Unexpectedly High Efficacy of SARS-CoV-2 BNT162b2 Vaccine in Liver versus Kidney Transplant Recipients-Is It Related to Immunosuppression Only?

The BNT162b2 vaccine is reportedly effective in preventing severe disease in more than 90% of the general population, but its efficacy in transplant recipients remains controversial. We aimed to determine the immune response to the BNT162b2 vaccine in kidney (KTRs) and liver transplant recipients (LTRs). In this retrospective cohort study, we included randomly 65 KTRs and 65 LTRs, who received two 30 µg doses of BNT162b2 vaccine in 3-to6-week intervals. We analyzed the anti-SARS-CoV-2 spike protein IgG antibody (anti-S1 Ab) titer, biochemical liver and renal tests, immunosuppressive drug trough level, and clinical follow up 4-6 weeks after the first dose and 4-8 weeks after the second dose. The level of protective antibodies was 57.1% in KTRs and 88.9% in LTRs after the second dose. The anti-S1 Ab response was significantly associated with sex, age, and history of COVID-19. A tacrolimus dose at vaccination but not its trough level was significantly correlated with the increase in anti-S1 Ab titer after the second vaccine dose in LTRs. Rejection episodes did not occur after vaccination. Our results showed a higher than previously reported humoral response to the BNT162b2 vaccine in KTRs and LTRs, which was dependent upon age, type of transplanted organ, and immunosuppression.

Detecting adrenal insufficiency in patients with immunoglobulin A nephropathy, lupus nephritis, and transplant recipients qualified for glucocorticoid withdrawal.

INTRODUCTION: Long­term glucocorticoid (GC) therapy is the most common cause of secondary adrenal insufficiency (AI), which undiagnosed may lead to life­threatening adrenal crisis. OBJECTIVES: The aim of the study was to evaluate AI in patients treated long­term with GCs, receiving a low maintenance dose (≤5 mg of prednisone or equivalent), namely, its prevalence and persistence, risk factors, and diagnostic accuracy of morning cortisol and dehydroepiandrosterone sulfate (DHEA­S) levels. PATIENTS AND METHODS: Adrenal function was evaluated in 40 patients before and after GC withdrawal and at least 1 year later. Based on morning cortisol levels and short Synacthen test, patients were divided into 3 groups: AI, intermediate (partial AI), and AS (adrenal sufficiency). Receiver operator characteristic curves were calculated to assess the diagnostic value of morning cortisol and DHEA­S levels before GC withdrawal. RESULTS: Before GC withdrawal, 42.5% of patients had AI or partial AI, which together persisted in 64.3% of those patients after withdrawal. After more than a year, the adrenal function returned to normal only in 14% of patients. Cushingoid feature occurred more often in the AI group compared with the AS group (60% vs 13%; P = 0.03). Morning cortisol levels of 14.91 µg/dl or higher (411 nmol/l) gave 100% negative predictive value to rule out AI. Morning cortisol of 6.51 µg/dl or less (179.6 nmol/l) gave 100% positive predictive value to rule in AI. DHEA­S proved to be a worse parameter for AI diagnosis. CONCLUSIONS: AI is common in patients treated with GCs and may persist for years after GC withdrawal. Cushingoid features are associated with a higher risk of AI. Morning cortisol levels may facilitate AI diagnosis.

Long-term outcome of renal transplantation: a 10-year follow-up of 765 recipients.

INTRODUCTION: Renal transplantation is a treatment of choice for patients with end­stage renal disease. The main goal of transplant care is to achieve the best long­term patient survival (PS) and graft survival (GS). OBJECTIVES: We aimed to assess the impact of various immunosuppression (IS) protocols on PS and GS following renal transplantation. PATIENTS AND METHODS: This was a retrospective single­center cohort study including a total of 765 consecutive adult renal transplant recipients (RTRs) who underwent transplantation between 1998 and 2003. The primary endpoints included PS and GS. The secondary endpoints were graft function determined by estimated glomerular filtration rate and hospitalization length per patient per year. RESULTS: Ten­year PS and GS rates were 88.6% and 78.7%, respectively. The intent­to­treat (ITT) group received IS that was later changed, whereas in the group on randomized therapy (ORT), the same IS protocol was maintained during follow­up. The ITT group had significantly better PS and GS than the ORT group. In the ITT group, patients treated with a combination of tacrolimus (TAC) and azathioprine (AZA), cyclosporine (CSA) and AZA, or CSA and mycophenolic acid metabolites (MPAs) had significantly better PS than those treated with TAC and MPA. The ORT group receiving AZA in any combination also had significantly better PS than MPA­treated individuals. CONCLUSIONS: The effect of IS protocols on long­term outcomes varies depending on patient subpopulations. Immunosuppressive therapy solves rejection­related problems but does not address the increasing mortality of RTRs due to cardiovascular diseases, malignancies, or infections. Therefore, treatment recommendations should be individualized and posttransplant care, provided mainly by internists, should be carefully structured to improve long­term outcomes of renal transplantation.

Structure of Post-Transplant Care in a Single Transplant Center.

BACKGROUND: The number of transplant surgeries across the globe has markedly increased in recent decades and is associated with improvement in outcomes. Factors that could improve the organization of post-transplant care are sought. The aim of our study was to evaluate the changes in post-transplant care in the largest Polish transplant center from 2010 to 2014. MATERIAL AND METHODS: Analysis was performed in all transplant recipients followed up at our center. The following factors were evaluated: changes in patient inflow and outflow, changes in the number of ambulatory visits, causes of loss to follow-up of the patients, and changes in National Health Fund financing. All factors were measured in 5-year period from 2010 to 2014. RESULTS: Stable year-to-year patient inflow increased by 31% in the total number of patients under follow-up within 5 years. In the same time, the total NHF spending increased by 32%, but spending per patient increased by only 11%. As a consequence, after the initial growth in the years 2010-2012, the number of ambulatory visits per patient per year tended to decline. CONCLUSIONS: Our study revealed that the real challenge in long-term post-transplant care is the increasing number of patients and the increasing length of their follow-up. Potential risks related to financial expenditure discrepancy between short-term and long-term transplantation procedures were also found.

The use of nonsteroidal anti-inflammatory drugs and analgesics by liver transplant recipients.

AIMS AND OBJECTIVES: This study aimed to assess the reasons and the frequency of the use of over-the-counter (OTC) nonsteroidal anti-inflammatory drugs (NSAIDs) or analgesics by liver transplant recipients (LTR). Patient awareness of possible drug-related side-effects was also assessed. BACKGROUND: NSAIDs and analgesics available without prescription belong to the most commonly used class of drugs. However, use of these drugs might be complicated by toxic adverse effects (AEs). Patients at risk for AEs include the transplant recipients. DESIGN/METHODS: This was a descriptive study. An anonymous survey was carried out in 73 randomly selected LTR, who represented 10% of all LTR at our centre. RESULTS: There were 64% of the patients who confirmed taking NSAIDs or analgesics; 16% of these patients took these drugs at least several times a week and 10% took them daily. For 39% of patients, the only way to manage their pain were OTC NSAIDs or analgesics. As many as 36% of patients were unaware of the risks associated with the use of these drugs. Ninety per cent of LTR consider physicians the most trusted source of drugs information. CONCLUSIONS: Our study shows that two-thirds of LTR take OTC NSAIDs or analgesics and one-third are unaware of the AEs associated with these drugs. Therefore, both transplant nurses and doctors should educate their patients about the use and possible AE of these drugs. RELEVANCE TO CLINICAL PRACTICE: Considering the high NSAIDs consumption rates, the side effects of these drugs should always be suspected. Especially in patients taking these drugs and referring to medical advisors with specific symptoms, such as: abdominal pain, anaemia, elevated serum creatinine concentration or liver enzymes activity. Awareness of the scale of the problem enables health professionals to cooperate in educating patients. Such practices may reduce uncontrolled abuse of these drugs and related health care costs.

Weight gain in renal transplant recipients in a Polish single centre.

BACKGROUND: Excess weight is a risk factor for adverse cardiovascular events and affects patient and graft survival after renal transplantation (RT). The aim of the study was to measure the awareness of body mass index (BMI), overweight, and obesity, and to compare it with renal function, BMI, and obesity-related morbidities in renal transplant recipients (RTRs). MATERIAL AND METHODS: Fifty-three randomly-selected RTRs completed a survey. The survey results were correlated to BMI and serum creatinine at 3 months after RT (+3), 1 year after RT (+12), at the moment of survey (+S), and to the incidences of new-onset diabetes after transplantation (NODAT) and arterial hypertension (AH). RESULTS: The time between (+3) and (+S) ranged from 1 to 20 years. The questionnaire revealed that 61.8% of patients did not use BMI to evaluate their body mass, they did not distinguish between overweight and obesity, and only 40% of RTRs obtained information about obesity from physicians. At (+3), obesity was found in 9% and overweight in 27% of RTRs in comparison to 17% and 39% at (+S), respectively (p<0.05). Serum creatinine between (+3) and (+S) increased insignificantly in all patients regardless of their BMI. NODAT was found in 9.6% of RTRs and was diagnosed exclusively in the overweight group. There were no significant correlations between BMI and NODAT or AH incidences. CONCLUSIONS: BMI increases significantly after RT and is associated with higher risk of NODAT, but most RTRs are not aware of their BMI. Therefore, educational programs for this patient population should be created.

Complement components, proteolysis­related, and cell communication­related proteins detected in urine proteomics are associated with IgA nephropathy.

INTRODUCTION: IgA nephropathy (IgAN) is the most common primary glomerulonephritis. The first symptoms of IgAN are erytrocyturia or hematuria, proteinuria, and decline in renal function, or any combination of the above. One of the promising diagnostic methods is urine proteomics. OBJECTIVES: We studied urine proteomics in patients with IgAN and age- and sex­matched healthy controls. To minimize the risk of protein degradation, we proposed a new protocol for urine collection and preparation. PATIENTS AND METHODS: A total of 30 patients with IgAN and 30 controls were enrolled into the study. Thirty urine samples of the IgAN group were divided into 3 disease pooled samples (DPS I, II, and III) and 30 urine samples of the control group were divided into 3 control pooled samples (CPS I, II, and III). We used isoelectric focusing/liquid chromatography-mass spectrometry/mass spectrometry (IEF/LC­MS/MS) to detect all proteins larger than 10 kDa. RESULTS: Using qualitative analysis, we identified 761, 951, and 956 proteins in each of the 3 IEF/LC­MS/MS experiments. The results were combined, yielding a dataset with 1238 proteins identified by at least 2 peptides. The statistical analysis of the quantitative results revealed 18 proteins that were differently populated in the urine of IgAN patients compared with healthy controls. We found increased urinary concentrations of complement components, coagulation factors, extracellular matrix, intracellular, transmembrane, and other proteins in patients with IgAN. Some of them have never been linked to IgAN before. CONCLUSIONS: We demonstrated that urine proteomics is a promising tool for diagnosing and monitoring patients with IgAN.