ENCAPSULATING PERITONEAL SCLEROSIS – THE ROLE OF COMPLEMENT

Peritonejska dijaliza (PD) najčešća je kućna metoda dijalitičkog liječenja i jednako je učinkovita kao i hemodijaliza. Potrbušnica bolesnika djeluje kao polupropusna membrana koja dopušta difuziju između dijalizata i cirkulirajuće krvi. Dugotrajna izloženost dijalizatu dovodi do njezina remodeliranja, što rezultira kroničnom upalnom reakcijom s posljedičnom fibrozom. Danas se rabe biokompatibilne dijalizne otopine koje sadrže manje ostatnih produkata degradacije glukoze što u konačnici rezultira manjim oštećenjem potrbušnice. Veza između PD i sustava komplementa nije toliko očita, jer ne dolazi do izravnog kontakta dijalizata s krvi. Međutim, mezotelne stanice proizvode i luče različite komponente komplementa, uključujući C4, C3 i C5-C9. Stanični ostaci kao rezultat izravnog oštećenja potrbušnice PD otopinama manje biokompatibilnosti, kao i protutijela protiv mikroorganizama mogu doprinijeti aktivaciji lokalnih komponenti komplementa tijekom liječenja. Inkapsulirana sklerozirajuća upala potrbušnice (ISUP) je klinički sindrom podmuklog nastanka, koji se kasno prezentira slikom kronične pothranjenosti sa znakovima i simptomima povremene, akutne ili subakutne gastrointestinalne opstrukcije. Ultrasonografija, dijagnostička primjena kontrasta topljivih u vodi i kompjuterizirana tomografija najčešće su korišteni radiološki testovi koji pomažu dijagnozi ISUP. Rezultati o mogućoj terapijskoj primjeni inhibicije komplementa u liječenju i/li prevenciji ISUP su obećavajući, ali preostaje rješavanje brojnih nedoumica na putu prema definitivnom zaključku. Infekcija, fibroza i kardiovaskularni događaji povezani su s aktivacijom sustava komplementa. Ove činjenice predstavljaju mogućnost za terapijsku intervenciju putem sustava komplementa s ciljem poboljšanja biokompatibilnosti dijaliznih otopina, učinkovitosti dijalize i dugoročnog ishoda liječenja.Peritoneal dialysis (PD) is the most widely used home dialysis technique and is as effective as hemodialysis for the treatment of end-stage renal disease. The peritoneum in the abdominal cavity of the patients acts as a semi-permeable membrane allowing diffusion between the dialysis fl uid and the circulation. More biocompatible solutions are now being used that contain less glucose degradation products, which results in reduced peritoneal damage. The link between the complement system and PD seems less obvious because there is no direct contact with blood. However, mesothelial cells produce and secrete different complement factors including C4, C3, and C5 to C9. Cellular debris as a result of direct peritoneal damage by bioincompatible PD fl uids, as well as antibodies against microorganisms could contribute to local complement activation during PD. Encapsulating peritoneal sclerosis (EPS) is a clinical syndrome of insidious onset, presenting late as chronic malnourishment with signs and symptoms of intermittent, acute or subacute gastrointestinal obstruction. Ultrasonography, water-soluble contrast studies and computed tomography scanning are the most widely used radiological tests to aid the diagnosis of EPS. Results on complement inhibition in PD look promising, but many hurdles remain to be solved. Infection, fi brosis, and cardiovascular events are linked to the complement system. These results indicate the possibility of complement interventions in dialysis to improve biocompatibility, dialysis effi cacy, and long-term outcome

ENCAPSULATING PERITONEAL SCLEROSIS – THE ROLE OF COMPLEMENT

Peritonejska dijaliza (PD) najčešća je kućna metoda dijalitičkog liječenja i jednako je učinkovita kao i hemodijaliza. Potrbušnica bolesnika djeluje kao polupropusna membrana koja dopušta difuziju između dijalizata i cirkulirajuće krvi. Dugotrajna izloženost dijalizatu dovodi do njezina remodeliranja, što rezultira kroničnom upalnom reakcijom s posljedičnom fibrozom. Danas se rabe biokompatibilne dijalizne otopine koje sadrže manje ostatnih produkata degradacije glukoze što u konačnici rezultira manjim oštećenjem potrbušnice. Veza između PD i sustava komplementa nije toliko očita, jer ne dolazi do izravnog kontakta dijalizata s krvi. Međutim, mezotelne stanice proizvode i luče različite komponente komplementa, uključujući C4, C3 i C5-C9. Stanični ostaci kao rezultat izravnog oštećenja potrbušnice PD otopinama manje biokompatibilnosti, kao i protutijela protiv mikroorganizama mogu doprinijeti aktivaciji lokalnih komponenti komplementa tijekom liječenja. Inkapsulirana sklerozirajuća upala potrbušnice (ISUP) je klinički sindrom podmuklog nastanka, koji se kasno prezentira slikom kronične pothranjenosti sa znakovima i simptomima povremene, akutne ili subakutne gastrointestinalne opstrukcije. Ultrasonografija, dijagnostička primjena kontrasta topljivih u vodi i kompjuterizirana tomografija najčešće su korišteni radiološki testovi koji pomažu dijagnozi ISUP. Rezultati o mogućoj terapijskoj primjeni inhibicije komplementa u liječenju i/li prevenciji ISUP su obećavajući, ali preostaje rješavanje brojnih nedoumica na putu prema definitivnom zaključku. Infekcija, fibroza i kardiovaskularni događaji povezani su s aktivacijom sustava komplementa. Ove činjenice predstavljaju mogućnost za terapijsku intervenciju putem sustava komplementa s ciljem poboljšanja biokompatibilnosti dijaliznih otopina, učinkovitosti dijalize i dugoročnog ishoda liječenja.Peritoneal dialysis (PD) is the most widely used home dialysis technique and is as effective as hemodialysis for the treatment of end-stage renal disease. The peritoneum in the abdominal cavity of the patients acts as a semi-permeable membrane allowing diffusion between the dialysis fl uid and the circulation. More biocompatible solutions are now being used that contain less glucose degradation products, which results in reduced peritoneal damage. The link between the complement system and PD seems less obvious because there is no direct contact with blood. However, mesothelial cells produce and secrete different complement factors including C4, C3, and C5 to C9. Cellular debris as a result of direct peritoneal damage by bioincompatible PD fl uids, as well as antibodies against microorganisms could contribute to local complement activation during PD. Encapsulating peritoneal sclerosis (EPS) is a clinical syndrome of insidious onset, presenting late as chronic malnourishment with signs and symptoms of intermittent, acute or subacute gastrointestinal obstruction. Ultrasonography, water-soluble contrast studies and computed tomography scanning are the most widely used radiological tests to aid the diagnosis of EPS. Results on complement inhibition in PD look promising, but many hurdles remain to be solved. Infection, fi brosis, and cardiovascular events are linked to the complement system. These results indicate the possibility of complement interventions in dialysis to improve biocompatibility, dialysis effi cacy, and long-term outcome

Vascular Access for Hemodialysis

In this book chapter are described different types of vascular access for hemodialysis, its forms, indications, placement and complications. The chapter is dedicated to health care professionals dealing with chronic kidney disease patients undergoing hemodialysis treatment

ANDERSON-FABRY NEPHROPATHY – CURRENT THERAPEUTIC OPTIONS AND FUTURE PERSPECTIVES

Anderson-Fabryjeva bolest uzrokovana je nedostatnom aktivnošću enzima α-galaktozidaze A što rezultira nakupljanjem glikosfi ngolipida u lizosomima stanica različitih organskih sustava. Bolest se nasljeđuje X-vezano te je zastupljena u oba spola, no u muškaraca, koji su hemizigoti za mutirani gen, simptomi se ispoljavaju ranije uz izraženiji fenotip. Nakupljanje u stanicama bubrega uzrokuje isprva reverzibilne, a potom i ireverzibilne patološke promjene u svim segmentima nefrona što dovodi do proteinurije i bubrežne disfunkcije s postepenom progresijom do terminalnog stadija bubrežnog zatajenja. U ovom radu osvrnuli smo se na trenutne terapijske mogućnosti u obliku intravenske enzimske nadomjesne terapije agalzidazom alfa i agalzidazom beta uz noviju peroralnu metodu liječenja molekularnim šaperonima. Razmotreni su trenutni dosezi istraživanja genske terapije ugradnjom funkcionalnog GLA gena u genom bolesnika, što je budućnost liječenja nasljednih bolesti. Pravovremeno prepoznavanje i liječenje Anderson-Fabryjeve bolesti značajno smanjuju mortalitet i morbiditet pacijenata te povećavaju njihovu kvalitetu života.Anderson-Fabry disease is a lysosomal storage disorder caused by insufficient α-galactosidase A enzyme activity. It is a hereditary X-linked disease that affects both men and women, although males express more typical symptoms at earlier age since they are hemizygotes for the mutated gene. Accumulation of glycosphingolipids in kidney cells has an impact on all nephron segments and causes proteinuria with progressive renal dysfunction, which can ultimately end in terminal renal failure. In this review of the literature, we present therapeutic options including intravenous enzyme replacement therapy with agalsidase alpha and agalsidase beta and oral treatment with molecular chaperons for patients with amenable mutations. Moreover, we investigated current progress in gene therapy of Fabry disease, which is an evolving field with promising results. Timely recognition and early start of treatment significantly reduces morbidity and mortality of patients with Fabry disease, leading to improved quality of life

The influence of erythropoietin treatment on oxidative stress parameters in cortex of rats exposed to transient middle cerebral artery occlusion

Background and Purpose: Erythropoietin (Epo) plays a central role in process of erythropoiesis. Recently, its neuroprotective potential was reported in various experimental models of brain damage. However, the mechanism of Epo protection is still unclear. In the present study, we examined the effect of Epo administration on lipid peroxidation levels and antioxidant enzymes’ (superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)) activities in rat cortex following focal cerebral ischemia. Material and Methods: Focal cerebral ischemia was induced in male HanoverWistar rats (250–350 g) by right middle cerebral artery occlusion (MCAO) model for 1 hr. After 23 hrs of reperfusion, ischemic animals were sacrificed and the levels of lipid peroxidation, SOD and GSH-Px activities were determined spectrophotometrically in the right cortex. Ischemic animals received either vehicle or Epo (5000 IU/kg, intraperitoneally) immediately or 3 hrs after MCAO, and were sacrificed 23 hrs or 21 hrs later, respectively. Sham operated, vehicle treated animals served as the control group. Results and Conclusion: Focal cerebral ischemia significantly increased the level of oxidative lipid damage parameters in the right cortex as compared to the control group without affecting SOD and GSH-Px activities. The decrease in level of lipid peroxidation after Epo treatment was registered but it was not statistically significant. Our results indicate that focal cerebral ischemia caused neuronal damage in the right cortex and that Epo treatment was not effective in preventing above mentioned alteration

VOLUME ASSESSMENT IN THE ACUTE HEART AND RENAL FAILURE

Akutno bubrežno oštećenje (ABO) je bitan klinički čimbenik, poglavito u bolesnika koji se liječe u jedinici intenzivnog liječenja. Prema mnogim studijama, predstavlja ključni čimbenik rizika smrtnosti, neovisno o demografskim karakteristikama ispitanika i težini bolesti. Pojavnost i smrtnost vezano uz taj klinički entitet variraju pa se zbog toga javila potreba za primjenjivim klasifikacijskim sustavom koji bi pomoga u postavljanju dijagnoze, standardizaciji definiranja jačine bubrežnog oštećenja te prognozi ishoda. Tako je 2004. godine utvrđena RIFLE (Risk-Injury-Failure-Loss-End-stage renal disease, engl.), a 2007. AKIN (Acute Kidney Injury Network, engl.) podjela ABO. U kliničkim jedinicama za liječenje kroničnog zatajivanja srca, hipervolemija (koja se u literaturi obično naziva dobivanje na težini) se uzima kao biljeg srčane dekompenzacije. Početak liječenja kontinuiranim metodama nadomještanja bubrežne funkcije poboljšava preživljenje u tih bolesnika na način da se prevenira akumulacija tekućine u organizmu te posljedična hipervolemija. Prevencija, a ne samo ispravak hipervolemije, bi trebala biti indikacija za početak liječenja vantjelesnim kontinuiranim metodama za uklanjanje viška tekućine, neovisno o potrebi za klirensom određenih molekula. Oligurija je definirana proizvodnjom urina manjom od 0,3 ml/kg/sat u najmanje 24 sata. Svaka odgoda liječenja oligurije može dovesti do ABO te je stoga njeno rano prepoznavanje izuzetno važno. Bolesnici u jedinicama intenzivnog liječenja s oliguričnim ABO su izloženi povećanom riziku neravnoteže tjelesne tekućine zbog sustavne upale, smanjenog onkotskog tlaka plazme te povećane kapilarne permeabilnosti. Osim toga, posebice su izloženi riziku za razvoj hipervolemije te je zbog toga restriktritvana strategija unosa tekućine u tih bolesnika prijeko potrebita kad god je to moguće.Acute kidney injury (aki) is an important clinical issue, especially in the setting of critical care. it has been shown in multiple studies to be a key independent risk factor for mortality, even after adjustment for demographics and severity of illness. there is wide agreement that a generally applicable classification system is required for aki which helps to standardize estimation of severity of renal disfunction and to predict outcome associated with this condition. that’s how rifLe (risk-injury-failure-Loss-end-stage renal disease), and akiN (acute kidney injury Network) classifications for aki were found in 2004 and 2007, espectively. in the clinical setting of heart failure, a positive fluid balance (often expressed in the literature as weight gain) is used by disease management programs as a marker of heart failure decompensation. oliguria is defined as urine output less than 0,3 ml/kg/h for at least 24 h. since any delay in treatment can lead to a dangerous progression of the aki, early recognition of oliguria appears to be crucial. critically ill patients with oliguric aki are at increased risk for fluid imbalance due to widespread systemic inflammation, reduced plasma oncotic pressure and increased capillary leak. these patients are particulary at risk of fluid overload and therefore restrictive strategy of fluid administration should be used. objective, rapid and accurate volume assessment is important in undiagnosed patients presenting with critical illness, as errors may result in interventions with fatal outcomes. the historical tools such as physical exam, and chest radiography suffer from significantlimitations. as gold standard, radioisotopic measurement of volume is impractical in the acute care enviroment. Newer technologies offer the promise of both rapid and accurate bedside estimation of volume status with the potential to improve clinical outcomes. Blood assessment with bioimpendance vector analysis, and bedside ultrasound seem to be promising technologies for this need

The influence of erythropoietin treatment on oxidative stress parameters in cortex of rats exposed to transient middle cerebral artery occlusion

Background and Purpose: Erythropoietin (Epo) plays a central role in process of erythropoiesis. Recently, its neuroprotective potential was reported in various experimental models of brain damage. However, the mechanism of Epo protection is still unclear. In the present study, we examined the effect of Epo administration on lipid peroxidation levels and antioxidant enzymes’ (superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)) activities in rat cortex following focal cerebral ischemia. Material and Methods: Focal cerebral ischemia was induced in male HanoverWistar rats (250–350 g) by right middle cerebral artery occlusion (MCAO) model for 1 hr. After 23 hrs of reperfusion, ischemic animals were sacrificed and the levels of lipid peroxidation, SOD and GSH-Px activities were determined spectrophotometrically in the right cortex. Ischemic animals received either vehicle or Epo (5000 IU/kg, intraperitoneally) immediately or 3 hrs after MCAO, and were sacrificed 23 hrs or 21 hrs later, respectively. Sham operated, vehicle treated animals served as the control group. Results and Conclusion: Focal cerebral ischemia significantly increased the level of oxidative lipid damage parameters in the right cortex as compared to the control group without affecting SOD and GSH-Px activities. The decrease in level of lipid peroxidation after Epo treatment was registered but it was not statistically significant. Our results indicate that focal cerebral ischemia caused neuronal damage in the right cortex and that Epo treatment was not effective in preventing above mentioned alteration

Health-related quality of life in patients on renal replacement therapy

U medicinskoj znanosti mjerenje zdravlja, praćenje kvalitete života i kvalitete života vezane uz zdravlje (KŽVZ) predstavljaju prihvaćene instrumente za procjenu utjecaja bolesti i različitih postupaka liječenja na bolesnikovo tjelesno ili emocionalno stanje u svakodnevnim aktivnostima. KŽVZ predstavlja dio općeg koncepta kvalitete života koji se odnosi specifično na zdravlje osobe, a označava mjerenje funkcioniranja, blagostanja i opće percepcije zdravlja bolesnika u tri domene: fizičkoj, mentalnoj i socijalnoj. Instrumenti za mjerenje KŽVZ temelje se na konceptu zdravlja koji je višedimenzionalan, a izvor informacija je sam bolesnik. Mogu se klasificirati kao generički ili specifični. Generički instrumenti procjenjuju koncept zdravlja koji predstavlja temeljnu humanu vrijednost i odnose se na zdravstveno stanje i blagostanje svakog pojedinca, neovisno o dobi, bolesti ili načinu liječenja. Specifični instrumenti usmjereni su na specifičnu bolest, stanje ili liječenje. Rezultati istraživanja KŽVZ u bolesnika u završnom stupnju bubrežnog zatajenja pokazali su nižu kvalitetu života kao i funkcionalni status bolesnika u usporedbi s općom populacijom. Prema navedenim podacima KŽVZ predstavlja novu mjeru ishoda liječenja bolesnika na hemodijalizi. U brojnim je studijama potvrđeno da KŽVZ, mentalna i fizička komponenta zasebno, predstavljaju nezavisne pretkazivače za povećan rizik od smrti i hospitalizacije bolesnika liječenih nadomještanjem bubrežne funkcije.In the medical field health status measurement, quality of life and health-related quality of life (HRQOL) assessment are adopted instruments to evaluate the effects that a disease and different treatment or intervention have on patient’s physical or emotional state in everyday activities. HRQOL as the subset of overall concept of quality of life that relates specifically to a person’s health refers to the measure of the patients’ functioning, well-being and general health perception in three domains: physical, psychological and social. HRQOL instruments are based on multidimensional health concept, in which the source of information is patient. Available instruments are classifiable as generic or specific. Generic instruments assess health concepts that represent basic human values and are relevant to everyone’s health status and well-being and are not specific for age, disease or treatment. Specific instruments focus on the specific disease, condition or treatment. Reports on HRQOL in end-stage renal disease patients have shown impairment of quality of life and functional status compared with general population. There is evidence that HRQOL predicts outcomes in hemodialysis patients. Many studies have found that HRQOL, physical and mental components, are independent predictors for higher risk of death and hospitalization among patients on renal replacement therapy