Prevalence, risk, and outcomes of venous thromboembolic events in kidney transplant recipients: a nested case-control study.

INTRODUCTION: Thromboembolism is more common in kidney transplant recipients (KTRs) than in the general population. Studies evaluating arterial and venous thromboembolism (VTE) in KTRs are scarce and the magnitude and risk factors are mostly undefined. METHODS: A nested control study was conducted from January 1, 2007, to December 31, 2019. Adult KTRs who were detected to have VTE events during this period were included. The primary outcome was to assess the prevalence of VTE in this population. Secondary outcomes were the assessment of the time to occurrence of the thromboembolic events after transplantation and assessing the risk factors and patient survival. For each subject studied, 4 controls were matched from the data set. RESULTS: Amongst 2158 patients, 97 (4.5%) were found to have VTE. The median follow-up time was 3.9 years (6-156 months). A total of 101 VTE events were recorded. The most common site of VTE was the lower limb deep vein thrombosis in 79 patients (0.03%)).In multivariate Cox regression analysis, serum creatinine of more than 3 mg/dl [HR 1.30, 95% CI (1.03-1.38)] was independently associated with increased VTE risk. Patients who developed a VTE had higher mortality as compared to patients who did not develop VTE. No increased risk of graft failure was found in VTE patients. CONCLUSION: This study suggests that kidney transplantation surgery is a moderate risk factor for VTE, and VTE is associated with higher morbidity and mortality. However, prospective studies are needed to establish a definite role of VTE in outcomes in KTRs.

Spectrum of fetal limb anomalies.

PURPOSE: Antenatal detection of limb anomalies is not uncommon, and pregnancies are usually terminated in view of the expected physical handicap. The aim of this retrospective observational study is to delineate the spectrum of fetal limb anomalies and provide evidence in support of complete postnatal evaluation in establishing recurrence risk. METHODS: We present 54 cases of limb malformations detected antenatally and discuss the spectrum of abnormalities, the utility of fetal autopsy, and genetic testing to establish recurrence risk in subsequent pregnancies. RESULTS: 16/54 cases were isolated radial ray anomalies. There were five cases of amniotic band syndrome, five limb body wall complex cases, three VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) associations, one case of sirenomelia, two cases of limb pelvis hypoplasia, and one case of OEIS (Omphalocele Exstrophy Imperforate anus and spinal defects). Four fetuses with non-isolated radial ray anomaly had trisomy 18. One case with bilateral radial ray defect had a mutation in the FANC-E gene confirming fanconi anemia. Twelve cases were unclassified. CONCLUSION: Autopsy is the most important investigation in fetuses with limb anomalies. We suggest chromosomal microarray (CMA) as a first-tier test after autopsy. However, in cases of bilaterally symmetrical limb anomalies, in case of previous similarly affected child, or history of consanguinity, whole exome sequencing (WES) can be offered as the primary investigation, followed by CMA if WES is normal.

Short- and long-term outcomes of early initiation of peritoneal dialysis following catheter insertion.

INTRODUCTION: Early-start peritoneal dialysis (PD) (use of PD catheter within 48 hours of insertion) is an innovative approach for prompt initiation of PD. AIM: This study was conducted to analyze the outcomes of early-start PD. MATERIALS AND METHODS: A total of 100 patients on PD were retrospectively analyzed. Patients were grouped according to the "break-in period": < 48 hours (PD1) and ≥ 14 days (PD2). PD was initiated with low dwell volumes (500 mL) in a recumbent position within 48 hours of surgery. PD prescription was gradually incremented over 10 days to minimize any complications. RESULTS: In our study, there were 48 patients in the PD1 group and 52 in the PD2 group. The most common cause of end-stage kidney disease (ESKD) was diabetes mellitus in both groups. Incidence of early mechanical complications (within 30 days of catheter insertion), such as catheter obstruction, early catheter leakage, catheter malposition, tip migration, and infectious complications, were not found to be higher in the PD1 group. 1- and 4-year catheter patency rates were 97.0% and 96.2% in the PD1 group, respectively. These rates were comparable with those in the PD2 group. Early-start PD was not associated with an increased incidence of catheter failure (HR = 1.0, 95% CI 0.28 - 3.47). CONCLUSION: An early break-in period of < 48 hours is a feasible option for ESKD patients without any significantly increased risk of mechanical or infectious complications. It offers a safe and efficacious option for renal replacement therapy.

CMV presenting as a skin growth in renal transplant patient.

CMV infection is one of the most common opportunistic infection in kidney transplant patients. If not treated, it is associated with increased mortality and graft loss. It can present as viremia or CMV disease in the form of CMV syndrome or tissue invasive CMV disease. The cutaneous presentation of CMV disease is a rare finding. Its identification is vital as cutaneous CMV infection can signal systemic infection and poor prognosis. In our case, 46-year-old male who was a post renal allograft recipient (RAR) presented as a protuberant growth over the medial side of the left ankle. On skin biopsy, nucleomegaly and inclusion bodies were seen in the epithelial cells. Immunohistochemistry was positive for CMV infection. Patient was treated with Ganciclovir, however, he succumbed to death because of severe sepsis due to secondary bacterial infection. Thus, CMV disease should always be kept in mind in immunocompromised patients like post RAR patients who present with cutaneous features like ulcerative lesions or fungating growth.

Renal failure due to granulomatous interstitial nephritis in native and allograft renal biopsies: experience from a tertiary care hospital.

Granulomatous interstitial nephritis is a rare cause of renal failure in both native and allograft renal biopsies. Drugs and sarcoidosis are the commonest causes of granulomatous interstitial nephritis as reported in Western countries. Unlike the west, tuberculosis is the commonest cause of granulomatous interstitial nephritis in Indian subcontinent. The etiological factors, clinical course, glomerular and tubulointerstitial changes associated with granulomatous interstitial nephritis have been analyzed in the present study along with the outcome in patients with granulomatous interstitial nephritis.

The curious case of light chain cast nephropathy in a renal allograft recipient.

ABSTRACT: Myeloma cast nephropathy in renal allograft recipients without pre-transplant diagnosis of multiple myeloma is rare. A 32-year-old hypertensive male presented to our institute as a prospective renal allograft recipient. Hemoglobin was 10.1 mg/dl. He did not have hypercalcemia, and the albumin/globulin ratio was 1.33. Urinalysis did not show any proteinuria or active sediments. Ultrasonography of the abdomen showed bilateral contracted kidneys. He underwent an uneventful renal transplant surgery and had immediate graft function. After 1 month, he tested positive for severe acute respiratory syndrome coronavirus 2 and developed graft dysfunction. Graft biopsy showed features of myeloma cast nephropathy. He had elevated lambda chains with an involved-to-uninvolved free light chain ratio of >100. Serum immunofixation electrophoresis showed a monoclonal band in the lambda region. Bone marrow biopsy showed plasmacytosis with 18.6% immature plasma cells. He improved on cyclophosphamide, bortezomib, and dexamethasone regimens.

Enhancing Success in the ABO-Incompatible Kidney Transplantation: A Case Report.

Kidney transplantation is the preferred treatment for end-stage renal disease (ESRD); however, ABO incompatibility (ABOi) poses challenges due to increased graft rejection risk. Desensitization strategies, including immunoadsorption (IA), aim to overcome ABOi barriers. The objective of this case report was to present the initial findings and patient outcomes of ABOi kidney transplantation (KT) using two different brands of IA columns (Glycosorb® ABO and SECORIM®-ABO) in reducing isoagglutinin titers to the desired target level. We present a case report of a 51-year-old male with ESRD secondary to diabetic kidney disease who underwent desensitization for ABOi KT, involving rituximab administration followed by IA using Glycosorb® and Vitrosorb SECORIM®-ABO columns and plasmapheresis (PP). Glycosorb® ABO column decreased anti-B titers from an initial level of 1:128/1:128 to 1:64/1:64 (target range ≤1:8); however, the titers rebounded to 1:64 following the fourth session of PP. Subsequent use of Vitrosorb SECORIM®-ABO column achieved target titers of 1:4, enabling successful transplantation with satisfactory graft function. Monitoring included anti-B IgG/IgM titer levels post IA columns, IA column reuse, kidney function, and adverse events. The IA columns were well tolerated. Desensitization using IA columns effectively reduced anti-B titers, facilitating successful ABOi KT.

Comparison of Clinico-pathologic features and outcomes of ANCA negative and ANCA positive pauci immune crescentic glomerulonephritis: A single centre study.

Introduction: Pauci-immune crescentic glomerulonephritis (PICN) is an important cause of rapidly progressive renal failure. 10-40% of PICN cases have ANCA (antineutrophil cytoplasmic antibody) negative serology. The present study compared clinico-pathologic features, Brix's renal risk score, Berden's histopathological classes and differences in outcome between ANCAnegative vs ANCA positive PICN patients. Materials and Methods: Sixty-one patients of biopsy-proven PICN were studied. Biochemical findings and ANCA serology were recorded. Renal biopsy slides were reviewed along with direct immunofluorescence. Clinical and histological features were compared between ANCA negative and positive PICN using the Man Whitney U test and Chi-square test. Patients were compared for distribution in Berden's histological classes and Brix's renal risk categories. Patient and renal survival were compared using Kaplan-Meier survival analysis. Results: ANCA negative PICN patients were younger (44.9 ± 16.5 years vs 53.6 ± 15.1 years, P = 0.049). Nasal (0 vs 18%, P = 0.035) and pulmonary involvement (9% vs 38%, P = 0.014) were lower in ANCA negative group. Both ANCA groups had similar renal biochemical profiles, percentage normal glomeruli, 16.3 ± 18.2 vs 21.7 ± 20.4 and percentage glomeruli with crescents, 64.5 ± 28.1 vs 64.3 ± 27.1. Twenty-seven per cent of ANCA negative cases fell in the sclerotic class in Berden's classification vs just 2.5% in ANCA positive group (p = 0.037) without significant difference in Brix's renal risk categories (p = 0.329). Thirteen per cent of ANCA negative patients achieved complete remission on treatment compared to 33% in ANCA positive patients. Patient survival and overall probability of progressing to ESRD were similar in the two groups. Conclusion: ANCA negative PICN cases present at younger ages. Nasal and pulmonary involvement is uncommon in these patients. Patient survival and progression to ESRD are similar in both ANCA groups.

Clinicopathologic Spectrum and Outcomes of Infections Diagnosed on Graft Biopsies and Nephrectomy in Live Renal Allograft Recipients: An Institutional Experience.

OBJECTIVES: Modern immunosuppressive regimens have reduced rejection episodes in renal allograft recipients but have increased the risk of opportunistic infections. Infections are considered to be the second leading cause of death after cardiovascular complications in renal allograft recipients. Data on opportunistic infections affecting the allograft itself are scarce. The present study describes the spectrum of renal opportunistic infections and their outcomes diagnosed on renal allograft biopsies and nephrectomy specimens. MATERIALS AND METHODS: Our retrospective observational study was conducted from December 2011 to December 2021. We analyzed infectious episodes diagnosed on renal allograft biopsies or graft nephrectomy specimens. We obtained clinical, epidemiological, and laboratory details for analyses from hospital records. RESULTS: BK virus nephropathy was the most common opportunistic infection affecting the allograft, accounting for 47% of cases, followed by bacterial graft pyelonephritis (25%). Mucormycosis was the most common fungal infection. The diagnosis of infection from day of transplant ranged from 14 days to 39 months. Follow-up periods ranged from 1 to 10 years. Mortality was highest among patients with opportunistic fungal infection (62%), followed by viral infections, and graft failure rate was highest in patients with graft pyelonephritis (50%). Among patients with BK polyomavirus nephropathy, 45% had stable graft function compared with just 33% of patients with bacterial graft pyelonephritis. CONCLUSIONS: BK polyoma virus infection was the most common infection affecting the renal allograft in our study. Although fungal infections caused the highest mortality among our patients, bacterial graft pyelonephritis was responsible for maximum graft failure. Correctly identifying infections on histology is important so that graft and patient life can be prolonged.

ABO-Incompatible Renal Transplant: A Single-Center Experience from India.

Introduction: In view of ever-increasing end-stage renal disease (ESRD) population but inadequate availability of suitable donors, ABO-incompatible (ABOi) transplantation can be an important void filler. However, at present, ABOi transplantation is limited to a few centers in India and there is a lack of adequate experience and expertise to guide this program to other centers in the country. Methods: Data of all the ABOi transplants performed from 2012 to 2021 in a tertiary care hospital was retrospectively analyzed. The anti-ABO antibody (IgG) titers (≤1:4) were considered safe before transplantation. Desensitization included rituximab, plasma exchange, or selective immunoadsorption column. Tacrolimus and mycophenolate mofetil were initiated at day -7. Induction agents included ATG, ATLG, basiliximab, or no induction. Postoperatively, anti-ABO titers were done daily for 2 weeks. Results: A total of 202 patients underwent transplantation; of these, 195 patients whose data were for available for 12 months were included in the study. Mean duration of follow-up was 28.9 ± 21.7 months. UTI was the most common source of infection, occurring in almost half (46.1%) of the patients. Antibody-mediated rejection (ABMR; 15%) was common in the first year. Patient survival was 86.6% (169/195) at 1 year. Sepsis was the most common of death in more than two-thirds of the population, including coronavirus disease 2019 (COVID-19)-associated mortality in nine patients (4.6%). Death-censored graft survival was 89.3% (174/195). AMR was the leading cause of graft loss in almost half of the patients. Conclusion: ABOi should be considered in ESRD patients for whom suitable ABO-compatible donor is not available. Higher rate of rejection and infection are still a major concern.

Nocardiosis in Renal Transplantation: Case Series from India.

Nocardiosis is a rare opportunistic infection seen in kidney transplant patients and is caused by aerobic actinomycete. Disease manifestations can vary from a localized infection to multisystem organ failure. In this retrospective case series, we present 16 cases of Nocardiosis. The median age of the patients was 44 years. The median time from transplant to nocardiosis was 21 months. Acute rejection episodes and CMV infection within 6 months of nocardiosis were found in 12.5% and 25%, respectively. The most common organ involvement was the lungs (75%), followed by the brain (12.5%). Only one patient showed cutaneous involvement (6.25%). Mean creatinine at presentation was 0.7 mg/dL (mean eGFR: 92 ± 27 mL/min/1.73 m2). Trimethoprim/sulfamethoxazole resistance was found in 25% of patients. Five patients (31.25%) succumbed to the infection. Nocardiosis has a very low incidence but a high rate of mortality.

Anti-T-Lymphocyte Immunoglobulin (Grafalon) as an Induction Agent for Renal Transplantation: A Real-World, Retrospective, Single-Center Experience.

OBJECTIVES: Polyclonal antithymocyte globulins are widely used in the induction regimens of solid-organ transplant recipients; however, their doses and outcomes remain to be standardized in Indian patients. We report our clinical experience from the real-world use of Grafalon (an anti-T-lymphocyte globulin; ATG-Fresenius) as an induction agentin renal transplant recipients from India. MATERIALS AND METHODS: In this retrospective, single- center, observational study, we analyzed the medical records of 177 consecutive, kidney-only transplant recipients who received induction therapy with Grafalon from September 2016 to March 2018 at our center. Incidences of biopsy-proven acute rejection and graft dysfunction, immunosuppression protocol, Grafalon dosage, 18-month post-transplant graft and patient survival, treatment-related adverse events, and infective complications were reported. RESULTS: Mean age of patients was 41.46 years (range, 14-68 years), (85% were males). The average dose of Grafalon was 5.81 ± 1.95 mg/kg (range, 2.41 to 10.07 mg/kg). Graft dysfunction (ie, at least 20% increase in serum creatinine from baseline) was observed in 26 patients (14%): 11 patients (6.2%) had biopsy-proven acute rejections, 11 patients (6.2%) had acute tubular necrosis, and 4 patients (2.2%) had calcineurin inhibitor toxicity. Seven deaths were recorded: 2 each from fungal pneumonia, bacterial pneumonia, and acute coronary syndrome and 1 with urinary tract infection with septicemia. Death-censored graft survival was 100% at 12 months and 98% at 18-month follow-up; overall patient survival was 96%. Infective complications occurred in 40 patients (22.5%), with the most common being urinary tract infection in 32 patients (18%). No malignancies were reported. CONCLUSIONS: Use of a potent induction therapy like anti-T-lymphocyte globulin (Grafalon) is often restricted by the risk of side effects and lack of local clinical evidence supporting its role in long-term graft survival. Real-world evidence support the safe and effective use of anti-T-lymphocyte globulin as an induction agent in renal transplant recipients with an individualized dosing approach.

Post-transplant Lymphoproliferative Disorder Presenting as Breast Nodule and Intestinal Obstruction in a Renal Transplant Recipient: A Case Report.

Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication among kidney transplant recipients. The clinical presentation of patients with PTLD is highly variable. The type of PTLD and the area of involvement determine its presentation, which includes constitutional symptoms such as fever, weight loss, fatigue, and other symptoms related to dysfunction of involved organs, or compression of surrounding structures. Most present with extranodal masses involving the gastrointestinal tract (stomach, intestine), lungs, skin, liver, central nervous system, and the allograft itself. In our case, a 33-year-old woman developed Epstein-Barr virus-negative PTLD plasmablastic lymphoma (PbL) in her right breast and small intestine presenting as intestinal obstruction, 15 years after renal transplant. Her condition was managed with intestinal mass resection and chemotherapy. A follow-up positron emission tomography scan showed near-complete resolution. Thus, PTLD should always be kept in mind in renal transplant recipients who present with features of a mass effect involving any organ.

Double whammy: anticoagulant-related nephropathy with leukocytoclastic vasculitis due to warfarin.

Anticoagulation-related nephropathy (ARN) is a rare form of acute kidney injury where the use of anticoagulation causes hemorrhage in various compartments of nephron including glomerulus, renal tubules, and interstitial compartment. Also, warfarin-induced vasculitis is an extremely rare condition characterized by the appearance of purpuric lesions on the skin which on biopsy are suggestive of leukocytoclastic vasculitis (LV). We hereby report a case presenting with coexistent warfarin-induced nephropathy and cutaneous vasculitis. A 64-year-old male, on warfarin for 10 years, presented with complaints of palpable purpuric rashes over lower limbs, hematuria, and decrease urine output. INR was in the supratherapeutic range (INR-6.3). Skin biopsy of the lesion was suggestive of LV and kidney biopsy showed RBCs in Bowman's capsule, RBCs and RBC casts in tubules suggestive of ARN. All vasculitic markers were negative. Thus, a diagnosis of warfarin-induced nephropathy and cutaneous vasculitis was made. Warfarin was discontinued and oral steroids were started. Gradually, his skin lesions improved, and he became dialysis independent. He was then discharged on apixaban. On follow-up after 3 months, his skin lesions had disappeared with partial recovery of kidney function (cr-5.49).

Stretching the boundaries: suitability of an arteriovenous fistula in elderly patients on hemodialysis-a northern India experience.

PURPOSE: Considering various factors, such as multiple co-morbidities, unsuitable vessels for access creation, non-maturation, vascular calcifications, the outcome of arteriovenous fistula (AVF) in the elderly population, may not be similar to the younger people. Our study aims to analyze the outcomes of AVF in elderly patients (> 65 year). METHODS: It was a prospective observational study. Patients of more than 65 years of age in whom AVF was created from January 2012 to December 2015 were included in the study. These patients were followed up for 4 years. The primary endpoint of our study was to assess primary and secondary patency rates. RESULTS: A total of 450 AVFs were included in the study. The mean age was 68.5 years. The most common site of AVF was radiocephalic (RCAVF) in 70% (n = 315), brachiocephalic (BCAVF) in 24% (n = 108) and basilic vein transposition (BVT) in 6% (n = 27). At 48 months, the primary patency rate of RCAVF, BCAVF, and BVT was 55%, 61.6%, and 60.4%, respectively. The commonest cause of access failure was thrombosis followed by non-maturation. CONCLUSION: AVF remains the preferred vascular access for hemodialysis even in the elderly population. Failure to mature and thrombosis continue to be a concern with AVF. Location of the AV access does not seem to impact the long-term patency.

Atypical HUS Triggered by COVID-19: A Case Report.

We hereby present a case of an atypical hemolytic uremic syndrome (aHUS) precipitated by coronavirus disease 2019 (COVID-19). A 26-year-old male was diagnosed with COVID-19 and acute kidney injury. His kidney biopsy was suggestive of thrombotic microangiopathy. Five sessions of plasmapheresis were done but were discontinued in view of nonrecovery of kidney function. He was then referred for a kidney transplant. On genetic analysis, he was found to have mutations in the complement system (CFHR1 and CFHR3), which suggested this was a case of aHUS precipitated by COVID-19. In view of the high risk of recurrence of the primary disease in live-related kidney donor transplantation, he was advised for simultaneous liver and kidney transplants.

Hypervitaminosis D and Acute Interstitial Nephritis: Tale of Injections.

A 33-year-old man came with nausea, vomiting and abdominal pain due to hypercalcaemia and renal dysfunction following two doses of intramuscular vitamin D injections. Levels of vitamin D were repeatedly above 300 ng/ml over a period of 10 months. Whole-body PET CT scan revealed a thin-walled collection in the right gluteal region. The patient refused a surgical intervention for the same. After 7 months of follow-up, the abscess ruptured spontaneously and was then surgically debrided. At this point, a history of pentazocine addiction was uncovered. One month later, vitamin D levels began to fall along with improvement in serum calcium and creatinine. This case unravels a diagnostic odyssey which ended with a simple surgical debridement. We aim to highlight that vitamin D supplementation in 'megadoses' in the presence of active infection can have an exaggerated response and may take months to resolve.