BACKGROUND: Tacrolimus is a critical component of immunosuppressive therapy for kidney transplant recipients. Intra-patient variation (IPV) of tacrolimus levels affects the function of transplanted kidney.
OBJECTIVE: This study aimed to investigate the impact of tacrolimus IPV on kidney function, examine its association with post-transplant duration, and assess its effect on the immune status of transplant recipients.
METHODS: This retrospective study was conducted from January 2016 to February 2022. IPV was evaluated using the coefficient of variation (CV) of tacrolimus trough levels from 6 to 48 months after transplantation. Patients were divided into low- and high-IPV groups based on the median CV. Significant differences in kidney function, CD4 + /CD8 + ratio, and post-transplant duration between these groups were analyzed.
RESULTS: Among 189 patients, tacrolimus IPV showed a strong correlation with serum creatinine clearance rate (Ccr) and estimated glomerular filtration rate (eGFR) (p < 0.05). Tacrolimus IPV was significantly correlated with post-transplant duration in only two patients (p < 0.05). Using a median CV of 15.4% to categorize patients, the high IPV group, compared to the low IPV group, exhibited significantly higher eGFR at 6-9 months (p < 0.05), lower Ccr at 9-12 months (p < 0.05), and reduced Ccr and eGFR at 15-18 months (p < 0.05). Six months after transplantation, the high IPV group had a significantly lower CD4 + /CD8 + ratio than the low IPV group (p < 0.05).
CONCLUSIONS: This study highlights the significant impact of tacrolimus IPV on transplant kidney function and immune status in transplant patients at various post-transplantation intervals.

Tertiary hyperparathyroidism is a complication of kidney transplantation. This complicated condition carries over from the dialysis period and varies according to the function of the transplanted allograft. Treatments include pharmacotherapy (mainly using calcimimetics) and parathyroidectomy, but calcimimetics are currently not covered by the national insurance system in Japan. Two types of parathyroidectomy can be performed: subtotal parathyroidectomy; and total parathyroidectomy with partial autograft. Both types can be expected to improve hypercalcemia. Concerns about the postoperative deterioration of allograft function are influenced by preoperative allograft function, which is even more likely to be affected by early surgery after kidney transplantation. In general, transient deterioration of allograft function after surgery is not expected to affect graft survival rate in the medium to long term. Tertiary hyperparathyroidism in kidney transplant recipients negatively impacts allograft and patient survival rates, and parathyroidectomy can be expected to improve prognosis in both kidney recipients and dialysis patients. However, studies offering high levels of evidence remain lacking.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD)-related end-stage kidney disease (ESKD) often necessitates transplantation. However, the impact of ADPKD on post-transplant outcomes, specifically hemoglobin levels, remains unknown.
METHODS: We retrospectively analyzed 513 Kidney Transplant Recipients (KTRs), of whom 81 had ESKD due to ADPKD (20 with pre-transplant native nephrectomy and 61 without). Hemoglobin levels were evaluated at multiple time intervals post-transplant.
RESULTS: Kidney transplant recipients with ADPKD vs. KTRs with ESKD due to other causes exhibited significantly higher hemoglobin levels in repeated measurement analysis. Multivariable analyses confirmed ADPKD as an independent predictor for elevated hemoglobin levels. In a multivariable logistic regression analysis, the odds for maximum hemoglobin > 15 mg/dL at 3-12 months post-transplant were more than twice as high in ADPKD patients vs. all the other KTRs (Odds Ratio [OR] 2.31, 95% Confidence Interval [CI] 1.3-4.13, p < 0.001). Pre-transplant native nephrectomy revealed a trend toward lower hemoglobin levels. Elevated hemoglobin levels were linked to improved estimated glomerular filtration rate (eGFR) at one year post-transplant. Patient survival was enhanced among KTRs with ADPKD compared to other ESKD causes.
CONCLUSIONS: Kidney transplant recipients with ADPKD exhibited elevated hemoglobin levels post-transplant, possibly due to prolonged native kidney erythropoietin production. These elevated hemoglobin levels were linked to improved outcomes, including allograft function and patient survival. Future research should further investigate the underlying mechanisms driving favorable ADPKD KTR outcomes.

Kidney transplant recipients (KTRs) are at a higher risk of severe coronavirus disease (COVID-19) because of their immunocompromised status. However, the effect of allograft function on the prognosis of severe COVID-19 in KTRs is unclear. In this study, we aimed to analyze the correlation between pre-infection allograft function and the prognosis of severe COVID-19 in KTRs.
This retrospective cohort study included 82 patients who underwent kidney transplantation at the Sichuan Provincial Peoples Hospital between October 1, 2014 and December 1, 2022 and were diagnosed with severe COVID-19. The patients were divided into decreased eGFR and normal eGFR groups based on the allograft function before COVID-19 diagnosis (n=32 [decreased eGFR group], mean age: 43.00 years; n=50 [normal eGFR group, mean age: 41.88 years). We performed logistic regression analysis to identify risk factors for death in patients with severe COVID-19. The nomogram was used to visualize the logistic regression model results.
The mortality rate of KTRs with pre-infection allograft function insufficiency in the decreased eGFR group was significantly higher than that of KTRs in the normal eGFR group (31.25% [10/32] vs. 8.00% [4/50], P=0.006). Pre-infection allograft function insufficiency (OR=6.96, 95% CI: 1.4633.18, P=0.015) and maintenance of a mycophenolic acid dose >1500 mg/day before infection (OR=7.59, 95% CI: 1.0853.20, P=0.041) were independent risk factors, and the use of nirmatrelvir/ritonavir before severe COVID-19 (OR=0.15, 95% CI: 0.030.72, P=0.018) was a protective factor against death in severe COVID-19.
Pre-infection allograft function is a good predictor of death in patients with severe COVID-19. Allograft function was improved after treatment for severe COVID-19, which was not observed in patients with non-severe COVID-19.

BACKGROUND: Hyperparathyroidism (HPT) and malignancy are the most common causes of hypercalcemia. Among kidney transplant (KT) recipients, hypercalcemia is mostly caused by tertiary HPT. Persistent tertiary HPT after KT is associated with allograft failure. Previous studies on managing tHPT were subjected to survivor treatment selection bias; as such, the impact of tertiary HPT treatment on allograft function remained unclear. We aim to assess the association between hypercalcemic tertiary HPT treatment and kidney allograft survival.
METHODS: We identified 280 KT recipients (2015-2019) with elevated post-KT adjusted serum calcium and parathyroid hormone (PTH). KT recipients were characterized by treatment: cinacalcet, parathyroidectomy, or no treatment. Time-varying Cox regression with delayed entry at the time of first elevated post-KT calcium was conducted, and death-censored and all-cause allograft failure were compared by treatment groups.
RESULTS: Of the 280 recipients with tHPT, 49 underwent PTx, and 98 received cinacalcet. The median time from KT to first elevated calcium was 1 month (IQR: 0-4). The median time from first elevated calcium to receiving cinacalcet and parathyroidectomy was 0(IQR: 0-3) and 13(IQR: 8-23) months, respectively. KT recipients with no treatment had shorter dialysis vintage (P = .017) and lower PTH at KT (P = .002), later onset of hypercalcemia post-KT (P < .001). Treatment with PTx (adjusted hazard ratio (aHR) = 0.18, 95%CI 0.04-0.76, P = .02) or cinacalcet (aHR = 0.14, 95%CI 0.004-0.47, P = .002) was associated with lower risk of death-censored allograft failure. Moreover, receipt of PTx (aHR = 0.28, 95%CI 0.12-0.66, P < .001) or cinacalcet (aHR = 0.38, 95%CI 0.22-0.66, P < .001) was associated with lower risk of all-cause allograft failure.
CONCLUSIONS: This study demonstrates that treatment of hypercalcemic tertiary HPT post-KT is associated with improved allograft survival. Although these findings are not specific to hypercalcemia of malignancy, they do demonstrate the negative impact of hypercalcemic tertiary HPT on kidney function. Hypercalcemic HPT should be screened and aggressively treated post-KT.

The aim of this study (CTOTC-09) was to assess the impact of \"preformed\" (at transplant) donor-specific anti-HLA antibody (DSA) and first year newly detected DSA (ndDSA) on allograft function at 3 years after pediatric heart transplantation (PHTx). We enrolled children listed at 9 North American centers. The primary end point was pulmonary capillary wedge pressure (PCWP) at 3 years posttransplant. Of 407 enrolled subjects, 370 achieved PHTx (mean age, 7.7 years; 57% male). Pre-PHTx sensitization status was nonsensitized (n = 163, 44%), sensitized/no DSA (n = 115, 31%), sensitized/DSA (n = 87, 24%), and insufficient DSA data (n = 5, 1%); 131 (35%) subjects developed ndDSA. Subjects with any DSA had comparable PCWP at 3 years to those with no DSA. There were also no significant differences overall between the 2 groups for other invasive hemodynamic measurements, systolic graft function by echocardiography, and serum brain natriuretic peptide concentration. However, in the multivariable analysis, persistent first-year DSA was a risk factor for 3-year abnormal graft function. Graft and patient survival did not differ between groups. In summary, overall, DSA status was not associated with worse allograft function or inferior patient and graft survival at 3 years, but persistent first-year DSA was a risk factor for late graft dysfunction.

BACKGROUND: COVID-19 pandemic had tremendously affected all the aspects of human life during the past 3 years. In this study, we focused on kidney transplant patients\' course from the COVID-19 diagnosis, immunosuppressive medication modification, hospitalization, and COVID-19 complications and how the COVID-19 infection affected the kidney and patients\' quality of life during the hospitalization and after the discharge.
METHODS: A retrospective analysis of a prospectively collected database of all kidney transplants adult patients who had a positive COVID-19 PCR from 1 January 2020 to 30 December 2022, and had a history of kidney transplant at the SUNY Upstate Medical Hospital was done to identify the cases.
RESULTS: 188 patients met the inclusion criteria and were included in the study. Based on the immunosuppressive regimen modification during COVID-19 infection, patients divided into two groups; in 143 (76%) patients, the immunosuppressive medication was reduced, and in 45 (24%) of patients, the immunosuppressive regimen continued as before during the COVID-19 infection. The mean time from the transplant to the diagnosis of COVID-19 was 67 months in the group we reduced the IM regimen, and 77 months in the group without changes in IM regimen. The mean recipients\' age was 50.7 ± 12.9 years in the group we reduced the IM regimen, and 51.8 ± 16.4 years in the group without changes in IM regimen (P = 0.64). The vaccination rate against COVID-19 with at least 2 doses of either the CDC recommended Moderna or Pfizer vaccines was 80.2% in the group we reduced the IM regimen, and 84.8% in the group without changes in IM regimen (P = 0.55). The hospitalization rate due to COVID-19 related symptoms was 22.4% % in the group we reduced the IM regimen, and 35.5% in the group without changes in IM regimen (P = 0.12). However, the ICU admission rate was higher in the group we reduced the IM regimen, but the difference was not significant (26.5% Vs.6.25%, P = 0.12). 6 episodes of biopsy-proven rejection in the group with IM reduction was observed, which were 3 episodes of acute antibody-mediated rejections (ABMR) and 3 episodes of acute T-Cell-mediated rejections (TCMR), and 3 episodes in the group without any change in IM regimen, which were 2 episodes of ABMR and 1 episode of TCMR (P = 0.51). No significant difference was mentioned in the eGFR and serum creatinine after the comparison between the groups after 12 months of follow up. 124 patients responded to the post-COVID-19 questionnaires and were included in the data analysis. The response rate was 66%. Fatigue and exertion were the most reported symptom with a 43.9% prevalence.
CONCLUSIONS: We found that immunosuppressive regimen minimization did not impact the kidney function in the long-term and it might be a helpful strategy to minimize the effect of COVID-19 infection on patients\' condition during the hospital stay. With all the treatments, vaccinations, and precautions, still some patients did not achieve the complete recovery compared to their pre-COVID-19 health status. Fatigue was the main reported symptom amongst all the reported symptoms.

The rate of solid organ transplant in reproductive-aged patients has increased in the past 3 decades. Concurrently, the range of medical immunosuppressive agents has increased, making it safer for reproductive-aged individuals who have received transplants to attempt and continue a pregnancy. In this Consult, we review the general considerations and contemporary approach to medical and obstetrical management of pregnant solid organ transplant recipients, discuss the perinatal outcomes and incidence of graft rejection specific to the most common types of organ transplants, and provide management recommendations based on the available evidence. The following are Society for Maternal-Fetal Medicine recommendations: (1) we recommend that all solid organ transplant recipients capable of pregnancy be offered prepregnancy counseling as part of the pretransplant evaluation and before any posttransplant pregnancy (Best Practice); (2) we recommend deferring pregnancy for at least 1 year (except for lung transplant recipients in which case a 2-year deferral is recommended) following solid organ transplant or any episode of acute cellular rejection (GRADE 1B); (3) we recommend that solid organ transplant recipients have stable allograft function and optimal control of chronic medical comorbidities before attempting pregnancy (GRADE 1B); (4) we recommend that solid organ transplant recipients of reproductive age use highly effective contraception when on mycophenolate or other immunosuppressive agents with known teratogenic risk (GRADE 1A); (5) we recommend that solid organ transplant recipients contemplating pregnancy transition to an appropriate immunosuppressive regimen before attempting pregnancy to establish stable medication dosing and allograft function (GRADE 1C); (6) we recommend close monitoring of serum drug levels during pregnancy and the postpartum period to guide immunosuppressive therapy dosing (GRADE 1C); (7) we recommend that solid organ transplant recipients who are pregnant or contemplating pregnancy receive all indicated vaccinations before and during pregnancy (GRADE 1C); (8) given the risk of fetal and neonatal sequelae secondary to cytomegalovirus infection in pregnancy, we suggest that solid organ transplant recipients ideally complete any indicated antiviral prophylaxis or treatment before pursuing pregnancy (GRADE 2B); (9) we recommend daily low-dose aspirin prophylaxis to reduce the risk for preeclampsia in pregnant solid organ transplant recipients and to reduce the risk for renal allograft failure in renal transplant recipients (GRADE 1C); (10) as for all pregnant people, we recommend that pregnant solid organ transplant recipients have access to mental health specialists and receive screening for depression during pregnancy and the postpartum period (Best Practice); (11) because of the increased incidence of fetal growth restriction and common coexisting medical morbidities, we recommend serial assessment of fetal growth every 4 to 6 weeks throughout gestation after the anatomic survey (GRADE 1C); (12) we suggest antenatal surveillance from 32 weeks of gestation unless other fetal or maternal factors are identified in which case initiation of surveillance at an earlier gestational age is indicated (GRADE 2C); (13) we recommend that renal function be assessed before pregnancy or in early pregnancy in all solid organ transplant recipients (kidney and non-kidney) (GRADE 1C); (14) we suggest individualized delivery timing for pregnant solid organ transplant recipients and to consider delivery at between 37+0/7 and 39+6/7 weeks of gestation; in the absence of other indications, we suggest delivery by 39+6/7 weeks gestation for pregnant solid organ transplant recipients (GRADE 2B); (15) given that a trial of labor is associated with a high success rate and lower neonatal morbidity without increasing maternal morbidity or compromising graft survival, we recommend that cesarean delivery be reserved for medical obstetrical indications in solid organ transplant recipients (GRADE 1C); (16) we recommend that blood pressure targets in pregnant renal transplant recipients with chronic hypertension follow guidelines for nonpregnant recipients with a target blood pressure of ≤130/80 mm Hg (GRADE 1C); (17) we recommend monthly urine cultures to screen for asymptomatic bacteriuria with treatment if positive to protect the graft in pregnant renal transplant recipients (GRADE 1C); (18) we recommend that pregnancies in pancreas-kidney transplant recipients be managed in a similar way as those of renal transplant recipients alone (GRADE 1C); (19) we recommend characterizing the underlying condition that led to liver transplantation and assessing baseline renal function in pregnant liver transplant recipients. (GRADE 1C); (20) because of the cardiovascular demand of pregnancy and the unique physiological implications of cardiac transplantation, we recommend that pregnant heart transplant recipients receive multidisciplinary care with cardiology, cardiac and/or obstetrical anesthesiology, and maternal-fetal medicine specialists (Best Practice); and (21) we recommend careful delivery planning to minimize hemodynamic stress (including considering operative vaginal delivery to minimize Valsalva) and suggest continuous intrapartum or intraoperative electrocardiographic monitoring for heart transplant recipients (GRADE 1C).

Kidney transplantation remains the best treatment for patients with end-stage kidney disease, and it could partially mitigate systemic disorders of mineral and bone metabolism caused by secondary hyperparathyroidism. However, persistent hyperparathyroidism is still observed in 30-60% of patients 1 year after kidney transplantation, leading to impairment of allograft function and a disturbance of mineral metabolism. The timing of parathyroidectomy varies among transplant centers because the possible negative effects of parathyroidectomy on allograft outcomes are still unclear. This review provides a comprehensive and detailed overview of the natural course of hyperparathyroidism following kidney transplantation and the effects of the timing and extent of parathyroidectomy on allograft function. It aims to provide useful information for surgeons to propose an appropriate intervention strategy to break the vicious cycle of post-kidney transplantation hyperparathyroidism and deterioration of allograft function.

Tacrolimus, in combination with mycophenolate mofetil and glucocorticoids, is the basis of immunosuppressive therapy after renal transplantation. Tacrolimus intrapatient variability (IPV) and the blood concentration normalized by the dose (concentration/dose ratio, C/D ratio) both have an effect on the function of the transplanted kidney. In this study, we examined whether the metabolism rate affected IPV, whether the C/D ratio value was stable in the long-term follow-up, and whether it could be used for IPV measurements. In addition, our study population was examined for the effect of the C/D ratio and IPV on long-term renal function. The C/D ratio and IPV were examined in 170 patients at appointments held at 3, 6, 12 and 24 months after RTx. The average time post renal transplantation was 70 months. Renal function defined as creatinine concentration at the last appointment was examined. Results: the mean C/D ratio in the study group was 1.63. A negative correlation between the C/D ratio and creatinine concentration at the end of the follow-up was observed. Between the C/D ratio < and ≥1.63 groups, significant differences in creatinine concentration at the last appointment were found. No relationship was identified between the mean C/D ratio and IPV. The C/D ratio values increased significantly over a longer post-transplant period (12, 24, 60 and 120 m). We did not find a correlation between the mean IPV and the creatinine concentration from the last appointment. Our study group was divided into terciles according to IPV, while no renal graft function differences were found at the same appointment. Conclusion: the C/D ratio is useful for assessing the effects of the metabolism rate of tacrolimus on the long-term renal graft function. The C/D ratio does not affect the IPV value. IPV calculated from variability of the C/D ratio does not influence transplanted kidney function. The C/D changes over time.