AIM 1. To determine whether implementation of current national standards in relation to their achievement or non-achievement, improves outcomes in ESRD patients, receiving dialysis. AIM 2. To assess the impact on outcomes in ESRD patients, receiving dialysis, of non-treatment factors (for example, ethnicity and socio-economic factors) at the start of dialysis treatment. AIM 3. To assess the impact of mode of referral to nephrology services and dialysis modality, including haemodialysis access, on outcomes in patients with ESRD. AIM 4. To report the strongest predictors of outcomes in terms of mortality, transplantation and hospitalisation in patients with ESRD, receiving dialysis.

Population based studies of early chronic kidney disease (CKD), acute renal failure (ARF) and acute on chronic renal failure (ACRF) are surprisingly sparse and bedevilled by differences in definition, which makes incidence, prevalence and particularly outcomes difficult to compare.  There are measures available to prevent progression of both ARF and CKD, emphasising the importance of early identification and referral for treatment.  The international Acute Dialysis Quality Initiative (ADQI) group have suggested a classification for ARF and ACRF.  Furthermore Kidney Dialysis Outcomes Quality Initiative (KDOQI) clinical practice guidelines have suggested a staging system for CKD based on severity.  In many countries it is difficult to obtain comprehensive, population based data because medical services are not linked to one population base.  The Grampian region has a population of 523,390 and only two hospitals with linked biochemistry laboratories and hence suitable for epidemiological studies.  I tested the hypotheses that incidence of ARF and ACRF is high and RIFLE classification predicts outcomes.  I also studied the epidemiology of CKD in this population by manually reviewing the case notes of the patients.

Acute renal failure (ARF) is a common condition on the intensive care unit (ICU) and may affect up to 40% of patients (de Mendonca, A. et al., 2000), (Korkeila, M. et al., 2000). Pathophysiological mechanisms remain unclear. Patients who die from sepsis have kidneys that look histologically normal (Hotchkiss, R.S. et al., 1999), while the renal prognosis in survivors is good with < 2% requiring long-term renal replacement therapy (Noble, J.S. et al., 2001). This has led some authors to suggest that acute renal failure is a physiological process designed to shut down vital processes and protect the kidney from irreversible damage during a severe insult (Singer, M. et al., 2004). As ninety percent of oxygen consumption is utilised by the mitochondrion (Babcock, G.T. and Wikstrom, M., 1992), metabolic control may be regulated by mitochondrial activity (Beltran, B. et al., 2000). This may be an important mechanism underlying renal failure but is difficult to assess in the intact animal.

Healthcare for patients with a learning disability is an important topic; one that is receiving increased attention by the media, government, and NHS. Management of chronic illness is also an important topic, prioritised by the Department of Health. There is little research looking at chronic illness and learning disability, and contemporary models of coping and adjustment do not take into account the possible effects of having a learning disability. This research looked at how patients with a learning disability cope with chronic illness and focused specifically upon the experiences of patients with a learning disability diagnosed with stage V renal failure. This condition involves making a number of difficult decisions about treatment and adhering to difficult treatment regimes, and is amongst the most intrusive of illnesses in terms of impact upon quality of life. Five consultant nephrologists and five families/carers were interviewed. The data were analysed using grounded theory. The interviews from the two participant groups were analysed as two separate groups, and two models emerged from the data describing how individuals with a learning disability may cope with kidney disease. The results showed a complicated relationship between the level of learning disability and coping. Other factors unique to the individual (such as their previous experiences), the level and type of support the patient has, and their experiences of hospital care (including the role of the consultant) are all additional important factors that can affect coping. The research findings are related to the literature, and possible clinical implications are discussed. Future areas of research are suggested.

Macrophages are the predominant immune effector cell found in one of the most severe causes of renal failure in humans, crescentic glomerulonephritis (Crgn). The Wistar Kyoto (WLY) rat is uniquely susceptible among rat strains to Crgn and susceptibility genes have previously been mapped to seven quantitative trait loci (Crgn1-7). The AP-1 transcription factor JunD is markedly overexpressed in WKY macrophages and was identified as a major determinant of macrophage activation associated with Crgn susceptibility at Crgn2. The work presented in this thesis aimed to investigate mechanisms underlying the regulation of macrophage activation and glomerular inflammation by JunD in the NTN-susceptible WKY rat strain and in patients with Crgn. Genomic-based approaches, including microarray analysis of bone marrow-derived macrophage transcriptomes, RNA interference and cistrome analysis using ChIP-Seq, along with histological techniques and genotyping studies, were used to identify key genes and pathways underlying JunD-mediated activation of macrophages. Transcriptome analyses showed that the Crgn2 locus regulates expression of over 800 genes in WKY macrophage responses to lipopolysaccharide (LPS). Acute changes in Jund expression by RNA interference also modulated gene expression in WKY macrophages, including effector genes for the macrophage LPS response. Cistrome analysis revealed that genetically determined differences in Jund expression alter its genome binding pattern and the increased numbers of JunD-bound genes in WKY macrophages were functionally linked with signalling pathways and cell activation. Integration of the data identified 47 genes, that were associated with JunD binding peaks and whose expression was both regulated by Crgn2 and altered by siRNA knockdown of Jund, as the key candidates through which JunD determines macrophage activation. Overall, this work provides the basis for understanding genes and pathways through which JunD regulates macrophage activation and has identified novel gene targets for modulation of macrophage phenotypes in WKY rat and human macrophages.

Background: Patients with chronic kidney disease (CKD) face a markedly increased risk of cardiovascular morbidity and mortality. In this setting, aberrant endothelial function is a key initiating event in vascular disease. Haemodialysis (HD) patients characteristically exhibit significant abnormalities in vascular structure and function, which impact cardiovascular morbidity and mortality. Micro- and macro-vascular dysfunctions are the principle factors contributing to the increased risk of morbidity and mortality associated with obesity. Impaired endothelial function represents the earliest abnormality in the development of vascular disease in obesity and exhibits increased risk of cardiovascular disease. We first aimed to investigate the effect of HO and obesity on the vascular reactivity through directly examines the isolated subcutaneous arteries using wire myography. The second goal was to study changes that might underlie altered vascular responses following bariatric surgery and whether reduction in weight improves endothelial function. We also intended to correlate the ex vivo myography data with the in vivo results of pulse wave velocity (PWV) and blood pressure (BP) in both HO and obese patients. Methods: Abdominal subcutaneous fat biopsies were obtained from HO patients (n= l l ) during non-HO visits through small lower abdominal incisions using local anaesthetics; obese patients (n=12) during the time of bariatric surgery (using a laparoscopic port); and non-HD, non-obese healthy controls (n=26) during the time of elective surgery (hernia repair). Additional abdominal subcutaneous fat samples (n=4) were also obtained from obese patients at six months after bariatric surgery through an extra incision in the lower abdominal region using local anaesthetics. Different-sized arteries (small with internal diameter between 200 urn - 500 urn and large between 600 urn - 900 urn) were dissected, mounted and conducted on a wire myography on the same day. Cumulative concentration-response curves were constructed for the following vasoactive agents: noradrenalin (NA), endothelin-I (ET-I), U46619, angiotensin II (AngII), vasopressin, bradykinin (BK), acetylecholine (Ach) and sodium nitroprusside (SNP). Carotid-to-femoral arterial PWV was measured using an oscillometric device (Vicorder, Skidmore Medical Ltd., UK) for HD and obese patients in addition to measuring blood pressure (BP). Laboratory data were expressed as mean ± SEM and groups were compared by t-test. Results: In both HD and obese patients, greater contractile response to different vasoconstrictors was observed in different-sized arteries compared to control group. Although the potency of these drugs was similar between HD patients and controls, large vessels of HD patients were highly potent to U46619 and vasopressin compared to controls. Similarly, in obese patients, large vessels were also significantly more sensitive to U46619 and vasopressin than that of controls, while small vessels were highly potent to vasopressin response. The maximum vasorelaxation response of small and large vessels to Ach and BK (endothelium-dependent vasodilators) was significantly lower in both HD and obese patients than vessels of controls. A similar response to SNP (an endothelium-independent vasodilator) was obtained in all groups. However, the potencies of all vasodilators in all groups were similar. In HD patients, in vivo PWV was significantly correlated with the maximum contractile response of large arteries to vasopressin response (r = 0.829, P = 0.042). PWV was positively correlated with the percentage of maximum contractile response of small arteries to vasopressin (r = 0.886, P = 0.019). The diastolic but not systolic BP of HD patients was significantly inversely correlated with the response of large vessels to SNP (r = -0.954, P = 0.012), it was also negatively correlated with the percentage of contractile response of small arteries to vasopressin (r = -0.829, P = 0.042). There was no correlation observed in the responses of isolated small arteries to the other vasoconstrictor substances in terms of PWV or BP. In obese patients, The PWV was significantly correlated with the maximum contractile response of large arteries to U46619 (r = 0.928, P = 0.006), and with the maximum contractile response of small arteries to vasopressin (r = 0.885, P = 0.033).However, positive correlation was obtained between systolic (but not diastolic BP) of obese patients and the response of large vessels to U46619 (r = 0.785, P = 0.048). There was no significant difference in the vasocontractile or vasorelaxation responses of isolated vessels in obese patients before and after surgery; however, a trend of more contractile response to vasoconstrictors was observed in the obese group before surgery compared to those after surgery. Conclusion: These results suggest that HO and obesity can alter endothelial function via an incremental increase in vasocontractility in response to various stimuli and an impaired vasodilatation response to endothelium-dependent agonists in isolated different-sized vessels. In both groups, ex vivo arterial responses were correlated to in vivo assessment of arterial function. The association between these risk groups and endothelial dysfunction in isolated arteries would be expected to accelerate cardiovascular events, which impacts cardiovascular morbidity and mortality among these groups of patients. Therefore. the development of cardiovascular disease is mediated, at least partly, by functional alterations at the level of microcirculation.

Τα επίπεδα φωσφόρου αλλάζουν με την ηλικία. Ο αυξητικός παράγοντας των ινοβλαστών 23 (FGF23) είναι μία φωσφατουρική ορμόνη που παίζει σημαντικό ρόλο στην ομοιόσταση φωσφόρου. Η πρωτεΐνη Klotho είναι ο συμπαράγοντας του FGF23 που μεσολαβεί τη σύνδεση του FGF23 στον υποδοχέα του. Στη βιβλιογραφία για τα υγιή παιδιά υπάρχουν λίγα δεδομένα για τον FGF23 και ακόμη λιγότερα για το Klotho. Σκοπός μελέτης: Nα διερευνήσουμε την ύπαρξη πιθανής συσχέτισης μεταξύ των κυκλοφορούντων επιπέδων FGF23 και Klotho με την ηλικία και το ρυθμό μέγιστης σωληναριακής επαναρρόφησης φωσφόρου (TmP/GFR) και να μελετήσουμε τις παραμέτρους που τυχόν επηρεάζουν τα επίπεδα FGF23 και Klotho. Μέθοδοι: Σε 159 υγιή παιδιά (82 αγόρια) με μέση ± SD ηλικία 8.78 ± 3.47 έτη μετρήθηκε ο FGF23 (τόσο ο iFGF23 όσο και ο cFGF23) και το κυκλοφορούν Klotho (sKlotho) με τεχνικές ELISA. Υπολογίσαμε επίσης τα επίπεδα του TmP/GFR. Αποτελέσματα: Η μέση τιμή ± SD του cFGF23 ήταν 51.14 ± 12.79 RU/ml ενώ η διάμεσος (εύρος) του iFGF23 και του Klotho ήταν 35 (8.8, 120) pg/ml and 1945 (372, 5866) pg/ml αντιστοίχως. Ούτε ο FGF23 αλλά ούτε και το Klotho δε σχετίζονταν με την ηλικία. Τα παιδιά που είχαν μπει στην εφηβεία είχαν υψηλότερα επίπεδα Klotho (p < 0.05). Τα κορίτσια είχαν υψηλότερα επίπεδα cFGF23 (p < 0.05) και Klotho (p < 0.001). Τα επίπεδα του κυκλοφορούντος φωσφόρου και TmP/GFR ήταν θετικώς συσχετιζόμενα με τον cFGF23 (p < 0.01 και p < 0.001), iFGF23 (p < 0.05 και p < 0.001) και Klotho (p < 0.05 και p < 0.01). Το Klotho ήταν θετικώς συσχετιζόμενο με τον IGF-I (p < 0.0001) και 1,25 (OH)2 βιταμίνη D (p < 0.05). Συμπεράσματα: Στην παρούσα μελέτη παρουσιάζουμε δεδομένα για τα επίπεδα cFGF23, iFGF23, και Klotho που μετρήθηκαν ταυτόχρονα σε υγιή παιδιά. Η θετική συσχέτιση μεταξύ κυκλοφορούντος φωσφόρου και TmP/GFR με τον FGF23 και το Klotho υποδηλώνει ότι έχουν έναν αντισταθμιστικό ρόλο στην ομοιόσταση φωσφόρου. Η ισχυρή συσχέτιση μεταξύ Klotho και IGF-I μπορεί να σημαίνει ότι το Klotho έχει κάποιο ρόλο στην κατά μήκος ανάπτυξη κατά την παιδική ηλικία μέσω ρύθμισης της ομοιόστασης του φωσφόρου αλλά περισσότερες μελέτες χρειάζονται για να διευκρινιστεί αυτό περαιτέρω. / Phosphate serum levels in children vary with age. Fibroblast Growth Factor 23 (FGF23) is a phosphaturic hormone that plays an important role in phosphate homeostasis. Klotho is the essential co-player of FGF23 that mediates the binding of FGF23 to its receptor. Data for fibroblast growth factor 23 (FGF23) and particularly for Klotho in healthy children are limited. Objective and hypotheses: We aimed to investigate the relationship between FGF23 and Klotho serum levels with age and TmP/GFR and to evaluate parameters that might affect FGF23 and Klotho. Methods: In 159 healthy children (82 boys) with a mean ± SD age of 8.78 ± 3.47 years we measured FGF23 (intact FGF23/ iFGF23 and C-terminal FGF23/ cFGF23) and soluble Klotho (sKlotho) serum levels by ELISA. We also determined the TmP/GFR. Results: Mean ± SD value for cFGF23 was 51.14 ±12.79 RU/ml whereas median (range) values for iFGF23 and Klotho were 35 (8.8, 120) pg/ml and 1945 (372, 5866) pg/ml respectively. Neither FGF23 nor Klotho were significantly associated with age. Pubertal children had higher Klotho (p < 0.05). Girls had higher levels of cFGF23 (p < 0.05) and Klotho (p < 0.001). Serum phosphate and TmP/GFR were positively associated with cFGF23 (p < 0.01 and p < 0.001), iFGF23 (p < 0.05 and p < 0.001) and sKlotho (p < 0.05 and p < 0.01). Klotho was positively correlated with IGF-I (p < 0.0001) and 1,25 (OH)2 vitamin D (p < 0.05). Conclusions: We provide data on FGF23, and Klotho measured simultaneously in healthy children. The positive association of serum phosphate and TmP/GFR with FGF23 and Klotho suggests that they have a counterregulatory effect on phosphate homeostasis. The strong association of Klotho with IGF-I could indicate a role of Klotho in linear growth through regulation of phosphate homeostasis, but further studies are required.

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Κάθε χρόνο τα άτομα που υποφέρουν από κάποιας μορφής νεφρική νόσο αυξάνονται παρά τις εξελίξεις στον τομέα της ιατρικής. Έχει παρατηρηθεί ότι η νεφρική νόσος, στις περισσότερες περιπτώσεις μπορεί να εξελιχθεί σε νεφρική ανεπάρκεια, είτε με πιο αργούς είτε με πιο γρήγορους ρυθμούς. Η νεφρική ανεπάρκεια αντιμετωπίζεται είτε με αιμοκάθαρση είτε με μεταμόσχευση. Το ανοσοποιητικό σύστημα διαδραματίζει σημαντικό ρόλο τόσο στην αντιμετώπιση όσο και στη πρόοδο των διάφορων μορφών νεφρικής νόσου. Ωστόσο, οι διάφοροι λεμφοκυτταρικοί τύποι, και ιδιαίτερα αυτοί της φυσικής ανοσίας, δεν έχουν μελετηθεί ιδιαίτερα και πολλές φορές από τις λίγες μελέτες που υπάρχουν προκύπτουν αντικρουόμενα αποτελέσματα. Η μελέτη μας επικεντρώθηκε στα Τ, στα ΝΚ και στα ΝΚ-Τ λεμφοκύτταρα. Επιλέξαμε να ερευνήσουμε αρχικά και τελικά στάδια νεφρικής νόσου. Έτσι οι ασθενείς κατηγοριοποιούνται σε τρεις ομάδες: ασθενείς με σπειραμαρονεφρίτιδα (αρχικό στάδιο), ασθενείς που υποβάλλονται σε αιμοκάθαρση και μεταμοσχευμένοι ασθενείς (τελικά στάδια). Σε κάθε πείραμα γίνεται σύγκριση με μια ομάδα ελέγχου (control, που αποτελείται από υγιή άτομα). Στην περίπτωση της σπειραματονεφρίδας παρατηρήθηκαν φυσιολογικά ποσοστά των λεμφοκυτταρικών τύπων και της έκφρασης του NKG2D υποδοχέα. Παρατηρήθηκε, όμως, αυξημένη έκφραση του TNF-α. Στην περίπτωση της αιμοκάθαρσης αν και παρατηρήθηκε μειωμένο ποσοστό ΝΚ και Τ κυττάρων, βρέθηκε ότι παρουσιάζουν αυξημένη κυτταροτοξικότητα και λειτουργικότητα. Αυτό φαίνεται και από την αύξηση στην έκφραση του CD107α και από την αύξηση στη συγκέντρωση του TNF-α. Όσον αφορά τα ΝΚ-Τ κύτταρα, αν και το ποσοστό τους είναι φυσιολογικό, εμφανίζουν αυξημένη έκφραση του υποδοχέα NKG2D. Τέλος, όσον αφορά την ομάδα των μεταμοσχευμένων ασθενών, δεν παρατηρήθηκε μεταβολή στο ποσοστό των Τ και των ΝΚ-Τ κυττάρων. Όταν όμως οι ασθενείς κατηγοριοποιούνται με βάση την φαρμακευτική αγωγή, το ποσοστό των ΝΚ-Τ κυττάρων είναι αυξημένο σε ασθενείς που τους χορηγείται κυκλοσπορίνη. Επίσης, η έκφραση του υποδοχέα NKG2D είναι φυσιολογική και στις δύο κατηγορίες λεμφοκυττάρων. Από την άλλη, αν και το ποσοστό των ΝΚ κυττάρων μειώνεται, αυτά εμφανίζουν φυσιολογική λειτουργικότητα και κυτταροτοξικότητα, όπως φαίνεται από τη φυσιολογική έκφραση του NKG2D υποδοχέα, της πρωτεΐνης CD107α και του TNF-α. / Every year, people who suffer from some form of kidney disease are increasing despite advances in medicine. It has been observed that the kidney disease, in most cases might progress to renal failure, either slower or faster. The renal failure is treated either by hemodialysis or renal transplantation. The immune system plays an important role in the treatment and in the progression of various forms of renal disease. However, the various types of lymphocytes, and especially those of innate immunity have not been widely studied and often the few studies that exist result in conflicting results. Our study focused on T, NK and NK-T lymphocytes. We chose to investigate initial and final stages of renal disease. Patients were categorized into three groups: patients with glomerulonephritis (initial stage), patients on dialysis and transplanted patients (final stages). In each experiment patients were compared with a control group consisting of healthy individuals. In the case of glomerulonephritis, we observed normal percentages of the lymphocyte population examined and normal expression of the NKG2D receptor, as well as increased expression of TNF-α. In the case of hemodialysis, NK and T cell percentages were reduced, while NK cells exhibited enhanced cytotoxicity and functionality. This was shown by the increase in the expression of CD107α and by the increase in the concentration of TNF-α. Regarding the NK-T cells, although their percentage was normal, they showed increased expression of NKG2D receptor. Finally, concerning the group of transplanted patients, no change was observed in the percentage of T and NK-T cells. However, when patients were categorized based on the medication, the percentage of NK-T cells was increased in patients receiving cyclosporine. In addition, the expression of NKG2D receptor was normal on T and NK-T cells. On the other hand, although the percentage of NK cells was reduced, those cells exhibited normal functionality and cytotoxicity, as shown by the normal expression of NKG2D receptor, CD107α protein and TNF-α.

Η πορεία μιας οξείας σπειραματικής νόσου προς τη χρόνια νεφρική ανεπάρκεια χαρακτηρίζεται από φλεγμονώδεις διεργασίες που εντοπίζονται αρχικά στο σπείραμα, εν συνεχεία στον ενδιάμεσο χώρο, στα ουροφόρα σωληνάρια και τέλος στα νεφρικά αγγεία. Το πρωταρχικό αίτιο για την έναρξη των διεργασιών αυτών είναι η εναπόθεση ανοσοσυμπλεγμάτων στην περιοχή του σπειράματος και η ενεργοποίηση αντιδράσεων που οδηγούν τελικά στην εμφάνιση σπειραματικής σκλήρυνσης, ίνωσης του διαμέσου ιστού και ατροφίας των ουροφόρων σωληναρίων. Οι διεργασίες αυτές φαίνεται να πυροδοτούνται από κυτταροκίνες, όπως είναι οι ιντερλευκίνες (IL-1, IL-2, IL-6) και να εξελίσσονται περαιτέρω κάτω από την επίδραση αυξητικών παραγόντων, όπως είναι ο Transforming Growth Factor (TGF-β1), Epidermal Growth Factor (EGF) και Insulin-like Growth Factor (IGF-1). Πέραν των διεργασιών όμως αυτών, σημαντικό ρόλο στην ολοκλήρωση της καταστροφής του νεφρώνα, φαίνεται να διαδραματίζει ο ρυθμός απόπτωσης των κυττάρων των ουροφόρων σωληναρίων. Πράγματι η απόπτωση αποτελεί ένα σημαντικό μηχανισμό αποικοδόμησης των κυττάρων που σε συνεργασία με την αναγέννησή τους συμβάλλει στη σταθερότητα όλων των βιολογικών συστημάτων (ομοιόσταση). Ο ρυθμός της απόπτωσης των κυττάρων βρίσκεται σε μια σταθερή σχέση με τον ρυθμό αναγέννησης, έτσι ώστε κάθε βιολογικό σύστημα να παραμένει δομικά και λειτουργικά σταθερό. Οι πρωτεΐνες bax και bcl-2 έχουν αποδειχθεί αξιόπιστοι δείκτες της αποπτωτικής διαδικασίας. Η παρούσα μελέτη έχει σαν στόχο να εξετάσει ποιοτικά και ποσοτικά τη συμμετοχή των αυξητικών παραγόντων (TGF-β1, EGF, IGF-1) και των δεικτών της κυτταρικής απόπτωσης (πρωτεΐνες bax και bcl-2) σε ασθενείς με σπειραματικές βλάβες, παρουσία ιστολογικών αλλοιώσεων διαφορετικής βαρύτητας και κατ’ επέκταση διαταραχή της λειτουργίας του νεφρού. Συμπεριελήφθησαν 76 ασθενείς (44 άνδρες και 32 γυναίκες) στους οποίους, με βάση τα ιστολογικά ευρήματα στις βιοψίες του νεφρικού ιστού, ετέθησαν οι διαγνώσεις: ιδιοπαθής μεμβρανώδης σπειραματονεφρίτιδα (n=26), IgA νεφροπάθεια (n=15), νόσος ελαχίστων αλλοιώσεων (n=12), ταχέως εξελισσόμενη σπειραματονεφρίτιδα (n=11), εστιακή σπειραματοσκλήρυνση (n=7) και νεφρίτιδα του λύκου (n=5). Η μέση χρονική διάρκεια παρακολούθησης των ασθενών ήταν 4 χρόνια. Το είδος και η βαρύτητα των δομικών αλλοιώσεων του νεφρικού ιστού συσχετίσθηκαν με την πορεία της νεφρικής λειτουργίας, αλλά και με παραμέτρους των φλεγμονωδών διεργασιών που προσδιορίσθηκαν ανοσοϊστοχημικά, όπως είναι οι αυξητικοί παράγοντες TGF-β1, EGF και IGF-1, οι μυοϊνοβλάστες (κύτταρα που συμμετέχουν στη διαδικασία ανάπτυξης της ίνωσης) και οι δείκτες της κυτταρικής απόπτωσης (πρωτεΐνες bax και bcl-2). Διαπιστώθηκε, λοιπόν, ότι σε ασθενείς με σπειραματική βλάβη η παρουσία των αυξητικών παραγόντων, των μυοϊνοβλαστών και των δεικτών κυτταρικής απόπτωσης στα σπειράματα, στο διάμεσο χώρο και στα ουροφόρα σωληνάρια είναι έντονη. Μάλιστα αυτή του αυξητικού παράγοντα TGF-β1 των μυοϊνοβλαστών και των πρωτεϊνών bax και bcl-2 είναι εντονότερη σε ασθενείς με σημαντικού βαθμού σπειραματική σκλήρυνση, ίνωση του διάμεσου ιστού και ατροφία των ουροφόρων σωληναρίων. Διαπιστώθηκε επίσης σημαντική συσχέτιση της έκφρασης των παραμέτρων αυτών με τη βαρύτητα των ιστολογικών αλλοιώσεων (r=0.444, p<0.05) και το βαθμό έκπτωσης της νεφρικής λειτουργίας (r= 0.454, p<0.05) ενώ αντίθετα δεν παρατηρήθηκε συσχέτιση με τον τύπο της σπειραματικής βλάβης. Αυξημένος ρυθμός κυτταρικής απόπτωσης παρατηρήθηκε στο νεφρικό ιστό ασθενών με έκπτωση της νεφρικής λειτουργίας κατά τη διάγνωση της νόσου. Συμπερασματικά διαπιστώθηκε ότι : 1) Σε όλους τους ασθενείς, ανεξάρτητα από τον τύπο της σπειραματονεφρίτιδας, εντοπίζονται ανοσοϊστοχημικά αυξητικοί παράγοντες στο σπείραμα, στο διάμεσο ιστό και στα ουροφόρα σωληνάρια και μυοϊνοβλάστες κυρίως στο διάμεσο χώρο. 2) Η ποσοτική έκφραση των αυξητικών παραγόντων και ιδιαίτερα του TGF-β1 φαίνεται να σχετίζεται άμεσα με το βαθμό έκπτωσης της νεφρικής λειτουργίας και τη βαρύτητα των ιστολογικών αλλοιώσεων. 3) Ο ρυθμός της κυτταρικής απόπτωσης είναι ανάλογος της βαρύτητας των ιστολογικών αλλοιώσεων και του βαθμού έκπτωσης της νεφρικής λειτουργίας. / The evolution of an acute glomerular injury towards chronic renal failure is characterized by an inflammatory process that is initially localized in the glomeruli and then in the tubulointerstitial area and vessels of the kidney. The deposition of immune complexes in the glomeruli is the main cause of this process that leads to the development of glomerular sclerosis, interstitial fibrosis and tubular atrophy. In this process various cytokines [interleukins (IL), (IL-1, IL-2, IL-6)] and growth factors [Transforming Growth Factor-β (TGF-β), Epidermal Growth Factor (EGF) and Insulin Growth Factor (IGF-1)] are involved. The phenomenon of cellular apoptosis is implicated in the development of renal scarring. Apoptosis represents the programmed cellular death that is in balance with the generation of cells. The rate of cellular apoptosis is responsible for the preservation of homeostasis in each organism. Various genes and proteins are involved in the regulation of apoptosis within kidney. Bax and bcl-2 proteins represent markers of the apoptotic process since bax is related to an enhanced apoptotic rate whereas bcl-2 provides a survival advantage to renal cells. The aim of this study is to investigate the expression of growth factors (TGF-β1, EGF, IGF-1) and apoptotic markers (bax and bcl-2 proteins) in the renal tissue of patients with various types of glomerulonephritis and to identify any correlation of this expression with the severity of histological injury and with the course of renal function. Seventy six patients (44 males and 32 females) were included in the study. The histological diagnoses were: idiopathic membranous nephropathy (n=26), IgA nephropathy (n=15), minimal changes disease (n=12), rapidly progressive glomerulonephritis (n=11), focal segmental glomerulosclerosis (n=7) and lupus nephritis (n=5). The mean follow-up period was 4 years. The expression of growth factors, apoptotic markers and myofibroblasts (cells that are involved in the development of scarring) in the renal tissue was investigated by immunohistochemical technique and quantitated by morphometric analysis. In the renal tissue of patients with glomerulonephritis presence of growth factors, myofibroblasts and apoptotic markers was identified in the glomeruli and in the tubulointerstitial area. The expression of TGF-β1, myofibroblasts and bax, bcl-2 proteins was particularly severe in patients with glomerular sclerosis, interstitial fibrosis and tubular atrophy. The severity of this expression was related to the degree of histological damage (r=0.444, p<0.05) and that of renal impairment (r=0.454, p<0.05) whereas it was not related to the type of glomerulonephritis. In conclusion, it was found that: 1. Growth factors and myofibroblasts are localized in the glomeruli and in the tubulointerstitial area of patients with glomerulonephritis. 2. The severity of growth factors and in particular that of TGF-β1 expression is related to the degree of renal function impairment and to the severity of histological involvement. 3. The rate of cellular apoptosis in the kidney of patients with glomerulonephritis is also related to the severity of histological involvement and to the degree of renal function imparment.