Transforming Growth Factor-ß1 C (+869) T Codon 10 Gene Polymorphism Significantly Associated with Rates of SARS-CoV-2 in Kidney Transplant Recipients in Kuwait.

OBJECTIVES: COVID-19, which began in Wuhan, China, in December 2019, has caused a large global pandemic and poses a serious threat to public health. As of March 20, 2023, over 13 billion COVID-19 vaccine doses had been administered worldwide, with the United States accounting for almost 672 million of total administered vaccine doses. Some COVID-19 patients experience sudden and rapid deterioration with onset of fatal cytokine storm syndrome, which increased interest in the mechanisms, diagnosis, and therapy of cytokine storm syndrome. Although the prototypic concept of cytokine storm syndrome was first proposed 116 years ago, we have only begun to study and understand it over the past 30 years. Clinical data suggest that Th1, Th2, and Th3 and macrophage origin cytokines have effects on cytokine storm syndrome. We aimed to study the effects of cytokine gene polymorphisms in cytokine storm syndrome mechanisms and progression of COVID-19 among kidney transplant recipients. MATERIALS AND METHODS: We screened 309 patients who had undergone kidney transplant at the Hamad Al Essa organ transplant center. From February 2020 through February 2022, 64 patients (20.7%) developed COVID-19 infection. Patient blood samples were screened for the key Th1, Th2, Th3, and macrophage cytokines gene polymorphisms. RESULTS: We observed that only transforming growth factor-ß C (+869) T codon 10, but not interferon-γ T (+874) A, interleukin 6 G (-174) C, and interleukin 4C (-490) T, was significantly associated with progression of COVID-19 and cytokine storm syndrome mechanisms (P < 0.001). CONCLUSIONS: Our finding can be a profoundly important factor in the initiation of cytokine storm syndrome and progress of COVID-19.

Effect of Repeated Structured Diabetes Education on Lifestyle Knowledge and Self-Care Diabetes Management in Kidney Transplant Patients With Posttransplant Diabetes.

OBJECTIVES: Diabetes knowledge among kidney transplant recipients with posttransplant diabetes has not been clearly assessed. We evaluated whether diabetes education in kidney transplant recipients with posttransplant diabetes affected self-care, metabolic control variables, and reversibility of early diabetic microangiopathies. MATERIALS AND METHODS: In this prospective randomized controlled study, we enrolled 210 renal transplant recipients with posttransplant diabetes. Group 1 patients (n = 140) received structured diabetes education, and group 2 patients (n = 70) received conventional education. Patient data were collected through patient identification and metabolic control parameter forms and a diabetes self-care scale questionnaire (scores between 0 and 7). RESULTS: Diet knowledge improved and waist circumference was reduced with mild to moderate exercise in group 1 (P < .001), despite no differences between the 2 groups in mean body weight or body mass index. Patients in group 1 (structured diabetes education with repeated reinforcement) showed significant improvement in healthy lifestyle parameter scores versus group 2 (P < .05) and versus values before education (P < .05). At end of study, these achievements were translated into proper blood sugar monitoring, management of both hypoand hyperglycemia, improvements in logbook use and healthy sharp disposal, Ramadan fasting, sick day management, and knowledge on the importance of HbA1c (P < .05), which translated to decrease of HbA1c in group 1 by 1.35%. In group 1, proteinuria decreased significantly compared with before education and compared with group 2 values (P = .016). Diabetic retinopathy and neuropathy remained comparable between groups (P > .05). CONCLUSIONS: Structured diabetes education improved lifestyle knowledge, self-care diabetes management, and metabolic control variables among kidney transplant recipients with posttransplant diabetes. Structured diabetes education also resulted in partial reversibility of the present early diabetic nephropathy. We recommended such education to be delivered to all kidney transplant recipients with diabetes.

Impact of Pretransplant Dialysis Modality on Posttransplant Outcomes: A Single-Center Experience.

OBJECTIVES: It remains unclear whether posttransplant outcomes differ according to the pretransplant dialysis modality (peritoneal dialysis vs hemodialysis). Our aim was to assess posttransplant outcomes in patients with different predialysis modalities. MATERIALS AND METHODS: Two thousand two hundred fifty-eight kidney recipients following up in Hamed Alessa Organ transplant center in Kuwait were included and divided into two groups according to pre-transplant dialysis modality: Group 1: those who received hemodialysis (HD) and group 2: those with peritoneal dialysis (PD). Demographics, pretransplant and posttransplant comorbidities, and patient and graft outcomes were studied. RESULTS: There were 1956 patients on hemodialysis, and 302 patients were on peritoneal dialysis. Most were male patients (1456 vs 802 female patients), with comparable mean age (P = .34). Chronic glomerulonephritis and diabetic nephropathy represented the most common original kidney disease before transplant (27.6% and 21.4%, respectively), with higher prevalence of glomerulonephritis in group 1 and diabetic nephropathy in group 2 (P = .001). The 2 groups were comparable with regard to immunosuppression (induction and maintenance) (P > .05). Posttransplant diabetes and hypertension were significantly higher in the hemodialysis group (P = .004 and P = 003, respectively). There was no significant difference between the 2 groups with regard to the graft outcome (P = .86). However, patient survival was significantly higher in the hemodialysis group (81.2% vs 64.4%). CONCLUSIONS: Compared with peritoneal dialysis, pretransplant hemodialysis is associated with better posttransplant patient survival despite no difference in the graft outcome. Diabetes-related complications could be attributed to such outcomes.

Inhibition of Proprotein Convertase Subtilisin/Kexin-9 After Kidney Transplant: Single-Center Experience Among Patients With High Cardiovascular Risk.

OBJECTIVES: The benefits of reduction in low-density lipoprotein cholesterol by evolocumab by nearly 60% has not been evaluated among kidney transplant recipients to our knowledge. We assessed the efficacy and safety of evolocumab, a proprotein convertase subtilisin/kexin-9 inhibitor, in reducing lipids and cardiovascular events among kidney transplant recipients in a randomized controlled study. MATERIALS AND METHODS: Between June 2017 and June 2019, we enrolled 197 kidney transplant recipients with high cardiovascular risk score (>20). Patients who received evolocumab (140 mg/2 weeks) comprised group 1 (n = 98), and patients maintained on statin therapy comprised group 2 (n = 99). We followed patients clinically and with necessary laboratory investigations over 24 months. RESULTS: The 2 groups had comparable demographic characteristics (P > .05). Before enrollment in the study, smokers were significantly more prevalent in group 1, whereas posttransplant diabetes mellitus was more prevalent in group 2 (P = .033). Moreover, baseline serum creatinine was higher in group 1, whereas immunosuppression was equivalent in both groups (P > .05). We found no significant differences between the 2 groups concerning cardiovascular events, and both graft and patient outcomes were comparable (P > .05). The higher baseline cholesterol in group 1 (5.5 vs 4.7 mmol/L; P < .001) decreased significantly after 3 months and thereafter (P = .031) compared with levels in group 2 and baseline values (P < .001). We reported 2 cases of acute myocardial infarction and 1 atrial fibrillation in group 2. CONCLUSIONS: Proprotein convertase subtilisin/kexin-9 inhibitors, as an added therapy to statins, are safe and effective in treating hypercholesterolemia after kidney transplant. Evolocumab can minimize cardiovascular events after kidney transplant in patients with high events at baseline. Longer-term trials with larger number of patients are needed to confirm its beneficial effects on cardiovascular complications and patient and graft survival.

Kidney Transplant Recipient With Cerebral Paradoxical Embolism Following Recurrent Idiopathic Deep Vein Thrombosis and Pulmonary Embolism: Case Report and Review of the Literature.

Paradoxical embolism occurs when a thrombus crosses an intracardiac defect into the systemic circulation. Here, we present the case of a 35-yearold male kidney transplant recipient with a cerebral paradoxical embolism associated with a spontaneous venous thromboembolism. This patient had recurrent deep venous thrombosis and showering emboli to the lung and paradoxically to the brain through patent foramen ovale, and we treated him successfully. The role of bubble echocardiography was essential in diagnosis to avoid contrast-induced nephropathy. This is the first successfully managed case of a kidney transplant recipient with recurrent idiopathic deep vein thrombosis, pulmonary embolism, and cerebral paradoxical embolism. Bubble echocardiography was an excellent alternative to contrast angiography to avoid nephrotoxicity. Vitamin K antagonists are superior to direct oral anticoagulants, especially among nonadherent/noncompliant patients.

Full Correction of Posttransplant Anemia Is Associated With Stabilized Cardiac Dimensions Among Kidney Transplant Recipients: A Prospective Randomized Controlled Trial.

OBJECTIVES: Posttransplant anemia might be associated with cardiovascular morbidity and increased mortality. To our knowledge, the debate on anemia correction has neither been revisited nor decided definitively. We aimed to assess the effects of full correction of posttransplant anemia on the cardiovascular system and quality of life among renal transplant recipients with stable graft function who were using erythropoietin-stimulating agents. MATERIALS AND METHODS: We enrolled 247 kidney recipients with stable graft function to be assessed for anemia. Eligible patients were randomized to achieve targeted hemoglobin of 11 to 12 g/dL (group 1, n = 183) or of 13 to 15 g/dL (group 2, n = 64) with the use of erythropoietin-stimulating agents. Patients underwent monthly clinical and laboratory evaluations of kidney graft function. Quality of life and echocardiography were assessed at study start and at 12 months. RESULTS: The 2 groups were comparable regarding pretransplant characteristics. In group 2, we observed comparable posttransplant complications (P > .05) but better graft function at 6 months and better cardiac indexes at 1 year of the study (P < .05). At 12 months, quality of life had improved after full correction of posttransplant anemia in the renal transplant recipients who received erythropoietinstimulating agents. CONCLUSIONS: Full correction of posttransplant anemia in renal transplant recipients was associated with improved quality of life and cardiac indexes without an effect on cardiovascular comorbidity.

Acute Kidney Injury Among COVID-19-Positive Patients Is Associated With Higher Mortality: A Single-Center Experience.

OBJECTIVES: Renal complications of COVID-19 are not yet well studied. We aimed to evaluate acute kidney injury prevalence among hospitalized patients with COVID-19 infection and explore its effect on patient outcomes. MATERIALS AND METHODS: We retrospectively evaluated 586 hospitalized patients with COVID-19. Of these patients, 267 (45.5%) developed acute kidney injury, as classified according to the Kidney Disease Improving Global Outcomes guidelines. We compared this group with 319 patients (54.5%) without acute kidney injury. RESULTS: Most patients in both study groups were men; mean age was 60.8 ± 14 versus 51.7 ± 16 years. Comorbid conditions that were substantially predominant among patients with acute kidney injury were diabetes mellitus (64% vs 42.9%), hypertension (72.6% vs 43.5%), and ischemic heart disease (25% vs 14.7%). Fever, cough, shortness of breath, and dehydration were the main presentations among patients with acute kidney injury, and patients in this group had greater prevalence of radiological findings concordant with COVID-19 (86.8% vs 59.8%). Sepsis, volume depletion, shock, arrhythmias, and acute respiratory distress syndrome were higher in patients with acute kidney injury. Anticoagulation (85% vs 59.2%), vasopressors, plasma infusions, antimicrobials, and steroids were more frequently used in patients with acute kidney injury. More patients with acute kidney injury had acute respiratory failure requiring mechanical ventilation (62.3% vs 32.9%), with higher overall mortality rate (63.2% vs 31.1%). CONCLUSIONS: We found more frequent prevalence of acute kidney injury associated with severe COVID-19 than shown in reports from Chinese, European, and North American cohorts. Patients with COVID-19 who developed acute kidney injury had risk factors such as hypertension and diabetes, greater need for mechanical ventilation, were males, and were older age. Mortality was high in this population, especially among older patients and those who developed Kidney Disease Improving Global Outcomes stage 3 disease.