Coronavirus Disease 2019 and Kidney Transplantation in Saudi Arabia: Outcomes and Future Opportunities.

BACKGROUND Kidney transplant services all over the world were severely impacted by the coronavirus disease 2019 pandemic. The optimum management of kidney transplant recipients with coronavirus disease 2019 remains uncertain. MATERIAL AND METHODS We conducted a multicenter cohort study of kidney transplant recipients with coronavirus disease 2019 infection in Saudi Arabia. Multivariable Cox regression analysis was used to study predictors of graft and patient outcomes at 28 days after coronavirus disease 2019 diagnosis. RESULTS We included 130 kidney transplant recipients, with a mean age of 48.7(±14.4) years. Fifty-nine patients were managed at home with daily follow-up utilizing a dedicated clinic, while 71 (54.6%) required hospital admission. Acute kidney injury occurred in 35 (26.9%) patients. Secondary infections occurred in 38 (29.2%) patients. SARS-CoV-2 antibodies testing was carried out in 84 patients, of whom 70 tested positive for IgG and/or IgM. Fourteen patients died (10.8%). A multivariable Cox regression analysis showed that age, creatinine at presentation, acute kidney injury, and use of azithromycin were significantly associated with worse patient survival. Graft loss was associated with requiring renal replacement therapy and development of secondary infections. CONCLUSIONS Despite kidney transplant recipients with coronavirus disease 2019 infection having higher rate of hospital admission and mortality compared to the general population, a significant number of them can be managed using a telemedicine clinic. Most kidney transplant patients seem to mount an antibody response following coronavirus disease 2019 infection, and it remains to be seen if they will have a similar response to the incoming vaccines.

Transplant tourism following the declaration of Istanbul: Poor outcomes and nephrologist dilemma.

AIM: Transplant tourism (TT) violates many international laws and documents. Despite all efforts, TT seems to be increasing. The aim of this study is to review outcomes of recipients of commercially transplanted kidneys since the Declaration of Istanbul. METHODS: All recipients of kidney transplantation done abroad and then returning to our centre, from September 2008 to December 2015, were included (tourists). Demographics and outcomes were collected from patients' charts. All data were compared with all recipients of living donor kidney transplants done at our centre (locals). RESULTS: A total of 86 tourists and 365 locals were included. Both groups had similar age and gender. Re-grafting rates were the same, however, more pre-emptive transplants were done abroad. TT increased over time. Tourists presented early after TT, median 17.5 (IQR 7-30) days, and 47.7% were encountered initially in the emergency department. One-year graft and patient survivals were significantly lower among tourists compared with locals (87.2% vs. 98.0%, P < 0.001 and 90.7% vs. 98.0%, P < 0.001, respectively). Tourists had a significantly higher rate of acute cellular rejection (19.8% vs. 7.1%, P < 0.001), and they sustained significantly higher rates of serious viral, bacterial and fungal infections compared with the locals. CONCLUSION: Transplant tourism seems to be increasing despite international condemnation and efforts to stop it. Outcomes are significantly worse when compared to local transplant recipients. Concerted effort is needed to better inform patients about the ethical and physical harms related to TT, and to point them towards ethically sound and medically safer alternatives.

Cost analysis of kidney transplantation in highly sensitized recipients compared to intermittent maintenance hemodialysis.

BACKGROUND: Kidney transplantation in allosensitized recipients has recently increased. Studies performing cost analysis of desensitization protocols are scarce. MATERIAL/METHODS: We performed an actual cost comparison between kidney transplantation following desensitization and maintenance hemodialysis. Group A (n=35) consisted of allosensitized recipients who underwent desensitization using immunoadsorption and/or plasmapheresis, intravenous immunoglobulin and anti-CD20 antibody who were followed for ≥ 2 years. Group B (n=49) consisted of matched patients who remained on hemodialysis throughout the study period. Actual costs of donor care, surgical procedures, out-patient visits, in-hospital admissions, medications, hemodialysis, immunoadsorption, plasmapheresis, and laboratory and radiology investigations were calculated. Health care services were provided by a single institution. RESULTS: Mortality rate was similar between both groups. The average 4-year actual total cost was $210,779 in group A and $317,186.3 in group B; respectively (p=0.017). Average total cost per patient in group A was $186,608; $14,233; $5,536; $4,402 in the first, second, third and fourth years after transplantation respectively while the average total annual cost per patient in group B was $79,296. The total cost in both groups became equal by month 31. The predicted annual cost savings in group A after 31 months was $33,943. CONCLUSIONS: Despite using costly desensitization protocols, kidney transplantation in sensitized patients provides long-term cost savings compared to maintenance hemodialysis.

Pretransplant risk score for new-onset diabetes after kidney transplantation.

OBJECTIVE: New-onset diabetes after kidney transplantation (NODAT) has adverse clinical and economic implications. A risk score for NODAT could help identify research subjects for intervention studies. RESEARCH DESIGN AND METHODS: We conducted a single-center retrospective cohort study using pretransplant clinical and laboratory measurements to construct a risk score for NODAT. NODAT was defined by hemoglobin A(1c) (HbA(1c)) ≥6.5%, fasting serum glucose ≥126 mg/dL, or prescribed therapy for diabetes within 1 year posttransplant. Three multivariate logistic regression models were constructed: 1) standard model, with both continuous and discrete variables; 2) dichotomous model, with continuous variables dichotomized at clinically relevant cut points; and 3) summary score defined as the sum of the points accrued using the terms from the dichotomous model. RESULTS: A total of 316 subjects had seven pretransplant variables with P < 0.10 in univariate logistic regression analyses (age, planned corticosteroid therapy posttransplant, prescription for gout medicine, BMI, fasting glucose and triglycerides, and family history of type 2 diabetes) that were selected for multivariate models. Areas under receiver operating curves for all three models were similar (0.72, 0.71, and 0.70). A simple risk score calculated as the sum of points from the seven variables performed as well as the other two models in identifying risk of NODAT. CONCLUSIONS: A risk score computed from seven simple pretransplant variables can identify risk of NODAT.

Relationship between inpatient hyperglycemia and insulin treatment after kidney transplantation and future new onset diabetes mellitus.

BACKGROUND AND OBJECTIVES: Approximately two-thirds of kidney transplant recipients with no previous history of diabetes experience inpatient hyperglycemia immediately after kidney transplant surgery; whether inpatient hyperglycemia predicts future new onset diabetes after transplant (NODAT) is not established. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A retrospective study was conducted to determine the risk conferred by inpatient hyperglycemia on development of NODAT within 1 year posttransplant. All adult nondiabetic kidney transplant recipients between June 1999 and January 2008 were included. Posttransplant inpatient hyperglycemia was defined as any bedside capillary blood glucose > or = 200 mg/dl or insulin therapy during hospitalization. NODAT was defined as HbA1C > or = 6.5%, fasting venous serum glucose > or = 126 mg/dl, or prescribed diet or medical therapy for diabetes mellitus. RESULTS: The study cohort included 377 patients. NODAT developed in 1 (4%) of the 28 patients without inpatient hyperglycemia, 4 (18%) of the 22 patients with inpatient hyperglycemia but not treated with insulin, and in 98 (30%) of the 327 of the patients who were diagnosed with inpatient hyperglycemia and were treated with insulin. In adjusted analyses, requirement of insulin therapy during hospitalization posttransplant was associated with a 4-fold increase in NODAT (relative risk 4.01; confidence interval, 1.49 to 10.7; P = 0.006). CONCLUSION: Development of inpatient hyperglycemia after kidney transplantation in nondiabetic patients significantly increased the risk of NODAT. Additionally, we observed a significantly increased risk of cardiovascular events in patients who developed NODAT.

Hyperglycemia during the immediate period after kidney transplantation.

BACKGROUND AND OBJECTIVES: Hyperglycemia and new-onset diabetes occurs frequently after kidney transplantation. The stress of surgery and exposure to immunosuppression medications have metabolic effects and can cause or worsen preexisting hyperglycemia. To our knowledge, hyperglycemia in the immediate posttransplantation period has not been studied. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective, observational study to characterize the prevalence and assess the pharmacologic management of hyperglycemia in kidney transplant recipients who underwent transplantation at our center between June 1999 and December 2006. Data were abstracted from electronic and pharmacy databases. RESULTS: The study cohort included 424 patients (mean age 51 yr; 58% men; 25% with pretransplantation diabetes). All patients with and 87% without pretransplantation diabetes had evidence of hyperglycemia (bedside glucose >or=200 mg/dl or physician-instituted insulin therapy), whereas the prevalence of hypoglycemia was low (4.5%). Hyperglycemia was sustained throughout hospitalization. All patients with and 66% without pretransplantation diabetes required insulin at hospital discharge. Patients with pretransplantation diabetes were treated primarily with short-acting insulin during the first 24 h after transplantation but were transitioned to long-acting insulin as the hospital stay progressed. CONCLUSIONS: Investigators have historically attempted to identify hyperglycemia after hospital discharge. Our data indicate that a substantial number of patients without pretransplantation diabetes develop hyperglycemia and require insulin during the hospital phase of their care immediately after kidney transplantation. Prospective studies are needed to delineate factors that contribute to development of new-onset diabetes after transplantation among patients with transient hyperglycemia.

Plasmapheresis therapy for rare but potentially fatal reaction to rituximab.

Rituximab (Rituxan), a genetically engineered chimeric murine and human IgG1 monoclonal antibody directed against CD20 antigen, is an emerging drug used for a wide spectrum of disease processes and found to be relatively safe. We report a near-fatal reaction to rituximab, which started 30 min after infusion and worsened over 24 to 48 h, resulting in hemodynamic and respiratory compromise that necessitated both intubation and high-dose vasopressors. Subsequent treatment with plasmapheresis helped stabilize and improve the patient's clinical condition, and the patient was discharged home on hospital day 5. There is no specific treatment for these severe and sometimes fatal reactions except supportive care with plasmapheresis. With the increased use of rituximab therapy in the medical management of numerous diseases, those in the medical community need to be cognizant of the rare fatal or near-fatal infusion reaction and the benefit that may accrue from plasmapheresis therapy.

Sirolimus induced dyslipidemia in tacrolimus based vs. tacrolimus free immunosuppressive regimens in renal transplant recipients.

BACKGROUND: Sirolimus is a potent immunosuppressive drug that has been shown to decrease the incidence of rejection post renal transplantation. Dyslipidemia is a well recognized side effect of sirolimus therapy, which may have an impact on patient survival and post-transplant cardiac morbidity and mortality. It is unknown whether sirolimus-induced dyslipidemia is aggravated by concomitant use of tacrolimus which may also affect lipid profile. To compare sirolimus induced dyslipidemia in tacrolimus based vs. tacrolimus free regimens in renal transplant recipients. MATERIAL/METHODS: Patients who received sirolimus post kidney transplantation for at least nine sequential months were included in our retrospective study. Forty-eight renal transplant recipients were divided into 2 groups based on the immunosuppressive regimen; Group 1 received prednisone, sirolimus and mycophenolate mofetil, while Group 2 received prednisone, sirolimus, mycophanolate mofetil and tacrolimus. Lipid profile was assessed pre-transplantation and at one, three, six and nine months post sirolimus therapy. RESULTS: Both groups showed significant but comparable elevation in total cholesterol, LDL-C and triglycerides with sirolimus therapy. The elevation was evident starting from the first month of sirolimus administration and remained to the ninth month at the end of the follow up period. At first month, mean triglycerides was 2.68 and 2.6 mmol/L (P>0.1) and mean total cholesterol was 6.3 and 5.7 mmol/L in group 1 and 2 (P>0.1); respectively. By the ninth month, triglycerides level was 2.6 and 3.9 mmol/L (P>0.1) while mean total cholesterol level was 6.2 and 6.1 mmol/L (P>0.1) in group 1 and 2 respectively. Lipid-lowering agents and total steroids dose were similar in both groups. CONCLUSIONS: Hypercholesterolemia and hypertriglyceridemia secondary to sirolimus therapy is independent from concomitant tacrolimus use. Lipid-profile should be monitored in all renal transplant recipients receiving sirolimus as early as first month regardless of the immunosuppressive regimen used.

The Kidney Transplant Program at King Faisal Specialist Hospital and Research Center.

More than 1,000 kidney transplants were performed at King Faisal Specialist Hospital and Research Center (KFSH&RC) between 1981-2005. The majority were from living donors. The renal transplant program at KFSH&RC was fundamentally transformed in 2001 with the introduction of renal transplant physicians and the emphasis on multidisciplinary teamwork. This fundamental change has resulted in tripling of the size of the program and in expanding its scope of services to include high-risk patients (highly sensitized with a positive crossmatch). These achievements were coupled with excellent outcome data. The 5-year patient and graft survival rates for adult transplants performed during 2000-2005 were 97% and 94%, respectively, for 268 living donor transplants and 97% and 76%, respectively, for 73 deceased donor transplants. The kidney transplant program at KFSH&RC is now a leading center in the Region and it ranks among the leading kidney transplant centers in the world in terms of size, scope of services and outcomes.

Outcomes of renal transplantation following bone marrow transplantation.

This single center retrospective study was undertaken to determine the outcome of kidney transplantation (KT) after bone marrow transplantation (BMT) and also to determine the need for immunosuppressive therapy after KT when the BMT marrow donor is the KT donor. Kidney transplantation was performed in 10 patients with BMT nephropathy (BMTN). In six patients, the KT donor was the BMT donor; these individuals were given no long-term immunosuppression. Four other patients received KT from donors who were not the marrow donor (two living donors, two cadaveric donors). After median follow up of 34 months, no patient had an episode of acute rejection. All graft losses (n = 4) resulted from patient death. Three were because of infectious processes, including two infectious deaths in patients not on immunosuppression. Median estimated actuarial patient and graft survival (Kaplan-Meier) was 105 months. We conclude that patients with BMTN who receive KT from their marrow donor do not require immunosuppression. Whether immunosuppressive therapy is given or not, outcome appears to be determined largely by BMT-related immune dysfunction.