in the production of the vitamin D active metabolite 1,25-dihydroxy-vitamin D3.CASE REPORT: We report the case of a patient diagnosed at 11 months with follow-up until 9 years of age.CONCLUSIONS: The pathophysiology of the disease and the relevance of early diagnosis and management are discussed.

Prevalencia de enfermedad renal en niños aparentemente sanos con antecedente familiar de terapia de reemplazo renal / Prevalence of kidney disease in asymptomatic children with family history of renal replacement therapy

ResumenIntroducción:Se ha mencionado que tener un familiar directo con enfermedad renal es un factor de riesgo para el padecimiento. El objetivo del estudio fue conocer la prevalencia de enfermedad renal temprana en niños familiares de pacientes con enfermedad renal crónica terminal (ERCT).Métodos:Se realizó un estudio de tamiz en niños aparentemente sanos, familiares en primer o segundo grado de pacientes con ERCT en programa reemplazo renal (hemodiálisis o trasplante renal). Previa firma de consentimiento informado se realizó el examen físico completo. Se tomó una muestra de sangre para la determinación de creatinina y electrolitos séricos, así como examen general de orina.Resultado:Se incluyeron 45 sujetos, mediana de edad 9.6 años, 24 (53%) fueron varones. Se encontraron alteraciones urinarias/enfermedad renal en 11 niños (24.4%). La alteración urinaria más frecuente fue hematuria, encontrada en seis sujetos, seguida de microalbuminuria, encontrada en cuatro. Siete estaban en estadio 2 de enfermedad renal y cuatro en estadio 1.Conclusiones: El estudio de los familiares de pacientes en terapia sustitutiva renal permite identificar individuos con etapas tempranas de enfermedad renal.

AbstractBackground:Having a first- or second-degree relative with chronic kidney disease (CKD) has been reported as a risk factor for CKD development. The aim of the study was to determine the prevalence of CKD in children with a first- or second-degree relative undergoing renal replacement therapy (hemodialysis or renal transplant).Methods:A screening study was performed in asymptomatic children with a family history of CKD in a first- or second-degree relative undergoing renal replacement therapy. Informed consent was obtained in all cases. A clinical examination was performed. Blood and urine samples were obtained for serum creatinine, serum electrolytes, urinalysis, and microalbumin/creatinine ratio.Results:There were 45 subjects included with a median age of 9.6 years; 24 (53%) were male. Urinary abnormality/CKD was observed in 11 subjects (24.4%). The most common urinary abnormalities were hematuria (6/11) and microalbuminuria (4/11). Stage 2 CKD was found in seven subjects and four subjects with stage 1 CKD.Conclusions:The study of families of patients undergoing renal replacement therapy is useful to identify children in early stages of kidney disease.

Diabetes insípida nefrogénica / Nephrogenic diabetes insipidus

La hormona antidiurética arginina vasopresina (AVP) es liberada de la hipófisis, y regula la reabsorción de agua en las células principales del túbulo colector renal. La unión de la AVP al receptor tipo 2 de la AVP en la membrana basolateral induce la translocación de los canales acuosos de la acuaporina-2 hacia la membrana apical de las células principales de los túbulos colectores, induciendo la permeabilidad al agua de la membrana. Lo anterior da como resultado la reabsorción de agua en el túbulo colector de la nefrona, bajo la influencia de un gradiente osmótico. La diabetes insípida nefrogénica es causada por la resistencia parcial o total al efecto de la AVP. La diabetes insípida nefrogénica congénita es una alteración asociada con mutaciones en los genes AVPR2 o AQP2, ocasionando la incapacidad del paciente para concentrar la orina. La diabetes insípida nefrogénica adquirida o secundaria puede ser causada por desbalances electrolíticos (hipercalcemia, hipokalemia), enfermedades renales o extrarrenales y fármacos (toxicidad por litio). En este artículo se revisan las causas, manifestaciones clínicas, diagnóstico y tratamiento de los pacientes con diabetes insípida nefrogénica. También, con base en la comprensión de los mecanismos íntimos de la alteración, se exploran nuevas estrategias terapéuticas.

The anti-diuretic hormone arginine-vasopressin (AVP) is released from the pituitary and regulates water reabsorption in the principal cells of the kidney collecting duct. Binding of AVP to the arginine-vasopressin receptor type-2 in the basolateral membrane leads to translocation of aquaporin-2 water channels to the apical membrane of the principal cells of the collecting duct, inducing water permeability of the membrane. This results in water reabsorption in the collecting duct of the nephron following an osmotic gradient. Nephrogenic diabetes insipidus is caused by partial or complete renal resistance to the effects of AVP. Congenital nephrogenic diabetes insipidus is a disorder associated with mutations in either the AVPR2 or AQP2 gene, causing the inability of patients to concentrate their urine. Acquired nephrogenic diabetes insipidus can be caused by electrolyte imbalances (e.g., hypercalcemia, hypokalemia), renal/extra-renal diseases and drugs (e.g., lithium toxicity). This article reviews the causes, clinical manifestations, diagnosis and treatment of patients with nephrogenic diabetes insipidus. Based on more in-depth mechanistic understanding, new therapeutic strategies are current being explored.

Tratamiento del síndrome nefrótico idiopático en niños / Treatment of idiopathic nephrotic syndrome in children

La incidencia anual del síndrome nefrótico se ha estimado en 1-3 por cada 100,000 niños menores de 16 años de edad. En niños, la causa más común del síndrome nefrótico es el síndrome nefrótico idiopático (SNI), que se define por la presencia de proteinuria e hipoalbuminemia y es, por definición, una enfermedad primaria. En el estudio de la biopsia renal se pueden encontrar alteraciones histológicas renales no específicas que incluyen lesiones mínimas, glomeruloesclerosis segmentaria y focal y proliferación mesangial difusa. En todos los pacientes con SNI se indica el tratamiento con corticosteroides, ya que, habitualmente, no se requiere de una biopsia renal antes de iniciar el tratamiento. La mayoría de los pacientes (80-90%) responden a este tratamiento. Los niños con SNI que no presentan remisión completa con el tratamiento con corticosteroides generalmente presentan glomeruloesclerosis segmentaria y focal, y requieren tratamiento con inhibidores de calcineurina (ciclosporina o tacrolimus), mofetil micofenolato o rituximab, además del bloqueo del sistema renina-angiotensina. En este artículo se revisan las recomendaciones recientes aceptadas para el tratamiento de los niños con SNI.

The annual incidence of the nephrotic syndrome has been estimated to be 1-3 per 100,000 children < 16 year of age. In children, the most common cause of nephrotic syndrome is idiopathic nephrotic syndrome (INS). INS is defined by the presence of proteinuria and hypoalbuminemia and by definition is a primary disease. Renal biopsy study shows non-specific histological abnormalities of the kidney including minimal changes, focal and segmental glomerular sclerosis, and diffuse mesangial proliferation. Steroid therapy is applied in all cases of INS. Renal biopsy is usually not indicated before starting corticosteroid therapy. The majority of patients (80-90%) are steroid-responsive. Children with INS who do not achieve a complete remission with corticosteroid therapy commonly present focal and segmental glomerular sclerosis and require treatment with calcineurin inhibitors (cyclosporine or tacrolimus), mycophenolate mofetil or rituximab, plus renin-angiotensin system blockade. In this article we review the recent accepted recommendations for the treatment of children with INS.

Síndrome de cascanueces: causa de hematuria y proteinuria masiva no glomerular / Nutcracker syndrome: Cause of non-glomerular hematuria and massive proteinuria

Introducción: El síndrome de cascanueces causado por la compresión de la vena renal izquierda entre la aorta y la arteria mesentérica superior es una causa no glomerular de sangrado renal y varicocele izquierdos. También ha sido reconocido como una causa importante de proteinuria ortostática. Caso clínico: Adolescente masculino de 17 años de edad con un cuadro de hematuria recurrente. En el examen físico se observó varicocele izquierdo. Índice de masa corporal de 16.3 kg/m². El examen de orina mostró hematuria y proteinuria masiva. La biopsia renal evidenció proliferación mesangial glomerular leve. El estudio de cistoscopia mostró el origen de la hematuria en el uréter izquierdo. La ultrasonografía Doppler y la angiotomografía de contraste revelaron velocidad pico de la vena renal izquierda de 20 cm/s, relación del índice de flujos de la vena renal izquierda de su porción aortomesentérica e hiliar de 7.7 y agrandamiento de la vena renal izquierda en la porción hiliar. Con el diagnóstico de síndrome de cascanueces se decidió proporcionar tratamiento conservador. En los meses siguientes mostró disminución importante de los episodios de hematuria recurrente, y se observó remisión de las manifestaciones clínicas y de las alteraciones en el examen de orina. A los 13 meses de evolución el índice de masa corporal fue de 19 kg/m². Conclusiones: Este caso clínico muestra la relación entre el incremento en la masa corporal y la remisión del síndrome de cascanueces manifestado como presencia de varicocele izquierdo, hematuria y proteinuria graves. Los síntomas desaparecieron al incrementar el índice de masa corporal, probablemente debido a un aumento en la grasa retroperitoneal que mejoró el ángulo aortomesentérico de la vena renal izquierda.

Background: Nutcracker syndrome caused by compression of the left renal vein between the aorta and superior mesenteric artery is a non-glomerular cause of left renal bleeding and left varicocele. It has also been recognized to be an important cause of orthostatic proteinuria. Case report: A 17-year-old male was evaluated due to recurrent macroscopic hematuria. Physical examination showed left varicocele. Body mass index 16.3 kg/m². Urinalysis demonstrated hematuria and massive proteinuria. Renal biopsy showed mild mesangial glomerular proliferation. Cystoscopy showed hematuria originating from the left ureter. Doppler ultrasonography and contrast-enhanced computed angiotomography revealed a peak velocity of the left renal vein of 20 cm/s, ratio of peak velocity of aortomesenteric and hilar portions of left renal vein of 7.7 and enlargement of the left renal vein in the hilar portion. With a diagnosis of nutcracker syndrome, the patient received conservative treatment. During follow-up, progressive remission of the recurrent episodes of hematuria and proteinuria was observed. The patient had no clinical symptoms or abnormal urinalysis. At 13 months of follow-up the body mass index was 19 kg/m². Conclusions: This case shows the relationship between the increase in body mass index and remission of nutcracker syndrome, manifested as left varicocele, hematuria and massive proteinuria. All symptoms disappeared with the increase of body mass index, probably due to increase in retroperitoneal fat with improvement of the aortomesenteric angle of the left renal vein.

Uso de antagonistas de aldosterona para detener la progresión de la enfermedad renal: de las bases fisiológicas a la aplicación clínica / Clinical use of aldosterone antagonists for slowing progression of chronic kidney disease: From the physiological basis to clinical application

La aldosterona, sintetizada en la zona glomerulosa de la corteza suprarrenal, es la principal hormona reguladora del metabolismo de sodio y potasio y del volumen extracelular. A través del receptor de mineralocorticoides, actúa como la señal endocrina final del sistema renina-angiotensina-aldosterona sobre el epitelio del túbulo renal y del colon distal, que estimula la reabsorción de sodio y la secreción de potasio. El agua se reabsorbe, vía ósmosis, favoreciendo la expansión del volumen circulante y, por ende, incrementando la presión arterial. Recientemente, se ha centrado el interés en las acciones no clásicas de la aldosterona sobre el endotelio vascular, corazón y riñón. Existe evidencia de que la aldosterona está involucrada en la remodelación vascular, la función endotelial y la formación de colágena, y que contribuye a la progresión de la insuficiencia cardiaca, así como del daño renal. Se revisa la evidencia clínica y experimental que fundamenta el uso de bloqueadores de aldosterona para detener la progresión del daño renal en diferentes modelos.

Aldosterone is synthesized in the adrenal cortex and is the main regulator of sodium and potassium metabolism and the extracellular volume. Acting through the mineralocorticoid receptor, it is the final endocrine signal of the renin-angiotensin-aldosterone system with effects on the renal tubular epithelium and distal colon stimulating sodium reabsorption and potassium secretion. Water is absorbed by osmosis favoring expansion of circulating volume and increasing arterial blood pressure. Recently there has been great interest in the non-classical actions of aldosterone on the vascular endothelium, heart and kidney. There is evidence suggesting that aldosterone participates in vascular remodeling, endothelial function and collagen deposition, contributing to heart failure progression and kidney damage. Clinical and experimental evidence supporting the use of aldosterone blocking agents in different models of kidney damage is reviewed.