Patients Receiving Kidney Transplants Research Articles

#1849 Returning to dialysis after kidney transplant failure: preliminary findings of a multi-centre database

Abstract Background and Aims Kidney transplant failure contributes to a considerable proportion of new dialysis starters. In some centres there are dedicated clinics for patients with failing kidney transplants, however, the specific needs of patients with dialysis after graft loss (DAGL) may be lost in the non-specific clinical review practiced in the general dialysis community. This study examines the mortality and morbidity risk in patients returning with DAGL and compares it to transplant-naïve (T-N) dialysis starters, to determine if the former warrant a more specialised approach. Method This is a retrospective observational study of mortality in all adult patients who started dialysis treatments in Fresenius Medical Care (North America, Latin America, Europe, Middle East, Africa, and Asia Pacific) from 1st January 2018 to 31st March 2021, were identified in the Apollo Dial DB dataset. DAGL was identified from the ICD-10 codes ‘Kidney transplant failure’, ‘Unspecified complication of kidney transplant’ and ‘Other complication of kidney transplant’ at dialysis start. The T-N control group had not previously received a kidney transplant and had not received immunosuppressive medication during the first six months of dialysis start. The first six months on dialysis were defined as baseline, months 7 to the end of year 5 were defined as the follow-up period. All-cause mortality was recorded during follow-up. Cox proportional hazards models were applied to explore the association between DAGL and all-cause mortality. Results A total of 360 469 dialysis starter patients from 41 countries were included in the analysis. 10 010 patients had DAGL and were compared with 350 459 in the T-N control group. In univariate analysis, DAGL patients were significantly younger in all age categories and had a higher proportion of male sex. Serum creatinine, ferritin, phosphate and neutrophil-to-lymphocyte ratio were higher in the DAGL group. Haemoglobin was lower in the DAGL group (Table 1). In the Cox proportional model adjusted for age, gender, and other laboratory and clinical markers, patients with DAGL had an equivalent survival probability compared with T-N dialysis starters (HR: 0.93, 95% CI: 0.86, 1.02) (Table 2). Conclusion DAGL patients appeared to have an increased mortality compared to T-N dialysis starters historically in the literature. Our large and recent study is in line with other recent publications suggesting a more equivalent survival in the two groups. Our results are compatible with younger patients receiving kidney transplantation early in their renal replacement therapy journey, thus constituting a significant proportion of DAGL patients. We posit that DAGL patients may start dialysis at a lower level of renal function, with higher levels of inflammation. Our analysis is preliminary and limited, not fully accounting for confounding factors. Future analysis of this large and well recorded dataset will allow us to examine these interesting associations and design a more specialised management approach to DAGL more closely.

Echocardiographic evaluation of myocardial structural and functional changes in patients with stage 5 chronic kidney disease before and after kidney transplantation

Introduction. Chronic kidney disease, stage 5, leads to structural remodeling of the myocardium, and heart failure. Kidney transplantation promotes normalization of structural and functional parameters of the myocardium through reverse remodeling with an improvement of its systolic function.Aim. To evaluate structural and functional changes of the myocardium in patients before and after kidney transplantation, using echocardiography.Material and methods. A retrospective cross-sectional study included 111 individuals of whom 36 patients underwent evaluation for kidney transplant waiting list placement program (Group I), and 51 patients received kidney transplants from deceased donors (Group II). Group III consisted of 24 individuals without kidney pathology. All patients underwent transthoracic two-dimensional echocardiography using the Phillips Epiq 7 device to determine the structural and functional parameters of the heart, including the use of speckle-tracking technique to assess longitudinal and circumferential myocardial deformation of the left ventricle.Results. There were no statistically significant differences in transthoracic echocardiography results between patients in Group I and Group II. When compared to the parameters of patients in Group III, statistically significant differences were found in the following parameters: volume and volume index of the left atrium, end-diastolic volume index, left ventricular mass index, interventricular septum thickness and posterior wall thickness of the left ventricle, as well as diastolic function parameters (E/A). Patients in Group I and Group II had significantly higher values of left atrium diameter: 32 (26.0;38.0) mmHg and 31.0 (27.3;40.0) mmHg, respectively, (p1-2=0.949), while in Group III this parameter value was 22.5 (20.8;25.3) mmHg (p1-3<0.001, p2-3<0.001). Correlation analysis revealed statistically significant correlations between left ventricular mass index and global circumferential strain (r=0.41, p=0.0027), as well as between E/e' ratio and left ventricular mass index (r=0.323, p=0.00197). It was found that after 3 months post kidney transplantation, there was a decrease in the left atrium diameter, volume, and volume index. The values of left atrium diameter immediately after kidney transplantation and after 3 months were 40 (32.5;45) mmHg and 35 (25.5;41.0) mmHg (p=0.049); those of the left atrium volume were 62.5 (50.0;77.3) and 51.5 (47.5;64.5) ml (p=0.03); and those of the left atrium volume index were 33.4 (29.3;40.2) and 28.3 (25.5;33.6) ml/m2 (p=0.01) respectively.Conclusions. Patients with chronic kidney disease stage 5 have a high incidence of functional and structural abnormalities of the left heart chambers; left ventricular mass index positively correlates with E/e' and global circumferential strain. At 3 months after kidney transplantation, there was a slight positive trend manifested in the form of a decrease in left atrium diameter and a decrease in left ventricle volume. Further dynamic study of this group of patients in the long term after kidney transplantation is planned.

Effect of a Hispanic outreach program on referral and liver transplantation volume at a single center

BackgroundAlthough Hispanic patients have high rates of end-stage liver disease and liver cancer, for which liver transplantation (LT) offers the best long-term outcomes, they are less likely to receive LT. Studies of end-stage renal disease patients and kidney transplant candidates have shown that targeted, culturally relevant interventions can increase the likelihood of Hispanic patients receiving kidney transplant. However, similar interventions remain largely unstudied in potential LT candidates. MethodsReferrals to a single center in Texas with a large Hispanic patient population were compared before (01/2018–12/2019) and after (7/2021–6/2023) the implementation of a targeted outreach program. Patient progress toward LT, reasons for ineligibility, and differences in insurance were examined between the two eras. ResultsA greater proportion of Hispanic patients were referred for LT after the implementation of the outreach program (23.2% vs 26.2%, p = 0.004). Comparing the pre-outreach era to the post-outreach era, more Hispanic patients achieved waitlisting status (61 vs 78, respectively) and received a LT (971 vs 82, respectively). However, the proportion of Hispanic patients undergoing LT dropped from 30.2% to 20.3%. In the post-outreach era, half of the Hispanic patients were unable to get LT for financial reasons (112, 50.5%). ConclusionsA targeted outreach program for Hispanic patients with end-stage liver disease effectively increased the total number of Hispanic LT referrals and recipients. However, many of the patients who were referred were ineligible for LT, most frequently for financial reasons. These results highlight the need for additional research into the most effective ways to ameliorate financial barriers to LT in this high-need community.

Collapsing glomerulopathy is likely a major contributing factor for worse allograft survival in patients receiving kidney transplants from black donors.

Although a few registry-based studies have shown associations between receiving kidney allografts from Black donors and shorter allograft survival, detailed, large, single-center studies accounting for common confounding factors are lacking. Furthermore, pathologic alterations underlying this potential disparity have not been systematically studied. We performed a retrospective clinical-pathological study of kidney transplant recipients who received kidney allografts from either Black (n = 407) or White (n = 1,494) donors at Columbia University Irving Medical Center from 2005 to 2018, with median follow-up of 4.5 years post-transplantation. Black donor race was independently associated with allograft failure (adjusted HR = 1.34, p = 0.02) and recipients of kidney allografts from Black donors had a higher incidence of collapsing glomerulopathy [7.4% vs. 1.9%, OR = 4.17, p < 0.001]. When causes of allograft failure were examined, only allograft failure following development of collapsing glomerulopathy was more frequent in recipients of allografts from Black donors [15% vs. 5%, OR = 3.16, p = 0.004]. Notably, when patients who developed collapsing glomerulopathy were excluded from analysis, receiving kidney allografts from Black donors was not independently associated with allograft failure (adjusted HR = 1.24, p = 0.10). These findings revealed that, compared with recipients of kidney allografts from White donors, recipients of kidneys from Black donors have modestly shorter allograft survival and a higher probability of developing collapsing glomerulopathy, which negatively impacts allograft outcome. Identification of collapsing glomerulopathy risk factors may help decrease this complication and improve allograft survival, which optimally may reduce racial disparities post-transplantation.

Risk factors and outcomes of IgA nephropathy recurrence after kidney transplantation: a systematic review and meta-analysis.

IgA nephropathy may recur in patients receiving kidney transplantation due to IgA nephropathy induced renal failure. The risk factors for recurrence are still at issue. The aim of this study was to conduct a systematic review and meta-analysis to assess risk factors and outcomes for IgA nephropathy recurrence. We used PubMed, EMBASE, Cochrane Library, Web of Science, Scopus, CNKI, WanFang, VIP and CBM to search for relevant studies published in English and Chinese. Cohort or case-control studies reporting risk factors or outcomes for IgA nephropathy recurrence were included. Fifty-eight studies were included. Compare to no recurrence group, those with IgAN recurrence had younger age (mean difference [MD]=-4.27 years; risk ratio [RR]=0.96), younger donor age (MD=-2.19 years), shorter time from IgA nephropathy diagnosis to end stage renal disease (MD=-1.84 years; RR=0.94), shorter time on dialysis (MD=-3.14 months), lower human leukocyte-antigen (HLA) mismatches (MD=-0.11) and HLA-DR mismatches (MD=-0.13). HLA-B46 antigen (RR=0.39), anti-IL-2-R antibodies induction (RR=0.68), mycophenolate mofetil (RR=0.69), and pretransplant tonsillectomy (RR=0.43) were associated with less IgAN recurrence. Of note, male recipient gender (RR=1.17), related donor (RR=1.53), retransplantation (RR=1.43), hemodialysis (RR=1.68), no induction therapy (RR=1.73), mTOR inhibitor (RR=1.51), angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (RR=1.63) were risk factors for IgAN recurrence. Recurrence increased the risk of graft loss (RR=2.19). This study summarized the risk factors for recurrence of IgA nephropathy after kidney transplantation. Well-designed prospective studies are warranted for validation. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=377480, identifier CRD42022377480.

Effect of vitaminK on improving post‑kidney transplant outcomes: a meta‑analysis.

The effect of vitamin K on clinical outcomes in patients receiving kidney transplantation is contested according to previous studies. This meta-analysis aimed to summarize the impact of vitamin K on all-cause mortality, renal function, inflammation, and vascular/bone health in patients receiving kidney transplantation. EMBASE, PubMed, and Cochrane were searched for literature concerning the effect of vitamin K on clinical outcomes of patients receiving kidney transplantation until December 2022. Normal vitamin K status/vitamin K supplementation was considered as the experimental group; while vitamin K deficiency/no vitamin K supplementation was considered as the control group. All-cause mortality, renal function indexes, C-reactive protein (CRP), and vascular/bone health indexes were extracted and analyzed. A total of seven studies with 1,101 patients in the experimental group and 651 patients in the control group were included. All-cause mortality was decreased in the experimental group vs. the control group [relative risk (95% confidence interval (CI)]: 0.72 (0.60-0.86), P<0.001]. Regarding renal function indexes, the estimated glomerular filtration rate was increased in the experimental group vs. the control group [mean difference (95% CI): 9.87 (1.48-18.26), P=0.021]; while creatinine and albumin remained unchanged between the two groups (both P>0.05). Moreover, CRP, systolic blood pressure, diastolic blood pressure, triglycerides, hemoglobin, calcium, and 25-hydroxyvitamin D were unchanged between the two groups (all P>0.05). Publication bias was low, and the robustness assessed by sensitivity analysis was generally acceptable. Thus vitamin K exerted a potential implication in reducing all-cause mortality and improving renal function in patients receiving kidney transplantation.

Influencing factors of post-transplantation diabetes mellitus in kidney transplant recipients and establishment of a risk prediction model.

The aim was to explore the influencing factors of post-trans-plantation diabetes mellitus (PTDM) in kidney transplant recipients and to es-tablish a risk prediction model. A retrospective analysis was performed on the clinical data of 408 patients subjected to kidney transplantation from May 2015 to March 2022. With the simple random sampling method, they were divided into a training set (n=306) and a test set (n=102) at a ratio of 3:1. According to the occurrence of PTDM, the training set was further classified into PTDM and non-PTDM groups. The influencing factors of PTDM were identified by least absolute shrinkage and selection operator and multivariate logistic regression analysis. A nomogram prediction model was constructed and validated. Non-PT-DM and PTDM groups had significantly different preoperative body mass index (BMI), family history of diabetes mellitus, 2-h preoperative and postprandial blood glucose, 2-hpreoperative and postprandial peptide index, postoperative hypomagnesemia, whole blood concentration of tacrolimus, triacylglycerol, glycated albumin and fasting blood glucose (P&lt;0.05). BMI, family history of diabetes mellitus, 2-h preoperative and postprandial blood glucose, and post-operative whole blood tacrolimus concentration were independent risk factors for PTDM. In contrast, the 2-h preoperative and postprandial peptide index was an independent protective factor (P&lt;0.05). The incidence of PTDM in patients receiving kidney transplantation correlates with the family history of diabetes mellitus, preoperative BMI, 2-h postprandial blood glucose, 2-h postprandial peptide index, and postoperative whole blood tacrolimus concentration.

The Impact of Intraoperative Graft Blood Flow Measurement on Early Graft Function

The aim of this study is to evaluate the impact of intraoperative allograft vascular flow on early kidney graft function. A total of 159 patients underwent kidney transplantation from January 2017 to March 2022 at Linkou Chang Gung Memorial Hospital. Graft arterial and venous blood flow was measured separately with a transient time flowmeter (Transonic HT353; Transonic Systems, Inc, Ithaca, NY, United States) after ureteroneocystostomy. The early outcomes, including the postoperative creatinine level, were analyzed accordingly. There were 83 males and 76 females, with a mean age of 44.5 years. The mean graft arterial flow measured was 480.6 mL/min, and the mean venous flow was 506.2 mL/min. Delayed graft function (DGF) incidence was 36.5%, 32.5%, and 40.8% in total, living, and deceased donor groups, respectively. Living donor and deceased donor kidney transplantation were analyzed separately. In the DGF subgroup, there were lower graft venous flows, higher body mass index (BMI), and more male patients in the living kidney transplant group. Similarly, the deceased donor kidney transplantation group with delayed graft function tended to have higher body height, higher body weight, higher BMI, and more diabetes mellitus. The multivariate analysis showed that lower graft venous blood flow (odds ratio [OR]=0.995, P=.008) and higher BMI (OR=1.144, P=.042) were significantly correlated with delayed graft function in living donor kidney transplantations. In the deceased donor group, a multivariate analysis of risk factors showed that BMI had a significant correlation with delayed graft function (OR=1.41, P=.039). Graft venous blood flow was significantly associated with delayed graft function in living donor kidney transplantation, and high BMI was correlated with DGF in all patients receiving kidney transplantation.

Potential Effects of Remdesivir on Tacrolimus Exposure in Transplant Recipients With COVID-19 Infection

Remdesivir has proven to have benefits against COVID-19 infection. However, data supporting drug-drug interactions are insufficient. Clinicians have noticed that calcineurin inhibitor (CNI) levels tend to change after starting remdesivir. This retrospective study aimed to evaluate the effect of remdesivir on CNI levels. This study included adult solid organ transplant recipients hospitalized for COVID-19 who received remdesivir while on CNI. Patients were excluded if they started on other medications known to interact with CNI. The primary end point was the percentage of change in CNI levels after starting remdesivir. Secondary end points included the time until CNI levels reached a maximum increase in trough levels, the incidence of acute kidney injury (AKI), and the time until CNI levels normalized. Of the 86 patients screened, 61 were included (56 on tacrolimus and 5 on cyclosporine). Most patients received kidney transplants (44.3%), and baseline demographics were similar among the transplanted organs. The median increase in tacrolimus level after starting remdesivir was 84.8%, and only 3 patients had no significant change in CNI levels. The median increase in tacrolimus level was more pronounced in lung and kidney recipients than in heart recipients (96.5% vs. 93.9% vs. 64.6 %, respectively). The median time to maximum increase in tacrolimus trough levels was 3 days, and it took 10 days after the remdesivir course for levels to return to baseline. This retrospective analysis demonstrates that CNI levels were significantly elevated after starting remdesivir. However, future studies are warranted to evaluate this interaction further.

Prognostic value of the 7-year protocol biopsy of adult kidney allografts: impact of mesangiosclerosis and proteinuria

Aim The aim of the present study was to clarify the relationship between the Banff score of the 7-year protocol biopsy and the allograft outcome. Methods One-hundred-and-eighty-four patients received kidney transplantation from 2002 to 2008. We excluded patients aged <20 years at transplantation (n = 24), those who did not undergo a 7-year protocol biopsy (n = 66), and those who underwent for-cause biopsy (n = 5). Consequently, 89 patients who underwent a 7-year protocol biopsy were enrolled. We analyzed the relationship between the clinicopathological findings 7 years after transplantation and the estimated glomerular filtration rate (eGFR) change per year and allograft survival. Histological evaluation was performed using the Banff 2015 classification. Results Among the clinicopathological findings, each Banff mesangial matrix increase (mm) score ≥1 and proteinuria ≥1+ was independently associated with the eGFR decline per year during a median follow-up of 73 months. Furthermore, in the model of the clinicopathological findings including the presence of mm with proteinuria, mm ≥1 alone and mm ≥1 with proteinuria were each independently associated with the eGFR decline. The graft survival was significantly worse for those with mm ≥1 with proteinuria than those with mm ≥1 without proteinuria. Conclusion Among the 7-year protocol biopsy findings, the presence of mm alone and mm with proteinuria were each significant predictors of eGFR decline. The presence of both proteinuria and mm had a negative impact on graft survival. These results underscore the significance of the Banff mm score and proteinuria at the time of the 7-year protocol biopsy to predict the allograft outcome.

Additional surgery in patients with bladder augmentation

Bladder augmentation is an option to protect kidneys and treat incontinence in frequent neurogenic and congenital non-neurogenic disorders. However, patients may need also other procedures to treat incontinence or to aid catheterizations. In addition, the patients are prone to complications. To evaluate complications or additional surgeries in augmentation cystoplasty according to the etiology of the bladder dysfunction. Data on additional surgical procedures related to bladder augmentation were collected from 128 patients who had undergone enterocystoplasty between 1990 and 2019, with a median age of 10.1 years (IQR 7.2-12.8) and a follow-up time of 11.8 years (IQR 5.7-18.6) after augmentation. Eighty-three patients had a neurogenic disease, and 45 patients had a non-neurogenic disease. Bladder neck operations were performed either at the time of or after augmentation for 62 patients (48.4%), more commonly in the non-neurogenic than neurogenic group <0.01. In addition, continent stoma operations in 56 (36.8%) patients were more common in the non-neurogenic group (p<0.01). Ten patients received kidney transplantation (four in the neurogenic, six in the non-neurogenic group); seven of these patients originally had dysplastic kidneys, two developed nephrological kidney disease, and one had hydronephrosis and renal insufficiency at the time of diagnosis of neurogenic bladder. Surgical problems resulting from bladder augmentation were treated in 28 patients (21.8%). The risk for surgical treatment because of complications was 4%, 17%, 24%, 27% and 27% at 1, 5, 10, 15 and 20 years follow up respectively. Complications were more common in patients in non-neurogenic than in patients with neurogenic group (p<0.01). However, the greater proportion of continent stomas in non-neurogenic group explained the difference (Fig.). The most frequent complication requiring surgery during follow-up was bladder stones, which occurred in 24 (18.8%) patients. The first stone was treated at a median of 3.3 years (range 0.3-14.2) after augmentation. Stones were more common in patients with a continent stoma than without (p<0.01). Other indications for surgical treatment were as follows: obstructive ileus in five patients, reduced bladder capacity in three patients, bladder perforation in two patients and lobulated bladder with infections in one patient. The risk for surgical treatment was about 27% in 20-year follow-up after bladder augmentation, because of augmentation related complications. The most prevalent complication was bladder stone, that was mainly associated with continent stomas. Continent stomas were most prevalent in patients with non-neurogenic diagnosis.

Clinical and Genetic Characterization of Cystinosis: Unmet Healthcare Needs in a Cohort Study from a Developing Country

Background Cystinosis is a rare disease caused by CTNS gene defects. The main clinical presentations are nephropathic infantile cystinosis (NIC) and nephropathic juvenile cystinosis (NJC); both develop chronic kidney disease (CKD) and extrarenal complications. Opportune diagnosis and access to therapy are challenging in developing countries. Methods To describe the clinical and genetic profile in all cystinosis patients known to be diagnosed in Chile, we performed a retrospective review of the medical records of those patients diagnosed from 1994 to 2022. Age at diagnosis, glomerular filtration rate, metabolic variables, anthropometric values, access to treatment, outcomes, and genetic results were analyzed. Results Nine patients (8NIC/1NJC) were diagnosed. Patients with NIC had a median age of 16.5 (IQR 13-23) months at diagnosis, and two patients died during follow-up. Most of the patients started cysteamine therapy up to 5 months after diagnosis and reached CKD stages 3-4 within four years. During the follow-up, all but one of the NIC patients showed height for age Z-score values between -1.5 and -4.0. Two patients received kidney transplants, and one of them remains functional after 15 years. The single NJC was a 21-year-old female patient who received irregular cysteamine therapy and rapidly reached CKD stage 5. Genetic testing was positive in 7/7 cases, being del57kb the predominant variant (10/14 alleles). Conclusions Developing countries face many challenges in providing adequate healthcare. Our findings show clinical and diagnostic aspects to the medical and patient community that might contribute to the diagnostic approach and treatment access for cystinosis in Chile. Opportune genetic testing may facilitate early diagnosis that is known to be associated with a better prognosis.

The percentage of circulating fibrocytes is associated with increased morbidity of pulmonary hypertension in patients on hemodialysis.

Pulmonary hypertension (PH) is highly prevalent in patients receiving dialysis. The precise mechanisms underlying PH in hemodialysis (HD) patients have not been adequately addressed. Emerging experimental evidence indicates that circulating fibrocytes may contribute significantly to this process. We measured the proportion of circulating fibrocytes using flow cytometry analysis and prospectively analyzed patients during HD from February 1, 2017, to February 1, 2022. Then we investigated correlations between circulating fibrocytes, inflammation cytokines, PH, and their affective factors that predict the prognosis of HD patients. The cohort included 192 patients. During a follow-up of 5years, we registered 66 all-cause deaths, and 11 patients received kidney transplantation. The incidence of PH among HD patients was 30.9%. We found that the circulating fibrocyte level significantly correlated with pulmonary arterial systolic pressure (r = 0.412, p < 0.05). In the multiple logistic regression analysis, the percentage of circulating fibrocytes was an independent predictor of PH (odds ratio [OR]: 2.080, 95% confidence interval [CI]: 1.539-2.812, p < 0.001). Controlling for confounding covariates in the multivariate Cox regression models, the presence of PH conferred an increased risk of all-cause mortality in HD patients [hazard ratio (HR): 2.183, 95% CI:1.257-3.788, p = 0.006]. The prevalence of PH was high in HD patients and was associated with higher all-cause mortality. Higher circulating fibrocyte level was an independent predictor of the presence of PH; these fibrocytes may serve as early detection markers and novel therapeutic targets.

Diabetes Mellitus as a Predictive Factor for Urinary Tract Infection for Patients Treated with Kidney Transplantation.

Background and Objectives: We aimed to investigate the rate of incidence and risk factors of post-transplant urinary tract infection (UTI) in patients receiving kidney transplantation (KT) at our institution. Materials and Methods: A retrospective cohort study was carried out on patients who underwent KT for end-stage kidney disease (ESKD) from January 2008 to December 2021 at Gifu University Hospital. UTI was defined as the existence of bacterial and/or fungal infection in urine with ≥105 colony-forming units/mL, with or without urinary and/or systemic symptoms of UTI. Patients were divided into two groups: those with UTI after KT (UTI group) and those without UTI (non-UTI group). The primary endpoint of this study was the relationship between covariates and UTI after KT. Results: Two hundred and forty patients with ESKD received KT at Gifu University Hospital. Thirty-four participants developed UTI after surgery, and the most common pathogen was Escherichia coli. At the end of the follow-up, graft loss was observed in six patients (2.5%), independent of UTI episodes. In the multivariate analysis, diabetes mellitus (DM) was statistically associated with post-transplant UTI in kidney transplant recipients. Conclusions: Preoperative serum glucose control in patients with DM may have a crucial role in preventing UTI and preserving renal function after KT.

Short-term outcome of kidney transplantation from deceased donors with nephrolithiasis.

Shortage of kidney allografts is a major barrier to end-stage renal disease patients receiving kidney transplantation, and it is necessary to enlarge the donor pool and find better ways of using available allografts. The global incidence of nephrolithiasis is increasing, nephrolithiasis affects approximately 10% of adults worldwide, and it also affects the kidney donors. However, there is little information about the use of cadaveric kidney allografts with nephrolithiasis. This study aims to evaluate the safety and outcome of kidney transplantation with allografts from the deceased donors with nephrolithiasis. A total of 520 deceased donors who was at least 10 years old, and 945 adult recipients with single kidney transplantation at the Department of Kidney Transplantation, the Second Xiangya Hospital from 2016 to 2020 were included in this study. The donors were divided into 2 groups according to nephrolithiasis diagnoses: The donors with nephrolithiasis (D + ) and the donors without nephrolithiasis (D - ). The recipients were assigned into 3 groups according to their donors and the allografts they received: The allografts from donors without nephrolithiasis (D - K - ), the allografts without nephrolithiasis from donors with nephrolithiasis (D + K - ), and the allografts with nephrolithiasis (D + K + ). The demographic and clinical data of enrolled subjects were retrospectively analyzed. The allograft discard ratio between different donors were analyzed. The one-year survival of allografts and recipients, as well as the allograft function and the complications of kidney transplantation were compared. Fifty out of 520 donors had nephrolithiasis, and the nephrolithiasis incidence was 9.6%. We recovered 1 040 kidneys, and total discard rate was 4.4% (46/1 040). The D + group had a rate of 7% discard. The donors with kidney discard accounted for 12% in the D + group, and this was higher than that of donors in the D - group (5.1%, P <0.05). The total incidence of delayed graft function (DGF) was 7.5%, and there were no significant differences in the incidence of DGF in recipients among the D - K - , D + K - , and D + K + group (7.5% vs 6.5% vs 8.2%, P> 0.05). During the one-year follow-up, 8 allografts lost function and 19 recipients died with a functional allograft. Recipients in the D - K - , D + K - ,and D + K + groups also had no significant difference between a one-year allograft and patient survival rate ( P >0.05). However, recipients in the D + K + group had a higher level of serum creatinine [(139.2±62.46) μmol/L vs (117.19±51.22) μmol/L, P <0.05] and lower estimated glomerular filtration rate [eGFR; (56.67±23.31) mL/(min·1.73 m -2 ) vs (66.86±21.90) mL/(min·1.73 m -2 ), P <0.05] compared with recipients in the D - K - group at 12 months after transplantation. During the first year after transplantation, 4 recipients developed urolithiasis, and recipients who received allografts from the D + group donors had a higher incidence of urolithiasis than those who received allografts from the D - group donors (2.2% vs 0.2%, P <0.05). There were no significant differences in the incidence of urinary tract infections and ureteral strictures at 1 year between recipients of D + and D - donors (both P >0.05). The cadaveric kidney allografts with nephrolithiasis could be safely used for transplantation, and the short-term outcome is acceptable. However, nephrolithiasis in donors may increase the rate of kidney discard, disturb the short-term function of allografts, and increase the risk of urolithiasis in recipients. Further research with a long-term study is needed to verify the long-term outcome of kidney transplantation using cadaveric kidney allografts with nephrolithiasis.

Posttransplant-Alloantibodies Against MICA Antigens Associated With Decreased Long-Term Allograft Survival of Kidney Transplant Recipients

Previous evidence showed that antibodies against major histocompatibility complex class I-related chain A (MICA) could lead to antibody-mediated rejection in kidney transplantation in case where the patients had no alloantibodies against HLA. However, the effects of posttransplant anti-MICA antibodies on long-term renal allograft survival and function remained unsettled. We tested the posttransplant anti-MICA antibodies in 150 kidney transplant patients. The aim of this study was to compare the long-term graft survival and function between patients who were MICA positive and those who were negative. The posttransplant serum samples from 150 patients receiving kidney transplantation in our center from 2012 to 2013 were tested for MICA antibodies and HLA antibodies by Luminex single antigen array technology. Graft survival and function were followed up for a mean time of 74.2 months. The research was conducted in accordance with the Helsinki Congress and the Declaration of Istanbul. Of the 150 patients, 38 (25.3%) were sensitized against MICA after transplantation. The anti-MICA antibodies-positive (anti-MICA+) group had a worse long-term renal allograft survival than that of anti-MICA-negative (anti-MICA-) group (P = .029), even when stratified by posttransplant HLA sensitization status or donor source. Anti-MICA antibodies also had a detrimental impact on renal allograft function, but only at 1 year posttransplantation (estimated glomerular filtration rates at 1 year: anti-MICA+ 66.6 mL/min/1.73 m2 vs anti-MICA- 78.7 mL/min/1.73 m2; P = .023). Posttransplant anti-MICA antibodies were associated with decreased long-term renal allograft survival and short-term renal allograft function.

Comparing the Frequency of Lymphoceles Which Needed Intervention in Recipients of Living Donor Versus Deceased Donor Kidney Transplants.

In this study, we aimed to compare the frequency of lymphoceles that needed intervention in recipients who received kidneys from living versus deceased donors. The records of all patients who underwent kidney transplantation at the Labbafinejad Hospital from 2012 to 2021 were retrospectively reviewed to determine the incidence of lymphoceles that needed intervention for management. From March 2012 to April 2021, 1752 patients received kidney transplantation in Labbafinejad Hospital including 975 transplantations from living donors and 777 transplantations from deceased donors. Symptomatic lymphoceles were observed postoperatively in 23 patients. Symptoms included compressive effect on the ureter, hydroureteronephrosis of the transplanted kidney, frequency, urinary retention, infection, abdominal discomfort, or rise in serum creatinine. Out of 23 patients who needed intervention for symptomatic lymphocele, 15 patients were recipients of living donors and 8 patients were recipients of deceased donors [1.53% versus 1.03%, P=.40]. Intervention consisted of open surgical drainage in 6 patients [4 recipients of living donors and 2 recipients of deceased donors], and nephrostomy insertion in 17 patients. Open operation was necessary in 5 (47%) patients in whom arterial anastomosis was made to the internal iliac artery versus 1 (9%) patient in whom the anastomosis was not made to the internal iliac artery (P=0.15). Symptomatic lymphoceles which needed intervention were observed in low frequency (1.31%). Most cases can be managed by endoscopic drainage without relapse. Type of donation had no relationship with the need for open or endoscopic intervention in lymphoceles. A higher proportion of open surgeries to control lymphocele were observed in recipients in whom the internal iliac artery was used for arterial anastomosis however the difference was not statistically significant.

Impact of pre-transplant dialysis modality on kidney transplant outcomes: a systematic review and meta-analysis.

For end-stage renal disease (ESRD), patients receiving kidney transplantation, peritoneal dialysis (PD) and hemodialysis (HD) are both appropriate modes of pre-transplant dialysis. The aim of this review is to assess the impact of pre-transplant PD compared to HD on kidney transplant outcomes in ESRD patients. A comprehensive search in digital databases, like PubMed, SCOPUS and EMBASE and a manual search were conducted to identify cohort studies comparing the kidney transplant outcomes of both pre-transplant dialysis modalities. The data were subjected to both qualitative and quantitative analysis. A meta-analysis was carried out to calculate the effect estimate for patient survival, graft survival and delayed graft function, death-censored graft survival, acute rejection-free graft survival, graft vessel thrombosis, urological complications, surgical complications, any infections, and onset of diabetes after transplantation. The qualities of the included studies were judged by the New-castle Ottawa scale. The overall patient survival is shown to be better with patients who underwent pre-transplant PD compared to HD with OR 1.34 95% CI [1.11, 1.61], p = 0.002. Delayed graft function was found to be highly associated with HD compared to PD with OR 0.60 [0.52, 0.70], p<0.0001 with moderate heterogeneity (i2 = 48%). However, no difference was observed in terms of graft survival, complications, infections, and new onset of diabetes mellitus compared to patients undergoing pre-transplant HD. Within the limitations of the review, it can be concluded that ESRD patients undergoing pre-transplant PD were found to have better patient survival and lower incidence of delayed graft function.

Amelioration of Renal Injury by Resveratrol in a Rat Renal Transplantation Model via Activation of the SIRT1/NF-κB Signaling Pathway.

Purpose The improvement of the long-term survival of patients receiving kidney transplantation remains challenging. Ischemia reperfusion injury (IRI) reduces long-term renal graft survival in the early posttransplantation phase. However, few studies have investigated the effects of IRI on the pathogenesis of chronic renal graft failure. Silent information regulator 1 (SIRT1) regulates antioxidative stress and inflammatory response and protects against IRI. This study is aimed at investigating the role of resveratrol (RSV), an SIRT1 activator, in preventing renal injury in a rat renal transplantation model. Methods A classical F334-to-LEW orthotopic renal transplantation rat model was established. The experiment group was treated with RSV from three days prior to kidney transplantation and the treatment lasted until the day of harvest. Uninephrectomized F344 and Lewis rats were used as controls. After 12 weeks, the effects of RSV were evaluated according to renal function, histopathology, immunohistochemistry, and western blotting. The activities of oxidative stress-related markers and proinflammatory cytokines were also assessed. Results RSV treatment significantly ameliorated renal function and histopathological lesions in kidney-transplanted rats and increased the levels of GSH, SOD, and CAT and decreased the levels of MDA and iNOS. Furthermore, RSV also inhibited the expression of proinflammatory cytokines/chemokines such as TNF-α, CD68, and IL-6 in kidney-transplanted rats. In addition, the transplant group displayed significantly lower level of SIRT1 and higher level of Ac-NF-κBp65. RSV increased the expression of SIRT1 and decreased the expression of Ac-NF-κBp65. Conclusion SIRT1 plays an important role in the pathogenesis of chronic renal allograft dysfunction. It is a potential therapeutic agent for ameliorating inflammation and oxidative stress-induced renal injury following kidney transplantation by activating the SIRT1/NF-κB signaling pathway.

Effects of preservative fluid associated possible donor-derived carbapenem-resistant Klebsiella Pneumoniae infection on kidney transplantation recipients

BackgroundInfections remain a major cause of morbidity and mortality in kidney transplant (KT) recipients. This study aimed to investigate the preservation fluid (PF) samples from deceased donors and report the impacts of possible donor-derived carbapenem-resistant Klebsiella pneumoniae (pdd-CRKP) infections on KT recipients.MethodsA retrospective study was performed that included all recipients who received kidney transplantation from deceased donors in our hospital between December 2018 and December 2020. A total of 212 patients received kidney transplantation from deceased donors, a total of 206 PF samples were collected, and 20 recipients had a CRKP-positive culture. Both donors and recipients with CRKP-positive PF cultures were divided into two groups, and continuous variables between the two groups were compared using independent-sample t tests and Mann-Whitney tests. Categorical variables were compared using the chi-square test or Fisher’s exact test. The significance level of p values was set at 0.05.ResultsA total of 337 recipients underwent kidney transplantation, including 212 recipients of organs from deceased donors and 110 corresponding deceased donors. A total of 206 PF samples were collected, and 20 recipients had CRKP-positive PF cultures. The donors’ length of ICU stay was a potential risk factor for CRKP positivity in the PF culture (P < 0.05). Fifteen recipients were infected with pdd-CRKP, and the incidence of pdd-CRKP infection was 7.3% (15/206). The use of antibiotics, including ceftazidime-avibactam (CAZ-AVI), was a potential protective factor against death and graft loss in recipients with a CRKP-positive PF culture (P < 0.05).ConclusionsThis study shows that the incidence of pdd-CRKP is high in our centre, recipients with pdd-CRKP infection can still achieve a good prognosis with the use of antimicrobial agents including CAZ-AVI.