Renal Allograft Recipients Research Articles

Large de novo Renal Cell Cancer in Renal Allograft

Renal cell cancer (RCC) in renal allograft is a rare entity. We report a case of RCC successfully diagnosed in a 42-year-old renal allograft recipient which developed 13 years after engraftment. The patient was initially evaluated using ultrasound for two episodes of hematuria followed by contrast-enhanced CT scan revealing 9.7 cm × 8.6 cm × 6.5 cm heterogeneously enhancing mass at mid-pole with involvement of renal sinus. Allograft nephrectomy was performed. A genetic study with DNA microsatellite analysis showed de novo RCC from donor origin. Seven months after surgery, the patient is alive with no evidence of tumor recurrence and is now planned for a second renal transplant. To the best of our knowledge, this is the largest allograft RCC reported in the Indian scenario.

CC Genotype of GNAS c.393C>T (rs7121) Polymorphism Has a Protective Effect against Development of BK Viremia and BKV-Associated Nephropathy after Renal Transplant

The GNAS gene encodes the alpha-subunit of the stimulatory G-protein (Gαs) in humans and mice. The single-nucleotide polymorphism of GNAS, c.393C>T, is associated with an elevated production of Gαs and an increased formation of cyclic adenosine monophosphate (cAMP). In the present study, we analyzed the effect of this GNAS polymorphism on a renal allograft outcome. We screened a cohort of 436 renal allograft recipients, who were retrospectively followed up for up to 5 years after transplant. GNAS genotypes were determined with polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assays. The 393T allele was detected in 319 (73%) recipients (113 recipients with TT and 206 with CT genotype) and the CC genotype in 117 (27%). The CC genotype was associated with a significantly lower frequency of BK viremia (CC, 17 recipients (15%); T 84 (26%)); p = 0.01; TT, 27 vs. CC, 17, p = 0.07; TT, 27 vs. CT, 57, p = 0. 46; CT, 57 vs. CC, 17, p = 0.01) and BKV-associated nephropathy (CC, 3 recipients (3%); T, 27 (8%); p = 0.03; TT,10 vs. CC, 3, p = 0.04; TT, 10 vs. CT,17, p = 0.85; CT, 17 vs. CC,3, p = 0.04) after transplant. BKV-associated nephropathy-free survival was significantly better among CC genotype carriers than among T allele carriers (p = 0.043; TT vs. CC, p = 0.03; CT vs. CC, p = 0.04; TT vs. CT, p = 0.83). Multivariate analysis indicated an independent protective effect of the CC genotype against the development of both BK viremia (relative risk. 0.54; p = 0.04) and BKV-associated nephropathy after renal transplant (relative risk. 0.27; p = 0.036). The GNAS 393 CC genotype seems to protect renal allograft recipients against the development of BK viremia and BKV-associated nephropathy.

Presence of CD163+ macrophages in DCD kidneys with high DGF reduces the risk for acute cellular rejection in 6 months after kidney transplantation

Acute cellular rejection (ACR) occurs in 10% of renal allograft recipients and is characterized by leukocyte infiltration as observed in needle biopsies. ACR onset is subject to several risk factors, including delayed graft function (DGF). As the impact of DGF on the etiology of ACR remains unclear, this study analyzed the association between presence of leukocyte subsets and ACR onset, in DCD kidney biopsies with extensive DGF following transplantation. Immunohistochemical analysis of protocol biopsies taken 10 days after kidney transplantation revealed that patients with high levels of renal CD163+ macrophages have a decreased risk (OR = 0.021, P = 0.008) for ACR in the first 6 months after transplantation. In pre-transplant biopsies of a comparable DCD cohort, with >80% DGF, presence of donor CD163+ macrophages showed no effect on ACR risk. Therefore, leukocyte infiltrate present during the inflammatory response at the time of DGF may contain anti-inflammatory macrophages that exert a protective effect against ACR development.

Combining donor-derived cell-free DNA and donor specific antibody testing as non-invasive biomarkers for rejection in kidney transplantation

Donor specific anti-HLA antibodies (DSA) and donor-derived cell-free DNA (dd-cfDNA) have lead to substantial progress in the non-invasive monitoring of the renal allograft by being able to detect or rule out subclinical rejection and guide immunosuppressive changes. In this study we sought to analyze the clinical, de novo DSA (dnDSA) and histological determinants of dd-cfDNA levels. The study included a cohort of stable renal function kidney transplant (KT) recipients who underwent anti-HLA dnDSA and dd-cfDNA testing between September 2017-December 2019. Statistical models were constructed to detect association with predictors of dd-cfDNA levels and other clinical characteristics. 171 renal allograft recipients were tested for dd-cfDNA and dnDSA at a median 1.06 years posttransplant (IQR: 0.37–4.63). Median dd-cfDNA was 0.25% (IQR: 0.19–0.51), 18.7% of patients having a dd-cfDNA ≥ 1%. In a multivariate linear regression model the presence of dnDSA MFI ≥ 2500 was the best independent determinant of dd-cfDNA level (p < 0.001). Among patients tested, 54 had concurrent dd-cfDNA determination at the time of an allograft biopsy. dd-cfDNA had an AUC of 0.82 (95% CI 0.69–0.91; p < 0.001) and of 0.96 (95% CI 0.87–0.99) to discriminate any rejection and ABMR, respectively. After multivariate adjustment, the models that included ABMR (R = 0.82, R2 = 0.67, p < 0.001), or ptc (R = 0.79, R2 = 0.63, p < 0.001) showed the best correlation with dd-cfDNA level. We are confirming a strong association of dd-cfDNA with dnDSA and underlying alloimmune-mediated injury in renal allograft recipients in a cohort of patients with unsuspecting clinical characteristics for rejection and excellent allograft function. Our findings support the need for noninvasive biomarker surveillance in KT recipients and we propose that dd-cfDNA may complement dnDSA screening.

Analysis of Cross-sectional and Longitudinal HLA and Anti-viral Responses After COVID Infection in Renal Allograft Recipients: Differences and Correlates.

Background.Characterization of anti-HLA versus anti-severe acute respiratory syndrome coronavirus 2 (anti–SARS-CoV-2) immune globulin isotypes in organ transplant recipients after coronavirus disease 2019 (COVID-19) infection has not been reported. We aimed to determine changes in anti-HLA antibodies in renal transplant patients with COVID-19 and compare the immunoglobulin and epitope-binding pattern versus anti–SARS-CoV-2 antibodies.Methods.This is a cross-sectional study of 46 kidney transplant recipients including 21 with longitudinal sampling. Using a semi-quantitative multiplex assay, we determined immunoglobulin (Ig) M, IgA, IgG, and IgG1-2-3-4 antibodies against Class I and Class II HLA, and 5 SARS-CoV-2 epitopes including the nucleocapsid protein and multiple regions of the spike protein.Results.Fourteen of 46 (30%) patients had donor-specific anti-HLA antibodies (donor-specific antibody [DSA]), 12 (26%) had non-DSA anti-HLA antibodies and 45 (98%) had anti–SARS-CoV-2 antibodies. Most DSAs targeted HLA-DQ (71%), with a dominant IgG isotype and IgG1 subtype prevalence (93%), and/or IgG3 (64%), followed by IgG2 (36%). Comparatively, there was a higher prevalence of IgA (85% versus 14%, P = 0.0001) and IgM (87%, versus 36%, P = 0.001) in the anti–SARS-CoV-2 antibody profile, when compared to DSAs, respectively. Anti–SARS-CoV-2 antibody profile was characterized by increased prevalence of IgM and IgA, when compared to DSAs. The median calculated panel reactive antibody before COVID-19 diagnosis (24%) tended to decrease after COVID-19 diagnosis (10%) but it was not statistically significant (P = 0.1).Conclusions.Anti-HLA antibody strength and calculated panel reactive antibody in kidney transplant recipients after COVID-19 do not significantly increase after infection. Although the IgG isotype was the dominant form in both HLA and SARS-CoV-2 antigens, the alloimmune response had a low IgA pattern, whereas anti–SARS-CoV-2 antibodies were high IgA/IgM.

Frequency of CD39+, LAG3+, and CTLA4+ Regulatory T Cells in Two Different Immunosuppressive Protocols in Renal Allograft Recipients (Sirolimus vs Mycophenolate mofetil): A Cohort Report.

Impaired renal function is considered as a significant risk factor for cardiovascular events in chronic kidney disease patients. Several immunosuppressive drugs are used in these patients, which necessitates to minimize the drug-related side effects by employing alternative strategies. This study aimed to evaluate prospectively the influence of low dose ATG induction therapy with two different protocols (Sirolimus versus Mycophenolate mofetil) on the expression of functional markers (LAG-3, CD39, and intracellular CTLA-4) on conventional Tregs in renal recipients. Thirty-eight renal transplant recipients were enrolled in this study. The patients were randomly assigned into two groups, including TMP: Tacrolimus (Tac), Mycophenolate mofetil (MMF), and Prednisolone (n=23); and TSP: Tac, Sirolimus (SRL), and Prednisolone (n=15). The frequency of LAG-3, CD39, and intracellular CTLA-4 on circulating Tregs was analyzed by flow cytometry before and after transplantation. Analysis of the flow cytometry data showed that the frequency of CD4+CD25+FOXP3+ Tregs increased 4 months post-transplantation compared to pre-transplantation in both groups, although this increase was only significant in TMP group. In TMP treated patients, the frequency of LAG-3+ Tregs and CD39+ Tregs increased, whereas the frequency of intracellular CTLA-4+ Tregs decreased 4 months post-transplantation. In TSP group, while the frequency of CD39+ Tregs increased, the frequency of CTLA-4+ Tregs decreased in post-transplantation compared to pre-transplantation. it seems that both treatment regimen protocols with a low dose ATG induction therapy may be clinically applicable in kidney transplant recipients.

310.6: Association of Human Leukocyte Antigen With Anti-sARS-cov-2 Spike Protein Humoral Response

Introduction: Cellular and humoral response are required for the SARS-CoV-2 eradication. Antigen presenting cells load SARS-CoV-2 peptides on human leukocyte antigen with different avidity and present to T and B cells for the differential humoral and cellular response. Due to immunosuppression, renal transplant recipient patients are speculated to poorly form the antibody against SARS-CoV-2 virus. Therefore, determining the association of specific HLA alleles with anti-SARS-CoV-2 spike protein antibody formation will be helpful in managing the renal transplant recipient patients having specific HLA alleles from SARS-CoV-2 infection and vaccination. Material and Methods: In this study anti-SARS-CoV-2 spike protein antibody in 161 renal allograft recipient patients were determined by the chemiluminescent microparticle immunoassay methods and human leukocyte antigen alleles were determined by the polymerase chain reaction-single strand oligonucleotide methods and analyzed to study, the HLA alleles association with anti-SARS-CoV-2 spike protein humoral response and severity of COVID-19 symptoms in recently SARS-CoV-2 infected patients. Seroconversion was defined if anti-SARS-CoV-2 spike protein antibody titer was >50AU/ml. Results: The anti-SARS-CoV-2 spike protein antibody seroconversion rate in renal allograft recipients was 90.06% with median titer 751.80 AU/ml. The frequency of HLA class I alleles A*11 was in 22.1%, A*24 in 21.37%, A*33 in 20.68%, HLA B*15 in 11%, B*07 in 8.27%, HLA-C*30 in 20.93% and C*70 in 23.25% and Class II HLA alleles -DRB1*07 was in 18.62%, DRB1*04 in 13.8%, HLA-DRB1*10 in 14.48% and HLA-DQA1*50 in 32.55% of patient and were associated with the seroconversion.HLA-B*04, B*52, and B*55 were associated with non-seroconversion in 18.75%, 12.5 and 6.25% of patients respectively, HLA- C*07, C*12, C*30 in 16.6% of patients and C*60 in 33.3% of patients were associated with non-seroconversion. HLA-DRB1*01, HLA-DRB1*03 in 12.5% and DRB1*70 in 6.25% of patients were associated with non- seroconversion. The mean post-infection time of patients recovery from COVID19 symptoms was 18.25±8.14 days. Conclusion: Renal transplant recipients with SARS-CoV-2 infection developed a robust seroconversion rate of 90.0% and different alleles of HLA-B, DRB1 and DQA1 were significantly associated with the seroconversion.

216.11: Higher Urinary Mitochondrial DNA Level From COVID19 Recovered Renal Allograft Recipient Patients Induces Inflammatory Cytokine Secretion in Peripheral Blood Mononuclear Cell

216.11: Higher Urinary Mitochondrial DNA Level From COVID19 Recovered Renal Allograft Recipient Patients Induces Inflammatory Cytokine Secretion in Peripheral Blood Mononuclear Cell

240.3: Detection of CMV Mediated Sub-Clinical Rejection by Urine Biomarkers

Methods: Research on early detection of Cytomegalovirus (CMV) mediated sub-clinical rejection (sAR) is in its nascence. This study explores the efficacy of urine-based biomarkers for sAR risk prognostication. Urine samples were serially collected (1 week- 2yrs) across 125 unique renal allograft recipients from UCSF and UCLA. These CMV+ (blood CMV-PCR) patients received valganciclovir therapy until CMV- for 3 consecutive months. Analysis: We computed a machine-learning based rejection prediction score incorporating urine cell-free DNA (cfDNA), methylated cfDNA, total protein, CXCL10, clusterin and creatinine. Rejection was determined between scores of 32-100; higher score associated with biopsy severity (Yang et al, STM 2021). In a cross-sectional analysis, Kruskal-Wallis test was performed on the urine-score distribution, to determine sAR during CMV+. Subsequently UCSF samples were analyzed longitudinally to establish the relationship between CMV and sAR; this was validated independently in UCLA samples. Results: Significant differences were observed in scores >32 between biopsy-confirmed AR vs. stable (p: 0.0034) and CMV vs. stable (p=0.003). Longitudinal analysis yielded 3 primary sAR patterns following CMV infection; (i)persistence of sAR leading to new development of chronic allograft injury; (ii)early sAR (score >32) followed by a further increase in score (>55) with biopsy confirmed cAR; (iii)sAR (>32) followed by recovery of injury with CMV resolution and a decline in score <32). Conclusions: We provide a urine-based method for detecting sAR at the time of CMV infection, and its potential clinical utility for titrating use of anti-viral therapy and recipient immunosuppression load.

P8.116: Evaluation of Traditional and Non-traditional Lipid Components in Renal Transplant Recipients

Introduction: Kidney transplantation is followed by development of additional cardiovascular risk factors. The conventional lipid markers like triglyceride, cholesterol, LDL and HDLs are generally measured as traditional lipids to identify subjects at risk of cardiovascular events. But there are other potent atherogenic risk elements like Apolipoprotein A-1, B and lipoprotein (a). When included, these may provide better assessment of dyslipidemias in renal transplant recipients. In this study we evaluated the dyslipidemia status in a group of living related kidney recipients by seeing the pattern and interaction of both groups of traditional and nontraditional lipids. Materials & Method: In this cross sectional study renal allograft recipients, at least 3-month post- transplant, were included. Laboratory investigations done were triglyceride (TG), cholesterol (TC), low density lipoprotein (LDL) and high-density lipoprotein (HDL) as traditional lipid marker and Apoliprotein B (APO B) and A1(APO A-1); and lipoprotein(a) (lipo(a)) as non-traditional lipid markers. Tests for glycemia (HbA1c), renal function (ACR, serum creatinine, eGFR), anemia (hemoglobin) and inflammation (hsCRP) were also done. Results: In this study 105 patients were included. They were mostly on triple drug therapy with tacrolimus, mycophenolate mofetyl and prednisolon. The duration of transplantation was 34±26 (4.5-112) months. Mean age was 34 ± 8 years with a male to female ratio was 7:1. The mean serum creatinine was 2.0±1.3 mg% and eGFR 52± 23 ml/mim/1.73m2. Among renal transplant recipients, 62% had elevated TG (> 150mg %), 33% had elevated TC (> 200mg %), 53% had elevated LDL (> 100mg %) and 61% had low HDL (<40mg %). The ApoA-1 was below normal (<120mg % in male and < 140 mg% in female) in 43%, Apo B elevated (> 130mg %) in 10% and Lipoprotein (a) elevated (> 30mg %) in 16%. According to abnormality in any of the traditional lipid markers 88% of the renal transplant recipients was identified with dyslipidemia. According to abnormal cut-offs dyslipidemia was identified by non-traditional lipid markers in 57%. In 12% subjects all traditional lipid markers was normal but abnormal when nontraditional ones were checked. In all subjects with traditional dyslipidemis 41% had normal nontraditional lipids. In 52% subjects both traditional and nontraditional lipid markers were in dyslipidemic range. Conclusion: Both traditional and nontraditional lipid parameters are needed to be measured in renal transplant recipients to identify the pattern and extent of dyslipidemia prevails among them. This will help in better lipid management and prescribing anti-lipid therapy to combat cardiovascular events. Partially from supports of MOE, Bangladesh and for technical support of ABC, Bangladesh.

342.3: Outcome Analysis of Patients With Genetic Mutations of Complement Regulatory Proteins in Relation to Incidence of Post Renal Transplant Thrombotic Microangiopathy

Introduction: Thrombotic Microangiopathy is an occlusive disorder of microvasculature characterized by thrombocytopenia, systemic or intrarenal platelet aggregation, thrombus formation and hemolytic anemia caused by fragmentation of erythrocytes due to the disturbed microvasculature. TMA developing after renal transplantation can be categorized into either De novo TMA, developing for the first time without any evidence of the disease before the transplant or recurrent TMA where native kidneys have failed due to TMA and recur after kidney transplantation. The contribution of complement regulatory gene (CRG) mutation to post-transplant Thrombotic Microangiopathy (TMA) in Indian kidney transplant recipients (KTR) is unknown. This is a study to determine the association of CRG on post-transplant TMA and graft failure. Methods: A Single Centre, Prospective Observational Cohort Study was undertaken in renal transplant recipients. All live and Deceased donor renal allograft recipients who underwent transplantation from 1st December 2019 onwards till 31st December 2020 were recruited and were followed up for 1 year beyond the last enrolment. Genetic testing was performed with MLPA and Clinical exome sequencing. Results: 78 KTRs with a mean age of 37.09 ± 13.23 years were enrolled. The Native cause of kidney disease in 55 (70.5%) patients was undetermined and 23 (29.5%) had established cause of chronic kidney disease. 58 (74.4%) were males and 20 (25.6%) were females. CRG mutation was seen in 48/78 (61.5%) KTRs. The allele frequency of the CRG mutation was seen in 48/78 (61.53%) of which duplication of CFHR gene was predominantly seen in 40/78 (51.2%) patients. CRG mutation in this cohort was seen more in the younger age group patients. There was no gender predominance for patients with CRG mutation. None of the patients had a mutation for CFH, CFI, CFB, C3, THBD, DGKE genes. One patient had a mutation for the PLG gene. The incidence of post-transplant TMA was seen in 4/78 (5.12%) patients. Mutation related to aHUS was seen in 2 patients. There was no significant difference in serum creatinine levels of patients with or without CRG mutation at the end of 1 year. Conclusion: The prevalence of CRG mutation in our KTR cohort was high and is associated with post-transplant TMA in 50% of patients with de novo TMA. The graft outcome at the end of 1 year was similar in patients with mutation and those without mutation. This study suggests that the presence of CRG mutation should not preclude renal transplantation in patients with ESRD.

427.11: Assessment of Music Therapy on Psychological Stress And Immune Function in the Early Postoperative Period of Renal Allograft Recipients: A Prospective RCT

427.11: Assessment of Music Therapy on Psychological Stress And Immune Function in the Early Postoperative Period of Renal Allograft Recipients: A Prospective RCT

Characterization of preoperative cardiovascular status and association with outcome following feline renal allograft transplantation: 166 cases.

To retrospectively evaluate preoperative historical, biochemical, and cardiovascular screening data for predictors of survival to discharge and long-term survival in feline renal allograft recipients from 1 institution. 166 cats that underwent renal transplantation at the University of Pennsylvania between 1998 and 2018. Medical records were reviewed for preoperative historical information, biochemical data, and cardiac assessment including auscultation findings, pre- and postoperative systolic blood pressure measurements, thoracic radiographic evaluation, and echocardiographic measurements. The need for hemodialysis, the number of surgical procedures, native kidney biopsy diagnosis and survival time was also recorded. Kaplan-Meier analysis was used to generate survival plots and estimate median survival times with a 95% CI. Univariable and multivariable analysis were performed to determine variables that were independently associated with survival to discharge and long-term survival. The patient population primarily consisted of adult male DSH cats (70%) diagnosed with IRIS stage 4 CKD (66.3%). Abnormalities identified on preoperative cardiac assessment, including hypertension, the presence of a murmur, echocardiographic changes, and radiographic signs of congestive heart failure, were not associated with survival to discharge or long-term survival. Age was the only single significant variable associated with survival, and the risk of death increased by 11% (95% CI, 6% to 17%) for every 1 year in patient age. The presence of cardiac abnormalities identified during the screening process of cats presenting for transplantation should not immediately exclude a potential candidate for the procedure. Owners considering transplantation should be educated on the impact of age on survival following surgery.

P8.111: Epstein-Barr Virus-Positive T-Cell Lymphoma Characterized by Intestinal Involvement With Multiple Perforation in an Adult Renal Allograft Recipient: Two Case Reports

P8.111: Epstein-Barr Virus-Positive T-Cell Lymphoma Characterized by Intestinal Involvement With Multiple Perforation in an Adult Renal Allograft Recipient: Two Case Reports

Tocilizumab in the treatment of active chronic humoral rejection resistant to standard therapy

IntroductionThere is no consensus on the most appropriate treatment for chronic active antibody-mediated rejection (cAMR). Recent studies suggest that treatment with tocilizumab (TCZ) may stabilize graft function, decrease the intensity of donor-specific HLA antibodies (DSAs) and reduce inflammation of microcirculation. Patients and methodsObservational study with renal allograft recipients diagnosed with cAMR (n = 5) who had not submitted a response to traditional treatment based on the combination of plasma replacements, immunoglobulins, and rituximab. Patients were told to be treated with TCZ as compassionate use in six doses per month (8 mg/kg/month). Renal function, proteinuria, and the intensity of DSAs were monitored during follow-up. ResultsFive patients, average age 60 ± 13 years, three male and two retrasplants (cPRA average 55%) with preformed DSAs. Treatment with TCZ was initiated within 47 ± 52 days of biopsy. In two cases treatment was discontinued after the first dose, by severe bicitopenia with cytomegalovirus viremia and by graft failure, respectively. In the three patients who completed treatment, no stability of renal function (serum creatinine from 1.73 ± 0.70 to 2.04 ± 0.52 mg/dL, e-FGR 4 6 ± 15 to 36 ± 16 mL/min), showed increased proteinuria (3.2 ± 4.0 to 6.9 ± 11.0 g/g) and the intensity of DSAs maintain stable. No changes were observed in the degree of inflammation of microcirculation (g+pt 4.2 ± 0.8 vs. 4.3 ± 1.0) or in the degree of transplant glomerulopathy (cg 1.2 ± 0.4 vs. 1.8 ± 1.0). ConclusionsTCZ therapy does not appear to be effective in modifying the natural history of chronic active antibody-mediated rejection, does not improve the degree of inflammation of microcirculation and does not reduces the intensity of DSAs.

GNB3 c.825C>T (rs5443) Polymorphism and Risk of Acute Cardiovascular Events after Renal Allograft Transplant

The c.825C>T single-nucleotide polymorphism (rs5443) of the guanine nucleotide-binding protein subunit β3 (GNB3) results in increased intracellular signal transduction via G-proteins. The present study investigated the effect of the GNB3 c.825C>T polymorphism on cardiovascular events among renal allograft recipients posttransplant. Our retrospective study involved 436 renal allograft recipients who were followed up for up to 8 years after transplant. The GNB3 c.825C>T polymorphism was detected with restriction fragment length polymorphism (RFLP) polymerase chain reaction (PCR). The GNB3 TT genotype was detected in 43 (10%) of 436 recipients. Death due to an acute cardiovascular event occurred more frequently among recipients with the TT genotype (4 [9%]) than among those with the CC/CT genotypes (7 [2%]; p = 0.003). The rates of myocardial infarction (MI)–free survival (p = 0.003) and acute peripheral artery occlusive disease (PAOD)–free survival (p = 0.004) were significantly lower among T-homozygous patients. A multivariate analysis showed that homozygous GNB3 c.825C>T polymorphism exerted only a mild effect for the occurrence of myocardial infarction (relative risk, 2.2; p = 0.065) or acute PAOD (relative risk, 2.4; p = 0.05) after renal transplant. Our results suggest that the homozygous GNB3 T allele exerts noticeable effects on the risk of MI and acute PAOD only in the presence of additional nonheritable risk factors.

Predictors of Short-Term Outcomes in Living Donor Renal Allograft Recipients: A Prospective Study From a Tertiary Care Center in North India.

BackgroundRenal transplantation is the optimal treatment for patients of all ages with end-stage kidney disease. The long-term outcomes of renal transplantation are assessed by graft and patient survival rates. These outcomes are, in turn, influenced by post-transplant events such as delayed graft function, rejections, post-transplant infections, and post-transplant diabetes mellitus (PTDM). Each of these short-term outcomes is, in turn, determined by the interplay of various factors in the pre-, peri-, and post-transplant period. This prospective study was designed to understand the factors affecting short-term outcomes in living donor transplantation and their effect on graft and patient survival.MethodologyA total of 86 patients underwent live donor renal transplantation between January 1, 2015, and March 31, 2016, at a tertiary care hospital in north India. Of these, five were lost to follow-up, and the remaining 81 patients were prospectively followed up to December 31, 2017.ResultsThe majority of the recipients were males (91%) and the donors were females (74%). Spousal and related donors comprised 49% and 51% of donations, respectively. The mean estimated glomerular filtration rate (eGFR) of donors was 98 ± 9.2 mL/minute/1.73m². Induction therapy with basiliximab was given to 21/81 (26%) recipients. The majority of recipients (68/81, 84%) received triple-drug immunosuppression with prednisolone, tacrolimus, and mycophenolate mofetil. Delayed graft function (DGF) occurred in 4/81 (4.9%) cases. Biopsy-proven acute rejections (BPARs) occurred in 15/81 (18.5%) cases, two-thirds of which were acute antibody-mediated rejections (ABMRs). During the follow-up period, 50 episodes of infections occurred in 35/81 (43.2%) recipients, with the most common being urinary tract infection (23/81, 28.5%). PTDM was diagnosed in 22/81 (27.2%) patients beyond six weeks of transplant. On multivariate logistic regression analysis, the most significant predictor of DGF was acute rejections and vice versa. Acute rejections also predicted the occurrence of post-transplant infections. Pre-transplant hepatitis C virus (HCV) infection and cyclosporine-based therapy were significant predictors of PTDM. At the six-month follow-up, 10/81 (12.3%) patients developed graft dysfunction. The predictors of graft dysfunction at six months were recipients of related donors and rural patients. One-year graft survival, death-censored graft survival, and patient survival rates were 85.2%, 92.6%, and 91.3%, respectively. The most common cause of death was post-transplant infections (5/7, 71.4%) of which the majority (4/5, 80%) were fungal infections. On multivariate logistic regression analysis, the most significant predictor of graft loss and patient loss was low pre-transplant donor eGFR and PTDM, respectively.ConclusionsGraft and patient survival in living donor kidney transplantation are influenced by a multitude of interdependent factors during the pre-transplant (donor eGFR, type of donor, socioeconomic status, HCV infection in recipient, type of immunosuppression) and the post-transplant (DGF, rejections, infections, and PTDM) period.

Dynamic risk prediction of BK polyomavirus reactivation after renal transplantation.

PurposeTo construct a dynamic prediction model for BK polyomavirus (BKV) reactivation during the early period after renal transplantation and to provide a statistical basis for the identification of and intervention for high-risk populations.MethodsA retrospective study of 312 first renal allograft recipients was conducted between January 2015 and March 2022. The covariates were screened using univariable time-dependent Cox regression, and those with P<0.1 were included in the dynamic and static analyses. We constructed a prediction model for BKV reactivation from 2.5 to 8.5 months after renal transplantation using dynamic Cox regression based on the landmarking method and evaluated its performance using the area under the curve (AUC) value and Brier score. Monte-Carlo cross-validation was done to avoid overfitting. The above evaluation and validation process were repeated in the static model (Cox regression model) to compare the performance. Two patients were presented to illustrate the application of the dynamic model.ResultsWe constructed a dynamic prediction model with 18 covariates that could predict the probability of BKV reactivation from 2.5 to 8.5 months after renal transplantation. Elder age, basiliximab combined with cyclophosphamide for immune induction, acute graft rejection, higher body mass index, estimated glomerular filtration rate, urinary protein level, urinary leukocyte level, and blood neutrophil count were positively correlated with BKV reactivation, whereas male sex, higher serum albumin level, and platelet count served as protective factors. The AUC value and Brier score of the static model were 0.64 and 0.14, respectively, whereas those of the dynamic model were 0.79 ± 0.05 and 0.08 ± 0.01, respectively. In the cross-validation, the AUC values of the static and dynamic models decreased to 0.63 and 0.70 ± 0.03, respectively, whereas the Brier score changed to 0.11 and 0.09 ± 0.01, respectively.ConclusionDynamic Cox regression based on the landmarking method is effective in the assessment of the risk of BKV reactivation in the early period after renal transplantation and serves as a guide for clinical intervention.

Observational Study of Early Outcomes in Single-Vessel and Multiple-Vessel Renal Allograft.

IntroductionEnd-stage renal disease (ESRD) is a global problem with a similar worldwide need for renal replacement therapy. However, the availability of transplant organs remains a challenge. Therefore, we conducted this study to measure early outcomes (up to one month) of renal allograft functions after renal transplant by assessing graft vascularity. We also measured the changes in serum creatinine and hemoglobin levels in single- and multiple-vessel renal allograft recipients.MethodsWe conducted an observational study of 108 renal allograft patients for two years. The study included all renal allograft recipients during the study period. The study excluded patients with a history of renal transplant, patients on antithrombotic therapy, a donor with previous surgery of graft kidney, and patients with anatomic abnormalities. Eighty-five patients were in the single-vessel group, and 23 were in the multiple-vessel group. Donors and recipients received standard pretransplant workup, including donor CT angiography and human leukocyte antigen crossmatching. We performed laparoscopic donor nephrectomies for all participants and perfused all renal arteries separately with Renograph solution (Claris Lifesciences, North Brunswick, NJ). A renal transplant was done in the right or left iliac fossa, noting warm and cold ischemia times. In single-vessel recipients, we anastomosed the renal artery to the external iliac artery (EIA), the renal vein to the external iliac vein (EIV), and the ureter to the bladder via a modified Lich-Gregoir technique. In multiple-vessel recipients, we performed bench anastomosis to make a single vessel, or we anastomosed vessels separately to the EIA, EIV, or the inferior epigastric artery for patients with a second small renal artery. We measured postoperative serum creatinine and hemoglobin levels for one month. In addition, we assessed graft vascularity with ultrasound-guided (USG) Doppler in the first postoperative week. We used IBM SPSS Statistics for Windows, version 21.0. (IBM Corp., Armonk, NY) for all data analyses.ResultsWarm ischemia time (WIT) was longer in multiple-vessel patients than in single-vessel patients, but the difference was insignificant (p=0.054). Cold ischemia time (CIT) was significantly longer in the multiple-vessel group than in the single-vessel group (p=0.048). We found no significant difference in serum creatinine or hemoglobin levels between groups during the study period. Perigraft collection occurred in three single-vessel patients and decreased vascularity in two multiple-vessel patients, according to USG Doppler.ConclusionsWe conducted this study to measure early outcomes of renal allograft functions after renal transplant by assessing graft vascularity, serum creatinine, and hemoglobin levels in single- and multiple-vessel renal allograft patients. According to our results, renal transplantation is not inferior in multiple-vessel allograft patients. We found no significant difference in serum creatinine levels one month postoperatively. Using multiple-vessel donors helps increase the limited donor pool, which is ultimately better for managing ESRD patients.

Correlation between Sonoelastography and Histopathological Findings in Evaluation of Chronic Renal Allograft Disease

Background Non-invasive evaluation tool for allograft kidney is important to predict chronic allograft dysfunction as it can be alternative to the invasive biopsy which is prone to so many complications. Sonoelastography can assess the stiffness of the allograft renal parenchyma, which is prone to undergo interstitial fibrosis.&#x0D; Objective To correlate sonoelastography with histopathology findings in the renal allografts.&#x0D; Method Sonoelastography was done in 60 renal allograft recipients prior to their biopsy for various indications. Estimated glomerular filtration rate (eGFR) of the patient were also obtained. Histopathology reports were collected to determine Banff score of interstitial fibrosis. Descriptive measurements (Mean ± standard deviation, Frequencies, Proportions) were calculated. Correlations among the variables were measured using Pearson’s correlation, independent sample t-test, and ANOVA.&#x0D; Result The mean strain index (SI) was lower in higher grades of fibrosis. There was significant difference in mean SI (F=18.264; df= 2,57; p &lt; 0.001) among the histological grades of fibrosis. Also a significant difference in SI among mild and moderate (S.E. 0.27, p value &lt; 0.001), mild and severe (S.E. 0.213, p value &lt; 0.001) as well as moderate and severe fibrosis (S.E. 0.244, p value &lt; 0.001) was seen. Significant correlation of eGFR with SI (p &lt; 0.001) was also seen.&#x0D; Conclusion Strain index, measured with sonoelastography, significantly correlated with different grades of tissue fibrosis. Thus it can be used as alternative method for evaluation of renal allograft patients to avoid complications of biopsy.