Acute kidney injury is followed by regeneration of damaged renal tubular epithelial cells. The purpose of this study was to test the hypothesis that renal stem cells exist in the adult kidney and participate in the repair process. A unique population of cells that behave in a manner that is consistent with a renal stem cell were isolated from rat kidneys and were termed multipotent renal progenitor cells (MRPC). Features of these cells include spindle-shaped morphology; self-renewal for >200 population doublings without evidence for senescence; normal karyotype and DNA analysis; and expression of vimentin, CD90 (thy1.1), Pax-2, and Oct4 but not cytokeratin, MHC class I or II, or other markers of more differentiated cells. MRPC exhibit plasticity that is demonstrated by the ability of the cells to be induced to express endothelial, hepatocyte, and neural markers by reverse transcriptase-PCR and immunohistochemistry. The cells can differentiate into renal tubules when injected under the capsule of an uninjured kidney or intra-arterially after renal ischemia-reperfusion injury. Oct4 expression was seen in some tubular cells in the adult kidney, suggesting these cells may be candidate renal stem cells. It is proposed that MRPC participate in the regenerative response of the kidney to acute injury.
Background Patients on hemodialysis have an elevated risk for COVID-19 infection but were not included in efficacy trials of SARS-CoV-2 vaccines. Methods We conducted a retrospective, observational study to estimate the real-world effectiveness and immunogenicity of two mRNA SARS-CoV-2 vaccines in a large, representative population of adult hemodialysis patients in the United States. In separate, parallel analyses, patients who began a vaccination series with BNT162b2 or mRNA-1273 in January and February 2021 were matched with unvaccinated patients and followed after they completed the first of two doses. In a subset of patients, blood samples were collected approximately 28 days after the second dose and anti-SARS-CoV-2 immunoglobulin G was measured. Results A total of 12,169 patients received the BNT162b2 vaccine (matched with 44,377 unvaccinated controls); 23,037 patients received the mRNA-1273 vaccine (matched with 63,243 unvaccinated controls). Compared with controls, vaccinated patients' risk of being diagnosed with COVID-19 post-vaccination became progressively lower after the first dose (day 1) to days ≥43. Following a COVID-19 diagnosis, vaccinated patients were significantly less likely than unvaccinated patients to be hospitalized (for BNT162b2, 28.0% versus 43.4%; for mRNA-1273, 37.2% versus 45.6%) and significantly less likely to die (for BNT162b2, 4.0% versus 12.1%; for mRNA-1273, 5.6% versus 14.5%). Antibodies were detected in 98.1% (309/315) and 96.0% (308/321) of BNT162b2 and mRNA-1273 patients, respectively. Conclusions In patients on hemodialysis, vaccination with BNT162b2 or mRNA-12 was associated with a lower risk of COVID-19 diagnosis and significantly lower risk of hospitalization or death among those diagnosed with COVID-19. SARS-CoV-2 antibodies were detected in nearly all patients after vaccination. These findings support the use of these vaccines in this population.
To better understand the implications for considering delayed graft function (DGF) as a performance measure, we compared outcomes associated with a 2-to 3-fold difference in the incidence of DGF at two transplant centers. RR's of DGF were similar at both centers. Thus, the lower incidence of DGF at UMMC likely resulted in a higher incidence and higher risk of SGF compared to HCMC. Indeed, graft survival for recipients with DGF at HCMC was similar (p = 0.3741) to that of recipients with SGF at UMMC. We conclude that dialysis per se is likely not a cause of worse graft outcomes. A better definition is needed to measure early graft dysfunction and its effects across transplant programs.
IntroductionPatiromer is a potassium (K+) binding polymer indicated for treating hyperkalemia. Among patients receiving chronic hemodialysis (HD), this study aimed to identify patient characteristics associated with patiromer initiation, describe patiromer utilization, and analyze serum K+ pre- and post-patiromer initiation.MethodsIn a retrospective cohort study, using electronic health record data from a large dialysis provider in the United States (study period: December 21, 2015, to December 20, 2016), HD patients were included who had a medication order for patiromer, sodium polystyrene sulfonate (SPS), or laboratory evidence of hyperkalemia (no K+ binder [NoKb] cohort). The index date was the first order for patiromer/SPS, or the first K+ ≥5.0 mEq/l (NoKb cohort), respectively. Using multivariable logistic regression, we identified patient characteristics associated with patiromer initiation. We evaluated patiromer utilization using Kaplan-Meier methodology and proportion of days covered. Serum K+ concentrations were assessed pre- versus post-patiromer initiation.ResultsStudy cohorts included 527 (patiromer), 852 (SPS), and 8747 (NoKb) HD patients. Median follow-up was 141 days. Patiromer initiators were 2.6 times more likely to have had multiple prior episodes of hyperkalemia (odds ratio [OR]: 2.6; 95% confidence interval [CI]: 1.8–3.7). Most (61%) commenced patiromer on 8.4 g once daily; 60% of patients’ first patiromer order remained open after 180 days. Statistically significant reductions in K+, averaging approximately −0.5 mEq/l, were observed post-patiromer initiation (48% pre-patiromer vs. 22% post-patiromer had K+ ≥6.0 mEq/l [P < 0.001]).ConclusionPatiromer initiators receiving chronic hemodialysis had comparatively more severe, uncontrolled baseline hyperkalemia. Medication order data show long-term patiromer use was associated with significantly reduced K+.
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