SARS-CoV-2 in Kidney Transplant and Waitlisted Patients During the First Peak: The Welsh Experience.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) global pandemic has led to many health care services, including transplantation, being temporarily suspended. For transplantation to safely recommence, there is a need to understand the effects of SARS-CoV-2 in transplant and waitlist patients. We identified 21 patients with proven SARS-CoV-2 infection (13 transplant; 8 waitlist) during the first peak of coronavirus disease 2019 in Wales. Median patient age was 57 years (range, 24-69), 62% were male, and all were white. Median body mass index was 29 kg/m2 (range, 22-42), and 81% had 1 or more significant comorbidities. Median time from transplant to SARS-CoV-2 infection was 135 months (range, 9-356) and median time since being listed was 17.5 months (range, 5-69) for waitlisted patients. Seventeen patients were admitted to the hospital (81%), 18% (n = 3) in intensive care unit, and 5 patients died (4 transplant recipients and 1 waitlist patient; 24%). Two of the 4 transplant patients who died had recent malignancy. Although the mortality of hospitalized transplant patients was high, their infection rate of 0.87% meant that the overall mortality of transplant patients due to SARS-CoV-2 was low and comparable to that of patients on the waitlist. These data provide confidence in restarting the transplant program, provided that a series of measures aiming to avoid infections in newly transplanted patients are taken.

GRANULOMATOUS DISEASE OF UNUSUAL SITES CAUSING HYPERCALCEMIA: TWO CASE REPORTS.

OBJECTIVE: Hypercalcemia with suppressed parathyroid hormone (PTH) levels is mostly due to granulomatous disease (GD) or neoplastic disease. In GD, autonomous activity of extra-renal 1α-hydroxylase enzyme is usually the underlying cause. We describe a pair of cases where hypercalcemia resulted from GD of unusual sites posing significant diagnostic challenges. METHODS: We describe 2 cases of PTH-independent hypercalcemia due to GD of the prostate gland and the stomach. RESULTS: Both cases presented with marked hypercalcemia and suppressed PTH levels. Case 1 is an elderly male who presented with marked symptomatic hypercalcemia on multiple occasions. Investigations revealed elevated levels of 1,25-dihydroxyvitamin D3 and prostate-specific antigen but normal PTH-related protein. Transrectal biopsy of the prostate gland confirmed the presence of chronic granulomatous prostatitis. The patient responded very well to steroids which entirely normalized his calcium level. Case 2 is a male who presented similarly with significant hypercalcemia but had upper gastrointestinal symptoms and anemia at onset. Endoscopy and biopsy established the presence of granulomatous gastritis likely due to Crohn disease which responded to steroids resulting in normalization of calcium levels within a short span of time. CONCLUSION: While the majority of PTH-independent hypercalcemia cases are due to GDs of lymph nodes or malignancy, our cases indicate that in uncertain cases, granulomatous processes involving unusual sites should be considered in the evaluation of hypercalcemia with suppressed PTH.

Impact of expanded criteria variables on outcomes of kidney transplantation from donors after cardiac death.

INTRODUCTION: To expand the donor pool, kidney transplants are being performed using donors who were previously considered unacceptable. We applied the United Network for Organ Sharing criteria to define expanded criteria donors (ECD) within the donation after cardiac death (DCD) and donation after brain stem death (DBD) cohorts. We compared outcomes of DCD and DBD transplants with and without (standard criteria donor [SCD]) the ECD criteria. METHODS: This was a single-center retrospective study of all deceased donor transplants from 2004 to 2010 (n=359). Four groups were identified--DBD-SCD (n=154), DBD-ECD (n=93), DCD-SCD (n=78), and DCD-ECD (n=34). Kaplan-Meier analysis of graft and patient survival and multiple regression analysis of 1-year graft function were performed. RESULTS: One-year and two-year uncensored graft survivals were similar between DCD-ECD and DCD-SCD cohorts (1 year, 90% and 93%; 2 years, 81% and 93% respectively; log-rank test P=0.2). Median estimated glomerular filtration rate (eGFR) was lower in DCD-ECD recipients at 12 months (41 vs. 53 mL/min, P=0.003) and 24 months (33 vs. 54 mL/min, P<0.001) compared with DCD-SCD recipients. Compared with DBD-ECD recipients also at 24 months, DCD-ECD recipients showed a lower graft function (median, eGFR 33 vs. 47 mL/min; P=0.007) but similar graft survival. Expanded criteria donor status (B=-9.7, P=0.01) was associated with a lower 1-year eGFR within the DCD cohort, with donor age (B=-0.42, P=0.002) being the only significant ECD variable. CONCLUSION: Short-term graft survival in DCD-ECD transplants was comparable to DCD-SCD and DBD-ECD transplants albeit with poorer allograft function at 2 years. Quality-of-life studies are needed to determine the true value of these transplants, particularly when performed to older recipients.

Long-term progression of abnormal glucose tolerance and its relationship with the metabolic syndrome after kidney transplantation.

BACKGROUND: Metabolic syndrome (MS) diagnosed early after kidney transplantation is a risk factor for developing new-onset diabetes. The aim of this study was to examine whether glucose intolerance and MS identified late after transplantation influence the progression of glycemic abnormalities in kidney transplant recipients. METHODS: This is a retrospective study in which 76 non-diabetic renal transplant recipients underwent oral glucose tolerance tests (OGTT) in 2005 to 2006 (baseline) and then in 2011 to 2012 (follow-up). MS was identified using the International Diabetes Federation criteria and OGTT was interpreted according to the WHO classification. RESULTS: At follow-up, median time from transplantation was 11.1 years (range 6.2-23.8). Mean 0-hour and 2-hour plasma glucose levels were significantly higher at follow-up compared to baseline (5.7 ± 0.7 vs. 5.9 ± 0.9 mmol/L, P=0.03 and 6.7 ± 1.9 vs. 7.5 ± 2.8 mmol/L, P=0.03, respectively). The proportion of patients with an abnormal OGTT increased from 42% at baseline to 61% at follow-up (P=0.007). Patients with MS were more likely to progress to a higher degree of glucose intolerance compared to those without MS (58% vs. 27%, P=0.01). On multivariable logistic regression adjusted for age and gender, MS was significantly associated with the progression of glucose intolerance (OR 3.5, CI 1.2-9.9, P=0.01), as was a fasting glucose greater than 5.6 mmol/L (OR 4.8, CI 1.6-14.8, P=0.006). CONCLUSION: MS is a risk factor for the progression of glucose intolerance in renal transplant recipients in the late posttransplant period. Therefore, MS has to be considered in tandem with OGTT results to assess cardiovascular risk.

Role of insulin resistance indices in predicting new-onset diabetes after kidney transplantation.

New-onset diabetes mellitus (NODAT) is a serious complication following renal transplantation. In this cohort study, we studied 118 nondiabetic renal transplant recipients to examine whether indices of insulin resistance and secretion calculated before transplantation and at 3 months post-transplantation are associated with the development of NODAT within 1 year. We also analysed the long-term impact of early diagnosed NODAT. Insulin indices were calculated using homeostasis model assessment (HOMA) and McAuley's Index. NODAT was diagnosed using fasting plasma glucose. Median follow-up was 11 years. The cumulative incidence of NODAT at 1 year was 37%. By logistic regression, recipient age (per year) was the only significant pretransplant predictor of NODAT (OR 1.04, CI 1.009-1.072), while age (OR 1.04, CI 1.005-1.084) and impaired fasting glucose (OR 2.97, CI 1.009-8.733) were significant predictors at 3 months. Pretransplant and 3-month insulin resistance and secretion indices did not predict NODAT. All-cause mortality was significantly higher in recipients developing NODAT within 1 year compared with those remaining nondiabetic (44% vs. 22%, log-rank P = 0.008). By Cox's regression analysis, age (HR 1.075, CI 1.042-1.110), 1-year creatinine (HR 1.007, CI 1.004-1.010) and NODAT within 3 months (HR 2.4, CI 1.2-4.9) were independent predictors of death. In conclusion, NODAT developing early after renal transplantation was associated with poor long-term patient survival. Insulin indices calculated pretransplantation using HOMA and McAuley's Index did not predict NODAT.

Influence of delayed graft function and acute rejection on outcomes after kidney transplantation from donors after cardiac death.

BACKGROUND: Delayed graft function (DGF) and acute rejection (AR) exert an adverse impact on graft outcomes after kidney transplantation using organs from donation after brain-stem death (DBD) donors. Here, we examine the impact of DGF and AR on graft survival in kidney transplants using organs from donation after cardiac death (DCD) donors. METHODS: We conducted a single-center retrospective study of DCD and DBD donor kidney transplants. We compared 1- and 4-year graft and patient survival rates, as well as death-censored graft survival (DCGS) rates, between the two groups using univariate analysis, and the impact of DGF and AR on graft function was compared using multivariate analysis. RESULTS: Eighty DCD and 206 DBD donor transplants were analyzed. Median follow-up was 4.5 years. The incidence of DGF was higher among DCD recipients (73% vs. 27%, P<0.001), and AR was higher among DBD recipients (23% vs. 9%, P<0.001). One-year and 4-year graft survival rates were similar (DCD 94% and 79% vs. DBD 90% and 82%). Among recipients with DGF, the 4-year DCGS rate was better for DCD recipients compared with DBD recipients (100% vs. 92%, P=0.04). Neither DGF nor AR affected the 1-year graft survival rate in DCD recipients, whereas in DBD recipients, the 1-year graft survival rate was worse in the presence of DGF (88% vs. 96%, P=0.04) and the 4-year DCGS rate was worse in the presence of AR (88% vs. 96%, P=0.04). CONCLUSION: Despite the high incidence of DGF, medium-term outcomes of DCD kidney transplants are comparable to those from DBD transplants. Short-term graft survival from DCD transplants is not adversely influenced by DGF and AR, unlike in DBD transplants.