COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic.

BACKGROUND: Kidney transplant recipients have an increased risk of complications from COVID-19. However, data on the risk of allograft damage or death in kidney transplant recipients recovering from COVID-19 is limited. In addition, the first and second waves of the pandemic occurred at different times all over the world. In Turkey, the Health Minister confirmed the first case in March 2020; after that, the first wave occurred between March and August 2020; afterward, the second wave began in September 2020. This study aims to demonstrate the clinical presentations of kidney transplant recipients in the first two waves of the pandemic in Turkey and explore the impact of COVID-19 on clinical outcomes after the initial episode. METHODS: Patients with COVID-19 from seven centers were included in this retrospective cohort study. Initially, four hundred and eighty-eight kidney transplant recipients diagnosed with COVID-19 between 1 March 2020 to 28 February 2021 were enrolled. The endpoints were the occurrence of all-cause mortality, acute kidney injury, cytokine storm, and acute respiratory distress syndrome. In addition, longer-term outcomes such as mortality, need for dialysis, and allograft function of the surviving patients was analyzed. RESULTS: Four hundred seventy-five patients were followed up for a median of 132 days after COVID-19. Forty-seven patients (9.9%) died after a median length of hospitalization of 15 days. Although the mortality rate (10.1% vs. 9.8%) and intensive care unit admission (14.5% vs. 14.5%) were similar in the first two waves, hospitalization (68.8% vs. 29.7%; p < 0.001), acute kidney injury (44.2% vs. 31.8%; p = 0.009), acute respiratory distress syndrome (18.8% vs. 16%; p = 0.456), and cytokine storm rate (15.9% vs. 10.1%; p = 0.072) were higher in first wave compared to the second wave. These 47 patients died within the first month of COVID-19. Six (1.4%) of the surviving patients lost allografts during treatment. There was no difference in the median serum creatinine clearance of the surviving patients at baseline (52 mL/min [IQR, 47-66]), first- (56 mL/min [IQR, 51-68]), third- (51 mL/min [IQR,48-67]) and sixth-months (52 mL/min [IQR, 48-81]). Development of cytokine storm and posttransplant diabetes mellitus were independent predictors for mortality. CONCLUSIONS: Mortality remains a problem in COVID-19. All the deaths occur in the first month of COVID-19. Also, acute kidney injury is common in hospitalized patients, and some of the patients suffer from graft loss after the initial episode.

Correlation of Luminex-Based Single Antigen Based Results With Complement-Dependent Cytotoxicity Crossmatch and Flow Cytometry Crossmatch Results: A Single-Center Experience From Istanbul.

BACKGROUND: This study aimed to retrospectively investigate the correlation of mean Class I donor-specific antibody (DSA) intensity values detected in Luminex-based techniques with the results of complement-dependent cytotoxicity crossmatch (CDC-XM) and flow cytometry crossmatch (FC-XM) results. METHODS: A total of 335 patients with kidney failure and their living donors whose CDC-XM, FC-XM, and single antigen based (SAB) tests were studied between 2018 and 2020 for transplant preparation from living donor candidates were included in the study. Patients were divided into 4 groups according to their mean fluorescence intensity (MFI) values of SAB assay. RESULTS: Anti-HLA antibodies (class I and/or class II) were detected using SAB in 91.6% patients included in the study (MFI >1000). Class I DSA was positive in 34.8% of patients with anti-HLA antibodies. When CDC-XM and FC-XM results were evaluated in the 4 groups separated according to MFI values, 3 patients with DSA MFI <1000 had negative CDC-XM and T-B-FC-XM results. Of 32 patients with DSA-MFI between 1000 and 3000, 93.75% (n = 30) had T-B-FC-XM or CDC-XM-negative results, and 6.25% (n = 2) had B-FC-XM-positive results. The CDC-XM, T, and B-FC-XM were negative in all 17 patients with DSA-MFI between 3000 and 5000. Our results showed that MFI >5834 DSA values were significantly correlated with positive T-FC-XM (P < .001), and MFI >6016 values were significantly correlated with positive CDC-XM (P = .002). In addition, MFI values >5000 were associated with both CDC-XM and FC-XM in our study. CONCLUSIONS: The MFI values >5000 correlated with both CDC-XM and FC-XM.

Living donor liver transplantation for hepatocellular carcinoma: a single center analysis of outcomes and impact of different selection criteria.

We examined the outcomes of patients who received living donor liver transplantation (LDLT) for HCC comparing the impact of up-to-seven criteria and Asan Criteria (AC) with Milan Criteria (MC). Between July 2004 and July 2009, of 175 consecutive LDLT, there were 45 consecutive patients with HCC. Forty patients who completed 12 months follow-up were enrolled. In search for the highest number of expansion, we selected AC as the extended criteria. Patients were divided into having tumors within MC, beyond MC within AC and Beyond Criteria (BC) groups. With a median follow-up of 46 months, overall 1, 3, and 5 years survival was -90%, -81%, and -70%, respectively. In patients within AC, estimated mean survival was 49.8 vs. 40.5 months for BC group (P = 0.2). Disease-free survival was significantly higher in patients within AC comparing with BC group; 48.0 vs. 38.6 months (P = 0.04). Preoperative AFP level >400 and poor tumor differentiation were factors adversely effecting recipient survival. On multivariate analysis, the presence of poor tumor differentiation (P = 0.018 RR: 2.48) was the only independent predictor of survival. Extension of tumor size and number to AC is feasible, without significantly compromising outcomes; however, the presence of poor tumor differentiation was associated with worse outcomes after LDLT.

Use of middle hepatic vein in right lobe living donor liver transplantation.

The harvesting of the middle hepatic vein (MHV) with the right lobe graft for living-donor liver transplantation allows an optimal venous drainage for the recipient; however, it is an extensive operation for the donor. This is a prospective, nonrandomized study evaluating liver functions and early clinical outcome in donors undergoing right hepatectomy with or without MHV harvesting. From August 2005 to July 2007, a total of 100 donor right hepatectomies were performed with (n = 49) or without (n = 51) the inclusion of the MHV. The decision to take MHV was based on an algorithm that considers various donor and recipient factors. There was no donor mortality in donors in either group. Overall complication rate was higher in MHV (+) donor group, however when remnant liver volume was kept above 30%, complication rates were similar between the groups. The results of this study show that right hepatectomy including the MHV neither affects morbidity nor impairs early liver function in donors when remnant volume is kept above 30%. The decision, therefore, of the extent of right lobe donor hepatectomy should be tailored to the particular conditions considering the graft quality and metabolic demand of the recipient.

Donor safety and remnant liver volume in living donor liver transplantation.

Living donor liver transplantation is now a common practice in countries in which the availability of cadaveric organs is limited. The preoperative preparation, intraoperative surgical technique, and postoperative care of donors and recipients have evolved in recent years. We retrospectively compared 67 donors with a remnant liver volume equal to or more than 30% (group 1) with 14 donors who had less than 30% remnant liver volume (group 2) for donor outcomes. All the complications in donors were systematically classified. Donors with less than 30% remnant liver volume showed significantly higher peak aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and bilirubin levels. There were 6 complications in group 1 and 4 complications in group 2. The difference between the 2 groups in terms of donor complications did reach statistical significance (P = 0.043); donors with a remnant liver volume < 30% had a 4 times greater relative risk of morbidity. In conclusion, the use of donors with less than 30% remnant liver volume is highly debatable as donor safety should be of utmost importance in living donor liver transplantation.

Short-term effects of gallbladder perforations during laparoscopic cholecystectomy on respiratory mechanics and depth of pain.

BACKGROUND: In this study the effects of gallbladder perforations during laparoscopic cholecystectomy on respiratory mechanics and depth of pain in the postoperative period was evaluated. METHODS: Between April 2004 and February 2006 we planned to perform 179 laparoscopic cholecystectomies. One hundred of these patients were included in this study. Patients were divided into two groups: group 1 with gallbladder perforation during the operation and group 2 without perforation. Two groups were compared regarding age, gender, comorbidities, mean hospital stay, respiratory function tests, and postoperative pain scores. RESULTS: Gallbladder perforation occurred in 33 patients (33%). The male-to-female ratio of group I was 5/28. In group 2 the male-to-female ratio was 12/55. Age and perforation had a significant correlation according to Spearman's correlation test (p < 0.05, r = 0.211). Regarding respiratory function tests and arterial blood gases analysis, there was a significant decrease in both groups postoperatively but perforation had no effect on them. No statistically significant difference occurred regarding mean hospital stay and postoperative visual pain scores (p > 0.05). CONCLUSION: Gallbladder perforation during laparoscopic cholecystectomy had no effect on postoperative respiratory mechanics and depth of pain.

Prospective, randomized trial of steroid withdrawal in kidney recipients treated with mycophenolate mofetil and cyclosporine.

UNLABELLED: Our transplant centre began a prospective, randomized trial of steroid withdrawal in low risk renal transplant recipients on triple immunosuppression consisting of mycophenolate mofetil (MMF), microemulsion cyclosporine (CSA), and prednisone. One hundred and twenty patients were randomized either to discontinue or remain on steroids (60 patients per group). Study design consisted of analyses of 1-yr outcomes after study entry. This report includes the 1-yr results plus results at last follow-up (mean follow-up 3.7 yr). There were no significant differences in rates of patient and graft survival at 1 yr or at last follow-up. Additionally, the incidences of acute and chronic rejection as well as graft function were the same at 1 yr and at last follow-up. Significant improvement was noted in total serum cholesterol and bone density at 1 yr and last follow-up. Initial improvement in patient weight at 1 yr was not sustained at last follow-up. No significant impact of steroid withdrawal on serum triglycerides, blood pressure, or post-transplant diabetes mellitus was observed. To date, we have observed no immunologic risk, and some significant benefit in regards to side effects, of steroid withdrawal between 6 and 36 months after transplantation in low risk renal transplant recipients maintained on prednisone, MMF, and microemulsion CSA. CONCLUSION: Steroid withdrawal in low risk kidney transplant recipients is safe and ameliorates many of the unwanted sides effects of steroid use.

The effect of hyaluronan-based agents on adhesion formation in an intraabdominal sepsis model.

Because of the technical difficulty during subsequent surgical intervention, adhesion remains the most important predictor of outcome in the staged procedures following emergent colorectal surgery. The aim of this study was to assess the long-term effects of hyaluronan (HA)-based adhesion barriers 3 months following the infectious insult to the peritoneal cavity. Wistar albino rats were divided into three sham and four infectious groups, each consisting of 20 rats. Sham groups consisted of a control group (I), which had undergone manipulation of the cecum in the first operation and saline irrigation following the cecal resection in the second operation; an HA-based bioresorbable membrane (BM) group (II), in which 20 x 20- and 35 x 25-mm pieces of HA-based bioresorbable membrane were placed over the cecectomy area and under the midline incision, respectively, with other conditions the same as for the control (I) group; and an HA-based solution (S) group (II), where HA solution was used as an irrigation solution, with other conditions the same as for the control group (I). Infectious groups consisted of a septic group (IV), which had undergone cecal ligation and puncture in the first operation and saline irrigation following the cecal resection in the second operation; a sepsis + HA-BM group (V), in which two sheets of membrane were applied, with other conditions the same as for the septic group (IV); a sepsis + HA-S group (VI), in which HA solution was used as an irrigation solution, with conditions otherwise the same as for the septic group (IV); and a sepsis + HA-BM + HA-S group (VII), where HA solution was used as an irrigation solution and two sheets of membrane were applied, with other conditions the same as for the septic group (IV). At the end of the 3-month period, mortality, septic complications, and intraabdominal adhesions (adhesion scores and adhesion tensile strength measurements) were recorded. Significantly denser adhesions were found in the septic group (IV) when compared to the others (P < 0.001). HA-S significantly reduced not only the incidence of adhesion but also the adhesion tensile strength in infectious groups (P < 0.001 compared to the sepsis group). However, HA-BM significantly reduced adhesion tensile strength only. Irrigation of the peritoneal cavity with HA-S may prove to be useful to shorten the reversal time period and decrease morbidity following staged procedures for intraabdominal sepsis.

The impact of mycophenolate mofetil dosing patterns on clinical outcome after renal transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) has proven to be a very effective drug for the prevention of acute rejection following renal transplantation when dosed as prescribed at 2 or 3 g/d. However, circumstances arise in clinical transplantation where the dose must be lowered, either to avoid drug toxicity or because of concurrent infection. The impact on the incidence of acute rejection and graft survival when the MMF dose must be lowered has not previously been investigated. METHODS: In this study, a cohort of 721 kidney transplant recipients who received immunosuppression using MMF in conjunction with cyclosporine and prednisone and OKT3 (n = 425) or Simulect (n = 296) induction were evaluated. Clinical outcomes were compared and contrasted between patients with and without MMF dose changes within the first year post-transplantation. RESULTS: The majority of patients (70.3%, n = 507) had at least one dose change within the first post-transplant year. Compared with the 214 patients who did not have a dose change, these patients had a much higher incidence of acute rejection within the first post-transplant year (23.3% vs. 3.7%, p < 0.001). This resulted in a significantly decreased 3-yr death-censored graft survival (76.3% vs. 88.3%, p = 0.003). The incidence of acute rejection for patients who had a dose change was highest if the dose change occurred within the first post-transplant month (34.4%). The incidence of acute rejection for the dose change patients was influenced by recipient ethnicity (African-American vs. Caucasian) and the type of induction agent used (OKT3 vs. Simulect). CONCLUSION: Altering the dose of MMF within the first post-transplant year correlated with a significantly worse clinical outcome in this cohort of renal transplant recipients. These data suggest that avoidance of MMF dose changes within the first year after renal transplantation would result in improved graft survival.

Magnetic resonance angiography for preoperative evaluation of potential kidney donors.

BACKGROUND: Careful evaluation of the renovascular anatomy for living kidney donors is essential to optimize donor and recipient outcomes. Arteriography has been the standard for delineating the renovascular anatomy. However, this procedure is invasive. Magnetic resonance angiography (MRA) is an attractive, noninvasive alternative. The aim of this study was to evaluate the accuracy of MRA in potential living kidney donors. METHODS: A retrospective comparison of the preoperative MRA results with the intraoperative anatomy was performed in 189 living kidney donors. RESULTS: MRA interpretations correctly identified the vascular anatomy of the donor kidneys in 173 donors (91.5%). In the remaining 16 patients (8.5%), the MRA interpretation was inaccurate. In 10 patients, the MRA reported fewer arteries than the number encountered during the donor operation, whereas in six patients MRA reported more arteries than what found during operation. In seven patients, MRA supplied additional important anatomical information, including kidney size disparity, the presence of nephrolithiasis, the presence of a renal cyst, and renal artery stenosis. All kidneys were successfully transplanted. The misinterpretation of the MRA did not adversely affect the recipient outcome. CONCLUSION: The noninvasive MRA evaluation of donor renovascular anatomy is an acceptable substitute for traditional angiography.

Simultaneous pancreas-kidney transplantation at a single center.

Simultaneous pancreas-kidney transplantation (SPKT) is the procedure of choice in our program to treat type I diabetic patients with end-stage renal disease. Its value in type II diabetic patients remains to be carefully evaluated. With the improvements in the technical results and immunosuppression medications, the procedures have become safer than those performed in the previous decade. However, the diabetic host is a high-risk individual. Careful evaluation and selection is prudent to maintain excellent results with this scarce organ. As we have seen in this series, death is the number one cause of graft loss and improved pre-operative evaluation will continue to be of significant value to lower the mortality rate of SPKT. The success of SPKT has led to wider application of this procedure to less than ideal recipients. Due to the shortage of organs, there is a trend to use more marginal donors. The use of marginal donors and marginal recipients requires careful evaluation to maintain safety and cost effectiveness. At our center, long-term patient and graft survival rates have been acceptable. We will continue to use SPKT as the procedure of choice for acceptable candidates. There has been a trend to change our philosophy to use living donors for the kidney transplant followed by a sequential pancreas transplant in order to overcome the shortage of organs. The issue of primary enteric drainage has not been addressed in this report due to our success with bladder drainage, as we feel that it is a safer procedure and are comfortable that patient education and outpatient therapy has minimized the problems with its use. Despite the lower threshold for enteric conversion, fewer than 10% of our patients undergo conversion when they are at low risk for complications.