Cardiorenal syndrome

Smanjena bubrežna funkcija česta je u bolesnika sa zatajivanjem srca i obrnuto, bubrežni bolesnici često imaju popratnu bolest srca. To je dovelo do stvaranja koncepta kardiorenalnog sindroma (KRS) kao patofiziološkog poremećaja u kojem akutna ili kronična disfunkcija jednog može dovesti do akutne ili kronične disfunkcije drugog organa. Dijeli se na pet podtipova ovisno o primarnoj disfunkciji organa i vremenskom nastanku. KRS u kojem su primarno zahvaćeni srce i bubrezi nazivamo primarnim, a ako je njihova disfunkcija posljedica sustavnog zbivanja u organizmu, onda govorimo o sekundarnom KRS-u. Složeni patofiziološki mehanizmi tek su djelomice poznati, a aktivacija renin-angiotenzin-aldosteronskog sustava, endotelna disfunkcija, aktivacija simpatičkog živčanog sustava i upala temeljne su značajke razvoja ovog sindroma. U ranoj dijagnostici KRS-a, osobito bubrežnog oštećenja, danas se sve više koriste novi proteinski biomarkeri, čije su vrijednosti povišene već kod blagog smanjenja bubrežne funkcije, daleko prije nego što dođe do porasta serumskog kreatinina. S obzirom na to da su bolesnici s KRS-om najčešće isključivani iz velikih kliničkih studija, ne postoje smjernice za liječenje ovog sindroma, stoga se u svakodnevnoj praksi najčešće služimo empirijskim liječenjem, a upravo zbog straha od pogoršanja bubrežne funkcije ovi bolesnici često ne dobivaju svu potrebnu terapiju. Prevencija nastanka KRS-a vrlo je važna s obzirom na to da nastanak KRS-a dovodi do nepotpuno reverzibilnih oštećenja srca i bubrega, povećane stope hospitalizacija te povećanog rizika od nastanka komplikacija, potreba za nadomjesnim liječenjem bubrežne funkcije i smrti. U ovom preglednom članku prikazali smo dosadašnje epidemiološke i patofiziološke spoznaje o KRS-u, kao i preporuke za njegovo liječenje i prevenciju.Renal dysfunction is often present in patients with heart failure, and vice versa, patients with kidney disease have often concomitant heart dysfunction. This has led to the concept of cardiorenal syndrome (CRS) as a pathophysiological disorder in which dysfunction of one organ induces dysfunction in the other. It is subdivided into five subtypes depending on the primacy of organ dysfunction and the time-frame of the syndrome. CRSs in which heart and kidney are primary involved are named primary, and CRS in which systemic conditions lead to simultaneous injury of heart and kidney are named secondary CRS. Involved complex pathophysiological mechanisms are poorly understood. Renin-angiotensinaldosteron system activation, endothelial dysfunction, sympathetic system activation and inflammation are the fundamental principles in the development of this syndrome. In the early diagnosis of renal dysfunction in CRS, new protein biomarkers are used, whose values have increased already at a mild renal impairment, far before an increase of serum creatinine. Since patients with CRS are often excluded from large clinical trials, we do not have guidelines for the treatment of this syndrome. In every-day practice we usually employ empirical treatment. Based on the concern of worsening kidney function, patients with CRS often do not receive appropriate medication. Prevention of CRS is of enormous importance because this syndrome is not completely reversible and are associated with higher hospitalization rate, complicated procedures, need for renal replacement therapy, and death. Current epidemiological and pathophysiological knowledge about CRS, as well as recommendations for its treatment and prevention are reviewed

EFFICACY AND SAFETY OF CERA IN ANEMIA CORRECTION IN PREDIALYSIS PATIENTS - CROATIAN EXPERIENCE

U ovoj opservacijskoj studiji prikazali smo sigurnost i učinkovitost primjene CERA u liječenju anemije kronične bubrežne bolesti (KBB) u predijaliznih bolesnika. U praćenje je bilo uključeno ukupno 27 bolesnika u 4. i 5. stadiju KBB s anemijom u kojih je bilo indicirana primjena lijekova koji stimuliraju eritropoezu (LSE). Svi su bolesnici primili ERA upkutano u dozi od 0,6 μg/kg svaka dva tjedna u razdoblju od korekcije anemije ili jednom mjesečno nakon toga. Bolesnici su praćeni u razdoblju od 3-12 mjeseci. Pod odgovorom na terapiju s CERA podrazumijevalo se ili porast vrijednosti Hb za barem 10 g/L unutra perioda od mjesec dana ili postizanje ciljnih vrijednosti Hb. Godinu dana nakon početka primjene CERA svi su bolesnici imali Hb u rasponu 100-120 g/L, a smanjila se i fluktuacija Hb. Nije bilo statistički značajne razlike u razini Hb ovisno o uzroku osnovne bubrežne bolesti i dobi bolesnika. Na kraju praćenja većina je bolesnika navela bolje podnošenje napora, te bolje spavanje i manju razdražljivost. Osim povišenja arterijskog tlaka koji je uspješno kontroliran primjenom antihipetenzivne terapije, nismo uočili druge nuspojave primjene CERA Rezultati pokazuju da je primjena CERA učinkovita i sigurna u liječenju anemije u bolesnika s KBB koji nisu započeli liječenje nadomještanjem bubrežne funkcije.Aim: to evaluate efficacy and safety of cera (continuous erythropoietin receptor activator) administration for correcting anemia in the patients with chronic kidney disease (ckd), not on dialysis. methods: We performed observational study on 27 ckd patients in stage 4 or 5 with renal anemia requiring use of erythropoiesis-stimulating agents (esa). all patients received cera (mircera®; roche, basel, switzerland) subcutaneously in dose of 0.6 μg per kg very two weeks during the correction phase of anemia treatment or once monthly during the maintenance treatment. dose of cera was modified according to manufacturer instructions. iron supplementation was administrated orally or intravenously in order to achieve serum ferritin 200-500 μg/L. Patients were followed up to 1 year (from 3-12 months). response riteria for cera were Hb increas

Cardiorenal syndrome

Smanjena bubrežna funkcija česta je u bolesnika sa zatajivanjem srca i obrnuto, bubrežni bolesnici često imaju popratnu bolest srca. To je dovelo do stvaranja koncepta kardiorenalnog sindroma (KRS) kao patofiziološkog poremećaja u kojem akutna ili kronična disfunkcija jednog može dovesti do akutne ili kronične disfunkcije drugog organa. Dijeli se na pet podtipova ovisno o primarnoj disfunkciji organa i vremenskom nastanku. KRS u kojem su primarno zahvaćeni srce i bubrezi nazivamo primarnim, a ako je njihova disfunkcija posljedica sustavnog zbivanja u organizmu, onda govorimo o sekundarnom KRS-u. Složeni patofiziološki mehanizmi tek su djelomice poznati, a aktivacija renin-angiotenzin-aldosteronskog sustava, endotelna disfunkcija, aktivacija simpatičkog živčanog sustava i upala temeljne su značajke razvoja ovog sindroma. U ranoj dijagnostici KRS-a, osobito bubrežnog oštećenja, danas se sve više koriste novi proteinski biomarkeri, čije su vrijednosti povišene već kod blagog smanjenja bubrežne funkcije, daleko prije nego što dođe do porasta serumskog kreatinina. S obzirom na to da su bolesnici s KRS-om najčešće isključivani iz velikih kliničkih studija, ne postoje smjernice za liječenje ovog sindroma, stoga se u svakodnevnoj praksi najčešće služimo empirijskim liječenjem, a upravo zbog straha od pogoršanja bubrežne funkcije ovi bolesnici često ne dobivaju svu potrebnu terapiju. Prevencija nastanka KRS-a vrlo je važna s obzirom na to da nastanak KRS-a dovodi do nepotpuno reverzibilnih oštećenja srca i bubrega, povećane stope hospitalizacija te povećanog rizika od nastanka komplikacija, potreba za nadomjesnim liječenjem bubrežne funkcije i smrti. U ovom preglednom članku prikazali smo dosadašnje epidemiološke i patofiziološke spoznaje o KRS-u, kao i preporuke za njegovo liječenje i prevenciju.Renal dysfunction is often present in patients with heart failure, and vice versa, patients with kidney disease have often concomitant heart dysfunction. This has led to the concept of cardiorenal syndrome (CRS) as a pathophysiological disorder in which dysfunction of one organ induces dysfunction in the other. It is subdivided into five subtypes depending on the primacy of organ dysfunction and the time-frame of the syndrome. CRSs in which heart and kidney are primary involved are named primary, and CRS in which systemic conditions lead to simultaneous injury of heart and kidney are named secondary CRS. Involved complex pathophysiological mechanisms are poorly understood. Renin-angiotensinaldosteron system activation, endothelial dysfunction, sympathetic system activation and inflammation are the fundamental principles in the development of this syndrome. In the early diagnosis of renal dysfunction in CRS, new protein biomarkers are used, whose values have increased already at a mild renal impairment, far before an increase of serum creatinine. Since patients with CRS are often excluded from large clinical trials, we do not have guidelines for the treatment of this syndrome. In every-day practice we usually employ empirical treatment. Based on the concern of worsening kidney function, patients with CRS often do not receive appropriate medication. Prevention of CRS is of enormous importance because this syndrome is not completely reversible and are associated with higher hospitalization rate, complicated procedures, need for renal replacement therapy, and death. Current epidemiological and pathophysiological knowledge about CRS, as well as recommendations for its treatment and prevention are reviewed

Online hemodiafiltration – new standard in the dialysis treatment?

Danas se u svijetu više od milijun bolesnika liječi dijalizom kao terapijom izbora u završnom stadiju kronične bubrežne bolesti. Hemodijaliza je jedan od postupaka nadomještanja bubrežne funkcije. Procesima difuzije, konvekcije i ultrafiltracije odstranjuju se uremijski toksini i višak tekućine, nadomještaju tvari koje su u manjku, te ispravljaju poremećaji ravnoteže elektrolita i acidobazne ravnoteže. Membrane dijalizatora koje se danas upotrebljavaju su sintetske membrane visoke biokompatibilnosti (niskoprotočne, koje se koriste za standardnu hemodijalizu i visokoprotočne, koje se koriste za hemodijafiltraciju – HDF). Dijalizat ili dijalizna tekućina je otopina točno određenog sastava, slična ljudskoj plazmi, a koristi se za uravnoteženje sastava tjelesnih tekućina. HDF je hemodijalizna procedura koja kombinira principe hemodijalize i hemofiltracije kako bi omogućila bolje odstranjenje molekula srednje i velike molekulske težine. Zbog brojnih mogućnosti koje pruža online pripremljena supstitucijska tekućina, online hemodiafiltracija – OLHDF mnogo je praktičniji način HDF. Brojne su prednosti OLHDF, a neke od njih su: smanjena stopa smrtnosti, veća doza isporučene dijalize, ispravak pothranjenosti, protuupalni učinak, bolja kontrola krvnog tlaka i hemodinamske stabilnosti, bolja kontrola razine fosfora u krvi, bolji utjecaj na ispravak anemije te veći stupanj biokompatibilnosti. Primjena OLHDF zbog svojih brojnih prednosti poželjna je u svih bolesnika liječenih hemodijalizom, međutim, zbog visoke cijene, primjena je za sada još uvijek ograničena i slabo zastupljena. OLHDF osigurava najpovoljniji fiziološki profil uklanjanja srednjih i velikih molekula, te poboljšanje brojnih patoloških stanja koja pogađaju bolesnike liječene hemodijalizom. Zato OLHDF predstavlja nov korak prema zlatnom standardu u liječenju dijalizom.Currently, more than a million patients worldwide are supporting renal function by dialysis as a treatment of choice in the End-stage Renal Disease. Hemodialysis is one of the modalities of renal replacement therapy. Hemodialysis removes nitrogenous and other waste products, corrects electrolyte, water and acid abnormalities by diffusion, convection and ultrafiltration. Hemodialiysis membranes which are presently in use are the synthetic membranes of high biocompatibility (low-flux for conventional hemodialysis and high-flux for hemodiafiltration). Dialysate is a solution of purified water and electrolytes and is used for balancing a composition of blood. Hemodiafiltration is hemodialysis modality that combines principles of hemodialysis and hemofiltration (diffusion and convection) to enhance removal of both, high and low molecular weight uremic toxins. Online hemodiafiltration (OLHDF) offers production of substitution fluid in dialysis machine from fresh dialysate, that’s why the technique of OLHDF is simplified to use and economically acceptable. There are many clinical advantages of OLHDF, some of them are: lower mortality risk, higher delivered dialysis dose, correction of malnutrition, anti-inflammatory effect, improvement of blood pressure and hemodynamic stability, better control of hyperphosphatemia, anemia and greater biocompatibility. Despite of numerous clinical advantages, OLHDF is not still widely in use in maintenance hemodialysis patients, mainly because of the higher price of high permeable filters. Although, any dialysis modality, regardless of performance and efficiency will only partially restore integrity of renal function, OLHDF seems to offer the most physiological way to enhance the removal of uremic toxins and improvement of many comorbidities that are renal patients faced with. OLHDF is a step forward to gold standard in renal replacement treatment

CONSENSUS STATEMENT OF THE CROATIAN SOCIETY FOR NEPHROLOGY, DIALYSIS AND TRANSPLANTATION REGARDING THE USE OF GENERIC IMMUNOSUPPRESSIVE DRUGS

Uporaba generičkih imunosupresijskih lijekova može smanjiti trošak transplantacije, iako je ukupan trošak vezan uz prevođenje bolesnika s originalnog na generički pripravak predmet trajnih rasprava s obzirom na potrebu učestalog praćenja bolesnika. Hrvatsko društvo za nefrologiju, arterijsku hipertenziju, dijalizu i transplantaciju osnovalo je radnu skupinu s ciljem donošenja preporuka za uporabu generičkih imunosupresiva nakon transplantacije bubrega. Imunosupresijski lijekovi pripadaju tzv. "lijekovima uske terapijske širine” s velikim varijacijama u serumskoj koncentraciji lijeka s obzirom na unos hrane i pića, druge lijekove, ali i funkciju jetre i bubrega. Nemogućnost održavanja odgovarajuće ravnoteže imunosupresije rezultira poremećajem funkcije presatka, ali ugrožava i život bolesnika. Podatci o terapijskoj ekvivalenciji različitih generičkih imunosupresiva su rijetki ili ih uopće nema. Radovi o toj temi se nedovoljno objavljuju. Postojanje velikog broja različitih generičkih oblika na tržištu nosi opasnost nekontroliranog prevođenja bolesnika s jednog na drugi oblik lijeka od strane ljekarnika ili liječnika obiteljske medicine, što može imati teške posljedice budući da generički lijekovi ne moraju biti međusobno bioekvivalentni, već se bioekvivalencija uspoređuje samo s originatorom. Hrvatsko društvo za nefrologiju, dijalizu i transplantaciju bubrega se ne protivi uporabi generičkih imunosupresiva, ali smatra da se smiju rabiti samo pod strogim nadzorom i uz indikaciju nefrologa koji se bave transplantacijskom medicinom. Potrebno je uložiti daljnje napore u edukaciju bolesnika, liječnika obiteljske medicine i ljekarnika kako bi se izbjegle neželjene pojave nekontrolirane uporabe imunosupresijskih lijekova.The use of generic immunosuppressive drugs may decrease the cost of immunosuppressive medication, although total cost savings are still a matter of debate since patients need close monitoring after conversion from original to the generic formulation. A working group of the Croatian Society of Transplantation was established to develop recommendations on the use of generic immunosuppression in renal transplant recipients based on a review of the available data. Immunosuppressive drugs belong to the ‘narrow therapeutic index’ drugs, with huge pharmacokinetic variations secondary to the impact of food, other drugs, as well as of kidney and liver function. Failure to maintain an appropriate balance of immunosuppression seriously influences graft and patient survival. Published evidence supporting therapeutic equivalence of generic formulations is scarce or completely lacking. Different generic formulations may expose patients to uncontrolled product switching by pharmacists or general practitioners, which is very dangerous for patients, since generic preparations are not required to demonstrate bioequivalence with each other. The Croatian Society for Nephrology, Dialysis and Transplantation is not against the use of generic immunosuppressive drugs, but it requires close supervision of nephrologists and respecting the strict rules of their use. More efforts should be invested in education of primary care physicians as well as of patients to be aware of differences between the original and generic, as well as between different generic formulations

Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in the Early Period after Kidney Transplantation

The role of renin-angiotensin system inhibitors (ACE-inhibitors) or angiotensin receptor blockers (ARB) in the renal transplant recipients (RTRs) is incompletely defined and according to the current guidelines they should be initiated af- ter six months post-transplantation. The aim of the present paper is to evaluate the efficiency and safety of early (within six months post-transplantation) versus late (after six months post-transplantation) initiation of ACE-inhibitors or ARB in RTRs. The study group compromised of 108 RTRs (50 male and 58 female) who received a kidney transplant. Beside other prescribed antihypertensive drugs all of them took and ACE inhibitors or ARB in order to achieve blood pressure control. For this analysis purpose, recipients were stratified into two groups according to the time of ACE inhibitors/ARB initiation into early (within six months post-transplantation) and late (after six months after transplantation) group. For each patient haemoglobin, serum creatinine and potassium levels were analyzed at the beginning of ACE inhibitors/ARB introduction and at the end of the first, third, sixth and twelfth month. In the 54 (50%) of the 108 patients ACE inhibi- tors/ARB were initiated within six months post-transplantation and in 49 (90.7%) of them within three months (in 29 pa- tients within one month; in 13 within two months; in 7 within 3 months) post-transplantation. In additional 54 (50%) patients ACE inhibitors/ARB were initiated, but after six months post-transplantation. There was no statistically signifi- cant difference between the two groups related to age or gender and due to the duration of dialysis treatment before the transplantation. Analyzing the haemoglobin, creatinine and potassium serum levels after initiation of therapy with ACE inhibitors/ARB trough observed period we did not found any statistically significant difference in all measured parame- ters between the two groups of patients and also within the same group of patients. Therefore, according to experience from our Institution early initiation of ACE inhibitors or ARB appears to be safe in carefully selected recipients with rela- tively good early graft function

Effect of Statin Therapy Duration on Bone Turnover Markers in Dyslipidemic Patients

Background and Purpose: Statins are cholesterol-lowering drugs decreasing bone resorption by inhibition of the farnesyl diphosphate synthase step in the mevalonic acid pathway and therefore are believed to have beneficial effects on bone status. The objective was to examine the relationship between statin therapy duration and bone turnover markers in dyslipidemic patients. Patients and Methods: Two hundred and eighty subjects were divided into five groups depending on duration of statin therapy: (controls 0 yrs); (0.1-1.5 yrs); (2-5 yrs); (6-10 yrs); (11-30 yrs). ELISA method was applied on fasting serums using bone formation markers: Osteoprotegerin (pmol/l) and Osteocalcin (ng/ml) and bone resorption markers: sRANKL (pmol/l) and CrossLaps (ng/ml). In statistical analysis, multiple regressions were used. Results: A common influence of studied predictor variables was statistically significant for sRANKL, Serum CrossLaps and osteocalcin (P<0.001), while statistical significance was not found for osteoprotegerin. The largest shares of contributions were recorded in Model 2 for the statin group (40%) and BMI (36%) and in Model 1 for statin group (35%) and total cholesterol (28%). Conclusions: Statins showed favorable influence on osteocalcin and sRANKL, indicating improved bone metabolism in patients with longer duration of statin therapy

Renal dysfunction and anemia in patients with heart failure — the cardio-renal anemia syndrome

Cardiovascular diseases are the leading cause of morbidity and mortality in patients with chronic kidney disease. The appearance of cardiovascular complications is strongly in positive correlation with the severity of kidney disease. About 40% of patients with moderate or severe kidney disease and even 60% of patients in the terminal phase have some degree of chronic heart failure. “The Cardio-Renal Syndrome” represents a variety of pathophysiological abnormalities of the heart and kidney, where acute or chronic dysfunction of one organ may provoke acute or chronic dysfunction of the other organ. Renal impairment and anemia are frequent in heart failure patients and negatively influence the quality of life and life expectancy. The coexistence of these three conditions has been described as “The Cardio-Renal Anemia Syndrome” (CRAS). Although the syndrome has been generally defined, there are no guidelines for CRAS diagnosis and treatment, and management of patients mostly depends on the specialty of the physician met first. Currently, anemia in CRAS must be treated according to the guidelines for anemia in chronic kidney disease. After several smaller clinical trials with encouraging results, larger ongoing cinical investigations will elucidate the real importance of anemia management in patients with heart failure. By the time specific guidelines for CRAS management are published, there will be a need for multidisciplinary approach, based on the existing separate guidelines for all components of the syndrome