First Experience in Management of Coronavirus Disease 2019 (COVID-19) in Kidney Transplant Patient – Case Report

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has recently emerged in the world. There are limited data describing the clinical progression of COVID-19 in transplanted patients. In the general population, clinical presentation ranges from asymptomatic infection to severe pneumonia and may also develop renal failure. In kidney transplant (KT) patients, management of these patients was mainly based on anecdotal experience. CASE REPORT: We report our first experience of KT patients with COVID-19. A 49-year-old male with KT in 2017 presented on March 20, 2020, with fever, weakness, smell loss, chest pain, and caught. On chest X-ray, he presented ground-glass opacities and bilateral pneumonia. There was a slight progression to acute hypoxic respiratory failure. We reduced immunosuppression therapy and since we suspected seasonal flu, we applied available antiviral oseltamivir till confirmation of RNA sequence of the SARS-CoV-2 virus. Moreover, we applied azithromycin and broad spectrum of antibiotics as well as an anticoagulant therapy. Graft function remained stable during 14 days of hospitalization. The patient clinically improved with decreasing oxygen requirements and manifested clinical recovery. After two negative PCR test, he was discharged and immunosuppression therapy was returned to previous. CONCLUSION: This case highlights the importance of earlier outpatient hospitalization and testing which may improve COVID-19 outcomes among transplanted patients

The Spectrum of Histopathological Changes in the Renal Allograft - a 12 Months Protocol Biopsy Study

INTRODUCTION: Renal transplantation became a routine and successful medical treatment for Chronic Kidney Disease in the last 30 years all over the world. Introduction of Luminex based Single Antigen Beads (SAB) and recent BANFF consensus of histopathological phenotypes of different forms of rejection enables more precise diagnosis and changes the therapeutic approach. The graft biopsies, protocol or cause, indicated, remain a golden diagnostic tool for clinical follow up of kidney transplant recipients (KTR).AIM: The study aimed to analyse the histopathological changes in renal grafts 12 months after the surgery in KTR with satisfactory kidney function.MATERIAL AND METHODS: A 12-month protocol biopsy study was performed in a cohort of 50 Kidney transplant recipients (42 from living and 8 from deceased donors). Usual work-up for suitable donors and recipients, standard surgical procedure, basic principles of peri and postoperative care and follow up were done in all KTR. Sequential quadruple immunosuppression including induction with Anti-thymocyte globulin (ATG) or Interleukin-2R antagonist (IL-2R), and triple drug maintenance therapy with Calcineurin Inhibitors (CNI), Mycophenolate Mofetil (MMF) and Steroids were prescribed to all pts. Different forms of Glomerulonephritis (16), Hypertension (10), End Stage Renal Disease (13), Hereditary Nephropathies (6), Diabetes (3) and Vesicoureteral Reflux (2) were the underlying diseases. All biopsies were performed under ultrasound guidance. The 16 gauge needles with automated “gun†were used to take 2 cores of tissue. The samples were stained with HE, PAS, Trichrome Masson and Silver and reviewed by the same pathologist. A revised and uploaded BANFF 2013 classification in 6 categories (Cat) was used.RESULTS: Out of 48 biopsies, 15 (31%) were considered as normal, 4 (8%), Borderline (BL-Cat 3), 5 (10%) as Interstitial Fibrosis/Tubular Atrophy (IF/TA-Cat 5), 5 (10%) were classified as non-immunological (Cat 6), 2 as a pure antibody-mediated rejection (ABMR-Cat 2) and T-cell Mediated Rejection (TCMR-Cat 4). The remaining 17 samples were classified as a “mixed†rejection: 7 (41%) ABMR + IF/TA, 5 (29%) ABMR + BL + IF/TA, 2 (11%) BL + IF/TA, 1 (5%) ABMR + BL, 1 (5%) ABMR + TCMR and 1 (5%) TCMR +  IF/TA. The mean serum creatinine at the time of the biopsy was 126.7 ± 23.4 µmol/L, while GFR-MDRD 63.4 ± 20.7 ml/min, which means that the majority of the findings were subclinical. Among the non-immunological histological findings (Cat 6), 3 cases belonged to CNI toxicity, 1 to BK nephropathy and 1 to recurrence of the primary disease.CONCLUSION: Our 12-month protocol biopsy study revealed the presence of different forms of mixed subclinical rejection. Use of recent BANFF classification and scoring system enables more precise diagnosis and subsequently different approach to the further treatment of the KTR. More correlative long-term studies including Anti HLA antibodies and Endothelial Cell Activation- Associated Transcripts (ENDAT) are needed

Excess Mortality in a Nephrology Clinic during First Months of Coronavirus Disease-19 Pandemic: A Pragmatic Approach

BACKGROUND: Excess mortality is defined as mortality above what would be expected based on the non-crisis mortality rate in the population of interest. AIM: In this study, we aimed to access weather the coronavirus disease (COVID)-19 pandemic had impact on the in-hospital mortality during the first 6 months of the year and compare it with the data from the previous years. METHODS: A retroprospective study was conducted at the University Clinic of Nephrology Skopje, Republic of Macedonia. In-hospital mortality rates were calculated for the first half of the year (01.01–30.06) from 2015 until 2020, as monthly number of dead patients divided by the number of non-elective hospitalized patents in the same period. The excess mortality rate (p-score) was calculated as ratio or percentage of excess deaths relative to expected average deaths: (Observed mortality rate–expected average death rate)/expected average death rate *100%. RESULTS: The expected (average) overall death mortality rate for the period 2015–2019 was 8.9% and for 2020 was 15.3%. The calculated overall excess mortality in 2020 was 72% (pscore 0.72). CONCLUSION: In this pragmatic study, we have provided clear evidence of high excess mortality at our nephrology clinic during the 1st months of the COVID-19 pandemic. The delayed referral of patients due to the patient and health care system-related factors might partially explain the excess mortality during pandemic crises. Further analysis is needed to estimate unrecognized probable COVID-19 deaths

Complications and Risks of Percutaneous Renal Biopsy

BACKGROUND: Renal biopsy performed in native and transplant kidneys is generally considered a safe procedure. AIM: In this study, we evaluated renal biopsy complications and risk factors in one nephrology facility. MATERIAL AND METHODS: We conducted a three-year retrospective study on patients who underwent renal biopsy between January 2014 and December 2016. Strict written biopsy protocol was followed. Clinical and laboratory data were obtained from medical charts. Complications were categorised as minor and major, according to the need for intervention. Minor complications included macrohematuria and/or hematoma that did not require intervention. Major complications included hematuria or hematoma with fall of hematocrit that required a blood transfusion, surgery or caused death. A binary logistic regression model was used to analyse the possible factors associated with complications after the biopsy. RESULTS: We analysed 345 biopsies; samples were taken from patients aged from 15-81 years, of whom 61% were men. A total of 21 (6%) patients developed a complication, 4.4% minor and 1.7% major complications. There were no nephrectomy or death due to biopsy intervention. Overweight patients, as well as those with higher creatinine, lower hemoglobin, higher blood pressure and biopsy due to AKI had higher chances to develop complications (p = 0.037, p = 0.023, p = 0.032, p = 0.002, p = 0.002, respectively). The patients’ age, gender, kidney dimension, number of passes and uninterrupted aspirin therapy were not found as significant predictors of complications. In the multivariate logistic model, body weight (OR = 1.031, 95%CI = 1.002-1.062), lower hemoglobin (OR = 0.973, 95%CI = 0.951–0.996) and hypertension (OR = 1.025, 95%CI = 1.007-1.044) increased the risk of complications in biopsied patients. CONCLUSION: Renal biopsy is a safe procedure with a low risk of complications when strict biopsy protocol is observed. Correction of anaemia and blood pressure is to be considered before the biopsy

Simulation-based modeling of building complexes construction management

The study reported here examines the experience in the development and implementation of business simulation games based on network planning and management of high-rise construction. Appropriate network models of different types and levels of detail have been developed; a simulation model including 51 blocks (11 stages combined in 4 units) is proposed

Simulation-based modeling of building complexes construction management

The study reported here examines the experience in the development and implementation of business simulation games based on network planning and management of high-rise construction. Appropriate network models of different types and levels of detail have been developed; a simulation model including 51 blocks (11 stages combined in 4 units) is proposed

DE NOVO ANTI HLA ANTIBODIES AFTER KIDNEY TRANSPLANTATION: CLINICAL SIGNIFICANCE AND ASSOCIATION WITH GRAFT FUNCTION

Background. Kidney transplantation (TR) is the best treatment of chronic kidney disease. Chronic cellular and antibody mediated rejections have still major impact on graft survival. Single antigen bead technology enabled detection of donor specific (DSA) and non-donor specific (Non-DSA) anti HLA antibodies (HLA-Ab). Our study investigates the impact of de novo HLA-Ab on graft function (GF) 12 months after TR. Material and methods. 50 pts with living (42) and deceased donor (8) transplantation were included in a 12-month prospective study. HLA-Ab were analyzed using LABScreen mixed kit in the 1st and 12th month after TR. According to the presence of HLA-Ab, pts were divided in group 1 (HLA+) and group 2 (HLA -). Both groups did not differ regarding gender, age, living or deceased donor, immunosuppression, underlying renal disease, rejection episodes, HLA mismatch, cold and warm ischemia time. Serum creatinine (SCr), GFR (Cockroft Gault) and proteinuria (Pr) were analyzed 1st and 12th month after TR. Results. HLA-Ab were detected in 17 pts (34%), 5 with DSA (10%) and 12 with Non-DSA (24%). Group 1 has a significant worsening of GFR (SCr increased from 112.1 to 141.5 ( p<0.002) compared with the group 2 where SCr decreased from 116.4 to 111.31 µol/L.( p<0.23). In the same time GFR decreased from 69.7 to 57.09 and increased from 67.8 to 69.3 while Pr increased from 0.42 to 0.58 ( p< 0.26) and decreased from 0.81 to 0.32 ( p<0.051) in the groups 1 and 2, respectively. Conclusion. De novo DSA and Non-DSA produce graft injuries in the first 12 months after TR. Regular follow- up of HLA-Ab together with systematic protocol graft biopsy could be essential for further therapeutic interventions