Perspectives on the optimal timing of advance care planning among Japanese patients undergoing dialysis and clinicians: a cross-sectional study.

KEY MESSAGES: The majority of dialysis patients and clinicians favor early advance care planning in our sample. Yet, there is a disconnect: only 11% of patients discussed future care with their clinicians. Our findings indicate Japanese dialysis patients and clinicians support proactive advance care planning at or before dialysis initiation. BACKGROUND: Little is known about the optimal timing of discussions about advance care planning among dialysis patients and clinicians engaged in dialysis care. We aimed to explore the preferred timing for advance care planning and assess actual participation in advance care planning among dialysis patients and their clinicians. METHODS: A scenario-based survey on Japanese patients aged ≥65 years on dialysis and clinicians involved in their dialysis care was performed. Participants were asked if they would feel prepared to engage in advance care planning with their clinicians, offering a choice among four hypothetical stages within the illness trajectory, extending from the initiation of dialysis to a later phase characterized by the patient's extreme frailty. RESULTS: Overall, 181 patients and 128 clinicians participated in the study. Among these, 131 (72%) patients, and 84 (66%) clinicians indicated that they would prefer to initiate advance care planning around the time of dialysis initiation. Only 20 patients (11%) indicated that they had participated in advance care planning with at least one clinician, including 11 (6%) who indicated that they had discussed their preferences around life-sustaining treatments and 8 (4%) who had discussed their preferences around dialysis continuation. CONCLUSIONS: While fewer than 11% of patients undergoing dialysis and their clinicians enrolled in our study had participated in advance care planning, most indicated that they would be comfortable initiating the discussion around the time of dialysis initiation. These findings suggest untapped opportunities to engage patients in advance care planning early in the course of their dialysis.

Development and validation of a machine learning model to predict time to renal replacement therapy in patients with chronic kidney disease.

BACKGROUND: Predicting time to renal replacement therapy (RRT) is important in patients at high risk for end-stage kidney disease. We developed and validated machine learning models for predicting the time to RRT and compared its accuracy with conventional prediction methods that uses the rate of estimated glomerular filtration rate (eGFR) decline. METHODS: Data of adult chronic kidney disease (CKD) patients who underwent hemodialysis at Oita University Hospital from April 2016 to March 2021 were extracted from electronic medical records (N = 135). A new machine learning predictor was compared with the established prediction method that uses the eGFR decline rate and the accuracy of the prediction models was determined using the coefficient of determination (R2). The data were preprocessed and split into training and validation datasets. We created multiple machine learning models using the training data and evaluated their accuracy using validation data. Furthermore, we predicted the time to RRT using a conventional prediction method that uses the eGFR decline rate for patients who had measured eGFR three or more times in two years and evaluated its accuracy. RESULTS: The least absolute shrinkage and selection operator regression model exhibited moderate accuracy with an R2 of 0.60. By contrast, the conventional prediction method was found to be extremely low with an R2 of -17.1. CONCLUSIONS: The significance of this study is that it shows that machine learning can predict time to RRT moderately well with continuous values from data at a single time point. This approach outperforms the conventional prediction method that uses eGFR time series data and presents new avenues for CKD treatment.

Effect of Low-Density Lipoprotein Apheresis on Quality of Life in Patients with Diabetes, Proteinuria, and Hypercholesterolemia.

INTRODUCTION: Treating diabetic nephropathy with low-density lipoprotein (LDL) apheresis reduces proteinuria and improves prognosis. However, its impact on patients' quality of life (QoL) is unclear. This study evaluated the effect of LDL apheresis on QoL in patients with diabetes, proteinuria, and hypercholesterolemia. METHODS: In this nationwide multicenter prospective study, we enrolled 40 patients with diabetes. Inclusion criteria were proteinuria (defined as an albumin/creatinine ratio ≥3 g/g), serum creatinine levels <2 mg/dL, and serum LDL ≥120 mg/dL despite drug treatment. LDL apheresis was performed 6-12 times within 12 weeks. The 36-item Short Form Health Survey (SF-36) was used to analyze QoL. RESULTS: The study enrolled 35 patients (27 men and 8 women; mean age 58.9 ± 11.9 years). A comparison of baseline SF-36 values with those at the end of the course of apheresis found an improvement in the mean physical component summary (37.9 ± 11.4 vs. 40.6 ± 10.5, p = 0.051) and a significant increase in the mean mental component summary (MCS) (49.4 ± 8.4 vs. 52.5 ± 10.9, p = 0.026). A multivariable linear regression analysis revealed a history of coronary heart disease negatively correlated with the MCS increase at the end of the course of apheresis (ß coefficient -6.935, 95% confidence interval, 13.313 to-0.556, p = 0.034). CONCLUSION: Our results suggest that LDL apheresis may improve the mental and physical QoL in patients with diabetes, proteinuria, and hypercholesterolemia.

A Parkinson's disease patient displaying increased neuromelanin-sensitive areas in the substantia nigra after rehabilitation with tDCS: a case report.

Previous studies have reported that transcranial direct current stimulation (tDCS) of the frontal polar area (FPA) ameliorated motor disability in patients with Parkinson's disease (PD). Here we report changes in neuromelanin (NM) imaging of dopaminergic neurons before and after rehabilitation combined with anodal tDCS over the FPA for 2 weeks in a PD patient. After the intervention, the patient showed clinically meaningful improvements while the NM-sensitive area in the SN increased by 18.8%. This case study is the first report of NM imaging of the SN in a PD patient who received tDCS.Abbreviations FPA: front polar area; PD: Parkinson's disease; NM: neuromelanin; DCI: DOPA decarboxylase inhibitor; STEF: simple test for evaluating hand function; TUG: timed up and go test; TMT: trail-making test; SN: substantia nigra; NM-MRI: neuromelanin magnetic resonance imaging; MCID: the minimal clinically important difference; SNpc: substantia nigra pars compacta; VTA: ventral tegmental area; LC: locus coeruleus; PFC: prefrontal cortex; M1: primary motor cortex; MDS: Movement Disorder Society; MIBG: 123I-metaiodobenzylguanidine; SBR: specific binding ratio; SPECT: single-photon emission computed tomography; DAT: dopamine transporter; NIBS: noninvasive brain stimulation; tDCS: transcranial direct current stimulation; MAOB: monoamine oxidase B; DCI: decarboxylase inhibitor; repetitive transcranial magnetic stimulation: rTMS; diffusion tensor imaging: DTI; arterial spin labeling: ASL.

Effects of LDL apheresis on proteinuria in patients with diabetes mellitus, severe proteinuria, and dyslipidemia.

BACKGROUND: Patients with diabetes mellitus and severe proteinuria present with poor renal prognoses, despite improvements in diabetes and kidney disease therapies. In this study, we designed a low-density lipoprotein (LDL)-cholesterol apheresis treatment for patients with diabetic nephropathy (DN)/diabetic kidney disease and severe proteinuria. This was a multicenter prospective LICENSE study to confirm the impact of LDL apheresis on proteinuria that exhibited hyporesponsiveness to treatment. In addition, we sought to determine the efficacy and safety of LDL apheresis by comparing the outcomes to those of historical controls in patients with diabetes, refractory hypercholesterolemia, and severe proteinuria. METHODS: This was a prospective, multicenter study, including 40 patients with diabetes, severe proteinuria, and dyslipidemia. LDL apheresis was performed 6-12 times over a 12-week period. The primary endpoint was the proportion of patients with a decrease in proteinuria excretion of at least 30% in the 6 months after starting therapy. The secondary endpoints included serum creatinine levels and laboratory variables, which were evaluated 4, 6, 12, 18, and 24 months after therapy initiation. RESULTS: LDL apheresis was performed on 40 registered patients with diabetes. The proportion of cases in which proteinuria decreased by 30% or more after 6 months of LDL apheresis was 25%, which was similar to that of historical controls. The overall survival and end-stage kidney disease-free survival rates were significantly higher in the LICENSE group compared to those in historical controls. CONCLUSION: Our results suggest that LDL apheresis may be effective and safe for patients with diabetes, proteinuria, and dyslipidemia. TRIAL REGISTRATION: Trial registration number: jRCTs042180076.

A questionnaire on prescription patterns of proton pump inhibitors for hemodialysis patients in Japan.

BACKGROUND: Proton pump inhibitors (PPIs) are widely used in the general population often without an endpoint. The practice of prescribing PPIs in the hemodialysis (HD) population is unknown. Thus, we aimed to identify the practice pattern related to PPI prescription for HD patients in Japan through a questionnaire survey. METHODS: We conducted a questionnaire survey for physicians engaged in dialysis practice through email. An email was sent to physicians listed in the Japanese Society of Nephrology (JSN) and iHOPE International registry. RESULTS: We received 187 physicians' answers. One-hundred twelve (60%) physicians would prefer to continuously prescribe PPIs after 8 weeks of treatment for peptic ulcer (PU) or gastroesophageal reflux disease (GERD). The main reason for continuous PPI prescription was the concern for recurrence of PU or GERD. Approximately 20% of physicians responded that they were not accustomed to de-prescribing PPIs for PU or GERD. The reason for PPI de-prescription was the concern for side effects or insurance adaptation period. Even in cases wherein PPIs were prescribed for uncertain reasons, 42% physicians would continuously prescribe PPIs. Most physicians (82%) who answered about stopping PPIs regarded HD patients as a high-risk group for PU. CONCLUSIONS: PPI prescription is often continued in HD patients. De-prescription is not a common practice in Japan. It remains unclear whether discontinuation of PPIs should be recommended in hemodialysis patients who have a high risk of gastrointestinal ulcer. Yet, considering the side effects and polypharmacy in the HD population, more discussions on preferable de-prescription of PPIs are needed.

Rationale and study design of a clinical trial to assess the effects of LDL apheresis on proteinuria in diabetic patients with severe proteinuria and dyslipidemia.

BACKGROUND: Diabetic nephropathy is a leading cause of end-stage kidney disease in the world. Although various types of treatment for diabetes, hypertension and dyslipidemia have improved prognosis and quality of life in patients with diabetic nephropathy, there still exist some diabetic patients with severe proteinuria showing poor prognosis. This clinical trial, LICENSE, aims to confirm the impact of LDL apheresis on proteinuria exhibiting hyporesponsiveness to treatment. METHODS: This ongoing trial is a multicenter, prospective study of diabetic patients with severe proteinuria. The objective is to examine the impact of LDL apheresis on proteinuria in patients with diabetic nephropathy. The other subject is to investigate safety of LDL apheresis in these patients. RESULTS: The subjects consist of diabetic patients with serum creatinine (Cr) levels below 2 mg/dL who present severe proteinuria above 3 g/g Cr or 3 g/day and LDL cholesterol above 120 mg/dL. The target number of registered patients will be 35 patients. Urinary protein excretion and renal function will be observed for 24 weeks after the treatment of LDL apheresis. CONCLUSION: This study will determine the effectiveness and safety of LDL apheresis for diabetic nephropathy patients with severe proteinuria and dyslipidemia.

[A case of hemangioma at the left renal papilla of the calix with anemia and gross hematuria].

An 18-year-old man was admitted to our hospital due to gross hematuria and proteinuria after a marathon race. Contrast-enhanced CT showed no remarkable findings. His gross hematuria and proteinuria disappeared with- out treatment. One year later, he was admitted to our hospital due to reburrent gross hematuria and anemia (serum hemoglobin level of 8.0 g/dL). Both contrast-enhanced CT and renal arteriography revealed no remarkable find- ings; however, cystoscopy showed that his hematuria came from the left ureteral orifice. Ureteroscopy revealed hemorrhage from a large hemangioma at the left renal papilla of the calix. He presented with intermittent gross hematuria, proteinuria, and hypocomplimentemia, suggesting the possibility of glomerulonephritis. His gross hematuria and proteinuria improved after laser coagulation was performed.

Significance of tonsillectomy combined with steroid pulse therapy for IgA nephropathy with mild proteinuria.

BACKGROUND: Medical intervention for patients with IgA nephropathy and mild proteinuria (<1.0 g/day) is controversial, and the effectiveness of tonsillectomy plus steroid pulse therapy (TSP) for such patients remains obscure. METHODS: Among 323 patients in our multicenter cohort study, 79 who had mild proteinuria (0.4-1.0 g/day) at diagnosis were eligible to participate in this study. We compared the clinicopathological findings at diagnosis, a decline in renal function defined as a 50 or 100% increase in serum creatinine (sCr) and clinical remission (CR) defined as the disappearance of hematuria and proteinuria (<0.3 g/day) among groups given TSP (n = 46), steroid therapy (ST) (n = 9), and non-ST (n = 24). Factors contributing to CR were also evaluated using multivariate analysis. RESULTS: Background factors at diagnosis including age, ratio (%) of patients with hypertension, sCr, proteinuria, and histological severity did not significantly differ among the groups. Only two patients each in the TSP (4.3%) and non-ST (8.3%) groups achieved a 50% increase in sCr during a mean follow-up period of 4.7 years. At the final observation, 71.7, 44.4, and 41.7% of patients in the TSP, ST, and non-ST groups, respectively, achieved CR (p = 0.032). Cox proportional hazards models revealed that TSP led to CR more effectively than non-TSP by a factor of about threefold (hazard ratio, 2.74; p = 0.008). CONCLUSION: TSP therapy has potential for inducing CR in patients with IgAN and mild proteinuria (<1.0 g/day).

Histological classification of Japanese IgA nephropathy with a small number of glomeruli using Bayes' theorem.

In Japan an original pathological classification of IgA nephropathy was used, while Oxford classification of IgA nephropathy was used globally. The Oxford classification requires ≥ 8 glomeruli while the Japanese classification requires ≥ 10. Ninety-nine patients diagnosed with IgA nephropathy were included. To determine the accuracy of histological staging, we calculated the posterior probability using Bayes' theorem and adopted three model of prior distribution. First, the actual staging distribution was reclassified using the beta distribution (reclassified distribution). Second a model with the same distribution (actual distribution) as the actual staging was used. Third, a model assuming that all cases are equally distributed (equal distribution) was used. The median number of collected glomeruli was 12 (8-19). There were 33 cases (33%) wherein the glomerular count was ≤ 9. When only cases with ≥ 10 glomeruli were included, the median posterior probability was 91% (74-99) (actual distribution, 90% [74-98]; equal distribution, 85% [73-96]). Even among the 33 cases with ≤ 9 glomeruli, there were approximately 7 cases in which the posterior probability was ≥ 90% for each model. Using Bayesian probabilistic analysis, it was possible to evaluate the histologic classification of IgA nephropathy, even when the number of obtained glomeruli was ≤ 9.

A Questionnaire Survey of Prescription Preferences and Leftover Medication Conversations: Comparisons Among Kidney Disease Patients and Healthcare Professionals.

BACKGROUND: Patients with chronic kidney disease (CKD) and patients with kidney failure receiving hemodialysis (HD) receive various types of medications. However, little is known about the differences in medication preference and how to deal with leftover medication among CKD patients and HD patients. The purpose of this study was to investigate the differences in medication preference and ways of dealing with leftover medication between CKD patients, HD patients, physicians, and pharmacists via a questionnaire survey. METHODS: The ethics committee of Oita University, Oita, Japan, approved this survey. Outpatients undergoing treatment by a nephrologist in four facilities in Oita prefecture, Japan, were asked to answer a questionnaire on their preference for medication and how to deal with leftover medication. Respondents gave their informed written consent. The same questionnaire was administered to nephrologists and pharmacists online. RESULTS: In this survey, 383 patients (260 patients with CKD and 123 patients with HD), 22 nephrologists, and 28 pharmacists responded. The response rate of valid responses was more than 90% for each of the groups. In particular, 41% of patients with CKD and 56% of patients with HD never inform their doctor about leftover medication or only inform them when there is a lot of leftover medication. On the other hand, 23% of physicians have never asked their patients about them. Ordinary logistic regression analysis indicated that there is no significant relationship between how often patients talk about leftover medication, patients' preferences, or patient states. CONCLUSIONS: Despite the age and state of the patients, it is important to discuss the perception of medication with each other and confirm the condition of the remaining medication to improve concordance and obtain the desired treatment effect.

Nephrotic Syndrome Associated with Buerger's Disease.

We herein report a 43-year-old woman with Buerger's disease who presented with nephrotic syndrome, renal dysfunction, and mild hypertension. A kidney biopsy revealed focal segmental glomerulosclerosis (FSGS), but there were no findings associated with frequent secondary FSGS or a history of long-term hypertension. A small focal renal infarction was seen on 99mTc-dimercaptosuccinic acid renal scintigraphy, suggesting that FSGS was due to renal microinfarction associated with Buerger's disease. After the commencement of angiotensin-converting enzyme inhibitor therapy, the hypertension immediately improved, along with significant attenuation of proteinuria. Renal ischemia by vasoconstriction of the glomerular efferent arterioles in association with Buerger's disease may result in glomerular hyperfiltration followed by FSGS.

The Relationship Between Edema and Body Functions in Patients With Chronic Kidney Disease: A Preliminary Study.

INTRODUCTION: Chronic kidney disease (CKD) is known to be a risk factor for falls. In addition, numerous factors such as impaired body balance and loss of muscle mass were reported as risk factors for falls. Patients with CKD often have edema in their lower extremes. In Japan, edema, as well as physical factors, are listed as fall assessment items. Little is known about the relation between body functions and edema in patients with CKD. Thus, we conducted a multivariate regression analysis to investigate the factors related to knee extension muscle strength and dynamic balance in motion (TUG). MATERIALS AND METHODS: Thirty patients with CKD participated in this study. The basic characteristics were sex, age, blood pressure, body mass index (BMI), and medications. The laboratory data were estimated glomerular filtration rate (eGFR), hemoglobin (Hb), and C-reactive protein (CRP). Edema and muscle mass was measured by using InBody S10 (Inbody Japan Inc., Tokyo, Japan). The balance function while standing at rest and motion was measured as the total trajectory length of the center of gravity and the index of postural stability (IPS) using a kinetogravicorder 7100 (Anima Inc., Tokyo, Japan). Dynamic balance was assessed by the timed up & go (TUG) test. Knee extension muscle strength was measured by the Micro Total Analysis System (µ-Tas) F-1 (Anima Inc., Tokyo, Japan) test. Nutritional assessment was measured by the geriatric nutritional risk index (GNRI). Activities of daily living were measured using the functional independence measure (FIM). We conducted a multivariate regression analysis to investigate the factors related to knee extension muscle strength and dynamic balance in motion. RESULTS: Extracellular water/total body water (ECW/TBW) was not significantly correlated with balance at rest and IPS. The ECW/TBW was associated with knee extension muscle strength, TUG, albumin (Alb), Hb, and GNRI with statistical significance. After adjusting for sex and age, knee extension muscle strength was associated with ECW/TBW and TUG (p=0.044). The TUG was also associated with ECW/TBW after being adjusted for age and sex (p=0.046).  Conclusion: Patients with CKD who have edema may have decreased knee extensor strength and body balance function. Investigation of knee extension muscle strength and the body balance test in addition to the presence of leg edema at the time of physical examination may help predict a functional decline in CKD patients.

Management of asymptomatic hyperuricaemia in patients with chronic kidney disease by Japanese nephrologists: a questionnaire survey.

AIM: Hyperuricaemia is associated with chronic kidney disease (CKD) progression and cardiovascular events (CVE). In a US study, only 4% of rheumatologists initiated urate-lowering therapy in patients with asymptomatic hyperuricaemia (AHU). The present study aimed to clarify how Japanese board-certified nephrologists manage AHU in CKD patients. METHODS: Questionnaires on management of AHU in CKD stage 3 or more were mailed to 1500 Japanese board-certified nephrologists, excluding paediatricians and urologists, randomly selected from the directory of the Japanese Society of Nephrology (n = 2976). RESULTS: Five hundred and ninety-five nephrologists (40%) responded. Most nephrologists (84-89%) recommended that AHU in patients in CKD stages 3-5 should be treated, but fewer nephrologists (63%) recommended that AHU in patients of CKD stage 5D should be treated. The serum urate level to start urate-lowering therapy and the target serum urate level to be achieved (mg/dL) were 8.2 ± 0.9 and 6.9 ± 0.9, 8.4 ± 0.9 and 7.0 ± 1.0, 8.6 ± 1.0 and 7.3 ± 1.1, and 9.1 ± 1.2 and 7.8 ± 1.3 at stages 3, 4, 5 and 5D, respectively. The most frequently used maximal dosage of allopurinol was 100 mg/day at each stage. Benzbromarone was used in 52% of patients at stage 3, but only in 29%, 13% and 5% of patients at stages 4, 5 and 5D, respectively. The most important reasons to treat AHU at CKD stages 3-5 were prevention of CKD progression (45%), CVE (33%), gout (18%) and urolithiasis (3%). CONCLUSION: Most Japanese nephrologists treat AHU in pre-dialysis CKD with an aim to prevent CKD progression or CVE mainly by allopurinol.

Association between MR-proADM concentration and treatment intensity of antihypertensive agents in chronic kidney disease patients with insufficient blood pressure control.

Response to antihypertensive drugs in patients with chronic kidney disease (CKD) has great interindividual variability. Adrenomedullin (ADM) is produced abundantly in hypertension, but clearance is very rapid. Mid-regional proADM (MR-proADM) produced from an ADM precursor is considered a surrogate biomarker for quantification of ADM. We investigated the association of MR-proADM with antihypertensive resistance in CKD patients with poor blood pressure (BP) control. This cross-sectional study analyzed 33 CKD patients with poor BP control defined as failure to achieve target BP despite at least two classes of antihypertensive drugs. Treatment intensity score was calculated to facilitate comparability of antihypertensive regimens across subjects taking different drugs. Plasma MR-proADM concentration was measured using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Plasma MR-proADM concentration correlated with estimated glomerular filtration rate (eGFR) (r = - 0.777, p < 0.001). Treatment intensity score correlated positively with plasma MR-proADM concentration (r = 0.355, p = 0.043), and the correlation was further enhanced after correction by weight (r = 0.538, p = 0.001). Single and multiple regression analysis identified MR-proADM concentration (p = 0.005) as independently associated with weight-corrected treatment intensity score. MR-proADM may be useful as a biomarker to determine the therapeutic intensity of antihypertensive drugs in CKD patients with poor BP control.

Two cases of idiopathic multicentric Castleman disease with nephrotic syndrome treated with tocilizumab.

We report two cases of idiopathic multicentric Castleman disease (iMCD) with nephrotic syndrome (NS) treated with tocilizumab. Case 1 was a 58-year-old man diagnosed with iMCD prior to the onset of NS. Renal biopsy revealed membranous nephropathy, which was considered to be secondary membranous nephropathy associated with iMCD. Case 2 was a 49-year-old woman diagnosed with iMCD prior to NS. Renal biopsy revealed renal amyloidosis positive for Congo red staining and amyloid A protein immunostaining. In both the cases, the proteinuria improved after the initiation of glucocorticoid and tocilizumab therapy. Tocilizumab may be a good therapeutic choice for iMCD with NS.

A case of denosumab-associated membranous nephropathy in a patient with rheumatoid arthritis.

We herein report a case of anti-RANKL monoclonal antibody-associated membranous nephropathy (MN). A 67-year-old woman with a history of rheumatoid arthritis treated with prednisolone and methotrexate for more than 30 years and osteoporosis treated with eldecalcitol and teriparatide for 4 years had achieved a stable disease condition. Her kidney function was normal and her urinalysis was negative for hematuria and proteinuria. An anti-RANKL monoclonal antibody (denosumab) was administered for the treatment of osteoporosis. Four months later, proteinuria appeared (2.3 g/g creatinine) and remained positive for about 6 months, therefore, she was admitted to our hospital. An immunofluorescence study revealed fine granular deposits of immunoglobulin G (IgG) and C3 along the capillary walls. Staining for IgG subclasses showed positive staining for IgG1 (3+), IgG2 (1+), IgG3 (1+), and IgG4 (1+); phospholipase A2 receptor was negative. Electron microscopy showed partial subepithelial and intramembranous deposits and focal thickening of the glomerular basement membrane. No evidence of malignancy or infectious disease was seen. After cessation of denosumab, the proteinuria gradually improved. Based on the renal biopsy results and clinical course (development of marked proteinuria in the presence of denosumab with subsequent amelioration in the absence of the drug), we diagnosed the patient with secondary MN due to denosumab. This is the first reported case of denosumab-associated MN.

Sensitive and selective quantification of mid-regional proadrenomedullin in human plasma using ultra-performance liquid chromatography coupled with tandem mass spectrometry.

Mid-regional pro-adrenomedullin (MR-proADM) is suggested to be a prognostic indicator for various diseases. Plasma MR-proADM concentration is commonly measured using immunoassays based on its immunochemical characteristics. However, some immunological interactions affect the measured concentration. We developed and validated a sensitive and selective method for measuring plasma MR-proADM concentration using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) and evaluated its clinical applicability. Plasma samples were prepared by protein precipitation and solid-phase extraction. Samples obtained from healthy volunteers (n = 38), patients with chronic kidney disease (CKD) stages 3 and 4-5 (non-dialysis; n = 20 and 17, respectively), and CKD stage 5D (dialysis; n = 34) were analyzed. Within-batch and batch-to-batch accuracy of the UPLC-MS/MS assay for quality control samples ranged from -0.69 % to 8.05 % and from 1.72 % to 5.76 %, respectively. The lower limit of quantification was 0.4 ng mL-1. The MR-proADM concentration determined using the UPLC-MS/MS assay correlated strongly with that determined using the immunoassay (Pearson's product-moment correlation coefficient [r] = 0.7875, p < 0.001). Median (range) plasma MR-proADM concentrations of healthy volunteers, patients with CKD stages 3 and 4-5, and patients with CKD stage 5D were 0.67 (0.43-1.27), 1.89 (0.65-6.68), 3.86 (1.60-8.75) and 3.97 (0.66-9.20) ng mL-1, respectively, and a significant difference among four groups was confirmed. We established a sensitive and selective method for determining plasma MR-proADM concentration using UPLC-MS/MS. Our novel UPLC-MS/MS assay for determining plasma MR-proADM concentration can be used in the clinical setting and may have better selectivity than the immunoassay method.