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

Abstract 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 \u2009=\u200924). 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\ua0week (M1) and 2\ua0weeks (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 \u2009=\u20090.002) was found. One week later (M2) the reduction of 1.6% after the HD was not significant ( p \u2009=\u20090.33). 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\ua0weeks using glucose-free dialysate ( p \u2009<\u20090.05). 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)

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 &lt; 0.000) and lower MCS: 2.452 (95%CI: 1.478-4.065), P &lt; 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 &lt; 0.000); 2.972 (95%CI: 1.622-5.490, P &lt; 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

“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

Teško oštećenje bubrežne funkcije u odraslih bolesnika s akutnim trovanjem octenom kiselinom

Acetic acid is a widely used organic acid with corrosive properties that depend on its concentration. If acetic acid is ingested in concentrations above 30 % it may severely damage the upper gastrointestinal tract and cause intravascular haemolysis, which can result in severe kidney and liver disorders and disseminated intravascular coagulation. In this retrospective study, we analysed acetic acid ingestion data collected at the University Clinic for Toxicology of Skopje, Macedonia from 1 January 2002 to 31 December 2011. The analysis included systemic complications, kidney damage, and the outcomes in particular. Over the ten years, 84 patients were reported at the Clinic to have ingested highly concentrated acetic acid. Twenty-eight developed kidney disorders, while the remaining 56 had no complications. Fatal outcome was reported for 11 patients, seven of whom had systemic complications and four severe gastrointestinal complications.Octena kiselina organska je kiselina s korozivnim svojstvima koja ovise o njezinoj koncentraciji. Ako se unese u koncentracijama iznad 30 %, može teško oštetiti gornji dio gastrointestinalnog sustava i izazvati intravaskularnu hemolizu, što može dovesti do teških oštećenja bubrega i jetara te do diseminirane intravaskularne koagulacije. U ovome retrospektivnom ispitivanju analizirani su slučajevi gutanja octene kiseline prikupljeni u Sveučilišnoj klinici za toksikologiju u Skopju od 1. siječnja 2002. do 31. prosinca 2011. Analize su obuhvatile sistemske komplikacije, oštećenja bubrega i ishode. Tijekom deset godina, u Kliniku su se javila 84 bolesnika zbog gutanja visokokoncentrirane octene kiseline. Njih 28 dobilo je bolest bubrega, a preostalih 56 nije imalo komplikacije. Smrtni je ishod bio zabilježen u 11 bolesnika, od kojih je sedam imalo sustavne komplikacije, a četiri teške gastrointestinalne komplikacije

KONCENTRACIJA JODA U MOKRAĆI: PREDSKAZATELJ POROĐAJNE TEŽINE ILI BIOLOŠKI BILJEG ZA PROCJENU JODNOG STATUSA SAMO U ZDRAVIH TRUDNICA?

Introduction: This study determined urine iodine concentration (UIC) during gestation, assessed the maternal iodine nutrition status and correlated it with gestational age at birth (GAB) and birth weight (BW).The measurement of UIC provides the best single measurement of the iodine nutritional status in population. Objective: Determination of UIC in pregnant women in North Macedonia. Methods: This prospective study assessed the iodine nutrition status during the course of pregnancy with reference of median UIC among 364 healthy pregnant women in different gestational age (in trimester and 5-week intervals). Results: The overall and the 1st to the 3rd trimester median UIC were: 183.7, 207, 189.75 and 169.28 [μg/L], respectively. The median UIC (μg/L) results according to 5-week interval in advancing gestation were: 232.34, 200.13, 152.81, 194.39, 181.28, 160.28, 169.41 and 175.24, respectively. We detected 5.22% (19/364) and 74.72% (272/364) with the median UIC < 50 μg/L and UIC ≥ 100 μg/L, respectively. In multiple regression, the median UIC (β = 0.0000767, P = 0.929) had no statistically signifi cant prediction to the GAB. Disease prevalence results for mean UIC in detecting BW had no statistical signifi cance: area under curve (AUC) = 0.521, z-statistic (0.340), sensitivity (45.83%), specifi city (66.27%), predictive (6.59%) and P value (0.734). Conclusion: Iodine status of pregnant women in our study is generally suffi cient by World Health Organization recommendations. The median UIC in each trimester and 5-week interval has statistically insignifi cant decrease in accordance to the advancing gestation. The median UIC has no signifi cance in predicting GAB and BW.Uvod: Ova je studija utvrdila koncentraciju joda u mokraći (UIC) tijekom trudnoće, procijenila prehrambeni status joda kod majke i povezala ga s gestacijskom dobi pri rođenju (GAB) i porođajnom težinom (BW). Mjerenje UIC-a omogućava najbolje pojedinačno mjerenje prehrambenog statusa joda u populaciji. Cilj: Određivanje UIC-a trudnicama u sjevernoj Makedoniji. Metode: Ova prospektivna studija procjenjivala je prehrambeni status joda tijekom trudnoće, pozivajući se na medijan UIC 364 zdrave trudnice u različitoj gestacijskoj dobi (u intervalima tromjesečja i 5 tjedana). Rezultati: Ukupna i prosječna UIC od 1. do 3. tromjesečja bila su: 183,7, 207, 189,75 i 169,28 [μg / L]. Srednji rezultati UIC (μg / L) prema intervalu od 5 tjedana u napredovanju trudnoće bili su: 232,34, 200,13, 152,81, 194,39, 181,28, 160,28, 169,41 i 175,24. Otkrili smo 5,22 % (19/364) i 74,72 % (272/364) s medijanom UIC <50 μg / L, odnosno UIC ≥ 100 μg / L. U višestrukoj regresiji, medijan UIC (β = 0,0000767, P = 0,929) nije imao statistički značajno predviđanje za GAB. Rezultati prevalencije bolesti za srednji UIC u otkrivanju BW nisu imali statističku značajnost: područje ispod krivulje (AUC) = 0,521, z-statistika (0,340), osjetljivost (45,83 %), specifi čnost (66,27 %), prediktivna (6,59 %) i P vrijednost (0,734). Zaključak: Jodni status trudnica u našem istraživanju u pravilu je dovoljan prema preporukama Svjetske zdravstvene organizacije. Medijan UIC-a u svakom tromjesečju i intervalu od 5 tjedana statistički je beznačajno smanjen u skladu s napredovanjem trudnoće. Medijan UIC nema značenje u predviđanju GAB i BW

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

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

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

Bone Strength and Arterial Stiffness Impact on Cardiovascular Mortality in a General Population

Osteoporosis and increased arterial stiffness independently have been found to be associated with higher cardiovascular events rates in the general population (GP). We examined 558 patients from GP by dual-energy X-ray absorptiometry (DXA) and pulse wave velocity (PWV) measurements at baseline, with 36-month follow-up period. DXA assessed bone mineral density of femoral neck (BMD FN) and lumbar spine (BMD LS). Carotid-femoral PWV was assessed by pulsed-Doppler. The aim of our study is to find correlation between bone strength and arterial stiffness and their impact on cardiovascular mortality in GP. The mean ± SD of BMD FN, BMD LS, and PWV was 0.852±0.1432 g/cm2, 0.934±0.1546 g/cm2, and 9.209±1.9815 m/s. In multiple regression analysis we found BMD FN (βst =-6.0094, p<0.0001), hypertension (βst = 1.7340, p<0.0091), and diabetes (βst=0.4595, p<0.0046). With Cox-regression analysis, after 17 cardiovascular events, the significant covariates retained by the backward model were BMD FN (b=-2.4129, p=0.015) and PWV (b=0.2606, p=0.0318). The cut-off values were PWV = 9.4 m/s, BMD FN = 0.783 g/cm2, and BMD LS = 0.992 g/cm2. The results for BMD FN and PWV hazard ratio risk were 1.116 and 1.297, respectively. BMD FN as a measure of bone strength and PWV as a measure of arterial stiffness are strong independent predictors of cardiovascular mortality in GP