CALCIFIC UREMIC ARTERIOLOPATHY: CLINICAL FEATURES AND TREATMEN

Kalcificirajuća uremijska arteriolopatija ili kalcifilaksija zloćudni je oblik kalcificiranja malih arterija i arteriola najčešće u bolesnika s nadomjesnim liječenjem kronične bubrežne bolesti. Uzrokuje visoku smrtnost. Histološka karakterističnost bolesti ogleda se u zahvaćenosti intimalnog sloja arterije gdje su prisutne proliferacija, linearna kalcificiranost unutarnje elastične membrane uz kalcificiranost medijalnoga mišićnog sloja arterije te često u upali i nekrozi potkožnoga masnog tkiva. Bolest započinje bolnim egzantemom, crvenkastolividnim nepravilnim plakovima ili mrežoliko oblikovanim lividnoljubičastim pjegama. Može napredovati prema eshari ili ranama koje se inficiraju i često uzrokuju sepsu. Prva prikazana bolesnica s proksimalnim tipom kalcifilaksije umrla je pod slikom ponovljene sepse. Druga bolesnica s distalnim tipom kalcifilaksije uspješno je liječena. Prijelomni trenutak liječenja nastupio je primjenom kalcimimetika. Liječenje je višestruko. Nužno je normaliziranje metabolizma P i Ca. Izdvaja se učinkovitost kalcimimetika, natrijskog tiosulfata, O2, pažljiva primjena bifosfonata i kirurških postupaka u liječenju rana. Potrebno je obustaviti liječenje varfarinom i razumno je primijeniti vitamin K. Karbonilirani hemoglobin mogao bi potaknuti brže cijeljenje neinficiranih rana.Calcific uremic arteriolopathy or calciphylaxis is a malignant form of calcification of small arteries and arterioles, usually present in patients with chronic kidney disease and dialysis therapy. It causes high mortality. Histological distinctive feature are calcium deposits lining vascular intima. Calcification of medial muscle layer, inflammation and necrosis of subcutaneous adipose tissue are frequent. The disease begins with painful violaceous mottling, resembling livedo reticularis. The skin lesion progresses to ulcers and eschars, sometimes it becomes very vulnerable to secondary infection which can often develop into fatal sepsis. Our first patient with the proximal form of calciphylaxis died in repeated sepsis. The second patient with the distal form of calciphylaxis was treated successfully. The decisive moment was the use of calcimimetic. A multiinterventional strategy is likely to be more effective than any single therapy. It is necessary to regulate metabolism of calcium phosphate and secondary hyperparathyroidism. Effectiveness has been demonstrated using calcimimetics, sodium thiosulfate, oxygen therapy, careful application of biphosphonates and surgical procedures. Warfarin withdrawal is urgently recommended and subsequent vitamin K supplementation is appropriate. The control of infection is critically important and the use of carbonylated hemoglobin in the stage without infection could accelerate the wound healing

Kalcificirajuća uremijska arteriolopatija: klinička slika i liječenje [Calcific uremic arteriolopathy: clinical features and treatment]

Calcific uremic arteriolopathy or alciphylaxis is a malignant form of calcification of small arteries and arterioles, usually present in patients with chronic kidney disease and dialysis therapy. It causes high mortality. Histological distinctive feature are calcium deposits lining vascular intima. Calcification of medial muscle layer, inflammation and necrosis of subcutaneous adipose tissue are frequent. The disease begins with painful violaceous mottling, resembling livedo reticularis. Ths skin lesion progresses to ulcers and eschars, sometimes it becomes very vulnerable to secondary infection which can often develop into fatal sepsis. Our first patient with proximal form of calciphylaxis dies in repeated sepsis. The second patient with the distal form of calciphylaxis was treated successfully. The decisive moment was the use of calcimimetic. A multiinterventional strategy is likely to be more effective than any single therapy. It is necessary to regulate metabolism of calcium phosphate and secondary hyperparathyroidism. Effectiveness has been demonstrated using calcimimetics, sodium thiosulfate, oxygen therapy, careful application of biphosphonates and surgical procedures. Warfarin withdrawal is urgently recommended and subsequent vitamin K supplementation is appropriate. The control of infection is critically important and the use of carbonylated hemoglobin in the stage without infections could accelerate the wound healing

CALCIFIC UREMIC ARTERIOLOPATHY: CLINICAL FEATURES AND TREATMEN

Kalcificirajuća uremijska arteriolopatija ili kalcifilaksija zloćudni je oblik kalcificiranja malih arterija i arteriola najčešće u bolesnika s nadomjesnim liječenjem kronične bubrežne bolesti. Uzrokuje visoku smrtnost. Histološka karakterističnost bolesti ogleda se u zahvaćenosti intimalnog sloja arterije gdje su prisutne proliferacija, linearna kalcificiranost unutarnje elastične membrane uz kalcificiranost medijalnoga mišićnog sloja arterije te često u upali i nekrozi potkožnoga masnog tkiva. Bolest započinje bolnim egzantemom, crvenkastolividnim nepravilnim plakovima ili mrežoliko oblikovanim lividnoljubičastim pjegama. Može napredovati prema eshari ili ranama koje se inficiraju i često uzrokuju sepsu. Prva prikazana bolesnica s proksimalnim tipom kalcifilaksije umrla je pod slikom ponovljene sepse. Druga bolesnica s distalnim tipom kalcifilaksije uspješno je liječena. Prijelomni trenutak liječenja nastupio je primjenom kalcimimetika. Liječenje je višestruko. Nužno je normaliziranje metabolizma P i Ca. Izdvaja se učinkovitost kalcimimetika, natrijskog tiosulfata, O2, pažljiva primjena bifosfonata i kirurških postupaka u liječenju rana. Potrebno je obustaviti liječenje varfarinom i razumno je primijeniti vitamin K. Karbonilirani hemoglobin mogao bi potaknuti brže cijeljenje neinficiranih rana.Calcific uremic arteriolopathy or calciphylaxis is a malignant form of calcification of small arteries and arterioles, usually present in patients with chronic kidney disease and dialysis therapy. It causes high mortality. Histological distinctive feature are calcium deposits lining vascular intima. Calcification of medial muscle layer, inflammation and necrosis of subcutaneous adipose tissue are frequent. The disease begins with painful violaceous mottling, resembling livedo reticularis. The skin lesion progresses to ulcers and eschars, sometimes it becomes very vulnerable to secondary infection which can often develop into fatal sepsis. Our first patient with the proximal form of calciphylaxis died in repeated sepsis. The second patient with the distal form of calciphylaxis was treated successfully. The decisive moment was the use of calcimimetic. A multiinterventional strategy is likely to be more effective than any single therapy. It is necessary to regulate metabolism of calcium phosphate and secondary hyperparathyroidism. Effectiveness has been demonstrated using calcimimetics, sodium thiosulfate, oxygen therapy, careful application of biphosphonates and surgical procedures. Warfarin withdrawal is urgently recommended and subsequent vitamin K supplementation is appropriate. The control of infection is critically important and the use of carbonylated hemoglobin in the stage without infection could accelerate the wound healing

Tunnelled haemodialysis catheter and haemodialysis outcomes: a retrospective cohort study in Zagreb, Croatia

OBJECTIVES: Studies have reported that the tunnelled dialysis catheter (TDC) is associated with inferior haemodialysis (HD) patient survival, in comparison with arteriovenous fistula (AVF). Since many cofactors may also affect survival of HD patients, it is unclear whether the greater risk for survival arises from TDC per se, or from associated conditions. Therefore, the aim of this study was to determine, in a multivariate analysis, the long-term outcome of HD patients, with respect to vascular access (VA). ----- DESIGN: Retrospective cohort study. ----- PARTICIPANTS: This retrospective cohort study included all 156 patients with a TDC admitted at University Hospital Merkur, from 2010 to 2012. The control group consisted of 97 patients dialysed via AVF. The groups were matched according to dialysis unit and time of VA placement. The site of choice for the placement of the TDC was the right jugular vein. Kaplan-Meier analysis with log-rank test was used to assess patient survival. Multivariate Cox regression analysis was used to determine independent variables associated with patient survival. ----- PRIMARY OUTCOME MEASURES: Patient survival with respect to VA. ----- RESULTS: The cumulative 1-year survival of patients who were dialysed exclusively via TDC was 86.4% and of those who were dialysed exclusively via AVF, survival was 97.1% (p=0.002). In multivariate Cox regression analysis, male sex and older age were independently negatively associated with the survival of HD patients, while shorter HD vintage before the creation of the observed VA, hypertensive renal disease and glomerulonephritis were positively associated with survival. TDC was an independent risk factor for survival of HD patients (HR 23.0, 95% CI 6.2 to 85.3). ----- CONCLUSION: TDC may be an independent negative risk factor for HD patient survival

VITAMIN D IN PATIENTS WITH CHRONIC KIDNEY DISEASE TREATED WITH HEMODIALYSIS

Cilj rada bio je odrediti status vitamina D u bolesnika s terminalnom kroničnom bubrežnom bolešću liječenih kroničnom hemodijalizom (KBB-5-HD) i povezanost s osnovnim kliničkim i laboratorijskim parametrima. Bolesnici i metode: Presječno opservacijsko retrospektivno istraživanje provedeno je u bolesnika liječenih u Poliklinici za internu medicinu i dijalizu B. Braun Avitum. Bolesnicima je određena koncentracija 25OH-vitamina D (25(OH)D) u serumu, praćeni su dob i spol bolesnika, dužina liječenja na hemodijalizi, postojanje šećerne bolesti, koncentracija PTH, Ca, P, albumina i C-reaktivni protein (CRP) u serumu te oblik vitamina D primijenjen u liječenju. Na osnovi koncentracije 25(OH)-D bolesnici su klasifi cirani u tri skupine: defi cijencija (75nmol/L). Značajnost razlike među skupinama testirana je t-testom i jednosmjernim ANOVA testom za kontinuirane varijable i χ2-testom za kategorijske varijable, a postavljena razina značajnosti bila je p50nmol/ L), oni s 25(OH)D75 nmol/L). Between group differences were analyzed with t-test and one-way ANOVA for continuous variables, and χ2-test for categorical variables. The level of statistical signifi cance was set at p50 nmol/L) showed that those with defi ciency had higher PTH (40.78 vs. 28.42 pmol/L, p=0.003), higher phosphate (1.72 vs. 1.53 mmol/L, p=0.039), lower CRP (18.9 vs. 26.7 mg/L, p=0.019) and more often diabetes (29/65 vs. 16/69, p=0.011). These results showed a high prevalence of vitamin D defi ciency and insuffi ciency in patients with ESKD despite supplementation and treatment. Additional randomized and prospective studies are necessary to determine optimal treatment regimen, as well as its effects on morbidity and mortality

VITAMIN D IN PATIENTS WITH CHRONIC KIDNEY DISEASE TREATED WITH HEMODIALYSIS

Cilj rada bio je odrediti status vitamina D u bolesnika s terminalnom kroničnom bubrežnom bolešću liječenih kroničnom hemodijalizom (KBB-5-HD) i povezanost s osnovnim kliničkim i laboratorijskim parametrima. Bolesnici i metode: Presječno opservacijsko retrospektivno istraživanje provedeno je u bolesnika liječenih u Poliklinici za internu medicinu i dijalizu B. Braun Avitum. Bolesnicima je određena koncentracija 25OH-vitamina D (25(OH)D) u serumu, praćeni su dob i spol bolesnika, dužina liječenja na hemodijalizi, postojanje šećerne bolesti, koncentracija PTH, Ca, P, albumina i C-reaktivni protein (CRP) u serumu te oblik vitamina D primijenjen u liječenju. Na osnovi koncentracije 25(OH)-D bolesnici su klasifi cirani u tri skupine: defi cijencija (75nmol/L). Značajnost razlike među skupinama testirana je t-testom i jednosmjernim ANOVA testom za kontinuirane varijable i χ2-testom za kategorijske varijable, a postavljena razina značajnosti bila je p50nmol/ L), oni s 25(OH)D75 nmol/L). Between group differences were analyzed with t-test and one-way ANOVA for continuous variables, and χ2-test for categorical variables. The level of statistical signifi cance was set at p50 nmol/L) showed that those with defi ciency had higher PTH (40.78 vs. 28.42 pmol/L, p=0.003), higher phosphate (1.72 vs. 1.53 mmol/L, p=0.039), lower CRP (18.9 vs. 26.7 mg/L, p=0.019) and more often diabetes (29/65 vs. 16/69, p=0.011). These results showed a high prevalence of vitamin D defi ciency and insuffi ciency in patients with ESKD despite supplementation and treatment. Additional randomized and prospective studies are necessary to determine optimal treatment regimen, as well as its effects on morbidity and mortality

Bone Fragility Fractures in Hemodialysis Patients: Croatian Surveys

Disturbances of bone mineral metabolism are common complications of chronic kidney disease with bone fractures as one of the most important consequences. The aim of this study was to estimate prevalence of bone fractures among Croatian hemodialysis patients and to determine the possible fracture risk. The study was carried out in 767 hemodialysis patients from nine Croatian hemodialysis centers. Demographic, laboratory and bone fracture data were collected from medical records as well as therapy with vitamin D analogs. Fragility fractures were defi ned according to the World Health Organization defi nition. In 31 patient a total of 36 fractures were recorded. The prevalence of patients with bone fractures was 4.0%. The mean age of patients with fractures was 68.6 years. There were 9 male and 22 female patients with fractures. The mean hemodialysis duration was 63.3 months. Among all fractures the most common were hip fractures (39%) followed by forearm fractures (22%). This is the fi rst study regarding epidemiology of bone fractures in Croatian hemodialysis patients. The prevalence of patients with bone fractures in our group of hemodialysis patients is high. Fractures were more frequent among women and older patients, patients who have been longer on dialysis and in patients with higher concentration of PTH

HYPOPARATHYROIDISM IN HEMODIALYSIS PATIENTS

Sekundarni hiperparatireoidizam (SHPT) česta je komplikacija u bolesnika na hemodijalizi, međutim u nekih bolesnika mogu biti prisutne relativno niske koncentracije parathormona (PTH), tj. relativni hipoparatireoidizam (RhPT). Cilj rada je ispitati povezanost pojave RhPT s kliničkim i laboratorijskim obilježjima bolesnika te s lijekovima koje uzimaju. Bolesnici i metode: Proveli smo opservacijsko presječno istraživanje u bolesnika na hemodijalizi u tri centra. Uključeno je 199 bolesnika (127 muškaraca, 72 žene) prosječne dobi 66 godina i srednjeg trajanja hemodijalize 5,7 godina. Bolesnicima su određeni sljedeći parametri: dob, spol, šećerna bolest (DM), trajanje hemodijalize, vrsta lijekova koje uzimaju te laboratorijski parametri: Ca, P, PTH, albumin, alkalna fosfataza. RhPT je defi niran kao koncentracija PTH < 21,6 pmol/L. Rezultati: RhPT je bio statistički značajno povezan sa starijom dobi (prosječne dobi 70,5 prema 65,1 godina, p=0,026), šećernom bolesti (DM) (p=0,042), neuzimanjem vezača fosfata u terapiji (p=0,001), neuzimanjem aktivatora receptora vitamina D (aVDR) (p<0,001) i s uzimanjem vitamina D (p<0,001). U multivarijatnoj logističkoj regresiji, kao nezavisni prediktori za RhPT nađeni su: DM (OR 2,585; 95 % CI=1,247-5,359) terapija vitaminom D (OR 3,704, 95 % CI=1,579-8,687), a negativni nezavisni prediktori uzimanje vezača fosfata (OR 0,221; 95 % CI=0,059-0,829) i uzimanje aVDR (OR 0,248; 95 % CI=0,107-0,575). Zaključak: Šećerna bolest i terapija vitaminom D povezani su s većim rizikom RhPT, a terapija vezačima fosfata i aVDR s manjim rizikom RhPT. U starijih bolesnika i onih s DM treba biti oprezan, jer je RhPT povezan s usporenom pregradnjom kosti.Although secondary hyperparathyroidism (SHPT) is a common complication in hemodialysis patients, in some patients the concentration of parathyroid hormone (PTH) is relatively low, which can be defi ned as relative hypoparathyroidism (RhPT). The aim of this study was to examine the association of the occurrence of RhPT with clinical and laboratory characteristics of patients and their medication. Patients and methods: We conducted an observational cross-sectional study in hemodialysis patients at three centers. Altogether 199 patients were included. There were 127 men and 72 women, mean age 66 years and mean duration of hemodialysis 5.7 years. The following parameters were determined: age, sex, diabetes (DM), duration of hemodialysis, drugs, and laboratory parameters (Ca, P, PTH, albumin, alkaline phosphatase). RhPT was defi ned as PTH concentration <21.6 pmol/L. Results: RhPT was statistically signifi cantly associated with older age (mean age 70.5 vs. 65.1 years, p=0.026), DM (p=0.042), not taking phosphate binders in therapy (p=0.001), not taking vitamin D receptor activator (aVDR) (p<0.001) and taking vitamin D (p<0.001). In multivariate logistic regression, the following independent predictors for RhPT were found: DM (OR 2.585; 95% CI=1.247-5.359), vitamin D therapy (OR 3.704, 95% CI=1.579-8.687), and negative independent predictors for RhPT were taking phosphate binders (OR 0.221; 95% CI=0.059-0.829) and taking aVDR (OR 0.248; 95% CI=0.107-0.575). Conclusion: Diabetes mellitus and vitamin D therapy are associated with a higher risk of RhPT, and therapy with phosphate binders and aVDRs with a lower risk of RhPT. The possible cause is that patients with signifi cant SHPT are treated with aVDR. In elderly patients and those with DM, caution is recommended because RhPT is associated with slow bone remodeling

HYPOPARATHYROIDISM IN HEMODIALYSIS PATIENTS

Sekundarni hiperparatireoidizam (SHPT) česta je komplikacija u bolesnika na hemodijalizi, međutim u nekih bolesnika mogu biti prisutne relativno niske koncentracije parathormona (PTH), tj. relativni hipoparatireoidizam (RhPT). Cilj rada je ispitati povezanost pojave RhPT s kliničkim i laboratorijskim obilježjima bolesnika te s lijekovima koje uzimaju. Bolesnici i metode: Proveli smo opservacijsko presječno istraživanje u bolesnika na hemodijalizi u tri centra. Uključeno je 199 bolesnika (127 muškaraca, 72 žene) prosječne dobi 66 godina i srednjeg trajanja hemodijalize 5,7 godina. Bolesnicima su određeni sljedeći parametri: dob, spol, šećerna bolest (DM), trajanje hemodijalize, vrsta lijekova koje uzimaju te laboratorijski parametri: Ca, P, PTH, albumin, alkalna fosfataza. RhPT je defi niran kao koncentracija PTH < 21,6 pmol/L. Rezultati: RhPT je bio statistički značajno povezan sa starijom dobi (prosječne dobi 70,5 prema 65,1 godina, p=0,026), šećernom bolesti (DM) (p=0,042), neuzimanjem vezača fosfata u terapiji (p=0,001), neuzimanjem aktivatora receptora vitamina D (aVDR) (p<0,001) i s uzimanjem vitamina D (p<0,001). U multivarijatnoj logističkoj regresiji, kao nezavisni prediktori za RhPT nađeni su: DM (OR 2,585; 95 % CI=1,247-5,359) terapija vitaminom D (OR 3,704, 95 % CI=1,579-8,687), a negativni nezavisni prediktori uzimanje vezača fosfata (OR 0,221; 95 % CI=0,059-0,829) i uzimanje aVDR (OR 0,248; 95 % CI=0,107-0,575). Zaključak: Šećerna bolest i terapija vitaminom D povezani su s većim rizikom RhPT, a terapija vezačima fosfata i aVDR s manjim rizikom RhPT. U starijih bolesnika i onih s DM treba biti oprezan, jer je RhPT povezan s usporenom pregradnjom kosti.Although secondary hyperparathyroidism (SHPT) is a common complication in hemodialysis patients, in some patients the concentration of parathyroid hormone (PTH) is relatively low, which can be defi ned as relative hypoparathyroidism (RhPT). The aim of this study was to examine the association of the occurrence of RhPT with clinical and laboratory characteristics of patients and their medication. Patients and methods: We conducted an observational cross-sectional study in hemodialysis patients at three centers. Altogether 199 patients were included. There were 127 men and 72 women, mean age 66 years and mean duration of hemodialysis 5.7 years. The following parameters were determined: age, sex, diabetes (DM), duration of hemodialysis, drugs, and laboratory parameters (Ca, P, PTH, albumin, alkaline phosphatase). RhPT was defi ned as PTH concentration <21.6 pmol/L. Results: RhPT was statistically signifi cantly associated with older age (mean age 70.5 vs. 65.1 years, p=0.026), DM (p=0.042), not taking phosphate binders in therapy (p=0.001), not taking vitamin D receptor activator (aVDR) (p<0.001) and taking vitamin D (p<0.001). In multivariate logistic regression, the following independent predictors for RhPT were found: DM (OR 2.585; 95% CI=1.247-5.359), vitamin D therapy (OR 3.704, 95% CI=1.579-8.687), and negative independent predictors for RhPT were taking phosphate binders (OR 0.221; 95% CI=0.059-0.829) and taking aVDR (OR 0.248; 95% CI=0.107-0.575). Conclusion: Diabetes mellitus and vitamin D therapy are associated with a higher risk of RhPT, and therapy with phosphate binders and aVDRs with a lower risk of RhPT. The possible cause is that patients with signifi cant SHPT are treated with aVDR. In elderly patients and those with DM, caution is recommended because RhPT is associated with slow bone remodeling