Adipose-derived mesenchymal stem cells from patients with atherosclerotic renovascular disease have increased DNA damage and reduced angiogenesis that can be modified by hypoxia

Representative flow cytometric plots (FACS) showing that AMSCs expressed HLA-ABC, CD44, CD90, CD29, CD73, and CD105 markers, and did not express HLA-DR, CD45, CD14 or CD34 markers. (JPG 233 kb

Severe Hyponatremia as the Initial Sign Preceding Guillain-Barré Syndrome, an Acute Inflammatory Demyelinating Polyneuropathy: A Case Report

Guillain-Barré syndrome is an immune-mediated polyneuropathy that frequently presents with progressive muscle weakness. Hyponatremia has recently been described as a feature of this condition, generally appearing over the course of the illness and following the diagnosis of this demyelinating process. We report a case of Guillain-Barré syndrome presenting with severe hyponatremia that is further exacerbated by intravenous immune globulin therapy. Awareness should be raised for consideration of both Guillain-Barré syndrome and its treatment with intravenous immune globulin therapy as the cause of hyponatremia

Progress toward the clinical application of mesenchymal stromal cells and other disease-modulating regenerative therapies

Drawing from basic knowledge of stem cell biology, embryonic development, wound healing and aging, regenerative medicine seeks to develop therapeutic strategies that complement or replace conventional treatments by actively repairing diseased tissue or generating new organs and tissues. Among the various clinical translational strategies within the field of regenerative medicine, several can be broadly described as promoting disease resolution indirectly through local or systemic interactions with a patient s cells without permanently integrating or directly forming new primary tissue. In this review, we focus on such therapies, which we term disease modulating regenerative therapies (DMRT), and on the extent to which they have been translated into the clinical arena in four distinct areas of nephrology: renovascular disease (RVD), sepsis-associate acute kidney injury (SA-AKI), diabetic kidney disease (DKD) and kidney transplantation (KTx). As we describe, the DMRT that has most consistently progressed to human clinical trials for these indications is mesenchymal stem/stromal cells (MSCs), which potently modulate ischemic, inflammatory, pro-fibrotic and immune-mediated tissue injury through diverse paracrine mechanisms. In KTx, several early-phase clinical trials have also tested the potential for ex vivo-expanded regulatory immune cell therapies to promote donor-specific tolerance and prevent or resolve allograft injury. Other promising DMRT, including adult stem/progenitor cells, stem cell-derived extracellular vesicles and implantable hydrogels/biomaterials remain at varying pre-clinical stages of translation for these renal conditions. To date (2021), no DMRT has gained market approval for use in patients with RVD, SA-AKI, DKD or KTx and clinical trials demonstrating definitive, cost-effective patient benefits are needed. Nonetheless, exciting progress in understanding the disease-specific mechanisms of action of MSCs and other DMRT, coupled with increasing knowledge of the pathophysiological basis for renal tissue injury and the experience gained from pioneering early-phase clinical trials provide optimism that impactful, regenerative treatments for diverse kidney diseases will emerge in the years ahead.LJH is supported by grants from Regenerative Medicine Minnesota (grant number RMM 091718), the National Institute of Health (NIH) (grant numbers DK109134 and DK123492), and NIDDK Diabetic Complications Consortium (RRID:SCR_001415, www.diacomp.org; grant numbers DK076169 and DK115255). SMH is supported by the NIH (grant number DK118120) and by a Mary Kathryn and Michael B. Panitch Career Development Award. MDG is supported by grants from the European Commission [Horizon 2020 Collaborative Health Project NEPHSTROM (grant number 634086) and FP7 Collaborative Health Project VISICORT (grant number 602470)], from Science Foundation Ireland [REMEDI Strategic Research Cluster (grant number 09/SRC-B1794; MDG) and CÚRAM Research Centre (grant number 13/RC/2073; MDG)] and the European Regional Development Fund

Validation of prognostic indices for short term mortality in an incident dialysis population of older adults >75.

Rational and objectivePrognosis provides critical knowledge for shared decision making between patients and clinicians. While several prognostic indices for mortality in dialysis patients have been developed, their performance among elderly patients initiating dialysis is unknown, despite great need for reliable prognostication in that context. To assess the performance of 6 previously validated prognostic indices to predict 3 and/or 6 months mortality in a cohort of elderly incident dialysis patients.Study designValidation study of prognostic indices using retrospective cohort data. Indices were compared using the concordance ("c")-statistic, i.e. area under the receiver operating characteristic curve (ROC). Calibration, sensitivity, specificity, positive and negative predictive values were also calculated.Setting & participantsIncident elderly (age ≥75 years; n = 349) dialysis patients at a tertiary referral center.Established predictorsVariables for six validated prognostic indices for short term (3 and 6 month) mortality prediction (Foley, NCI, REIN, updated REIN, Thamer, and Wick) were extracted from the electronic medical record. The indices were individually applied as per each index specifications to predict 3- and/or 6-month mortality.ResultsIn our cohort of 349 patients, mean age was 81.5±4.4 years, 66% were male, and median survival was 351 days. The c-statistic for the risk prediction indices ranged from 0.57 to 0.73. Wick ROC 0.73 (0.68, 0.78) and Foley 0.67 (0.61, 0.73) indices performed best. The Foley index was weakly calibrated with poor overall model fit (p LimitationsSmall sample size, use of secondary data, need for imputation, homogeneous population.ConclusionMost predictive indices for mortality performed moderately in our incident dialysis population. The Wick and Foley indices were the best performing, but had issues with under and over calibration. More accurate indices for predicting survival in older patients with kidney failure are needed

High rates of cancer screening among dialysis patients seen in primary care a cohort study

Routine preventive cancer screening is not recommended for patients with end-stage renal disease (ESRD)11 Notable abbreviations: primary care (PC), End Stage Renal Disease (ESRD), United States Renal Data System (USRDS). due to their limited life expectancy. The current extent of cancer screening in this population is unknown. Primary care (PC) reminder systems or performance incentives may encourage indiscriminate cancer screening. We compared rates of cancer screening in patients with ESRD, with and without PC visits. This is a retrospective cohort study using United States Renal Data System (USRDS) billing data and electronic medical record data. Patients aged ≥18 years starting dialysis from 2001 to 2008, Midwest regional dialysis network were categorized with or without a PC visit (defined as an office visit in family practice, internal medicine, pediatrics, geriatrics or preventive medicine during the first two years of dialysis). Cancer screening was based on Current Procedural Terminology codes in USRDS. We identified 2512 incident dialysis patients (60% men, median age 65y). Cancer screening rates were more frequent among those seen in PC: 38% vs 19% (P = 0.0002), for breast; 18% vs 10% (P = 0.047) for cervical; 13% versus 8% (P = 0.024) for prostate; and 18% vs 9% (P = 0.0002) for colon cancer. Multivariable analyses found that those with PC were more likely to be screened after adjusting for age, sex, and comorbidities.In our practice, cancer screening rates among chronic dialysis patients are lower than those previously reported for our general population (64% for breast cancer). However, a sizeable proportion of our ESRD population does receive cancer screening, especially those still seen in primary care. Keywords: Breast cancer screening, Cervical cancer screening, Colon cancer screening, Dialysis, ESRD, Preventive screening, Prostate cancer screenin