ISOLATED MATERNAL HYPOTHYROXINEMIA AND ITS PERINATAL OUTCOME IN NORTH MACEDONIA.

Isolated maternal hypothyroxinemia (IMH) is defined as the presence of low maternal total thyroxine (TT4) level in conjunction with normal maternal thyroid-stimulating hormone (TSH) level. The aim was to investigate whether IMH is associated with adverse pregnancy outcome in North Macedonia. Dried blood spot samples were obtained from 359 pregnant women meeting the inclusion criteria and analyzed for TT4 and TSH. Postpartum data were entered from their medical histories. Out of 359 women, 131 (37.42%) belonged to IMH group. There were statistically significant differences in birth weight (p=0.043), intrauterine growth restriction (IUGR) (p=0.028), Apgar score at 1 min <7 (p=0.018) and cesarean section for dystocia/disproportion (p=0.024) between the IMH and normal thyroid function (NTF) groups. In regression analysis, TSH was a significant variable predicting Apgar score (ßst=0.05597, p=0.047), body mass index predicting birth weight (ßst=0.02338, p=0.045) and TT4 predicting small for gestational age/IUGR (ßst=-0.089834, p=0.029) in IMH group. TT4 was a strong predictor of birth weight (ßst=-0.004778, p=0.003) and premature delivery (ßst=0.028112, p=0.004) in NTF group. The impact of IMH in pregnancy remains controversial. IMH was associated with an increased maternal BMI and higher birth weight of neonates. Overweight could be a potential risk factor for thyroid dysfunction in pregnant women, and specifically IMH. The worst fetal outcome was seen in IMH mothers examined in second trimester. We found TSH, TT4 and BMI to be strong predictors of perinatal outcomes.

Thyroid Function of Pregnant Women and Perinatal Outcomes in North Macedonia.

OBJECTIVE: Thyroid diseases are the second most common endocrine disorders in the reproductive period of women. They can be associated with intrauterine growth restriction (IUGR), preterm delivery, low Apgar score, low birthweight (LBW) or fetal death. The aim of the present study is to explore thyroid dysfunction and its relationship with some poor perinatal outcomes (Apgar Score, low birthweight, and preterm delivery). METHODS: Dried blood spot samples from 358 healthy pregnant women were analyzed for thyroid stimulating hormone (TSH), total thyroxine (TT4), and thyroglobulin (Tg). Neonatal data were collected upon delivery. Four groups were formed based on thyroid function tests (TFTs). RESULTS: Of the 358 tested women, 218 (60.72%) were euthyroid. Isolated hypothyroxinemia was present in 132 women (36.76%), subclinical hyperthyroidism in 7 women (1.94%), and overt hypothyroidism in 1 (0.28%). The perinatal outcomes IUGR (p = 0.028) and Apgar score 1 minute (p = 0.015) were significantly different between thyroid function test [TFT]-distinct groups. In the multiple regression analysis, TT4 showed a statistically significant inverse predictive impact on LBW (p < 0.0001), but a positive impact of Tg on LBW (p = 0.0351). CONCLUSION: Thyroid hormones alone do not have a direct impact on neonatal outcomes, but the percentage of their participation in the total process cannot be neglected. Based on the regression analysis, we can conclude that TT4 and Tg can be used as predictors of neonatal outcome, expressed through birthweight and Apgar score. The present study aims to contribute to determine whether a test for thyroid status should become routine screening during pregnancy.

OBJETIVO: As doenças da tireoide são as segundas doenças endócrinas mais comuns no período reprodutivo das mulheres. Elas podem estar associadas à restrição de crescimento intrauterino (RCIU), parto prematuro, baixo índice de Apgar, baixo peso ao nascer (BPN) ou morte fetal. O objetivo do presente estudo é explorar a disfunção tireoidiana e sua relação com alguns resultados perinatais insatisfatórios (índice de Apgar, baixo peso ao nascer e parto prematuro). MéTODOS: Amostras secas de sangue em 358 gestantes saudáveis foram analisadas para hormônio estimulador da tireoide (TSH), tiroxina total (TT4) e tireoglobulina (Tg). Os dados neonatais foram coletados no momento do parto. Quatro grupos foram formados com base em testes de função tireoidiana (TFT). RESULTADOS: Das 358 mulheres testadas, 218 (60,72%) eram eutireoidianas. Hipotiroxinemia isolada estava presente em 132 mulheres (36,76%), hipertireoidismo subclínico em 7 mulheres (1,94%) e hipotireoidismo evidente em 1 (0,28%). Os resultados perinatais RCIU (p = 0,028) e índice de Apgar de 1 minuto (p = 0,015) foram significativamente diferentes entre os grupos distintos de TFT. Na análise de regressão múltipla, TT4 mostrou impacto preditivo inverso estatisticamente significativo no BPN (p < 0,0001), mas impacto positivo da Tg no BPN (p = 0,0351). CONCLUSãO: Isoladamente, os hormônios tireoidianos não têm impacto direto no desfecho neonatal, mas o percentual de sua participação no processo total não pode ser desprezado. Com base na análise de regressão, podemos concluir que TT4 e Tg podem ser usados como preditores do resultado neonatal, expressos por meio do peso ao nascer e do índice de Apgar. O presente estudo tem como objetivo contribuir para que um teste para verificar o estado da tireoide deva se tornar um rastreamento de rotina durante a gravidez.

Thyroid Function of Pregnant Women and Perinatal Outcomes in North Macedonia / Função tireoidiana de mulheres grávidas e resultados perinatais na Macedônia do Norte

Abstract Objective Thyroid diseases are the second most common endocrine disorders in the reproductive period of women. They can be associated with intrauterine growth restriction (IUGR), preterm delivery, low Apgar score, low birthweight (LBW) or fetal death. The aim of the present study is to explore thyroid dysfunction and its relationship with some poor perinatal outcomes (Apgar Score, low birthweight, and preterm delivery). Methods Dried blood spot samples from 358 healthy pregnant women were analyzed for thyroid stimulating hormone (TSH), total thyroxine (TT4), and thyroglobulin (Tg). Neonatal data were collected upon delivery. Four groups were formed based on thyroid function tests (TFTs). Results Of the 358 tested women, 218 (60.72%) were euthyroid. Isolated hypo thyroxinemia was present in 132 women (36.76%), subclinical hyperthyroidism in 7 women (1.94%), and overt hypothyroidism in 1 (0.28%). The perinatal outcomes IUGR (p = 0.028) and Apgar score 1 minute (p = 0.015) were significantly different between thyroid function test [TFT]-distinct groups. In the multiple regression analysis, TT4 showed a statistically significant inverse predictive impact on LBW (p < 0.0001), but a positive impact of Tg on LBW (p = 0.0351). Conclusion Thyroid hormones alone do not have a direct impact on neonatal outcomes, but the percentage of their participation in the total process cannot be neglected. Based on the regression analysis, we can conclude that TT4 and Tg can be used as predictors of neonatal outcome, expressed through birthweight and Apgar score. The present study aims to contribute to determine whether a test for thyroid status should become routine screening during pregnancy.

Resumo Objetivo As doenças da tireoide são as segundas doenças endócrinas mais comuns no período reprodutivo das mulheres. Elas podem estar associadas à restrição de crescimento intrauterino (RCIU), parto prematuro, baixo índice de Apgar, baixo peso ao nascer (BPN) ou morte fetal. O objetivo do presente estudo é explorar a disfunção tireoidiana e sua relação com alguns resultados perinatais insatisfatórios (índice de Apgar, baixo peso ao nascer e parto prematuro). Métodos Amostras secas de sangue em 358 gestantes saudáveis foram analisadas para hormônio estimulador da tireoide (TSH), tiroxina total (TT4) e tireoglobulina (Tg). Os dados neonatais foram coletados no momento do parto. Quatro grupos foram formados com base em testes de função tireoidiana (TFT). Resultados Das 358 mulheres testadas, 218 (60,72%) eram eutireoidianas. Hipotiroxinemia isolada estava presente em 132 mulheres (36,76%), hipertireoidismo subclínico em 7 mulheres (1,94%) e hipotireoidismo evidente em 1 (0,28%). Os resultados perinatais RCIU (p = 0,028) e índice de Apgar de 1 minuto (p = 0,015) foram significativamente diferentes entre os grupos distintos de TFT. Na análise de regressão múltipla, TT4 mostrou impacto preditivo inverso estatisticamente significativo no BPN (p < 0,0001), mas impacto positivo da Tg no BPN (p = 0,0351). Conclusão Isoladamente, os hormônios tireoidianos não têm impacto direto no desfecho neonatal, mas o percentual de sua participação no processo total não pode ser desprezado. Com base na análise de regressão, podemos concluir que TT4 e Tg podem ser usados como preditores do resultado neonatal, expressos por meio do peso ao nascer e do índice de Apgar. O presente estudo tem como objetivo contribuir para que um teste para verificar o estado da tireoide deva se tornar um rastreamento de rotina durante a gravidez.

Using the World Apheresis Association Registry Helps to Improve the Treatment Quality of Therapeutic Apheresis.

Therapeutic apheresis (TA) is prescribed to patients that suffer from a severe progressive disease that is not sufficiently treated by conventional medications. A way to gain more knowledge about this treatment is usually by the local analysis of data. However, the use of large quality assessment registries enables analyses of even rare findings. Here, we report some of the recent data from the World Apheresis Association (WAA) registry. Data from >104,000 procedures were documented, and TA was performed on >15,000 patients. The main indication for TA was the collection of autologous stem cells (45% of patients) as part of therapy for therapy. Collection of stem cells from donors for allogeneic transplantation was performed in 11% of patients. Patients with indications such as neurological diseases underwent plasma exchange (28%). Extracorporeal photochemotherapy, lipid apheresis, and antibody removal were other indications. Side effects recorded in the registry have decreased significantly over the years, with approximately only 10/10,000 procedures being interrupted for medical reasons. CONCLUSION: Collection of data from TA procedures within a multinational and multicenter concept facilitates the improvement of treatment by enabling the analysis of and feedback on indications, procedures, effects, and side effects.

Which Better Determines the Renal Function and Glomerular Filtration Rate: Renal Parenchymal Thickness or Renal Resistive Index?

Resistive index (RI) could provide more useful diagnostic and prognostic information for kidney disease than parenchymal thickness (PT) only. The aims of this study were to find the association between PT, glomerular filtration rate (GFR), and RI and their determination of renal function. B-mode and Doppler ultrasonography and standard biochemical laboratory testing (urea and creatinine) were performed among 75 participants (57.1 ± 10.6 years). We measured PT and RI and calculated GFR. The mean and standard deviation were 0.671 ± 0.041, 12.24 ± 1.98 mm, and 86.38 ± 15.96 mL/min/1.73 m2 for RI, PT, and GFR, respectively. The mean RI in two subgroups with PT smaller or greater than 12.5 mm was RI1 = 0.692 ± 0.038 or RI2 = 0.648 ± 0.03 (P <0.0001). Strong inverse correlation between RI (y) and PT (x) presented by the linear regression equation: y = 0.744 + (-0.005932 x). By multiple regression, we show GFR and PT as predictors for increasing of RI (R2 = 0.2063, ßst = -0.0009176, P = 0.0012 and ßst = -0.006003, P = 0.0078), respectively. Renal RI inversely strongly correlates with the PT and GFR. Renal PT and GFR are independent predictors for increasing of RI in general population.

Impact of preoperative arterial and venous diameter on achievement of the adequate blood flow in arteriovenous fistula for hemodialysis.

An arteriovenous fistula (AVF) remains the best choice of vascular access (VA) for hemodialysis (HD). The aim of the study was to determine the factors associated with the achievement of adequate blood flow (BF) of AVFs at the 4th week after creation. Created AVFs in 63 patients with chronic kidney disease (CKD) stage 4/5 and CKD stage 5 on hemodialysis (CKD5D) were analyzed in a prospective study. Doppler ultrasound (DUS) was used for measuring the diameter of the radial artery, the brachial artery and the cephalic vein before AVF creation. The BF of AVF was calculated by DUS at the 4th week after creation and adequate BF was defined as ≥ 600 mL/min. The average age of patients was 61.31 ± 12.9 years. An adequate BF of AVF at the 4th week after creation was achieved in 43.54% of patients. The BF of AVF measured in male patients was significantly higher compared to the BF of AVF obtained in females (576.03 mL/min vs 375.12 mL/min, P = 0.004). The diameter of the blood vessels with achieved adequate BF was significantly larger compared to the diameter of the blood vessels without adequate BF (radial artery: 2.45 mm vs 2.03 mm, P = 0.000; brachial artery: 4.78 mm vs 4.06 mm, P = 0.001 and cephalic vein: 3.12 mm vs 2.83 mm P = 0.018). The gender and the diameter of the blood vessels before AVF creation were significantly associated with achievement of adequate BF of AVF at the 4th week of creation.

Primary Failure of the Arteriovenous Fistula in Patients with Chronic Kidney Disease Stage 4/5.

BACKGROUND: An Arteriovenous fistula (AVF) is a creation of the natural blood vessels. It is a "gate of life" for the patients on hemodialysis. AIM: The study aimed to analyze the predictors for primary failure of AVF such as gender, age, number and location of AVF, and primary renal disease in patients with chronic kidney disease (CKD) stage 4/5. MATERIAL AND METHODS: The medical records of 178 created arteriovenous fistulae in patients with CKD stage 4/5, were retrospectively studied. Primary failure of AVF was defined as thrombosis or inability for cannulation of AVF within 3 months. Adequate maturation of AVF was defined as successful cannulation of AVF treatment and blood flow of > 600 ml/min. RESULTS: The mean age of the patients was 59.75 ± 14.65 years, and 65.16% (116/178) were men. Adequate maturation of AVF was achieved in 83.71% (149/178). Primary failure of AVF occurred in 16.29% (29/178) of the created fistulae, while 10.11% (18/178) had early thrombosis. The distal arteriovenous fistulae were significantly more frequently created in male patients (51 vs 18; p = 0.015). The female patients were significantly older than the male patients (63.27 vs 57.86 years; p = 0.018). CONCLUSION: Male gender was associated with better maturation of AVF. The age, number and location of AVF, and primary renal disease in patients with CKD stage 4/5 were not associated with primary failure of AVF.

Hypertension after Kidney Transplantation: Clinical Significance and Therapeutical Aspects.

Most of the kidney transplanted patients develop arterial hypertension after renal transplantation. Together with very well-known and usual risk factors, post-transplant hypertension contributes to the whole cardiovascular morbidity and mortality in the kidney transplant population. The reasons of post-transplant hypertension are factors related to donors and recipients, immunosuppressive therapy like Calcineurin Inhibitors (CNI) and surgery procedures (stenosis and kinking of the renal artery and ureteral obstruction). According to Eighth National Committee (JNC 8) recommendations, blood pressure > 140/90 mmHg is considered as hypertension. The usual antihypertensive drugs used for the control of hypertension are Calcium channel blockers (CCB), Angiotensin-converting enzyme (ACE) inhibitors, Angiotensin -II receptor blockers (ARB), B- blockers and diuretics. Follow the KDIGO guidelines the target blood pressure < 140/90 mmHg for patients without proteinuria and < 125/75 mmHg in patients with proteinuria is recommended. Better control of post-transplant hypertension improves the long-term graft and patient's survival.

Complications and Risks of Percutaneous Renal Biopsy.

BACKGROUND: Renal biopsy performed in native and transplant kidneys is generally considered a safe procedure. AIM: In this study, we evaluated renal biopsy complications and risk factors in one nephrology facility. MATERIAL AND METHODS: We conducted a three-year retrospective study on patients who underwent renal biopsy between January 2014 and December 2016. Strict written biopsy protocol was followed. Clinical and laboratory data were obtained from medical charts. Complications were categorised as minor and major, according to the need for intervention. Minor complications included macrohematuria and/or hematoma that did not require intervention. Major complications included hematuria or hematoma with fall of hematocrit that required a blood transfusion, surgery or caused death. A binary logistic regression model was used to analyse the possible factors associated with complications after the biopsy. RESULTS: We analysed 345 biopsies; samples were taken from patients aged from 15-81 years, of whom 61% were men. A total of 21 (6%) patients developed a complication, 4.4% minor and 1.7% major complications. There were no nephrectomy or death due to biopsy intervention. Overweight patients, as well as those with higher creatinine, lower hemoglobin, higher blood pressure and biopsy due to AKI had higher chances to develop complications (p = 0.037, p = 0.023, p = 0.032, p = 0.002, p = 0.002, respectively). The patients' age, gender, kidney dimension, number of passes and uninterrupted aspirin therapy were not found as significant predictors of complications. In the multivariate logistic model, body weight (OR = 1.031, 95%CI = 1.002-1.062), lower hemoglobin (OR = 0.973, 95%CI = 0.951-0.996) and hypertension (OR = 1.025, 95%CI = 1.007-1.044) increased the risk of complications in biopsied patients. CONCLUSION: Renal biopsy is a safe procedure with a low risk of complications when strict biopsy protocol is observed. Correction of anaemia and blood pressure is to be considered before the biopsy.

Acute-phase proteins as promoters of abdominal aortic calcification in chronic dialysis patients.

The aim of this study was to find a correlation between acute-phase proteins (APPs) and abdominal aortic calcification (AAC) as well as the impact APPs on AAC in chronic dialysis patients (CDPs). Native lateral lumbar radiography and biochemical analysis were performed in 112 CDPs (aged 60.0 ± 5.43 years) to estimate and score AAC and biochemical values of APPs. The mean AAC score was 8.39 ± 5.43. We detected 16 (14.28%) CDPs without AAC and 96 (85.71%) CDPs with AAC (10 ± 5.43). The number of CDPs with AAC ≤4 was 34 (30.36%) with mean AAC score of 1.85 ± 1.94. By multiple regression analysis, we found positive correlation between AAC and ferritin (ß = 0.004398, P = 0.0085) and AAC and C-reactive protein [(CRP), ß = 0.1972, P = 0.0178]. Sensitivity/specificity pairs and criterion variables (CrVs) were as follows: for CRP: 44.21%, 100%, and CrV ≥6 and for ferritin: 83.16%, 56.25%, and CrV ≥196.32. The area under curve (AUC) for CRP and ferritin was 0.721 (P <0.0001) and 0.730 (P <0.0026), respectively. Fibrinogen and serum iron AUC in the prediction of AAC were 0.533 (P = 0.5749) and 0.618 (P = 0.0795), respectively. CRP and ferritin were the most powerful APPs involved in the promotion of AAC; serum iron and fibrinogen were shown as lower activity promoters in CDPs. Serum albumin showed inverse activity on AAC.

Active Smoking is Associated with Lower Dialysis Adequacy in Prevalent Dialysis Patients.

BACKGROUND: Dialysis adequacy measured by single pool Kt/V (spKt/V) lower than 1.2 or urea reduction rate (URR) lower than 65% is associated with a significant increase in patient mortality rate. Patients' adherence to the medical treatment is crucial to achieve recommended targets for spKt/V. Smoking is a recognized factor of non-adherence. AIM: In this study we sought to assess the association of active smoking and dialysis adequacy. METHODS: A total of 134 prevalent dialysis patients from one dialysis center were included in an observational cross-sectional study. Clinical, laboratory and dialysis data were obtained from medical charts in previous 6 months. The number of missed, on purpose interrupted or prematurely terminated dialysis sessions was obtained. Dialysis adequacy was calculated as spKt/V and URR. Patients were questioned about current active smoking status. T-test and Chi-Square test were used for comparative analysis of dialysis adequacy with regard to smoking status. RESULTS: The majority of patients declared a non-smoking status (100 (75%)) and 34 (25%) were active smokers. Male gender, younger age and shorter dialysis vintage were significantly more often present in the active smokers ((9 (26%) vs 25 (73%), p = 0.028; 57.26 ± 12.59 vs 50.15 ± 14.10, p = 0.012; 118.59 ± 76.25 vs 88.82 ± 57.63, p = 0.030)), respectively. spKt/V and URR were significantly lower and Kt/V target was less frequently achieved in smokers ((1.46 ± 0.19 vs. 1.30 ± 0.021, p = 0.019; 67.14 ± 5.86 vs. 63.64 ± 8.30, p = 0.002; 14 (14%) vs. 11 (32%), p = 0.023), respectively. Shorter dialysis sessions, larger ultra filtrations and higher percentage of missed/interrupted dialysis session on patients' demand were observed in smokers (4.15 ± 0.30 vs. 4.05 ± 0.17, p = 0.019; 3.10 ± 0.78 vs. 3.54 ± 0.92, p = 0.017; 25 (0.3%) vs. 48 (1.8%), p = 0.031), respectively. CONCLUSION: Active smokers, especially younger men, achieve lower than the recommended levels for dialysis adequacy. Non-adherence to treatment prescription in smokers is a problem to be solved. Novel studies are recommended in patients on dialysis, to further elucidate the association of dialysis adequacy with the active smoking status.

B - Flow assessment of femoral artery as predictor of coronary artery disease in patients evaluated for chest pain by radionuclide myocardial perfusion scintigraphy.

In the evaluation of patients with suspected coronary artery disease (CAD), the presence of the superficial femoral artery (SFA) plaque is more informative than a carotid plaque and at least as informative as coronary plaque in the identification of coronary death individuals. In 60 patients with chest pain with a normal electrocardiogram, B-flow ultrasound estimation of SFA plaque and radionuclide myocardial perfusion scintigraphy (MPS) estimation for CAD was performed. We found significant positive correlations between age and SFA plaque score (PS) (P = 0.0084), myocardial ischemia in rest and SFA PS (P < 0.0001), and between transient ischemic dilation (TID) and SFA PS (P = 0.0069), too. The TID correlates only with myocardial ischemia in rest (P = 0.0022) and SFA PS (P = 0.0069). The results we got by the receiver operating characteristics (ROC) curve analysis with TID/without TID were the area under curve (0.704, P = 0.0038). The multiple regression analysis showed standardized coefficient ß coefficients for SFA PS and TID (3.4577 and 1.9903, P < 0.001 and P = 0.0021), respectively. By proven correlative relationship of SFA atherosclerotic plaques and CAD, we can use B-flow as a screening method for triage of patients with chest pain before being sent to the assessment of coronary circulation with radionuclide MPS.

Skin Autofluorescence, a Measure of Cumulative Metabolic Stress and Advanced Glycation End Products, Decreases During the Summer in Dialysis Patients.

Tissue advanced glycation end products (AGEs) are a measure of cumulative metabolic and oxidative stress and cytokine-driven inflammatory reactions. AGEs are thought to contribute to the cardiovascular complications of hemodialysis (HD) patients. Skin autofluorescence (SAF) is related to the tissue accumulation of AGEs and rises with age. SAF is one of the strongest prognostic markers of mortality in these patients. The content of AGEs is high in barbecue food. Due to the location in northern Sweden, there is a short intense barbecue season between June and August. The aim of this study was to investigate if seasonal variations in SAF exist in HD patients, especially during the barbecue season. SAF was measured noninvasively with an AGE Reader in 34 HD-patients (15 of those with diabetes mellitus, DM). Each time the median of three measures were used. Skin-AF was measured before and after each one HD at the end of February and May in 31 patients (22 men/9 women); the end of May and August in 28 (20 m/8 w); the end of August and March in 25 (19 m/6 w). Paired statistical analyses were performed during all four periods (n = 23, 17 m/6 w); as was HbA1c of those with DM. There was at a median 5.6% increase in skin-AF during the winter period (February-May, P = 0.004) and a 10.6% decrease in the skin-AF during the summer (May-August, P < 0.001). HbA1c in the DM rose during the summer (P = 0.013). In conclusion, skin-AF decreased significantly during the summer. Future studies should look for favorable factors that prevent skin-AF and subsequently cardiovascular diseases.

Quality of Life-Repeated Measurements Are Needed In Dialysis Patients.

BACKGROUND: There is a general agreement that, besides survival, the quality of life is a highly relevant outcome in the evaluation of treatment in patients with the end-stage renal disease. Moreover, it is very important to determine whether the quality of life impacts survival. AIM: This study aims to assess whether changes or absolute scores of the quality of life (QOL) measurements better predict mortality in dialysis patients. MATERIAL AND METHODS: In a longitudinal study comprising 162 prevalent hemodialysis patients QOL was assessed with the 36-item - Short Form Health Survey Questionnaire (SF-36) at baseline and after 12 months. Patients were followed for 60 months. Mortality risk was assessed using Cox proportional hazards analysis for patients with below and above median levels of both physical and mental QOL component scores (PCS and MCS, respectively). RESULTS: At the beginning of the study the mean Physical Component score was 47.43 ± 26.94 and mean Mental Component Score was slightly higher 50.57 ± 24.39. Comparative analysis of the changes during the first year showed a marked deterioration of all quality of life scores in surviving patients. The 5-point decline for PCS was noted in 39 (24%) patients and 42 (26%) for MCS. In the follow-up period of 60 months, 69 (43%) patients died. In the Cox analysis, mortality was significantly associated with lower PCS: HR = 2.554 [95% confidence interval (CI): 1.533-4.258], (P < 0.000) and lower MCS: 2.452 (95% CI: 1.478-4.065), P < 0.001. The patients who had lower levels of PCS and MCS in the second QOL survey 1 year later, had similarly high mortality risk: 3.570 (95% CI: 1.896-6.727, P < 0.000); 2.972 (95% CI: 1.622-5.490, P < 0.000), respectively. The hazard ratios for mortality across categories for the change of PCS and MCS were not significant. In the multivariate model categorising the first and second scores as predictors and adjusted for age, only the second PCS and MCS score were associated with mortality. CONCLUSION: Low QOL scores are associated with mortality in repeated measurements, but only the more recent overwhelmed the power of the decline.

The Spectrum of Histopathological Changes in the Renal Allograft - a 12 Months Protocol Biopsy Study.

INTRODUCTION: Renal transplantation became a routine and successful medical treatment for Chronic Kidney Disease in the last 30 years all over the world. Introduction of Luminex based Single Antigen Beads (SAB) and recent BANFF consensus of histopathological phenotypes of different forms of rejection enables more precise diagnosis and changes the therapeutic approach. The graft biopsies, protocol or cause, indicated, remain a golden diagnostic tool for clinical follow up of kidney transplant recipients (KTR). AIM: The study aimed to analyse the histopathological changes in renal grafts 12 months after the surgery in KTR with satisfactory kidney function. MATERIAL AND METHODS: A 12-month protocol biopsy study was performed in a cohort of 50 Kidney transplant recipients (42 from living and 8 from deceased donors). Usual work-up for suitable donors and recipients, standard surgical procedure, basic principles of peri and postoperative care and follow up were done in all KTR. Sequential quadruple immunosuppression including induction with Anti-thymocyte globulin (ATG) or Interleukin-2R antagonist (IL-2R), and triple drug maintenance therapy with Calcineurin Inhibitors (CNI), Mycophenolate Mofetil (MMF) and Steroids were prescribed to all pts. Different forms of Glomerulonephritis (16), Hypertension (10), End Stage Renal Disease (13), Hereditary Nephropathies (6), Diabetes (3) and Vesicoureteral Reflux (2) were the underlying diseases. All biopsies were performed under ultrasound guidance. The 16 gauge needles with automated "gun" were used to take 2 cores of tissue. The samples were stained with HE, PAS, Trichrome Masson and Silver and reviewed by the same pathologist. A revised and uploaded BANFF 2013 classification in 6 categories (Cat) was used. RESULTS: Out of 48 biopsies, 15 (31%) were considered as normal, 4 (8%), Borderline (BL-Cat 3), 5 (10%) as Interstitial Fibrosis/Tubular Atrophy (IF/TA-Cat 5), 5 (10%) were classified as non-immunological (Cat 6), 2 as a pure antibody-mediated rejection (ABMR-Cat 2) and T-cell Mediated Rejection (TCMR-Cat 4). The remaining 17 samples were classified as a "mixed" rejection: 7 (41%) ABMR + IF/TA, 5 (29%) ABMR + BL + IF/TA, 2 (11%) BL + IF/TA, 1 (5%) ABMR + BL, 1 (5%) ABMR + TCMR and 1 (5%) TCMR + IF/TA. The mean serum creatinine at the time of the biopsy was 126.7 ± 23.4 µmol/L, while GFR-MDRD 63.4 ± 20.7 ml/min, which means that the majority of the findings were subclinical. Among the non-immunological histological findings (Cat 6), 3 cases belonged to CNI toxicity, 1 to BK nephropathy and 1 to recurrence of the primary disease. CONCLUSION: Our 12-month protocol biopsy study revealed the presence of different forms of mixed subclinical rejection. Use of recent BANFF classification and scoring system enables more precise diagnosis and subsequently different approach to the further treatment of the KTR. More correlative long-term studies including Anti HLA antibodies and Endothelial Cell Activation- Associated Transcripts (ENDAT) are needed.

"Bladder Effect" - An Urodynamic Parameter to Distinguish Subtypes of Urinary Incontinence in Women.

BACKGROUND: Urinary incontinence (UI) is defined by the International Continence Society (ICS) as the involuntary loss of urine that represents a hygienic or social problem to the individual. The aetiology is multifactorial. The diagnosis of UI is important because it can result in the application of appropriate therapy. Urodynamics is a golden standard, without which every UI diagnosis is insufficient. AIM: The goal of this study was, based on urodynamic results, to prove the existence of evident differences between the subtypes of UI. METHODS: Eighty patients with UI were evaluated (50 with urinary stress incontinence-USI and 30 with detrusor instability-DI) according to a standard evaluation protocol. Exclusion criteria were: mixed UI and diseases that simulated UI. All patients were 36-65 years of age (mean 56). The following parameters were measured: maximal and average flow, maximal and average voiding pressure. These parameters were compared between both groups, to determine the diagnostic significance of the parameter "Bladder Effect" (BE). It is a product of the urine flow and the pressure during voiding. RESULTS: The results showed a significant difference with a high confidence interval. Mean BEmax was 577 units in the patient group with USI, and 1014 in the DI group. Similarly, BEav was 313 units in the USI group, and 499 units in the DI group, with a significant difference and a high interval of confidence. CONCLUSION: In conclusion, the results of the study suggested that BE could be a useful diagnostic parameter to distinguish between USI and DI.

Carnitine Palmitoyltransferase II Deficiency (CPT II) Followed By Rhabdomyolysis and Acute Kidney Injury.

BACKGROUND: Carnitine palmitoyltransferase II deficiency (CPT II) is an autosomal recessive disorder and the most common inherited disorder of mitochondrial long-chain fatty acid oxidation, characterised by attacks of myalgia and myoglobinuria. The most common "classic" myopathic form occurs in young adults and is characterised by recurrent episodes of rhabdomyolysis triggered by prolonged exercise, fasting or febrile illness. CASE PRESENTATION: We present a case of a 22-year-old Caucasian male admitted to our hospital with fever, dyspnea, fatigue, myalgia and dark urine (brown-coloured). The symptoms appeared after viral infection followed by fever. Acute kidney injury (AKI) developed as a complication, and there was a need for treatment with hemodialysis. At the clinical presentation, the patient had plasma creatine kinase (pCK) level of 130.383 U/L and plasma myoglobin level over 5000 µg/L. Genetic testing (molecular analysis) confirmed the diagnosis of inherited rhabdomyolysis, a metabolic disorder of carnitine palmitoyltransferase II deficiency. A previous episode with the same symptoms, the patient had four years ago but did not ask for medical treatment. The patient was discontinued from hemodialysis because of the resolution of acute kidney injury. The patient was discharged from the hospital in good condition, with a recommendation about his future lifestyle in order to prevent similar episodes. CONCLUSION: Every patient presenting with myalgia, dark urine (brown-coloured), high level of pCK and development of AKI requiring hemodialysis, should be explored for inherited rhabdomyolysis induced by CPT II deficiency.

Hepatitis C Virus Infection in Kidney Transplant Patients: Current Treatment Options.

Hepatitis C virus infection is highly prevalent among kidney transplant recipients, occurring consequently to their previous treatment with hemodialysis. Hepatitis C virus infection has been associated with lower graft and patient survival compared with that shown in patients without infection. The lower survival has been associated with the posttransplant progression of liver disease and increased risk for development of extrahepatic complications. The choice of immunosuppressive drugs could significantly affect the course of the infection with an accelerated viral replication after kidney transplant. Eradicating hepatitis C virus infection with antiviral treatment is imperative to increasing graft and patient survival after transplant. Antiviral treatment options include standard interferon-based therapy and new directacting antiviral agents. Interferon-based treatment is rarely used in kidney transplant recipients because it has been associated with high risk of interferoninduced acute graft rejection. Several novel studies have shown that the new direct-acting antiviral agents are highly efficacious for treatment of hepatitis C infection in kidney transplant patients.

Hepatitis C virus infection in maintenance hemodialysis patients: recommendations for diagnostics and treatment.

Hepatitis C virus (HCV) infection is highly prevalent among patients treated with maintenance hemodialysis and is an important cause of morbidity and mortality. It is necessary to determine the HCV genotype and the viral load to monitor the clinical and laboratory features and to establish an optimal antiviral treatment strategy. Antiviral treatments are presented with a standard interferon-based regimen and new direct-acting antiviral agents. The advent of direct-acting antivirals has improved the efficacy and safety of HCV treatment for most patients, even in difficult-to-treat populations such as patients on hemodialysis. HCV treatment with direct-acting antivirals in hemodialysis patients is highly effective, with viral eradication rates similar to those seen in patients without chronic kidney disease and with acceptable adverse event profiles.

Skin- and Plasmaautofluorescence in hemodialysis with glucose-free or glucose-containing dialysate.

BACKGROUND: Haemodialysis (HD) patients suffer from an increased risk of cardiovascular disease (CVD). Skin autofluorescence (SAF) is a strong marker for CVD. SAF indirectly measures tissue advanced glycation end products (AGE) being cumulative metabolites of oxidative stress and cytokine-driven inflammatory reactions. The dialysates often contain glucose. METHODS: Autofluorescence of skin and plasma (PAF) were measured in patients on HD during standard treatment (ST) with a glucose-containing dialysate (n = 24). After that the patients were switched to a glucose-free dialysate (GFD) for a 2-week period. New measurements were performed on PAF and SAF after 1 week (M1) and 2 weeks (M2) using GFD. Nonparametric paired statistical analyses were performed between each two periods. RESULTS: SAF after HD increased non-significantly by 1.2% while when a GFD was used during HD at M1, a decrease of SAF by 5.2% (p = 0.002) was found. One week later (M2) the reduction of 1.6% after the HD was not significant (p = 0.33). PAF was significantly reduced during all HD sessions. Free and protein-bound PAF decreased similarly whether glucose containing or GFD was used. The HD resulted in a reduction of the total PAF of approximately 15%, the free compound of 20% and the protein bound of 10%. The protein bound part of PAF corresponded to approximately 56% of the total reduction. The protein bound concentrations after each HD showed the lowest value after 2 weeks using glucose-free dialysate (p < 0.05). The change in SAF could not be related to a change in PAF. CONCLUSIONS: When changing to a GFD, SAF was reduced by HD indicating that such measure may hamper the accumulation and progression of deposits of AGEs to protein in tissue, and thereby also the development of CVD. Glucose-free dialysate needs further attention. Protein binding seems firm but not irreversible. TRIAL REGISTRATION: ISRCTN registry: ISRCTN13837553 . Registered 16/11/2016 (retrospectively registered).