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1.
Article in English | MEDLINE | ID: mdl-38327216

ABSTRACT

BACKGROUND AND HYPOTHESIS: Primary glomerular disease (PGD) is a major cause of end-stage kidney disease (ESKD) leading to kidney replacement therapy (KRT). We aimed to describe incidence (trends) in individuals starting KRT for ESKD due to PGD and to examine their survival and causes of death. METHODS: We used data from the European Renal Association (ERA) Registry on 69 854 patients who started KRT for ESKD due to PGD between 2000 and 2019. ERA primary renal disease codes were used to define six PGD subgroups. We examined age and sex standardized incidence, trend of the incidence, and survival. RESULTS: The standardized incidence of KRT for ESKD due to PGD was 16.6 per million population (pmp), ranging from 8.6 pmp in Serbia to 20.0 pmp in France. IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) had the highest incidence of 4.6 pmp and 2.6 pmp, respectively. Histologically non-examined PGDs represented over 50% of cases in Serbia, Bosnia and Herzegovina, and Romania and were also common in Greece, Estonia, Belgium, and Sweden. The incidence declined from 18.6 pmp in 2000 to 14.5 pmp in 2013, after which it stabilized. All PGD subgroups had five-year survival probabilities above 50%, with crescentic glomerulonephritis having the highest risk of death (adjusted hazard ratio: 1.8 [95% confidence interval: 1.6-1.9]) compared with IgAN. Cardiovascular disease was the most common cause of death (33.9%). CONCLUSION: The incidence of KRT for ESKD due to PGD showed large differences between countries and was highest and increasing for IgAN and FSGS. Lack of kidney biopsy facilities in some countries may have affected accurate assignment of the cause of ESKD. The recognition of the incidence and outcomes of KRT among different PGD subgroups may contribute to a more individualized patient care approach.

2.
Int Urol Nephrol ; 56(2): 615-623, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37410303

ABSTRACT

PURPOSE: End-stage renal disease patients on chronic hemodialysis (HD) have a shortened life expectancy compared to the general population. The aim of this study was to evaluate a possible link between three new and emerging factors in renal pathophysiology: Klotho protein, telomere length in peripheral blood mononuclear cells (TL) and redox status parameters before HD (bHD) and after HD (aHD), and to test mortality prediction capability of these emerging parameters in a population of HD patients. METHODS: The study included 130 adult patients with average age 66 (54-72), on HD (3 times per week; 4-5 h per session). Klotho level, TL, routine laboratory parameters, dialysis adequacy and redox status parameters: advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), superoxide anion (O2.-), malondialdehyde (MDA), ischemia-modified albumin (IMA), total sulfhydryl group content (SHG), and superoxide dismutase (SOD) were determined. RESULTS: Klotho concentration was significantly higher aHD; 68.2 (22.6-152.9) vs. bHD 64.2 (25.5-119.8) (p = 0.027). The observed increase in TL was not statistically significant. AOPP, PAB, SHG, and SOD activity were significantly increased aHD (p > 0.001). The patients with the highest mortality risk score (MRS) had significantly higher PAB bHD (p = 0.002). Significantly lower O2.- (p < 0.001), SHG content (p = 0.072), and IMA (p = 0.002) aHD were found in patients with the lowest MRS values. Principal component analysis revealed redox balance-Klotho factor as a significant predictor of high mortality risk (p = 0.014). CONCLUSION: Decreased Klotho and TL attrition as well as redox status disturbance could be connected with higher mortality rate in HD patients.


Subject(s)
Antioxidants , Kidney Failure, Chronic , Adult , Humans , Aged , Antioxidants/metabolism , Reactive Oxygen Species , Oxidative Stress , Biomarkers , Advanced Oxidation Protein Products/metabolism , Leukocytes, Mononuclear/chemistry , Leukocytes, Mononuclear/metabolism , Serum Albumin/metabolism , Renal Dialysis , Superoxide Dismutase
3.
Int J Mol Sci ; 24(19)2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37834207

ABSTRACT

The complications of type 2 diabetes mellitus (T2DM) are well known and one of them is diabetic chronic kidney disease (DCKD). Over time, it has become clear that patients with T2DM can have nondiabetic chronic kidney diseases (NDCKD), especially those that affect the glomeruli. Clinical indicators for identifying DCKD from NDCKD with high sensitivity and specificity have not yet been identified. Therefore, kidney biopsy remains the golden standard for DCKD diagnosis in patients with T2DM. Despite some indications for kidney biopsy, criteria for a biopsy differ between countries, regions, and doctors. The aim of the study was to analyze the biopsy findings in our T2DM population and the justification of the biopsy according to widely accepted criteria. This single center retrospective study analyzed data from 74 patients with T2DM who underwent kidney biopsy from January 2014 to January 2021. According to the biopsy data, we categorized31 patients in the DN group, patients with typical diabetic glomerulopathy, 11 patients in the mixed group, patients who had pathohistological elements for both DN and non-DN glomerulopathy, and 32 patients in the non-DN group, patients with primary glomerulopathy not linked with DM. In the non-DN and mixed groups, the most frequent glomerulopathy was mesangioproliferative glomerulonephritis, including IgA and non-IgA forms, found in 10 patients, and membranous nephropathy (MN) in 10 patients. We analyzed several parameters and only the amount of proteinuria was found to be significantly linked to biopsy findings related to DN. With the existing criteria for kidney biopsy, we managed to detect changes in the kidneys in about half of our patients with T2DM. These patients required specific treatment, different from that which we use for DCKD patients.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Kidney Diseases , Renal Insufficiency, Chronic , Humans , Retrospective Studies , Risk Factors , Diabetic Nephropathies/pathology , Kidney/pathology , Kidney Diseases/pathology , Renal Insufficiency, Chronic/pathology , Biopsy
4.
Cent Eur J Immunol ; 48(2): 163-166, 2023.
Article in English | MEDLINE | ID: mdl-37692031

ABSTRACT

A 69-year-old woman presented with severe anemia, proteinuria, microscopic hematuria and rapidly progressive renal failure. She was admitted to the nephrology department due to severe deterioration of renal function with complaints of malaise, fever, dry cough and occasional epistaxis that appeared 2 months prior to admission. Histopathologic examination of a specimen from kidney biopsy and immunologic findings revealed ANCA positive pauci-immune crescentic glomerulonephritis. The patient had a history of ovarian granulosa cell tumor and lung metastases that were treated surgically with postoperative radiotherapy and chemotherapy. Thoracic computed tomography showed tissue neoplasm in the right lung and ultrasound-guided percutaneous transthoracic biopsy confirmed granulosa cell tumor. That was a relapse, thirty-nine years after initial treatment of malignant disease and twenty-four years after surgical resection of metastases from both lungs. Although the association between malignancy and vasculitis has been well known for decades, this is the first described case of ANCA vasculitis associated with any type of gynecological malignancy and glomerulonephritis.

5.
Nephrol Dial Transplant ; 38(6): 1528-1539, 2023 05 31.
Article in English | MEDLINE | ID: mdl-36610723

ABSTRACT

BACKGROUND: The aim of this study was to identify trends in total, deceased donor (DD) and living donor (LD) kidney transplantation (KT) rates in European countries. METHODS: The European Renal Association (ERA) Registry and the Global Observatory on Donation and Transplantation (GODT) databases were used to obtain the number of KTs in individual European countries between 2010 and 2018. General population counts were obtained from Eurostat or the national bureaus of statistics. The KT rate per million population (p.m.p.) and the average annual percentage change (APC) were calculated. RESULTS: The total KT rate in the 40 participating countries increased with 1.9% annually  [95%  confidence  interval  (CI) 1.5, 2.2] from 29.6 p.m.p. in 2010 to 34.7 p.m.p. in 2018, reflecting an increase of 3.4 p.m.p. in the DD-KT rate (from 21.6 p.m.p. to 25.0 p.m.p.; APC 1.9%; 95% CI 1.3, 2.4) and of 1.5 p.m.p. in the LD-KT rate (from 8.1 p.m.p. to 9.6 p.m.p.; APC 1.6%; 95% CI 1.0, 2.3). The trends in KT rate varied widely across European countries. An East-West gradient was observed for DD-KT rate, with Western European countries performing more KTs. In addition, most countries performed fewer LD-KTs. In 2018, Spain had the highest DD-KT rate (64.6 p.m.p.) and Turkey the highest LD-KT rate (37.0 p.m.p.). CONCLUSIONS: The total KT rate increased due to a rise in the KT rate from DDs and to a lesser extent from LDs, with large differences between individual European countries.


Subject(s)
Kidney Transplantation , Humans , Living Donors , Kidney , Europe/epidemiology , Registries
6.
J Pathol Inform ; 13: 100108, 2022.
Article in English | MEDLINE | ID: mdl-36277955

ABSTRACT

Background Fractal dimension is an indirect indicator of signal complexity. The aim was to evaluate the fractal and textural analysis parameters of glomeruli in obese and non-obese patients with glomerular diseases and association of these parameters with clinical features. Methods The study included 125 patients mean age 46 ±â€¯15.2 years: obese (BMI ≥ 27 kg/m2-63 patients) and non-obese (BMI < 27 kg/m2-62 patients). Serum concentration of creatinine, protein, albumin, cholesterol, trygliceride, and daily proteinuria were measured. Formula Chronic Kidney Disease Epidemiology Colaboration (CKD-EPI) equation was calculated. Fractal (fractal dimension, lacunarity) and textural (angular second moment (ASM), textural correlation (COR), inverse difference moment (IDM), textural contrast (CON), variance) analysis parameters were compared between two groups. Results Obese patients had higher mean value of variance (t = 1.867), ASM (t = 1.532) and CON (t = 0.394) but without significant difference (P > 0.05) compared to non-obese. Mean value of COR (t = 0.108) and IDM (t = 0.185) were almost the same in two patient groups. Obese patients had higher value of lacunarity (t = 0.499) in comparison with non-obese, the mean value of fractal dimension (t = 0.225) was almost the same in two groups. Significantly positive association between variance and creatinine concentration (r = 0.499, P < 0.01), significantly negative association between variance and CKD-EPI (r = -0.448, P < 0.01), variance and sex (r = -0.339, P < 0.05) were found. Conclusions Variance showed significant correlation with serum creatinine concentration, CKD-EPI and sex. CON and IDM were significantly related to sex. Fractal and textural analysis parameters of glomeruli could become a supplement to histopathologic analysis of kidney tissue.

7.
Diagnostics (Basel) ; 12(9)2022 Aug 23.
Article in English | MEDLINE | ID: mdl-36140438

ABSTRACT

Transcription factor PAX8, expressed during embryonic kidney development, has been previously detected in various kidney tumors. In order to investigate expression of PAX8 transcription factor in acute kidney injury (AKI) and chronic kidney diseases (CKD), immunohistochemical analysis was performed. Presence, location and extent of PAX8 expression were analyzed among 31 human kidney samples of AKI (25 autopsy cases, 5 kidney biopsies with unknown etiology and 1 AKI with confirmed myoglobin cast nephropathy), as well as in animals with induced postischemic AKI. Additionally, expression pattern was analyzed in 20 kidney biopsy samples of CKD. Our study demonstrates that various kidney diseases with chronic disease course that results in the formation of tubular atrophy and interstitial fibrosis, lead to PAX8 expression in the nuclei of proximal tubules. Furthermore, patients with PAX8 detected within the damaged proximal tubuli would be carefully monitored, since deterioration in kidney function was observed during follow-up. We also showed that myoglobin provoked acute kidney injury followed with large extent of renal damage, was associated with strong nuclear expression of PAX8 in proximal tubular cells. These results were supported and followed by data obtained in experimental model of induced postischemic acute kidney injury. Considering these findings, we can assume that PAX8 protein might be involved in regeneration process and recovery after acute kidney injury. Thus, accordingly, all investigation concerning PAX8 immunolabeling should be performed on biopsy samples of the living individuals.

8.
Int J Med Inform ; 164: 104805, 2022 08.
Article in English | MEDLINE | ID: mdl-35653828

ABSTRACT

BACKGROUND AND OBJECTIVES: The importance of clinical natural language processing (NLP) has increased with the adoption of electronic health records (EHRs). One of the critical tasks in clinical NLP is named entity recognition (NER). Clinical NER in the Serbian language is a severely under-researched area. The few approaches that have been proposed so far are based on rules or machine-learning models with hand-crafted features, while current state-of-the-art models have not been explored. The objective of this paper is to assess the performance of state-of-the-art NER methods on clinical narratives in the Serbian language. MATERIALS AND METHODS: We designed an experimental setup for a comprehensive evaluation of state-of-the-art NER models. The gold standard corpus we used for the evaluation is comprised of discharge summaries from the Clinic for Nephrology at the University Clinical Center of Serbia. The following models were evaluated: conditional random fields (CRF), multilingual transformers (BERT Multilingual and XLM RoBERTa), and long short-term memory (LSTM) recurrent neural networks, and their ensembles. In addition, we investigated the necessity of the pretraining task of transformer based models and the use of pretrained word embeddings with LSTM model. RESULTS: Our results show that individually CRF had the best precision, the pretrained BERT Multilingual model had the best recall values, and the LSTM model had the best F1 score. The best performance was achieved by combining the existing models in a majority voting ensemble with an F1 score of 0.892. The presented results are similar to the inter annotator agreement on our gold standard corpus and are comparable to existing state-of-the-art results for clinical NER reported in literature. CONCLUSION: Existing state-of-the-art models can provide viable results for clinical named entity recognition when applied to languages with the complexity of the Serbian language without major modifications.


Subject(s)
Electronic Health Records , Natural Language Processing , Humans , Machine Learning , Neural Networks, Computer , Serbia
9.
J Int Med Res ; 49(9): 3000605211048366, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34586926

ABSTRACT

Churg-Strauss syndrome (CSS) is a granulomatous small-vessel vasculitis. Asthma is seen in the majority of patients with CSS, but atypical nonasthmatic forms of CSS are also being recognized. We herein describe a 67-year-old woman with a history of chronic pyelonephritis and drug allergy reactions who was admitted to our hospital because of worsening renal function preceded by fever, purpura, sinusitis, and a positive urine culture that confirmed a urinary infection. She was initially treated with pipemidic acid for 7 days, followed by clarithromycin for sinusitis. Laboratory tests on admission showed an absolute eosinophil count of 1750 cells/µL and serum creatinine concentration of 4.72 mg/dL. Urine and blood cultures showed no growth. Kidney biopsy revealed crescent formations with diffuse interstitial fibrosis and foci of eosinophil infiltration. An atypical form of CSS was diagnosed based on tissue eosinophilia, peripheral eosinophilia, and sinusitis. Intravenous methylprednisolone and cyclophosphamide pulse therapy together with hemodialysis treatment improved the patient's clinical condition but did not resolve the kidney damage. The onset of an atypical form of CSS in our patient manifested as symptoms and signs mimicking those of chronic pyelonephritis and drug allergy reactions. The patient's chronic kidney disease finally progressed to dialysis dependence.


Subject(s)
Asthma , Churg-Strauss Syndrome , Pyelonephritis , Vasculitis , Aged , Asthma/complications , Asthma/drug therapy , Churg-Strauss Syndrome/complications , Churg-Strauss Syndrome/diagnosis , Churg-Strauss Syndrome/drug therapy , Female , Humans , Methylprednisolone , Pyelonephritis/complications , Pyelonephritis/drug therapy
10.
Exp Clin Transplant ; 19(1): 25-31, 2021 01.
Article in English | MEDLINE | ID: mdl-33441057

ABSTRACT

OBJECTIVES: Our objective was to evaluate the influence of pretransplant risk factors on posttransplant anemia recovery. MATERIALS AND METHODS: This single-center observational retrospective study included 80 deceased donor kidney transplant recipients who had been followed up to 16 months after kidney transplant. Time point of posttransplant anemia recovery was considered the time when hemoglobin of 11.0 g/dL was achieved and maintained for 3 consecutive monthly visits. We collected donor/transplant characteristics (age, sex, hypertension history, cause of death, donor kidney function, expanded criteria donor status, deceased donor score, HLA mismatch, and cold ischemia time) and recipient data (pretransplant hemoglobin, parathyroid hormone, kidney graft function, delayed graft function, acute rejection, infections, surgical bleeding, posttransplant parathyroid hormone, iron stores, and C-reactive protein and tacrolimus levels). We used univariate and multivariate Cox proportional hazards analyses and Kaplan-Meier plots to determine associations between variables and posttransplant anemia recovery rate. P < .05 was considered significant. RESULTS: We identified 62 deceased donors (33 male; mean age 50 ± 15.1 years) and 80 kidney transplant recipients (52 male; mean age 47.0 ± 10.6 years). Mean pretransplant hemoglobin was 11.4 ± 1.5 g/dL. Donor age, deceased donor score, pretransplant parathyroid hormone, posttransplant transferrin saturation (all P < .05), and tacrolimus level (P < .01) were significantly related to posttransplant anemia recovery. Kaplan-Meier curve identified that recipients of deceased donors below 60 years old achieved hemoglobin of 11.0 g/dL more frequently and earlier than recipients of deceased donors above 60 years old (P < .05). CONCLUSIONS: Deceased donor age, deceased donor score, pretransplant serum parathyroid hormone, posttransplant transferrin saturation, and tacrolimus level were significantly associated with posttransplant anemia recovery rate in deceased donor kidney transplant recipients. Anemia recovery was more frequent and earlier in recipients of deceased donors below 60 years than in recipients of donors 60 years old and above.


Subject(s)
Anemia , Kidney Transplantation , Adult , Aged , Anemia/diagnosis , Anemia/therapy , Female , Hemoglobins/analysis , Humans , Male , Middle Aged , Parathyroid Hormone/blood , Retrospective Studies , Tacrolimus/blood , Transferrins/blood , Transplant Recipients
11.
Toxins (Basel) ; 12(6)2020 05 27.
Article in English | MEDLINE | ID: mdl-32471186

ABSTRACT

BACKGROUND: Increased oxidative stress is a hallmark of end-stage renal disease. Hemodialysis (HD) patients lacking glutathione transferase M1 (GSTM1) enzyme activity exhibit enhanced oxidative DNA damage and higher mortality rate than those with active GSTM1 enzyme. To our knowledge, this is the first study to use the vitamin E-bonded membranes (VEM) in patients with homozygous GSTM1 gene deletion, and we aimed to determine the effect of VEM on oxidative and inflammatory status in HD patients with homozygous GSTM1 gene deletion. METHODS: GSTM1 genotypes were determined by polymerase chain reaction (PCR) in 170 chronic HD patients. Those with GSTM1-null genotype were randomized and 80 were included in the study. Forty of them were dialyzed for three months with VEM, while the other forty were dialyzed with high-flux same-surface polysulfone dialyzers. Markers of protein and lipid oxidative damage and inflammation (thiol groups, malondialdehyde (MDA), Interleukin-6 (IL-6)), together with plasma antioxidant activity (glutathione peroxidase (GPX), superoxide dismutase (SOD)) were determined. RESULTS: Seventy-five patients finished the study. There were no differences at baseline in markers of protein and lipid oxidative damage, inflammation and plasma antioxidant activity. After three months of therapy, GPX, MDA, and thiol groups increased significantly in both groups, but without statistical significance between groups. SOD and C reactive protein (CRP) did not change significantly during the three-month period. IL-6 increased in the control group, and at the same time, decreased in the VEM group, but without statistical significance. Hemoglobin (Hb) value, red blood cells, erythropoiesis resistance index (ERI), serum ferritin and iron did not change significantly within or between groups. Regarding other laboratory parameters, proteins, albumins, triglycerides, serum phosphorus, serum bicarbonate and Kt/V showed significant improvements within groups but with no significant difference between groups. CONCLUSIONS: Our data shows that therapy with VEM over three months had no benefit over standard polysulfone membrane in decreasing by-products of oxidative stress and inflammation in dialysis patients lacking GSTM1 enzyme activity.


Subject(s)
Antioxidants/therapeutic use , Gene Deletion , Glutathione Transferase/genetics , Kidney Failure, Chronic/therapy , Membranes, Artificial , Oxidative Stress/drug effects , Renal Dialysis/instrumentation , Vitamin E/therapeutic use , Aged , Biomarkers/blood , Female , Homozygote , Humans , Inflammation Mediators/blood , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/genetics , Lipid Peroxidation/drug effects , Male , Middle Aged , Serbia , Single-Blind Method , Time Factors , Treatment Outcome
13.
Arch Med Res ; 49(2): 101-108, 2018 02.
Article in English | MEDLINE | ID: mdl-29754746

ABSTRACT

BACKGROUND AND AIMS: Transplantation is the best treatment option for end stage kidney disease. The most common early complications in post-transplant period are acute rejection (AR) of the graft and delayed graft function (DGF). The underlying mechanisms in these events are heterogeneous and at least in part involve cytokine genes which regulate immune response to allograft. We have investigated whether functional single nucleotide polymorphisms (SNP) in the genes encoding IFN-γ (IFNG), TNF (TNFA), IL-10 (IL10) and p40 subunit of IL-12/IL-23 (IL12B) could predict risk of AR and DGF in kidney allograft recipients. METHODS: Our study involved 152 kidney transplant recipients on standard immunosuppressive regimen which included calcineurin inhibitors, mycophenolic acid derivatives and corticosteroids. Genotyping of IFNG, TNFA, IL10 and IL12B was performed using commercial TaqMan assays. RESULTS: We found association between the carriers of AA genotype of IL12B +1188A/C polymorphism (rs3212227) and a lower rate of DGF (p = 0.037, OR = 0.45, 95% CI = 0.21-0.96), implying protective role of A allele in the pathogenesis of DGF in kidney transplant recipients, whereas no such association was observed with AR. None of the analyzed SNPs in TNFA (-308G/A), IFNG (+874T/A), IL10 (-1082G/A, -819T/C, -592C/A) were associated with AR or DGF in our patients. CONCLUSIONS: Our study shows a preliminary evidence that the AA genotype of rs3212227 SNP in the IL12B gene might be associated with a lower risk for DGF after kidney transplantation. In the future, additional well-designed large studies are required for the validation of our results.


Subject(s)
Delayed Graft Function/genetics , Graft Rejection/genetics , Interleukin-12 Subunit p40/genetics , Kidney Failure, Chronic/surgery , Kidney Transplantation , Adult , Alleles , Female , Genetic Association Studies , Genotyping Techniques , Humans , Interferon-gamma/genetics , Interleukin-10/genetics , Kidney Failure, Chronic/genetics , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , Tumor Necrosis Factor-alpha/genetics
14.
Sci Rep ; 7(1): 16915, 2017 12 05.
Article in English | MEDLINE | ID: mdl-29208969

ABSTRACT

Chronic kidney disease (CKD) is a prevalent cause of morbidity and mortality worldwide. A hallmark of CKD progression is renal fibrosis characterized by excessive accumulation of extracellular matrix (ECM) proteins. In this study, we aimed to investigate the correlation of the urinary proteome classifier CKD273 and individual urinary peptides with the degree of fibrosis. In total, 42 kidney biopsies and urine samples were examined. The percentage of fibrosis per total tissue area was assessed in Masson trichrome stained kidney tissues. The urinary proteome was analysed by capillary electrophoresis coupled to mass spectrometry. CKD273 displayed a significant and positive correlation with the degree of fibrosis (Rho = 0.430, P = 0.0044), while the routinely used parameters (glomerular filtration rate, urine albumin-to-creatinine ratio and urine protein-to-creatinine ratio) did not (Rho = -0.222; -0.137; -0.070 and P = 0.16; 0.39; 0.66, respectively). We identified seven fibrosis-associated peptides displaying a significant and negative correlation with the degree of fibrosis. All peptides were collagen fragments, suggesting that these may be causally related to the observed accumulation of ECM in the kidneys. CKD273 and specific peptides are significantly associated with kidney fibrosis; such an association could not be detected by other biomarkers for CKD. These non-invasive fibrosis-related biomarkers can potentially be implemented in future trials.


Subject(s)
Fibrosis/pathology , Kidney/pathology , Liquid Biopsy/methods , Peptides/urine , Renal Insufficiency, Chronic/pathology , Adult , Collagen/urine , Electrophoresis, Capillary , Female , Fibrosis/urine , Humans , Male , Mass Spectrometry , Middle Aged , Renal Insufficiency, Chronic/urine
16.
Curr Med Chem ; 23(19): 1941-52, 2016.
Article in English | MEDLINE | ID: mdl-26687832

ABSTRACT

The purpose of this review is to summarize current data on the role of immunosuppressants in the pathogenesis of hypertension and the efficacy and tolerability of major antihypertensive classes in kidney transplant recipients. Arterial hypertension is a common complication after kidney transplantation and a major risk factor for adverse outcome and graft rejection due to blood pressure elevation by immunosuppressive medications. Calcineurin inhibitors induce hypertension by a mechanism related to the imbalance of vasoactive substances endothelin and nitric oxide, and probably by causing overactivity of thiazide-sensitive sodium-chloride-cotransporter. Corticosteroids are well known for their hypertensive effects. The interactions of calcineurin inhibitors and mammalian target of rapamycin inhibitor sirolimus also promote hypertension. Management of arterial hypertension is a complex problem in the care of kidney transplant recipients. Target blood pressure values of <130/80 mm Hg are suggested by the National Kidney Foundation/ Kidney Disease Outcomes Quality Initiative. Calcium channel blockers may be useful in antagonizing the vasoconstrictive effects of calcineurin inhibitors. The renin-angiotensin system inhibitors seem a good option, especially in patients with proteinuria, however their effects on long-term graft and patient survival are controversial. ß-Blockers could be beneficial in patients with coronary heart disease, but caution is required due to metabolic adverse effects. Thiazide diuretics could be the reasonable option for patients with glomerular filtration rate ≥30 mL/min/1.73 m2, also with caution regarding hypokalemia and glycemia. Until more evidence is provided, the choice of optimal antihypertensive therapy in kidney transplant recipients should be based on previous individual antihypertensive tolerability and efficacy, comorbidities, concomitant medications and post-transplant kidney function.


Subject(s)
Graft Rejection/prevention & control , Hypertension/etiology , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Adrenal Cortex Hormones/adverse effects , Adrenal Cortex Hormones/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Calcineurin/adverse effects , Calcineurin/therapeutic use , Calcium Channel Blockers/therapeutic use , Diuretics/therapeutic use , Humans , Hypertension/chemically induced , Hypertension/drug therapy , Immunosuppressive Agents/adverse effects , Risk Factors
17.
Eur J Pharm Sci ; 83: 109-13, 2016 Feb 15.
Article in English | MEDLINE | ID: mdl-26705892

ABSTRACT

Polymorphisms of the multi drug resistance (MDR1) gene cause variability in P-glycoprotein mediated metabolism of tacrolimus. The aim of this study was to examine the relationship between MDR1 gene single nucleotide polymorphisms (SNPs) and their haplotypes with dosage of tacrolimus in kidney transplant recipients who were cytochrome (CYP) 3A5*3 homozygotes. This study included 91 kidney transplant recipients followed two years after transplantation. Detection and analysis of MDR1 gene polymorphisms in positions C1236T, G2677T/A and C3435T were performed using PCR method. Patients with variant alleles for SNPs G2677T/A and C3435T required higher doses of tacrolimus and had a lower level/dose (L/D) ratio than patients with wild alleles or heterozygotes. That difference was the most obvious for SNP G2677T/A where TT homozygotes required significantly higher doses of tacrolimus during whole follow-up. Their L/D was significantly lower in the first month after transplantation. Recipients with CTT/TTT haplotype also had lower L/D than those with CGC/TTT and CGC/CGC, significantly in the 10th and 20th days after transplantation respectively (p<0.05). Our results demonstrate that TT homozygotes at positions G2677T/A and C3435T required a higher tacrolimus dose than those with wild alleles or heterozygotes. It may be helpful in the prevention of tacrolimus nephrotoxicity early after transplantation.


Subject(s)
Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Tacrolimus/administration & dosage , ATP Binding Cassette Transporter, Subfamily B/genetics , Adult , Cytochrome P-450 CYP3A/genetics , Female , Haplotypes , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/pharmacokinetics , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Polymorphism, Single Nucleotide , Tacrolimus/blood , Tacrolimus/pharmacokinetics , Tacrolimus/therapeutic use
18.
Srp Arh Celok Lek ; 144(5-6): 325-8, 2016.
Article in English | MEDLINE | ID: mdl-29648755

ABSTRACT

Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a common malignancy following organ transplantation. Risk for PTLD is associated with the use of anti-thymocyte globulin in the prevention and treatment of acute rejection following kidney transplantation. Case Outline: We report a case of fatal PTLD presented with sudden onset of fever. A 33-year-old male patient with primary diagnosis of left kidney agenesia underwent kidney transplantation six years following hemodialysis treatment initiation. Deceased donor was a 66-year-old female whose cause of death was cerebrovascular accident. Immunosuppressive regimen consisted of basiliximab, corticosteroids, tacrolimus, and mycophenolate mofetil. Six months upon transplantation the patient was hospitalized due to fever of unknown origin. All microbiological samples were negative, but abdominal ultrasound revealed round solid mass in the right native kidney. Right nephrectomy was performed showing tumor 35 × 35 × 20 mm in size within the 70 × 40 × 35 mm kidney. Pathohistological analysis confirmed very rare monomorphic B-cell PTLD ­ B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma. Conclusion: We consider this case of PTLD following kidney transplantation particular because of the tumor mass in native kidney after basiliximab induction and rare pathohistology. In a transplanted patient with fever, PTLD must always be considered, irrespective of immunosuppressive regimen.


Subject(s)
Kidney Transplantation/adverse effects , Lymphoma, B-Cell/diagnosis , Lymphoproliferative Disorders/etiology , Adult , Antibodies, Viral/blood , Fatal Outcome , Herpesvirus 4, Human/immunology , Humans , Immunoglobulin G/immunology , Immunosuppressive Agents/therapeutic use , Lymphoproliferative Disorders/diagnosis , Male
19.
Ren Fail ; 37(4): 589-96, 2015 May.
Article in English | MEDLINE | ID: mdl-25656832

ABSTRACT

BACKGROUND: In order to evaluate the predictive value of echocardiograph parameters for mortality of hemodialysis patients and their relation to Kt/V and anthropometry, a prospective, single center study was analyzed post-hoc. METHODS: This analysis encompassed 106 patients on maintenance hemodialysis monitored for 108 months from 1996 to 2004. spKt/V was calculated using the Daugirdas formula. Anthropometric measurements included mid-arm muscle measurements (MAMC) and percentage of body fat (%fat). Echocardiography included the estimations of left ventricular wall thickness, dimensions and volumes (EDV, ESV), systolic LV function (ejection fraction - EFLV, fractional shortening - VCF, stroke volume - SV) and diastolic LV function (E/A, VTI-A wave of transmitral flow velocity), left atrial diameter, as well as assessment of clinical and biochemical parameters. The Cox proportional hazard model was used to estimate predictive values of echocardiograph parameters. RESULTS: Kt/V correlated significantly with left ventricular systolic and diastolic volumes and function, septal and posterior wall thickness and left atrium dimension. MAMC and %fat also correlated with many echocardiograph parameters. Multivariate Cox regression selected age [HR 1.07; CI (1.03-1.12); p < 0.01], albumin [HR 0.88; CI (0.79-0.97); p < 0.05] and left atrium dimension - binary [values > 4 cm were marked as "1" and others "0" - HR 3.76; CI (1.56-9.03); p < 0.01] as independent predictors of death. CONCLUSION: Left atrium dimension was the most important predictor of mortality among the echocardiograph parameters. Many of these parameters were related to Kt/V and anthropometric measurements and could be the combined consequence of hypervolemia and hypertension.


Subject(s)
Body Weights and Measures , Echocardiography , Heart Diseases/diagnostic imaging , Heart Diseases/etiology , Renal Dialysis , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/therapy , Female , Heart Diseases/metabolism , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Renal Insufficiency, Chronic/metabolism
20.
Ren Fail ; 37(2): 230-6, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25394528

ABSTRACT

BACKGROUND/AIM: Besides peritonitis, the most common complication, indicators of chronic inflammation are also present in patients treated by peritoneal dialysis. The aim of this study was to analyze the predictive value of inflammatory parameters on mortality of continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Eighty-seven patients (57 males), aged from 30 to 85 [62.92 (10.61)] years who had been treated by a chronic program of CAPD for 3-113 months were analyzed. The basal period lasted 3 months with a follow-up of 30 months. Clinical parameters, dialysis adequacy and laboratory parameters including some inflammatory markers: serum amyloid-A (SAA), high sensitive C-reactive protein (hs-CRP), fibrinogen, erythrocyte sedimentation rate (ESR) and leukocytes were determined for each patient. Cox regression analysis selected the parameters of univariate and multivariate survival analysis. RESULTS: During the follow-up period, 37 patients (42.5%) died. Univariate analysis selected the following potential mortality predictors (p<0.10): age, months on CAPD, residual urine output, presence of cerebrovascular insult (CVI), KT/V, serum urea and albumin concentrations, SAA, hs-CRP, fibrinogen and ESR. In the multivariate survival analysis four models were created, each with a single inflammatory parameter. In all of these models, besides the age and CVI, inflammatory parameters were the most significant mortality predictors. When the inflammatory markers were analyzed altogether, multivariate analysis established that independent mortality predictors in this group of patients were: SAA, age and CVI. CONCLUSION: It may be concluded that in this studied group treated by CAPD, SAA was the most significant independent mortality predictor among the analyzed inflammatory markers.


Subject(s)
Blood Sedimentation , C-Reactive Protein/analysis , Fibrinogen/analysis , Inflammation , Kidney Failure, Chronic , Leukocyte Count/methods , Peritoneal Dialysis/adverse effects , Aged , Biomarkers/analysis , Chronic Disease , Female , Humans , Inflammation/blood , Inflammation/etiology , Inflammation/physiopathology , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/therapy , Kidney Function Tests , Male , Middle Aged , Peritoneal Dialysis/methods , Predictive Value of Tests , Serbia/epidemiology , Survival Analysis
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