Ovariectomy exacerbates glycerol-induced acute kidney injury in rats / A ovariectomia intensifica a lesão renal aguda induzida pelo glicerol em ratas

Objective: This study aimed to evaluate the effects of ovariectomy on glycerol-induced renal changes in rats. Methods: Twenty-four female Wistar rats were submitted to ovariectomized (OVX) or sham surgery. One week after surgery, the animals received an intramuscular injection (8ml/kg) of 50% glycerol or saline (0.15 M) solution. These animals were divided into the following groups (n=6 per group): Sham, sham-operated female rats injected with saline; OVX, ovariectomized female rats injected with saline; Sham+Gly, sham-operated female rats injected with glycerol; OVX+Gly, ovariectomized female rats injected with glycerol. All rats were euthanized 3 days after the injections and the kidneys were removed for histological and immunohistochemical studies. Blood and urine samples were also collected for renal function studies. Results: The OVX+Gly group presented higher creatinine serum levels, as well as greater fractional excretion of sodium and urinary flow than the Sham+Gly group. Histological lesions and tubulointerstitial staining for macrophages, nuclear factor-kappa B, and nitrotyrosine were more pronounced in the renal cortex of the OVX+Gly group compared to the Sham+Gly group. Conclusion: We conclude that ovariectomy aggravated changes in renal function and structure in glycerol-induced acute kidney injury by the intensification of the proinflammatory tissue response.

Objetivo: Avaliar os efeitos da ovariectomia nas alterações renais induzidas pelo glicerol em ratas. Métodos: Vinte e quatro ratas Wistar foram submetidas à ovariectomia (OVX) ou cirurgia sham (intervenção falsa). Uma semana após a cirurgia, os animais receberam injeção intramuscular (8ml/kg) de glicerol a 50% ou solução salina (0,15 M). As ratas foram divididas nos seguintes grupos (n=6 por grupo): Sham, fêmeas sham-operadas e injetadas com solução salina; OVX, fêmeas ovariectomizadas e injetadas com solução salina; Sham+Gly, fêmeas sham-operadas e injetados com glicerol; OVX+Gly, fêmeas ovariectomizadas e injetadas com glicerol. Todas as ratas foram eutanasiadas 3 dias após as injeções e os rins foram removidos para estudos histológicos e imuno-histoquímicos. Amostras de sangue e urina também foram coletadas para estudos de função renal. Resultados: O grupo OVX+Gly apresentou maiores níveis séricos de creatinina, assim como maiores fração de excreção de sódio e fluxo urinário do que o grupo Sham+Gly. As lesões histológicas e imunomarcação tubulointersticial para macrófagos, fator nuclear-kappa B e nitrotirosina foram mais pronunciadas no córtex renal do grupo OVX+Gly em comparação ao grupo Sham+Gly. Conclusão: Concluímos que a ovariectomia agravou as alterações na função e estrutura renal, na lesão renal aguda induzida por glicerol, pela intensificação da resposta tecidual pró-inflamatória.

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.

Participaçäo de fatores de crescimento na regeneraçäo celular pós-necrose tubular aguda / Participation of growth factors in cell regeneration after acute tubular necrosis

A recuperaçäo da funçao renal após a necrose tubular aguda (NTA) depende da proliferaçäo de células e da substituiçäo de células necróticas e lesadas por células recém-formadas. Várias linhas de evidências indicam que o EGF (Epidermal Growth Factor), IGF-I (Insulin Growth Factor-I) e o HGF (Hepatocyte Growth Factor) devem participar da regeneraçäo célular pós-NTA: a) o EGF e o HGF säo capazes de desencadear potentes estímulos mitóticos em células de túbulos proximais; b) receptores para EGF e IGF-I estäo presentes em células de túbulos proximais; c) após a NTA ocorre um aumento dos receptores renais para IGF-I e EGF; d) a administraçäo de EGF, IGF-I ou HGF a ratos com NTA aumenta a velocidade de regeneraçäo celular e de recuperaçäo da funçao renal e e) o IGF-I é capaz de induzir a proliferaçäo de células renais e além disso tem efeitos no anabolismo celular e na hemodinâmica renal (aumenta o fluxo plasmático renal e a taxa de filtraçao glomerular). Tem sido proposto por vários autores o uso terapêutico de um ou mais desse fatores em pacientes com NTA. Contudo, consideramos necessária a realizaçäo de maior número de estudos para melhor entendimento dos mecanismos de açäo desses polipeptideos e avaliaçäo de seus efeitos na NTA.

Distúrbios do equilíbrio hidroeletrolítico e insuficiência renal aguda / Hydroelectrolytic disturbances and acute renal insufficiency

Nesta revisäo säo apresentadas as bases fisiopatológicas e as condutas terapêuticas dos distúrbios do equilíbrio hidroeletrolítico e da insuficiência renal aguda. Säo discutidos os desequilíbrios dos íons sódio, potássio e cálcio, a necrose tubular aguda e a azotemia pré-renal