Everolimus-facilitated calcineurin inhibitor reduction in Asian de novo kidney transplant recipients: 2-year results from the subgroup analysis of the TRANSFORM study.

OBJECTIVE: We analyzed the efficacy and safety of an everolimus with reduced-exposure calcineurin inhibitor (EVR+rCNI) versus mycophenolic acid with standard-exposure CNI (MPA+sCNI) regimen in Asian patients from the TRANSFORM study. METHODS: In this 24-month, open-label study, de novo kidney transplant recipients (KTxRs) were randomized (1:1) to receive EVR+rCNI or MPA+sCNI, along with induction therapy and corticosteroids. RESULTS: Of the 2037 patients randomized in the TRANSFORM study, 293 were Asian (EVR+rCNI, N = 136; MPA+sCNI, N = 157). At month 24, EVR+rCNI was noninferior to MPA+sCNI for the binary endpoint of estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73 m2 or treated biopsy-proven acute rejection (27.0% vs. 29.2%, P = .011 for a noninferiority margin of 10%). Graft loss and death were reported for one patient each in both arms. Mean eGFR was higher in EVR+rCNI versus MPA+sCNI (72.2 vs. 66.3 ml/min/1.73 m2 , P = .0414) even after adjusting for donor type and donor age (64.3 vs. 59.3 ml/min/1.73 m2 , P = .0582). Overall incidence of adverse events was comparable. BK virus (4.4% vs. 12.1%) and cytomegalovirus (4.4% vs. 13.4%) infections were significantly lower in the EVR+rCNI arm. CONCLUSION: This subgroup analysis in Asian de novo KTxRs demonstrated that the EVR+rCNI versus MPA+sCNI regimen provides comparable antirejection efficacy, better renal function, and reduced viral infections (NCT01950819).

Filtering for the best policy: An economic evaluation of policy options for kidney replacement coverage in the Philippines.

AIM: Kidney failure patients in the Philippines have free choice on their kidney replacement therapy (KRT), with a majority choosing haemodialysis (HD) over peritoneal dialysis (PD) and transplantation despite the inadequate coverage of HD. Although national health insurance coverage is limited, KRT remains to be one of the top benefits pay-outs in the country. The study aims to identify the most cost-effective policy strategy for financing KRT in the Philippines, in the context of a universal healthcare policy. METHODS: A Markov model was developed to estimate and compare the costs and benefits of different policy options with the comparator being partial HD coverage. Direct medical, non-medical and indirect costs were measured, while outcomes were reported through quality-adjusted life years (QALYs). Parameters were derived from the kidney disease registry, hospital statistics from a tertiary hospital and a patient survey. RESULTS: The results of the cost-effectiveness analysis showed that shifting to a PD-First policy provides better value-for-money with an incremental cost-effectiveness ratio (ICER) of 570 029 Philippine Pesos (PHP) per QALY gained, compared with the ICER of the PD-First combined with pre-emptive transplant option of 577 989 PHP per QALY gained. Expanding existing HD coverage to 156 sessions was the least cost-effective policy (1 522 437 PHP per QALY gained). CONCLUSION: Government should consider shifting to a PD-First strategy and support policies that promote kidney transplants among existing PD and HD patients. This study also highlights the need for proper evaluation of partial coverage policies to ensure that government investments represent good value-for-money and patients receive optimal care.

Outcomes of Kidney Transplantation Among COVID-19 Recovered Patients in a Single Transplant Center.

BACKGROUND: The COVID-19 pandemic significantly lowered kidney transplantation (KT) rates worldwide, and studies regarding outcomes of patients who developed COVID-19 infection before KT are limited, especially in low to middle-income countries. BACKGROUND: To determine the 1-year graft and patient survival of kidney transplant recipients who recovered from COVID-19 infection before KT. METHODS: We retrospectively reviewed all adult end-stage renal disease patients who underwent KT at the National Kidney and Transplant Institute from June 2020 through October 2021. Transplant parameters, graft and patient survival, pretransplant COVID-19 infection, and post-KT infectious complications were recorded. Data was analyzed using two-tailed descriptive statistical tests. RESULTS: Of the 219 recipients, 23 (11%) had COVID-19 infection within 1 to 16 months before KT. The mean age of KT recipients was 36 years (range, 25-57), and 61.9% had chronic glomerulonephritis as primary renal disease. The mean duration from COVID-19 recovery to KT was 79 days (range, 21-207). There was no significant difference in the 1-year biopsy-proven acute rejection in the 2 groups, at 4.5% vs 12.5% for the COVID-19 and non-COVID-19 group, respectively. Both the 1-year graft and patient survival were similar in the COVID-19 and non-COVID-19 groups at 98.4% vs 100% and 100% vs 98.44%, respectively. CONCLUSION: There was no significant difference in biopsy-proven acute rejection, 1-year graft, and patient survival among patients who had a prior COVID-19 infection vs those who did not. Kidney transplantation appears safe when performed at least 1 month from COVID-19 infection.

Hemoperfusion in Leptospirosis.

Leptospirosis is the most common zoonosis frequently seen in the tropics and subtropics especially during the rainy season when humans wade in floods contaminated by the urine of infected rats in urban areas. Aside from direct toxicity of the leptospires, the role of an exuberant immune response to the pathogen leading to secondary organ damage has been recognized. Thus, our treatment protocol for patients with severe leptospirosis characterized by renal failure, acute liver injury, and lung hemorrhage now includes a short course of methylprednisolone and intravenous cyclophosphamide. In some patients, however, hemodynamic collapse and acute respiratory distress syndrome ensue, which may be due to the release of cytokines resulting from the dysregulated immune response. Blood purification in the form of hemoperfusion (HP) with neutral macroporous resin-adsorbing beads adsorbs cytokines and other inflammatory mediators leading to cardiovascular stability and stabilization of endothelial membranes. HP may be considered part of a multiorgan system therapeutic approach in diseases with reversible multiorgan failure that can lead to an improvement in patient survival.

Incidence of, and Risk Factors and Outcomes Associated with, Acute Kidney Injury in COVID-19 at the National Kidney and Transplant Institute, Philippines.

(1) Background: Acute kidney injury (AKI) in COVID-19 leads to an increase in patient mortality, especially among chronic kidney disease (CKD) patients. (2) Methods: A retrospective cohort of 519 adults admitted from 1 March 2020 to 1 March 2022 were reviewed for baseline characteristics and their association with renal outcomes. Patients were divided into diagnosed CKD, undiagnosed CKD, and normal eGFR. Chronic dialysis and kidney-transplant patients were excluded. Kaplan-Meier survival analysis at 7, 14, and 30 days from admission was performed. (3) Results: The overall incidence of AKI was 45.66%; the proportions among patients with diagnosed CKD, undiagnosed CKD, and normal eGFR were 76.64%, 38.75%, and 7.59%, respectively (p < 0.0001). Multivariate analysis showed that being male and inotrope use were significant risk factors for AKI, while higher eGFR was protective. AKI was associated with dialysis, invasive ventilation (p < 0.0001), prolonged hospitalization (p = 0.0001), and mortality (p < 0.0001). Renal recovery was 64%, 59%, and 23% in stages 1, 2, and 3 AKI, respectively, until 14 days from discharge (p < 0.0001). Patient survival was lower in cases of AKI: 83.16%, 70.59%, and 47.5% compared to non-AKI figures of 91.27%, 87.82%, and 76.95% at 7, 14, and 30 days respectively(p = 0.0001). (4) Conclusion: There was a higher incidence of AKI with worsening renal function. Intensified preventive measures for AKI are crucial to prevent its devastating consequences.

Emerging Role of Sodium-Glucose Co-Transporter 2 Inhibitors for the Treatment of Chronic Kidney Disease.

Chronic kidney disease is one of the leading causes of morbidity and mortality in the Philippines. It is associated with a growing health burden as many patients progress to end-stage renal disease. Until recently, therapeutic options for the management of chronic kidney disease were limited. Sodium-glucose co-transporter 2 inhibitors offer an alternative therapeutic approach for patients with chronic kidney disease. Several trials have shown renal benefits with sodium-glucose co-transporter 2 inhibitors in patients with cardiovascular disease with and without type 2 diabetes and across a range of estimated glomerular filtration rate levels. In the Philippines, the sodium-glucose co-transporter 2 inhibitors dapagliflozin and canagliflozin are approved for the prevention of new and worsening nephropathy in type 2 diabetes. With emerging treatment options, an urgent need exists for guidance on the management of chronic kidney disease within the Philippines. In this review, we focus on the putative renal-protective mechanisms of sodium-glucose co-transporter 2 inhibitors, including effects on tubuloglomerular feedback, albuminuria, endothelial function, erythropoiesis, uric acid levels, renal oxygen demand, and hypoxia. Furthermore, we discuss the findings of recent large clinical trials using sodium-glucose co-transporter 2 inhibitors in patients with chronic kidney disease and diabetic kidney disease, summarize safety aspects, and outline the practical management of patients with chronic kidney disease in the Philippines.

Incidence of acute pancreatitis among patients with leptospirosis requiring extracorporeal membrane oxygenation (ECMO): a descriptive study.

BACKGROUND: Acute pancreatitis (AP) is an infrequently reported manifestation of leptospirosis. It is more commonly seen in patients with acute respiratory distress syndrome. Despite novel modalities such as extracorporeal membrane oxygenation (ECMO), the mortality rate remains high and whether this is associated with the lung injury caused by the inflammation in AP remains unclear. OBJECTIVES AND METHODS: A descriptive study was conducted at a tertiary hospital in the Philippines. Primary outcome was defined as the presence or absence of AP. Secondary outcomes were defined as 28-day mortality rate, length of hospital stay, ECMO days, renal replacement therapy (RRT) days, days on mechanical ventilation, presence of local complications of AP and development of nosocomial infections. RESULTS: A total of 27 patients were included in the study, and 88.89% (n=24) were men. The mean age for all patients was 33.59±10.22 years. Out of the 27 patients, 19 (70.37%) were diagnosed with AP. Among these 19 patients, one (5.26%) had necrotising pancreatitis and two (10.52%) developed local complications of pancreatitis. Six patients (31.58%) died among those who developed AP, while one (12.50%) died among those who did not. The duration of hospital stay, ECMO, RRT, mechanical ventilation and development of nosocomial infections was also higher in the group who presented with AP. CONCLUSION: AP is an under-reported complication of leptospirosis. Our study demonstrated a higher mortality and morbidity in patients with leptospirosis who developed AP.

Incentives for organ donation: proposed standards for an internationally acceptable system.

Incentives for organ donation, currently prohibited in most countries, may increase donation and save lives. Discussion of incentives has focused on two areas: (1) whether or not there are ethical principles that justify the current prohibition and (2) whether incentives would do more good than harm. We herein address the second concern and propose for discussion standards and guidelines for an acceptable system of incentives for donation. We believe that if systems based on these guidelines were developed, harms would be no greater than those to today's conventional donors. Ultimately, until there are trials of incentives, the question of benefits and harms cannot be satisfactorily answered.

Comparison of Outcomes among Chronic Kidney Disease V Patients with COVID-19 at the National Kidney and Transplant Institute: A Retrospective Cohort Study.

BACKGROUND: There is very little published data on outcomes of COVID-19 among chronic kidney disease (CKD) patients. We compared the outcomes of COVID-19 in a tertiary care renal hospital among CKD V patients on hemodialysis (HD), peritoneal dialysis (PD), and dialysis initiation, in terms of duration of hospitalization, in-patient mortality, and 30-day mortality. METHODS: A total of 436 CKD V patients, on either HD, PD, or dialysis initiation, with COVID-19 who were admitted at the National Kidney and Transplant Institute (NKTI) from March 13, 2020, to August 31, 2020, were included. Kaplan-Meier survival analysis was performed. Comparison of probability of mortality by group was performed using Log-Rank test. p values ≤0.05 were considered statistically significant. RESULTS: Among 436 CKD V patients, 298 (68%) were on HD, 103 (24%) were on PD, and 35 (8%) required dialysis initiation. Overall in-hospital mortality was 34%; 38% were on HD, 20% on PD, and 37% on dialysis initiation. Total 30-day mortality was 27%; 32% were on HD, 26% on PD, and 16% on dialysis initiation. Median follow-up was 24 days. Among the 137 deaths recorded, total median time to death was 10 days; 8.5 days, 15.5 days, and 9 days for HD, PD, and dialysis initiation groups, respectively. Probability of mortality was significantly higher in HD patients versus PD patients (p < 0.00001) and in the dialysis initiation group compared to PD patients (p=0.0234). Mortality probability, however, was not significantly different in HD patients versus the dialysis initiation group (p=0.63). CONCLUSION: Among CKD V patients diagnosed with COVID-19 at the NKTI, those on HD and on dialysis initiation had significantly higher in-hospital and 30-day mortality, compared to patients on PD.

A Scoring Tool to Predict Pulmonary Complications in Severe Leptospirosis with Kidney Failure.

Rapid identification of patients likely to develop pulmonary complications in severe leptospirosis is crucial to prompt aggressive management and improve survival. The following article is a cohort study of leptospirosis patients admitted at the National Kidney and Transplant Institute (NKTI). Logistic regression was used to predict pulmonary complications and obtain a scoring tool. The Kaplan-Meir method was used to describe survival rates. Among 380 patients with severe leptospirosis and kidney failure, the overall mortality was 14%, with pulmonary hemorrhage as the most common cause. In total, there were 85 (22.4%) individuals who developed pulmonary complications, the majority (95.3%) were observed within three days of admission. Among the patients with pulmonary complications, 56.5% died. Patients placed on mechanical ventilation had an 82.1% mortality rate. Multivariate analyses showed that dyspnea (OR = 28.76, p < 0.0001), hemoptysis (OR = 20.73, p < 0.0001), diabetes (OR = 10.21, p < 0.0001), renal replacement therapy (RRT) requirement (OR = 6.25, p < 0.0001), thrombocytopenia (OR = 3.54, p < 0.0029), and oliguria/anuria (OR = 3.15, p < 0.0108) were significantly associated with pulmonary complications. A scoring index was developed termed THe-RADS score (Thrombocytopenia, Hemoptysis, RRT, Anuria, Diabetes, Shortness of breath). The odds of developing pulmonary complications were 13.90 times higher among patients with a score >2 (63% sensitivity, 88% specificity). Pulmonary complications in severe leptospirosis with kidney failure have high mortality and warrant timely and aggressive management.

Factors influencing dialysis modality for end-stage renal disease in developing countries: a survey of Filipino nephrologists.

BACKGROUND: In the Philippines, 86% of incident dialysis patients are started on hemodialysis (HD) and 14% are treated with peritoneal dialysis (PD), representing a decline over a 2-year period. One important factor which affects patients' choice of dialysis modality is the input of their physicians. Our objective was to identify the factors affecting attitudes and recommendations of Filipino nephrologists regarding HD and PD. METHODS: Attendees of the annual national nephrology meeting completed an anonymous self-administered questionnaire. RESULTS: Respondents were heavily involved in clinical dialysis work, and 86.7% had most/all of their patients on HD. Recommendations about dialysis modality were based most strongly on overall cost to patient (4.4 on a scale of 1 [not important] to 5 [most important], residual renal function (RRF) preservation (4.4), patient preference (4.3) availability of dialysis support staff (4.3), and comparative quality of life data (4.3). Least important was physician reimbursement (2.8). Patient-related factors favoring HD were: poor personal hygiene, impaired vision and manual dexterity; while favoring PD were: age <10 years, living far from HD unit, and the availability of trainable family members. When asked which modality they would recommend to an equally eligible patient, 49.2% responded they would not recommend either modality and would allow the patient to choose, while 40.7% would recommend HD and 10.2% would recommend PD. CONCLUSION: Respondents consider overall cost and RRF preservation as the most important factors in dialysis modality selection, yet only 10.2% would recommend PD as first choice. It is likely that factors other than those addressed in the survey are stronger determinants of the patient's final choice of modality.

Clinical characteristics, outcomes, and management of COVID-19 in kidney transplant recipients across Asia: an ASTREGO report.

Background: Asia is the global epicenter of the coronavirus disease 2019 (COVID-19) pandemic; however, COVID-19-related mortality in Asia remains lower than in other parts of the world. It is uncertain whether the mortality of COVID-19-infected kidney transplant recipients (KTXs) from Asia follows the lower mortality trends of the younger Asian population. Methods: Specific transplant centers from countries in the Asian Society of Transplantation were invited to participate in a study to examine the epidemiology, clinical features, natural history, and outcomes of COVID-19 infections in KTXs. Data were analyzed and compared with those of large cohort studies from other countries. Results: The study population was 87 KTXs from nine hospitals in seven Asian countries. Within the study population, 9% were aged 60 years and older, and 79% had at least one comorbidity. The majority of patients (69%) presented with mild-to-moderate COVID-19 severity. Disease progression was more frequently encountered among those with moderate or severe infection (23%) and non-survivors (55%). The mortality rate was 23% (n=20) and differed according to the level of care 12% (n=1/8), 15% (n=10/67), and 100% (n=9/9) of patients managed as outpatients, in the general ward, and in the intensive care unit, respectively. Disease severity at the time of presentation was an independent predictor of mortality. Compared with the mortality rates in other studies worldwide, mortality rates in the current study were comparable. Conclusions: Mortality in Asian KTXs who were infected with COVID-19 remains high and could be related to comorbidity burden and the constraints of the general healthcare system when the COVID-19 caseload is high.

Development of the Asian Transplant Registry Under the Asian Society of Transplantation.

INTRODUCTION: In the Asian region, no international organ transplantation registry exists. Individual centers maintain their own database, or some countries developed a national registration system. To promote collaboration among Asian transplantation societies, the Asian Society of Transplantation (AST) has developed an international transplantation registry for the Asian countries that has been named as the Asian Society Transplant Registry (ASTREG). METHODS: In 2017, the AST council formed a registry committee to develop 2 kinds of databases: ASTREG-N (nationwide level), which collects yearly aggregated data of participating countries, and ASTREG-H (hospital level), which collects the data of transplant recipients and donors from individual centers. RESULTS: ASTREG-N collects each country's aggregate data of solid-organ transplantation, such as the total number of transplantations and deceased donors. ASTREG-H collects 5 transplant domains, namely recipient baseline characteristics, immunosuppression, post-transplant event, annual post-transplant evaluation, and donor traits. For the ASTREG-H project, South Korea, Philippines, Mongolia, and Myanmar are the current participants. A web-based secure data entry platform with real-time data visualization and automated data verification systems is currently available. Any participating centers can run this platform as their own data collection system. CONCLUSION: The ASTREG is a collaborative project that will be the representative solid-organ transplantation database in the Asian region. It can aid in the harmonization of transplantation data in the Asian region.

Transplantation in Asia during the coronavirus disease-19 (COVID-19) pandemic: briefs from member countries of the Asian Society of Transplantation.

The coronavirus disease-19 (COVID-19) pandemic has affected 1,029,968 people in Asia as of May 16, 2020. Although Asia was the first continent to be affected, many countries in the region continue to battle COVID-19, which challenges the way transplant programs provide their services. Given the diversity of healthcare systems in Asia, the countermeasures in response to COVID-19 are as potentially diverse. This review reports the experiences of transplant services in member countries of the Asian Society of Transplantation (AST) as well as provides a platform for sharing of best practices during the COVID-19 pandemic. AST invited member countries to provide a short description of their transplant experiences during the COVID-19 pandemic. Whenever information is available, countries were asked to provide information on COVID-19 related statistics, status of transplant programs, mitigation measures taken to prevent COVID-19, and other areas of transplant programs impacted by COVID-19. Ten countries responded to the invitation of which seven still have active transplant programs at varying levels of activity. All countries have protocols for donor/recipient screening and countermeasures to prevent COVID-19 infections in recipients and healthcare providers. Interestingly, these countries report only 16 transplant recipients with COVID-19 infection but no cases of donor-transmitted COVID-19 infection. Despite the diversity of healthcare systems in Asia, transplant centers in Asia have taken appropriate precautions to avoid COVID-19 infections, though the long-term impact of COVID-19 remains unclear.

Pilot Study Comparing the Efficacy, Safety, Convertibility, and Tacrolimus Trough Levels of Twice-Daily Tacrolimus (Prograf) to Once-Daily Tacrolimus (Advagraf) Among Standard-Risk Kidney Transplant Patients at the National Kidney and Transplant Institute.

BACKGROUND: Recently, a once-daily formulation of tacrolimus (Advagraf) was released in the Philippines. Studies have shown that these 2 formulations are bioequivalent at a 1:1 conversion. This study aims to determine the efficacy, safety, convertibility, and tacrolimus trough level of once-daily tacrolimus at the end of 6 months post transplant. METHODS: This is a randomized study among standard-risk primary kidney transplant patients performed at the National Kidney and Transplant Institute, Philippines. A total of 40 patients completed the 6-month follow-up. Patients in Group A who failed to meet the criteria for conversion to once-daily tacrolimus were considered to have reached the end of the study, while patients who satisfied the conversion criteria will be followed up for an additional 6 months. RESULTS: Baseline characteristics were similar in both groups. The area under the curve, maximum concentration, time to achieve the maximum concentration, and the coefficient of variation were similar. The twice-daily tacrolimus (Prograf) group patients had significantly higher mean tacrolimus trough levels than the Group B once-daily tacrolimus patients. An increase of a once-daily tacrolimus mean dose of 8% was required to achieve a therapeutic drug level post conversion. The graft and patient survival were 100%. There was no biopsy-proven acute rejection noted either both group. CONCLUSION: In conclusion, conversion from twice-daily tacrolimus to once-daily tacrolimus in kidney transplant in both de novo and converted patients after KT is safe, ensuring greater stability of drug blood concentrations than the standard form. The results also suggest an 8% increase when converting stable KT patients from twice-daily tacrolimus to once-daily tacrolimus.

A case of leptospirosis with acute respiratory failure and acute kidney injury treated with simultaneous extracorporeal membrane oxygenation and haemoperfusion.

A 47-year-old man with a recent history of wading in floodwaters presented with a 1-week history of cough, myalgia, conjunctival suffusion and decreasing urine output. The patient had uraemia, hypotension, leukocytosis, thrombocytopenia, elevated liver enzymes and oliguria. His condition quickly worsened with haemoptysis, and respiratory distress which subsequently required intubation and mechanical ventilation. Continuous renal replacement therapy was started together with haemoperfusion (HP). The patient initially required norepinephrine and this was discontinued after the first session of HP. He was referred for veno-venous extracorporeal membrane oxygenation (ECMO) due to severe hypoxia and pulmonary haemorrhage. Oxygenation and lung compliance improved, and serum creatinine levels continued to normalise with improved urine output. He was placed off ECMO, extubated and eventually discharged. Patient was diagnosed with severe leptospirosis, acute respiratory failure and acute kidney injury successfully treated with simultaneous ECMO and HP. Blood samples were positive for Leptospira spp. DNA via PCR assay.

Randomized trial of Alemtuzumab for prevention of graft rejection and preservation of renal function after kidney transplantation.

BACKGROUND: A randomized, multicenter, controlled trial was undertaken to evaluate the safety and efficacy of Alemtuzumab, a powerful lytic agent for both T and B lymphocytes, in the prophylaxis of rejection in renal transplantation (RTx). METHODS: Thirty patients were randomized to receive Alemtuzumab together with low-dose cyclosporine (CsA) monotherapy (CAMPATH, n = 20) or to full doses of CsA with azathioprine and corticosteroids (Standard, n = 10). CsA was administered at doses to achieve whole-blood trough CsA levels of 90 to 110 ng/mL and 180 to 225 ng/mL in CAMPATH and Standard groups, respectively. RESULTS: Per protocol, CsA trough levels were lower in patients assigned to CAMPATH post-RTx (median trough level of 119 vs. 166 ng/mL at 6 months, CAMPATH vs. Standard; 95% confidence interval, -92 to -34). At 6 months post-RTx, serum creatinine, graft and patient survivals, incidence of biopsy proven acute rejection (25% vs. 20%, CAMPATH vs. Standard), overall treatment failure, and severe and moderate infections were comparable. Whereas all patients receiving Standard therapy required maintenance corticosteroids at 6 months, of the 17 of 20 patients with functioning grafts in CAMPATH, 15 (88%, 95% confidence interval, 53%-97%) were steroid free. CONCLUSION: These results suggest that Alemtuzumab is an effective induction agent that permits low-dose steroid-free immunosuppression in RTx.