Extracorporeal blood purification in patients with liver failure: Considerations for the low-and-middle income countries of Latin America.

Severe liver failure is common in Low-and-Medium Income Countries (LMIC) and is associated with a high morbidity, mortality and represents an important burden to the healthcare system. In its most severe state, liver failure is a medical emergency, that requires supportive care until either the liver recovers or a liver transplant is performed. Frequently the patient requires intensive support until their liver recovers or they receive a liver transplant. Extracorporeal blood purification techniques can be employed as a strategy for bridging to transplantation or recovery. The most common type of extracorporeal support provided to these patients is kidney replacement therapy (KRT), as acute kidney injury is very common in these patients and KRT devices more readily available. However, because most of the substances that the liver clears are lipophilic and albumin-bound, they are not cleared effectively by KRT. Hence, there has been much effort in developing devices that more closely resemble the clearance function of the liver. This article provides a review of various non-biologic extracorporeal liver support devices that can be used to support these patients, and our perspective keeping in mind the needs and unique challenges present in the LMIC of Latin America.

Low-dose Thymoglobulin vs Basiliximab Induction Therapy in Low-Risk Living Related Kidney Transplant Recipients: A Prospective Randomized Trial.

CONTEXT: Thymoglobulin is used effectively as induction agent in kidney transplantation but the optimal dose is not well established. OBJECTIVE: Demonstrate that low-dose thymoglobulin (3 mg/kg) has similar efficacy and safety compared to basiliximab induction in low-risk kidney transplantation under standard maintenance immunosuppression DESIGN, SETTING, PARTICIPANTS: Prospective randomized study in kidney transplant patients (12/2016-05/2018). INCLUSION CRITERIA: Recipients > 18 years, first living donor transplant. EXCLUSION CRITERIA: Second and multiorgan transplant, ABO incompatibility, positive cross-match, panel reactive antibodies (PRA) > 30%, positive donor-specific antibody, human immunodeficiency virus, hepatitis B surface antigen, hepatitis C virus positive, white blood cells < 2000 cells/mm3, platelets < 75,000 cells/mm3 and malignancy. INTERVENTION: Group A: basiliximab (20 mg D0 and D4). Group B: thymoglobulin (3 mg/kg total). Maintenance immunosuppression: tacrolimus, mycophenolate mofetil, and steroids. MAIN OUTCOME MEASURES: Biopsy-proven acute rejection (BPAR), delayed graft function, slow graft function, leukopenia, infections, adverse events, graft loss, estimated glomerular filtration rate, and death within 12 months. RESULTS: 100 patients (basiliximab, n = 53) (thymoglobulin, n = 47) were included. Donor and recipient characteristics were similar except for longer dialysis (basiliximab), PRA class I (1.2% basiliximab, 4.5% thymoglobulin), HLA match (basiliximab 2.8, thymoglobulin 2.2), and cytomegalovirus status. BPAR rate was basiliximab 3.8% and thymoglobulin 6.4% (P = ns). Delayed graft function (basiliximab 3.8%; thymoglobulin 4.3%), slow graft function, and 12-month leukopenia (basiliximab 11.3%, thymoglobulin 21.3%) were similar between groups (P = ns). There was no difference in infections and adverse events between groups. Patient and graft survival were as follows: basiliximab 98.1% and 92.5%, thymoglobulin 100% and 93.6% (P = ns). CONCLUSION: Low-dose thymoglobulin induction (3 mg/kg) can be used effectively and safely in low-risk kidney transplantation with good results during the first year post-transplant.

Retroactive Application of a New Risk Index for Living Donor Kidney Transplantation to Renal Transplants in Veracruz, Mexico.

BACKGROUND: The Living Kidney Donor Profile Index (LKDPI) was recently created. This model predicts recipient risk of graft loss after living donor transplant. Herein, we applied the LDKPI to our population to analyze its performance. METHODS: A retrospective analysis of all living donor kidney transplants from 2003 to 2018 from 2 transplant centers in Veracruz, Mexico, was used. LKDPI was calculated in a webpage (www.transplantmodels.com). Donor and recipient demographics and transplant data included in the model were registered. Pearson correlation between the LKDPI percentage and death-censored graft survival was performed. Kaplan-Meier survival (log-rank) and Cox regression analysis were compared between the LKPDI quartiles. P < .05 was considered statistically significant. RESULTS: In total, 821 transplants were included (mean age 31.7 ± 10.5 years, 62.5% male, n = 513). Mean follow-up was 64.7 ± 46.2 months. Mean estimated survival (Kaplan-Meier) was 128.9 ± 3 months (95% confidence interval [CI], 123-134). Ten-year death-censored graft survival was 61.4%. Median LKPDI was -2%, and mean LKDPI was -2.6% ± 14.6% (range, -50% to 42%). Pearson coefficient correlation between the LKDPI and death-censored graft survival was 0.024 (P = .4). Area under the curve (receiver operating characteristic [ROC]) for the LKDPI and death-censored graft loss was 0.54 (95% CI, 0.505-0.591) (P = .04). Recipients with the lowest LKDPI had lower risk of death-censored graft loss than other quartiles (P = .014 log-rank). Cox regression analysis was significant for the lower LKDPI quartile (<20%) (Exp B = 0.35; 95% CI, 0.14-0.9; P = .03). CONCLUSION: The LKDPI applies with moderate discrimination predictive power in our population. The best LKDPI patient has better death-censored graft survival. Further studies might continue to validate the LKDPI in other cohorts.

Annual Analysis (2018) of the Kidney Transplant Waiting List of a Social Security Hospital in Veracruz, Mexico.

BACKGROUND: In Mexico during 2018, 15,072 patients were waiting for a deceased donor kidney transplant, and 969 deceased donor kidney transplants were performed. There is no annual data report of the waiting list activity in Mexico. Herein, we analyzed our kidney transplant waiting list activity in 2018. METHODS: We performed a waiting list analysis in our unit during 2018. Patient and status characteristics (active, deceased, inactive, or transplant) were registered. Differences between status were determined. A P < .05 was considered statistically significant. RESULTS: In total, 467 patients were waiting, and 74 patients were included on the list (57.7% male, mean age 38.5 ± 11.3 years and mean BMI 24.9 ± 4.7 kg/m2); 92.8% were state residents. The most common end-stage renal disease diagnosis was unknown (40.9%). In total, 94.9% were on dialysis (mean time 5.1 ± 3.14 years), and for 90.9%, this was the first transplant. PRA class I and class II were 19.9% ± 30.6% and 12.9% ± 27.1%, respectively. Mean EPTS was 19.8% ± 9.4%. Mean waiting time was 2.88 ± 2.3 years. In total, 21 deceased donor patients (3.9%) were transplanted; 57 (10.5%) patients had an inactive status, and 3 (0.6%) received a living donor kidney transplant with a proven mortality of 1.8% (n = 10). Patients who underwent deceased donor transplant were younger and had more time on dialysis, lower PRA class I, and more time on the waiting list (P < .05 by analysis of variance). CONCLUSION: There are more patients included on the list than patients off the list. There are significant differences between patients who received a transplant and inactive and active patients that needs to be shortened.

Effect of Panel-Reactive Antibody on Graft Survival in Living Kidney Donor Transplantation: Analysis of 10 Years in a Transplant Center in Veracruz, Mexico.

BACKGROUND: Pretransplant anti-HLA antibodies are a risk factor for graft rejection and loss, and its percentage estimate is known as panel-reactive antibody (PRA). Our objective was to evaluate the influence of PRA on the survival of renal grafts from living donors over a period of 10 years. METHODS: Retrospective analysis was completed in all living donor transplants with PRA class I and class II from October 2008 to December 2018 with follow-up until June 2019. The methods used for the PRA were flow cytometry and Luminex. Graft survival (not censored) was evaluated by Kaplan-Meier (log-rank) and Cox regression. P < .05 was considered significant. RESULTS: The study included 393 patients. PRA class I mean was 9.8 ± 20% (0%-98%) and class II mean was 8.6 ± 17.8% (0%-97.8%). Of the patients, 81.9% had a PRA <20% for any class. Uncensored graft survival at 1, 5, and 10 years was 90.3%, 76.2%, and 69.3%, respectively. Mean estimated uncensored graft survival in PRA <20% patients (103.9 ± 2.7, 95% confidence interval [CI] 96.6-11.2) was higher than that of PRA >20% patients (61.5 ± 5.7, 95% CI 50.3-72.8) (P = .005 log-rank). Cox regression (univariate) was statistically significant for PRA class I (Exp [B] 1.01, 95% CI 1.003-1.02, P = .009) and for PRA >20% any class (Exp [B] 2.074, 95% CI 1.222-3.520, P = .007). CONCLUSION: PRA class I and PRA >20% any class are associated with lower graft survival. PRA must be considered to determine immunologic risk and to choose an immunosuppressive regimen in kidney transplantation.

Acute Rejection Is a Strong Negative Predictor of Graft Survival in Living-Donor Pediatric Renal Transplant: 10-Year Follow-Up in a Single Mexican Center.

OBJECTIVES: Kidney transplant is the optimal treatment for children with end-stage renal disease. Multiple factors affect patient and graft survival. We assessed determinants of long-term patient/graft survival in our center by a retrospective review of pediatric living donor (< 18 years) kidney transplants from February 2003 to December 2016. MATERIALS AND METHODS: Donor and recipient demo-graphic data and immunosuppression use were gathered for analyses. Transplant outcomes included patient/graft survival, acute rejection, and 1-year estimated glomerular filtration rate. Patient/graft survival results were analyzed by Kaplan-Meier, and Cox proportional hazards regression model was used for risk factors (univariate/multivariate). P ≤ .05 was statistically significant. RESULTS: Ninety-nine patients were included. Age was 13.4 ± 3.08 years, 64.6% were male, and 88.9% were on dialysis with time of 17.1 ± 12.6 months. Mean donor age was 36.6 ± 7.7 years, and most were females (63.6%). Donor estimated glomerular filtration rate was 89.4 ± 16.9 mL/min/1.73 m2. HLA match was 3.2 ± 1.05. Panel reactive antibody showed 8.6 ± 20.5%. Of total patients, 47.5% used induction, 88.9% used cyclo-sporine, and 100% used mycophenolate mofetil. Five- and 10-year patient survival rates were 93.2% and 93.2%. One-year acute rejection was 14.1%, with rate of 24.2% throughout follow-up. One-year estimated glomerular filtration rate was 76.4 ± 25.6 mL/min/1.73 m2. Five- and 10-year graft survival rates were 62.6% and 43.3%. Multivariate analysis confirmed donor age and acute rejection episodes throughout follow-up as risk factors for graft survival (P < .05). CONCLUSIONS: Acute rejection and donor age are important risk factors for 10-year graft survival in living-donor pediatric kidney transplant in our program.

Long-term results after conversion from calcineurin inhibitors to sirolimus in renal transplant patients.

UNLABELLED: BACKGROUND: Calcineurin inhibitors (CNI) toxicity is one of the contributing factors for the development and progression of chronic allograft dysfunction (CAD). Conversion to sirolimus (SRL) from CNI improves renal function kidney in transplant recipients. METHODS: A retrospective review from patients abruptly converted from CNI to SRL over a three yr period is reported. RESULTS: Thirty-nine patients were converted 55.2±58 months after renal transplantation. 24 month patient and graft survival was 100% and 92%. Acute rejection incidence was 7.6%. Overall, serum creatinine (SCr) and Cockcroft-Gault creatinine clearance (CGCrCl) improved. In responders, SCr improved from 2.48±0.8 to 1.94±0.8 mg/dL (p<0.05) CGCrCl improved from 37.8±17.4 to 51.9±23.8 mL/min at two years. An increase in proteinuria was observed from conversion to month 12 in responders (189.4±512.8 to 488.3±890.6 mg/day, p<0.05) and from conversion to month six in non-responders (1179.4±2001.1 to 2357±4172.9 mg/day, p<0.05). Low proteinuria had positive predictive value for renal response after conversion. CONCLUSION: Conversion from CNI to SRL with CAD is associated with improved renal function with an increase in proteinuria. Low proteinuria is a possible positive predictive factor for successful conversion.

Abdominal wall hernias in end-stage renal disease patients on peritoneal dialysis.

OBJECTIVE: To describe our experience with hernioplasty in peritoneal dialysis patients and to identify possible risk factors for surgical complications. DESIGN: A 4-year retrospective chart review of data. SETTING: Peritoneal dialysis unit of a university hospital. PATIENTS AND METHODS: 58 hernias in 50 patients were included. Detailed surgical technique and complications were recorded. Possible risk factors included age, gender, weight, height, body mass index, previous surgery, diabetes, time on dialysis, emergency surgery, hospital stay, type of hernia, mesh use, blood hemoglobin, and serum urea, creatinine, and potassium. RESULTS: Complications occurred in 12 hernioplasties (4 wound infections, 2 peritonitis, 4 catheter dysfunction, and 5 re-operations). Recurrence rate was 12% without mesh use and 0% with mesh hernioplasty. Dialysis was re-instituted in 96% of cases within 3 days postoperatively. Identified risk factors for complications were diabetes, low weight, low height, small body mass index, and low serum creatinine. CONCLUSIONS: Mesh hernioplasty in peritoneal dialysis patients is advisable. Postoperative dialysis with low volume is feasible after surgery. Prospective studies will corroborate our risk factors for morbidity.

Pediatric renal transplantation with mycophenolate mofetil immunosuppression in a single center from Mexico.

An MMF-based immunosuppression has reduced the acute rejection rate in adults and in children in the early post-transplantation period. In the present study, pediatric renal transplantation patients on a CyA, MMF, and steroids regimen were prospectively evaluated. Patients with CyA, MMF, and steroid therapy without antibody induction were evaluated for surgical aspects, renal function, rejection, and survival, growth after transplantation, adverse events and medication discontinuation. Between February 2003 and May 2005, 21 kidney transplantation patients under 18 yr old were followed for at least 12 months. Within one year after transplantation, three patients developed four episodes of acute rejection (19%). Graft loss because of rejection occurred in one patient. One-year mean serum creatinine was 1.19 +/- 0.3 mg/dL. Mean calculated CrCl by Schwartz formula was 82.3 +/- 19.7 mL/min*1.73 m(2). Major adverse events included infections of the urinary tract and diarrhea, abdominal pain, and GI symptoms. No patients have discontinued the use of MMF. Good results in pediatric kidney transplantation can be achieved by using CyA/MMF/steroids. MMF is effective and relatively safe in reducing the incidence of acute rejection even without induction therapy 12 months after transplantation.

Living related kidney transplantation without calcineurin inhibitors: initial experience in a Mexican center.

We performed a prospective randomized trial comparing sirolimus/mycophenolate mofetil (MMF)/prednisone to cyclosporine/MMF/prednisone and selected induction therapy with basiliximab. Twenty patients received sirolimus (10 mg loading dose followed by 3 mg/m body surface area/day, keeping 24-hr trough levels at 10-15 ng/mL for six months and 5-10 ng/mL thereafter. Twenty-one patients began cyclosporine (4 to 8 mg/kg/day, keeping 12-hour trough levels at 150-300 ng/mL for 6 months and 100-200 ng/mL afterwards). Mean follow up was 15.8 months. One-year patient and graft survival was similar in both groups (>90%). Acute rejection rate was 16.6% in the sirolimus group and 5.2% in the cyclosporine group (P=NS). There were no differences in mean serum creatinine between groups. No patients who received basiliximab and had sirolimus target levels suffered acute rejection at one year. The sirolimus group had significantly higher cholesterol and triglycerides. A calcineurin inhibitor-free regimen using sirolimus produces comparable one-year transplant outcomes in living related kidney transplants compared to a calcineurin inhibitor regimen.

Conversion from calcineurin inhibitor to sirolimus for renal function deterioration in kidney allograft recipients.

BACKGROUND: Calcineurin inhibitors play an important role in chronic allograft dysfunction. Sirolimus is an interesting alternative in renal transplant patients because it is less nephrotoxic than calcineurin inhibitors. METHODS: A chart review of the clinical outcome of kidney transplant patients converted to sirolimus with progressive allograft dysfunction is reported herein. Fifteen patients (average age: 32.3 years, 44 months mean time of conversion) were included. Indication for conversion was a >20% increase in serum creatinine over the last 6 months or progression to the range of 2-4.5 mg/dL. Patients underwent abrupt cessation of cyclosporine and sirolimus addition at 2-5 mg/day. RESULTS: Concomitant immunosuppression remained unchanged during conversion. Targeted sirolimus level was 8-12 ng/mL. Serum creatinine dropped from pre-conversion level of 2.75 +/- 0.83 to 2.14 +/- 0.67 and 1.97 +/- 0.66 mg/dL at 3 and 6 months (p <0.05). There was a significant decrease in blood urea nitrogen, hemoglobin and serum calcium at 3 months post-conversion as well as serum calcium and potassium at 6 months post-conversion (p <0.05). There were no rejection episodes. Patient and graft survival was 100% with three infectious complications. CONCLUSIONS: Monitored sirolimus conversion with sharp withdrawal of calcineurin inhibitor is an alternative for patients with deteriorating renal function and chronic allograft nephropathy.