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.

Antiviral prophylaxis, male sex, and killer immunoglobulin-like receptor KIR2DL3 as markers for stratifying the risk of BK polyomavirus-associated nephropathy in kidney transplant recipients.

INTRODUCTION: The risk of polyomavirus­associated nephropathy (PyVAN) currently ranges from 1% to 10%, and the risk of graft loss is 10% to 50% within 2 years post­diagnosis. There is currently no specific antiviral therapy against BK polyomavirus (BKPyV), and no therapeutic approach has been proven superior. Natural killer cells play a key role in the defense against viral infections. OBJECTIVES: A retrospective, single­center cohort study was performed to investigate the association between the kidney transplant recipients' killer­cell immunoglobulin­like receptor (KIR) genotype and PyVAN. We also evaluated other possible risk factors for the occurrence of PyVAN in a population of kidney transplant recipients. PATIENTS AND METHODS: DNA samples from 134 kidney transplant recipients were identified for the presence or absence of variable KIR genes and their HLA ligands using polymerase chain reaction with sequence­specific primers. RESULTS: The analysis revealed that the presence of the inhibitory KIR2DL3 (P = 0.03) was a risk factor for posttransplant PyVAN. We also found that the presence of acute rejection before PyVAN (P = 0.02), male sex (P = 0.04), and the lack of antiviral prophylaxis (P = 0.01) were additional risk factors for posttransplant PyVAN. CONCLUSIONS: Our findings confirm that the KIR/HLA genotype plays a significant role in the development of PyVAN and suggest the contribution of both environmental and genetic factors to the incidence of BKPyV infection after kidney transplantation.

Transplant Renal Artery Stenosis: Underrecognized, Not So Rare, but Curable Complication.

Transplant renal artery stenosis (TRAS) constitutes 75% of all vascular complications in kidney transplant recipients, being a significant source of graft dysfunction and loss. TRAS is a heterogeneous disease with different risk factors and causes. The incidence differs greatly, and it is likely it will increase because of the aging population of potential recipients and donors of renal grafts and the expanding use of extended-criteria donors. Prompt diagnosis and treatment of TRAS can prevent irreversible allograft dysfunction and loss. Current evidence of risk factors, diagnostic challenges, and therapeutic options are presented in this short review.

National Organ Transplant Registry in Poland. Poltransplant Activity.

BACKGROUND: In 2006 the National Transplants Registry administered by national transplant organization was introduced in Poland to monitor the results of organ transplantations. Statistical analysis is published yearly in the Poltransplant Bulletin, publicly available on the website and reported to European institutions. The transplant registry cooperates with other registers functioning online, based on the tool https://rejestrytx.gov.pl/. We present the formal analysis of data collected for the years 1996-2019. MATERIALS AND METHODS: Analysis covered the total number of organ transplantations in every transplant center; outcomes are related to recipients living with a functioning graft 1, 5, and 10 years after transplantation; results presented are real, not extrapolated. RESULTS: The total number of deceased-donor kidney transplantations was 20,606, the 1-year survival rate of recipients with a functioning graft was 90% (data completeness of 97%), and the 10-year survival rate was 59% (data completeness of 99%). The total number of deceased-donor liver transplantations was 4790; the 1-year survival rate of recipients with a functioning graft was 59% (data completeness of 98%). SUMMARY: The National Transplant Registry is an important tool for quality and safety systems in the transplantation field on the national level. The registry efficiently and effectively fulfills its tasks related to collecting records of all transplantations performed. Monitoring function for graft and recipient survival is also satisfied. The data provide an important and unique source of information to be used by transplant institutions and referred to in the literature.

The Current Status of Organ Donation and Transplantation in Poland. Poltransplant Activity.

BACKGROUND: This article summarizes comprehensive information about the current status of organ donation and transplantation in Poland. MATERIAL AND METHODS: Reported statistical data of solid organs and vascularized composite allograft donation and transplantation from both deceased and living donors in Poland in 2015-2020 (presented in tables according to selected variables) are based on the national transplant registries, gathering information on donation and transplantation activity in medical centers involved in donation and transplantation programs in Poland. RESULTS: In 2020 during the COVID-19 pandemic, 529 potential deceased donors were referred to the Polish Transplant Coordinating Centre Poltransplant; 1310 solid organs from 393 actual deceased donors (10.2 per million population) were procured, mostly kidneys (758), livers (285), and hearts (157). Eighty percent were multiorgan retrievals (314). In 2020, 1231 organs procured from deceased donors and 59 organs from living donors were transplanted to 1236 recipients. CONCLUSION: This overview indicates that donation and transplantation activity from deceased donors in Poland decreased about 20% in 2020 compared with 2019, which is comparable with worldwide rates. As the unprecedented pandemic situation affected donation and transplantation procedures, there are measures that must to be taken to return to prepandemic donation and transplantation rates in both deceased and living transplant programs and then continue to improve in the years to come.

Statistical evaluation of growth parameters in biofuel waste as a culture medium for improved production of single cell protein and amino acids by Yarrowia lipolytica.

Yarrowia lipolytica is an oleaginous yeast species with the ability to grow on a number of substrates types, especially industrial wastes. This paper concerns the statistical optimization of fermentation parameters and media to ensure consistent and improved Y. lipolytica protein production. A strain of Y. lipolytica A-101 was observed to be proficient in producing single cell protein, amino acids, and vitamin B12 while utilizing biofuel waste instead of a complete YPD medium for yeast growth. A fractional fractal design experiment was then applied, and the two fermentation parameters of temperature and pH were recognized to have a significant effect on the protein and amino acid production. Subsequently, the response surface methodology with a three-level complete factorial design was employed to optimize these influential parameters. Therefore, five different measuring systems were utilized to construct a quadratic model and a second-order polynomial equation. Optimal levels of parameters were then obtained by analysis of the model and the numerical optimization method. When the Y. lipolytica A-101 was cultivated at optimized pH (5.0) using biofuel waste as a medium, the protein concentration was increased to 8.28-a 44% enhancement as compared to the original (3.65). This study has thus demonstrated a beneficial way to cultivate Y. lipolytica A-101 on biofuel waste for enhanced production of single cell protein and amino acids for use in human diet and in animal feed.

Severe cytomegalovirus infection in a second kidney transplant recipient treated with ganciclovir, leflunomide, and immunoglobulins, with complications including seizures, acute HCV infection, drug-induced pancytopenia, diabetes, cholangitis, and multi-organ failure with fatal outcome: a case report.

BACKGROUND: Cytomegaly remains one of the most common infectious complications in organ transplant recipients, and the course of the infection may have a negative effect on survival of the transplant and recipient. CASE REPORT: We describe the case of a 32-year-old female patient who received a second kidney transplant from a cadaveric donor in July 2012, treated successfully with ganciclovir for primary CMV infection in August 2012 and then re-treated from November due to re-infection. The viral load at the start of re-treatment was 6 million copies. In view of ganciclovir treatment failure, Sando immunoglobulins were administered. Subsequently, when CMV viral load increased to 18 million copies, a decision was made to use combination treatment with leflunomide and ganciclovir. Immunosuppressive treatment was also modified by administering everolimus in view of its potential antiviral activity. Seizures, pancytopenia, diabetes, diarrhoea, and (probably) drug-induced liver damage and cholangitis were observed in the course of treatment. At 3 months of hospitalization, the patient was discharged home with viral load of 8000 copies. As treatment continuation, she received valganciclovir at the full therapeutic dose in view of very good kidney function (creatinine 0.7 mg/dl). The patient was re-hospitalized after 10 days due to fever and cough. Due to abnormal liver function test results and negative serum markers of viral hepatitis, HCV RNA was tested, with a positive result (above 10^8 copies). Subsequently, decline in clinical status, overhydration, increasing creatinine levels, hepatic failure signs, and renewed CMV DNA increase to 520 000 copies were observed. Despite intensive treatment, the patient died of multi-organ failure. CONCLUSIONS: The case described illustrates the difficulties in the treatment of CMV infection and its possible dramatic complications.

AD-O53.2--a novel recombinant fusion protein combining the activities of TRAIL/Apo2L and Smac/Diablo, overcomes resistance of human cancer cells to TRAIL/Apo2L.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors became promising molecules for selective targeting of tumor cells without affecting normal tissue. Unfortunately, cancer cells have developed a number of mechanisms that confer resistance to TRAIL\Apo2L-induced apoptosis, which substantiates the need for development of alternative therapeutic strategies. Here we present a recombinant variant of TRAIL\Apo2L peptide, named AD-O53.2, fused to the peptide-derived from Smac/Diablo protein-the natural inhibitor of the apoptotic X-linked IAP (XIAP) protein considered as a pro-apoptotic agent. The proposed mechanism of action for this construct involves specific targeting of the tumor by TRAIL\Apo2L followed by activation and internalization of pro-apoptotic peptide into the cancer cells. While in the cytoplasm , the Smac\Diablo peptide inhibits activity of X-linked IAP (XIAP) proteins and promotes caspase-mediated apoptosis. AD-O53.2 construct was expressed in E.coli and purified by Ion Exchange Chromatography (IEC). Derived protein was initially characterized by circular dichroism spectroscopy (CD), HPLC-SEC chromatography, surface plasmon resonance, protease activation and cell proliferation assays. Our Smac/Diablo-TRAIL fusion variant was tested against a panel of cancer cells (including lung, colorectal, pancreatic, liver, kidney and uterine) and showed a potent cytotoxic effect with the IC50 values in femtomolar range for the most sensitive cell lines, while it remained ineffective against non-transformed HUVEC cells as well as isolated normal human and rat hepatocytes. Importantly, the construct was well tolerated by animals and significantly reduced the rate of the tumor growth in colon and lung adenocarcinoma animal models.

Multisite-directed inhibitors of protein kinase CK2: new challenges.

New 4,5,6,7-tetrabromo benzotriazole derivatives have been synthesized, and their activities against CK2 have been tested. A click chemistry approach based on the copper-catalyzed azide-alkyne cycloaddition has been utilized to connect benzotriazoles, which efficiently interact with the ATP-binding site, to other subunits designed to simultaneously bind to the active and the substrate-binding sites of the enzyme. Docking studies allowed us to identify key interactions between CK2 and the designed ligands, which will be useful to optimize this series of multisite-directed inhibitors.