The ABCG8 polymorphism increases the risk of gallbladder cancer in the general population and gallstones in obese patients from Poland.

BACKGROUND: Gallstone disease (GD) is common but remains asymptomatic in most cases. However, gallstones can lead to complications like choledocholithiasis or gallbladder cancer. In this study, we analyse the common genetic risk factor for GD, the p.D19H variant in the sterol transporter ABCG8, in Polish patients with gallstones and gallbladder cancer. METHODS: Three adult cohorts were prospectively recruited: 65 patients with gallbladder cancer, 170 obese individuals scheduled for bariatric surgery and 72 patients who underwent endoscopic retrograde cholangiopancreatography due to recurrent choledocholithiasis. The control cohort consisted of 172 gallstone-free adults. The ABCG8 p.D19H (rs11887534) polymorphism was genotyped using TaqMan assays. RESULTS: The minor allele frequency (MAF) of the ABCG8 p.D19H polymorphism was significantly (p = .02) higher among cases with either gallstones or gallbladder cancer (MAF = 8.4%) as compared to controls (MAF = 4.0%). The highest frequency of the risk allele was detected in patients with gallbladder cancer (18.5%) and obese patients with GD (17.5%), followed by individuals with choledocholithiasis (13.9%). Notably, the p.19H variant was associated with an increased risk of developing gallbladder cancer (OR 2.76, 95% CI 1.16-6.54, p = .01) and an increased risk of GD in obese individuals scheduled for bariatric surgery (OR = 2.70, 95% CI 1.05-6.49, p = .03), but did not significantly affect the risk of choledocholithiasis. CONCLUSIONS: The ABCG8 p.D19H common risk variant increases the risk of developing gallbladder cancer in Central Europeans and enhances the risk of gallstones in the obese. Carriers of the p.D19H variant might benefit from personalized preventive strategies, particularly regarding gallbladder cancer.

Common variant p.D19H of the hepatobiliary sterol transporter ABCG8 increases the risk of gallstones in children.

INTRODUCTION: Gallstones are increasingly common in children. Genetic analyses of adult cohorts demonstrated that the sterol transporter ABCG8 p.D19H and Gilbert UGT1A1*28 variants enhance the odds of developing gallstones. The genetic background of common lithiasis in children remains unknown. METHODS: Overall, 214 children with gallstone disease (1 month-17 years, 107 boys) were inclueded. The control cohorts comprised 214 children (age 6-17 years, 115 boys) and 172 adults (age 40-92 years, 70 men) without gallstones. The ABCG8 p.D19H and UGT1A1*28 polymorphisms as well as ABCB4 (c.504C>T rs1202283, c.711A>T rs2109505) and NPC1L1 variants (p.V1296V rs217434, c.-18C>A rs41279633) were genotyped using TaqMan assays. Serum concentrations of plant sterols and cholesterol precursors were measured by gas chromatography/mass spectrometry. RESULTS: The ABCG8 risk allele was associated with an increased risk of stones (OR = 1.82, p = .03). Children carrying the p.19H allele presented with lower serum concentrations of surrogate markers of intestinal cholesterol absorption and decreased ratios of phytosterols to the cholesterol precursor desmosterol. Carriers of the common NPC1L1 rs217434 allele had an increased gallstone risk compared with stone-free adults (OR 1.90, p < .01). This variant also affected the ratio of phytosterols to cholesterol precursors (p = .03). Other tested variants were not associated with gallstone risk. CONCLUSIONS: The p.D19H ABCG8 and, to a lesser extent, NPC1L1 rs217434 variants increase the risk of early-onset gallstone formation. These results point to the presence of a common lithogenic pathway in children and adults.

The rs12532734 Polymorphism Near the Solute Carrier 26A3 Gene Locus Is Associated With Gallstone Disease in Children.

Gallstones are increasingly frequent in children. In this candidate gene study, we genotyped 5 gene variants ( ANO1 , SPTLC3 , TMEM147 , TNRC6B , rs12532734) from a recent gallstone genome-wide association study (GWAS) in a cohort of 214 children with gallstones and 172 gallstone-free adult controls. In total, 138 genotyped children presented with symptomatic gallstone disease, 47 underwent cholecystectomy, and 126 received ursodeoxycholic acid (UDCA) as therapy for stones. Among 5 tested variants, the rs12532734 polymorphism modulated the gallstone risk in the studied cohort. Its genotype distribution significantly ( P = 0.025) departed from the Hardy-Weinberg equilibrium among cases, and the common allele was associated with increased odds of developing gallstones at young age (OR = 1.69, P = 0.014). SLC26A3 is the nearest gene to rs12532734 and is involved in the transepithelial bicarbonate and chloride transport. The association of rs12532734 with pediatric gallstones is a novel finding warranting further investigations also with regard to biliary bicarbonate flux and bile composition.

Pregnancy after liver transplant: maternal and perinatal outcomes.

BACKGROUND: Liver transplantation is a life-saving and successful therapeutic procedure which is more and more frequent worldwide, also among women of reproductive age. Consequently, there is an increasing number of reports of pregnancy following liver transplantation, but doubts still exist regarding preconception counseling and the optimal method of managing pregnancy. The aim of this study was to report and evaluate pregnancy outcomes in women who had undergone liver transplantation. METHODS: We retrospectively analyzed female patients after orthotopic liver transplantation who reported pregnancy and were under medical care of a single transplant center. RESULTS: We identified 14 pregnancies in 10 women who had undergone liver transplantation (12 childbirths, one induced abortion due to fetal death in the first trimester, one pregnancy is still ongoing). Causes of transplantation include congenital or acquired disorders and the most common indication was autoimmune hepatitis (50%). The mean age at the point of transplantation was 28.5 (range 21-36), mean maternal age at pregnancy was 32 (range 26-43), and transplant-to-pregnancy interval was 4.07 years (range 1.5-7). The mean gestational week was 36.67 (range 31-40). Immunosuppression was maintained with combinations of prednisone (n = 11), tacrolimus (n = 13), and azathioprine (n = 8) prior to and during pregnancy. Two pregnancies were unintended, so women took mycophenolate mofetil in the first weeks of gestation. Another two women stopped taking azathioprine due to increasing anemia. Maternal complications included increase of aspartate transaminase and alanine transaminase (n = 2), anemia (n = 4) and hyperthyroidism (n = 2). Among the 12 childbirths, five (41.67%) were preterm. Only five women entered labor spontaneously, while seven (58,33%) had cesarean delivery. CONCLUSIONS: Pregnancy after liver transplantation can achieve relatively favorable outcomes. Liver transplantation does not influence women's fertility and, during pregnancy, we report low rates of minor graft complications. A multidisciplinary team should be involved in contraceptive, fertility and consequently pregnancy counseling of female transplant recipients.

Cutaneous nocardiosis in a liver transplant recipient - case report.

Solid organ transplant recipients are specific group due to taken immunosuppressive agents. This can result in side effects including infections caused by rare opportunistic pathogens. A CASE REPORT: A 64-year old woman after orthotopic liver transplantation due to primary biliary cirrhosis and autoimmune hepatitis was admitted to hospital because of several infections. A painful lesion on left lower leg was noticed 3 months after surgery, while the patient was hospitalized with pneumonia. The Doppler ultrasound showed no signs of deep vein thrombosis. In the course of next month, the inflammatory infiltration has increased and the patient was readmitted to the hospital. After another ultrasound and MRI, which revealed solid-cystic character of the lesion, erythema nodosum was suspected. However, no pathogens were detected in blood and tissue cultures. After empiric antibiotic therapy regression of the lesion were observed. Recurrence of inflammation of the skin, the subcutaneous tissue and the knee joint resulted in readmission to the hospital after 3 months. Empiric antimicrobial therapy was administrated again and the dose of immunosuppressive agent was reduced. Since there was no bacterial growth in another routine culture of blood and synovial fluid, samples were cultured for opportunistic bacteria - Nocardia spp, Cryptococcus spp, Nontuberculous mycobacteria. Nocardia abscessus has grown after few weeks. Ceftriaxone, then trimethoprim-sulfamethoxazole (3x960 mg for 6 months) was administered according to antibiogram. Treatment resulted in regression of the lesion, pain alleviation and simultaneous liver function tests elevation. CONCLUSIONS: Cutaneous and subcutaneous nocardiosis is a rare infection. Solid organ transplant recipients are at risk of nocardiosis so it should be considered in differential diagnosis, especially when infections are hard to treat.

Successful transplantation of kidneys from deceased donors with terminal acute kidney injury.

BACKGROUND: There are many doubts with regards to accepting deceased kidneys with acute kidney injury (AKI) for transplantation. PURPOSE: The aim of this study was to present the 5-years outcome of kidney transplantation cases where deceased donors developed AKI before organ procurement. METHODS: Two hundred twenty-six deceased renal transplants were analyzed. Data regarding donors and recipients were collected. Terminal AKI was defined as terminal serum creatinine concentration higher than 1.99 mg/dL and 66 such cases were diagnosed. All kidney transplant recipients were followed for 60 months. RESULTS: AKI group presented more episodes of delayed graft function (DGF) compared to the non-AKI group (56% vs 35%, p < .05). No differences were observed between the groups in the rate of acute rejection episodes, kidney function as well as patient and graft survival. CONCLUSIONS: Transplants with AKI present more often DGF and comparable graft survival to transplants without AKI. Kidneys with AKI can be a valuable source of organs provided attentive selection and appropriate care of deceased donors.

Killer Immunoglobulin-Like Receptor 2DS2 (KIR2DS2), KIR2DL2-HLA-C1, and KIR2DL3 as Genetic Markers for Stratifying the Risk of Cytomegalovirus Infection in Kidney Transplant Recipients.

Infection with cytomegalovirus (CMV) remains a major problem in kidney transplant recipients, resulting in serious infectious complications and occasionally mortality. Accumulating evidence indicates that natural killer cell immunoglobulin-like receptors (KIRs) and their ligands affect the susceptibility to various diseases, including viral infections (e.g., CMV infection). We investigated whether KIR genes and their ligands affect the occurrence of CMV infection in a group of 138 kidney transplant recipients who were observed for 720 days posttransplantation. We typed the recipients for the presence of KIR genes (human leukocyte antigen C1 [HLA-C1], HLA-C2, HLA-A, HLA-B, and HLA-DR1) by polymerase chain reaction with sequence-specific primers. The multivariate analysis revealed that the lack of KIR2DS2 (p = 0.035), the presence of KIR2DL3 (p = 0.075), and the presence of KIR2DL2⁻HLA-C1 (p = 0.044) were risk factors for posttransplant CMV infection. We also found that a lower estimated glomerular filtration rate (p = 0.036), an earlier time of antiviral prophylaxis initiation (p = 0.025), lymphocytopenia (p = 0.012), and pretransplant serostatus (donor-positive/recipient-negative; p = 0.042) were independent risk factors for posttransplant CMV infection. In conclusion, our findings confirm that the KIR/HLA genotype plays a significant role in anti-CMV immunity and suggest the contribution of both environmental and genetic factors to the incidence of CMV infection after kidney transplantation.

Diagnostic utility of monitoring cytomegalovirus-specific immunity by QuantiFERON-cytomegalovirus assay in kidney transplant recipients.

BACKGROUND: Despite universal prophylaxis, late cytomegalovirus (CMV) infection occurs in a high proportion of kidney transplant recipients. We evaluated whether a specific viral T-cell response allows for the better identification of recipients who are at high risk of CMV infection after prophylaxis withdrawal. METHODS: We conducted a prospective study in 19 pretransplant anti-CMV seronegative kidney graft recipients R- (18 from seropositive donors [D+] and one from a seronegative donor [D-]) and 67 seropositive recipients R(+) (59 from seropositive donors and eight from seronegative donors) who received antiviral prophylaxis with valganciclovir. The QuantiFERON-CMV (QF-CMV) assay was performed within the first and third months after transplantation. Blood samples were monitored for CMV DNAemia using a commercial quantitative nucleic acid amplification test (QNAT) that was calibrated to the World Health Organization International Standard. RESULTS: Twenty-one of the 86 patients (24%) developed CMV viremia after prophylaxis withdrawal within 12 months posttransplantation. In the CMV R(+) group, the QF-CMV assay yielded reactive results (QF-CMV[+]) in 51 of 67 patients (76%) compared with 7 of 19 patients (37%) in the CMV R(-) group (p = 0.001). In the CMV R(+) group, infection occurred in seven of 16 recipients (44%) who were QF-CMV(-) and eight of 51 recipients (16%) who were QF-CMV(+). In the CMV R(-) group, infection evolved in five of 12 recipients (42%) who were QF-CMV(-) and one of 7 recipients (14%) who were QF-CMV(+). No difference was found in the incidence of CMV infection stratified according to the QF-CMV results with regard to the recipients' pretransplant CMV IgG serology (p = 0.985). Cytomegalovirus infection occurred in 15 of 36 patients (42%) with hypogammaglobulinemia (HGG) 90 days posttransplantation compared with two of 34 patients (6%) without HGG (p = 0.0004). Cytomegalovirus infection occurred in seven of 13 patients (54%) with lymphocytopenia compared with 14 of 70 patients (20%) without lymphocytopenia (p = 0.015). The multivariate analysis revealed that the nonreactive QuantiFERON-CMV assay was an independent risk factor for postprophylaxis CMV infection. CONCLUSIONS: In kidney transplant recipients who received posttransplantation prophylaxis, negative QF-CMV results better defined the risk of CMV infection than initial CMV IgG status after prophylaxis withdrawal. Hypogammaglobulinemia and lymphocytopenia were risk factors for CMV infection.

Different Relevance of Peripheral, Central or Nighttime Blood Pressure Measurements in the Prediction of Chronic Kidney Disease Progression in Patients with Mild or No-Proteinuria.

BACKGROUND/AIMS: Arterial hypertension is one of the leading factors aggravating the course of chronic kidney disease (CKD). It seems that the novel parameters used in the assessment of the blood pressure (BP) load (i.e. central blood pressure, nighttime blood pressure) may be more precise in predicting the cardiovascular risk and the progression of CKD in comparison with the traditional peripheral blood pressure measurements in the office conditions. The aim of the study was to assess the impact of the central, or nighttime blood pressure on the progression of CKD in patients with mild or no-proteinuria (autosomal, dominant polycystic kidney disease or IgA nephropathy). METHODS: In each of the enrolled 46 patients with CKD stage 3 or 4, serum creatinine concentration was assessed, eGFR (MDRD) was calculated, also central blood pressure and pulse wave velocity (PWV) was assessed and the 24-hour ambulatory blood pressure monitoring (ABPM) was conducted at the beginning of the study and then repeated after one-year observation period. RESULTS: During the observation period mean eGFR decreased from 44.1 (33.2-50.6) mL/min to 36.7 (29.7-46.3) mL/min. No significant differences were observed in the peripheral blood pressure or central blood pressure parameters. After one-year observation period the values of diastolic blood pressure dipping during the night significantly decreased from 16 (13-19) mmHg to 12 (10-15) mmHg; p< 0.05. The values of systolic dipping during the night or the mean BP values recorded in ABPM did not change significantly. Additionally, no significant differences in the PWV values were found. In the multivariate regression model the change of serum creatinine concentration was explained by the initial diastolic dipping values. CONCLUSION: 1. In patients with CKD stages 3 or 4 and mild or no- proteinuria, peripheral and central blood pressure did not change significantly during a one-year observation period despite the significant decline of eGFR and seems not to participate in the CKD progression. 2. Reduced magnitude of the diastolic dipping, which reflects the increase of diastolic blood pressure load during the nighttime, may play an important role in the pathogenesis of deterioration of kidney function in these patients.

Cardiac status of persons qualified for living kidney donation--single-center experience.

UNLABELLED: Some of living kidney donors have medical conditions associated with future risk of cardiovascular diseases. It seems justified to identify risk factors and cardiological disorders prior to the donation. AIM: To determine the cardiological status of persons qualified as a living kidney donor. MATERIAL AND METHODS: We analyzed the data of 109 potential living kidney donors, aged 25-70 (mean 45.7 ± 10.9) years. They underwent clinical and biochemical examination. In some of them extended diagnostics was performed. The presence of risk factors of coronary artery disease were registered. RESULTS: Only 46 (42%) persons were qualified for kidney donation. As many as 40 of them had 21 risk factor. In 75 (68.8%) patients without hypertension, 24-hours ambulatory blood pressure monitoring was done. The masked hypertension was found in 6 persons. In 22 candidates aged > 50 years the exercise test was performed (positive or inconclusive in 3 persons). Coronarography was done in 5 individuals (in no any significant atherosclerotic lesions were found). 63 (58%) person were disqualified. In 15 (23.8%) person the reasons were cardiological. In 2 patient the abdominal aneurysms were found. Both men smoked and had severe dyslipidaemias. In 3rd patient we observed persistent atrial fibrillation. The next 2 men had the peripheral occlusive arterial disease. In 9 patients ≥ 2 risk factors and in the last one morbid obesity were present. CONCLUSION: In Poland candidates for living kidney donation have very often risk factors of cardiovascular disease. Among the persons proceeded for kidney donation cardiovascular problems are an important cause of disqualification.

Difficulties in the Diagnosis of Fibrinogen Aα-Chain Amyloidosis-Literature Review and Case Report of a Patient After Kidney Transplantation.

BACKGROUND: Amyloidosis is a very heterogeneous disease. Correct diagnosis is extremely important because of the various treatment options for different types of amyloidosis. This study presents a case report and literature review of the misdiagnosis of fibrinogen Aα-chain amyloidosis (AFib amyloidosis). CASE PRESENTATION: We report a 65-year-old man diagnosed with proteinuria in 2009. The kidney biopsy revealed the presence of Congo red-stained amyloid deposits. During differential diagnosis, amyloid deposits were discovered in adipose tissue and gingiva. Bone marrow trephine biopsy showed a predominance of lambda chains presenting plasmocytes. Based on performed medical examination, light chain amyloidosis was identified. Therefore, the patient received high-dose melphalan and underwent successful autologous peripheral blood stem cell transplantation. However, proteinuria, worsening of the kidneys' function, and incorrect levels of free light chains were still observed. In 2019, due to continuous treatment failure, a previously acquired kidney biopsy was examined by mass spectrometry, and numerous fibrinogen deposits were identified. Recommended DNA analysis revealed that the patient had AFib amyloidosis. Therefore, chemotherapy treatment was abandoned, and successful kidney transplantation was performed. CONCLUSION: Today, it is essential for medical practitioners to remember the possibility of rare and hereditary types of amyloidosis. There are multiple cases where a diagnosis was wrong or delayed because of the atypical course of the disease, the coexistence of another disease, and the rarity of AFib amyloidosis, and all of these reasons may result in the wrong treatment that will delay the right therapy. However, with the new, more precise diagnostics methods, such situations will become rare.

Potential utility of urinary chemokine CCL2 to creatinine ratio in prognosis of 5-year graft failure and mortality post 1-year protocol biopsy in kidney transplant recipients.

BACKGROUND: Chemokines (chemotactic cytokines) are small proteins which are engaged in many pathophysiological processes, including inflammation and homeostasis. In recent years, application of chemokines in transplant medicine was intensively studied. The aim of this study was to determine the utility of urinary chemokines CCL2 (C-C motif ligand 2) and CXCL10 (C-X-C motif chemokine ligand 10) in prognosis of 5-year graft failure and mortality post 1-year protocol biopsy in renal transplant recipients. METHODS: Forty patients who had a protocol biopsy 1 year after renal transplantation were included. Concentrations of CCL2 and CXCL10 in urine with reference to urine creatinine were measured. All patients were under the supervision of one transplant center. Long-term outcomes within 5 years after 1-year posttransplant biopsy were analyzed. RESULTS: Urinary CCL2:Cr at the time of biopsy was significantly increased in patients who died or had graft failure. CCL2:Cr was proven to be a significant predictor of 5-year graft failure and mortality (odds ratio [OR]: 1.09, 95% confidence interval [CI]: 1.02-1.19, p = .02; OR: 1.08, 95% CI: 1.02-1.16, p = .04; respectively). CONCLUSION: Chemokines are easily detected by current methods. In the era of personalized medicine, urinary CCL2:Cr can be considered as a factor providing complementary information regarding risk of graft failure or increased mortality.

The Importance of 1-Year Protocol Biopsy in the Long-Term Prognosis of Kidney Transplants-5-Years Follow-Up.

BACKGROUND: Protocol biopsies are performed to detect subclinical pathologies that may lead to future graft dysfunction. However, they are not routinely performed interventions in every transplant center. There is no established regimen for performing them. PURPOSE: The study aimed to evaluate if protocol biopsies can improve long-term patient outcomes after detecting early disorders and modifying treatment. MATERIAL AND METHODS: Our observational study included 61 patients who underwent protocol biopsy 12 months after the transplantation. Based on the biopsy results, patients with abnormal histologic material (n = 37) were divided into 3 study groups as follows: patients with mild inflammatory lesions (n = 21), patients with interstitial fibrosis and tubular atrophy (IFTA) grade II to III (n = 12), and patients with BK virus nephropathy (n = 4). The control group (n = 24) included kidney recipients with IFTA 0 to I grade. Outcomes after 5-year follow-up were evaluated. RESULTS: Five years after the biopsy, patients in the control group had stable graft function (5-year change in serum creatinine was -0.09 mg/dL). An increase in serum creatinine levels was observed in patients with IFTA II to III compared with the control group (0.14 mg/dL, P = .04). Immunosuppressive treatment was modified in the group with mild inflammatory changes and in the BKV group after the biopsy result. In the group with mild inflammatory lesions, renal function was stable (change of serum creatinine was -0.01 mg/dL, P = .51). In the BKV nephropathy group, there was a significant reduction in serum creatine levels (-0.48 mg/dL, P = .016). The analysis showed no diagnostic value for serum creatinine concentration (95% CI 0.49-0.78, P = .08). CONCLUSIONS: Protocol biopsies are useful for detecting early pathologies and preventing allograft failure. They greatly benefit patients with detectable pathology that can be treated or in whom therapy modification is possible.

Clinical significance of low pre-transplant donor specific antibodies (DSA) in living donor kidney recipients with negative complement-dependent cytotoxicity crossmatches (CDCXM), and negative flow cytometry crossmatches (FLXM) - A single-center experience.

BACKGROUND: It is controversial whether all donor-specific antibodies (DSA) detected by the solid-phase single antigen bead (SAB) assay negatively affect kidney transplantation outcomes. The study aimed to evaluate the possible clinical significance of low pre-transplant DSA in living donor kidney recipients. We analyzed a group of patients with HLA-A, B, and -DR DSA reactivities below a virtual crossmatch (VXM) value of 5000 MFI but with all VXM DSA reactivities at HLA-DQ, -DP, and -Cw, which were not typed routinely for donors prior to transplantation. We also investigated the incidence of persistent and de novo DSAs in available posttransplant SAB assays. METHODS: From the historical cohort of living donor recipients transplanted between 2014 and 2018 at our center (n = 82), 55 patients met the inclusion criteria, namely: these patients were > 18 years old with non-HLA identical sibling donors, who were not desensitized, who had available pre-transplant SAB results, and who had negative both complement-dependent cytotoxicity crossmatch (CDCXM) and flow cytometry crossmatch (FLXM) results. An additional donor HLA typing, performed for all 55 recipients, identified donor additional HLA-DQ, -DP, and -Cw DSA reactivities. These patients were then divided by SAB reactivity into three groups: 1) those with DSA-positive reactivities; 2) those with non-donor-specific anti-HLA reactivities (NDSA); and, 3) those who were anti-HLA-negative. All these recipients were followed for three years and checked for their de novo or persistent DSA. RESULTS: In the studied cohort, DSA-positive, NDSA reactive, and anti-HLA negative recipients constituted 33%, 36%, and 31% of 55 patients, respectively. Non-routinely considered pre-transplant HLA-DQ, -DP, and -Cw DSA-positive reactivities were shown in as many as 78% of DSA-positive cases (group 1) with the lowest MFI value of 319 to DP4 and the highest MFI of 5767 to DQ2. Of the pre-transplant HLA-A, B, and -DR DSA reactivities, only -DR52 DSA reactivity reached the highest MFI value of 2191. These detected DSAs did not reduce the mean estimated glomerular filtration rate (eGFR) values and did not increase the incidence of proteinuria in recipients. While the 3-year graft survival was lower in the DSA-positive group (94.4%) with one recipient who lost kidney transplant, the difference was not significantly different (p = 0.7) from the NDSA (100%) and negative (100%) groups. In terms of the incidence of de novo acute antibody-mediated rejection (AMR) at three years after transplantation, no case has been reported in the cohort. This may suggest that low DSA-positive recipients do not experience higher rejection rate. However, DSA-positive recipients had a tendency for a higher frequency of C4d deposits in peritubular capillaries (PTC) and de novo DSA. CONCLUSION: Our 3-year follow-up of patients with low pre-transplant DSA found no association with a deterioration in graft function and worse graft survival. Furthermore, we did not observe an increase in AMR in our patients with low DSA. A larger cohort and a longer follow-up period may be needed to evaluate the tendency of low DSA-positive recipients towards the higher incidence of C4d deposits in PTC and/or de novo DSA.

Accuracy of virtual crossmatch (VXM) prediction of physical crossmatch (PXM) results of donor specific antibody (DSA) in routine pretransplant settings-a single-center experience.

BACKGROUND: Virtual crossmatch (VXM) is a new powerful tool in pre-transplant risk assessment. However, the ability of VXM to predict physical crossmatch (PXM) results remains controversial. Our work evaluated the predictive potential of VXM results, measured by SAB (single antigen bead assay), for CDCXM (complement-dependent cytotoxicity crossmatch) and FLXM (flow cytometry crossmatch) results of DSA (donor specific antibody) in sensitized patients. METHODS: In total, 261 CDCXM and FLXM measurements were performed for 180 potential kidney transplant candidates, each with a single HLA-A, B, or -DR DSA against a potential deceased donor. Analysis was conducted with two SAB datasets of four-month distant and collected prior to and after PXM results. Optimal MFI (mean fluorescence intensity) thresholds and likelihood ratios were assigned based on low (<2000 MFI), medium (2001-5000 MFI) and high risk (>5000 MFI). The impact of VXM predictability was determined by the ROC curves comparison. In addition, inter-assay changes of MFI were evaluated. RESULTS: The accuracy of VXM to predict CDCXM was inferior to that of FLXM with the AUC (area under ROC curve) of 0.644 vs. 0.849. In contrast, the initial ROC analysis showed that the VXM prediction was good for both T-FLXM with ROC value of 0.849 and by B-FLXM with ROC value of 0.706 for a single antigen of HLA-A, B, or -DR DSA. In fact, the best VXM prediction was for FLXM with good sensitivity for B-FLXM against HLA-DR-specific DSA (0.851). Similar results of VXM predictability were observed for pre- and post-crossmatch ROC curves. CONCLUSION: VXM predictability is better for positive/negative FLXM than for positive/negative CDCXM results to evaluate a single HLA-A, B, -DR DSA disparity. This may be related to the fact that VXM and FLXM rely on binding of antibodies to beads or cells, respectively. In contrast, VXM is less predictive for CDCXM because the latter measures complement-dependent cytotoxic function. We intend expand VXM analysis to correlate their results with FLXM results to select low/medium risk patients for kidney transplantation in Poland.

Kidney Transplantation in a Patient With Tuberous Sclerosis Complex: A Case Report.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disease caused by mutations of either of 2 genes, TSC1 and TSC2. Renal manifestations include angiomyolipomas (AMLs), multiple cysts, and renal cell carcinoma. AMLs increase bleeding tendency and the risk of renal insufficiency which end-stage develops in 1% of affected patients. CASE REPORT: A 38-year-old woman suffering from TSC since early childhood has developed multiple complications associated with this disease. The patient was diagnosed with brain tumor-giant cell astrocytoma-which was removed in 1992. In 2006, right nephrectomy was performed due to the unsuccessful right renal artery embolization after the massive hemorrhage into the AML. Moreover, the right idiopathic pneumothorax occurred twice. Therefore, the video-assisted thoracoscopic surgery and pleurodesis were conducted (2006, 2013). The patient is intellectually disabled and unable to make decisions on her own. Her legal guardians (parents) make all decisions associated with her treatment. Diagnostic and therapeutic procedures demanding cooperation were conducted under anesthesia. Because of end-stage renal failure, the patient required the renal replacement therapy (RRT). Preemptive kidney transplantation (KTx) was the best solution for this patient. Procedures such as hemodialysis and peritoneal dialysis were infeasible to perform due to the intellectual disability that inhibits essential cooperation. During KTx qualification tests, the expanding AML with risk of hemorrhage was noticed. The patient was qualified for simultaneous left nephrectomy and KTx from the living donor (her father). The surgery was performed on the 2nd of June 2020. The patient is looked after by her parents, stays in good general condition. The patient's creatinine level is maintained at 0.6 to 0.8 mg/dL. CONCLUSION: Patients with significant intellectual disability that prevents maintaining conscious cooperation who require RRT must have individually adjusted therapy. In the case of the presented patient, it was decided to perform the preemptive kidney transplantation from her determined father.

Extrapulmonary Manifestations of SARS-CoV-2: A Report of 3 Cases and a Literature Review.

BACKGROUND COVID-19 disease, caused by the SARS-CoV-2 virus, has been one of the greatest challenges in modern medicine. It is mostly known to affect the pulmonary system, leading to pneumonia and acute respiratory distress syndrome, but there is a growing body of evidence of extrapulmonary manifestations of COVID-19 disease. CASE REPORT This article presents 3 cases of various extrapulmonary symptoms of COVID-19 disease and a literature review of similar clinical cases. Two patients had a medical history of living-donor kidney transplantation, and 1 patient was a kidney donor. We present symptoms, diagnostic processes, laboratory and imaging results, and treatment approach. Patient 1 was 29-year-old woman with new-onset diabetes mellitus due to SARS-CoV-2, which required temporary insulin treatment. Patient 2 was a 34-year-old man with fever, chronic fatigue, back pain, and abdominal pain. Imagining showed acalculous cholecystitis, epiploic appendagitis of the right colic flexure, and inflammation of pericardial fat pad in the left cardiophrenic angle. Coagulopathy due to COVID-19 was the most probable cause of the described processes. Therapeutic doses of low-molecular-weight heparin were administered. Patient 3 was a 68-year-old male kidney donor who had painless, nodular, reddening lesions on both shins, accompanied by itching on both shins and recurrent fever. The diagnosis of erythema nodosum during COVID-19 was made. After treatment with low-molecular-weight heparin, significant decreases of symptoms were observed. CONCLUSIONS We conclude that SARS-CoV-2 infection can have a varied course and can involve other systems and organs. Physicians should be aware of possible extrapulmonary symptoms associated with infection with this virus. Correct diagnosis is a prerequisite for proper treatment and prevention of unexpected complications.

Formulas Estimating Glomerular Filtration Rate in the Evaluation of Living Kidney Donor Candidates: Comparison of Different Formulas With Scintigraphy-Measured Glomerular Filtration Rate.

INTRODUCTION: Estimation of kidney function is crucial in the evaluation of living kidney donor candidates. Despite the multitude of glomerular filtration rate (GFR) formulas, no equation is universal, and none were validated in the population of kidney donors. Novel biomarkers, including beta trace protein (BTP) and cystatin C, are studied to help estimate GFR and improve the safe qualification of living kidney donors. AIM: This study compares the accuracy of different formulas that estimate GFR with reference scintigraphy-measured GFR in the population of living kidney donor candidates. MATERIAL AND METHODS: This study enrolled 30 healthy living kidney donor candidates. GFR was measured using the following 11 different formulas. For reference, GFR was assessed using 99m-Technetium-diethylenetriaminepentaacetic acid. RESULTS: The accuracy of estimation was generally low in all formulas. The strongest correlation between measured GFR (mGFR) and estimated GFR (eGFR) was achieved by the Nankivell formula (R = 0.47, P = .009); however, in the group of patients with a body mass index of >25 kg/m2, only the equations based on BTP had a statistically significant correlation with mGFR: White (R = 0.59; P = .016) and Poge (R = 0.53; P = .035). Bland-Altman plots revealed wide limits of agreement between eGFRs and mGFR in all groups of patients. CONCLUSION: In living kidney donor candidates, GFR estimation formulas should be chosen individually. White formula, which is based on BTP, may be a promising tool in estimating GFR in overweight potential living kidney donor candidates. More than 1 formula and personalized choice of GFR estimation method regarding the given patient should be performed in qualification of kidney donors.

Post-Traumatic Growth among Patients after Living and Cadaveric Donor Kidney Transplantation: The Role of Resilience and Alexithymia.

The aim of this study was to determine the role of resilience and alexithymia in the post-traumatic growth as a response to extreme stress in patients after kidney transplantation and to determine whether there are differences in the level of posttraumatic growth in patients after living and cadaveric donor kidney transplantation. The relationships between these variables were also evaluated. The questionnaire survey of 91 kidney recipients took place in 2018 and 2019. The following tools were used: authorial post-transplant questionnaire for recipients and validated questionnaires, Post Traumatic Growth Inventory (PTGI-R), Resilience Coping Scale Questionnaire, and Toronto Alexithymia Scale Questionnaire (TAS20). The results obtained showed significant differences between the group of kidney recipients from living donors and recipients from cadaveric donors, in terms of overall post-traumatic growth, as well as changes in self-perception and a greater appreciation for life. Post-traumatic growth in both groups was related to the level of resilience and the level of alexithymia. Resilience is an accurate predictor of posttraumatic growth in general and for each of the groups of recipients separately.

Massive Ascites of Unknown Origin: A Case Report.

Ascites is the excessive accumulation of fluid in the peritoneal cavity and predominantly caused by liver cirrhosis, cancers, or heart failure. In this study, a 31-year-old woman with chronic renal failure of unknown etiology treated with hemodialysis and peritoneal dialysis was often hospitalized because of ascites, which appeared 4 years after the second kidney transplantation. The patient was regularly (every 2-3 weeks) treated with paracentesis. Peritoneal fluid tested negative for bacterial (including atypical) and fungal infections and tuberculosis. Doppler ultrasound and liver FibroScan did not show any irregularities. Computed tomography (CT) revealed an enlarged left ovary. A high level of CA 125 was found. The second diagnostic laparoscopy revealed no changes in the ovaries, and there were no tumor cells. Diagnostics were extended, but no deviations were revealed. Suspecting drug etiology, mycophenolic acid was discontinued, bringing no improvement. Diagnostic tests caused suspicion of Meigs' syndrome; therefore, oophorectomy of left ovary was conducted, revealing numerous small cysts filled with serous fluid, without tumor cells in the ovary or peritoneal fluid. Despite the procedure performed, ascites was recurrent. Five month later, ascites spontaneously stopped growing. Paracentesis to decompress ascites was no longer required. There were 9 paracenteses performed from oophorectomy (the latest on May 23, 2019). The need for repetitive paracentesis, significantly reducing the patient's quality of life, required diagnosis for casuistic diseases. The described case is atypical because of the confusing etiology of ascites and its spontaneous cessation. Despite numerous examinations and recession of ascites, the cause of the problem is not entirely clear.