Renal Injury in DENV-4 Fatal Cases: Viremia, Immune Response and Cytokine Profile.

Dengue virus (DENV) infections may result in asymptomatic cases or evolve into a severe disease, which involves multiple organ failure. Renal involvement in dengue can be potentially related to an increased mortality. Aiming to better understand the role of DENV in renal injury observed in human fatal cases, post-mortem investigations were performed in four DENV-4 renal autopsies during dengue epidemics in Brazil. Tissues were submitted to histopathology, immunohistochemistry, viral quantification, and characterization of cytokines and inflammatory mediators. Probably due the high viral load, several lesions were observed in the renal tissue, such as diffuse mononuclear infiltration around the glomerulus in the cortical region and in the medullary vessels, hyalinosis arteriolar, lymphocytic infiltrate, increased capsular fibrosis, proximal convoluted tubule (PCT) damage, edema, PCT debris formation, and thickening of the basal vessel membrane. These changes were associated with DENV-4 infection, as confirmed by the presence of DENV-specific NS3 protein, indicative of viral replication. The exacerbated presence of mononuclear cells at several renal tissue sites culminated in the secretion of proinflammatory cytokines and chemokines. Moreover, it can be suggested that the renal tissue injury observed here may have been due to the combination of both high viral load and exacerbated host immune response.

Um índice clínico preditor de sobrevida renal / A clinical predictor index for renal survival

Introdução: Um índice capaz de antecipar a progressão da doença renal independente dos achados histológicos seria de inestimável valor para a indicação da biópsia renal. Objetivo: Avaliar se um índice clínico baseado na ecogenicidade cortical renal, na relação diâmetro longitudinal do rim/altura do indivíduo (KL/H) e na creatinina sérica pode predizer a sobrevida renal. Métodos: As lesões crônicas (obsolesc~encia glomerular, esclerose segmentar e focal, atrofia tubular e fibrose intersticial) e agudas (proliferação mesaginal, permeação leucocitária, necrose fibrinoide e crescentes e infiltrado intersticial) das biópsias de 154 pacientes foram graduadas e somadas para geração de índices. Um índice clínico de cronicidade foi criado pela soma da gradação da ecogenicidade cortical relativa a do fígado ou baço, dos níveis de creatinina sérica e da relação KL/H. O desfecho do estudo foi a necessidade de iniciar a diálise. Resultados: Os maiores graus do índice clínico de cronicidade e do índice crônico de biópsia foram associados com sobrevida renal mais curta. Dos seis pacientes com creatinina sérica >2,5 mg/dL, maior ecogenicidade cortical e KL/H<0,60 antes da biópsia, cinco iniciaram diálise e um elevou a creatinina para 4,5 mg/dL. O índice clínico apresentou boa correlação com o índice crônico de biópsia. Conclusões: O índice clínico pode ser útil para predizer uma situação na qual a biópsia mostrará lesões crônicas avançadas e irreversíveis. Nos pacientescom os graus mais altos dos parãmetros clínicos, a biópsia pode ser descartada. Para grupos de pacientes, o índice pode ser utilizado na comparação de desfechos e eficácia terapêutica.

Introduction: An index able to anticipate the progression of renal disease independent of histological findings would be invaluable for the indication of renal biopsy. Objective: To evaluate whether a clinical index based on renal cortical echogenicity in longitudinal diameter ratio of kidney / height of the individual (KL / H) and serum creatinine to predict renal survival. Methods: The chronic lesions (obsoletes ~ ence glomerular focal segmental sclerosis, tubular atrophy and interstitial fibrosis) and acute (mesaginal proliferation, leukocyte permeation, fibrinoid necrosis and crescents and interstitial infiltration) of biopsies from 154 patients were graded and summed to generate indices. A clinical index of chronicity was created by the sum of gradation on the echogenicity of the liver or spleen, the levels of serum creatinine and the ratio KL / H. The study endpoint was the need to start dialysis. Results: The highest degree of clinical index and chronicity index of chronic biopsy were associated with shorter renal survival. Of the six patients with serum creatinine> 2.5 mg / dL, increased cortical echogenicity and KL / H <0.60 before biopsy, five started dialysis and a raised creatinine to 4.5 mg / dL. The clinical index had good correlation with chronic biopsy. Conclusions: The clinical index may be useful to predict a situation in which the biopsy shows chronic lesions advanced and irreversible. In pacientescom the highest levels of clinical parameters, the biopsy may be discarded. For groups of patients, the index can be used to compare outcomes and therapeutic efficacy.

[A clinical predictor index for renal survival].

INTRODUCTION: A clinical index that discriminates disease progression independent of histopathologic features may be valuable in the best timing of biopsy. OBJECTIVE: This study addresses the question if a clinical index based on cortical echogenicity, renal length to body height ratio (KL/H), and serum creatinine levels predicts renal survival. METHODS: The study enrolled 154 patients. Biopsy specimens were graded for chronic (glomerular obsolescence, segmental glomerular sclerosis, tubular atrophy and interstitial fibrosis) and acute (mesangial proliferation, leucocyte permeation, crescent and fibrinoid necrosis and interstital infiltrate) index by the sum of scored lesions. A chronic clinical index was created by the sum of scored cortical echogenicity relative to liver or spleen, creatinine serum levels and KL/H. The study end point was start on dialisis. RESULTS: Higher grade of chronic clinical and biopsy indices were associated with poorer long-term renal survival. Five out of six patients with serum creatinine levels > 2.5mg/dL, highest cortical echogenicity and KL/H < 0.60, before biopsy, started on dialysis and one increased creatinine levels up to 4.5 mg/dL. The chronic clinical index correlates well with chronic biopsy index. CONCLUSIONS: The chronic clinical index could be useful to predict a clinical setting in which a renal biopsy will show advanced chronic and irreversible lesion. In patients with highest grade of clinical parameters renal biopsy can be obviate. As a chronicity of illness index for groups of patients with renal medical diseases, the system could be useful in outcome comparisons and evaluation of therapeutic efficacy.

[Renal parenchymal disease: histopathologic-sonographic correlation]. / Doença parenquimatosa renal: correlação histológico-sonográfica.

PURPOSE: This study was designed to address the correlation between sonography of a kidney with histological lesions and clinical findings in patients with renal parenchymal disease based on a multivariate logistic regression analysis. METHODS: Clinical and laboratory data, sonograms and renal biopsies were evaluated in 154 patients. Cortical echogenicity was graded as less than (0), equal to (1) or greater than (2) liver/spleen parenchyma. Histological lesions - mesangial proliferation (MP), leukocyte permeation (LP), fibrinoid necrosis and crescents (FNC), interstitial infiltrate (II), segmental glomerular sclerosis (SGS), glomerular obsolescence (GO), tubular atrophy (TA) interstitial fibrosis (IF) and interstitial edema (IE) - were graded according to extension and severity as normal (0%), mild (<25%), moderate (>25% <50%), and severe (>50%). RESULTS: a) II, IF, SGS, IE and increased creatinine occurred less in cortical echogenicity grade 0; b) MP, arterial hypertension and normal parenchymal thickness predict cortical echogenicity grade 1; c) IF, IE, increased creatinine and thin parenchyma predict occurrence of echogenicity grade 2; d) Excluding obese patients, both youth and hematocrit accounted for pyramid prominence; e) increased creatinine and GO was probable in patients with small kidneys. CONCLUSIONS: Increased cortical echogenicity was a very sensitive marker of renal parenchymal disease. Different lesions rather than degree of lesion severity accounted for progressive increase of cortical echogenicity. IE exponentially increased the effect of IF on cortical echogenicity.

Doença parenquimatosa renal: correlação histológico-sonográfica / Renal parenchymal disease: histopathologic-sonographic correlation

OBJETIVO: Este estudo foi planejado para avaliar a correlação da ecografia do rim com as lesões histológicas e com os achados clínico-laboratoriais na doença parenquimatosa renal, por análise de regressão logística multivariada. MÉTODOS: Os dados clínicos, laboratoriais, ecográficos e as biópsias foram avaliados em 154 pacientes. A ecogenicidade cortical foi graduada como menor que grau zero, igual a grau um ou maior que grau dois a do parênquima hepático ou esplênico. As lesões histológicas - proliferação mesangial (PM), permeação leucocitária (PL), crescente e necrose fibrinóide (CNF), infiltrado inflamatório intersticial (II), esclerose glomerular segmentar (ES), obsolescência glomerular (OG), atrofia tubular (AT), fibrose intersticial (FI) e edema intersticial (EI) - foram graduadas de acordo com a extensão, em normal (0 por cento), leve (<25 por cento), moderada (>25 por cento <50 por cento), e grave (>50 por cento). RESULTADOS: a) II, FI, ES, EI e creatinina elevada ocorreram menos no grau 0 de ecogenicidade cortical; b) PM, hipertensão arterial e espessura normal do parênquima foram preditores do grau 1 de ecogenicidade cortical; c) FI, EI, creatinina elevada e parênquima fino foram preditores do grau 2 de ecogenicidade cortical; d) Excluindos os obesos, em jovens com hematócrito baixo, a pirâmide proeminente foi mais comum; e) Creatinina elevada e OG foram preditores de rins pequenos. CONCLUSÃO: A ecogenicidade cortical foi um sensível marcador de doença parenquimatosa renal. Lesões distintas mais do que o grau de severidade da lesão contribuiram para o aumento da ecogenicidade cortical. O EI aumenta exponencialmente o efeito da FI na ecogenicidade cortical.

PURPOSE: This study was designed to address the correlation between sonography of a kidney with histological lesions and clinical findings in patients with renal parenchymal disease based on a multivariate logistic regression analysis. METHODS: Clinical and laboratory data, sonograms and renal biopsies were evaluated in 154 patients. Cortical echogenicity was graded as less than (0), equal to (1) or greater than (2) liver/spleen parenchyma. Histological lesions - mesangial proliferation (MP), leukocyte permeation (LP), fibrinoid necrosis and crescents (FNC), interstitial infiltrate (II), segmental glomerular sclerosis (SGS), glomerular obsolescence (GO), tubular atrophy (TA) interstitial fibrosis (IF) and interstitial edema (IE) - were graded according to extension and severity as normal (0 percent), mild (<25 percent), moderate (>25 percent <50 percent), and severe (>50 percent). RESULTS: a) II, IF, SGS, IE and increased creatinine occurred less in cortical echogenicity grade 0; b) MP, arterial hypertension and normal parenchymal thickness predict cortical echogenicity grade 1; c) IF, IE, increased creatinine and thin parenchyma predict occurrence of echogenicity grade 2; d) Excluding obese patients, both youth and hematocrit accounted for pyramid prominence; e) increased creatinine and GO was probable in patients with small kidneys. CONCLUSIONS: Increased cortical echogenicity was a very sensitive marker of renal parenchymal disease. Different lesions rather than degree of lesion severity accounted for progressive increase of cortical echogenicity. IE exponentially increased the effect of IF on cortical echogenicity.