Alleviation of renal ischemia/reperfusion injury by exosomes from induced pluripotent stem cell-derived mesenchymal stem cells

Background/Aims@#Renal ischemia followed by reperfusion (I/R) is a leading cause of acute kidney injury (AKI), which is closely associated with high morbidity and mortality. Studies have shown that induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) exert powerful therapeutic effects in renal ischemia. However, the efficacy of iMSC-derived exosomes (iExo) on I/R injuries remains largely unknown. @*Methods@#Human iPSCs were differentiated into iMSCs using a modified one-step method. Ultrafiltration, combined with purification, was used to isolate iExo from iMSCs. iExo was administered following I/R injury in a mouse model. The effect of iExo on I/R injury was assessed through changes in renal function, histology, and expression of oxidative stress, inflammation, and apoptosis markers. Further, we evaluated its association with the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. @*Results@#Mice subjected to I/R injury exhibited typical AKI patterns; serum creatinine level, tubular necrosis, apoptosis, inflammatory cytokine production, and oxidative stress were markedly increased compared to sham mice. However, treatment with iExo attenuated these changes, significantly improving renal function and tissue damage, similar to the renoprotective effects of iMSCs on I/R injury. Significant induction of activated ERK 1/2 signaling molecules was observed in mice treated with iExo compared to those in the I/R injury group. @*Conclusions@#The present study demonstrates that iExo administration ameliorated renal damage following I/R, suggesting that iMSC-derived exosomes may provide a novel therapeutic approach for AKI treatment.

Kidney transplantation in highly sensitized recipients

In kidney transplantation (KT), overcoming donor shortage is particularly challenging in patients with preexisting donor-specific antibodies (DSAs) against human leukocyte antigen (HLA), called HLA-incompatible KT (HLAi KT), carrying the risk of rejection and allograft loss. Thus, it is necessary to accurately evaluate the degree of sensitization before HLAi KT, and undertake appropriate pretreatment strategies. To determine the degree of sensitization, complement-dependent cytotoxicity has been the only method employed; the development of a method using flow cytometry further improved the test sensitivity. However, these tests present disadvantages, including the need for living cells, with a solid-phase assay developed to resolve this problem. Currently, the method using Luminex (Luminex Corp.) is widely used in clinical practice. As this method measures DSAs using single antigen beads, it is possible to classify immunological risks by measuring the type and amount of DSAs. Furthermore, there have been major advances in methods that involve DSA removal before HLAi KT. In the early stages of desensitization, plasmapheresis and intravenous immunoglobulins were the main treatment methods employed; however, the introduction of CD20 monoclonal antibody and proteasome inhibitors further increased the success rate of desensitization. Currently, HLAi KT has been established as an important transplant method, but an understanding of DSAs and a novel desensitization treatment are warranted.

Modeling of endothelial cell dysfunction using human induced pluripotent stem cells derived from patients with end-stage renal disease

Background@#Endothelial cell (EC) dysfunction is a frequent feature in patients with end-stage renal disease (ESRD). The aim of this study was to generate human induced pluripotent stem cells, differentiate ECs (hiPSC-ECs) from patients with ESRD, and appraise the usefulness of hiPSC-ECs as a model to investigate EC dysfunction. @*Methods@#We generated hiPSCs using peripheral blood mononuclear cells (PBMCs) isolated from three patients with ESRD and three healthy controls (HCs). Next, we differentiated hiPSC-ECs using the generated hiPSCs and assessed the expression of endothelial markers by immunofluorescence. The differentiation efficacy, EC dysfunction, and molecular signatures of EC-related genes based on microarray analysis were compared between the ESRD and HC groups. @*Results@#In both groups, hiPSCs and hiPSC-ECs were successfully obtained based on induced pluripotent stem cell or EC marker expression in immunofluorescence and flow cytometry. However, the efficiency of differentiation of ECs from hiPSCs was lower in the ESRD-hiPSCs than in the HC-hiPSCs. In addition, unlike HC-hiPSC-ECs, ESRD-hiPSC-ECs failed to form interconnecting branching point networks in an in vitro tube formation assay. During microarray analysis, transcripts associated with oxidative stress and inflammation were upregulated and transcripts associated with vascular development and basement membrane extracellular matrix components were downregulated in ESRD-hiPSC-ECs relative to in HC-hiPSC-ECs. @*Conclusion@#ESRD-hiPSC-ECs showed a greater level of EC dysfunction than HC-hiPSC-ECs did based on functional assay results and molecular profiles. hiPSC-ECs may be used as a disease model to investigate the pathophysiology of EC dysfunction in ESRD.

Water-soluble coenzyme Q10 provides better protection than lipid-soluble coenzyme Q10 in a rat model of chronic tacrolimus nephropathy

Background/Aims@#Coenzyme Q10 (CoQ10), is a promising antioxidant; however, low bioavailability owing to lipid-solubility is a limiting factor. We developed water-soluble CoQ10 (CoQ10-W) and compared its effects with conventional lipid-soluble CoQ10 (CoQ10-L) in an experimental model of chronic tacrolimus (Tac) nephropathy. @*Methods@#CoQ10-W was developed from a glycyrrhizic-carnitine mixed layer CoQ10 micelle based on acyltransferases. Chronic nephropathy was induced in rats with 28-day Tac treatment; they were concomitantly treated with CoQ10-L or CoQ10-W. CoQ10 level in plasma and kidney were measured using liquid chromatography–mass spectrometry. CoQ10-W and CoQ10-L effects on Tac-induced nephropathy were assessed in terms of renal function, histopathology, oxidative stress, and apoptotic cell death. Their effects on cell viability and reactive oxygen species (ROS) production were assessed in cultured proximal tubular cells, human kidney 2 (HK-2) cells. @*Results@#The plasma CoQ10 level was significantly higher in the CoQ10-W group than in the CoQ10-L group. Tac treatment caused renal dysfunction, typical pathologic lesions, and oxidative stress markers. Serum creatinine was restored in the Tac + CoQ10-L or CoQ10-W groups compared with that in the Tac group. CoQ10-W administration reduced oxidative stress and apoptosis markers. Mitochondrial ultrastructure assessment revealed that the addition of CoQ10-L or CoQ10-W with Tac increased mitochondrial size and number than Tac treatment alone. In vitro investigations revealed that both CoQ10-L and CoQ10-W improved cell viability and reduced ROS production in the Tac-induced HK-2 cell injury. @*Conclusions@#CoQ10-W has a better therapeutic effect in Tac-induced renal injury than conventional CoQ10-L, possibly associated with improved CoQ10 bioavailability

Mortality prediction of serum neutrophil gelatinase-associated lipocalin in patients requiring continuous renal replacement therapy

Background/Aims@#We investigated whether serum neutrophil gelatinase-associated lipocalin (NGAL) can predict mortality in patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). @*Methods@#This study enrolled 169 patients who underwent serum NGAL testing at CRRT initiation from June 2017 to January 2019. The predictive power of serum NGAL level for 28-day mortality was compared to the Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score and Sequential Organ Failure Assessment (SOFA) score via area under the receiver operating characteristic curve (AuROC) value. @*Results@#There were 55 survivors and 114 non-survivors at 28 days post-CRRT initiation. Median serum NGAL level was significantly higher in the non-survivor group than in the survivor group (743.0 ng/mL vs. 504.0 ng/mL, p = 0.003). The AuROC value of serum NGAL level was 0.640, which was lower than APACHEII score and SOFA score values (0.767 and 0.715, respectively). However, in the low APACHE-II score group (< 27.5), AuROC value of serum NGAL was significantly increased (0.698), and it was an independent risk factor for 28 day-mortality (hazard ratio, 2.405; 95% confidence interval, 1.209 to 4.783; p = 0.012). @*Conclusions@#In patients with AKI requiring CRRT, serum NGAL levels may be useful for predicting short-term mortality in those with low APACHE-II scores.

Usefulness of BK virus-specific interferon-γ enzyme-linked immunospot assay for predicting the outcome of BK virus infection in kidney transplant recipients

Background/Aims@#To investigate if BK virus (BKV)-specific T cell immunity measured by an interferon-γ enzyme-linked immunospot (ELISPOT) assay can predict the outcome of BK virus infection in kidney transplant recipients (KTRs). @*Methods@#We included 68 KTRs with different viremia status (no viremia [n = 17], BK viremia [n = 27], and cleared viremia [n = 24]) and 44 healthy controls (HCs). The BK viremia group was divided into controller ( 3 months) according to sustained duration of BKV infection. We compared BKV-ELISPOT results against five BKV peptides (large tumor antigen [LT], St, VP1-3). @*Results@#BKV-ELISPOT results were higher in three KTRs groups with different BKV infection status than the HCs group (p < 0.05). In KTR groups, they were higher in cleared viremia group than no viremia or BK viremia group. Within the BK viremia group, controller group had higher LT-ELISPOT results compared to noncontroller group (p = 0.032). Also, KTRs without BK virus-associated nephropathy (BKVN) had higher LT, St, VP1, and VP2-ELISPOT results than those with BKVN (p < 0.05). @*Conclusions@#BKV-ELISPOT assay may be effective in predicting clinical outcomes of BKV infection in terms of clearance of BK virus and development of BKVN.

Water-soluble coenzyme Q10 provides better protection than lipid-soluble coenzyme Q10 in a rat model of chronic tacrolimus nephropathy

Background/Aims@#Coenzyme Q10 (CoQ10), is a promising antioxidant; however, low bioavailability owing to lipid-solubility is a limiting factor. We developed water-soluble CoQ10 (CoQ10-W) and compared its effects with conventional lipid-soluble CoQ10 (CoQ10-L) in an experimental model of chronic tacrolimus (Tac) nephropathy. @*Methods@#CoQ10-W was developed from a glycyrrhizic-carnitine mixed layer CoQ10 micelle based on acyltransferases. Chronic nephropathy was induced in rats with 28-day Tac treatment; they were concomitantly treated with CoQ10-L or CoQ10-W. CoQ10 level in plasma and kidney were measured using liquid chromatography–mass spectrometry. CoQ10-W and CoQ10-L effects on Tac-induced nephropathy were assessed in terms of renal function, histopathology, oxidative stress, and apoptotic cell death. Their effects on cell viability and reactive oxygen species (ROS) production were assessed in cultured proximal tubular cells, human kidney 2 (HK-2) cells. @*Results@#The plasma CoQ10 level was significantly higher in the CoQ10-W group than in the CoQ10-L group. Tac treatment caused renal dysfunction, typical pathologic lesions, and oxidative stress markers. Serum creatinine was restored in the Tac + CoQ10-L or CoQ10-W groups compared with that in the Tac group. CoQ10-W administration reduced oxidative stress and apoptosis markers. Mitochondrial ultrastructure assessment revealed that the addition of CoQ10-L or CoQ10-W with Tac increased mitochondrial size and number than Tac treatment alone. In vitro investigations revealed that both CoQ10-L and CoQ10-W improved cell viability and reduced ROS production in the Tac-induced HK-2 cell injury. @*Conclusions@#CoQ10-W has a better therapeutic effect in Tac-induced renal injury than conventional CoQ10-L, possibly associated with improved CoQ10 bioavailability

The differential effects of anemia on mortality in young and elderly end-stage renal disease patients

Background@#The aim of this study was to compare the effect of anemia on clinical outcomes according to age in patients with end-stage renal disease (ESRD). @*Methods@#A total of 3,409 patients from the Clinical Research Center for ESRD were included and divided into three groups by age: age < 40 (n = 488), 40 ≤ age < 60 (n = 1,650), and age ≥ 60 (n = 1,271). We compared overall and cardiovascular mortality, and all-cause and cardiovascular hospitalization according to mean hemoglobin (Hb) concentration. @*Results@#Among participants ≥ 60 years of age, the Hb < 10 g/dL group had greater all-cause mortality (adjusted hazard ratio [HR], 2.098; 95% confidence interval [CI], 1.567-2.808; P < 0.001) than the 10 ≤ Hb < 12 g/dL group, whereas among participants < 40 years of age, the Hb ≥ 12 g/dL group had greater mortality than the 10 ≤ Hb < 12 g/dL group. Moreover, in participants ≥ 60 years of age, the HR for all-cause hospitalization for the Hb < 10 g/dL group was significantly greater than that of the 10 ≤ Hb < 12 g/dL group (HR, 1.472; 95% CI, 1.057-2.051; P = 0.022), whereas it was significantly lower in the Hb ≥ 12 g/dL group (HR, 0.544; 95% CI, 0.362-0.820; P = 0.004) However, among participants < 40 years of age, the incidence of all-cause hospitalization did not differ according to the Hb concentration (HR, 1.273; 95% CI, 0.814-1.991; P = 0.290 for the Hb < 10 g/dL group; reference, 10 ≤ Hb < 12 g/dL; HR, 0.787; 95% CI, 0.439-1.410; P = 0.265 for Hb ≥ 12 g/dL group). @*Conclusion@#The impact of anemia on mortality was more significant in elderly ESRD patients. Strict monitoring and management of anemia should be required for elderly ESRD patients.

The therapeutic efficacy of water-soluble coenzyme Q10 in an experimental model of tacrolimus-induced diabetes mellitus

Background/Aims@#Coenzyme Q10 (CoQ10) has antioxidant effects and is commercially available and marketed extensively. However, due to its low bioavailability, its effects are still controversial. We developed a water-soluble CoQ10-based micelle formulation (CoQ10-W) and tested it in an experimental model of tacrolimus (TAC)-induced diabetes mellitus (DM). @*Methods@#We developed CoQ10-W from a glycyrrhizic-carnitine mixed layer CoQ10 micelle preparation based on acyltransferases. TAC-induced DM rats were treated with either lipid-soluble CoQ10 (CoQ10-L) or CoQ10-W for 4 weeks. Their plasma and pancreatic CoQ10 concentrations were measured using liquid chromatography- tandem mass spectrometry. The therapeutic efficacies of CoQ10-W and CoQ10-L on TAC-induced DM were compared using functional and morphological parameters and their effects on cell viability and reactive oxygen species (ROS) production were also evaluated in cultured rat insulinoma cells. @*Results@#The plasma CoQ10 level was significantly increased in the CoQ10-W group compared to that in the CoQ10-L group. Intraperitoneal glucose tolerance tests and glucose-stimulated insulin secretion revealed that CoQ10-W controlled hyperglycemia and restored insulin secretion significantly better than CoQ10-L. The TAC-mediated decrease in pancreatic islet size was significantly attenuated by CoQ10-W but not by CoQ10-L. TAC-induced oxidative stress and apoptosis were significantly more reduced by CoQ10-W than CoQ10-L. Electron microscopy revealed that CoQ10-W restored TAC-induced attenuation in the number of insulin granules and the average mitochondrial area, unlike CoQ10-L. In vitro studies showed that CoQ10-L and CoQ10-W both improved cell viability and reduced ROS production in TAC-treated islet cells to a similar extent. @*Conclusions@#CoQ10-W has better therapeutic efficacy than CoQ10-L in TAC-induced DM.

Assessment of nephrotoxicity of herbal medicine containing aristolochic acid in mice

Background/Aims@#It is undetermined if herbal medicines (HM) containing aristolochic acid (AA)-containing have similar nephrotoxicity to AA itself. @*Methods@#We administered HM containing a high concentration of AA for 5 days (short-term study) or a low concentration of AA for 30 days (long-term study) to C57BL/6 mice; for comparison, same dose of AA compound was used as controls. @*Results@#The nephrotoxicity in the HM- and AA-treated mice was compared in terms of renal function, histopathology, oxidative stress, apoptotic cell death, and mitochondrial damage. Short-term HM treatment resulted in acute kidney injury (marked renal dysfunction, acute tubular necrosis, and neutrophil gelatinase-associated lipocalin [NGAL] expression) in which the severity of renal dysfunction and histopathology was comparable with that induced by the administration of AA alone. Long-term HM treatment resulted in features of chronic kidney disease (CKD, mild renal dysfunction and tubular atrophy and dilatation). No significant differences in these parameters were observed between the HM- and AA-treated mice. HM-induced oxidative stress (8-hydroxy-2’-deoxyguanosine and manganese- dependent superoxide dismutase expression) and apoptotic cell death (terminal deoxynucleotidyl transferase dUTP nick end labelling [TUNEL]-positive cells and active caspase-3 expression) were similar in HM- and AA-treated mice in the short-term and long-term studies. Mitochondrial injury, evaluated by electron microscopy, was also similar in HM- and AA-treated mice in the short-term and long-term studies. @*Conclusions@#The nephrotoxic potential of HM containing AA was similar to that of AA itself.

Development of End Stage Renal Disease after Long-Term Ingestion of Chaga Mushroom: Case Report and Review of Literature

Chaga mushrooms are widely used in folk remedies and in alternative medicine. Contrary to many beneficial effects, its adverse effect is rarely reported. We here report a case of end-stage renal disease after long-term taking Chaga mushroom. A 49-year-old Korean man with end stage renal disease (ESRD) was transferred to our hospital. Review of kidney biopsy finding was consistent with chronic tubulointerstitial nephritis with oxalate crystal deposits and drug history revealed long-term exposure to Chaga mushroom powder due to intractable atopic dermatitis. We suspected the association between Chaga mushroom and oxalate nephropathy, and measured the oxalate content of remained Chaga mushroom. The Chaga mushroom had extremely high oxalate content (14.2/100 g). Estimated daily oxalate intake of our case was 2 times for four years and 5 times for one year higher than that of usual diet. Chaga mushroom is a potential risk factor of chronic kidney disease considering high oxalate content. Nephrologist should consider oxalate nephropathy in ESRD patients exposed to Chaga mushrooms.

Effects of Simulation-Based Education before Clinical Experience on Knowledge, Clinical Practice Anxiety, and Clinical Performance Ability in Nursing Students / 한국간호교육학회지

PURPOSE: This study aimed to examine the effects of simulation-based education on nursing knowledge, anxiety, and clinical performance ability in nursing students before their first clinical practice. METHODS: Third-year university students who had not yet entered their first clinical practice were recruited to participate in the study. Nineteen students formed the experimental group and participated in simulation-based education for 7 sessions. The 19 students in the control group were provided with clinical practice orientation in the form of traditional lectures. Outcome measures assessed nursing knowledge, clinical practice anxiety, and clinical performance ability. Data were collected before and immediately after the simulation-based education and after six weeks of clinical practice. RESULTS: Nursing knowledge and clinical anxiety were not statistically significant between the groups. However, there was a significant improvement in the clinical performance abilities of the experimental group. Among the subcategories, the ability to apply the nursing process and the ability to educate and cooperate were shown to maintain significant differences from the control group by the end of the six weeks of clinical practice. CONCLUSION: The simulation prior to nursing students’ first clinical practice could be useful to improve clinical performance ability. Nursing educators should consider building programs to reduce anxiety and improve performance ability through simulations.

Usefulness of valacyclovir prophylaxis for cytomegalovirus infection after anti-thymocyte globulin as rejection therapy

BACKGROUND/AIMS@#Anti-thymocyte globulin (ATG) treatment for acute T-cell mediated rejection (TCMR) can increase the risk of cytomegalovirus (CMV) infection. We aimed to evaluate the effect of valacyclovir prophylaxis against CMV infection after ATG administration as anti-rejection therapy.@*METHODS@#We retrospectively analyzed 55 kidney transplant recipients (KTRs) receiving ATG for steroid resistant TCMR. In all KTRs, we used intravenous ganciclovir during ATG injection. In 34 KTRs treated before July 2013, we performed preemptive therapy for CMV infection after ATG therapy. They were regarded as the historic control group (CONT). After July 2013, we used valacyclovir maintenance for 1 month after ATG therapy in 21 patients (VAL). The primary outcome was the incidence of CMV infection, and the secondary outcomes were subsequent acute rejection, and graft and patient outcome.@*RESULTS@#Valacyclovir prophylaxis significantly reduced the incidence of CMV infection (VAL, 9.6% vs. CONT, 67.6%; p < 0.001), and CMV-free survival rate was higher in the VAL group compared to the CONT group (p = 0.009). In the VAL group, two cases of CMV infection were limited to CMV viremia, but CMV disease or syndrome (n = 3) was detected in the CONT group. There was no difference in graft failure (CONT, 70.5% vs. VAL, 47.6%; p = 0.152), incidence of subsequent rejection after ATG treatment (CONT, 41.1% vs. VAL, 33.3%; p = 0.776), and graft or patient survival between the two groups. There were no major adverse events associated with valacyclovir prophylaxis.@*CONCLUSIONS@#In conclusion, valacyclovir prophylaxis is effective in the prevention of CMV infection after ATG treatment for steroid resistant TCMR.

Effects of Simulated Interdisciplinary Communication Training for Nursing Students on Self-confidence in Communication, Communication Behavior and Technical Skill Performance / 한국간호교육학회지

PURPOSE: Ineffective communication between healthcare professionals leads to medical errors and puts patients at risk of harm. The aim of this study was to examine the effects of interdisciplinary communication training in simulated settings on self-confidence in communication, observed communication behavior, and technical skill performances of nursing students. METHODS: A repeated measures design with one group was conducted. Data was collected from 92 nursing students through a self-administered questionnaire and an observed behavior checklist. Data analysis was performed using descriptive statistics, a paired t-test, the Wilcoxon signed rank test, the Friedmann test, a Repeated Measures ANOVA, and the Spearman correlation coefficient. RESULTS: Self-confidence in communication, observed Identification-Situation-Background-Assessment-Recommendation-Read Back communication behavior, and technical skill performances of nursing students were significantly improved. In observed communication behavior, the performance of Assessment and Read Back communication significantly improved. However, communication of Background, Assessment, and Recommendation did not improve to a satisfactory level. Observed communication behavior was not correlated with the overall technical skill performance. CONCLUSION: These results indicate that interdisciplinary communication training in simulated settings was effective in improving nursing students' confidence and communication skills with physicians. Longitudinal studies with larger samples are recommended in order to verify the effects of interdisciplinary communication training on clinical outcomes as well as communication competence.

Rare Concurrence of Triple Primary Thyroid Cancer: A Patient of Papillary Carcinoma, Follicular Carcinoma, and Primary Lymphoma of the Thyroid

We report a rare case of co-occurrence of papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC) and primary thyroid lymphoma. A 55-year-old woman presented with a large mass in left lobe of thyroid, biopsy confirmed diffuse large B-cell lymphoma. After 4 cycles of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisolone chemotherapy, positron emission tomography scan revealed markedly decreased in size, but still present. Repeated ultrasonography-guided gun biopsies of 2 lesions indicated Hurthle cell neoplasm. After total thyroidectomy and bilateral central lymph node dissection, residual hypermetabolic lesion of left lobe was determined to be FTC and right lower lesion to be nodular hyperplasia. Besides, a PTC was incidentally detected in left lobe. If there are multiple nodular lesions at diagnosis or there is insufficient response after 1st line chemotherapy for primary thyroid lymphoma, each lesion should be biopsied to confirm its pathological type.

Chemotherapy in Small Cell Lung Cancer with End-Stage Renal Disease on Hemodialysis / 이화의대지

Small cell lung cancer is primarily treated with chemotherapy. For patients with end-stage renal disease (ESRD), systemic chemotherapy is often challenging since renal excretion of chemotherapeutic agents might be decreased due to impaired renal function, leading to increased toxicity. No consensus is made so far regarding appropriate dosage and combination of chemotherapeutic agents for patients on hemodialysis. We report two cases of chemotherapy without significant toxicity in small cell lung cancer patients who were on hemodialysis for ESRD.

Recurrent Hypoglycemia Triggered by Sorafenib Therapy in a Patient with Hemangiopericytoma

Targeted therapy has been proven to be one of the most effective cancer treatments. However, some endocrine disorders can occur during treatment with targeted agents. We report the case of a patient who exhibited a wax and wane pattern of hypoglycemia that was attributed to sorafenib therapy. A 32-year-old woman with metastatic hemangiopericytoma visited the emergency department in a stuporous state. Nonhyperinsulinemic hypoglycemia was diagnosed, was exacerbated shortly after sorafenib therapy, and was improved by the cessation of sorafenib with additional glucocorticoid therapy. Patients with metastatic hemangiopericytoma should be carefully monitored with particular attention to hypoglycemia when sorafenib therapy is initiated.

Development of Nursing Practice Guidelines for Non-humidified Low Flow Oxygen Therapy by Nasal Cannula / 간호행정학회지

PURPOSE: The purpose of this study was to provide a basis for non-humidified low flow oxygen by nasal cannula and to provide a guide for consistent care in nursing practice. METHODS: A methodological study on the development of guidelines with experts' opinions on collected items, framing PICO questions, evaluating and synthesizing texts which were searched with the key words (low flow oxygen, nasal cannula, humidification of oxygen, guideline) from web search engines. RESULTS: Of the 45 researched texts on the web, 9 texts relevant to the theme were synthesized and evaluated. All patients with humidified or non-humidified oxygen therapy reported that they had no discomfort. CONCLUSION: The results indicate that there are no tangible grounds for patients' perceived differences between the humidified and non-humidified oxygen under 4L/min supplied by nasal cannula. with oxygen. Therefore, non-humidification oxygen therapy is strongly advised when suppling under 4L/min oxygen by nasal cannula (recommended grade A).