Orientador: Margareth Aparecida Santini de Almeida / Banca: Cristiane Lara Mendes Chiloff / Banca: Maria Silvia de Moraes / Resumo: As doenças crônicas, não transmissíveis são problemas de saúde pública de âmbito mundial. Dentre estas, encontra-se a doença renal crônica (DRC), que acarreta prejuízos físicos, psicológicos e sociais ao portador. O tratamento para DRC é dividido em tratamento conservador e terapia renal substitutiva (TRS). O diagnóstico de uma doença crônica pode provocar diversas mudanças no cotidiano do individuo, sendo muitas vezes acompanhado de desorganização psicológica e reações emocionais variadas. Assim, considera-se relevante conhecer e abordar o paciente, sua percepção e conhecimento sobre sua doença. Este estudo objetivou identificar a percepção do paciente com doença renal crônica (estágios 3 e 4) e sua vivência a respeito da mesma. Trata-se de pesquisa qualitativa, de cunho descritivo, com os pacientes portadores de DRC, atendidos no Ambulatório de Nefrologia do Hospital das Clínicas da Faculdade de Medicina de Botucatu - UNESP. Foram realizadas entrevistas semiestruturadas, onde a quantidade de pessoas a serem entrevistadas foi determinado pelo ponto de saturação. No total participaram 14 pessoas, sendo 7 mulheres e 7 homens, com idade médica de 59,9 anos. A maioria residia com seu cônjuge, apresentava renda familiar de até dois salários mínimos e havia cursado até o ensino fundamental completo. Apesar da maioria já apresentar uma doença crônica (diabetes mellitus e ou hipertensão arterial sistêmica), a preocupação mais intensa com o tratamento e a adesão às recomendações médicas ocorreram efetivamente após o diagnóstico da DRC que se deu, em média, há 6,2 anos. Os entrevistados apresentaram diferentes sentimentos e vivencias relacionados a doença. A DRC ocasiona inicialmente um misto de sentimentos como revolta, tristeza, e medo, que em alguns se transforma posteriormente em uma postura mais positiva para o enfrentamento. As principais mudanças relatadas dizem respeito à própria... / Abstract: The non-communicable chronic diseases are public health problems worldwide . Among these, we find the chronic kidney disease, which causes physical, psychological and social damage to the bearer. The pair treatment CKD is divided into conservative and TRS treatment. The diagnosis of a chronic disease results several changes in the individual's daily life, often accompanied by psychological disorganization and varied emotional reactions. Thus, it is considered relevant to know and approach the patient, their perception and knowledge of the disease. This study aimed to identify the perception of the patient with chronic kidney disease (stages 3 and 4) and their experience about the same. It is a qualitative research, of descriptive nature, with patients suffering from CKD who have been treated at the Nephrology Clinic of the Hospital of the Medical School of Botucatu - UNESP. Semistructured interviews were conducted, which, with the amount of people to be interviewed determined by the saturation point. In total 14 people participated, 7 women and 7 men with medical age of 59.9 years. Most of them have lived with their spouse, have had family income of up to two minimum wages and had attended to complete primary school. Although most already follow a chronic disease (diabetes and or hypertension), the most intense concern about the treatment and adherence to medical recommendations effectively occur after diagnosis of CKD that happened, on average, 6.2 years ago .The interviewees had different feelings and experiences related to the disease. The DRC initially causes mixed feelings as resentment, sadness, and fear, that in some was later transformed into a more positive attitude to face. The main changes relate to own family relationship around the sick one, in addition to dietary restrictions and physical impairment. Thus, it was observed that experience the DRC, means facing physical, psychological and social changes, requiring a great ... / Mestre

Doctor of Medicine / Publications 1-49 represent studies that I have undertaken myself or conjointly over a 34 year period to investigate a variety of issues relating to diseases of the kidney and urinary tract in children. The studies were carried out at the Royal Alexandra Hospital for Children, Camperdown when I was Clinical Superintendent from 1968 - 1970; The Department of Paediatrics, University of Minnesota, Minneapolis, USA when I was Overseas Research Fellow of the Post Graduate Foundation in Medicine, University of Sydney, 1970 - 1972, then as Staff Physician in Nephrology at the Royal Alexandra Hospital for Children, Camperdown, 1972 - 1977, and then Head of that Department at the Hospital until 1995 and then as an Honorary Staff Specialist at that hospital. Some of the studies were done conjointly with members of the Renal Unit of Royal Prince Alfred Hospital where I hold an Honorary appointment and others conjointly with members of the Renal Unit of Prince Henry Hospital, Little Bay. I was appointed Clinical Associate Professor to the Department of Paediatrics and Child Health, University of Sydney in 1993. In 1966 paediatric nephrology was in the early phase of development as a medical subspecialty. There was no definitive textbook, the first was published in 1975 (Pediatric Nephrology, Ed. Mitchell I. Rubin. Williams and Wilkins.). In the preface to the 2nd edition of Renal Disease (Blackwell) in 1967 the editor D.A.K. Black noted that he had included a chapter on paediatric aspects which had been planned for the 1st edition in 1962 but ”it could not be arranged”. In the chapter on Renal Disease in Children the author, D.Macauly, comments that the mortality rate of acute renal failure in children was 50%. When I joined the resident staff of the Royal Alexandra Hospital for Children in 1966, children with renal disease were managed by general paediatricians. There was no active program for the treatment of children with acute or chronic renal failure. A small number of kidney biopsies had been performed by Dr Trefor Morgan who, together with Dr Denis Wade, had taught me the technique while I was a resident medical officer at the Royal Prince Alfred Hospital in the preceding year. With the guidance and support of Dr S.E.J. Robertson and Dr C. Lee, Honorary Medical Officers, and Dr R.D.K. Reye, Head of the Department of Pathology, I began performing kidney biopsies on children at the request of the paediatrician in charge. In the same year, encouraged again by Doctors Robertson and Lee, and by J.C.M. Friend and J. Brown, I introduced peritoneal dialysis for the treatment of children with acute renal failure, a technique which I had also been taught by Dr Trefor Morgan whilst I was a resident at Royal Prince Alfred Hospital. Dr Robertson encouraged me to present my experience in percutaneous renal biopsy in children at the Annual Meeting of the Australian Paediatric Association in 1968 and this study became the first paper I published in relation to disease of the urinary tract in children (1). In 1970 I was granted an Overseas Research Fellowship by the Post Graduate Foundation in Medicine, University of Sydney, to enable me to undertake a fellowship in the Department of Paediatrics at the University of Minnesota. I had the great fortune in undertaking studies in the new discipline of paediatric nephrology and related research under the guidance of Dr A. F. Michael, Dr R.L.Vernier and Dr A. Fish. I acquired the techniques of immunopathology and electron microscopy. On my return to Australia I established a Department of Nephrology at the Royal Alexandra Hospital for Children. I introduced immunofluorescent and electron microscopic studies for the kidney biopsies that I continued to perform and, with the support of Dr R.D.K. Reye, I provided the official reports of these studies until 1990. As a result these studies became part of the histopathologic service provided by the hospital. I continue to be consulted concerning the interpretation of some electron microscopic findings in renal tissue. With the assistance of Dr J.D. Harley I set up a laboratory in the Children’s Medical Research Foundation to continue and expand the studies I had commenced during my Fellowship. Establishing a dialysis and transplant program for children with end stage renal disease (ESRD) was extremely time consuming. At that time most children with ESRD died. The program was initially established jointly with the Renal Unit at Royal Prince Alfred Hospital in 1972 and eventually dialysis facilities were established at the Children’s Hospital using predominantly peritoneal dialysis. By 1978 the existence of the Unit was well known in the general community and articles appeared in the press. One prompted the late Sir Lorimer Dods, the first Professor of Paediatrics in Australia to write to me congratulating me on what I had achieved. He remarked “I have just read with special interest Shaun’s review in the SMH of some of your recent achievements in the field of renal failure in infancy and childhood and want to offer you my personal congratulations on all that you have achieved and are achieving in this area of paediatrics which, in my little world of yesterday, meant nothing more than progressive and unrelenting fatal illness”. Taking part in the development of a relatively new discipline led me to study a number of areas. I encouraged trainees to write reports concerning clinical observations and eventually I was joined by Fellows whom I encouraged and supported to study a number of different areas to ensure that children were being cared for in an environment of strong and open enquiry. This led to studies on investigations of chronic renal failure which Dr Elisabeth Hodson pursued and studies on urinary tract infection in small children for which Dr Jonathon Craig was awarded a PhD. As I had been a contributor and co-author in a number of these studies they have been included in my list of publications. As a result of this diversity I have listed the publications in 9 sections. The overall theme is to study diseases of the renal tract in children and treatments used to understand the processes and ensure the most effective treatment. Some published abstracts of papers presented at scientific meetings have been included to clarify invitations I received to prepare reviews and chapters on various subjects and my involvement in some conjoint studies. I was author or coauthor of several book chapters, reviews, editorials and certain published studies to which I was invited to contribute as a result of my primary studies and these I have included as “Derivative References”numbered 50-76.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Community Medicine / Master / Master of Public Health

This KwaZulu-Natal (KZN) based study investigates hypertension, glomerulonephritides and the rarity of IgA Nephropathy (IgAN) in Africans in association with the Human Leukocyte Antigen (HLA). A retrospective hypertensive study found a positive association with HLA-B40 (P c<0.05) and HLA-B15 (Pc<0.02) in Indians and Africans respectively. No association was found in Whites. A prospective study showed glomerulonephritides to be positively associated with HLA-A33 in Indians (Pc 0.049). No associations were found with glomerulonephritides in Africans and Whites. Combined Race groups show no HLA associations. HLA-A30; HLA-A34; HLA-A29; HLA-B42; HLA-B58; HLA-B70 and HLA-DR11 were extremely significantly higher in Africans compared to Indians and Whites (all P<0.0001). In conclusion, HLA-B40 and I 1LA-B15 are possible disease susceptibility markers in Indian and African hypertensives; HLA-A33 is a possible disease susceptibility marker for glomerulonephritides in Indians and alleles in linkage might be responsible for the rarity of IgAN in Africans but further studies need to be employed. / Thesis (M.Med)-University of KwaZulu-Natal, 2007.

The purpose of this retrospective study was to determine the effectiveness of an innovative unit-wide phosphorus football contest and nutrition education intervention directed at improving the serum phosphorus levels and calcium-phosphorus products of patients undergoing routine hemodialysis. Patients at the Clarian Health Partners dialysis center located at 2140 North Capitol Avenue in Indianapolis, Indiana participated in the "National Fosphorus League Phootball" contest, a theme game that allowed patients to join a team and compete against other teams in the dialysis center over a four month time period from September 2005 to December 2005. Additional nutrition education was also provided to all the hemodialysis patients during the months of the phosphorus football contest. Identical patient information from September 2004 to December 2004 was also collected for baseline comparison of serum phosphorus levels and calcium-phosphorus products when only routine education and instruction was provided.Pearson Chi-Square analyses and a series of three-way ANOVAs were performed on the data collected. Overall, it was determined that patients who participated in the phosphorus football contest and received Vitamin D therapy were potentially two times likely to have serum phosphorus levels and calcium-phosphorus products in the goal ranges. / Department of Family and Consumer Sciences

No description available.

Sub-Saharan Africa bears 70% of the global HIV burden with KwaZulu-Natal (KZN) identified as the epicenter of this pandemic. HIV related nephropathy (HIVRN) exceeds any other causes of kidney diseases responsible for end stage renal disease, and has been increasingly recognized as a significant cause of morbidity and mortality. There is nonetheless a general lack of surveillance and reporting for HIVRN exists in this geographical region. Consequentially, the aim of this study was to outline the histopathogical spectrum of HIVRN within KZN. Moreover, from a pathology standpoint, it is important to address whether HIVRN was a direct consequence of viral infection of the renal parenchyma or is it a secondary consequence of systemic infection. Additionally, an evaluation of the efficacy of Highly Active Anti-Retroviral Therapy (HAART) in combination with angiotensin converting enzyme inhibitors (ACE-I) was performed via a genetic appraisal of localized replication of HIV-1 in the kidney, ultrastructural review and immunocytochemical expression of a podocyte maturity and proliferation marker pre and post-HAART. Blood and renal biopsies were obtained from 30 children with HIV related nephropathy pre- HAART, followed-up clinically for a period of 1 year. This cohort formed the post-HAART group. Clinical and demographic data were collated and histopathology, RT-PCR, sequencing, immunocytochemistry and transmission electron microscopy was performed. The commonest histopathological form of HIVRN in children (n = 30) in KZN was classical focal segmental glomerular sclerosis (FSGS) presented in 13(43.33%); mesangial hypercellularity 10(30%); mesangial, HIV associated nephropathy 3(11%) and minimal change disease 2(6.67%). Post-HAART (n = 9) the predominant pathology was mesangial hypercellularity 5(55.56%); FSGS 3(33.33%) and sclerosing glomerulopathy 1(11.11%). This study also provides data on the efficacy of HAART combined with ACE-I. The immunostaining pattern of synaptopodin, Ki67 and p24 within the glomerulus expressed as a mean field area percentage was significantly downregulated in the pre-HAART compared to the post-HAART group respectively (1.14 vs. 4.47%, p = 0.0068; 1.01 vs.4.68, p < 0.001; 4.5% vs 1.4%, p = 0.0035). The ultrastructural assessment of all biopsies conformed to their pathological appraisal however, features consistent with viral insult were observed. Latent HIV reservoirs were observed within the podocyte cytoplasm but was absent in mesangial or endothelial cells. Real-Time polymerase chain reaction assays provided evidence of HIV-1 within the kidney. Sequence analysis of the C2-C5 region of HIV-1 env revealed viral diversity between renal tissue to blood. In contrast to a collapsing type of FSGS that occurs in adults, the spectrum of paediatric nephropathy in treatment-naive children within KwaZulu-Natal was FSGS with mesangial hypercellularity. Additionally, our study demonstrates podocyte phenotype dysregulation pre- HAART and reconstitution post therapy. Evidence of ultrastructural viral reservoirs within epithelial cells is supported by a genetic appraisal confirming the ubiquitous presence of HIV DNA in renal tissue. Moreover, sequence analysis showed viral evolution and compartmentalization between renal viral reservoirs to blood. Finally, the interplay of viral genes and host response, influenced by genetic background, may contribute to the variable manifestations of HIV-1 infection in the kidney in our paediatric population. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2012.

Patients with end-stage renal disease undergoing hemodialysis have a high incidence of oxidative stress-related diseases. This study evaluated oxidative stress and inflammatory markers in patients undergoing hemodialysis before and during vitamin E supplementation. Blood samples were obtained before and after dialysis during two separate dialysis sessions to establish baseline measurements. For the next two months, subjects consumed 400 IU RRR-α-tocopherol daily. At one month and two months of supplementation, blood samples were also obtained before and after dialysis. Circulating concentrations of α- and γ-tocopherols and their metabolites (carboxyethyl-hydroxychromans, α- and γ-CEHCs), vitamin C, and uric acid were determined by HPLC with electrochemical detection. C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured using standard clinical assays. F₂-isoprostanes were evaluated using an enzyme immunoassay. Dietary vitamins E and C were assessed using two 24-hour recalls. In response to vitamin E supplementation, plasma α-tocopherol concentrations increased from 18 ± 1.7 μM to 31 ± 5.4 μM (p<0.0001), while γ-tocopherol concentrations decreased from 2.8 ±1.0 μM to 1.7 ± 0.6 μM (p=0.001). Additionally, serum vitamin E metabolites increased, α-CEHCs from 68 ± 20 pmol/ml to 771 ± 161 (p<0.0001) and γ-CEHC from 837 ± 161.8 pmol/ml to 1136 ± 225.9 (p=0.0083). Both CEHCs are well above reported normal values (p<0.0001). Dietary antioxidants (vitamins E and C) were low in most subjects; thus, plasma ascorbic acid levels were low in most subjects, but high in a few, resulting a wide range of responses (88 ± 84 μM). Nonetheless, ascorbic acid concentrations decreased significantly after dialysis to 33 ± 34 μM (p=0.0124), but were unaffected by vitamin E supplementation. Indeed, many parameters decreased significantly by dialysis but were unchanged by vitamin E supplementation, including plasma concentrations of uric acid and TNF-α. Both IL-6 and F₂-isoprostane concentrations were elevated in the subjects but were unaffected by either vitamin E supplementation or dialysis. CRP increased significantly after dialysis (p=0.0161, ANOVA main effect), but in the vitamin E supplemented subjects CRP concentrations were slightly lower before dialysis , but increased following dialysis (p=0.0041, ANOVA interaction). Taken together, the data suggest that there is a complex relationship between chronic inflammation and oxidative stress. Longer supplementation with vitamin E might be necessary in order to observe beneficial effects. / Graduation date: 2003

Research to improve artificial renal replacement therapies is varied across the many different parts of a hemodialysis system. Work largely focuses on developing a better dialyzer - the component that is directly responsible for removing wastes from the blood - but less study is devoted to the entire hemodialysis system. This work seeks to improve hemodialysis in two ways: by proposing a new renal replacement therapy that does not rely on traditional hemodialysis components, and by investigating the feasibility of adapting current hemodialysis practices to a portable format. While an alternative renal replacement therapy may be the best solution to today's dialysis problems, this work further focuses on reducing hemodialysis to a portable format through systematic engineering design. In that process, a detailed system model is made in Simulink that can account for the large number of inputs of such a system - the blood flow rate, dialyzer size, treatment time, etc. - allowing for detailed exploration of the design space. Once the model is completed, it is verified through in vitro experiments carried out with porcine blood. Additionally, the model is verified against published human hemodialysis data. After model verification, hemodialysis concepts are generated that allow for maximum portability under different patient conditions.