Graft function and pregnancy outcomes after kidney transplantation

Background After kidney transplantation, pregnancy and graft function may have a reciprocal interaction. We evaluated the influence of graft function on the course of pregnancy and vice versa. Methods We performed a retrospective observational study of 92 pregnancies beyond the first trimester in 67 women after renal transplantation from 1972 to 2019. Pre-pregnancy eGFR was correlated with outcome parameters; graft function was evaluated by Kaplan Meier analysis. The course of graft function in 28 women who became pregnant after kidney transplantation with an eGFR of < 50 mL/min/1.73m2 was compared to a control group of 79 non-pregnant women after kidney transplantation during a comparable time period and with a matched basal graft function. Results Live births were 90.5% (fetal death n = 9). Maternal complications of pregnancy were preeclampsia 24% (graft loss 1, fetal death 3), graft rejection 5.4% (graft loss 1), hemolytic uremic syndrome 2% (graft loss 1, fetal death 1), maternal hemorrhage 2% (fetal death 1), urinary obstruction 10%, and cesarian section. (76%). Fetal complications were low gestational age (34.44 ± 5.02 weeks) and low birth weight (2322.26 ± 781.98 g). Mean pre-pregnancy eGFR was 59.39 ± 17.62 mL/min/1.73m2 (15% of cases < 40 mL/min/1.73m2). Pre-pregnancy eGFR correlated with gestation week at delivery (R = 0.393, p = 0.01) and with percent eGFR decline during pregnancy (R = 0.243, p = 0.04). Pregnancy-related eGFR decline was inversely correlated with the time from end of pregnancy to chronic graft failure or maternal death (R = -0.47, p = 0.001). Kaplan Meier curves comparing women with pre-pregnancy eGFR of ≥ 50 to < 50 mL/min showed a significantly longer post-pregnancy graft survival in the higher eGFR group (p = 0.04). Women after kidney transplantation who became pregnant with a low eGFR of > 25 to < 50 mL/min/1.73m2 had a marked decline of renal function compared to a matched non-pregnant control group (eGFR decline in percent of basal eGFR 19.34 ± 22.10%, n = 28, versus 2.61 ± 10.95%, n = 79, p < 0.0001). Conclusions After renal transplantation, pre-pregnancy graft function has a key role for pregnancy outcomes and graft function. In women with a low pre-pregnancy eGFR, pregnancy per se has a deleterious influence on graft function. Trial registration Since this was a retrospective observational case series and written consent of the patients was obtained for publication, according to our ethics’ board the analysis was exempt from IRB approval. Clinical Trial Registration was not done. The study protocol was approved by the Ethics Committee of Hannover Medical School, Chairman Prof. Dr. H. D. Troeger, Hannover, December 12, 2015 (IRB No. 2995–2015).

Estimated Renal Metabolomics at Reperfusion Predicts One-Year Kidney Graft Function

Renal transplantation is the gold-standard procedure for end-stage renal disease patients, improving quality of life and life expectancy. Despite continuous advancement in the management of post-transplant complications, progress is still needed to increase the graft lifespan. Early identification of patients at risk of rapid graft failure is critical to optimize their management and slow the progression of the disease. In 42 kidney grafts undergoing protocol biopsies at reperfusion, we estimated the renal metabolome from RNAseq data. The estimated metabolites’ abundance was further used to predict the renal function within the first year of transplantation through a random forest machine learning algorithm. Using repeated K-fold cross-validation we first built and then tuned our model on a training dataset. The optimal model accurately predicted the one-year eGFR, with an out-of-bag root mean square root error (RMSE) that was 11.8 ± 7.2 mL/min/1.73 m2. The performance was similar in the test dataset, with a RMSE of 12.2 ± 3.2 mL/min/1.73 m2. This model outperformed classic statistical models. Reperfusion renal metabolome may be used to predict renal function one year after allograft kidney recipients.

Employment status at transplant influences ethnic disparities in outcomes after deceased donor kidney transplantation

Background African American (AA) recipients of deceased-donor (DD) kidney transplants (KT) have shorter allograft survival than recipients of other ethnic groups. Reasons for this disparity encompass complex interactions between donors and recipients characteristics. Methods Outcomes from 3872 AA and 19,719 European American (EA) DDs who had one kidney transplanted in an AA recipient and one in an EA recipient were analyzed. Four donor/recipient pair groups (DRP) were studied, AA/AA, AA/EA, EA/AA, and EA/EA. Survival random forests and Cox proportional hazard models were fitted to rank and evaluate modifying effects of DRP on variables associated with allograft survival. These analyses sought to identify factors contributing to the observed disparities in transplant outcomes among AA and EA DDKT recipients. Results Transplant era, discharge serum creatinine, delayed graft function, and DRP were among the top predictors of allograft survival and mortality among DDKT recipients. Interaction effects between DRP with the kidney donor risk index and transplant era showed significant improvement in allograft survival over time in EA recipients. However, AA recipients appeared to have similar or poorer outcomes for DDKT performed after 2010 versus before 2001; allograft survival hazard ratios (95% CI) were 1.15 (0.74, 1.76) and 1.07 (0.8, 1.45) for AA/AA and EA/AA, compared to 0.62 (0.54, 0.71) and 0.5 (0.41, 0.62) for EA/EA and AA/EA DRP, respectively. Recipient mortality improved over time among all DRP, except unemployed AA/AAs. Relative to DDKT performed pre-2001, employed AA/AAs had HR = 0.37 (0.2, 0.69) versus 0.59 (0.31, 1.11) for unemployed AA/AA after 2010. Conclusion Relative to DDKT performed before 2001, similar or worse overall DCAS was observed among AA/AAs, while EA/EAs experienced considerable improvement regardless of employment status, KDRI, and EPTS. AA recipients of an AA DDKT, especially if unemployed, had worse allograft survival and mortality and did not appear to benefit from advances in care over the past 20 years.

Urinary Tract Infections in Kidney Transplant Recipients—Is There a Need for Antibiotic Stewardship?

(1) Background: Urinary tract infections (UTI) are the most common infections after kidney transplantation. Given the risk of urosepsis and the potential threat to the graft, the threshold for treating UTI and asymptomatic bacteriuria with broad spectrum antibiotics is low. Historically fluoroquinolones were prescription favorites for patients that underwent kidney transplantation (KT). After the recent recommendation to avoid them in these patients, however, alternative treatment strategies need to be investigated (2) Methods: We retrospectively analyzed the charts of 207 consecutive adult kidney transplantations that were performed at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020. All charts were screened for the diagnosis and treatment of asymptomatic bacteriuria (ASB) and urinary tract infections (UTI) and the patients’ clinical characteristics and outcomes were evaluated. (3) Results: Of the 207 patients, 68 patients suffered from urinary tract infections. Patients who developed UTI had worse graft function at discharge (p = 0.024) and at the 12 months follow-up (p < 0.001). The most commonly prescribed antibiotics were Ciprofloxacin and Piperacillin/Tazobactam. To both, bacterial resistance was more common in the study cohort than in the control group. (4) Conclusions: Urinary tract infections appear to be linked to worse graft functions. Thus, prevention and treatment should be accompanied by antibiotic stewardship teams.

Living Donor Kidney Transplantation for a Recipient after 41 Years of Hemodialysis

Due to atrophic bladder, patients undergoing long-term dialysis experience vesicoureteral reflux and complicated urinary tract infections after kidney transplantation. A 58-year-old woman underwent living donor kidney transplantation after 41 years of dialysis. She had no contraindications, with good cardiac function and minimal artery calcification despite the long history of hemodialysis. Immunosuppression was initiated with tacrolimus, mycophenolate mofetil, prednisolone, and basiliximab. Ureteroneocystostomy with an antireflux technique was carefully conducted as her bladder volume was 15 mL. The postoperative clinical course was uneventful with immediate graft function. The bladder volume gradually increased to 81 mL at discharge, 3 weeks postoperatively. The patient was initially depressed due to frequent urination early post-transplant but recovered soon after as the bladder volume gradually increased to 400 mL. The patient has not yet reported a urinary tract infection episode. This case highlights living donor kidney transplantation-induced recovery of bladder function with careful ureteroneocystostomy, despite the long dialysis history.

RELATIONSHIP BETWEEN WARM ISCHEMIC TIME AND RESISTIVE INDEX ON CREATININ REDUCTION RATIO DAY TWO AFTER LIVING KIDNEY DONOR TRANSPLANTATION

Kidney transplantation (KT) may improve kidney function, via filtration, excretion, and hormonal function better than other kidney replacement therapies. Many factors may cause graft rejection or delayed graft function which may decrease the prognosis for graft survival. This study aims to determine associated factors of serum creatinine reduction ratio day 2 (CRR2) after living kidney donor transplants. This research used a retrospective cohort study design, with total sampling based on complete documents was done. A total 44 respondents (from 2012 to January 2020) and 22 respondents (based on the complete Resistive Index (RI) were recorded since 2018). Early Graft Function was defined using CRR2. Immediate Graft Function (IGF) was defined if CRR2 > 30% and Delayed Graft Function (DGF) if CRR2 ≤ 30%. The results of Multiple logistic regression analysis from 44 samples showed that Warm Ischemic Time (WIT) ≤ 40 minutes was significantly associated with IGF (OR 10.78; 95%CI: 1.66 to 70.16; p=0.01). A result with 22 samples showed that, only RI ≤ 0.7was significantly associated with IGF (OR 0.11; 95%CI: 0.03-0.41; p=0.002). In conclusion, WIT and RI influence on EGF with parameters CRR2 of living-donors. KT Patients with WIT ≤40 minutes and RI ≤0.7 had a higher risk of IGF.

Ex-vivo Kidney Machine Perfusion: Therapeutic Potential

Kidney transplantation remains the gold standard treatment for patients suffering from end-stage kidney disease. To meet the constantly growing organ demands grafts donated after circulatory death (DCD) or retrieved from extended criteria donors (ECD) are increasingly utilized. Not surprisingly, usage of those organs is challenging due to their susceptibility to ischemia-reperfusion injury, high immunogenicity, and demanding immune regulation after implantation. Lately, a lot of effort has been put into improvement of kidney preservation strategies. After demonstrating a definite advantage over static cold storage in reduction of delayed graft function rates in randomized-controlled clinical trials, hypothermic machine perfusion has already found its place in clinical practice of kidney transplantation. Nevertheless, an active investigation of perfusion variables, such as temperature (normothermic or subnormothermic), oxygen supply and perfusate composition, is already bringing evidence that ex-vivo machine perfusion has a potential not only to maintain kidney viability, but also serve as a platform for organ conditioning, targeted treatment and even improve its quality. Many different therapies, including pharmacological agents, gene therapy, mesenchymal stromal cells, or nanoparticles (NPs), have been successfully delivered directly to the kidney during ex-vivo machine perfusion in experimental models, making a big step toward achievement of two main goals in transplant surgery: minimization of graft ischemia-reperfusion injury and reduction of immunogenicity (or even reaching tolerance). In this comprehensive review current state of evidence regarding ex-vivo kidney machine perfusion and its capacity in kidney graft treatment is presented. Moreover, challenges in application of these novel techniques in clinical practice are discussed.