Recycling transplanted organs: An exceptional case and literature review.

BACKGROUND: Recycling transplant kidneys, in other words using an allograft which has previously been transplanted in one recipient for transplant in a second recipient, can be a source of opportunity for expanding the pool of available grafts in the United States and beyond. SUMMARY: We describe a case of renal transplantation from a donor who had undergone a kidney transplant 3 years prior and had good graft function at the time of procurement. The recipient underwent transplantation uneventfully and to date has demonstrated excellent graft function. We also include a literature review of reported cases of recycled/retransplanted kidneys. KEY MESSAGES: -Recycling transplanted kidneys is a largely untapped resource which could help decrease the transplant waitlist. -Utilizing such kidneys does need special considerations in terms of procurement technique, backtable, crossmatch, recipient selection and follow-up.

Stability and compatibility of intraperitoneal antimicrobials in peritoneal dialysate solutions.

To optimise antimicrobial administration in patients with peritoneal dialysis (PD)-related peritonitis, healthcare providers need literature-based information to develop patient-centred pharmacotherapeutic plans. Traditional PD solutions promote osmosis using dextrose or icodextrin with a lactate buffer. Newer PD solutions have modified the osmotic vehicle and buffer. Knowledge of antimicrobial compatibility and stability with newer PD solutions will assist with determining the route of antimicrobial administration as compatible and stable solutions could be delivered directly to the peritoneum using intraperitoneal administration. This review updates the compatibility and stability of antimicrobial additives in newer PD solutions for PD-related peritonitis.

Electronic Patient Portal Use After Kidney Transplant: A Single-Center Retrospective Study.

INTRODUCTION: Online patient portals have become a core component of patient-centered care. Limited research exists on such portal use in patients after kidney transplantation. The aim of this study was to examine preoperative, perioperative, and postoperative factors associated with post-transplantation portal use. METHODS: This cross-sectional study included all patients who underwent kidney transplantation from April 2016 to May 2019 at the University of Toledo Medical Center. Exclusion criteria included international travel for transplantation and those without available postoperative lab or follow-up records. Data were collected for 2 y post-transplantation. Univariable and multivariable linear regression was performed to determine associations with portal use. RESULTS: Two hundred and forty-seven kidney transplant recipients were included in the study; 35.6% (n = 88) used the portal versus 64.4% (n = 159) did not. Preoperative factors associated with increased use included income >$40,000 (odds ratio [OR], 2.95; P = 0.006) and cancer history (OR, 2.46; P = 0.007), whereas diabetes history had reduced use (OR, 0.51; P = 0.021). The Black race had the least use. Perioperatively, reduced use was associated with dialysis before transplant (OR, 0.25; P < 0.001) and hospital stay ≥4 d (OR, 0.49; P = 0.009). Postoperatively, associations with increased use included average eGFR >30 (P = 0.04) and hospital readmissions (n = 102), whereas those with ER (n = 138) visits had decreased use. Multivariable analysis revealed increased use with income >$40,000 (OR, 2.51; P = 0.033). CONCLUSIONS: There was no observed difference in clinical outcomes for portal users and nonusers undergoing kidney transplantation, although portal use may decrease the likelihood of ER visits. Socioeconomic status and ethnicity may play a role on who utilizes the patient portals.

False Positive Pregnancy Test Before Kidney Transplant: Case Report and Review of Literature.

Pregnancy tests are routinely done before any surgery under general anesthesia including kidney transplantation. Positive test usually leads to more investigations to detect a possible pregnancy or malignancy and the surgery gets canceled or postponed. Because a kidney transplant from a deceased donor is not elective, it usually gets canceled in this scenario. Some groups have reported on normally elevated human chorionic gonadotrophin (hCG) levels in perimenopausal women and in patients with chronic kidney disease. This is thought to be from the pituitary. We present a highly sensitized prospective kidney transplant recipient with a positive pregnancy test with low levels of serum human chorionic gonadotrophin. She underwent additional preoperative testing after which we proceeded with the kidney transplant. Herein, we discuss the management of patients who have an unexpected positive pregnancy test before transplant.

Optimal Timing of COVID-19 Vaccination in the Peri-Transplant Period: A Single Institution Case Series.

The outcomes of vaccination against Severe Acute Respiratory Syndrome Coronavirus 2 in organ transplant recipients are unclear. Recent studies have investigated outcomes for patients who are several years post transplant. There has not been much data in peri-transplant patients. This is important because patients are highly immunosuppressed during this period owing to induction immunosuppression and are thus susceptible to infection. We looked at 6 patients who were transplanted at our center after receiving their first dose of mRNA vaccines. We assessed their antibody response after 1, 2, and in two patients, 3 doses of the vaccine. Out of the two patients who received their third booster dose, one had a detectable antibody level after the third dose. We report that the overall antibody response to vaccination was weaker in transplant patients compared with the general population, with a rapid attrition of antibody response over time. There is a need for more studies that follow-up antibody levels in transplant patients over time, especially those in the peri-transplant period to help guide the vaccination plan for immunosuppressed transplant patients.

Survivin-induced abnormal ploidy contributes to cystic kidney and aneurysm formation.

BACKGROUND: Cystic kidneys and vascular aneurysms are clinical manifestations seen in patients with polycystic kidney disease, a cilia-associated pathology (ciliopathy). Survivin overexpression is associated with cancer, but the clinical pathology associated with survivin downregulation or knockout has never been studied before. The present studies aim to examine whether and how cilia function (Pkd1 or Pkd2) and structure (Tg737) play a role in cystic kidney and aneurysm through survivin downregulation. METHODS AND RESULTS: Cysts and aneurysms from polycystic kidney disease patients, Pkd mouse, and zebrafish models are characterized by chromosome instability and low survivin expression. This triggers cytokinesis defects and formation of nuclear polyploidy or aneuploidy. In vivo conditional mouse and zebrafish models confirm that survivin gene deletion in the kidneys results in a cystic phenotype. As in hypertensive Pkd1, Pkd2, and Tg737 models, aneurysm formation can also be induced in vascular-specific normotensive survivin mice. Survivin knockout also contributes to abnormal oriented cell division in both kidney and vasculature. Furthermore, survivin expression and ciliary localization are regulated by flow-induced cilia activation through protein kinase C, Akt and nuclear factor-κB. Circumventing ciliary function by re-expressing survivin can rescue polycystic kidney disease phenotypes. CONCLUSIONS: For the first time, our studies offer a unifying mechanism that explains both renal and vascular phenotypes in polycystic kidney disease. Although primary cilia dysfunction accounts for aneurysm formation and hypertension, hypertension itself does not cause aneurysm. Furthermore, aneurysm formation and cyst formation share a common cellular and molecular pathway involving cilia function or structure, survivin expression, cytokinesis, cell ploidy, symmetrical cell division, and tissue architecture orientation.

Calciphylaxis: a devastating complication of derangements of calcium-phosphorus metabolism--a case report and review of the literature.

Calciphylaxis is a rare and potentially devastating condition also referred to as uremic gangrene syndrome, calcific uremic arteriolopathy, metastatic calcification, and uremic small-vessel disease that can present in patients with end stage renal disease. This article reports a case of a 38-year-old African-American female on peritoneal dialysis for six years with a known history of non-adherence with diet, medications, and prescribed peritoneal dialysis treatment regimen. At her monthly clinic visit, the patient complained of burning sensation in the fingers of both hands with limited fine motor movement due to edema and severe pain. A presumptive diagnosis of calciphylaxis led to hospital admission with confirmation by X-ray of her hands. The patient was switched to hemodialysis with low calcium dialysate, aggressive reduction in phosphorus, diet counseling, use of cinacalcet, and six weeks of intravenous sodium thiosulfate infusion with hemodialysis treatments. The patient's condition improved with resolution of symptoms. This case was chosen based on the rarity of a calciphylaxis presentation and paucity of knowledge regarding diagnosis and treatment.

Conservative management of post-transplant central nervous system lymphoma.

Primary CNS lymphoma (PCNSL) is a rare B cell variant non-Hodgkins lymphoma that is confined to the brain, leptomeninges, spinal cord and eyes. Its incidence is increasing, primarily due to increase in the number of organ transplantations being undertaken. The majority of the PTLD (post-transplant lymphoproliferative disorder) is seen in kidney transplant recipients simply because they constitute a larger group of transplant recipients each year as compared to other solid organ transplantations. Primary infection of previously infected EBV seronegative patients and immunosuppression are found to be the main etiologic factors in the development of PTLD-PCNSL. There are no clear guidelines on treatment regimens, and it should be individualized according to patient comorbidities. We report a case of PCNS lymphoproliferative disorder in a kidney transplant recipient, which underwent complete remission with decreasing immunosuppression. The patient could not undergo chemotherapy/radiotherapy due to underlying comorbidities. We highlight the available treatment modalities for PTLD-PCNSL.

Successful preemptive renal retransplantation in a patient with previous acute graft loss secondary to HIT type II: a case report and review of literature.

Type II heparin-induced thrombocytopenia (HIT II) is an immune-mediated reaction to heparin administration associated with thrombocytopenia and thrombotic complication with potentially serious outcome. We report a case of a 50-year-old man with history of autosomal dominant polycystic kidney disease (ADPKD), homocystinemia, and history of deep vein thrombosis (DVT), who was switched to intravenous heparin from oral coumadin preoperatively in preparation for preemptive living related renal transplant. Following the operation heparin-induced thrombocytopenia type II lead to graft renal artery thrombosis and subsequent graft loss. One year after first transplant patient underwent successful second living unrelated kidney transplantation with no complications with continued anticoagulation with coumadin and with no reexposure to heparin. Two years after the second transplant and 1 year after stopping anticoagulation, patient was readmitted with bilateral lower extremity DVT and high probability of pulmonary embolism. He was given argatroban on admission as a bridge to anticoagulation with lifelong coumadin therapy and is doing well with excellent graft function. To our knowledge, this is the third reported case of HIT in renal transplantation, second reported case associated with graft loss secondary to HIT and the first reported case of successful retransplantation after initial HIT with graft loss. Heparin-induced thrombocytopenia in transplantation can lead to catastrophic consequences in organ recipients. Successful management of this condition emphasizes promptness of diagnosis and treatment and complete cessation of heparin exposure.

Endothelial cells from humans and mice with polycystic kidney disease are characterized by polyploidy and chromosome segregation defects through survivin down-regulation.

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common hereditary and systemic disorder associated with various cardiovascular complications. It has been implicated with dysfunction in primary cilia. We and others have shown that the immediate function of endothelial cilia is to sense extracellular signal. The long-term function of cilia is hypothesized to regulate cell cycle. Here, we show that ciliary function (polycystins) and structure (polaris) are required for proper cellular division. Cilia mutant cells undergo abnormal cell division with apparent defects in mitotic spindle formation, cellular spindle assembly checkpoint and centrosome amplification. Down-regulation of the chromosomal passenger survivin contributes to these abnormalities, which further result in cell polyploidy. Re-expression of survivin restores a competent spindle assembly checkpoint and reduces polyploidy. Aged animals show a more severe phenotype in cellular division, consistent with progression of cardiovascular complications seen in older ADPKD patients. For the first time, we show that structure and function of mechanosensory cilia are crucial in maintaining proper cellular proliferation. Furthermore, developmental aging plays a crucial role in the progression of these abnormal cellular phenotypes. We propose that abnormal function or structure of primary cilia not only causes failure to transmit extracellular signals, but also is associated with cytokinesis defects in both mice and humans with polycystic kidney disease.

Aggressive posttransplant lymphoproliferative disease in a renal transplant patient treated with alemtuzumab.

Post transplant lymphoproliferative disease (PTLD) is a rare but potentially fatal complication after solid organ transplantation. The risk of PTLD varies with type of organ transplant, Epstein-Barr virus serostatus of the donor and recipient, age, and intensity of immunosuppression. We report a case of a 45-year-old man who developed aggressive PTLD 7 months after receiving a cadaveric renal transplant. He received 30 mg alemtuzumab intravenously intraoperatively as induction immunosuppression followed by maintenance immunosuppression with tacrolimus and mycophenolate mofetil. The patient presented with intestinal perforation and gastrointestinal bleeding. Histopathology revealed Epstein-Barr virus-positive diffuse large B-cell lymphoma with a high mitotic index involving multiple segments of small and large intestines and leading to perforation of the ileum, jejunum, and cecum. The patient had Stage IV disease and treatment consisted of immunosuppression reduction and 375 mg/m rituximab weekly for four doses. Unfortunately, the patient had recurrent intestinal perforation followed by fatal gastrointestinal bleeding. There have been very few case reports of PTLD after alemtuzumab induction in renal transplant and the case discussed had simultaneous multiple perforations in the small intestine and colon.

Microscopic polyangiitis triggered by recurrent methicillin-resistant Staphylococcus aureus bacteremia.

Most of the purported links between microbial agents and primary small-vessel anti-neutrophilic antibody-positive (ANCA) vasculitides remain speculative. There is strong circumstantial evidence for the role of Staphylococcus aureus in the development of Wegener's granulomatosis, but its role in other ANCA-positive vasculitis syndromes is less clear. We describe a patient who developed a non-granulomatous, necrotizing small-vessel vasculitis with a positive anti-neutrophil cytoplasmic antibody of a perinuclear type (p-ANCA), along with anti-myeloperoxidase antibodies after recurrent episodes of methicillin-resistant Staphylococcus aureus bacteremia.

Hypertension in Autosomal Dominant Polycystic Kidney Disease: A Clinical and Basic Science Perspective.

BACKGROUND AND AIMS: Cardiovascular complications are major causes of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). In particular, hypertension is insidious and remains a continuous problem that evolves during the course of the disease. Hypertension in ADPKD has been associated with abnormality in the renin-angiotensin-aldosterone system (RAAS). Early vascular changes have also been reported in young ADPKD patients. In addition, the cellular functions of mechanosensory cilia within vascular system have emerged recently. The basic and clinical perspectives of RAAS, vascular remodeling and sensory cilia are reviewed with regard to hypertension in ADPKD.

Ciliary polycystin-2 is a mechanosensitive calcium channel involved in nitric oxide signaling cascades.

Cardiovascular complications such as hypertension are a continuous concern in patients with autosomal dominant polycystic kidney disease (ADPKD). The PKD2 encoding for polycystin-2 is mutated in approximately 15% of ADPKD patients. Here, we show that polycystin-2 is localized to the cilia of mouse and human vascular endothelial cells. We demonstrate that the normal expression level and localization of polycystin-2 to cilia is required for the endothelial cilia to sense fluid shear stress through a complex biochemical cascade, involving calcium, calmodulin, Akt/PKB, and protein kinase C. In response to fluid shear stress, mouse endothelial cells with knockdown or knockout of Pkd2 lose the ability to generate nitric oxide (NO). Consistent with mouse data, endothelial cells generated from ADPKD patients do not show polycystin-2 in the cilia and are unable to sense fluid flow. In the isolated artery, we further show that ciliary polycystin-2 responds specifically to shear stress and not to mechanical stretch, a pressurized biomechanical force that involves purinergic receptor activation. We propose a new role for polycystin-2 in transmitting extracellular shear stress to intracellular NO biosynthesis. Thus, aberrant expression or localization of polycystin-2 to cilia could promote high blood pressure because of inability to synthesize NO in response to an increase in shear stress (blood flow).

Insulin acutely decreases hepatic fatty acid synthase activity.

Insulin is viewed as a positive regulator of fatty acid synthesis by increasing fatty acid synthase (FAS) mRNA transcription. We uncover a new mechanism by which insulin acutely reduces hepatic FAS activity by inducing phosphorylation of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and its interaction with FAS. Ceacam1 null mice (Cc1(-/-)) show loss of insulin's ability to acutely decrease hepatic FAS activity. Moreover, adenoviral delivery of wild-type, but not the phosphorylation-defective Ceacam1 mutant, restores the acute effect of insulin on FAS activity in Cc1(-/-) primary hepatocytes. Failure of insulin to acutely reduce hepatic FAS activity in hyperinsulinemic mice, including L-SACC1 transgenics with liver inactivation of CEACAM1, and Ob/Ob obese mice, suggests that the acute effect of insulin on FAS activity depends on the prior insulinemic state. We propose that this mechanism acts to reduce hepatic lipogenesis incurred by insulin pulses during refeeding.