Overcoming Inequity in Access to Kidney Transplantation: A Quality Improvement Project.

BACKGROUND: In 2018, DaVita dialysis clinics in Poland introduced a new pathway to improve the referral of dialysis patients for kidney transplantation. It was designed to meet formal requirements for timely referral for transplant assessment and measures to have the patient "active" on the waiting list. The pathway aimed to mitigate the existing inequitable access to transplantation surgery for patients with end stage kidney disease under the care of ambulatory dialysis clinics. The consequences to the patient of lack of contact with nephrologist when called in for transplant surgery during out-of-office hours was a major concern. We reviewed the effectiveness of whether the new procedure impacted facilitating a patient's call for a transplant surgery when dialysis clinics were not operating. METHODS: We collected data on the number of transplantations performed and the number of calls for surgery according to a conventional or new procedure over a 30-month period. RESULTS: In our study, 269 patients received a deceased donor kidney transplant, and 205 candidates (75%) were called for transplantation during the working hours of dialysis clinics, according to the standard procedure, of which 4 patients were discharged for various reasons. In addition, 69 candidates (25%) were called outside clinic working hours through the new procedure process, of which 1 patient was discharged during a phone call due to infection. CONCLUSIONS: DaVita's Poland new transplant access procedure effectively supports a patient's call for transplantation during outpatient dialysis clinics' closure hours.

Improvements in six aspects of quality of care of incident hemodialysis patients - a real-world experience.

BACKGROUND: The transition from chronic kidney disease stage 5 to initiation of hemodialysis has gained increased attention in recent years as this period is one of high risk for patients with an annual mortality rate exceeding 20%. Morbidity and mortality in incident hemodialysis patients are partially attributed to failure to attain guideline-based targets. This study focuses on improvements in six aspects of quality of dialysis care (adequacy, anemia, nutrition, chronic kidney disease-mineral bone disorder (CKD-MBD), blood pressure and vascular access) aligning with KDIGO guidelines, during the first 6 months of hemodialysis. METHODS: We analyzed patient demographics, practice patterns and laboratory data in all 3 462 patients (mean age 65.9 years, 41% females) on hemodialysis (incident <90 days on hemodialysis, n=603, prevalent ≥90 days on hemodialysis, mean 55 months, n=2 859) from all 56 DaVita centers in Poland (51 centers) and Portugal (5 centers). 80% of patients had hemodialysis and 20% hemodiafiltration. Statistical analyses included unpaired and paired Students t-test, Chi-2 analyses, McNemar test and logistic regression analysis. RESULTS: Incident patients had lower Kt/V (1.4 vs 1.7, p<0.001), lower serum albumin (37 vs 40 g/l, p=0.001), lower Hb (9.9 vs 11.0 g/dl, p<0.001), lower TSAT (26 vs 31%, p<0.001), lower iPTH (372 vs 496 pg/ml, p<0.001), more often a central venous catheter (68 vs 26%, p<0.001), less often an AV fistula (34 vs 70 %, p<0.001) compared with all prevalent patients. Significantly more prevalent patients achieved international treatment targets. Improvements in quality of care was also analyzed in a subgroup of 258 incident patients who were followed prospectively for 6 months. We observed significant improvements in Kt/V (p<0.001), albumin (p<0.001), Hb (p<0.001) transferrin saturation (TSAT, p<0.001), iPTH (p=0.005) and an increased use of AV fistula (p<0.001). Furthermore, logistic regression analyses identified treatment time and TSAT as major factors influencing the attainment of adequacy and anemia treatment targets. CONCLUSION: This large real-world European multicenter analysis of representative incident hemodialysis patients indicates that the use of medical protocols and medical targets assures significant improvements in quality of care, which may correspond to better outcomes. A selection bias of survivors with less comorbidities in prevalent patients may have influenced the results.

[Water-sodium homeostasis in hemodialysis - the eternal problem in nephrology practice]. / Homeostaza wodno-sodowa w hemodializie ­ odwieczny problem w praktyce nefrologicznej.

The kidney is an organ that maintains the body's sodium and water balance and plays a significant role in blood pressure regulation. Chronic kidney disease (CKD) and a progressive loss of its function, among others, leads to sodium and water retention and, as a consequence, to arterial hypertension. The supply of salt and fluids delivered with the diet significantly affects the cardiovascular system's functioning particularly in hemodialysis patients. The critical element in clinical care is maintaining appropriate water and electrolyte homeostasis. Overhydration is manifested as oedema and blood preassure increase, but a more accurate assessment of subtle variations is possible by measuring bioelectric impedance (BIA), which determines the extracellular water index (ECW). Actions to maintain euvolemia include limiting sodium and fluid intake, regular assessment of "dry" body weight, proper selection of ultrafiltration (UF), correction of sodium concentration, and dialysate temperature.

Influence of gender and age on haemodialysis practices: a European multicentre analysis.

BACKGROUND: Women of all ages and elderly patients of both genders comprise an increasing proportion of the haemodialysis population. Worldwide, significant differences in practice patterns and treatment results exist between genders and among younger versus older patients. Although efforts to mitigate sex-based differences have been attempted, significant disparities still exist. METHODS: This retrospective cohort study included all 1247 prevalent haemodialysis patients in DaVita units in Portugal (five dialysis centres, n = 730) and Poland (seven centres, n = 517). Demographic data, dialysis practice patterns, vascular access prevalence and the achievement of a variety of Kidney Disease: Improving Global Outcomes (KDIGO) treatment targets were evaluated in relation to gender and age groups. RESULTS: Body weight and the prescribed dialysis blood flow rate were lower in women (P < 0.001), whereas treated blood volume per kilogram per session was higher (P < 0.01), resulting in higher single-pool Kt/V in women than in men (P < 0.001). Haemoglobin was significantly higher in men (P = 0.01), but the proportion of patients within target range (10-12 g/dL) was similar. Men more often had an arteriovenous fistula than women (80% versus 73%; P < 0.01) with a similar percentage of central venous catheters. There were no gender-specific differences in terms of dialysis adequacy, anaemia parameters or mineral and bone disorder parameters, or in the attainment of KDIGO targets between women and men >80 years of age. CONCLUSIONS: This large, multicentre real-world analysis indicates that haemodialysis practices and treatment targets are similar for women and men, including the most elderly, in DaVita haemodialysis clinics in Europe.

Achievement of renal anemia KDIGO targets by two different clinical strategies - a European hemodialysis multicenter analysis.

BACKGROUND: The optimal treatment algorithm for iron therapy and the use of erythropoiesis-stimulating agents (ESA) in anemic hemodialysis (HD) patients has not been established. Hemoglobin (Hb) target levels can be achieved through more frequent intravenous (IV) iron use with lower ESA dose, or with less iron dosing but higher ESA. ESA therapy to correct anemia may result in severe arterial and venous thrombotic complications and the evidence base evaluating hard clinical outcomes related to the use of IV iron is sparse. METHODS: A total of 1247 maintenance HD patients from 12 dialysis centers in Portugal (n = 730) and Poland (n = 517) were considered. We assessed achievement of KDIGO renal anemia targets with focus on treatment strategies, which typically differ between countries. In Poland the use and dose of IV iron was 35-72% higher than that in Portugal (p <  0.001) during three consecutive months; use and dose of ESA was 61% higher in Portugal (5034 vs 3133 IU (adjusted)/week, p <  0.001). RESULTS: Mean Hb concentration was similar (11.0 vs 11.0 g/dL) in patients treated in both countries and the proportion of patients within KDIGO anemia target was 69.5% in Poland vs 65.8% in Portugal (NS). Ferritin and TSAT levels and the proportion of patients with TSAT > 20 and > 50% were both significantly higher in patients in Poland (88.8 and 14.6%) than in Portugal (76.3 and 5.7% respectively, p <  0.001). Significantly more patients in Poland had a ferritin concentration > 800 µg/L (35.6%) compared to Portugal (15.8%, p <  0.001). The ESA resistance index (ERI) was significantly higher in patients treated in Portugal (p <  0.001). Correlation analyses showed confounding by treatment indication in unadjusted models. Multiple and logistic regression analyses showed that with ferritin within KDIGO recommended range of 200-800 µg/L the odds for Hb within guidelines increased significantly. Annual gross mortality was 16% in Poland and 13% in Portugal (NS); there were no differences in cause-specific mortality. CONCLUSIONS: Administration of high doses of IV iron in routine clinical HD practice may not be associated with considerable harm. However, large randomized controlled trials are needed to provide absolute evidence of iron safety.

C-terminal and intact FGF23 in critical illness and their associations with acute kidney injury and in-hospital mortality.

BACKGROUND: FGF23 proved its value in prognostication of cardiovascular events and mortality among renal patients and general population. Limited data exist whether FGF23 may have any use in prediction of negative outcomes among critically ill patients admitted to intensive care unit (ICU). METHODS: Single center cohort study performed among patients admitted to ICU. The primary exposure was FGF23 plasma concentration measured within 24 h of ICU admission. The primary outcome was incident Acute Kidney Injury (AKI) and in-hospital mortality during the ICU stay. RESULTS: The study enrolled 79 patients admitted to ICU. C-terminal FGF23 (cFGF23) but not intact FGF23 (iFGF23) concentration was significantly elevated in patients, who acquired AKI and non-survivors (p < .001). ROC analysis of cFGF23 yielded an AUC of 0.81 and 0.85 for prediction of incident AKI and death during ICU stay, respectively. Multivariate analysis showed higher odds for AKI (OR 1.80; 95% CI 1.10-2.96) and in-hospital mortality (OR 2.85; 95% CI 1.60-5.06) for one unit increase of log transformed cFGF23. CONCLUSIONS: cFGF23 measurement may serve as a novel biomarker for incident AKI and death among critically ill patients.

[Skin cancers in kidney transplant recipients].

Kidney transplantation is the best treatment for end-stage renal failure. It prolongs the patient's life, improves quality of life and reduces costs associated with renal replacement therapy. Increasingly, newer immunosuppressive regimens allow for the proper functioning of the transplanted organ for many years. The progress in transplantation, qualification patients in older age for the procedure and longer survival of kidney graft lead to an increase in the number of patients receiving immunosuppressive drugs. They are exposed to various side effects associated with long-term suppression of the immune system, including an increased risk of cancer development. The most common malignancies (40- 50%) diagnosed in renal transplant recipients are skin cancers. Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the most common types of tumors occurring in this population. The use of immunosuppression resulted in the increase of the incidence of tumors that in the general population are relatively rare such as melanoma, Merkel cell cancer, Kaposi's sarcoma, anogenital cancer as well as sebaceous carcinoma.

The effect of nephrectomy on Klotho, FGF-23 and bone metabolism.

BACKGROUND: Increased concentration of fibroblast growth factor 23 (FGF-23) and decreased levels of soluble Klotho (sKL) are linked to negative clinical outcomes among patients with chronic kidney disease and acute kidney injury. Therefore, it is reasonable to hypothesize that GFR reduction caused by nephrectomy might alter mineral metabolism and induces adverse consequences. Whether nephrectomy due to urological indications causes derangements in FGF-23 and sKL has not been studied. The aim of the study was to evaluate the effect of acute GFR decline due to unilateral nephrectomy on bone metabolism, FGF-23 and sKL levels. METHODS: This is a prospective, single-centre observational study of patients undergoing nephrectomy due to urological indications. Levels of C-terminal FGF-23 (c-FGF-23), sKL and bone turnover markers [ß-crosslaps (CTX), bone-specific alkaline phosphatase (bALP) and tartrate-resistant acid phosphatase 5b (TRAP 5b)] were measured before and after surgery (5 ± 2 days). RESULTS: Twenty-nine patients were studied (14 females, age 63.0 ± 11.6, eGFR 87.3 ± 19.2 ml/min/1.73 m2). After surgery, eGFR significantly declined (p < 0.0001). Nephrectomy significantly decreased sKL level [709.8 (599.9-831.2) vs. 583.0 (411.7-752.6) pg/ml, p < 0.001] and did not change c-FGF-23 concentration [70.5 (49.8-103.3) vs. 77.1 (60.5-109.1) RU/ml, p = 0.9]. Simultaneously, alterations in bone turnover markers were observed. Serum concentration of CTX increased [0.49 (0.4-0.64) vs. 0.59 (0.46-0.85) ng/ml, p = 0.001], while bALP and TRAP 5b decreased [23.6 (18.8-31.4) vs. 17.9 (15.0-22.0) U/l, p < 0.0001 and 3.3 (3.0-3.7) vs. 2.8 (2.3-3.2) U/l, p < 0.001, respectively]. CONCLUSIONS: Nephrectomy among patients with preserved renal function before surgery does not increase c-FGF-23 but reduces sKL. Moreover, nephrectomy results in derangements in bone turnover markers in short-term follow-up. These changes may participate in pathogenesis of bone disease after nephrectomy.

Overuse of proton pump inhibitors and its consequences.

Direct inhibition of H+ ion excretion to the gastric lumen makes proton pump inhibitors (PPI) the most effective drugs against gastric acid-related diseases. Over recent years usage of proton pump inhibitors has increased dramatically. Due to the low costs, high efficacy and rarity of adverse effects, their use is prevalent and often it does not correspond with existing medical guidelines. The literature lists stress ulcer prophylaxis among patients with low risk of bleeding, routine 'gastroprotective' medication during treatment and non-specific abdominal symptoms as the most common patterns of off-label PPI use. This article summarizes the influence of PPI therapy on gastric mucosa, absorption and occurrence of adverse effects. The authors note that their low awareness among physicians contributes to wide and imprudent use of drugs of this group.

[Risk factors for cancer development in patients after kidney transplantation].

Kidney transplantation in patients with ESRD (end-stage renal disease) improves quality of life and is associated with an increase in both survival rates and the reduction in medical costs compared with patients waiting for a transplant as well as dialysis population. Cancers, next to the cardiovascular disease and infection, present as one of the most common causes of kidney transplant recipients deaths. Incidence of neoplasm after kidney transplantation is between 2.3 and 31%. Risk factors for carcinogenesis after transplantation can be divided into three main groups which include traditional factors (genetic predisposition, exposure to UVA and UVB radiation, smoking, abuse of painkillers, cancer in the pretransplant period), factors connected with kidney disease (cause and treatment of kidney failure) and related to transplantation (immunosuppressive regimen, chronic viral infection, cancer transition with graft). Immunosuppressive treatment undoubtedly has a huge impact on the development of tumours in patients after transplantation. It is to be remembered to include mTOR inhibitors in immunosuppressive regimen in patients with a history of cancer. In kidney recipients the frequency of reactivation as well as de novo infection of oncogenic virus is increased, particularly: EBV (Epstein-Barr virus), HBV (hepatitis type B virus), HCV (hepatitis type C virus), HPV (human papilloma virus) i HHV8 (human herpes virus type 8). An important aspect is the awareness of patients about the increased risk of cancer development and necessity of respecting and applying of preventive recommendations.

Validation of Mini Nutritional Assessment Scale in peritoneal dialysis patients.

INTRODUCTION: Malnutrition is a negative predictive factor for survival in end stage renal disease (ESRD) patients. Coincidence of malnutrition, inflammation and atherosclerosis (MIA syndrome) in the dialysis population is an exceptionally poor outcome event. Due to flexibility, ease of performance and reproducibility, clinical scales are of particular value in assessment of nutritional status in ESRD patients. The aim of the present study was to evaluate the clinical value of Mini Nutritional Assessment (MNA) in peritoneal dialysis (PD) patients. MATERIAL AND METHODS: Nutritional status was assessed in 41 peritoneal dialysis patients by means of the MNA scale and malnutrition inflammation score (MIS). Some other clinical and laboratory parameters associated with nutritional status were analyzed. Patients were followed up for 30 months. RESULTS: In the analyzed group of patients a good nutritional state was diagnosed in 22 patients (54%), risk of malnutrition in 17 (41%) and malnutrition in 2 patients (5%) based on the MNA scale. A strong correlation between MNA based nutritional status and MIS was found (r = -0.85, p < 0.01, ANOVA, p < 0.01). Differences in time on dialysis, body mass index, concentration of albumin, cholesterol and triglycerides were noted between at risk/malnourished and well-nourished (according to MNA) patients. Statistically significant factors determining survival of patients by Cox proportional hazard analysis were age (HR 1.07), being at risk/malnourished according to MNA (HR 5.7), MIS (HR 1.2), and albumin (HR 0.13). CONCLUSIONS: The MNA scale is a valuable, clinically suitable tool for assessment of nutritional status in peritoneal dialysis patients. Risk of malnutrition and malnutrition diagnosed by MNA identifies patients at high mortality risk.

Cholecalciferol supplementation reduces soluble Klotho concentration in hemodialysis patients.

INTRODUCTION: Low levels of vitamin D are linked to numerous adverse clinical conditions in hemodialysis (HD) patients, including disturbances of mineral and bone metabolism and increased mortality. Klotho, a molecule involved in such processes as phosphate homeostasis and aging, exists in 2 forms: a transmembrane protein acting as a coreceptor for fibroblast growth factor 23 (FGF-23) and soluble form, which is formed by cleavage of the extracellular domain of this molecule. OBJECTIVES: The aim of the study was to evaluate the effect of cholecalciferol supplementation on soluble Klotho levels in HD patients. PATIENTS AND METHODS: This was a prospective, open-label trial examining the effects of cholecalciferol supplementation on selected laboratory markers in 22 patients on HD. Vitamin D deficiency was assessed by the measurement of 25-hydroxyvitamin D [25(OH)D] levels. Soluble Klotho, intact FGF-23, intact parathormone (iPTH), and markers of bone formation and resorption were measured at baseline and after 12 weeks of cholecalciferol supplementation. RESULTS: The levels of 25(OH)D increased, while those of iPTH and cross-linked C-telopeptide of type 1 collagen decreased significantly. Cholecalciferol treatment reduced the median concentration of soluble Klotho (from 438.73 pg/ml; interquartile range, 257.99-865.51 pg/ml; to 370.94 pg/ml; 181.72-710.91 pg/ml; P <0.05). FGF­23 levels were not affected by the treatment. CONCLUSIONS: Supplementation with cholecalciferol in HD patients decreases soluble Klotho levels without affecting the FGF-23 concentration. Replenishment of vitamin D stores results in a decrease in iPTH levels and reduced bone resorption.

Low concentration of heparin used for permanent catheters canal locking is effective and diminishes the risk of bleeding.

PURPOSE: There is an increasing number of patients being dialyzed with permanent catheters (PC). In the majority of cases, heparin is used to maintain PC patency. This practice causes clotting disturbances due to heparin leakage and may predispose the patient to bleeding episodes. It has not been well studied whether lowering heparin concentration for canal locking decreases short-term bleeding complications after PC placement. METHODS: This was a prospective single-center randomized open-label trial conducted in hemodialyzed patients undergoing PC insertion. Low concentration of heparin (LCH) 2,500 IU/ml versus high concentration of heparin (HCH) 5,000 IU/ml was randomly used for catheter lumens locking. The primary endpoint was the occurrence of bleeding within 24 h after catheter placement. The effects of clinical and laboratory data on bleeding events were analyzed as secondary endpoints. RESULTS: Seventy-five patients (37 in LCH) were enrolled in the study. Only in the HCH group we found a significant prolongation of activated partial thromboplastin time (APTT) 2 h after PC placement (p < 0.001). There was a higher number of bleeding episodes in the HCH group (n = 16; 42.1%) than in the LCH group (n = 7; 18.9%) (χ(2) = 4.74; p = 0.029). In univariate analysis, assignment to HCH, baseline APTT, use of low molecular weight heparin, and femoral localization were associated with bleeding events. In multivariate analysis, the use of HCH (odds ratio [OR] 3.64; 95% confidence interval [95% CI] 1.10-12.05) and baseline APTT (OR 1.12; 95% CI 1.002-1.250) predicted bleeding after PC insertion. CONCLUSION: LCH used for canals locking decreases bleeding events in the first 24 hours after permanent catheter placement, compared to HCH.

Low molecular weight iron dextran increases fibroblast growth factor-23 concentration, together with parathyroid hormone decrease in hemodialyzed patients.

Fibroblast growth factor (FGF)-23 inhibits PTH production. Elevated FGF-23 and parathyroid hormone (PTH) levels are characteristic of hemodialyzed patients. Iron polymaltose was shown to increase FGF-23 concentration. The effect of intravenous low molecular weight iron dextran (LMID) on these hormones and bone metabolism has not been studied in hemodialysis (HD). Twelve HD patients were prospectively followed up for 3 weeks after a single infusion of LMID. Calcium, phosphate, FGF-23, PTH, degradation products of C-terminal telopeptides of type I collagen (CTX) and procollagen I N-terminal propeptide (PINP) were measured prior to, and at week 1 and week 3 after the LMID administration. FGF-23 increased significantly from 453.4 (68.6-3971.5) pg/mL at baseline to 971.8 (779.5-3361.4) pg/mL (P = 0.001) at week 1 and started to decrease toward the initial value at week 3. The changes were accompanied by a significant decline in PTH from 367.6 (21.4-1487.4) pg/mL at baseline to 315.7 (16.4-1339.8) pg/mL (P = 0.018) at week 1 and subsequently began to increase toward the initial values. Phosphate, calcium, CTX and PINP did not change over the study course. LMID causes an increase in FGF-23 concentration together with a decrease in PTH. Our study highlights a pathophysiological element, which may connect suppression of parathyroid glands with intravenous iron supplementation.

Effect of secondary hyperparathyroidism treatment with cinacalcet on selected adipokines and markers of endothelial injury in hemodialysis patients: a preliminary report.

INTRODUCTION:  Disturbances in endothelial function, adipokines, and mineral metabolism due to secondary hyperparathyroidism (SHPT) shorten the lifespan in hemodialysis (HD) patients. OBJECTIVES:  The aim of the study was to evaluate the effect of SHPT treatment with cinacalcet on selected adipokines and markers of endothelial injury in HD patients. PATIENTS AND METHODS:  Soluble thrombomodulin (sTM), E-selectin, leptin, and adiponectin levels were measured in patients with SHPT at baseline and at 6 months of cinacalcet treatment. RESULTS:  A total of 18 patients completed the study. SHPT treatment with cinacalcet decreased calcium, phosphate, and intact parathormone (iPTH) levels; however, no significant changes in sTM, E-selectin, leptin, or adiponectin were observed. iPTH levels after treatment correlated with age (r = -0.51, P = 0.031), mean cinacalcet dose (r = 0.65, P = 0.004), as well as baseline calcium (r = 0.65 P = 0.003), iPTH (r = 0.59, P = 0.01), E-selectin (r = 0.56, P = 0.016), and leptin (r = -0.49, P = 0.039). CONCLUSIONS:  Cinacalcet treatment does not affect the markers of endothelial function and selected adipokines. Effectiveness of treatment may be modulated by E-selectin and leptin.

Cinacalcet lowers FGF-23 level together with bone metabolism in hemodialyzed patients with secondary hyperparathyroidism.

PURPOSE: Secondary hyperparathyroidism (sHPT) is associated with elevated levels of FGF-23, which in turn are connected to adverse outcomes in ESRD patients. The relationship between FGF-23 and bone metabolism in patients with sHPT treated with cinacalcet has not been studied. METHODS: Thirty-four stable chronically hemodialyzed patients with sHPT were prospectively followed during the treatment with cinacalcet without any changes in concurrent vitamin D or phosphate binder dose. Blood samples were collected at the start and after 6 months of study. Levels of osteocalcin (OC), cross-linked C-telopeptide of type I collagen (CTX), and FGF-23 were measured. RESULTS: Eighteen patients finished the study. Levels of calcium, phosphate, and iPTH decreased during 6 months of treatment with cinacalcet. Serum level of FGF-23 decreased significantly (log FGF-23 from 7.58 ± 1.7 to 6.61 ± 1.7 pg/ml) (P < 0.001). Cinacalcet lowered the concentration of CTX from 3.1 ± 0.6 ng/ml to 2.6 ± 0.9 ng/ml (P < 0.05) and OC from 91.8 (41.5-558.6) to 70.3 (11.3-419.7) ng/ml (P < 0.05). The magnitude of change in FGF-23 concentration before and after treatment correlated significantly with suppression of osteoblasts' function assessed by ΔOC (r = 0.5, P < 0.05) but not with changes in bone resorption marker ΔCTX. CONCLUSIONS: Cinacalcet treatment of sHPT results in reduction of FGF-23 levels, probably due to the suppression of osteoblasts function.

Kidney disease is a negative predictor of 30-day survival after acute ischaemic stroke.

BACKGROUND/AIMS: Impaired renal function is a strong risk factor for cardiovascular diseases and worsens a patient's prognosis. Renal dysfunction predicts mortality after acute stroke in the long term. On the other hand, in-hospital mortality after acute stroke is strongly associated with disorders of consciousness at the onset of stroke, severity of stroke, body temperature, blood sugar and some other comorbidities. The aim of the study was to analyze the possible role of renal dysfunction and/or signs of renal disease (proteinuria) on 30-day mortality after acute ischaemic stroke (AIS) based on the hospital medical records of one county. METHODS: Medical records of 312 consecutive patients admitted to Ostroleka County Hospital (Department of Neurology) between March 2000 and October 2002 for AIS were retrieved retrospectively to determine factors influencing 30-day survival. None of patients received thrombolytic therapy. RESULTS: Among the patients analyzed, 74 (23.7%) died during the 30-day period. In a simple Cox proportional hazards regression model, negative predictive factors were: older age, higher pulse rate, lower estimated glomerular filtration rate (eGFR), proteinuria, elevated plasma glucose level, diabetes mellitus, atrial fibrillation and chronic heart failure. In a multivariate analysis, independent negative predictors of 30-day morbidity were: age hazard ratio (HR) 1.05 (95% CI 1.02-1.08), eGFR <60 ml/min HR 1.75 (95% CI 1.21-2.19), dipstick proteinuria HR 2.28 (95% CI 1.74-2.82) and plasma glucose level >100 mg/dl HR 2.96 (95% CI 2.22-3.70). CONCLUSION: The results of this study identify decreased eGFR and presence of dipstick proteinuria as a strong negative predictor of 30-day survival after AIS in patients not treated with thrombolytic agents.

Kynurenine, quinolinic acid--the new factors linked to carotid atherosclerosis in patients with end-stage renal disease.

Increased oxidative stress (SOX), inflammation and accelerated atherosclerosis have been reported in end-stage renal disease (ESRD), but their associations with kynurenine pathway activation remain unknown. We determined the plasma concentrations of kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA); three distinct SOX markers: Cu/Zn superoxide dismutase (Cu/Zn SOD), total peroxide and malondialdehyde (MDA), high sensitivity C-reactive protein (hs CRP) as a indicator of inflammation, and intima-media thickness (IMT)--an early reflection of the systemic atherosclerosis in the population of 124 patients with ESRD. In uraemia, the concentrations of KYN, KYNA and QA were increased by 37-105%, by 84-428%, and by 394-1018% of the control values; respectively. These changes were accompanied by significant increase in kyna/kyn and qa/kyn ratios, reflecting increased activity of kynurenine pathway enzymes. KYN, QA and qa/kyn ratio were positively associated with inflammation, SOX markers, and IMT values in uraemics. Moreover, multiple stepwise regression analysis identified age, presence of diabetes mellitus, QA and qa/kyn ratio as the independent variables significantly associated with increased IMT in this population. In conclusion, the results of the present study suggest a relationship between kynurenine pathway activation and increased oxidative stress, inflammation and the progression of atherosclerosis in end-stage renal disease patients.