Delayed exacerbation of COVID-19 pneumonia in vaccinated kidney transplant recipients receiving immunosuppressants: a case series.

Coronavirus disease 2019 (COVID-19) increases the risk of mortality and hospitalization in immunocompromised patients, including kidney transplant recipients (KTRs) receiving immunosuppressants. Several vaccines for COVID-19 have been developed and proven effective in decreasing the incidence of COVID-19 and the rate of progression to severe COVID-19. However, breakthrough infections have also been reported in vaccinated patients. We report cases from our center of delayed exacerbated pneumonia from COVID-19 in vaccinated KTRs receiving immunosuppressants. Of the 900 KTRs who had been vaccinated for COVID-19 and were followed up at our center from January 1, 2022, to April 30, 2022 (during the Omicron variant outbreak), 126 contracted COVID-19 (incidence rate, 14%). Thirty-four (27%) in this group were hospitalized due to COVID-19. Twenty patients did not have pneumonia but had symptoms of upper respiratory tract infection or diarrhea, which improved with conservative treatment. Nine of the 14 patients with pneumonia had delayed onset or exacerbated pneumonia 1 week after their COVID-19 diagnosis. They were treated with remdesivir, and most recovered. One patient died due to progressive pneumonia and pneumothorax. It is important that KTRs who are taking immunosuppressants be observed closely and for a prolonged period after a COVID-19 diagnosis, irrespective of their COVID-19 vaccination status.

Association of nutritional status with osteoporosis, sarcopenia, and cognitive impairment in patients on hemodialysis.

BACKGROUND AND OBJECTIVES: Inadequate nutrition in patients on hemodialysis causes various complications. This study aimed to investigate the association between nutritional status and risk of osteoporosis, sarcopenia, and cognitive impairment in patients on hemodialysis. METHODS AND STUDY DESIGN: We enrolled 131 older patients on maintenance hemodialysis. Geriatric Nutrition Risk Index (GNRI) was used to assess nutritional status. Patients were divided into quartile groups according to the GNRI. Dual-energy X-ray absorptiometry, bioimpedance analysis and handgrip strength measurement, and the Korean version of the Montreal Cognitive Assessment were used to assess osteoporosis, sarcopenia, and cognitive impairment, respectively. Biochemical laboratory tests were also performed before mid-week hemodialysis session. RESULTS: Patients from higher GNRI quartiles had a lower prevalence of osteoporosis and sarcopenia. Cognitive impairment was not associated with any GNRI quartile. In the multivariable models, longer dialysis periods (OR 1.696, 95% CI 1.053-2.729, p=0.030) and higher intact parathyroid hormone levels (OR 3.136, 95% CI 1.781-5.518, p<0.001) were significantly associated with osteoporosis risk. GNRI quartile 2 (OR 0.064, 95% CI 0.005-0.883, compared to quartile 1, p=0.040) and higher hemoglobin A1c levels (OR 3.728, 95% CI 1.033-86.4, p=0.043) were associated with a higher sarcopenia risk. Lower hemoglobin levels (OR 0.585, 95% CI 0.360-0.950, p=0.030) were associated with a higher risk of cognitive impairment. CONCLUSIONS: In patients on hemodialysis, inadequate nutrition was associated with the risk of osteoporosis and sarcopenia, but not cognitive impairment. Proper nutritional assessment and management in these patients could prevent complications related to bone and muscle loss.

ABO incompatible living donor kidney transplantation in Korea: highly uniform protocols and good medium-term outcome.

The organ shortage is as serious in Korea as in other parts of the world. As about one-third of the potential living donors are ABO incompatible (ABOi), transplantation across the blood group barrier can help overcome this shortage. One hundred and twenty-five ABOi kidney transplantations (KTs) were performed between 2007 and 2010 in Korea. We collected the perioperative and follow-up data for 118 of these patients until September 2011. The preconditioning and immunosuppressive protocols were almost identical across the different transplant centers, with rituximab but no splenectomy; pre-transplant plasmapheresis (PP) with target anti-A/B titer 8 or 16 on transplant day, on-demand, rather than routine, post-transplant PP, and tacrolimus-based immunosuppressants. The number of patients and participating centers showed a rapid increase over time, and in 2010, ABOi KT (n = 79) comprised 10% of all the living donor KTs in Korea. The mean follow-up period was 21 months (range, 1-56 months). Sixteen (14%) patients developed acute rejection, and three of these had antibody-mediated rejection (AMR). Two-yr patient and graft survival were 99.2% and 97.5%, respectively. No graft was lost due to AMR. ABOi KT is rapidly expanding in Korea with excellent medium-term outcome and will help mitigate the organ shortage.

Hypoxia-inducible factor activation protects the kidney from gentamicin-induced acute injury.

Gentamicin nephrotoxicity is one of the most common causes of acute kidney injury (AKI). Hypoxia-inducible factor (HIF) is effective in protecting the kidney from ischemic and toxic injury. Increased expression of HIF-1α mRNA has been reported in rats with gentamicin-induced renal injury. We hypothesizd that we could study the role of HIF in gentamicin-induced AKI by modulating HIF activity. In this study, we investigated whether HIF activation had protective effects on gentamicin-induced renal tubule cell injury. Gentamicin-induced AKI was established in male Sprague-Dawley rats. Cobalt was continuously infused into the rats to activate HIF. HK-2 cells were pre-treated with cobalt or dimethyloxalylglycine (DMOG) to activate HIF and were then exposed to gentamicin. Cobalt or DMOG significantly increased HIF-1α expression in rat kidneys and HK-2 cells. In HK-2 cells, HIF inhibited gentamicin-induced reactive oxygen species (ROS) formation. HIF also protected these cells from apoptosis by reducing caspase-3 activity and the amount of cleaved caspase-3, and -9 proteins. Increased expression of HIF-1α reduced the number of gentamicin-induced apoptotic cells in rat kidneys and HK-2 cells. HIF activation improved the creatinine clearance and proteinuria in gentamicin-induced AKI. HIF activation also ameliorated the extent of histologic injury and reduced macrophage infiltration into the tubulointerstitium. In gentamicin-induced AKI, the activation of HIF by cobalt or DMOG attenuated renal dysfunction, proteinuria, and structural damage through a reduction of oxidative stress, inflammation, and apoptosis in renal tubular epithelial cells.

Kidney transplantation after desensitization in sensitized patients: a Korean National Audit.

INTRODUCTION: The number of end-stage renal disease (ESRD) patients with preformed antibodies waiting for a kidney transplant has been increasing lately. We conducted a nationwide study on the outcomes of kidney transplantation after desensitization in Korea. METHODS: Six transplant centers have run desensitization programs. The patients who underwent living donor kidney transplantation after desensitization from 2002 to 2010 were retrospectively analyzed. RESULTS: A total of 86 cases were enrolled. Thirty-five of these were cases of re-transplantation (40.7 %). Indications of desensitization were positive complement-dependent cytotoxicity (CDC) cross-match responses (CDC(+), 36.0 %), positive flow-cytometric cross-match responses (FCX(+), 54.7 %), and positive donor-specific antibodies (DSA(+), 8.1 %). The desensitization protocols used pre-transplant plasmapheresis (95.3 %), intravenous immunoglobulin (62.8 %), and rituximab (67.4 %). Acute rejection occurred in 18 patients (20.9 %), graft failure occurred in 4 patients, and the 3-year graft survival rate was 93.8 %. The presence of DSA increased the acute rejection rate (P = 0.015) and decreased the 1-year post-transplant estimated glomerular filtration rate (P = 0.006). Although rejection-free survival rates did not differ significantly between the CDC(+) and FCX(+) groups, the 1-year estimated glomerular filtration rate was lower in the CDC(+) group (P = 0.010). Infectious and significant bleeding complications occurred in 15.5 % and 4.7 % of cases, respectively. CONCLUSION: Kidney transplantation after desensitization had good graft outcomes and tolerable complications in Korea, and therefore, this therapy can be recommended for sensitized ESRD patients.