Correlación anátomo-clínica entre clases y subclases roliferativas de nefritis lúpica en biopsias renales: experiencia de un centro único / Clinicopathological correlation among proliferative classes and subclasses of lupus nephritis in renal biopsies

Background Lupus nephritis (LN) is a complication of systemic lupus erythematosus that requires renal biopsy (RB). Proliferative classes III, IV-S, IV-G have especial clinical and pathological characteristics. Aim To determine the association between pathological features in RB with serum creatinine and urine protein levels. Material and Methods We analyzed 186 RB performed in adults aged 18 to 73 years, from a renal pathology reference center. Histopathological variables such as class and subclass of proliferative LN, endocapillary and extracapillary proliferation, activity and chronicity indexes, and vascular sclerosis were correlated with serum creatinine and urine protein levels, at the time of diagnosis. Results As compared with LN III, all the morphological and laboratory values were significantly more deteriorated in LN IV, with special focus on vascular sclerosis. Serum creatinine was the only variable that significantly differentiated LN IV-S from LN IV-G. Proteinuria was non-significantly higher in LN IV-G compared to LN IV-S. However, the difference became significant when proteinuria was compared between LN IV-G and LN III. Conclusions The significant difference in serum creatinine between LN IV-S and LN IV-G supports the concept that they are different subclasses. Proteinuria is a variable that differentiates classes III from IV-G, being significantly higher in the second. Severe arteriosclerosis is a constant and significant finding that differentiates LN III from LN IV. Thus, we propose its usefulness for distinguishing LN classes, and eventually, to be considered in the chronicity index.

Effects of Interleukin-13 and Montelukast on the Expression of Zonula Occludens-1 in Human Podocytes

PURPOSE: The aim of this study was to investigate whether pathologic changes in zonula occludens-1 (ZO-1) are induced by interleukin-13 (IL-13) in the experimental minimal-change nephrotic syndrome (MCNS) model and to determine whether montelukast, a leukotriene receptor antagonist, has an effect on ZO-1 restoration in cultured human podocytes. MATERIALS AND METHODS: Human podocytes cultured on bovine serum albumin-coated plates were treated with different doses of IL-13 and montelukast and then examined for distribution using confocal microscopy and for ZO-1 protein levels using Western blotting. RESULTS: ZO-1 was internalized and shown to accumulate in the cytoplasm of human podocytes in an IL-13 dose-dependent manner. High doses (50 and 100 ng/mL) of IL-13 decreased the levels of ZO-1 protein at 12 and 24 h (both p<0.01; n=3), which were significantly reversed by a high dose (0.5 microM) montelukast treatment (p<0.01; n=3). CONCLUSION: Our results suggest that IL-13 alters the expression of ZO-1, and such alterations in the content and distribution of ZO-1 may be relevant in the pathogenesis of proteinuria in the MCNS model.

Effects of Interleukin-13 and Montelukast on the Expression of Zonula Occludens-1 in Human Podocytes

PURPOSE: The aim of this study was to investigate whether pathologic changes in zonula occludens-1 (ZO-1) are induced by interleukin-13 (IL-13) in the experimental minimal-change nephrotic syndrome (MCNS) model and to determine whether montelukast, a leukotriene receptor antagonist, has an effect on ZO-1 restoration in cultured human podocytes. MATERIALS AND METHODS: Human podocytes cultured on bovine serum albumin-coated plates were treated with different doses of IL-13 and montelukast and then examined for distribution using confocal microscopy and for ZO-1 protein levels using Western blotting. RESULTS: ZO-1 was internalized and shown to accumulate in the cytoplasm of human podocytes in an IL-13 dose-dependent manner. High doses (50 and 100 ng/mL) of IL-13 decreased the levels of ZO-1 protein at 12 and 24 h (both p<0.01; n=3), which were significantly reversed by a high dose (0.5 microM) montelukast treatment (p<0.01; n=3). CONCLUSION: Our results suggest that IL-13 alters the expression of ZO-1, and such alterations in the content and distribution of ZO-1 may be relevant in the pathogenesis of proteinuria in the MCNS model.

Fracción de excreción de magnesio y estado del túbulo-intersticio en pacientes nefróticos / Fractional excretion of magnesium and status of tubulointerstitium in nephrotic patients

INTRODUCCIÓN: la fracción de excreción de los electrólitos puede constituir un marcador temprano de daño renal en las glomerulopatías. OBJETIVO: identificar la posible relación existente entre variables clínicas, fracción de excreción de magnesio y estado del túbulo-intersticio, en pacientes con proteinuria nefrótica a los que se les realizó biopsia renal en el Instituto de Nefrología entre abril de 2012 y junio de 2013. MÉTODOS: se realizó un estudio observacional analítico, transversal, en el que se excluyeron los pacientes con factores que modificaran la fracción de excreción de magnesio. A los 40 pacientes incluidos en el estudio se les recogieron datos antropométricos, demográficos y clínicos, se les midió la fracción de excreción de magnesio, se les practicó biopsia renal y se les cuantificó el porcentaje de fibrosis con el programa Image J. La información fue procesada mediante el paquete estadístico SPSS 15.0. Se utilizó la técnica estadística de análisis de distribución de frecuencias, en las variables cuantitativas se calcularon estadígrafos descriptivos. Fueron empleados los tests de Wilcoxon, de Kruskal Wallis y el coeficiente de correlación de Spearman's-rho, en las pruebas de hipótesis. RESULTADOS: se encontró correlación estadísticamente significativa de la fibrosis intersticial con la fracción de excreción de magnesio (rsp= 0,37, p= 0,02) y con la tasa de filtración glomerular (rsp= -0,56, p= 0,00). No fue encontrada asociación de la fracción de excreción de magnesio con el empleo de medicamentos, ni con el antecedente de hipertensión arterial. CONCLUSIÓN: la fibrosis intersticial se relaciona con la fracción de excreción de magnesio y con la tasa de filtración glomerular en pacientes con proteinuria nefrótica.

INTRODUCTION: fractional excretion of electrolytes can be used as an early marker of renal damage in glomerulopathies. OBJECTIVE: to identify the possible relationship between some clinical variables, the fractional excretion of magnesium and the tubulointerstitial status in patients with nephrotic proteinuria assisted at The National Institute of Nephrology from April 2012 to June 2013. METHODS: an observational analytical study was conducted. Patients with conditions that modify the fractional excretion of magnesium were excluded. 40 patients were included in this study at the Institute of Nephrology from April 2012 until June 2013, and their demographic, anthropometric and clinical data were collected; the fractional excretion of magnesium was measured as well. Renal biopsies were practiced to all patients and the percent of fibrosis was measured with the aid of image J program. Data were processed with Statistical package for Social Science (SPSS) version 15.0. The statistical technique of frequency distribution analysis was used; quantitative variables descriptive statistics were calculated. Wilcoxon tests, Kruskal Wallis and correlation coefficient Spearman's- rho were used in hypothesis tests. RESULTS: the percent of interstitial fibrosis was related to fractional excretion of magnesium (rsp= 0,37, p= 0,02) and glomerular filtration rate (rsp= -0,56, p= 0,00). No association of the fractional excretion of magnesium with the use of drugs or with history of hypertension was found. CONCLUSIONS: tubulointerstitial fibrosis is related to the fractional excretion of magnesium and glomerular filtration rate in patients with nephrotic proteinuria.

Renal macrophage infiltration is associated with a poor outcome in IgA nephropathy

OBJECTIVES: The objectives of our study were as follows: 1) to analyze the prognostic value of macrophage infiltration in primary IgA nephropathy (IgAN) and 2) to study the relationship between macrophages and other factors associated with the development of renal fibrosis, including mast cells, TGF-β1, α-SMA and NF-kB. METHODS: We analyzed 62 patients who had been diagnosed with IgAN between 1987 and 2003. Immunohistochemical staining was performed with monoclonal antibodies against CD68 and mast cell tryptase and polyclonal antibodies against TGF-β1, α-SMA and NF-kB p65. We also used Southwestern histochemistry for the in situ detection of activated NF-kB. RESULTS: The infiltration of macrophages into the tubulointerstitial compartment correlated with unfavorable clinical and histological parameters, and a worse clinical course of IgAN was significantly associated with the number of tubulointerstitial macrophages. Kaplan-Meier curves demonstrated that increased macrophage infiltration was associated with decreased renal survival. Moreover, the presence of macrophages was associated with mast cells, tubulointerstitial α-SMA expression and NF-kB activation (IH and Southwestern histochemistry). In the multivariate analysis, the two parameters that correlated with macrophage infiltration, proteinuria and tubulointerstitial injury, were independently associated with an unfavorable clinical course. CONCLUSION: An increased number of macrophages in the tubulointerstitial area may serve as a predictive factor for poor prognosis in patients with IgAN, and these cells were also associated with the expression of pro-fibrotic factors.

The Relationship between Coronary Artery Calcification and Renal Function in Nondialyzed Patients

PURPOSE: Coronary artery calcification (CAC) has been described in individuals with chronic kidney disease (CKD), and its presence is associated with an increased risk of cardiovascular death. However, it is unclear whether there is an independent relationship between renal function and CAC. Therefore, we evaluated the association between renal function and CAC. MATERIALS AND METHODS: We retrospectively reviewed 870 Korean patients who had undergone computed tomographic coronary angiography. The glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease study formula with an ethnic factor for the Korean population. The CKD stages were classified using estimated GFR (eGFR) and proteinuria. RESULTS: The mean age of the participants was 56.8+/-11.8 years, and the mean eGFR was 89.4+/-16.5 mL/min/1.73 m2. Hypertension and diabetes were noted in 41.5 and 17.0% of patients, respectively. There were 584 and 286 patients with no CAC and with CAC, respectively. After adjusting for confounding variables, late stage CKD was associated with CAC [odds ratio (OR) 2.80, 95% confidence interval (CI) 1.05-7.46]. However, early stage CKD was not associated with CAC (OR 1.61, 95% CI 0.92-2.82). Diabetes was an independent risk factor of CAC (OR 2.06, 95% CI 1.36-3.13). There was no significant association between proteinuria and CAC (OR 1.65, 95% CI 0.96-2.85). CONCLUSION: CAC is related to late stage CKD in nondialyzed patients. These findings emphasize that individuals with CAC should be considered a high-risk population for decreased renal function.

Compromiso renal en pacientes HIV+ / Renal abnormalities in HIV infected patients

Varias complicaciones nefrológicas pueden ocurrir durante la infección por el virus de la inmunodeficiencia humana (HIV) especialmente en estadios avanzados de la enfermedad o relacionadas con otras infecciones o drogas. Poco conocida es la prevalencia de alteraciones renales subclínicas de pacientes HIV+ surgidas como complicación o relacionadas a la infección y/o tratamiento. Realizamos un corte transversal de pacientes asintomáticos HIV+ referidos en forma consecutiva al consultorio de nefrología para la detección de alteraciones nefrológicas. Se estudiaron 52 pacientes adultos mediante exámenes de sangre y orina, ultrasonido y biopsia renal. Edad media 39.9 ± 10.6 años, 88% varones, tiempo de diagnóstico de la infección: 53.2 ± 41.2 (2-127) meses. El 71% tenían síndrome de inmunodeficiencia adquirida (HIV-sida) y el 77% recibían con antirretrovirales. La carga viral al momento del estudio fue 7043 ± 3322 copias y el recuento de CD4+ 484 ± 39 cel/mm³. El 30.7% presentó alteraciones del sedimento urinario: albuminuria: 16.6%, hematuria microscópica: 11.5%, hipercalciuria: 10.8% y cristaluria 6%. La media del filtrado glomerular fue 102.2 ± 22.9 ml/min (rango: 34-149). El 41% presentó anormalidades que corresponderían a enfermedad renal crónica (estadios 1 a 3). Los pacientes con alteraciones tenían mayor edad, con duración más prolongada de la infección. Las anomalías renales no se asociaron con mayor prevalencia de HIV-sida. Dos pacientes fueron biopsiados, con hallazgos de nefritis túbulo-intersticial crónica con cristales y glomerulonefritis por IgA. No hubo hallazgos de nefropatía por HIV. El amplio espectro y la alta prevalencia de anormalidades nefrológicas subclínicas encontradas sugieren que los pacientes asintomáticos HIV+ deberían realizar evaluaciones nefrológicas de rutina.

Several renal complications may occur during HIV infection, especially in advanced stages related to HIV, to other infectious agents and/or drugs. Little is known about the prevalence of renal diseases that may occur as a complication of or related to HIV infection in asymptomatic patients. This is a single center cross-sectional study of asymptomatic HIV+ patients referred to a nefrology care service at an Argentine hospital to look for the presence of renal abnormalities. Fifty two consecutive patients were studied between April and November 2008. Patients underwent plasma and urine analysis, ultrasound, and kidney biopsy as needed. Mean age was 39.9 ± 10.6 years, 88% were male, time from HIV diagnosis 53.2 ± 41.2 months (2-127); 71% had HIV-disease and 77% were on antiretroviral therapy. Mean plasma HIV-RNA copies number was 7.043 ± 3.322 and CD4+ cell count: 484 ± 39. Pathologic findings in urine analysis were present in 30.7% of patients: albuminuria 16.6%, microscopic hematuria 11.5%, hypercalciuria 10.8% and crystalluria 6%. Mean glomerular filtration rate was 102.2 ± 22.95 ml/min (34-149) and 41% of patients could be classified in stages 1 to 3 of chronic kidney disease. Renal abnormalities prevaled in older patients without relationship with presence of HIV-disease. Two patients were biopsied and the findings included: tubulointerstitial nephritis with presence of crystal deposition in one and IgA nephropathy in the other. No HIV-associated nephropathy was detected. The broad spectrum and the high prevalence of lesions found in this series suggest that asymptomatic HIV-infected patients should routinely undergo renal evaluation.

Expresión de las óxido nítrico sintasas constitutiva endoletal e inducible en pacientes venezolanas con preeclampsia / Endothelial and inducible nitric oxide synthase expression in venezuelan patients with pre-eclampsia

La preeclampsia (PE) es una enfermedad que se presenta en la segunda mitad de embarazo. Es una condición caracterizada por hipertensión, proteinuria y frecuentemente cierto grado de restricción del crecimiento intrauterino (RCIU). El óxido nítrico (ON) regula el flujo de sangre en la placenta humana, induce vasodilatación, inhibe la agregación plaquetaria, y previene la adhesión de plaquetas a las células endoteliales. En este trabajo se evaluó, en sangre periférica de mujeres embarazadas normales (n = 46) y con PE (n = 50), los niveles séricos de nitritos y se analizó la expresión de las óxido nítrico sintasas constitutiva endotelial (eNOS) e inducible (iNOS) en tejido placentario. Se observó un aumento significativo en la concentración sérica de nitritos en las pacientes con PE al compararlas con mujeres embarazadas normales (150,64 ± 8,94 vs 40,62 ± 1,65 µM, p < 0,00001) y un aumento significativo en la expresión de las enzimas NOS (eNOS e iNOS) en las placentas de esas mismas pacientes, con respecto a las mujeres con embarazo normal (iNOS 4,29 ± 1,51 vs 0,59 ± 0,13; eNOS 1,78 ± 0,74 vs 0,46 ± 0,22, p < 0,005). Nuestros resultados muestran que existe una relación entre los valores de nitritos en suero de sangre periférica y el análisis de la expresión de las enzimas eNOS e iNOS en extracto de proteínas de tejido de placenta

Systemic amyloidosis in Hodgkin's disease.

Secondary amyloidosis as a complication of Hodgkin's disease has been described as being unusual to rare in occurrence. We report a case in which the clinical picture was that of a renal failure, etiology of which could not be determined but which proved to be amyloidosis secondary to clinically unrecognised Hodgkin's disease.

Glomeruloesclerosis focal y segmentaria en el trasplante renal / Focal segmental glomeruloesclerosis in renal transplantation

In 179 patients subjected to 186 renal tranplants, 30 renal biopsies were performed due to the presence of a proteinuria over 3.5 g/24 h or due to a reduction in glomerular filtration rate. Six of these biopsies, coming from 5 patients, disclosed morphological alterations compatible with focal segmental glomerulosclerosis. Five of these were due to recurrence of the primary disease (in 4 patients) and in all, massive proteinuria appeared from 1 to 23 days after transplantation. Two patients with three transplants evolved to renal failure and required dialysis in a period 12 months as a mean. The third patient, developed a nephrotic syndrome without renal failure and died 14 months after the renal transplant due to stroke. In the fourth patient, the nephrotic syndrome disappeared 38 days after the transplant and remained with minimal proteinuria until his last follow up visit two years later. The primary disease of the fifth patient is unknown, the nephrotic syndrome appeared 68 months after the transplant and remitted spontaneously in 2 months. The renal biopsy showed focal and segmental lesions with partial effacement of epithelial foot processes. It is concluded that focal segmental glomerulosclerosis recurrence in renal transplant occurs with aerly massive proteinuria and frequently leads to renal failure and graft loss in no more than two years

Correlation of microproteinuria and histopathological changes in kidney in diabetes mellitus.

Single attempt kidney biopsy was successful in 60 cases of diabetes mellitus out of 83. Histopathological evidence of nephropathy was found in 30 (50%) out of 60 (4 of IDDM and 56 of NIDDM). Microproteinuria was a sensitive indicator of histopathological evidence of nephropathy (by biopsy) and should be used as a non invasive method of evidence of kidney involvement in diabetes mellitus regardless of duration of the disease. Routine renal function tests--commonly used indicators of kidney disease in the presence of hypertension were of no value and should not be relied upon. Duration of diabetes mellitus was important correlation with the evidence of the disease and and its severity but nephropathy was found in newly detected cases of diabetes mellitus (NIDDM). Nephropathy was present in case of DM who had retinopathy and is a better factor of correlation.