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.
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.
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Objectives: Our objective was to evaluate the influence
of pretransplant risk factors on posttransplant anemia
recovery.
Materials and Methods: This single-center obser -
vational 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 charac -
teristics (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.
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
gene deletion, and we aimed to determine the effect of VEM on oxidative and inflammatory status in HD patients with homozygous
gene deletion.
genotypes were determined by polymerase chain reaction (PCR) in 170 chronic HD patients. Those with
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.
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.
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.
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 ± 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.
•Variance showed significant correlation with eGFR calculated by CKD- EPI formula.•Significant correlation between variance and serum creatinine was found.•Textural contrast and inverse difference moment were significantly related to sex.•Fractal analysis of glomeruli could become supplement to histopathologic analysis.•Textural analyses of kidney tissue should become useful to histopathologic analysis.
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.
Abstract Background and Aims An increased risk of mortality and hospitalization has been consistently demonstrated in patients with CKD who are additionally affected by corona virus disease 19 ...(COVID-19). In this study, we tried to identify predictive factors of mortality and hospitalizations, especially the ratio of neutrophils to lymphocytes (NLR), lactate dehydrogenase (LDH), c-reactive protein (CRP), disease status of COVID-19, telomere length in peripheral blood cells (TL) and 2-year risk score. Method A total of 130 chronic hemodialysis patients, were enrolled in the present study and followed up for 18 months. Routine laboratory parameters including LDH, were determined by standard automated methods, redox status parameters SOD and O2. - Using spectrophotometric methods.TL was determined using the modified Cawthon method and was calculated as the T/S ratio. Kaplan-Meier analysis was used to test survival predictors. Results Patients in deceased group (30%) were significantly older (p <0.001), with higher body mass index (BMI), (p < 0.01) than survived patients. Also, patients in the deceased group had higher levels of LDH, NLR index, CRP compared to survivors. Lower lymphocytes and shortened TL were characteristic of these patient groups, but the deceased group had the lowest lymphocytes (p < 0.005) and telomeres (p<0.002), and had the highest NLR (0.004). The difference in 2-years risk score also was significant (p < 0.001), with higher scores in the deceased group. Kaplan-Meier survival analysis showed six parameters were significant predictors in the following order of significance: COVID-19 status, 2-years risk score, NLR, TL, CRP, LDH. Using binary logistic regression analysis Summary risk score, a combination of these six parameters revealed as the best predictor of patients’ survival in this group of parameters (Log rank=25.4, P < 0.001). Conclusion Independent predictors of mortality in chronic haemodialysis patients are higher NLR, CRP, LDH, Lower lymphocytes and shortened TL, and COVID -19 made the situation even worse by significantly arising these patients’ mortality rate.
Abstract Background and Aims Preexisting hypoalbuminemia in many studies was an independent factor of mortality in patients with acute kidney injury (AKI). Albumin replacement in patients with AKI ...did not affect their survival. Each 1.0 g/l decrease in serum albumin was associated with an increased probability of developing AKI (OR 1.685). Also, it was shown that serum albumin level below 32 g/l is a significant risk factor for the occurrence of AKI. The mortality of patients with AKI is extremely high, approximately 50%, in patients with AKI who require dialysis treatment it is 50-70%, while in patients on supportive ventilation or with multisystem organ failure it is even 80-90%. Method The retrospective study included 280 patients diagnosed with AKI in the period from 2014 to 2018. Demographic, laboratory parameters and therapeutic procedures were analyzed in order to determine their influence on the treatment outcome. Binary logistic regression was used to test statistical significance to identify potential mortality factors. Results The incidence of AKI was 6.5%. The mean age was 67.8±13.8 years (19, 91) without statistically significant difference by gender (50.4% men) (p = 0.22). The most prevalent is prerenal AKI 57.1%, followed by renal 24.3% and postrenal 18.6%. Renal replacement therapy is required in 15.7% of patients. Intermittent HD was applied statistically significantly more often, 90.9%, and continuous renal replacement therapy (CRRT) procedures were applied in 9.1% of patients (p < 0.001). Mortality was 18.6%. With each increase in the patient's age by one year, the probability of a fatal outcome increases by 1.045 times (p = 0.000; OR: 1.045). Hypoproteinemia and hypoalbuminemia increase the probability of death. For each unit decrease in albumin by 1 g/l, the risk of death increases by 13% (p = 0.000; OR: 0.872), and each decrease in protein by 1 g/l increases the risk of death by 7% (p = 0.000 ; OR: 0.939). Among other factors that showed statistical significance are hyperphosphatemia (p = 0.001; OR: 1.990), acidosis (p = 0.007; OR: 0.002), inflammation (p = 0.029; OR: 1.003). Conclusion Acute kidney injury is accompanied by a high mortality rate. Low serum albumin levels at the time of diagnosis are a significant independent factor of acute kidney function impairment and death. Other risk factors that contribute to a poor outcome in patients with AOB are age, hyperphosphatemia, acidosis, and inflammation.
Abstract
Background and Aims
In December 2019, an outbreak of coronavirus disease 2019 (covid 19) due to SARS Cov2 began in China and spread worldwide. Hemodialysis patients represent a unique group ...of patients, mostly elderly, imunocompromised, with numerous comorbidities. Patients with end stage renal disease are thought to be at increased risk of disease, severe disease and death from Covid 19 infection. In addition, dialysis centers are a suitable place for an outbreak of the epidemic. All of the above represents a group of hemodialysis patients particularly susceptible to infection and the development of serious disease.
Method
We reviewed data of all maintenance hemodialysis patients in hemodialysis centar of Zvezdara Hospital, Belgrade, Serbia. We include all patients with COVID 19 infection in period between April 1 2020 and January 10 2021.
Results
Of 232 patients undergoing hemodialysis, 68 (29,31%) were infected with Sars-Cov-2. 46 (67,64%) patients were males and 22 (32,35%) females. The age range of the patients was 35 to 87 years, the mean age was 65,25. The underlyind cause of terminal renal failure in 25 patients was hipertensiv nefroangiosklerosis, 14 diabetic nephropathy, 10 opstructiv nephropathy, 9 polycystic kidney disease, and 10 other cause of kidney failure. The average of hemodialysis duration was 70,70 months. The average durations of disease was 15 days. Mortality has been estimated at 33,82% (23 patients). Among patients who died 8 (34,78%) were females, and 15 (65,21%) males.
Conclusion
The mortality among hemodialysis patients diagnosed with Covid 19 is high. Hemodialysis patients typically present with multiple comorbidities and are considered to be a high-risk group for infections. Hemodialysis patients with Covid-19 may have prolonged hospital stays and unfavorable prognoses and should be closely monitored.
•Data on immunosuppressive regimens used in KTRs in South-eastern Europe are limited.•Triple therapy was the most common immunosuppressive regimen.•The most common regimen was a CNI, an ...antiproliferative drug and corticosteroids.•Individual CNI C0 were below the target range in a substantial proportion of KTRs.
Objective: To examine current immunosuppressive regimens administered to kidney transplant recipients (KTRs) in South-eastern Europe.
Methods: This was a 12-month, multicenter, non-interventional, prospective, observational study of immunosuppressive regimens in adult de novo and maintenance KTRs. The primary endpoint was to identify the number, type, dosage and trough concentrations (C0) of immunosuppressive medications.
Results: Data were available for 1774 KTRs from five countries (Bulgaria n = 109, Croatia n = 339, Romania n = 647, Serbia n = 434 and Slovenia n = 245). The most common immunosuppressive regimen in all countries was a triple therapy regimen (de novo KTRs, 67.9 – 100% at baseline and 67.3 – 100% at end of study; maintenance KTRs, 48.8 – 90.7% and 43.2 – 90.1%, respectively). The most frequent regimen in de novo KTRs comprised tacrolimus, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), and corticosteroids. In maintenance KTRs, the most frequent regimen was tacrolimus or cyclosporine, and MMF or MPS, with or without corticosteroids. A C0 of <5 ng/mL was recorded in 40.2% of immediate-release and 48.7% of prolonged-release tacrolimus patients; 79.5% of patients taking cyclosporine had a C0 of <75 ng/mL. Infections were the most common adverse event (358/597, 60.0%), mainly urinary tract infections (208/358, 58.1%).
Conclusions: Triple therapy—comprising a calcineurin inhibitor (CNI; tacrolimus or cyclosporine), antiproliferative drugs (MMF or MPS) and corticosteroids—was the most common immunosuppressive regimen used in KTRs in South-eastern Europe. Individual CNI C0 were below the target range in a substantial proportion of KTRs, highlighting the need to maintain therapeutic drug monitoring of immunosuppressive therapy in this patient population.
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