RESUMEN
INTRODUCTION: In 2017, the Centers for Medicare and Medicaid Services allowed survivors of hospitalized acute kidney injury requiring dialysis (AKI-D) who were ambulatory and still dependent on hemodialysis (HD) to receive treatment in outpatient dialysis facilities. This policy change generated the ongoing need to improve AKI-D care in the outpatient setting. METHODS: Quality improvement study in adult patients admitted to an outpatient HD unit with the diagnosis of AKI-D. We developed a protocol to manage these patients that included: (a) multidisciplinary evaluations; (b) personalized 3-tier HD prescription for dose/ultrafiltration rate and frequency; (c) weekly assessment of kidney recovery; and (d) patient empowerment. Patient- and protocol-specific characteristics were described. We analyzed hourly HD data and protocol adherence, and relevant hemodynamic data were compared according to HD-free survival at 90 days. RESULTS: A total of 457.3 h of HD from 9 patients under the AKI-D protocol were interrogated. Three out of 9 patients were alive and liberated from HD within the first 90 days of outpatient HD. Overall protocol adherence was 53.8% and did not differ by HD-free survival (54.5% vs. 53.7% in those that recovered vs. not). Protocol adherence was associated with fewer intradialytic hypotension events (peak to nadir blood pressure, p < 0.01), while intradialytic hypotension (pre- to post-blood pressure) occurred more frequently in patients who did not recover kidney function (p = 0.009). CONCLUSION: We demonstrated the feasibility of implementing a management protocol for AKI-D patients in an outpatient dialysis facility. We found that fewer episodes of intradialytic hypotension occurred when the outpatient HD management was adherent to the protocol. The feasibility of this protocol should be confirmed in other facilities, and importantly, efficacy testing to evaluate its impact on AKI-D outpatient care is necessary.
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Lesión Renal Aguda , Hipotensión , Diálisis Renal , Adulto , Anciano , Humanos , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/terapia , Hipotensión/epidemiología , Hipotensión/etiología , Hipotensión/terapia , Medicare , Pacientes Ambulatorios , Mejoramiento de la Calidad , Diálisis Renal/efectos adversos , Diálisis Renal/métodos , Estados Unidos/epidemiologíaRESUMEN
Fibrillary glomerulonephritis (FGN) is a rare disorder with poor renal prognosis. It is a heterogeneous disease associated with significant risk of end-stage renal disease (ESRD). Its etiology and pathogenesis have not been clearly identified. We report a case of a patient presenting with hypertensive crisis, nephrotic range proteinuria, and rapidly progressive glomerulonephritis (RPGN). The kidney biopsy demonstrates crescentic GN on light microscopy (LM) and strong pseudo-linear/globular glomerular basement membrane (GBM) staining for immunoglobulin G on immunofluorescence (IF), suggestive of anti-GBM disease. However, circulating anti-GBM antibodies were negative. Electron microscopy (EM) revealed fibrillary deposits in the GBM, confirming the diagnosis of FGN. Review of the literature revealed very few reported similar cases. It appears that severe hypertension and heavy proteinuria, while uncommon in anti-GBM disease, are consistent findings in RPGN form of FGN.
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Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Glomerulonefritis/diagnóstico , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/patología , Autoanticuerpos/análisis , Femenino , Membrana Basal Glomerular/patología , Glomerulonefritis/patología , Humanos , Persona de Mediana EdadRESUMEN
We identified a mechanism whereby retina regeneration in the embryonic chick can be induced by the contribution of stem/progenitor cells. We show that bone morphogenetic protein (BMP) signaling is sufficient and necessary to induce retina regeneration and that its action can be divided into two phases. By 3 days after postretinectomy (d PR), the BMP pathway directs proliferation and regeneration through the activation of Smad (canonical BMP pathway) and the up-regulation of FGF signaling by the MAPK pathway. By 7d PR, it induces apoptosis by activating p38 (a noncanonical BMP pathway) and down-regulating FGF signaling (by both MAPK and AKT pathways). Apoptosis at this later stage can be prevented, and BMP-induced regeneration can be further induced by inhibition of p38. These results unravel a mechanism for stem/progenitor cell-mediated retina regeneration, where BMP activation establishes a cross-talk with the FGF pathway and selectively activates the canonical and noncanonical BMP pathways. Retina stem/progenitor cells exist in other species, including humans. Thus, our findings provide insights on how retinal stem cells can be activated for possible regenerative therapies.
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Proteínas Morfogenéticas Óseas/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Regeneración/genética , Retina/fisiología , Células Madre/fisiología , Animales , Apoptosis , Proteínas Morfogenéticas Óseas/genética , Proliferación Celular , Embrión de Pollo , Ojo/química , Ojo/metabolismo , Regiones Promotoras Genéticas , Retina/citología , Transducción de Señal , Proteínas Smad/genética , Células Madre/citología , Activación Transcripcional , Proteínas Quinasas p38 Activadas por Mitógenos/genéticaRESUMEN
The embryonic chick is able to regenerate the retina after it has been removed. We have previously shown that proliferating stem/progenitor cells present in the ciliary body/ciliary marginal zone (CB/CMZ) of the chick eye are responsible for regeneration, which can be induced by ectopic fibroblast growth factor-2 (FGF2) or Sonic hedgehog (Shh). Here, we reveal the mechanisms showing how FGF2 and Shh signaling are interdependent during retina regeneration. If the FGF pathway is inhibited, regeneration stimulated by Shh is inhibited. Likewise, if the Hedgehog pathway is inhibited, regeneration stimulated by FGF2 is inhibited. We examined early signaling events in the CB/CMZ and found that FGF2 or Shh induced a robust Erk phosphorylation during the early stages of retina regeneration. Shh also up-regulated the expression of several members of the FGF signaling pathway. We show that ectopic FGF2 or Shh overexpression increased the number of phosphohistone 3 (PH3)-positive cells in the CB/CMZ and inhibition of either pathway decreased the number of PH3-positive cells. Additionally, both FGF and Hh signaling are required for cell survival in the CB/CMZ, whereas Hh and not FGF signaling plays a role in maintaining the identity of the retinal progenitor population in this region. Combined, our results support a model where the FGF and Hedgehog pathways work together to stimulate retina regeneration.
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Factores de Crecimiento de Fibroblastos/fisiología , Proteínas Hedgehog/fisiología , Regeneración/fisiología , Retina/fisiología , Animales , Proliferación Celular , Supervivencia Celular , Embrión de Pollo , Cuerpo Ciliar/citología , Cuerpo Ciliar/embriología , Cuerpo Ciliar/fisiología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Factor 2 de Crecimiento de Fibroblastos/genética , Factor 2 de Crecimiento de Fibroblastos/farmacología , Factor 2 de Crecimiento de Fibroblastos/fisiología , Factores de Crecimiento de Fibroblastos/genética , Proteínas Hedgehog/antagonistas & inhibidores , Proteínas Hedgehog/genética , Modelos Biológicos , Fosforilación , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Proteínas Recombinantes/farmacología , Regeneración/genética , Retina/embriología , Transducción de Señal , Regulación hacia ArribaRESUMEN
PURPOSE: To elucidate the early cellular events that take place during induction of retina regeneration in the embryonic chick, focusing on the relationship between fibroblast growth factor (FGF) signaling and the regulation of Pax6 and Mitf. METHODS: The retina of embryonic day 4 (E4) chicks was removed and a heparin coated bead soaked in fibroblast growth factor 2 (FGF2) was placed into the optic cup. The pharmacological inhibitor PD173074 was used to inhibit FGF receptors, PD98059 was used to inhibit MAP kinase-kinase/extracellular signal-regulated kinase (MEK/Erk) signaling. Retroviral constructs for paired box 6 (Pax6), MEK, and microphthalmia (Mitf) were also used in overexpression studies. Immunohistochemistry was used to examine pErk, Pax6, Mitf, and melanosomal matrix protein 115 (MMP115) immunoreactivity and bromodeoxyuridine (BrdU) incorporation at different time points after removing the retina. RESULTS: The embryonic chick has the ability to regenerate a new retina by the process of transdifferentiation of the retinal pigment epithelium (RPE). We observed that during the induction of transdifferentiation, downregulation of Mitf was not sufficient to induce transdifferentiation at E4 and that FGF2 was required to drive Pax6 protein expression and cell proliferation, both of which are necessary for transdifferentiation. Furthermore, we show that FGF2 works through the FGFR/MEK/Erk signaling cascade to increase Pax6 expression and proliferation. Ectopic Mitf expression was able to inhibit transdifferentiation by acting downstream of FGFR/MEK/Erk signaling, likely by inhibiting the increase in Pax6 protein in the RPE. CONCLUSIONS: FGF2 stimulates Pax6 expression during induction of transdifferentiation of the RPE through FGFR/MEK/Erk signaling cascade. This Pax6 expression is accompanied by an increase in BrdU incorporation. In addition, we show that Mitf is spontaneously downregulated after removal of the retina even in the absence of FGF2. This Mitf downregulation is not accompanied by Pax6 upregulation, demonstrating that FGF2 stimulated Pax6 upregulation is required for transdifferentiation of the RPE. Furthermore, we show that ectopic Mitf expression is able to protect the RPE from FGF2 induced transdifferentiation by inhibiting Pax6 upregulation.