論文

This review article series on water and electrolyte disorders is based on the “Electrolyte Winter Seminar” that is held annually for young nephrologists in Japan. This seminar includes lively discussions based on cases, which have been partly included in this series as self-assessment questions. In this fourth article of the series, we have focused on the pathophysiology of potassium and the diagnosis of hyperkalemia. Hyperkalemia is associated with increased overall mortality, cardiovascular mortality, hospitalization, and progression to end-stage renal disease. Although most patients with hyperkalemia exhibit impaired kidney function, some exhibit normal kidney function. Therefore, accurately diagnosing the underlying cause of hyperkalemia is crucial for its appropriate management. In this review, we have first discussed the pathophysiology of potassium regulation. We have then highlighted the causes of hyperkalemia other than chronic kidney disease, including pseudohyperkalemia, which is often overlooked in clinical practice, and hypoaldosteronism, which can cause hyperkalemia even in patients with normal or mildly impaired kidney function. Finally, we have shared practical “Tips and Pearls” on hyperkalemia for clinicians that are applicable in daily practice.

This article is part of a review series on water and electrolyte disorders, based on the annual “Electrolyte Winter Seminar” for early-career nephrologists in Japan. The seminar features interactive case-based discussions, some of which are included as self-assessment questions. The fifth installment addresses the management of hyperkalemia. Hyperkalemia frequently occurs in patients with chronic kidney disease (CKD) and can become life-threatening when severe, necessitating prompt treatment regardless of its underlying cause. Renin–angiotensin system inhibitors (RASi) are a recognized risk factor for hyperkalemia in CKD; however, discontinuing RASi in response to elevated potassium levels may adversely affect patient outcomes. Although there are no formal criteria distinguishing acute from chronic hyperkalemia, symptoms presentation and potassium levels offer a practical guide for clinical management. This review covers standard treatment strategies for severe (symptomatic or acute) hyperkalemia in emergency and inpatient settings and discusses how to manage mild-to-moderate (asymptomatic or chronic) cases in CKD patients while continuing RASi therapy.

Aging is associated with metabolic dysfunction and cardiovascular abnormalities. Defective nicotinamide adenine dinucleotide (NAD+) biosynthesis correlates with aging and aging-associated complications. However, the precise molecular mechanisms linking aging-associated NAD+ deficiency to cardiometabolic dysfunction remain unclear. Herein, we examined whether nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in NAD+ biosynthesis, influences vascular endothelial function and whole-body metabolic and hemodynamic homeostasis during aging. Vascular endothelial cell–specific Nampt knockout (VeNKO) mice fed a regular chow diet exhibited no cardiometabolic abnormalities, whereas male VeNKO mice fed a high-fat diet exhibited reduced angiogenesis, resulting in impaired subcutaneous adipogenesis, impaired glucose metabolism, and hemodynamic disturbances. Mechanistically, NAMPT loss attenuated NAD+-dependent deacetylase sirtuin-1 (SIRT1) and endothelial nitric oxide synthase (eNOS) signaling, impairing angiogenesis. Aged mice exhibited endothelial NAD+ depletion driven by an imbalance between NAMPT-mediated NAD+ biosynthesis and consumption, leading to impaired eNOS signaling and associated angiogenic and cardiometabolic dysfunction, similar to that observed in VeNKO mice. Nicotinamide mononucleotide administration replenished vascular endothelial NAD+ levels, improved angiogenesis, restored subcutaneous adipose tissue volume, and ameliorated aging-associated cardiometabolic dysfunction. Collectively, our findings provide mechanistic and therapeutic insights into vascular endothelial NAMPT–NAD+–SIRT1–eNOS signaling related to aging-associated cardiometabolic disorders.

The “preconditioning effect” in AKI is a phenomenon in which an episode of ischemia-reperfusion results in tolerance to subsequent ischemia-reperfusion injury. However, its relationship between DNA damage repair has not been elucidated. Here, we show the role of KAT5 in the preconditioning effect. Preconditioning attenuated DNA damage in proximal tubular cells with elevated KAT5 expression. Ischemia-reperfusion (IR) injuries were exacerbated, and preconditioning effect vanished in proximal tubular-cell-specific KAT5 knockout mice. Investigation of tubuloglomerular feedback (TGF) by MALDI-IMS and urinary adenosine revealed that preconditioning caused attenuated TGF at least in part via KAT5. In addition, K-Cl cotransporter 3 (KCC3) expression decreased in damaged proximal tubular cells, which may be involved in accelerated TGF following IR. Furthermore, KAT5 induced KCC3 expression by maintaining chromatin accessibility and binding to the KCC3 promoter. These results suggest a novel mechanism of the preconditioning effect mediated by the promotion of DNA repair and attenuation of TGF through KAT5.

Hyperkalemia is a well-recognized electrolyte abnormality in patients with chronic kidney disease (CKD). Potassium binders are often used to prevent and treat hyperkalemia. However, few studies have evaluated the difference in serum potassium (K+) level-lowering effect during the post-acute phase between the novel potassium binder, sodium zirconium cyclosilicate (ZSC), and conventional agents. This retrospective study included patients who received potassium binders (either ZSC or calcium polystyrene sulfonate [CPS]) in our hospital between May 2020 and July 2022. The patients were divided into the ZSC and CPS groups. After propensity score matching, we compared changes from baseline to the first follow-up point, at least 4 weeks after initiating potassium binders, in electrolytes including K+ level between the two groups. Of the 132 patients, ZSC and CPS were administered in 48 and 84 patients, respectively. After matching, 38 patients were allocated to each group. The ZSC group showed greater reduction in K+ levels than did the CPS group (P < 0.05). Moreover, a significant increase in serum sodium minus chloride levels, a surrogate marker for metabolic acidosis, was observed in the ZSC group (P < 0.05). Our results demonstrated that ZSC could potentially improve hyperkalemia and metabolic acidosis in patients with CKD.

The common histopathology of antineutrophil cytoplasmic antibody-associated vasculitis comprises pauci-immune crescentic glomerulonephritis with concomitant tubulointerstitial nephritis. Tubulointerstitial nephritis in the absence of glomerular involvement in patients with antineutrophil cytoplasmic antibody-associated vasculitis is uncommon. We report a case of antineutrophil cytoplasmic antibody-associated vasculitis-associated acute kidney injury manifesting as tubulointerstitial nephritis without glomerulonephritis. A 75-year-old woman with fever, cough, and myalgia developed kidney dysfunction with inflammatory reactions and tubular-type proteinuria, without glomerular hematuria. A kidney biopsy revealed tubulointerstitial nephritis with arteritis. We ruled out important underlying etiologies of tubulointerstitial nephritis, including infection, drug reactions, and autoimmune diseases. Since chest high-resolution computed tomography demonstrated mild interstitial pneumonia in bilateral lower lung fields, myeloperoxidase antineutrophil cytoplasmic antibody was measured and found to be positive. Therefore, we diagnosed the patient with antineutrophil cytoplasmic antibody-associated vasculitis-associated tubulointerstitial nephritis but not glomerulonephritis, and interstitial pneumonia. The patient’s kidney function and symptoms markedly improved with prednisolone treatment. Clinicians should maintain high-level vigilance for antineutrophil cytoplasmic antibody-associated vasculitis as a possible underlying component of tubulointerstitial nephritis, particularly when kidney function deteriorates with tubulointerstitial injuries without glomerular features.

Chronic kidney disease (CKD) is associated with multiple complications, with recent scholarly attention underscoring cognitive impairment as a salient manifestation. Considering societal aging, preserving cognitive function has emerged as an urgent medical concern. Prolonged dialysis, encompassing hemodialysis (HD) and peritoneal dialysis (PD), has been associated with a decline in cognitive function. Here, we present the cases of three patients undergoing PD who exhibited a noticeable improvement in cognitive function upon the initiation of HD. One patient had exhibited mild cognitive decline, whereas the remaining two presented more severe impairment. Apart from a mild tendency for fluid retention, none of the three patients exhibited abnormalities in physical or imaging examinations. Evaluation using the Japanese version of the Montreal Cognitive Assessment (MoCA-J) yielded decreased scores across multiple domains, notably in executive and attention functions. However, after HD initiation, all patients demonstrated a marked enhancement in multiple MoCA-J parameters, accompanied by a significant improvement in subjective symptoms. Moreover, improvements in anemia and hypoalbuminemia were observed in all three patients, whereas consistent trends in other parameters were absent. These clinical observations suggest that the integration of HD into the therapeutic regimen of patients undergoing PD may enhance cognitive function, highlighting the contributory roles of hemoglobin and albumin in CKD-associated cognitive impairment.

Purpose: In 2021, we introduced a new simulation-based learning program focusing on a roleplay conference before patient discharge. This study aimed to evaluate the program’s effectiveness and highlight the significance of cross-training in interprofessional education (IPE). Methods: In September 2023, the program included 346 students (98 medical, 110 nursing, and 138 pharmacy students). The students’ reflective writing was analyzed using inductive content analysis to describe their learning and perspectives. The original items, subcategories, and main categories were extracted. The simulation involved the students role-playing various healthcare professionals during a discharge-planning conference for a stroke patient. This allowed them to experience the challenges and dynamics of interprofessional collaboration. Results: Student feedback emphasized the importance of understanding what constitutes a good healthcare team. A total of 203 items were grouped into eight main categories and 17 subcategories, including patient-centered care (related to the importance of patient-centered care, supporting patient decision-making, communicating with patients during conferences, and facilitating decision-making processes), contrasts in patient and interprofessional communication, conference communication (challenge of building consensus, the way to proceed conferences, importance of conference preparation, and process of information aggregation and realization of outcomes), mutual recognition and role contribution, building relationships (importance of daily interprofessional communication), understanding one’s profession (reflection on one’s own profession, understanding the roles of different professions, and communication within one’s own professional context), recursion into learning (motivation for continuous learning and improvement), and understanding other professions (understanding the role and perspectives of other professions and recognizing professional differences). Specific feedback highlighted improved empathy and communication skills. Students recognized the value of each profession’s contribution to patient care. Moreover, students reported a deeper appreciation of patient-centered approaches and the complexities of coordinating care across different healthcare roles. Conclusion: Simulated interprofessional team conferences using cross-training effectively taught junior students to understand the essence of a good healthcare team and the importance of a patient-centered approach. Cross-training significantly enhanced students’ interprofessional competencies, communication skills, and empathy toward other professions. This case underscores the necessity of incorporating cross-training into IPE to prepare healthcare professionals for collaborative practice and improve patient outcomes. Future research should consider expanding the scope to include more diverse scenarios and longitudinal assessments to measure longterm impacts on professional practice.

Introduction: Peritonitis is a common and serious complication of peritoneal dialysis (PD) that leads to its discontinuation and death. Icodextrin (ICO) improves peritoneal ultrafiltration and its early use reduces mortality. However, its effectiveness in reducing PD-associated infections remains to be elucidated. Methods: This retrospective observational study enrolled patients who underwent PD between September 2011 and March 2020. The patients were classified into two groups: those who received ICO at the initiation of PD therapy (early ICO) and those who received ICO later or not at all (late/no ICO) and were followed up from PD induction until PD cessation, death, or 3 years had passed. Results: Of the 82 patients (age, 61 [53–72] years), 21 received early ICO. During follow-up (36 [14–36] months), the incidence of PD-associated peritonitis was 0.17 episodes per patient-year. Log-rank tests indicated that PD-associated peritonitis and tunnel infection (TI)-free survival rates were significantly better with the early use of ICO than with late/no ICO (p = 0.02 and p = 0.01, respectively). The early use of ICO remained significantly associated with decreased incidence of both peritonitis and TI (hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.06–0.69 and HR, 0.10; 95% CI, 0.01–0.78, respectively) using Cox regression analysis adjusted for potential confounders. Conclusion: Beginning ICO administration at the initiation of PD shows promise for mitigating the risks of PD-associated peritonitis and TI.

This review article series on water and electrolyte disorders is based on the 'Electrolyte Winter Seminar' held annually for young nephrologists in Japan. The seminar includes lively discussions based on cases, which are also partly included in this series as self-assessment questions. The first article in this series focuses on pathophysiology, symptoms, outcomes, and evaluation of hyponatremia, a common water and electrolyte disorder in clinical practice. Diagnosing the root cause(s) of hyponatremia can be challenging due to various etiologies and co-morbidities that affect water and electrolyte homeostasis, which can result in inappropriate management and worse outcomes in acute and chronic hyponatremia. This review provides an overview of pathophysiology, symptoms, outcomes, and evaluation of hyponatremia for better comprehension and improved clinical practice.

Mitochondrial diseases (MDs) are inherited metabolic disorders that affect multiple organ systems, including the kidneys. Variability in disease onset and phenotypic expression, combined with the absence of specific kidney pathological findings, pose significant challenges in diagnosing MD. Consequently, many undiagnosed cases of MD may exist among patients undergoing dialysis. No effective treatment for mitochondrial nephropathy has been established. We report the case of a 27-year-old female patient who presented with leg edema, nephrotic range proteinuria attributed to focal segmental glomerulosclerosis, and bilateral sensorineural hearing loss. Immunosuppressive therapy failed to achieve remission, resulting in progressive kidney function decline and eventual end-stage kidney disease. At hemodialysis initiation, worsening atypical cardiac function and hypertrophy prompted genetic testing, which identified an MT-TL1 m.3243 A > G mutation and confirmed the diagnosis of MD. After hemodialysis initiation, the patient experienced persistent fatigue and decreased physical activity levels despite dry weight management. Suspected stroke-like symptoms prompted the initiation of taurine supplementation, which significantly improved headache severity, cardiac function, and physical activity levels. This case highlights the therapeutic potential of taurine supplementation in patients with MD undergoing dialysis and the importance of maintaining clinical vigilance for MD across all stages of chronic kidney disease, even without characteristic renal pathological findings of mitochondrial nephropathy.

This review article series on water and electrolyte disorders is based on the ‘Electrolyte Winter Seminar’ held annually for young nephrologists in Japan. The seminar features dynamic case-based discussions, some of which are included as self-assessment questions in this series. The second article in this series focuses on treatment of hyponatremia, a common water and electrolyte disorder frequently encountered in clinical practice. Hyponatremia presents diagnostic challenges due to its various etiologies and the presence of co-morbidities that affect water and electrolyte homeostasis. Furthermore, limited evidence, including a lack of robust randomized controlled trials, complicates treatment decisions and increases the risk of poor outcomes from inappropriate management of both acute and chronic hyponatremia. This review provides a comprehensive overview of treatment of hyponatremia for better comprehension and improved clinical practice.

This review article series on water and electrolyte disorders is based on the ‘Electrolyte Winter Seminar’ held annually for young nephrologists in Japan. This is the third article in this series that focuses on water and electrolyte disturbances caused by novel pharmacological agents for kidney disease and cancer. The advent of novel pharmacological agents in cardiorenal medicine and oncology has introduced both therapeutic benefits and challenges in managing medication-induced water and electrolyte disturbances. These medications, including sodium–glucose cotransporter-2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (ns-MRAs), and immune checkpoint inhibitors (ICIs), significantly impact water and electrolyte homeostasis. SGLT2 inhibitors used widely in diabetes mellitus, heart failure, and chronic kidney disease mitigate hyperkalemia and hypomagnesemia but increase the risk of hypernatremia in patients on fluid restriction. Conversely, they are beneficial for managing hyponatremia in the syndrome of inappropriate antidiuresis (SIAD). ns-MRAs, prescribed for diabetic kidney disease, exhibit a high risk of hyperkalemia, particularly when combined with renin–angiotensin system inhibitors. ICIs, a breakthrough in oncology, frequently induce hyponatremia through immune-related adverse events, such as hypophysitis and non-immune-related adverse events like SIAD. Understanding the pathophysiology of these disturbances and implementing timely interventions, including hormone replacement and water and electrolyte management, is critical for optimizing treatment outcomes.

Background: The use of simulated patients (SPs) to assess medical students’ clinical performance is gaining prominence, underscored by patient safety perspective. However, few reports have investigated the validity of such assessment. Here, we examined the validity and reliability of an assessment tool that serves as a standardized tool for SPs to assess medical students’ medical interview. Methods: This longitudinal survey was conducted at Keio University School of Medicine in Japan from 2014 to 2021. To establish content validity, the simulated patient assessment tool (SPAT) was developed by several medical education specialists from 2008 to 2013. A cohort of 36 SPs assessed the performance of 831 medical students in clinical practice medical interview sessions from April 2014 to December 2021. The assessment’s internal structure was analyzed using descriptive statistics (maximum, minimum, median, mean, and standard deviation) for the SPAT’s 13 item total scores. Structural validity was examined with exploratory factor analysis, and internal consistency with Cronbach’s alpha coefficients. The mean SPAT total scores across different SPs and scenarios were compared using one way analysis of variance (ANOVA). Convergent validity was determined by correlating SPAT with the post-clinical clerkship obstructive structured clinical examination (post-CC OSCE) total scores using Pearson’s correlation coefficient. Results: Of the 831 assessment sheets, 36 with missing values were excluded, leaving 795 for analysis. Thirty-five SPs, excluding one SP who quit in 2014, completed 795 assessments, for a response rate of 95.6%. Exploratory factor analysis revealed two factors, communication and physician performance. The overall Cronbach’s alpha coefficient was 0.929. Significant differences in SPAT total scores were observed across SPs and scenarios via one-way ANOVA. A moderate correlation (r =.212, p <.05) was found between SPAT and post-CC OSCE total scores, indicating convergent validity. Conclusions: Evidence for the validity of SPAT was examined. These findings may be useful in the standardization of SP assessment of the scenario-based clinical performance of medical students.

Background: Exit-site infection (ESI) is a common recurring complication in patients undergoing peritoneal dialysis (PD). Sucrose and povidone–iodine (SPI) mixtures, antimicrobial ointments that promote wound healing, have been used for the treatment of ulcers and burns, but their efficacy in exit–site care is still unclear. Methods: This single-center retrospective observational study included patients who underwent PD between May 2010 and June 2022 and presented with episodes of ESI. Patients were divided into SPI and non-SPI groups and followed up from initial ESI onset until PD cessation, death, transfer to another facility, or June 2023. Results: Among the 82 patients (mean age 62, [54–72] years), 23 were treated with SPI. The median follow-up duration was 39 months (range, 14–64), with an overall ESI incidence of 0.70 episodes per patient-year. Additionally, 43.1% of second and 25.6% of third ESI were caused by the same pathogen as the first. The log-rank test demonstrated significantly better second and third ESI-free survival in the SPI group than that in the non-SPI group (p < 0.01 and p < 0.01, respectively). In a Cox regression analysis, adjusting for potential confounders, SPI use was a significant predictor of decreased second and third ESI episodes (hazard ratio [HR], 0.22; 95% confidence interval [CI], 0.10–0.52 and HR, 0.22; 95%CI, 0.07–0.73, respectively). Conclusions: Our results showed that the use of SPI may be a promising option for preventing the incidence of ESI in patients with PD. Trial registration: This study was approved by the Keio University School of Medicine Ethics Committee (approval number 20231078) on August 28, 2023. Retrospectively registered.

In this study, we developed and validated the Clinical Student Version of the Japanese Interprofessional Competency Self-Assessment Scale (C-JASSIC) for healthcare students in their clinical practice phase. Data obtained from 331 students (medical, 98; nursing, 99; pharmacy, 134) during orientation for interprofessional education (pre-IPE) and from 319 students (medical, 94; nursing, 93; pharmacy, 132) within a week following IPE (post-IPE) were analyzed. Exploratory pre-IPE and Confirmatory post-IPE factor analyses revealed a consistent 6-factor structure aligning with the Japanese Interprofessional Competency domains. The scale exhibited strong internal consistency, with Cronbach’s α values exceeding 0.8 for all factors both pre- and post-IPE. Scores for overall competency and individual domains increased post-IPE in 234 matched cases. A notable significant pre vs post difference concerned “Understanding of Others,” indicating enhanced interprofessional comprehension after clinical practice. There was a weak but significant positive correlation between IPE satisfaction and difference in pre- and post-IPE scores. However, no significant differences were observed among medical, nursing, and pharmacy students. Despite its strengths, such as its competency-based design and cultural relevance to Japan, a limitation of the study may be potential self-reporting bias. Nonetheless, C-JASSIC represents a valuable tool for seamless competency evaluations from student to professional stages, with implications for broader Asian contexts.

Background: In the enhancement of allergy care involving multidisciplinary and multiple medical departments, there is a perceived need for education that targets not only specialists but also non-specialists. However, research on the need for and methods of such education remains inadequate. Objective: To design a remote allergy care education program for all medical practitioners and to validate its necessity and utility. Methods: The Empowering Next Generation Allergist/immunologist toward Global Excellence Task Force (ENGAGE-TF), supported by the Japanese Society of Allergology, initiated a virtual educational program called 'Outreach Lectures' in collaboration with Keio University and Fukui University. This initiative was widely promoted through social media and various institutions, and a survey was conducted through its mailing list. Results: 1139 responses were obtained. More than half were physicians from non-allergy specialties, representing a diverse range of healthcare professions. Over 70% expressed being 'very satisfied, ' and over 60% found the difficulty level 'appropriate. ' Free-form feedback revealed differences in learning focus based on profession and learning approach based on years of experience. Conclusion: The high participation rate (90%) of non-specialist physicians underscores the demand for addressing allergic conditions in primary care. The effectiveness of virtual/recurrent education, particularly for healthcare professionals with over 11 years of experience, was implied. Further follow-up investigation focusing on quantitative and objective assessment of educational effectiveness is indispensable.

IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis worldwide and leads to end-stage kidney disease. The proteinuria selectivity index (PSI) has been used to assess the prognosis in nephrotic syndrome, but its predictive value in patients with IgAN remains unclear. This single-center retrospective cohort study included patients who diagnosed with IgAN between March 2012 and March 2020. The PSI was calculated at the time of kidney biopsy. Patients were followed up from the time of kidney biopsy to kidney replacement therapy, death, transfer to another facility, or study completion. Ninety-four patients with a median age of 51 years were enrolled and divided according to the cutoff value of PSI determined by the receiver operating characteristic curve analysis into low-PSI (PSI <0.243, n = 39) and high-PSI groups (PSI ≥0.243, n = 55). The median follow-up duration was 70 months. Rates of remission of proteinuria and survival without a two-fold increase in serum creatinine were significantly better in the low-PSI group (both p < 0.01, log-rank test). Cox regression analysis showed that a low PSI was significantly associated with an increased likelihood of remission of proteinuria and hematuria (hazard ratio [HR] 1.96; 95% confidence interval [CI] 1.02–3.85 and HR 1.75; 95% CI 1.01–3.13, respectively), and a decreased risk of a two-fold increase in serum creatinine (HR 0.10; 95% CI 0.01–0.81). In conclusion, The PSI could have the potential to support the assessment of the prognosis of IgAN, in addition to established prognostic markers, by reflecting the overall glomerular permeability.

Idiopathic multicentric Castleman disease (iMCD) is a systemic and polyclonal lymphoproliferative disease involving multiple organs, including the kidneys, due to the overproduction of interleukin-6 (IL-6). Recently, several reports have suggested that excessive IL-6 actions in iMCD could have a causal relationship with the development of diverse histopathological renal manifestations that cause nephrotic syndrome. However, the treatment for such cases remains unclear. We report a series of three cases of nephrotic syndrome due to iMCD that helps to delineate the importance of early and continuous therapy with the anti-interleukin-6 receptor antibody tocilizumab. First, treatment was suspended for infectious control, and the patient presented with nephrotic syndrome due to diffuse mesangial and endocapillary hypercellularity without immune deposits complicating acute kidney injury. Second, iMCD was treated with prednisolone alone. The patient suddenly developed nephrotic syndrome due to immune-complex glomerulonephritis, not otherwise specified, complicated with acute kidney injury. In the third case, nephrotic syndrome secondary to membranous glomerulonephritis was diagnosed, with a skin rash and IgE antibodies to tocilizumab, and was therefore treated with prednisolone alone. In contrast to the first two cases, the third progressed to end-stage renal disease on hemodialysis. Taken together, this series suggests that clinicians should maintain clinical vigilance for iMCD as a possible underlying component of nephrotic syndrome, since iMCD presents with a variety of renal pathologies. Prompt initiation and continuous administration of tocilizumab are likely key determinants of renal outcomes in such cases. In particular, when tocilizumab is suspended due to infection or in the perioperative period, consideration of its expeditious resumption should be made, taking into account both the withdrawal period and systemic conditions.

© 2019, The Author(s). The derivation of kidney tissues from human pluripotent stem cells (hPSCs) and its application for replacement therapy in end-stage renal disease have been widely discussed. Here we report that consecutive transfections of two sets of synthetic mRNAs encoding transcription factors can induce rapid and efficient differentiation of hPSCs into kidney tissues, termed induced nephron-like organoids (iNephLOs). The first set - FIGLA, PITX2, ASCL1 and TFAP2C, differentiated hPSCs into SIX2+SALL1+ nephron progenitor cells with 92% efficiency within 2 days. Subsequently, the second set - HNF1A, GATA3, GATA1 and EMX2, differentiated these cells into PAX8+LHX1+ pretubular aggregates in another 2 days. Further culture in both 2-dimensional and 3-dimensional conditions produced iNephLOs containing cells characterized as podocytes, proximal tubules, and distal tubules in an additional 10 days. Global gene expression profiles showed similarities between iNephLOs and the human adult kidney, suggesting possible uses of iNephLOs as in vitro models for kidneys.