A holistic review of sodium intake in kidney transplant patients: More questions than answers.

Kidney transplantation (KT) is the best treatment option for end-stage kidney disease (ESKD). Acute rejection rates have decreased drastically in recent years but chronic kidney allograft disease (CKAD) is still an important cause of allograft failure and return to dialysis. Thus, there is unmet need to identify and reverse the cause of CKAD. Additionally, cardiovascular events after KT are still leading causes of morbidity and mortality. One overlooked potential contributor to CKAD and adverse cardiovascular events is increased sodium/salt intake in kidney transplant recipients (KTRs). In general population, the adverse effects of high sodium intake are well known but in KTRs, there is a paucity of evidence despite decades of experience with KT. Limited research showed that sodium intake is high in most KTRs. Moreover, excess sodium intake is associated with elevated blood pressure and albuminuria in some studies involving KTRs. There is also experimental evidence suggesting that increased sodium intake is associated with histologic graft damage. Critical knowledge gaps still remain, including the exact amount of sodium restriction needed in KTRs to optimize outcomes and allograft survival. Additionally, best methods to measure sodium intake and practices to follow-up are not clarified in KTRs. To meet these deficits, prospective long term studies are warranted in KTRs. Moreover, preventive measures must be determined and implemented both at individual and societal levels to achieve sodium restriction in KTRs.

Sociodemographic disparities in sodium-glucose cotransporter-2 inhibitor use among US kidney transplant recipients: An observational study of real-world pharmacy records.

BACKGROUND: Recent clinical trials demonstrate benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with chronic kidney disease, but data on use in kidney transplant (KTx) recipients are limited. METHODS: We examined a novel database linking SRTR registry data for KTx recipients (2000-2021) with outpatient fill records from a large pharmaceutical claims warehouse (2015-2021). Adult (≥18 years) KTx recipients treated with SGLT2i were compared to those who received other noninsulin diabetes medications without SGLT2i. Characteristics associated with SGLT2i use were quantified by multivariable logistic regression (adjusted odds ratio, 95%LCLaOR95%UCL). RESULTS: Among 18 988 KTx recipients treated with noninsulin diabetes agents in the study period, 2224 filled an SGLT2i. Mean time from KTx to prescription was 6.7 years for SGLT2i versus 4.7 years for non-SGLT2i medications. SGLT2i use was more common in Asian adults (aOR, 1.091.311.58) and those aged > 30-59 years (compared with 18-30 years) or with BMI > 35 kg/m2 (aOR, 1.191.411.67), and trended higher with self-pay status. SGLT2i use was lower among KTx recipients who were women (aOR, .79.87.96), Black (aOR, .77.881.00) and other (aOR, .52.751.07) race, publicly insured (aOR, .82.921.03), or with less than college education (aOR, .78.87.96), and trended lower in those age 75 years and older. SGLT2i use in KTx patients increased dramatically in 2019-2021 (aOR, 5.015.636.33 vs. prior years). CONCLUSION: SGLT2i use is increasing in KTx recipients but varies with factors including race, education, and insurance. While ongoing study is needed to define risks and benefits of SGLT2i use in KTx patients, attention should also focus on reducing treatment disparities related to sociodemographic traits.

Complexities and outcomes of pulmonary hypertension in kidney transplant patients: a comprehensive review.

Pulmonary hypertension (PH) is often present in patients presenting for kidney transplant listing. While PH can complicate kidney transplant (KTx), with multidisciplinary management that includes both the transplant center and pulmonary hypertension center or experts both pre- and post-transplant. This review summaries the approach and management of PH in KTx candidates and recipients, along with expected outcomes and controversies surrounding arteriovenous fistula and graft management.

Outcomes of kidney, liver, and simultaneous liver and kidney transplants from hepatitis c infected donors to hepatitis c naïve recipients: A large single center experience.

BACKGROUND: With the introduction of direct-acting antiviral therapies (DAAs), the non-use rate of hepatitis C virus (HCV)-positive donor organs (D+) has decreased significantly. We present the donor, recipient, and transplant allograft characteristics, along with recipient outcomes, in one of the largest cohorts of HCV-D+ transplants into HCV-naïve recipients (R-). METHODS: Charts of HCV D+/R- kidney (KT), liver (LT), and simultaneous liver-kidney (SLKT) transplant recipients between January 2019 and July 2022 were reviewed. Primary outcomes of interest included waitlist times and 1-year graft failure. Secondary outcomes included hospital and intensive care unit length of stay, post-transplant complications, effectiveness of DAA therapy, and characteristics of patients who relapsed from initial DAA therapy. RESULTS: Fifty-five HCV D+/R- transplants at our center [42 KT (26 nucleic acid testing positive [NAT+], 16 NAT-), 12 LT (eight NAT+, four NAT-), and one SLKT (NAT+)] had a median waitlist time of 69 days for KT, 87 days for LT, and 15 days for SLKT. There were no graft failures at 1 year. All viremic recipients were treated with a 12-week course of DAAs, of which 100% achieved end of treatment response (EOTR)-85.7% (n = 30) achieved sustained virologic response (SVR) and 14.3% relapsed (n = 5; four KT, one LT). All relapsed recipients were retreated and achieved SVR. The most common post-transplantation complications include BK virus infection (n = 9) for KT and non-allograft infections (n = 4) for LT. CONCLUSIONS: Our study has demonstrated no graft failures or recipient deaths at 1 year, and despite a 14.3% relapse rate, we achieved 100% SVR. Complications rates of D+/R- appeared comparable to national D-/R- complication rates. Further studies comparing D+/R- to D-/R- outcomes are needed.

The Effect of a Merit Point Incentive System on the Willingness to Donate Organs.

PURPOSE: Although over 90% of the population of the United States supports organ donation, only 60% of the population is registered as donors. Currently, there is a need for a nonmonetary incentive that will improve willingness to donate. We assessed the young adult population's perspective on their willingness to donate organs when merit points are granted to their family members to prioritize their potential transplant if needed. METHODS: We administered a Qualtrics survey from March 2022 to September 2022 to the undergraduate students volunteering to participate at Saint Louis University, which comprised 10 questions that addressed the attitudes of participants regarding the effects of various factors, including the type of donation and the presence of merit points (vouchers granted to self or a family member to facilitate a potential transplant if needed), on participant's willingness to donate an organ while alive or after death. The responses were analyzed by using SAS software (SAS Institute). RESULTS: A total of 572 participants completed the survey. Overall, only 6.5% of surveyed students were unwilling to donate after death. The willingness to donate while alive to a family member was significantly higher than donating to a stranger (95.8% vs 71.2%, P < .0001). When merit points were added, the unwillingness to donate significantly decreased from 6.5% to 3.8%. However, this change was observed only when the merit points were given to a family member and not to self. When merit points were granted, unwillingness to provide a living donation to a stranger decreased from 28.8% to 16.4% (P < .0001). CONCLUSIONS: Merit points to first-degree family members improve students' expressed willingness to donate organs after death; however, self-merit points did not decrease the rate of "unwillingness to donate after death." When living donation is assessed, offering merit points appears to decrease the "unwillingness to donate to strangers." The adoption of a merit point system in the United States may increase the rates of organ donation.

Normothermic ex vivo perfusion of deceased donor kidneys and its clinical potential in kidney transplantation outcomes.

In recent years, normothermic machine perfusion (NMP) has emerged in conversation surrounding organ preservation and transplantation techniques with the goal of improving patient and clinical outcomes. This is in great attempt to address the rate of non-utilization and the shortage of available organs in kidney transplantation. This focus in mind, normothermic perfusion presents itself as a potential tool to mimic physiological conditions and improve current preservation methods, such as static cold storage. This review serves to improve understanding of the observed connection between the consequences of ischemia and reperfusion injury and traditional preservation techniques as well as how renal NMP may mitigate these issues. Previous studies suggest that reducing time in static cold storage methods by promoting the normothermic perfusion model results in decreased delayed graft function and post-transplant complications. This review also aims to present the immense clinical potential NMP has on future kidney transplantation success and what this means for the fields of nephrology and transplantation. While great strides have been made to evaluate normothermic perfusion's impact on kidney graft viability and transplant success, future research into unified protocol, clinically relevant biomarkers, cost-utility analysis, and use with associated therapeutic and imaging modalities is paramount.

Long-term Effects of Gastric Acid Prophylaxis in Kidney Transplant Recipients.

Objectives: Prophylactic acid suppression with proton pump inhibitors or H2 receptor antagonists is often administered after kidney transplantation. The Association of proton pump inhibitors or H2 receptor antagonists with acute rejection, hypomagnesemia, and graft loss in kidney transplant recipients is not well established. Material and Methods: We performed a retrospective cohort study of 302 kidney transplant recipients at one center (57% male; mean age 35.5±11.2 years) with more than 6 months post-transplant follow-up. Recipients were grouped according to gastric acid prophylaxis: only proton pump inhibitors (n=179), only H2 receptor antagonists (n=42), proton pump inhibitors and H2 receptor antagonists (n=55), and nonusers (n=26). The primary outcome was biopsy-proven acute rejection. Graft loss and hypomagnesemia were defined as secondary outcomes. Results: Nonusers were younger and mostly under steroid-free immunosuppression compared to other study groups (p=0.030 and p=0.009, respectively). The primary outcome was similar across study groups (p=0.266). Kaplan-Meier analyses also demonstrated similar 10-year graft survival rates: 95.5% for proton pump inhibitors, 97.6% for H2 receptor antagonists, 100% for proton pump inhibitors/H2 receptor antagonists, and 96.2% for nonusers (p=0.275). Conclusions: The use of proton pump inhibitors is not associated with acute rejection or graft loss but may cause mild hypomagnesemia in kidney transplant recipients.

Pregnancy in Living Kidney Donors: An Evidence-Based Review.

Purpose of review: To review the current studies and guidelines on the risk of adverse pregnancy outcomes in female kidney donors. Recent findings: Living kidney donors include a significant amount of young women of child-bearing age. Safety and possible risks of pregnancy after donation are a concern for female kidney donor candidates. Many current studies indicate a higher risk of preeclampsia in women after kidney donation. Considering the increasing number of living kidney donors, the maternal outcomes of living kidney donation is an active area of research. Summary: Guidelines and consensus statements on the risk of pregnancy in living kidney donors recommend close monitoring of blood pressure, weight gain, and proteinuria during pregnancy. Current studies indicate an increased risk of hypertensive disorders of pregnancy in living kidney donors. Counseling and informing donor candidates about the possible risks is important.

Kidney paired donation in developing countries: A global perspective.

Purpose of review: We review the key principles of kidney paired donation (KPD) and discuss the status and unique considerations for KPD in developing countries. Recent findings: Despite the advantages of KPD programs, they remain rare among developing nations, and the programs that exist have many differences with those of in developed countries. There is a paucity of literature and lack of published data on KPD from most of the developing nations. Expanding KPD programs may require the adoption of features and innovations of successful KPD programs. Cooperation with national and international societies should be encouraged to ensure endorsement and sharing of best practices. Summary: KPD is in the initial stages or has not yet started in the majority of the emerging nations. But the logistics and strategies required to implement KPD in developing nations differ from other parts of the world. By learning from the KPD experience in developing countries and adapting to their unique needs, it should be possible to expand access to KPD to allow more transplants to happen for patients in need world-wide.

Outcomes of kidney transplantation in patients with congenital anomalies of the kidney and urinary tract: a propensity-score-matched analysis with case-control design.

BACKGROUND: We compared long-term outcomes after kidney transplantation (KTx) in patients with and without congenital anomalies of the kidney and urinary tract (CAKUT). METHODS: KTx recipients (KTRs) with CAKUT in 1980-2016 were identified; their hard copy and electronic medical records were reviewed and compared to a propensity-score-matched control group (non-CAKUT) from the same period. The primary outcomes were graft loss or death with a functioning graft; secondary outcomes included posttransplant urinary tract infections (UTIs) and biopsy-proven rejection (BPR). RESULTS: : We identified 169 KTRs with CAKUT and 169 matched controls. Median follow-up was 132 (IQR: 75.0-170.0) months. UTIs were more common in CAKUT patients compared to non-CAKUT group (20.7% vs 10.7%; p = 0.01). Rates of BPR were similar between the two groups. In Kaplan-Meier analysis, 10-year graft survival rates were significantly higher in the CAKUT group than in the non-CAKUT group (87.6% vs 69.2%; p < 0.001), while patient survival rates were similar. In multivariate Cox regression analyses, CAKUT (HR: 0.469; 95% CI: 0.320-0.687; p < 0.001) and PRA positivity before transplantation (HR: 3.756; 95% CI: 1.507-9.364; p = 0.005) predicted graft loss. DISCUSSION: Graft survival in KTRs with CAKUT appears superior to KTRs without CAKUT. Transplant centers should develop multidisciplinary educational and social working groups to support and encourage CAKUT patients with kidney failure to seek for transplants.

Patterns in Use and Transplant Outcomes Among Adult Recipients of Kidneys From Deceased Donors With COVID-19.

Importance: While the COVID-19 pandemic enters a new phase and the proportion of individuals with a previous COVID-19 diagnosis increases, the national patterns in kidney use and medium-term kidney transplant (KT) outcomes among patients receiving kidneys from active or resolved COVID-19-positive donors remain unknown. Objective: To evaluate the patterns in kidney use and KT outcomes among adult recipients of kidneys from deceased donors with active or resolved COVID-19. Design, Setting, and Participants: This retrospective cohort study was conducted using national US transplant registry data from 35 851 deceased donors (71 334 kidneys) and 45 912 adult patients who received KTs from March 1, 2020, to March 30, 2023. Exposure: The exposure was donor SARS-CoV-2 nucleic acid amplification test (NAT) results, with positive NAT results within 7 days before procurement defined as active COVID-19 and positive NAT results 1 week (>7 days) before procurement defined as resolved COVID-19. Main Outcomes and Measures: Primary outcomes were kidney nonuse, all-cause kidney graft failure, and all-cause patient death. Secondary outcomes were acute rejection (ie, rejection in the first 6 months after KT), transplant hospitalization length of stay (LOS), and delayed graft function (DGF). Multivariable logistic regression analyses were performed for kidney nonuse, rejection, and DGF; multivariable linear regression analyses were performed for LOS; and multivariable Cox regression analyses were performed for graft failure and all-cause death. All models were adjusted for inverse probability treatment weighting. Results: Among 35 851 deceased donors, the mean (SD) age was 42.5 (15.3) years; 22 319 (62.3%) were men and 23 992 (66.9%) were White. Among 45 912 recipients, the mean (SD) age was 54.3 (13.2) years; 27 952 (60.9%) were men and 15 349 (33.4%) were Black. The likelihood of nonuse of kidneys from active or resolved COVID-19-positive donors decreased over time. Overall, kidneys from active COVID-19-positive donors (adjusted odds ratio [AOR], 1.55; 95% CI, 1.38-1.76) and kidneys from resolved COVID-19-positive donors (AOR, 1.31; 95% CI, 1.16-1.48) had a higher likelihood of nonuse compared with kidneys from COVID-19-negative donors. From 2020 to 2022, kidneys from active COVID-19-positive donors (2020: AOR, 11.26 [95% CI, 2.29-55.38]; 2021: AOR, 2.09 [95% CI, 1.58-2.79]; 2022: AOR, 1.47 [95% CI, 1.28-1.70]) had a higher likelihood of nonuse compared with kidneys from donors without COVID-19. Kidneys from resolved COVID-19-positive donors had a higher likelihood of nonuse in 2020 (AOR, 3.87; 95% CI, 1.26-11.90) and 2021 (AOR, 1.94; 95% CI, 1.54-2.45) but not in 2022 (AOR, 1.09; 95% CI, 0.94-1.28). In 2023, kidneys from both active COVID-19-positive donors (AOR, 1.07; 95% CI, 0.75-1.63) and resolved COVID-19-positive donors (AOR, 1.18; 95% CI, 0.80-1.73) were not associated with higher odds of nonuse. No higher risk of graft failure or death was found in patients receiving kidneys from active COVID-19-positive donors (graft failure: adjusted hazard ratio [AHR], 1.03 [95% CI, 0.78-1.37]; patient death: AHR, 1.17 [95% CI, 0.84-1.66]) or resolved COVID-19-positive donors (graft failure: AHR, 1.10 [95% CI, 0.88-1.39]; patient death: AHR, 0.95 [95% CI, 0.70-1.28]). Donor COVID-19 positivity was not associated with longer LOS, higher risk of acute rejection, or higher risk of DGF. Conclusions and Relevance: In this cohort study, the likelihood of nonuse of kidneys from COVID-19-positive donors decreased over time, and donor COVID-19 positivity was not associated with worse KT outcomes within 2 years after transplant. These findings suggest that the use of kidneys from donors with active or resolved COVID-19 is safe in the medium term; further research is needed to assess longer-term transplant outcomes.

Genetic evaluation of living kidney donor candidates: A review and recommendations for best practices.

The growing accessibility and falling costs of genetic sequencing techniques has expanded the utilization of genetic testing in clinical practice. For living kidney donation, genetic evaluation has been increasingly used to identify genetic kidney disease in potential candidates, especially in those of younger ages. However, genetic testing on asymptomatic living kidney donors remains fraught with many challenges and uncertainties. Not all transplant practitioners are aware of the limitations of genetic testing, are comfortable with selecting testing methods, comprehending test results, or providing counsel, and many do not have access to a renal genetic counselor or a clinical geneticist. Although genetic testing can be a valuable tool in living kidney donor evaluation, its overall benefit in donor evaluation has not been demonstrated and it can also lead to confusion, inappropriate donor exclusion, or misleading reassurance. Until more published data become available, this practice resource should provide guidance for centers and transplant practitioners on the responsible use of genetic testing in the evaluation of living kidney donor candidates.

Efficacy and Safety of Sofosbuvir and Ledipasvir for Hepatitis C in Kidney Transplant Recipients: A Single-center Retrospective Observational Study

Background: Treatment using direct-acting antivirals provides high rates of sustained virologic response and a favorable safety profile for patients with chronic hepatitis C virus infection. However, data on the efficacy of direct-acting antivirals in kidney transplant recipients are still limited. Aims: To evaluate the safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination in kidney transplant recipients. Study Design: Retrospective, observational, single-center study. Methods: Data of 29 kidney transplant recipients who received a fixed-dose safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination for 12 or 24 weeks with or without ribavirin were analyzed. The primary outcome was SVR12, which was defined as undetectable HCV-RNA levels 12 weeks after the treatment. Secondary outcomes were graft function, proteinuria, and calcineurin inhibitor trough level variability. Results: The predominant hepatitis C virus genotype was 1b (n = 19, 65.6%). All patients achieved SVR12. No graft failures nor deaths were reported during the study period. Throughout and after the treatment, the levels of aspartate aminotransferase [21 (range: 18-29.5) to 16 (range: 14-20) U/l, p < 0.001] and alanine aminotransferase [22 (range: 15-34) to 14 (range: 12-17.5) U/l, p < 0.001] improved significantly, unlike bilirubin, hemoglobin, and platelet levels. Renal function remained stable. Dose adjustments for calcineurin inhibitors were required. Serious adverse events were not observed. Conclusion: Safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination was effective and safe in kidney transplant recipients with hepatitis C virus. However, cautious monitoring of trough levels of calcineurin inhibitorss is needed due to potential drug-drug interactions during the treatment episode.

Propensity score-matched analysis of long-term outcomes for living kidney donation in alternative complement pathway diseases: a pilot study.

BACKGROUND: Atypical hemolytic syndrome (aHUS) and C3 glomerulopathy (C3G) are complement-mediated rare diseases with excessive activation of the alternative pathway. Data to guide the evaluation of living-donor candidates for aHUS and C3G are very limited. The outcomes of living donors to recipients with aHUS and C3G (Complement disease-living donor group) were compared with a control group to improve our understanding of the clinical course and outcomes of living donation in this context. METHODS: Complement disease-living donor group [n = 28; aHUS(53.6%), C3G(46.4%)] and propensity score-matched control-living donor group (n = 28) were retrospectively identified from 4 centers (2003-2021) and followed for major cardiac events (MACE), de novo hypertension, thrombotic microangiopathy (TMA), cancer, death, estimated glomerular filtration rate (eGFR) and proteinuria after donation. RESULTS: None of the donors for recipients with complement-related kidney diseases experienced MACE or TMA whereas two donors in the control group developed MACE (7.1%) after 8 (IQR, 2.6-12.8) years (p = 0.15). New-onset hypertension was similar between complement disease and control donor groups (21.4% vs 25%, respectively, p = 0.75). There were no differences between study groups regarding last eGFR and proteinuria levels (p = 0.11 and p = 0.70, respectively). One related donor for a recipient with complement-related kidney disease developed gastric cancer and another related donor developed a brain tumor and died in the 4th year after donation (2, 7.1% vs none, p = 0.15). No recipient had donor-specific human leukocyte antigen antibodies at the time of transplantation. Median follow-up period of transplant recipients was 5 years (IQR, 3-7). Eleven (39.3%) recipients [aHUS (n = 3) and C3G (n = 8)] lost their allografts during the follow-up period. Causes of allograft loss were chronic antibody-mediated rejection in 6 recipients and recurrence of C3G in 5. Last serum creatinine and last eGFR of the remaining patients on follow up were 1.03 ± 038 mg/dL and 73.2 ± 19.9 m/min/1.73 m2 for aHUS patients and 1.30 ± 0.23 mg/dL and 56.4 ± 5.5 m/min/1.73 m2 for C3G patients. CONCLUSION: The present study highlights the importance and complexity of living related-donor kidney transplant for patients with complement-related kidney disorders and motivates the need for further research to determine the optimal risk-assessment for living donor candidates to recipients with aHUS and C3G.

Maximizing opportunities for kidney transplantation in older adults.

PURPOSE OF REVIEW: To summarize the current state of evidence related to the outcomes of older adults who need and receive kidney transplants, and strategies to facilitate appropriate transplant access in this at-risk group. RECENT FINDINGS: Older adults are a rapidly growing subgroup of the kidney transplant waitlist. Compared to younger adults, older kidney transplant recipients have increased mortality after kidney transplant and lower death-censored graft survival. In determining suitability for transplantation in older patients, clinicians must balance procedural and immunosuppression-related risk with incremental survival when compared with dialysis. To appropriately increase access to transplantation in this population, clinicians and policy makers consider candidates' chronological age and frailty, as well as the quality of and waiting time for a donated allograft. Given risk of deterioration prior to transplant, candidates should be rapidly evaluated, listed, and transplanted using living donor and or less than ideal deceased donor organs when available. SUMMARY: Access to transplantation for older adults can be increased through targeted interventions to address frailty and reduce waiting times through optimized organ use. Focused study and educational interventions for patients and providers are needed to improve the outcomes of this vulnerable group.

Efficacy and safety of interleukin-1 blockers in kidney transplant recipients with familial Mediterranean fever: a propensity score-matched cohort study.

BACKGROUND: Data on use of interleukin (IL)-1 blockers in kidney transplant recipients (KTRs) with familial Mediterranean fever (FMF) are very limited. We aimed to evaluate the efficacy and safety of anakinra and canakinumab in the transplantation setting. METHODS: In this retrospective cohort study, we included KTRs who suffered from AA amyloidosis caused by FMF and treated with anakinra or canakinumab (study group, n = 36). Using propensity score matching, we selected 36 patients without FMF or amyloidosis from our database of 696 KTRs as the control group. Primary outcomes were patient and graft survival. Biopsy-confirmed graft rejection, changes in estimated glomerular filtration rate (eGFR), high-sensitivity CRP (hsCRP), erythrocyte sedimentation rate (ESR), proteinuria and number of monthly attacks were secondary outcomes. RESULTS: All KTRs with FMF began IL-1 blocker therapy with anakinra and nine (25%) were switched to canakinumab. Overall death was more frequent in the study group (19.4% vs 0%) (P = .005); however, overall graft loss was comparable between study (27.8%) and control groups (36.1%) (P = .448). Five- and 10-year graft survival rates were significantly higher in the study group (94.4% and 83.3%, respectively) than in the control group (77.8% and 63.9%, respectively) (P = .014 and P < .001, respectively). Rejections were numerically lower in study group (8.3% vs 25%), but it did not reach to statistical significance (P = .058). When compared with the pre-treatment period, with IL-1 blockers, the number of attacks per month (P < .001), and eGFR (P = .004), hsCRP (P < .001) and ESR (P = .026) levels were lower throughout the follow-up, whereas proteinuria levels were not. CONCLUSIONS: Anakinra and canakinumab are effective in KTRs suffering from FMF; however, the mortality rate may be of concern.