Post-transplant complications, patient, and graft survival in pediatric and adolescent kidney transplant recipients at a tropical tertiary care center across two immunosuppression eras.

BACKGROUND: We report pediatric PAKT patient and graft outcomes at a large tropical tertiary center spanning two transplant eras. METHODS: In this retrospective cohort study, all children ≤18 years who underwent kidney transplantation at our center between 1991 and 2016 were included. Data pertaining to their baseline characteristics, post-transplant events, and outcome were retrieved from transplant records and compared between transplant eras (1991-2005 and 2006-2016). RESULTS: A total of 139 children (mean age 15.2 ± 2.9 years) underwent PAKT during this period. The incidence of UTIs, CMV disease, BKVN, invasive fungal infections, new-onset diabetes after transplant, leucopenia, and recurrent NKD was higher in the 2006-2016 era (P < .001 for all), while 1-year cumulative BPAR was comparable (P = .100). Five-year graft and patient survival in the two eras were 89.9% and 94.2% (P = .365) and 92.1% and 95.3% (P = .739), respectively. Incidence of CMV disease, BKVN, graft loss, and death was lower in the calcineurin withdrawal group. Non-adherence accounted for 36% of graft loss; infections caused 43.7% of deaths. On multivariate Cox proportional hazards analysis, independent predictors for graft loss were UTIs and blood transfusion naïve status and for death were serious infections and glomerular NKD. CONCLUSIONS: PAKT in India has excellent long-term graft outcomes, though patient outcomes remain suboptimal owing to a high burden of infections. Current immunosuppression protocols need to be re-examined to balance infection risk, graft, and patient survival.

Spectrum of biopsy proven renal disease in South Asian children: Two decades at a tropical tertiary care centre.

AIM: We report findings from a large single centre paediatric renal biopsy cohort in South Asia. METHODS: We analyzed all renal biopsies performed on children aged ≤18 years between 1996 and 2015 at our centre. The clinical characteristics and histological diagnosis pertaining to each case, distribution of renal diseases in children with various clinical presentations, and changes in the pattern of kidney disease during the study period were analyzed. RESULTS: A total of 1740 paediatric kidney biopsies were performed during the study period. The mean age was 12.8 ± 4.9 years (8 months to 18 years) and the male: female ratio was 1.5:1. The most common indication for renal biopsy was nephrotic syndrome (63.2%) followed by acute nephritic syndrome (13%). Minimal change disease was the most common cause of nephrotic syndrome while endocapillary proliferative glomerulonephritis (65.7% infection related), remained the commonest cause of acute nephritic syndrome. IgA nephropathy was the commonest cause of chronic kidney disease. Contrary to trends in European paediatric cohorts, the frequency of lupus nephritis increased over the two decades of the study, while that of endocapillary proliferative glomerulonephritis did not show any appreciable decline. CONCLUSION: This study provides the largest data on biopsy proven renal disease in children from South Asia published till date and highlights important differences in the spectrum and trends of kidney disease compared to data from other regions.

Randomised controlled trial for efficacy of unfractionated heparin (UFH) versus low molecular weight heparin (LMWH) in thrombo-prophylaxis.

OBJECTIVE: To study if low dose Unfractionated heparin (UFH) is as effective and safe as Low-molecular weight heparin (LMWH) and also economical as a prophylactic agent for venous thromboembolism in medically ill patients. METHODOLOGY: A prospective double blind randomised controlled trial consisting of 92 patients fulfilling the inclusion criteria who were admitted to Bangalore Baptist Hospital, Bengaluru, between March 2008 and July 2009 were randomised to receive Unfractionated heparin (UFH) or Low-molecular weight heparin (LMWH). RESULTS: The result based on intention to treat (ITT)analysis with best outcome scenario: in the UFH arm there were 47 (97.9%) patients who had not developed DVT/PE as compared to 42 (95.5%) in the LMWH arm. The difference in proportion of patients who had not developed DVT/PE between UFH and LMWH was 2.4% (-5.0, 9.8). The results based on per protocol analysis: In the UFH arm there were 44 (97.8%) patients who had not developed DVT/PE as compared to 39 (95.1%) in the LMWH arm. The difference in proportion of patients who had not developed DVT/PE between the UFH and LMWH arm was 2.7% (-5.2, 10.5). Patients on UFH had higher major bleeding complications 4 (8.9%) as compared to 0 in LMWH arm. But with respect to other complications like thrombocytopenia (HIT) and mild or minimal bleeding both arms were comparable. CONCLUSION: This study has demonstrated that low dose UFH is as effective as LMWH as a prophylactic agent for venous thromboembolism in medically ill patients and economical also.

Difficult cannulation of hemodialysis arteriovenous fistula - Role of imaging in access management (DICAF STUDY).

BACKGROUND: Difficulty in cannulation of arteriovenous fistula (AVF) can lead to inadequate dialysis, transient to permanent loss of access and increases dependency on bridging catheters. This study aimed to analyze the causes for difficult fistula cannulation, using various imaging modalities. METHODOLOGY: This was a retrospective single-center observational study conducted between October 2017 and June 2018. Patients whose fistulae were difficult to cannulate were initially evaluated by physical examination followed by doppler ultrasonography or/and fistulogram as necessary. The patients were divided into two groups that is, primary difficult cannulation (within first three months of creation of fistula) or secondary difficult cannulation (after three months). RESULTS: We encountered difficult cannulation in 43 patients. About 60% were primary difficult cannulations. Most common causes for difficulty in cannulation were cannulation zone (CZ) stenosis (23.3%), immature fistula (20.9%), outflow stenosis (18.6%), inflow stenosis (11.6%), anatomical abnormalities (11.6%), outflow plus CZ stenosis (9.3%) and inflow plus CZ stenosis (4.7%). Among patients with primary difficult cannulation, immature fistula (34.6%) was the most common cause, whereas CZ stenosis (47.1%) was the most common etiology for secondary difficult cannulation. Edema leading to difficult cannulation was found in 12 patients (27.9%), all of which was due to central vein stenosis. Cannulation resulted in hematoma, fistula thrombosis, failure of fistula and pseudoaneurysm in 83.7%, 27.9%, 16.3%, and 2.3% of cases respectively. Bridging temporary dialysis catheter placement was required in 67.4% patients. Ultrasound doppler had lower diagnostic value when compared to fistulogram (71.4% vs 93.9%, p = 0.014). CONCLUSION: Difficulty in cannulating the arteriovenous fistula is a common problem in hemodialysis patients. We suggest that patients whose fistulae are difficult to cannulate should undergo early radiological evaluation to decrease catheter dependency and access failure.

Skin Colonizers and Catheter Associated Blood Stream Infections in Incident Indian Dialysis Patients.

Introduction: Skin colonization is a risk factor for multi-drug resistant (MDR) catheter-associated bloodstream infections (CABSI). This study aimed to determine the prevalence and spectrum of skin colonizing MDR organisms in incident HD patients and their correlation with CABSI. Methods: This single-center prospective cohort study included consecutive adult incident HD patients who underwent tunneled or non-tunneled internal jugular vein HD catheter insertion between June 1, 2017 and October 31, 2017. Nasal, axillary, and exit site swabs were obtained prior to catheter insertion, at 14-21 days, and 28-35 days after catheter insertion. Results: Forty-three patients (69.7% male, 32.5% diabetic) were included and provided baseline swabs, while 29 and 10 patients respectively were available for follow-up swabs. MDR bacterial colonization, MRSA colonization, and MDR gram-negative colonization on the baseline set of swabs were seen in 76.7%, 69.7%, and 9.3% patients respectively. Of the 29 patients with at least two consecutive sets of swabs, 79.3% showed persistent colonization by MDR gram-positive organisms, most commonly by MRSA. Six patients developed a CABSI during the follow-up period (incidence rate 3.7 per 1000 patient days), 83.4% were gram negative, and in only one instance (16.6%) was the bacterial strain identical to that which had previously colonized the skin. Conclusions: Three-fourths of HD patients were colonized by MDR bacteria prior to HD initiation. Despite the majority being persistently colonized by MDR gram-positive organisms, CABSIs were predominantly gram negative.

Management strategies and outcomes in renal transplant recipients recovering from COVID-19: A retrospective, multicentre, cohort study.

Background: There is an enormous knowledge gap on management strategies, clinical outcomes, and follow-up after kidney transplantation (KT) in recipients that have recovered from coronavirus disease (COVID-19). Methods: We conducted a multi-center, retrospective analysis in 23 Indian transplant centres between June 26, 2020 to December 1, 2021 on KT recipients who recovered after COVID-19 infections. We analyzed clinical and biopsy-confirmed acute rejection (AR) incidence and used cox-proportional modeling to estimate multivariate-adjusted hazard ratios (HR) for predictors of AR. We also performed competing risk analysis. Additional outcome measures included graft loss, all-cause mortality, waiting time from a positive real-time polymerase test (RT-PCR) to KT, laboratory parameters, and quality of life in follow-up. Findings: Among 372 KT which included 38(10·21%) ABO-incompatible, 12(3·22%) sensitized, 64(17·20%) coexisting donors with COVID-19 history and 20 (5·37%) recipients with residual radiographic abnormalities, the incidence of AR was 34 (9·1%) with 1(0·26%) death censored graft loss, and 4(1·07%) all-cause mortality over a median (interquartile range) follow-up of 241 (106-350) days. In our cox hazard proportional analysis, absence of oxygen requirement during COVID-19 compared to oxygen need [HR = 0·14(0·03-0·59); p-value = 0·0071], and use of thymoglobulin use compared to other induction strategies [HR = 0·17(0·03-0.95); p-value = 0·044] had a lower risk for AR. Degree of Human leukocyte antigen (HLA) DR mismatch had the highest risk of AR [HR = 10.2(1·74-65·83); p-value = 0·011]. With competing risk analysis, with death as a competing event, HLA DR mismatch, and oxygen requirement continued to be associated with AR. Age, gender, obesity, inflammatory markers, dialysis vintage, steroid use, sensitization and ABO-incompatibility have not been associated with a higher risk of AR. The median duration between COVID-19 real time polymerase test negativity to transplant was 88(40-145) days (overall), and ranged from 88(40-137), 65(42-120), 110(49-190), and 127(64-161) days in World Health Organization ordinal scale ≤ 3, 4, 5, and 6-7, respectively. There was no difference in quality of life, tacrolimus levels, blood counts, and mean serum creatinine assessed in patients with a past COVID-19 infection independent of severity. Interpretation: Our findings support that the outcomes of KT after COVID-19 recovery are excellent with absence of COVID-19 sequelae during follow-up. Additionally, there does not seem to be a need for changes in the induction/immunosuppression regimen based on the severity of COVID-19. Funding: Sanofi.

Does Hemodialysis Need to be Initiated to Improve Platelet Function in CKD G5 Patients? A Pilot Prospective, Observational Cohort Study.

INTRODUCTION: We previously showed that patients with chronic kidney disease (CKD) Stage G4-5 have normal bleeding times. This made us question whether hemodialysis (HD) initiation was really necessary solely to improve platelet function. METHODS: In this prospective observational study, two 5 ml citrated blood samples and one 2 ml EDTA blood sample were collected from incident HD patients fulfilling inclusion criteria prior to HD initiation (baseline sample) and after three sessions of short duration, low flow, counter-current HD. In each instance, one sample was used to perform Collagen adenosine diphosphate closure time (CADPCT) using the Platelet function analyzer (PFA 200, normal range 68-142 seconds) and the second for light transmission aggregometry (LTA) with ADP as agonist (normal ≥50%). RESULTS: This study included 20 patients between October 2017 and February 2019. Overall, and in the subgroup with normal baseline CADPCT or LTA, there was no statistically significant improvement after HD. However, of the 30% of patients who had an abnormal baseline CADPCT, 50% attained a normal value after three HD sessions, and the overall reduction in CADPCT in this group was statistically significant (P = 0.02). Of those with a baseline normal CADPCT, 21% developed abnormal prolongation post HD. CONCLUSION: HD for the sole purpose of improving platelet function is only of benefit in the subgroup of patients with an abnormal CADPCT at baseline, with close to 50% normalizing their platelet function after three sessions of low flow, short duration, counter-current HD.

A Multicenter Cohort Study From India of 75 Kidney Transplants in Recipients Recovered After COVID-19.

BACKGROUND: There is limited current knowledge on feasibility and safety of kidney transplantation in coronavirus disease-19 (COVID-19) survivors. METHODS: We present a retrospective cohort study of 75 kidney transplants in patients who recovered from polymerase chain reaction (PCR)-confirmed COVID-19 performed across 22 transplant centers in India from July 3, 2020, to January 31, 2021. We detail demographics, clinical manifestations, immunosuppression regimen, laboratory findings, treatment, and outcomes. Patients with a previous diagnosis of COVID-19 were accepted after documenting 2 negative severe acute respiratory syndrome coronavirus 2 PCR tests, normal chest imaging with complete resolution of symptom for at least 28 d and significant social distancing for 14 d before surgery. RESULTS: Clinical severity in patients ranged from asymptomatic (n = 17, 22.7%), mild (n = 36.48%), moderate (n = 15.20%), and severe (n = 7.9.3%) disease. Median duration between PCR positive to transplant was 60 d (overall) and increased significantly from asymptomatic, mild, moderate, and severe disease (49, 57, 83, 94 d, P 0.019), respectively. All recipients and donors were asymptomatic with normal creatinine after surgery at a median (interquartile range) follow-up of 81 (56-117) d without any complications relating to surgery or COVID-19. Patient and graft survival was 100%, and acute rejection was reported in 6.6%. CONCLUSIONS: Prospective kidney transplant recipients post-COVID-19 can be considered for transplantation after comprehensive donor and recipient screening before surgery using a combination of clinical, radiologic, and laboratory criteria, careful pretransplant evaluation, and individualized risk-benefit analysis. Further large-scale prospective studies with longer follow-up will better clarify our initial findings. To date, this remains the first and the largest study of kidney transplantation in COVID-19 survivors.

The long-term impact of hepatitis C infection in kidney transplantation in the pre-direct acting antiviral era.

Hepatitis C virus (HCV) infection in kidney transplantation is an important issue with effects on patient and graft survival. The current standard of care involves using oral Direct Acting Antiviral drugs. Till recently, pre-transplant treatment with interferon was the only option for treatment. We studied 677 consecutive kidney transplant recipients with HCV infection. 5.2% patients had evidence of HCV infection. 2.0% were newly detected to have HCV infection after transplant (de novo HCV group). Nearly 28.6% had negative antibody tests but positive Nucleic Acid Test at the time of diagnosis. Eighty-five percent of pre-transplant HCV-positive patients were treated with interferon-based regimens. Early virologic response was seen in 66.6%. End of treatment response was achieved by 94.1%. Sustained virologic response was seen in 81.2%. Overall, patient and graft survival were not different between HCV and control groups (log-rank P = 0.154). Comparing HCV and control groups, there was a tendency toward increased fungal (11.4% vs. 5.6%, P = 0.144) and CMV infections (25.7% vs. 17.1%, P = 0.191) in the HCV group, though it did not reach statistical significance. Eighty-percent of the interferon-treated patients suffered side effects. On comparing, the pre-transplant HCV-positive group (85% treated) with the de novo HCV group (none treated), the de novo group had significantly reduced patient survival (P = 0.020) and NODAT (35.7 vs 4.8%, P = 0.028), and a tendency toward higher CMV infections (35.7% vs 19%, P = 0.432). In addition, death and hepatic complications (decompensated liver disease, fibrosing cholestatic hepatitis) occurred only in de novo HCV group. These results highlight the need for continued post-transplant treatment of HCV positive patients. The newer anti-HCV drugs are expected to fulfill this felt-need in kidney transplantation but long-term results are awaited. This study can serve as a benchmark for future studies to compare the long-term effect of Direct Acting Antiviral drugs.

Superior thyroid artery pseudoaneurysm and arteriovenous fistula following attempted internal jugular venous access and its management.

Vascular injury during common jugular venous (IJV) access is a rare complication, usually involving injury to the common carotid artery. We describe a previously unreported complication of iatrogenic injury of IJV access involving a branch of the superior thyroid artery, and its endovascular management.