Publications by authors named "Paul Grimm"

Article Synopsis
  • Natural killer (NK) cells play a crucial role in managing both viral infections and immune responses during kidney transplants in children, as shown in a study using data from the CTOTC project.
  • The study analyzed NK cell phenotypes in 98 pediatric kidney transplant patients and found specific NK cell traits linked to either viral infections or alloimmune events, such as acute rejection.
  • These findings suggest that understanding NK cell profiles could help distinguish between risk factors for infections versus those for immune responses after transplantation.
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In this paper, we present a new processing method, called MOSES-Impacts, for the detection of micrometer-sized damage on glass plate surfaces. It extends existing methods by a separation of damaged areas, called impacts, to support state-of-the-art recycling systems in optimizing their parameters. These recycling systems are used to repair process-related damages on glass plate surfaces, caused by accelerated material fragments, which arise during a laser-matter interaction in a vacuum.

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Background: Normative blood pressure (BP) values and definition of hypertension (HTN) in children in outpatient setting cannot be reliably used for inpatient therapy initiation. No normative exists to describe HTN in hospitalized pediatric populations. We aimed to study the prevalence of hypertension and produce normative BP values in hospitalized children.

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Infants with congenital bilateral renal agenesis are at significant risk for morbidity and mortality, despite substantial and continuing advances in fetal and neonatal therapeutics. Infants with bilateral renal agenesis may episodically develop severe hypotension that can be refractory to traditional vasopressors. Synthetic angiotensin-II has been successfully used in adult and a few pediatric patients with refractory hypotension but has not been extensively studied in infants.

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Objectives: Differences in creatinine and cystatin C-based estimates of glomerular filtration rate (eGFR = eGFR - eGFR) may reflect differences in muscle mass. We sought to determine if eGFR (1) reflects lean mass, (2) identifies sarcopenic individuals beyond estimates based on age, body mass index (BMI), and sex; and (3) demonstrates associations differently in those with and without chronic kidney disease (CKD).

Design And Methods: This cross-sectional study included 3,754 participants, ages 20-85 years, with creatinine and cystatin C concentration levels, and dual-energy X-ray absorptiometry scans from National Health and Nutrition Examination Survey data (1999-2006).

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Dietary potassium (K+) supplementation is associated with a lowering effect in blood pressure (BP), but not all studies agree. Here, we examined the effects of short- and long-term K+ supplementation on BP in mice, whether differences depend on the accompanying anion or the sodium (Na+) intake and molecular alterations in the kidney that may underlie BP changes. Relative to the control diet, BP was higher in mice fed a high NaCl (1.

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Article Synopsis
  • Antibody-mediated rejection contributes significantly to early kidney transplant failure, but there is a lack of consistent guidelines for measuring antibodies and determining treatment approaches.
  • This study evaluated the effectiveness of monitoring donor-specific antibodies (DSA) in children who received kidney transplants at Stanford from 2010 to 2018, including 233 patients with an average follow-up of 45 months.
  • The findings revealed that C1q-binding DSA was particularly indicative of graft failure risk; patients with persistent C1q-DSA had a much higher chance of losing their graft, identifying it as a superior biomarker compared to standard DSA.
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Background: Malnutrition, including obesity and undernutrition, among children is increasing in prevalence and is common among children on renal replacement therapy. The effect of malnutrition on the pre-transplant immune system and how the pediatric immune system responds to the insult of both immunosuppression and allotransplantation is unknown. We examined the relationship of nutritional status with post-transplant outcomes and characterized the peripheral immune cell phenotypes of children from the Immune Development of Pediatric Transplant (IMPACT) study.

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Background And Objectives: High tacrolimus intrapatient variability has been associated with inferior graft outcomes in patients with kidney transplants. We studied baseline patterns of tacrolimus intrapatient variability in pediatric patients with kidney transplants and examined these patterns in relation to C1q-binding donor-specific antibodies.

Design, Setting, Participants, & Measurements: All tacrolimus levels in participants who underwent kidney-only transplantation at a single pediatric center from 2004 to 2018 (with at least 12-month follow-up, followed until 2019) were analyzed to determine baseline variability.

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Lifelong immunosuppression is required for allograft survival after kidney transplantation but may not ultimately prevent allograft loss resulting from chronic rejection. We developed an approach that attempts to abrogate immune rejection and the need for post-transplantation immunosuppression in three patients with Schimke immuno-osseous dysplasia who had both T-cell immunodeficiency and renal failure. Each patient received sequential transplants of αβ T-cell-depleted and CD19 B-cell-depleted haploidentical hematopoietic stem cells and a kidney from the same donor.

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Aberrant activation of with-no-lysine kinase (WNK)-STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) kinase signaling in the distal convoluted tubule (DCT) causes unbridled activation of the thiazide-sensitive sodium chloride cotransporter (NCC), leading to familial hyperkalemic hypertension (FHHt) in humans. Studies in FHHt mice engineered to constitutively activate SPAK specifically in the DCT (CA-SPAK mice) revealed maladaptive remodeling of the aldosterone sensitive distal nephron (ASDN), characterized by decrease in the potassium excretory channel, renal outer medullary potassium (ROMK), and epithelial sodium channel (ENaC), that contributes to the hyperkalemia. The mechanisms by which NCC activation in DCT promotes remodeling of connecting tubule (CNT) are unknown, but paracrine communication and reduced salt delivery to the ASDN have been suspected.

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Background: Currently, there is no consensus among pediatric kidney transplant centers regarding the use and regimen for immunosuppressive induction therapy.

Methods: In this single center, retrospective cohort study, pediatric kidney transplant recipients transplanted between 1 May 2013 and 1 May 2018 with rabbit antithymocyte globulin (rATG) induction were included. We stratified patients based on immunological risk, with high risk defined as those with repeat transplant, preformed donor specific antibody, current panel-reactive antibodies > 20%, 0 antigen match and/or African-American heritage.

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Unlabelled: Lack of noninvasive diagnostic and prognostic biomarkers to reliably detect early allograft injury poses a major hindrance to long-term allograft survival in pediatric kidney transplant recipients.

Methods: Validating Injury to the Renal Transplant Using Urinary Signatures Children's Study, a North American multicenter prospective cohort study of pediatric kidney transplant recipients, aims to validate urinary cell mRNA and metabolite profiles that were diagnostic and prognostic of acute cellular rejection (ACR) and BK virus nephropathy (BKVN) in adult kidney transplant recipients in Clinical Trials in Organ Transplantation-4. Specifically, we are investigating: (1) whether a urinary cell mRNA 3-gene signature (-normalized mRNA, and ribosomal RNA) discriminates biopsies with versus without ACR, (2) whether a combined metabolite profile with the 3-gene signature increases sensitivity and specificity of diagnosis and prognostication of ACR, and (3) whether mRNA levels in urinary cells are diagnostic of BKVN and prognostic for allograft failure.

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Background And Objectives: In December 2014, the Kidney Allocation System (KAS) was implemented to improve equity in access to transplantation, but preliminary studies in children show mixed results. Thus, we aimed to assess how the 2014 KAS policy change affected racial and ethnic disparities in pediatric kidney transplantation access and related outcomes.

Design, Setting, Participants, & Measurements: We performed a retrospective cohort study of children <18 years of age active on the kidney transplant list from 2008 to 2019 using the Scientific Registry of Transplant Recipients.

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The phenotype of individuals with glycogen storage disease (GSD) IX appears to be highly variable, even within subtypes. Features include short stature, fasting hypoglycemia with ketosis, hepatomegaly, and transaminitis. GSD IXɑ2 is caused by hemizygous pathogenic variants in , and results in deficiency of the phosphorylase kinase enzyme, particularly in the liver.

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Article Synopsis
  • Urinary extracellular vesicles (uEVs) are tiny particles released in urine by kidney and urinary tract cells, and there's ongoing debate about how well they reflect kidney health or disease.
  • A mass spectrometry study compared protein levels in uEVs and kidney tissue of rats on different diets, finding a positive correlation between the two, particularly with transmembrane proteins.
  • This research suggests that changes in uEV proteins can reliably indicate kidney protein levels, making them a valuable resource for studying kidney physiology and disease.
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Depletional induction using antithymocyte globulin (ATG) reduces rates of acute rejection in adult kidney transplant recipients, yet little is known about its effects in children. Using a longitudinal cohort of 103 patients in the Immune Development in Pediatric Transplant (IMPACT) study, we compared T cell phenotypes after ATG or non-ATG induction. We examined the effects of ATG on the early clinical outcomes of alloimmune events (development of de novo donor specific antibody and/or biopsy proven rejection) and infection events (viremia/viral infections).

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Background: During kidney transplantation, the transplanted kidney undergoes ischemia reperfusion injury, with adenosine being a major mediator. This study aimed to assess whether aminophylline, an adenosine receptor antagonist, improves early graft function and reduces incidence of delayed graft function (DGF) and slow graft function (SGF).

Methods: Single center, double-blinded, placebo-controlled randomized clinical trial.

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STK39 encodes a serine threonine kinase, SPAK, which is part of a multi-kinase network that determines renal Na reabsorption and blood pressure (BP) through regulation of sodium-chloride co-transporters in the kidney. Variants within STK39 are associated with susceptibility to essential hypertension, and constitutively active SPAK mice are hypertensive and hyperkalemic, similar to familial hyperkalemic hyperkalemia in humans. SPAK null mice are hypotensive and mimic Gitelman syndrome, a rare monogenic salt wasting human disorder.

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Introduction: Urinary diversion in pediatric renal transplant candidates with bladders not amenable to primary reconstruction can be achieved by pre-transplant ileal conduit creation. We performed cutaneous ureterostomies to limit pre-transplant surgery, protect the peritoneum for dialysis, transplant patients sooner, and preserve ureter length for future surgical reconstruction.

Methods: We compared four pediatric transplant recipients with ureterostomies to four recipients with ileal conduits from 2009 to 2017.

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Bilateral renal agenesis is associated with severe oligohydramnios and was considered incompatible with postnatal life due to severe pulmonary hypoplasia. The use of renal replacement therapy was limited by significant morbidity and mortality associated with dialysis in very young infants with major pulmonary pathology. In the United States, there is a tremendous controversy about whether or not the use of prenatal amniotic fluid infusions provides a benefit to fetuses with bilateral renal agenesis.

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Purpose Of Review: Kidney transplantation is the preferred treatment modality for children with end-stage renal disease. In this review, we discuss the factors affecting the selection of the appropriate donor to ensure the best possible short and long-term outcomes.

Recent Findings: Outcomes of pediatric renal transplantation from living donors are superior to those obtained from deceased donors.

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Purpose: The treatment of VUR in children with UTI has changed significantly, due to studies showing that antibiotic prophylaxis does not decrease renal scarring. As children with kidney transplants are at higher risk for UTI, we investigated if select patients with renal transplant VUR could be managed without surgery.

Materials And Methods: A total of 18 patients with VUR into their renal grafts were identified, and 319 patients underwent transplantation from 2006 to 2016.

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