Results in the ESPN/ERA-EDTA Registry suggest disparities in access to kidney transplantation but little variation in graft survival of children across Europe.

One of the main objectives of the European health policy framework is to ensure equitable access to high-quality health services across Europe. Here we examined country-specific kidney transplantation and graft failure rates in children and explore their country- and patient-level determinants. Patients under 20 years of age initiating kidney replacement therapy from January 2007 through December 2015 in 37 European countries participating in the ESPN/ERA-EDTA Registry were included in the analyses. Countries were categorized as low-, middle-, and high-income based on gross domestic product. At five years of follow-up, 4326 of 6909 children on kidney replacement therapy received their first kidney transplant. Overall median time from kidney replacement therapy start to first kidney transplantation was 1.4 (inter quartile range 0.3-4.3) years. The five-year kidney transplantation probability was 48.8% (95% confidence interval: 45.9-51.7%) in low-income, 76.3% (72.8-79.5%) in middle-income and 92.3% (91.0-93.4%) in high-income countries and was strongly associated with macro-economic factors. Gross domestic product alone explained 67% of the international variation in transplantation rates. Compared with high-income countries, kidney transplantation was 76% less likely to be performed in low-income and 58% less likely in middle-income countries. Overall five-year graft survival in Europe was 88% and showed little variation across countries. Thus, despite large disparities transplantation access across Europe, graft failure rates were relatively similar. Hence, graft survival in low-risk transplant recipients from lower-income countries seems as good as graft survival among all (low-, medium-, and high-risk) graft recipients from high-income countries.

The Therapeutic Hypothermia in Treatment of Hyperammonemic Encephalopathy due to Urea Cycle Disorders and Organic Acidemias.

BACKGROUND: Hyperammonemic encephalopathy in newborns with urea cycle disorders and certain organic acidurias can cause severe brain injury, coma and death. Standard therapy includes protein restriction, nitrogen-scavenging drugs, prevention of catabolism and hemodialysis. Neuroprotective hypothermia as part of the treatment has been reported only 3 times. It has been suggested that mild systemic hypothermia can contribute to better neurological outcomes in hyperammonemic encephalopathy. However, the limited experience precludes accurate conclusions on safety and efficacy. METHODS: Whole body therapeutic hypothermia was included in the standard treatment of hyperammonemic encephalopathy in 4 neonates with urea cycle disorder or organic aciduria. RESULTS: Two patients survived the initial crisis. One patient has a developmental quotient of 0.8, while the other shows severe developmental delay. The cooling protocol had to be discontinued in 3 patients due to the otherwise untreatable complications (hypotension and hemorrhage). CONCLUSION: The efficacy and safety of therapeutic hypothermia in the treatment of neonatal hyperammonemic encephalopathy depend on various factors, requiring further evaluation.

High-urgency kidney transplantation in the Eurotransplant Kidney Allocation System: success or waste of organs? The Eurotransplant 15-year all-centre survey.

BACKGROUND: In the Eurotransplant Kidney Allocation System (ETKAS), transplant candidates can be considered for high-urgency (HU) status in case of life-threatening inability to undergo renal replacement therapy. Data on the outcomes of HU transplantation are sparse and the benefit is controversial. METHODS: We systematically analysed data from 898 ET HU kidney transplant recipients from 61 transplant centres between 1996 and 2010 and investigated the 5-year patient and graft outcomes and differences between relevant subgroups. RESULTS: Kidney recipients with an HU status were younger (median 43 versus 55 years) and spent less time on the waiting list compared with non-HU recipients (34 versus 54 months). They received grafts with significantly more mismatches (mean 3.79 versus 2.42; P < 0.001) and the percentage of retransplantations was remarkably higher (37.5 versus 16.7%). Patient survival (P = 0.0053) and death with a functioning graft (DwFG; P < 0.0001) after HU transplantation were significantly worse than in non-HU recipients, whereas graft outcome was comparable (P = 0.094). Analysis according to the different HU indications revealed that recipients listed HU because of an imminent lack of access for dialysis had a significantly worse patient survival (P = 0.0053) and DwFG (P = 0.0462) compared with recipients with psychological problems and suicidality because of dialysis. In addition, retransplantation had a negative impact on patient and graft outcome. CONCLUSIONS: Facing organ shortages, increasing wait times and considerable mortality on dialysis, we question the current policy of HU allocation and propose more restrictive criteria with regard to individuals with vascular complications or repeated retransplantations in order to support patients on the non-HU waiting list with a much better long-term prognosis.

[Hepatitis C virus and chronic progressive kidney disease. Guidelines for detection, evaluation, treatment and prevention of infection transmission in hemodialysis units; procedure for infected patients-candidates for kidney transplantation and procedure for patients suspected of HCV infection-related kidney disease]. / Hepatitis C virus i kronicna progresivna bolest bubrega. Smjernice za otkrivanje, prosudbu, lijecenje, sprjecavanje sirenja infekcije u jedinicama za hemodijalizu, postupak sa zarazenim bolesnicima-kandidatima za transplantaciju bubrega i postupak s bolesnicima u kojih se sumnja na bolest bubrega povezanu s HCV infekcijom.

Hepatitis C virus (HCV) infection is a relatively frequent complication among long-term dialysis patients. The paper presents guidelines for serologic and molecular diagnosis of hepatitis C in patients with chronic kidney disease, recommendations for the treatment of HCV infection in these patients and the prevention of transmission of HCV in hemodialysis units. A separate chapter provides guidance on the management of patients who are infected with HCV before and after kidney transplantation, and guidelines for the treatment of renal disease resulting from HCV infection.

[Viralhepatitis. Croatian Consensus Statement 2013]. / Virusni hepatitis. Hrvatska konsenzus konferencija 2013.

Croatian Consensus Conferences on Viral Hepatitis took place in 2005 and 2009. Considering the numerous novel concepts on the epidemiology, diagnosis and management of viral hepatitis (chronic hepatitis C genotype 1 in particular) that have emerged in the past four years, a new Croatian Consensus Conference on Viral Hepatitis was held in Zagreb on February 28, 2013. The abridged text of the Croatian Consensus Conference on Viral Hepatitis 2013 presents the new concepts on the epidemiology of viral hepatitis, serologic and molecular diagnosis of viral hepatitis, determination of the IL-28 gene promoter polymorphism, fibrosis grading, algorithm for patient diagnostic follow up, treatment of chronic hepatitis C (genotypes 1-6) and hepatitis B, treatment of special populations (children, dialysis patients, transplanted patients, individuals with HIV/HCV co-infection), and therapy side effects.

Pegylated interferon for treatment of chronic hepatitis C in hemodialysis patients in Croatia.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection is a frequent complication among long-term dialysis patients. The aim of the present study was to evaluate the efficacy and side effects of pegylated interferon-α(2a) (PEG-IFN-α(2a)) treatment in hemodialysis patients. METHODS: We retrospectively reviewed charts of 16 HCV-RNA-positive hemodialysis patients. RESULTS: There were 11 male and 5 female patients treated with dialysis for 6-28 years. Twelve patients had HCV genotype 1b, 2 patients had 3a, and 1 patient had genotype 2a. Although only 10 out of 16 patients completed 48 weeks of treatment, early virological response and end-of-treatment virological response were achieved in 9 and 13 patients, respectively. Sustained virological response was recorded in 9 patients. The most common side effect was anemia. A flu-like syndrome was documented in 6, myalgia in 4, and arthralgia in 5 patients. Rectorrhagia, endocarditis and severe cough were recorded in 1 patient each. Nine patients received a renal transplant, and all 6 responders remained HCV-RNA-negative. CONCLUSIONS: PEG-IFN-α(2a) has limited efficacy in dialysis patients. A significant proportion of patients discontinued treatment because of side effects. Additional studies with long-term follow-up are needed to determine the optimal treatment of HCV infection in the dialysis population.

[Outcome of renal transplantation in patients with chronic virus hepatitis]. / Ishod transplantacije bubrega u bolesnika s kronicnim virusnim hepatitisom.

The objective is to present results of renal transplantation in patients with end-stage renal disease and chronic virus C/B hepatitis. We retrospectively reviewed outcome of transplantation in patients having received renal allograft from 1985 to 2009 at Zagreb University Hospital Center: graft function, graft and patient survival, hepatic function, and complications of transplantation, i.e. episodes of acute rejection, manifestation of diabetes mellitus, and proteinuria. There were 91 patients, 50 men and 41 women, mean age 40.9. Patients were previously treated with dialysis for 7.8 years, with the mean follow-up after transplantation of 7.3 years. The most frequent diagnoses of end-stage renal disease were chronic glomerulonephritis, reflux nephropathy, tubulointerstitial nephritis, renal hypoplasia/aplasia, and polycystic renal disease. Good graft function (creatinine 200 micromol/L) was recorded in 59.5% of patients. One-year, 5-year and 10-year graft survival was 93%, 64% and 39%, and 1-year, 5-year and 10-year patient survival after transplantation was 98%, 72% and 42%, respectively. Normal values of liver chemistry (AST, ALT) were found in 59.5% and elevated values in 40.5% of patients. Episodes of acute rejection occurred in 56% of patients. Proteinuria was recorded in 27%, diabetes mellitus in 18% and elevated blood pressure in 66% of patients. Patients with chronic C/B virus hepatitis having undergone renal transplantation had worse graft function and worse graft and patient survival than patients without chronic hepatitis. The most common causes of death were cardiovascular diseases, cerebrovascular diseases and cirrhosis hepatitis.

ATP synthase deficiency due to m.8528T>C mutation - a novel cause of severe neonatal hyperammonemia requiring hemodialysis.

OBJECTIVES: Hyperammonemia in a newborn is a serious condition, which requires prompt intervention as it can lead to severe neurological impairment and death if left untreated. The most common causes of hyperammonemia in a newborn are acute liver failure and inherited metabolic disorders. Several mitochondrial disorders have been described as a cause of severe neonatal hyperammonemia. CASE PRESENTATION: Here we describe a new case of adenosine-triphosphate (ATP) synthase deficiency due to m.8528T>C mutation as a novel cause of severe neonatal hyperammonemia. So far six patients with this mutation have been described but none of them was reported to need hemodialysis in the first days of life. CONCLUSION: This broadens the so far known differential diagnosis of severe neonatal hyperammonemia requiring hemodialysis.

[Hepatitis B virus and chronic progressive kidney disease]. / Hepatitis B virus i kronicna progresivna bolest bubrega.

The prevalence and incidence of hepatitis B virus (HBV) infection in end-stage renal disease patients has significantly decreased over the past few decades. HBV infection in dialysis patients presents a distinct clinical problem in view of the immunosuppressive effect of renal failure, susceptibility to de novo infection and nosocomial transmission, long-term implications on morbidity and mortality, and change in clinical course after kidney transplantation. In order to prevent nosocomial transmission, standard precautionary measures must be rigorously followed. In addition to these standard precautions, measures specific to hemodialysis units are also important to prevent nosocomial HBV infection. Hepatitis B vaccination of patients and medical personnel is important both to prevent susceptible patients from acquiring HBV and to reduce the pool of HBV infected patients. Decisions on the treatment of chronic HBV infection are based in part upon an accurate assessment of the presence or absence of virus replication and active liver disease. Optimal therapy may involve the administration of interferon-alfa, nucleotide or nucleoside analogues, combination therapy, liver transplantation, or only observation. In patients infected with HBV that undergo kidney transplantation, the use of a preventive or preemptive approach is recommended to reduce the risk of HBV reactivation post-transplantation. The prophylactic strategy includes the administration of antiviral agents to patients at an increased risk of developing HBV reactivation either prior to or immediately after transplantation. The preemptive strategy includes periodic post-transplantation monitoring for viremia with prompt treatment upon detection and/or increase in HBV DNA levels. HBV infection may be directly associated with a variety of renal diseases, including polyarteritis nodosa, membranous glomerulonephritis and membranoproliferative glomerulonephritis. In the patient suspected of having renal disease associated with HBV, testing for HBV DNA is recommended to confirm active viral replication and kidney biopsy to confirm the presence of an underlying glomerular process, or biopsy at another tissue site to confirm polyarteritis nodosa. It is recommended to treat these patients with an antiviral agent using appropriate dose adjustment for the level of kidney function. In patients with associated vasculitis or rapidly progressive glomerulonephritis, a short course of glucocorticoids may be considered.

[Hepatitis C virus and chronic progressive kidney disease]. / Virus hepatitisa C i kronicna progresivna bolest bubrega.

Soon upon its discovery, hepatitis C virus (HCV) was recognized as an important cause and consequence of chronic kidney disease (CKD). HCV is a significant cause of some forms of glomerulonephritis (GN), especially membranoproliferative GN (MPGN). Subsequent population-based studies found an association between HCV positivity and CKD markers such as albuminuria or proteinuria. HCV infection is a frequent sequel of CKD. Blood transfusions (before effective screening of blood donors for HCV was instituted), nosocomial transmission in dialysis units, and transmission by kidney grafts all have contributed to the much higher prevalence of HCV infection in end-stage renal disease (ESRD) and transplant patients as compared to the general population. The current prevalence of HCV in dialysis centers is between 5% and 10% in European Union, and around 8.4% in Croatia. Strict adherence to 'universal precautions', careful attention to hygiene and strict sterilization of dialysis machines is recommended. The prevalence of HCV infection in CKD transplant patients is also high. Consistent risk factors include total time spent on dialysis and a history and/or number of blood transfusions, yet paralleling the prevalence in the general population of the same country or region. Patients with CKD who are considered for treatment should have virologic evidence of chronic HCV infection (i.e. HCV RNA detectable in serum). Treating chronic HCV infection in CKD patients is associated with a number of challenges. As the glomerular filtration rate (GFR) decreases, the half-life of both interferons (IFNs) (standard and pegylated) and ribavirin increases, resulting in a potentially poorer tolerance and the need for dosage adaptations in severe CKD. In kidney graft recipients, the use of IFNs and immunostimulants further entails a substantial risk of rejection. IFN therapy in hemodialysis patients results in good biochemical and virologic response and appears to exert a beneficial effect on the course of liver disease following renal transplantation. IFN-alpha therapy for the treatment of HCV-infected ESRD patients on maintenance dialysis, administered prior to renal transplantation, is associated with high rates of sustained biochemical and virologic response in the post-transplant period. Thus, IFN-alpha therapy seems to be advisable for HCV-infected dialysis patients that are candidates for renal transplantation.

[Viral hepatitis. Croatian consensus conference--2009]. / Virusni hepatitis. Hrvatska konsenzus konferencija 2009.

Summarized text of Croatian Consensus Conference on Viral Hepatitis of 2009 comprises the following chapters: 1) Epidemiology, 2) Clinical Picture, 3) Diagnostic Procedure, 4) Aims of Treatment of Viral Hepatitis, 5) Terminology, 6) Medicaments (6.1. Interferon, 6.2. Analogues of Nucleozides and Nucleotides), 7) Hepatitis B (7.1. Serologic and Molecular HBV Diagnostics, 7.2. Terminology, 7.3.Whom to Treat? 7.4. Therapy), 8) Hepatitis C (8.1. Serologic and Molecular HCV Diagnostics, 8.2. Terminology, 8.3. Whom to Treat? 8.4. Therapy). Clinical, laboratory and histologic assessment of patients with chronic viral hepatitis (algorythm of pretherapeutic treatment; histologic evaluation) and notions related to therapy of viral hepatitis (category of the patient and category of the response to treatment) are presented in related tables.

Efficacy of interferon-alpha in the treatment of chronic hepatitis C in dialysis patients: two therapeutic protocols compared.

BACKGROUND: Data on the efficacy of particular therapeutic protocols of interferon-alpha (IFN-alpha) treatment for chronic hepatitis C in patients on hemodialysis (HD) vary. AIM: To compare the efficacy of two different therapeutic protocols for HD patients. PATIENTS AND METHODS: 15 hepatitis C virus (HCV)-positive patients on chronic HD at two dialysis centers: 8 patients treated with IFN-alpha 3 x 3 MU/week s.c. for 6 months (group A), and 7 patients treated with IFN-alpha 3 x 5 MU/week for 3 months, then 1 x 5 MU/week for another 3 months (group B). End of treatment response (ETR) and sustained virologic response (SVR) were evaluated by HCV-RNA determination. There was no statistically significant difference between the two patient groups according to age, sex, duration of HD and HCV infection. RESULTS: ETR was 87.5% (7/8) in group A and 28.5% (2/7) in group B, being statistically significant (p < 0.05). Although better SVR [50% (4/8) vs. 28.5% (2/7)] and lower drop-out rate [0% (0/8) vs. 28.5% (2/7)] were achieved in group A compared to group B, these differences did not reach statistical significance (p > 0.05). CONCLUSION: Therapy with IFN-alpha 3 x 3 MU/week s.c. for 6 months seems to be more appropriate for treatment of hepatitis C in HD patients, mostly due to better tolerability, i.e. lower drop-out rate. These differences could be attributed to different pharmacokinetic properties of the particular therapy protocol.

[Prevention and treatment of hepatitis C in patients on dialysis]. / Smjernice za sprjecavanje i lijecenje hepatitisa C u dijaliziranih bolesnika.

Nosocomial transmission of blood-borne pathogens, including hepatitis C virus infection, is the most common one in a dialysis center setting. The prevalence of HCV antibodies is by far higher in patients undergoing maintenance hemodialysis therapy than in those on peritoneal dialysis. Standard infection prevention measures in hospital settings and measures of infection prevention in dialysis units should be performed. They include serologic testing for HCV of every new patient in a dialysis unit as well as routine testing of all patients every six months. Hepatitis C therapy is recommended in patients on dialysis who have detectable HCV RNA, positive liver biopsy (portal or bridging fibrosis or moderate stage of necroinflammation), younger patients (less than 65 years), and transplantation candidates. When evaluating ALT, it should be kept in mind that ESRD patients have ALT levels lower than general population, making ALT level not relevant parameter of liver disease activity in these patients. Results of hepatitis C therapy with interferon alpha and peginterferon alpha are similar to those in the general population but with more common side effects, which may require therapy discontinuation. Due to the possibility of anemia, ribavirin is contraindicated in patients with ESRD. Around 30% of patients treated with peginterferon have sustained viral response, 25%-45% of them have end of treatment viral response, and 50%-80% have end of treatment biochemical response (ALT normalization). Numerous clinical trials have established that the decrease in HCV load and prolonged suppression of viral replication during interferon therapy significantly reduce hepatic inflammation and consequently postpone progression of fibrosis to cirrhosis.

[Prevention and treatment of hepatitis B in patients on hemodialysis and vaccination of hemodialysis health personnel against hepatitis B]. / Smjernice za sprjecavanje, kontrolu i lijecenje hepatisa B na dijalizi, kao i za cijepljenje zdravstvenih radnika na dijalizi protiv hepatitisa B.

The prevalence and incidence of hepatitis B in hemodialysis patients in Croatia have been estimated to 1.3% and 0.03%, respectively. HBV infection in dialysis patients is usually asymptomatic, has a prolonged course, and progresses to chronic HBsAg hepatitis in 50% of cases. Some 15%-40% of HBsAg carriers on dialysis will develop cirrhosis, liver decompensation or hepatocellular carcinoma. Strict adherence to the standard infection prevention measures, continuous monitoring of HBV markers in patients on hemodialysis, patient and personnel immunization and hepatitis B treatment in hemodialyzed patients are mandatory. Each new patient in a dialysis center must be tested for HBV markers irrespective of prior immunization. All patients in the center should be routinely screened every 3-4 months. HBV immunization is mandatory for all patients on dialysis. In patients with uremia the anti-HBs antibody production is decreased (antibodies will develop in 50%-60% of cases after immunization). It is recommended to immunize all patients with progressive kidney disease, preferably in the preterminal stage. Hepatitis B therapy is recommended in all patients with biopsy proven chronic liver disease. Patients should be treated with standard interferon alpha and/or lamivudine, or peginterferon alpha monotherapy. Hepatitis B treatment is most important in kidney and/or liver transplant candidates. HBV immunization is obligatory for all hospital personnel who are in close contact with infected patients and infective materials.

[Long-term monitoring of children with focal segmental glomerulosclerosis and a transplanted kidney]. / Dugotrajno pracenje djece s fokalnom segmentalnom glomerulosklerozom i presadenim bubregom.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is an important cause of nephrotic syndrome and end-stage renal disease. Children with FSGS are at a risk of recurrence of disease following renal transplantation. The rate of recurrence has been estimated to range from 15% to 50%, having a potentially detrimental course towards the loss of renal function. The factors associated with an increased probability of recurrence are not well known. PATIENTS: The authors followed 8 pediatric patients (3 girls and 5 boys) with FSGS who had undergone renal transplantation (16% of all transplanted pediatric patients) over a long period (1982-2001). The mean age of the children at the time of disease onset was 4 years and 8 months (range: 2 months-12 years). Children were monitored from 10 months to 4 years before the first dialysis. On average, the first dialysis was performed at 7 years of age (range: 12 months-16 years). Time elapsed between the first dialysis and transplantation ranged from 1 to 3 years (mean 1.5 year), and mean age at transplantation was 8 years and 6 months (range: 4-18 years). The grafts were from 2 living-related and 6 cadaveric donors. Five recipients were immunosuppressed with cyclosporin A (CsA) -steroids-azathioprine (Aza), 2 with CsA-steroids-mycophenolate mofetil (MMF), and 1 with CsA-steroids regimen. Follow-up period after transplantation ranged from 2 to 15 years (mean time 7 years and 8 months). RESULTS: Creatinine values, proteinuria range and blood pressure were monitored every 3 months after transplantation, and were as follows: creatinine 41-386 mumol/l (mean value 153 mumol/l), proteinuria 0.01-3,14 g/l (mean 0.27 g/l, median 0.03 g/l), systolic blood pressure 90-140 mm Hg (mean 110 mm Hg), diastolic blood pressure 60-90 mm Hg (mean 80 mm Hg). Two patients developed hypertension grade I and III after renal transplantation. There were 5 (0.6 per patient) acute rejection episodes. Two grafts (25%) were rejected 5 and 9 years after transplantation, but recurrence of FSGS was not confirmed by renal biopsy. CONCLUSION: Due to the small sample size no firm conclusions about recurrence of FSGS could be made. However, the fact that none of 8 children developed recurrence of FSGS after renal transplantation speaks against the relatively high recurrence rates in our pediatric population.

[Primary cytomegalovirus infection after combined cadaveric transplantation of the liver and kidney]. / Primoinfekcija citomegalovirusom nakon kombinirane kadavericne transplantacije jetre i bubrega.

Seronegative transplant recipients are at a high risk of developing primary cytomegalovirus (CMV) infection. The D+/R--constellation produces a 60%-80% probability of CMV disease. In such cases CMV prophylaxis is justified. Presentation of a 12-year old boy who developed a primary CMV infection following A combined liver-kidney transplantation; evaluation of prophylactic options and review of some difficulties in the diagnosis of CMV infection. A cadaveric liver-kidney transplantation (Tx) was done in a 12-year old boy with ESRD due to type I primary hyperoxaluria. CMV status: D+, R-; number of mismatches: 5. PRA 0; kidney cold ischemia time (CIT): 13.54 h; liver CIT: 10.10 h; immediate diuresis; Immunosuppression protocol: anti IL-2 receptor antibodies, steroids, mycophenolate mofetil (MMF); cyclosporine introduced on day 6. Over the first week, daily hemodialyses were done in order to remove oxalate deposits. Kidney and liver biopsies: no ACR, no oxalate deposits. CMV prophylaxis with ganciclovir started on day 0. Routine serology and PCR for CMV follow-up showed: pp 65, IgM and IgG, CMV. DNA (Murex CMV. DNA Hybrid Capture test 2.0): negative over the first 3 months. Day 98: CMV pp 65 positive, IgM neg, DNA neg. Day 108: pp 65 neg, IgM positive, IgG neg. CMV. DNA positive (15 x 105 copies/ml). Clinical status: except for mild Cushing, liver tests and kidney function were normal. Ganciclovir was administered intravenously (i.v.) and after 14 days continued perorally. A few days later, leukopenia with severe neutropenia (neutrophil count: 400) and right otitis media developed. MMF and ganciclovir were withdrawn for a few days and reintroduced after WBC count reconstitution. We had no possibility to monitor MMF. Day 150 pp 65 neg, IgM still positive, IgG neg. No clinical signs of infection. Liver and kidney functions normal. After liver-kidney transplantation in a CMV high-risk pediatric patient (D+/R-), asymptomatic CMV primary infection developed. Although ganciclovir prophylaxis could not prevent the infection, it was mild and delayed. Due to bone marrow suppression, discontinuation of MMF and ganciclovir was necessary. Antigenemia assay pp 65 did not correlate very well with CMV viremia so it could not be recommended as a routine test. It should be used in combination with other CMV tests.

Cytokines and growth factors in mostly atherosclerotic patients on hemodialysis determined by biochip array technology.

BACKGROUND: The lifespan of patients with chronic renal failure (CRF) is reduced, and coronary artery disease is the leading cause of morbidity and mortality in these patients. The progression of atherosclerosis is accelerated and angiogenesis is impaired in CRF. Risk factors that could contribute to further understanding of vascular pathology include markers of inflammation and growth factors. The purpose of this study was to determine the levels of cytokines (IL-2, IL4, IL-6, IL-8, IL-10, IL-1 alpha, IL-1 beta), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), interferon-gamma (IFN gamma), tumor necrosis factor-alpha (TNFalpha) and monocyte chemotactic protein-1 (MCP-1) in patients on chronic hemodialysis (HD; n=75), and to compare values with those of control subjects (n=113). METHODS: Evidence((R)) biochip array analyzer was used for quantification of plasma concentrations in samples. RESULTS: Significant differences were found between the control subjects and HD patients. IL-2 (p<0.001), IL-4 (p<0.001) and EGF (p<0.001) levels were higher in controls than in HD patients, while IL-6 (p<0.001), IL-8 (p=0.081), IL-10 (p=0.008), TNFalpha (p<0.001), IL-1 beta (p<0.001) and MCP-1 (p<0.001) levels were higher in HD patients. We also found IL-2 (p=0.015) and IL-1 alpha (p=0.035) levels to be significantly higher in males than females, while IL-4 (p=0.025) and IL-1 beta (p=0.049) levels were significantly higher in females. Among HD patients, IL-2 levels were higher in patients under the age of 50 years (p<0.048). It was also higher in female than in male patients (p<0.035) and in patients on HD for more than 10 years (p<0.009). IL-6 levels were higher in patients over the age of 50 years (p<0.047). Patients with previous glomerulonephritis had the highest level of IL-6 compared to patients with previous pyelonephritis and diabetes mellitus (p<0.063). IL-6 levels were higher in patients with concomitant hepatitis C virus (HCV) infection (p<0.036) and in patients with developed atherosclerosis (p<0.003). IL-8 levels were higher in patients over the age of 50 years (p<0.003) and in the group with previous glomerulonephritis (p<0.031). IL-10 levels were higher in the group with developed atherosclerosis (p<0.045). EGF was the highest in the group of patients with previous diabetes mellitus compared to pyelonephritis and glomerulonephritis groups (p<0.073). TNFalpha levels were higher in the patient population on HD for more than 10 years (p<0.032) and in the concomitant HCV group (p<0.073). IL-1 beta levels were higher in the HCV group (p<0.088). CONCLUSIONS: Plasma concentrations of some cytokines and growth factors could serve as useful diagnostic and prognostic parameters for patients with CRF on HD.