Allograft tissue under the microscope: only the beginning.

PURPOSE OF REVIEW: To review novel modalities for interrogating a kidney allograft biopsy to complement the current Banff schema. RECENT FINDINGS: Newer approaches of Artificial Intelligence (AI), Machine Learning (ML), digital pathology including Ex Vivo Microscopy, evaluation of the biopsy gene expression using bulk, single cell, and spatial transcriptomics and spatial proteomics are now available for tissue interrogation. SUMMARY: Banff Schema of classification of allograft histology has standardized reporting of tissue pathology internationally greatly impacting clinical care and research. Inherent sampling error of biopsies, and lack of automated morphometric analysis with ordinal outputs limit its performance in prognostication of allograft health. Over the last decade, there has been an explosion of newer methods of evaluation of allograft tissue under the microscope. Digital pathology along with the application of AI and ML algorithms could revolutionize histopathological analyses. Novel molecular diagnostics such as spatially resolved single cell transcriptomics are identifying newer mechanisms underlying the pathologic diagnosis to delineate pathways of immunological activation, tissue injury, repair, and regeneration in allograft tissues. While these techniques are the future of tissue analysis, costs and complex logistics currently limit their clinical use.

Telemedicine services for living kidney donation: A US survey of multidisciplinary providers.

Individuals considering living kidney donation face geographic, financial, and logistical challenges. Telemedicine can facilitate healthcare access/care coordination. Yet difficulties exist in telemedicine implementation and sustainability. We sought to examine centers' practices and providers' attitudes toward telemedicine to improve services for donors. We surveyed multidisciplinary providers from 194 active adult US living donor kidney transplant centers; 293 providers from 128 unique centers responded to the survey (center representation rate = 66.0%), reflecting 83.9% of practice by donor volume and 91.5% of US states/territories. Most centers (70.3%) plan to continue using telemedicine beyond the pandemic for donor evaluation/follow-up. Video was mostly used by nephrologists, surgeons, and psychiatrists/psychologists. Telephone and video were mostly used by social workers, while video or telephone was equally used by coordinators. Half of respondent nephrologists and surgeons were willing to accept a remote completion of physical exam; 68.3% of respondent psychiatrists/psychologists and social workers were willing to accept a remote completion of mental status exam. Providers strongly agreed that telemedicine was convenient for donors and would improve the likelihood of completing donor evaluation. However, providers (65.5%) perceived out-of-state licensing as a key policy/regulatory barrier. These findings help inform practice and underscore the instigation of policies to remove barriers using telemedicine to increase living kidney donation.

Clinically adjudicated deceased donor acute kidney injury and graft outcomes.

BACKGROUND: Acute kidney injury (AKI) in deceased donors is not associated with graft failure (GF). We hypothesize that hemodynamic AKI (hAKI) comprises the majority of donor AKI and may explain this lack of association. METHODS: In this ancillary analysis of the Deceased Donor Study, 428 donors with available charts were selected to identify those with and without AKI. AKI cases were classified as hAKI, intrinsic (iAKI), or mixed (mAKI) based on majority adjudication by three nephrologists. We evaluated the associations between AKI phenotypes and delayed graft function (DGF), 1-year eGFR and GF. We also evaluated differences in urine biomarkers among AKI phenotypes. RESULTS: Of the 291 (68%) donors with AKI, 106 (36%) were adjudicated as hAKI, 84 (29%) as iAKI and 101 (35%) as mAKI. Of the 856 potential kidneys, 669 were transplanted with 32% developing DGF and 5% experiencing GF. Median 1-year eGFR was 53 (IQR: 41-70) ml/min/1.73m2. Compared to non-AKI, donors with iAKI had higher odds DGF [aOR (95%CI); 4.83 (2.29, 10.22)] and had lower 1-year eGFR [adjusted B coefficient (95% CI): -11 (-19, -3) mL/min/1.73 m2]. hAKI and mAKI were not associated with DGF or 1-year eGFR. Rates of GF were not different among AKI phenotypes and non-AKI. Urine biomarkers such as NGAL, LFABP, MCP-1, YKL-40, cystatin-C and albumin were higher in iAKI. CONCLUSION: iAKI was associated with higher DGF and lower 1-year eGFR but not with GF. Clinically phenotyped donor AKI is biologically different based on biomarkers and may help inform decisions regarding organ utilization.

Unilateral leg pain caused by cryptococcal myositis: An unusual presentation of disseminated cryptococcosis in a kidney transplant recipient.

Cryptococcal disease is a rare but often serious infection in solid organ transplant recipients, commonly presenting as meningitis and pneumonia but can rarely cause myositis. We report the case of a 43-year-old female kidney transplant recipient with two previous graft failures requiring re-transplantations who presented with a 1-month duration of worsening unilateral leg pain, swelling, and shortness of breath. Blood cultures isolated Cryptococcus neoformans. A calf biopsy was performed and histopathology revealed myonecrosis with yeast forms consistent with Cryptococcus spp. Liposomal amphotericin B (LamB) was administered. Her course was complicated by hypoxemic respiratory failure with development of ground glass opacities on chest imaging. Work-up revealed bacterial and C neoformans pneumonia and probable Pneumocystis jirovecii pneumonia (PJP) She received trimethoprim-sulfamethoxazole and LamB and was discharged on fluconazole. Shortly thereafter she was re-admitted with confusion, septic shock, and multi-organ failure. Work-up revealed PJP with subsequent development of cryptococcal meningitis. Despite aggressive management, she expired. Disseminated cryptococcal infection may manifest as myositis. Presence of cryptococcal infection is a marker of severe net state of immunosuppression (IS), hence, presence of other opportunistic infections is likely. Early recognition of cryptococcal infection, institution of targeted therapy, and IS reduction are important to improve overall survival.

Identifying a Kidney Transplant Recipient COVID Phenotype to Aid Test Utilization in the Setting of Limited Testing Availability-Does One Exist?

The high morbidity and mortality of COVID-19 in immunocompetent patients raises significant concern for immunosuppressed kidney transplant recipients (KTRs). This level of concern, both on the part of the KTRs and transplant professionals, is heightened by a lack of prior knowledge on how Severe Acute Respiratory Syndrome 2 virus (SARS-CoV-2) may manifest differently in immunosuppressed patients. Characterizing how KTRs may present differently than the general population would allow for more targeted and timely evaluation and treatment of KTRs with COVID-19 infection. METHODS: Without prior knowledge of how this virus would affect our transplant center's delivery of care to KTRs who are SARS-CoV-2 positive or patients under investigation, and in the setting of limited testing availability, we initiated a quality assurance and improvement project (QAPI) to track KTRs followed at our transplant center through the SARS-CoV-2 testing process. RESULTS: Of the 53 symptomatic patients, 20 (38%) tested positive for SARS-CoV-2 either on presentation to the emergency department or referral to a designated outpatient testing center. In addition, 16 (80%) of the 20 patients who tested positive required inpatient treatment. Intriguingly, patients with a history of polyoma BK viremia (BKV) had a higher incidence of testing positive for SARS-CoV-2 compared to patients without a history of BKV (80% and 28%, respectively; P = .002). The Positive Predictive Value and Likelihood ratio was 80% and 6.6 for this association, respectively. Among our KTRs tested, those receiving belatacept had a lower likelihood of testing positive for SARS-CoV-2. This finding approached, but did not achieve, statistical significance (P = .06).

The Role of the General Nephrologist in Evaluating Patients for Kidney Transplantation: Core Curriculum 2020.

Transplantation is the preferred modality of replacement therapy for most patients with kidney failure. In the United States, more than 3,000 new patients are registered each month on the kidney transplant waiting list for this life-saving therapy. A potential kidney transplant recipient's evaluation typically begins with a referral by the general nephrologist to a transplantation center. In this installment in the Core Curriculum in Nephrology, we endeavor to achieve a shared understanding of the patient factors that contribute to optimal patient and allograft outcomes following kidney transplantation. In addition, we provide a primer on the routine listing, evaluation, testing, and candidate selection process in an effort to demystify the current criteria commonly used by transplantation centers. Issues common to a majority of candidates, including cardiovascular health, frailty as a measure of biological age, history of prior malignancy, and high body mass index are reviewed in detail. With this knowledge, we hope to facilitate improved communication between general and transplantation nephrologists.

Propofol Induced Hyperkalemia and Its Management in End Stage Renal Disease Patients.

Propofol related infusion syndrome (PRIS) is a rare, but extremely dangerous complication of propofol administration. Unexplained anion-gap metabolic acidosis, rhabdomyolysis, hyperkalemia, acute kidney injury, elevated liver enzymes, and potentially fatal cardiac arrhythmias are characteristic of PRIS. Risk factors for the develop- ment of PRIS include dose and duration of propofol infusion, severe illness, and concomitant administration of catecholamine and glucocorticoids. PRIS causing hyperkalemia is a well-known clinical entity. Although the development of PRIS depends on the duration and total amount of drug infused, repeated boluses of propofol, commonly used for rapid sequence intubation and conscious sedation, can potentially precipitate fatal hyperkalemia. This is of particular concern in advanced chronic kidney disease (CKD) and end stage renal disease (ESRD) patients. We report a case of a propofol induced hyperkalemia causing near fatal cardiac arrhythmia in a dialysis dependent ESRD patient. We report successful revival from cardiac arrest by intensive calcium regimen and hemodialysis. This case highlights underrecognized problem of propofol-induced hy- perkalemia, which can be of particular concerns in advanced CKD and ESRD.