Relative Survival of Transplant Patients: Quantifying Surplus Mortality Among Renal Transplant Recipients Compared With the General Population

Abstract Background Compared to the general population, the risk of death is substantially higher in renal transplant recipients than in age and sex matched individuals in the general population. In the general population, coronary artery calcification (CAC) predicts all-cause and cardiovascular mortality. In this study, we aimed to analyze these relationships in renal transplant recipients. Methods We examined 178 renal transplant patients in this prospective observational cohort study. We measured coronary artery calcification with multidetector spiral computed tomography using Agatston score at multiple time points. Overall, 411 scans were performed in 178 patients over an average 12.8 years follow up. The clinical end point was a composite including all cause death and non-fatal cardiovascular events. Data analysis was performed by the joint model. Results During a follow-up of 12.8 ± 2.4 years, coronary calcification progressed over time (P < 0.001) and the clinical endpoint occurred in 54 patients. In the analysis by the joint model both the baseline CAC score and the CAC score progression were strongly associated with the incidence rate of the composite event (HR: 1.261, 95% CI: 1.119-1.420, p = 0.0001) Conclusion Coronary artery calcification at baseline and coronary calcification progression robustly predict the risk of death and cardiovascular events in renal transplant recipients. These findings support the hypothesis that the link between the calcifying arteriopathy of renal transplant patients and clinical end points in these patients is causal in nature.

Download Full-text

Cytomegalovirus the Predominant Cause of Pneumonia in Renal Transplant Patients: A Two-year Study of Pneumonia in Renal Transplant Recipients with Evaluation of Fiberoptic Bronchoscopy

Scandinavian Journal of Infectious Diseases ◽

10.3109/00365548909035693 ◽

1989 ◽

Vol 21 (3) ◽

pp. 245-253 ◽

Cited By ~ 15

Author(s):

Nadja Heurlin ◽

Christina Brattström ◽

Gunnar Tydén ◽

Anneka Ehrnst ◽

Jan Andersson

Keyword(s):

Renal Transplant ◽

Fiberoptic Bronchoscopy ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Transplant Patients ◽

Renal Transplant Patients

Download Full-text

Human BK Polyomavirus Nephropathy (BKVN) In Non- Kidney-Transplant Patients

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.258 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S118-S118

Author(s):

Y Chen Wongworawat ◽

C Zuppan

Keyword(s):

Renal Transplant ◽

Kidney Transplant ◽

Graft Loss ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Transplant Patients ◽

Bk Polyomavirus ◽

Pathologic Features ◽

Renal Biopsies ◽

Renal Transplant Patients

Abstract Introduction/Objective Human BK polyomavirus nephropathy (BKVN) occurs in up to 10% of renal transplant recipients, and can result in graft loss. Transplant biopsy is the gold standard to diagnose BKVN, and SV40 immunohistochemical (IHC) staining is helpful in confirming the diagnosis. BKVN is uncommon outside the setting of renal transplantation. To understand more about its occurrence in other contexts, we reviewed our renal biopsies files for cases of BKVN. Methods Our renal biopsy files for the past 20 years were reviewed for all cases with a diagnosis of BKVN or polyoma virus infection, and the clinical characteristics of the affected patients noted. Results Evidence of BKVN was found in 44 renal biopsies, of which 39 (86%) were renal transplant patients. Of the remaining five patients (14%), two had undergone heart transplantation, one lung transplantation, one was undergoing chemotherapy for acute lymphoblastic leukemia, and one patient had active HIV infection. All patients had elevated serum creatinine, and four out of five patients had documented BK viremia. Four of the five biopsies showed typical tubular injury with viral nuclear cytopathic changes (inclusions). In the lung transplant patient, the biopsy showed advanced chronic tubulointerstitial injury without distinct viral inclusions, but SV40 staining confirmed the presence of BK virus antigen. Conclusion The BKVN is distinctly uncommon outside the context of kidney transplantation. In our series, 14% of patients with BKVN were not kidney transplant recipients, but all were immune compromised in some fashion. The pathologic features of BKVN appear similar, regardless of whether the host is a renal transplant recipient or not. Although uncommon, it is important to consider the possibility of BKVN in non-renal transplant patients with persistent or progressive renal dysfunction.

Download Full-text

Cigarette Smoking in Renal Transplant Recipients

Journal of the American Society of Nephrology ◽

10.1681/asn.v114753 ◽

2000 ◽

Vol 11 (4) ◽

pp. 753-759 ◽

Cited By ~ 3

Author(s):

BERTRAM L. KASISKE ◽

DAGMAR KLINGER

Keyword(s):

Cardiovascular Disease ◽

Relative Risk ◽

Renal Transplant ◽

General Population ◽

Cigarette Smoking ◽

Graft Failure ◽

Renal Transplant Recipients ◽

Adjusted Relative Risk ◽

Transplant Recipients ◽

Quit Smoking

Abstract. Cigarette smoking increases the risk for cancer and cardiovascular disease in the general population, but the effects of smoking in renal transplant recipients are unknown. The effects of smoking were investigated among patients transplanted at Hennepin County Medical Center between 1963 and 1997. Information on smoking was available in 1334 patients. The 24.7% prevalence of smoking at the time of transplantation was similar to that in the general population. After adjusting for multiple predictors of graft failure, smoking more than 25 pack-years at transplantation (compared to smoking less than 25 pack-years or never having smoked) was associated with a 30% higher risk of graft failure (relative risk 1.30; 95% confidence interval [CI], 1.04 to 1.63;P= 0.021). Having quit smoking more than 5 yr before transplantation reduced the relative risk of graft failure by 34% (relative risk 0.66; 95% CI, 0.52 to 0.85;P< 0.001). The increase in graft failure was due to an increase in deaths (adjusted relative risk 1.42; 95% CI, 1.08 to 1.87;P= 0.012). The relative risk for major cardiovascular disease events with smoking 11 to 25 pack-years at transplant was 1.56 (95% CI, 1.06 to 2.31;P= 0.024), whereas that of smoking more than 25 pack-years was 2.14 (95% CI, 1.49 to 3.08;P< 0.001). The relative risk of invasive malignancies was 1.91 (95% CI, 1.05 to 3.48;P= 0.032). Smoking had no discernible effect on the rate of return to dialysis or on serum creatinine during the first year after transplantation. Thus, cigarette smoking is associated with an increased risk of death after renal transplantation. The effects of smoking appear to dissipate 5 yr after quitting. These results indirectly suggest that greater efforts to encourage patients to quit smoking before transplantation may decrease morbidity and mortality.

Download Full-text

CD4+CD25+CD127-Foxp3+ and CD8+CD28- Tregs in Renal Transplant Recipients: Phenotypic Patterns, Association With Immunosuppressive Drugs, and Interaction With Effector CD8+ T Cells and CD19+IL-10+ Bregs

Frontiers in Immunology ◽

10.3389/fimmu.2021.716559 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mostafa G. Aly ◽

Eman H. Ibrahim ◽

Hristos Karakizlis ◽

Rolf Weimer ◽

Gerhard Opelz ◽

...

Keyword(s):

Renal Transplant ◽

Negative Impact ◽

Immunosuppressive Drugs ◽

Acute Cellular Rejection ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Regulatory Cells ◽

Transplant Patients ◽

Antibody Induction ◽

Cellular Rejection

IntroductionGaps still exist regarding knowledge on regulatory cells in transplant recipients. We studied the phenotypic patterns of CD4+, CD8+CD28- Tregs, and CD19+IL-10+ Bregs in the blood of healthy controls (HC), end-stage kidney disease patients (ESKD), early and late stable renal transplant recipients (Tx), and transplant recipients with steroid-treated acute cellular rejection 1 week–3 months after successful treatment. We also investigated the relationship between immunosuppressive drugs and the aforementioned regulatory cells in transplant recipients.MethodsWe recruited 32 HC, 83 ESKD, 51 early Tx, 95 late Tx, and 9 transplant patients with a recent steroid-treated acute cellular rejection. Besides CD19+IL-10+ Bregs, we analyzed absolute and relative frequencies of CD4+CD25+CD127-Foxp3+ Tregs and CD8+CD28- Tregs and their expression of IL-10, TGF-ß, IFN-g, and Helios.ResultsWe found a negative correlation between absolute CD4+CD25+CD127-Foxp3+ Treg and relative CD19+IL-10+ Breg frequencies in early Tx recipients (r=-0.433, p=0.015, n=31). In that group, absolute CD4+CD25+CD127-Foxp3+ Tregs were negatively associated with steroid dose and tacrolimus trough levels (r=-0.377, p = 0.021, n=37; r=-0.43, p=0.033, n=25, respectively), opposite to IL-10+ Bregs, whose frequency apparently was not negatively affected by potent immunosuppression early posttransplant. We found also lower CD4+CD25+CD127-Foxp3+ Tregs in patients treated with basiliximab or rATG as compared with ESKD patients (p=0.001 and p <0.001, respectively). No difference in absolute IL-10+ Bregs could be detected among these 3 patient groups. Early Tx recipients showed lower CD4+CD25+CD127-Foxp3+ Tregs within 3 months of antibody induction than after 3 months (p = 0.034), whereas IL-10+ Bregs showed higher relative counts during the first 3 months post antibody induction than after 3 months (p = 0.022). Our findings suggest that IL-10+ Bregs decrease with time posttransplantation independent of the effect of antibody induction and dose of other immunosuppressive drugs.ConclusionThese findings suggest that CD19+IL-10+ Bregs and CD4+CD25+CD127-Foxp3+ Tregs behave in opposite ways during the early posttransplant period, possibly due to a predominant negative impact of high doses of immunosuppressants on Tregs. CD19+IL-10+Bregs do not seem to be suppressed by antibody induction and early potent immunosuppression with chemical drugs.

Download Full-text

Comparative Methylprednisolone Pharmacokinetics in Renal Transplant Patients Receiving Double- or Triple-Drug Immunosuppression

Annals of Pharmacotherapy ◽

10.1177/106002809302700501 ◽

1993 ◽

Vol 27 (5) ◽

pp. 545-549 ◽

Cited By ~ 6

Author(s):

Kathleen M. Tornatore ◽

J. Joseph Walshe ◽

Kris A. Reed ◽

Mark T. Holdsworth ◽

Rocco C. Venuto

Keyword(s):

Renal Transplant ◽

Group Versus ◽

Volume Of Distribution ◽

Drug Group ◽

Pharmacokinetic Parameters ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Transplant Patients ◽

Renal Transplant Patients ◽

Plasma Half Life

OBJECTIVE: To assess the pharmacokinetics of chronic methylprednisolone therapy in renal transplant patients receiving double-drug (methylprednisolone and azathioprine) and triple-drug (methylprednisolone, azathioprine, and cyclosporine) immunosuppression. DESIGN: Parallel, randomized trial. PATIENTS: Fourteen renal transplant recipients (aged 29–65 y) evaluated in a public, university-affiliated hospital clinic. INTERVENTIONS: All patients received their chronic oral dose of methylprednisolone via a 10–20-minute intravenous infusion. MAIN OUTCOME MEASURES: Serum methylprednisolone concentrations were determined by HPLC and were used to generate pharmacokinetic parameters for this drug. RESULTS: The mean daily methylprednisolone dosage was 19 ± 19 mg in the double-drug group and 9 ± 2 mg in the triple-drug group. Mean serum creatinine concentrations were 124 ± 44 and 124 ± 27 μmol/L, respectively. Mean methylprednisolone clearances were similar in both groups: 405 ± 205 (double-drug) and 373 ± 365 mL/h/kg (triple-drug) (p>0.05). Mean steady-state volume of distribution was 1.5 ± 0.8 L/kg in the double-drug group and 1.3 ± 0.8 L/kg in the triple-drug group (p>0.05). Plasma half-life ranged from 1.7 to 4.3 h (mean 2.7) in the double-drug group versus 1.4 to 3.4 h (mean 2.6) in the triple-drug group (p>0.05). CONCLUSIONS: These data indicate that cyclosporine had no definitive influence on methylprednisolone disposition. The results reveal a wide variation in methylprednisolone metabolism in renal transplant recipients receiving either a double- or triple-drug immunosuppressive regimen. Typically, methylprednisolone is prescribed according to a standardized dosing protocol that assumes minimal interpatient variation. Therefore, the pharmacokinetic variability noted in this study may have important clinical implications regarding the development of chronic toxicity (e.g., osteoporosis, hypothalamic-pituitary-adrenal suppression) and the attainment of successful immunosuppression.

Download Full-text

P1763TUBERCULOSIS IN RENAL TRANSPLANT RECEPIENTS - DO RITUXIMAB AND OTHER IMMUNOSUPRESSION HAVE A ROLE?

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1763 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Anupma Kaul ◽

Dharmendra Bhaduria ◽

Narayan Prasad ◽

Amit Gupta

Keyword(s):

Renal Transplantation ◽

Renal Transplant ◽

Immunosuppressive Agents ◽

Induction Agent ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Transplant Patients ◽

Significant Difference ◽

High Prevalence ◽

Mean Time

Abstract Background and Aims Rituximab is an anti CD 20 agent used widely in renal transplant recipients. Its use is associated with various infections;however, its association with Tuberculosis (TB) is not well established and has not been studied in post renal transplantation patients. Method This is a single centre, retrospective analysis of 56 renal transplant recipients who received rituximab for various reasons and 287 post renal transplant patients who did not receive rituximab during the study period from January 2013 to June 2017. The association between use of rituximab and incidence of TB was studied. Other factors associated with tuberculosis were also investigated. Results Baseline characteristics were similar in both the groups. Mean time for occurrence of TB was 18.4 + 10.6 months after renal transplantation. Rituximab use was not significantly associated with tuberculosis or any other infection. Higher number of rejection episodes (60% vs 32.72%, p=0.029) was the only factor associated with greater incidence of TB. However, no specific type of rejection was associated with tuberculosis. Use of plasmapheresis in post transplant period for treatment of humoral rejections was associated with significantly higher incidence of TB (33.33% vs 13.41%, p=0.031), however when pre- transplant plasmapheresis was also considered, there was no significant difference. The choice of induction agent was not associated with higher incidence of TB. Conclusion Use of rituximab is not associated with higher incidence of TB when compared to other immunosuppressive agents. Routine screening and prophylaxis may not be advisable especially in a country like India with high prevalence of TB; as it will further delay transplantation and may adversely affect the outcome of the patients.

Download Full-text