Background: Lipid abnormalities are a common feature of the nephrotic syndrome that is also characterised by oedema, hypoalbuminaemia, proteinuria, and hypercoagulability. Concern has arisen over the increased incidence of cardiovascular disease that has been reported in individuals with nephrotic syndrome, particularly since the syndrome may occur early in life and become a chronic illness. The presence of proteinuria is a prognostic indicator for the progression of renal disease, but its possible contribution as a cardiovascular risk factor in patients with nephrotic syndrome is not known. In contrast, disordered lipoprotein metabolism, in isolation, is a conventional risk factor for the development of atherosclerosis. An early phase of atherosclerosis, vascular endothelial dysfunction, has been identified. Endothelial function can be measured non-invasively using ultrasonography and plethysmography allowing the impact of risk factors to be assessed in vivo.Aim: To test the hypothesis that endothelial dysfunction occurs in the nephrotic syndrome primarily as a consequence of dyslipidaemia.Methods: A cross-sectional design was used to study vascular function of the peripheral circulation in 45 individuals: fifteen patients with nephrosis (NP), 15 control subjects with primary hyperlipidaemia (HL) and 15 normolipidaernic controls (NC). The groups were matched for age, gender and body mass index. The NP group and the HL group had similar serum lipid and lipoprotein concentrations. High-resolution ultrasonography assessed endothelial function of the brachial artery. This non-invasive technique measured post- ischaemic flow-mediated dilatation (FMD) and endothelium-independent vasodilatation in response to glyceryl trinitrate (GTNMD). Post-ischaemic microcirculatory function was measured using venous occlusion strain gauge plethysmography.Results: Post-ischaemic FMD of ++ / the brachial artery was significantly lower in the NP and HL groups, compared with the NC group, with no significant difference found between the former two groups. There were no significant differences in GTNMD of the brachial artery, or in microcirculatory responses. In the patients with nephrosis, non-esterified free fatty acids were inversely associated with FMD, and maximal blood flow with insulin resistance.Conclusion: Dyslipidaemia is associated with endothelial dysfunction in patients with nephrosis and provides a plausible basis for the increased risk of cardiovascular disease observed in individuals with nephrotic syndrome.

Submitted by Mario BC (mario@bc.ufrpe.br) on 2016-08-01T16:02:52Z No. of bitstreams: 1 Thais Heloise da Silva Almeida.pdf: 1679068 bytes, checksum: 41dfbddddc98490ed23f15614d7f0173 (MD5) / Made available in DSpace on 2016-08-01T16:02:52Z (GMT). No. of bitstreams: 1 Thais Heloise da Silva Almeida.pdf: 1679068 bytes, checksum: 41dfbddddc98490ed23f15614d7f0173 (MD5) Previous issue date: 2015-02-27 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / The objective of this study was to describe the epidemiological, clinical and pathological aspects of poisoning by Thiloa glaucocarpa in the semiarid Northeast of the Brazil. Technical visits to various properties in two municipalities of Paraíba and in two municipalities of Pernambuco eight adult cattle naturally poisoned by T. glaucocarpa were examined and these, five were necropsied. The disease lasted on average 8-12 days. The main clinical signs consisted of apathy, anorexia, dehydration, dry nose and progressive weight loss, ascites, subcutaneous edema, dryness of rumen, reticulum, omasum contents. At necropsy, the lesions consisted of a significant accumulation of fluid in the abdominal and thorax cavity, pulmonary edema, subcutaneous mesentery, perirenal tissue and abomasal folds edema. Histologically, the main lesions consisted of epithelial coagulation necrosis of renal convoluted tubules with presence of amorphous eosinophilic material in the lumen of the tubules. The diagnosis of poisoning by T. glaucocarpa was based on epidemiological data, clinical signs, necropsy findings, histopathological evaluation, renal serum biochemistry and plant identification in the areas of cattle pastures. After the start of the rainy season in this region, T. glaucocarpa is the main toxic plant responsible for significant economic losses. Since there is no effective treatment for animals with renal failure, prophylaxis of intoxication is recommended that the animals must be removed from the areas where the plant grows in the period after the first rains. / O objetivo deste trabalho foi descrever os aspectos epidemiológicos e clínicopatológicos da intoxicação por Thiloa glaucocarpa no semiárido Nordestino. Durante visitas técnicas a diversas propriedades em dois municípios do Agreste do Estado da Paraíba e em dois municípios da Zona da Mata Setentrional do Estado de Pernambuco. Oito bovinos adultos, naturalmente intoxicados por T. glaucocarpa foram examinados e destes, cinco foram necropsiados. A evolução da doença durou em média 8-12 dias. Os principais sinais clínicos consistiram em apatia, anorexia, desidratação, narinas ressecadas e perda progressiva de peso, ascite, edemas subcutâneos, ressecamento dos conteúdos do rúmen, reticulo, omaso e ampola retal, com fezes sob a forma de cíbalos. À necropsia, as lesões consistiam em significativo acúmulo de líquido na cavidade abdominal, torácica e saco pericárdico, edema pulmonar, edemas subcutâneos, de mesentério, tecido perirrenal e pregas do abomaso. Histologicamente, as principais alterações foram observadas nos rins e consistiam em necrose de coagulação do epitélio dos túbulos contorcidos renais com presença de material eosinofílico amorfo no lúmen dos túbulos. O diagnóstico da intoxicação por T. glaucocarpa foi baseado nos dados epidemiológicos, sinais clínicos, achados de necropsia, avaliação histopatológica, bioquímica sérica renal e identificação da planta nas áreas de pastagens de bovinos. Após o início do período chuvoso nessa região, T. glaucocarpa é responsável por perdas econômicas significantes. Como não há um tratamento efetivo para os animais que apresentam falência renal, na profilaxia da intoxicação recomenda-se que os bovinos sejam removidos das áreas onde a planta vegeta no período após as primeiras chuvas.

Abstract The aim of this work was to evaluate the outcome of childhood Henoch-Schönlein purpura (HSP), the effectiveness of Cyclosporine A (CyA) for treating severe HSP nephritis (HSN), and more particularly the possibility for influencing the course of HSP disease by early prednisone treatment. A total of 47 adults who had had childhood HSP were evaluated after a mean of 24.1 years (16.4–35.6). The outcome was highly dependent on the renal symptoms at onset, since 7 out of 20 adults (20%) who had severe renal symptoms at onset had renal impairment as adults, compared with 2 out of 27 (7%) with mild or no renal symptoms at onset (relative risk 4.7; 95% CI 1.3–18.7). 70% of pregnancies in women after childhood HSN were complicated by hypertension or proteinuria. The annual incidence of HSN with nephrotic-range proteinuria was 2 per million children under 15 years. After a mean follow-up of 4.6 years, only three patients out of 19 were in complete remission. Kidney biopsy did not predict the outcome in these patients. CyA seemed to be promising for the treatment of severe HSN with nephrotic-range proteinuria, since four out of seven patients treated with CyA achieved stable remission and three had preserved their renal function after a mean follow-up of 6.0 years. Treatment at an early stage in the disease was associated with stable remission. The efficacy of early prednisone treatment was evaluated in a randomized double-blind trial involving 171 patients (84 prednisone, 87 placebo). Prednisone, given at a dose of 1 mg/kg/day for 2 weeks, with weaning over the next two weeks, was effective in reducing the intensity of abdominal pain (pain score 2.5 vs. 4.8; t-test p = 0.029) and shortening its duration (1.5 days vs. 2.7 days; t-test p = 0.028) compared with the placebo. The mean scores for joint pain were lower in the prednisone group (4.6 vs. 7.3; t-test p = 0.030) and the improvement from joint symptoms was faster (log rank p = 0.007). Prednisone did not prevent the development of renal symptoms but it was effective in treating them, since renal symptoms resolved in 61% of the prednisone patients after treatment compared with 34% of the placebo patients (difference 27%, 95% CI 3–47%, p = 0.024). Prednisone was most effective for children aged 6 or more with renal symptoms at onset, since only two patients needed to be treated in order to save one from renal involvement (95% CI's for NNT 2–6). The long-term outcome of HSP is dependent on renal symptoms. Severe renal symptoms indicate early immunosuppressive treatment for HSN, and patients with renal involvement at the acute phase need long-term follow-up, especially women during and after pregnancy. Early treatment with prednisone is effective in reducing the abdominal and joint symptoms involved in HSP and is also effective in altering, but not preventing, the course of renal involvement. / Tiivistelmä Väitöskirjatyön tarkoituksena oli selvittää lapsuusiän Henoch-Schönleinin purppuran (HSP) pitkäaikaisennustetta, Siklosporiini-A:n (CyA) tehoa vaikean HSP-nefriitin hoidossa ja tutkia varhain aloitetun prednisonihoidon hyötyä HSP-taudin oireisiin. HSP:n pitkäaikaisennustetta selvitettiin tarkastamalla 47:n lapsena HSP-taudin sairastaneen aikuisen terveystilanne keskimäärin 24.1 vuoden (16.4-35.6) seuranta-ajan jälkeen. HSP-taudin ennuste oli vahvasti riippuvainen munuaisoireen vaikeusasteesta: 20 % niistä, joilla taudin alussa oli vaikeat munuaisoireet, kärsi vielä aikuisiällä munuaisoireista; vastaava luku munuaisoireettomilla ja niillä, joilla oli ollut vain lievää veri- tai valkuaisvirtsaisuutta, oli 7 %, (RR 4.7; 95 % CI 1.3–18.7). Raskauskomplikaatiot olivat yleisiä lapsuusiällä HSP-taudin sairastaneilla naisilla, sillä 70 % raskauksista komplisoi korkea verenpaine tai valkuaisvirtsaisuus. Vuosittain 2 lasta miljoonasta sairastuu vaikeaan nefroottistasoiseen HSP-nefriittiin Suomessa. Vain kolme nefroottistasoiseen HSP-nefriittiin sairastuneesta 19 lapsesta oli 4.6 vuoden seurannan jälkeen parantunut oireettomaksi. Ensimmäisen munuaisbiopsian vaikeusaste ei ennakoinut selviytymistä. CyA näytti olevan lupaavan tehokas lääke vaikean HSP-nefriitin hoidossa, sillä neljä seitsemästä CyA-hoitoa saaneesta lapsesta, oli oireeton 6.0 vuoden seurannan jälkeen. Mitä aikaisemmin vaikean nefriitin hoito oli aloitettu, sen parempi hoitotulos oli. Varhain aloitetun prednisonihoidon hyötyä HSP-taudin oireisiin selvitettiin satunnaistetulla kaksoissokkotutkimuksella, johon satunnaistettiin 171 lasta (84 prednisoni, 87 lumelääke) saamaan joko prednisonia 1 mg/kg/päivä 2 viikon ajan tai lumelääkettä. Prednisoni vähensi tehokkaasti vatsa- ja nivelkipuja ja se lyhensi merkitsevästi myös niiden kestoa. Prednisoni ei estänyt munuaisoireen kehittymistä lapselle, mutta niiltä, joille se kehittyi, oireet hävisivät merkitsevästi nopeammin lumelääkitykseen verrattuna (61 % versus 34 %, 95 % CI 3–47 %, p = 0.024). Kaikkein tehokkainta prednisoni oli yli 6 vuotiaille lapsille, joilla oli munuaisoire heti taudin alussa (NNT 2, 95 % CI 2–6). Tutkimuksen perusteella voidaan sanoa, että lapsuusiällä HSP-nefriitin sairastaneet lapset tarvitsevat seurantaa aikuisiällä, erityisesti naiset raskauden aikana. HSP-nefriitin varhainen hoitaminen on tärkeää. Varhainen prednisonihoito ei estä munuaisoiretta, mutta hoitaa jo kehittynyttä nefriittiä ja vähentää vatsa- ja nivelkipuja tehokkaasti.