Evaluating the associations between compliance with CKD guideline component metrics and renal outcomes.

Understanding the association between compliance to the Chronic Kidney Disease (CKD) guidelines in real-world clinical settings and renal outcomes remains a critical gap in knowledge. A comprehensive analysis was conducted using data from a national, multicenter CKD registry. This study included 4,455 patients with an estimated glomerular filtration rate (eGFR) measurement on the index date and eight additional metrics recorded within six months. These metrics comprised serum electrolyte levels, low-density lipoprotein cholesterol, hemoglobin, and the use of renin-angiotensin system inhibitors. The primary outcome was a composite of renal events, defined by a decline in eGFR to < 15 mL/min/1.73 m2 or a reduction of ≥ 30% in eGFR, confirmed by follow-up tests. Over a median follow-up of 513 days, 838 renal events were observed. High serum potassium levels (> 5.4 mmol/L) were associated with increased event rates compared to lower levels. Similarly, low serum sodium-chloride levels (< 33) correlated with higher event rates. Usage of renin-angiotensin system inhibitors, low serum calcium (< 8.4 mg/dL), and high uric acid levels (> 7.0 mg/dL) were also linked to increased events. Conversely, higher hemoglobin levels (≥ 13 g/dL) were associated with lower event rates. Compliance to guidelines, categorized into quartiles based on the number of met metrics, revealed a significantly reduced risk of events in the highest compliance group (meeting 8 metrics) compared to the lowest (0-5 metrics). Compliance to CKD guidelines in clinical practice is significantly associated with improved renal outcomes, emphasizing the need for guideline-concordant care in the management of CKD.

Association of serum magnesium levels with renal prognosis in patients with chronic kidney disease.

BACKGROUND: Magnesium deficiency is associated with various health conditions, but its impact on the progression of chronic kidney disease (CKD) remains unclear. This study aimed to investigate the association between serum magnesium levels and prognosis of renal function in CKD patients. METHODS: This is an analysis of the Japan Chronic Kidney Disease Database Ex　(J-CKD-DB-Ex), which is a multicenter prospective cohort including CKD patients enrolled from January 1, 2014 to December 31, 2020. We included adult outpatients with CKD stage G3 and G4 at the time of initial magnesium measurement. Patients were classified by magnesium levels as low (<1.7 mg/dl), normal (1.7-2.6 mg/dl), or high (>2.6 mg/dl). The primary outcomes were the composite of an eGFR < 15 ml/min/1.73 m2 or a ≥30% reduction in eGFR from the initial measurement, which was defined as CKD progression. We applied the Kaplan-Meier analysis and Cox regression hazard model to examine the association between magnesium levels and CKD progression. RESULTS: The analysis included 9868 outpatients during the follow-up period. The low magnesium group was significantly more likely to reach CKD progression. Cox regression, adjusting for covariates and using the normal magnesium group as the reference, showed that the hazard ratio for the low magnesium group was 1.20 (1.08-1.34). High magnesium was not significantly associated with poor renal outcomes compared with normal magnesium. CONCLUSION: Based on large real-world data, this study demonstrated that low magnesium levels are associated with poorer renal outcomes.

A case series of Fabry diseases with CKD in Japan.

BACKGROUND: It is well known that kidney injury is vital organ damage in Fabry disease (FD). Renin-angiotensin system (RAS) inhibitors are known to reduce proteinuria in patients with chronic kidney disease (CKD) by dilating the glomerular export arteries and reducing intraglomerular pressure. This improvement in intraglomerular pressure, although lowering the glomerular filtration rate, is thought to prevent renal damage and be renoprotective in the long term. RAS inhibitors may be effective in FD patients with proteinuria to prevent the progression of kidney disease, however, the degree to which they are used in clinical practice is unknown. METHODS: The J-CKD-DB-Ex is a comprehensive multicenter database that automatically extracts medical data on CKD patients. J-CKD-DB-Ex contains data on 187,398 patients in five medical centers. FD patients were identified by ICD-10. Clinical data and prescriptions of FD patients between January 1 of 2014, and December 31 of 2020 were used for the analysis. RESULTS: We identified 39 patients with FD from the J-CKD-DB-Ex including those with suspected FD. We confirmed 22 patients as FD. Half of the patients received RAS inhibitors. RAS inhibitors tended to be used in CKD patients with more severe renal impairment. CONCLUSIONS: This case series revealed the actual clinical practice of FD patients with CKD. In particular, we found cases in which patients had proteinuria, but were not treated with RAS inhibitors. The database was shown to be useful in assessing the clinical patterns of patients with rare diseases.

Oxidative stress and the role of redox signalling in chronic kidney disease.

Chronic kidney disease (CKD) is a major public health concern, underscoring a need to identify pathogenic mechanisms and potential therapeutic targets. Reactive oxygen species (ROS) are derivatives of oxygen molecules that are generated during aerobic metabolism and are involved in a variety of cellular functions that are governed by redox conditions. Low levels of ROS are required for diverse processes, including intracellular signal transduction, metabolism, immune and hypoxic responses, and transcriptional regulation. However, excess ROS can be pathological, and contribute to the development and progression of chronic diseases. Despite evidence linking elevated levels of ROS to CKD development and progression, the use of low-molecular-weight antioxidants to remove ROS has not been successful in preventing or slowing disease progression. More recent advances have enabled evaluation of the molecular interactions between specific ROS and their targets in redox signalling pathways. Such studies may pave the way for the development of sophisticated treatments that allow the selective control of specific ROS-mediated signalling pathways.

IL-1ß may be an indicator of peritoneal deterioration after healing of peritoneal dialysis-associated peritonitis.

BACKGROUND: Peritoneal dialysis (PD) is an essential lifesaving treatment for end-stage renal disease. However, PD therapy is limited by peritoneal inflammation, which leads to peritoneal membrane failure because of progressive peritoneal deterioration. Peritonitis is the most common complication in patients undergoing PD. Thus, elucidating the mechanism of chronic peritoneal inflammation after PD-associated peritonitis is an urgent issue for patients undergoing PD. This first case report suggests that an increased interleukin-1ß (IL-1ß) expression in the peritoneal dialysate after healing of peritonitis can contribute to peritoneal deterioration. CASE PRESENTATION: A 64-year-old woman was diagnosed with diabetes mellitus 10 years ago and had been started on PD for end-stage renal disease. One day, the patient developed PD-associated acute peritonitis and was admitted to our hospital for treatment. Thus, treatment with antimicrobial agents was initiated for PD-associated peritonitis. Dialysate turbidity gradually disappeared after treatment with antimicrobial agents, and the number of cells in the PD fluid decreased. After 2 weeks of antimicrobial therapy, peritonitis was clinically cured, and the patient was discharged. Thereafter, the patient did not develop peritonitis; however, residual renal function tended to decline, and peritoneal function also decreased in a relatively short period. We evaluated pro-inflammatory cytokine levels before and after PD-associated peritonitis; interestingly, the levels of IL-1ß remained high in the PD fluid, even after remission of bacterial peritonitis. In addition, it correlated with decreased peritoneal function. CONCLUSIONS: This case suggests that inflammasome-derived pro-inflammatory cytokines may contribute to chronic inflammation-induced peritoneal deterioration after PD-related peritonitis is cured.

Activation of the inflammasome drives peritoneal deterioration in a mouse model of peritoneal fibrosis.

During peritoneal dialysis (PD), the peritoneum is exposed to a bioincompatible dialysate, deteriorating the tissue and limiting the long-term effectiveness of PD. Peritoneal fibrosis is triggered by chronic inflammation induced by a variety of stimuli, including peritonitis. Exposure to PD fluid alters peritoneal macrophages phenotype. Inflammasome activation triggers chronic inflammation. First, it was determined whether inflammasome activation causes peritoneal deterioration. In the in vivo experiments, the increased expression of the inflammasome components, caspase-1 activity, and concomitant overproduction of IL-1ß and IL-18 were observed in a mouse model of peritoneal fibrosis. ASC-positive and F4/80-positive cells colocalized in the subperitoneal mesothelial cell layer. These macrophages expressed high CD44 levels indicating that the CD44-positive macrophages contribute to developing peritoneal deterioration. Furthermore, intravital imaging of the peritoneal microvasculature demonstrated that the circulating CD44-positive leukocytes may contribute to peritoneal fibrosis. Bone marrow transplantation in ASC-deficient mice suppressed inflammasome activation, thereby attenuating peritoneal fibrosis in a high glucose-based PD solution-injected mouse model. Our results suggest inflammasome activation in CD44-positive macrophages may be involved in developing peritoneal fibrosis. The inflammasome-derived pro-inflammatory cytokines might therefore serve as new biomarkers for developing encapsulating peritoneal sclerosis.

The novel preventive effect of a Japanese ethical Kampo extract formulation TJ-90 (Seihaito) against cisplatin-induced nephrotoxicity.

BACKGROUND AND PURPOSE: Chinese herbal medicine has been developed as the traditional Japanese Kampo medicine, and it has been widely used to cure various symptoms in clinical practice. However, only a few studies are currently available on the effect of the Kampo medicine on renal disease. Nephrotoxicity is one of major side effect of cisplatin, the first metal-based anticancer drug. In the present study, we examined the effect of the Kampo medicine against cisplatin-induced nephrotoxicity (CIN). METHODS: First, we screened the ethical Kampo extract formulation having positive effect against CIN using HK-2 cells. Next, we examined the preventive action of the selected ethical Kampo extract formulation against CIN in vivo using a mouse model. RESULTS: Cisplatin-induced cell death was significantly suppressed by TJ-43 (Rikkunshito) and TJ-90 (Seihaito); however, cisplatin-induced cleaved caspase-3 expression was inhibited only by TJ-90. In an in vivo mouse model of cisplatin-induced kidney injury with dysfunction and increased inflammatory cytokine expression, TJ-90 showed amelioration of these damaging effects. Cisplatin-induced apoptosis and superoxide production were inhibited by treatment with TJ-90. The expression of cleaved caspase-3, 4-hydroxynonenal, and MAPK phosphorylation increased after cisplatin administration, but decreased after the administration of TJ-90. Among 16 crude drug extracts present in Seihaito, Bamboo Culm (Chikujo in Japanese) inhibited cisplatin-induced cell death and cleaved caspase-3 expression in HK-2 cells. Moreover, the anti-tumor effect of cisplatin was not affected by TJ-90 co-treatment in cancer cell lines. CONCLUSION: TJ-90 might have a novel preventive action against CIN through the suppression of inflammation, apoptosis, and oxidative stress without interfering with the anti-tumor effect of cisplatin. Collectively, these findings might contribute to innovations in supportive care for cancer treatment-related side effects.

KIM-1 mediates fatty acid uptake by renal tubular cells to promote progressive diabetic kidney disease.

Tubulointerstitial abnormalities are predictive of the progression of diabetic kidney disease (DKD), and their targeting may be an effective means for prevention. Proximal tubular (PT) expression of kidney injury molecule (KIM)-1, as well as blood and urinary levels, are increased early in human diabetes and can predict the rate of disease progression. Here, we report that KIM-1 mediates PT uptake of palmitic acid (PA)-bound albumin, leading to enhanced tubule injury with DNA damage, PT cell-cycle arrest, interstitial inflammation and fibrosis, and secondary glomerulosclerosis. Such injury can be ameliorated by genetic ablation of the KIM-1 mucin domain in a high-fat-fed streptozotocin mouse model of DKD. We also identified TW-37 as a small molecule inhibitor of KIM-1-mediated PA-albumin uptake and showed in vivo in a kidney injury model in mice that it ameliorates renal inflammation and fibrosis. Together, our findings support KIM-1 as a new therapeutic target for DKD.

Dual disruption of eNOS and ApoE gene accelerates kidney fibrosis and senescence after injury.

The relationship between cellular senescence and fibrosis in the kidney is being elucidated and we have identified it as therapeutic target in recent studies. Chronic kidney disease has also become a lifestyle disease, often developing on the background of hypertension and dyslipidemia. In this study, we clarify the effect of interaction between these two conditions on kidney fibrosis and senescence. Wild type mice (WT), apolipoprotein E-/- mice (ApoEKO), and endothelial nitric oxide synthase (eNOS)-/- ApoE-/- mice (DKO) were obtained by breeding. Unilateral ureteral obstruction (UUO) was performed on 8-10 week old male mice and the degree of renal tubular injury, fibrosis and kidney senescence were evaluated. DKO manifested elevated blood pressure, higher total cholesterol and lower HDL than WT. DKO showed sustained kidney injury molecule-1 protein expression. Kidney fibrosis was significantly higher in ApoEKO and DKO. mRNA expression of genes related to kidney fibrosis was the highest in DKO. The mRNA expression of Zinc-α2-Glycoprotein and heme oxygenase-1 were significantly decreased in DKO. Furthermore, mRNA expression of p53, p21 and p16 were increased both in ApoEKO and DKO, with DKO being the highest. Senescence associated ß-gal positive tubule area was significantly increased in DKO. Increased DNA damage and target of rapamycin-autophagy spatial coupling compartments (TASCCs) formation was found in DKO. Mice with endothelial dysfunction and dyslipidemia developed kidney fibrosis and accelerated senescence even in young mice after injury. These data highlight the fact managing lifestyle-related diseases from a young age is important for CKD prevention.

Human reconstructed kidney models.

The human kidney, which consists of up to 2 million nephrons, is critical for blood filtration, electrolyte balance, pH regulation, and fluid balance in the body. Animal experiments, particularly mice and rats, combined with advances in genetically modified technology have been the primary mechanism to study kidney injury in recent years. Mouse or rat kidneys, however, differ substantially from human kidneys at the anatomical, histological, and molecular levels. These differences combined with increased regulatory hurdles and shifting attitudes towards animal testing by non-specialists have led scientists to develop new and more relevant models of kidney injury. Although in vitro tissue culture studies are a valuable tool to study kidney injury and have yielded a great deal of insight, they are not a perfect model. Perhaps, the biggest limitation of tissue culture is that it cannot replicate the complex architecture, consisting of multiple cell types, of the kidney, and the interplay between these cells. Recent studies have found that pluripotent stem cells (PSCs), which are capable of differentiation into any cell type, can be used to generate kidney organoids. Organoids recapitulate the multicellular relationships and microenvironments of complex organs like kidney. Kidney organoids have been used to successfully model nephrotoxin-induced tubular and glomerular disease as well as complex diseases such as chronic kidney disease (CKD), which involves multiple cell types. In combination with genetic engineering techniques, such as CRISPR-Cas9, genetic diseases of the kidney can be reproduced in organoids. Thus, organoid models have the potential to predict drug toxicity and enhance drug discovery for human disease more accurately than animal models.

Diphenhydramine may be a preventive medicine against cisplatin-induced kidney toxicity.

Cisplatin is widely used as an anti-tumor drug for the treatment of solid tumors. Unfortunately, it causes kidney toxicity as a critical side effect, limiting its use, given that no preventive drug against cisplatin-induced kidney toxicity is currently available. Here, based on a repositioning analysis of the Food and Drug Administration Adverse Events Reporting System, we found that a previously developed drug, diphenhydramine, may provide a novel treatment for cisplatin-induced kidney toxicity. To confirm this, the actual efficacy of diphenhydramine was evaluated in in vitro and in vivo experiments. Diphenhydramine inhibited cisplatin-induced cell death in kidney proximal tubular cells. Mice administered cisplatin developed kidney injury with significant dysfunction (mean plasma creatinine: 0.43 vs 0.15 mg/dl) and showed augmented oxidative stress, increased apoptosis, elevated inflammatory cytokines, and MAPKs activation. However, most of these symptoms were suppressed by treatment with diphenhydramine. Furthermore, the concentration of cisplatin in the kidney was significantly attenuated in diphenhydramine-treated mice (mean platinum content: 70.0 vs 53.4 µg/g dry kidney weight). Importantly, diphenhydramine did not influence or interfere with the anti-tumor effect of cisplatin in any of the in vitro or in vivo experiments. In a selected cohort of 98 1:1 matched patients from a retrospective database of 1467 patients showed that patients with malignant cancer who had used diphenhydramine before cisplatin treatment exhibited significantly less acute kidney injury compared to ones who did not (6.1 % vs 22.4 %, respectively). Thus, diphenhydramine demonstrated efficacy as a novel preventive medicine against cisplatin-induced kidney toxicity.

Clinical characteristics associated with 1-year tolvaptan efficacy in autosomal dominant polycystic kidney disease with a wide range of kidney functions.

Autosomal dominant polycystic kidney disease (ADPKD) develops into end-stage kidney disease by 65 years of age in an estimated 45%-70% of patients. Recent trials revealed that tolvaptan inhibits disease progression both in early-stage or late-stage ADPKD ; however, stratified analysis showed a difference of favorable factors correlated with tolvaptan efficacy between early-stage and late-stage ADPKD. Thus, we examined the efficacy of tolvaptan in ADPKD with a wide range of estimated glomerular filtration rates (eGFR). We enrolled 24 patients with eGFR 35.3 (28.0-65.5) ml / min / 1.73m2 and evaluated treatment effect as ΔΔeGFR (ml / min / 1.73m2 / year) or ΔΔtotal kidney volume (TKV) (% / year) that was calculated as post-treatment annual change - pre-treatment annual change. Pre ΔeGFR was significantly low in eGFR responders, defined as ΔΔeGFR > 0 ml / min / 1.73m2 / year. In eGFR responders, pre ΔeGFR, post ΔeGFR, eGFR, TKV, and proteinuria were significantly correlated with ΔΔeGFR. In TKV responders defined as ΔΔTKV > 5 % / year, we identified hypertension history, proteinuria, TKV, and post ΔTKV as significantly correlated factors with ΔΔTKV. In conclusion, pre ΔeGFR may be a predictive factor of therapeutic efficacy on kidney function. Tolvaptan may have greater efficacy in early-stage ADPKD with rapid GFR decline or with well-controlled blood pressure. J. Med. Invest. 67 : 315-320, August, 2020.

Author Correction: Circulating Apolipoprotein L1 is associated with insulin resistance-induced abnormal lipid metabolism.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Proximal tubule ATR regulates DNA repair to prevent maladaptive renal injury responses.

Maladaptive proximal tubule (PT) repair has been implicated in kidney fibrosis through induction of cell-cycle arrest at G2/M. We explored the relative importance of the PT DNA damage response (DDR) in kidney fibrosis by genetically inactivating ataxia telangiectasia and Rad3-related (ATR), which is a sensor and upstream initiator of the DDR. In human chronic kidney disease, ATR expression inversely correlates with DNA damage. ATR was upregulated in approximately 70% of Lotus tetragonolobus lectin-positive (LTL+) PT cells in cisplatin-exposed human kidney organoids. Inhibition of ATR resulted in greater PT cell injury in organoids and cultured PT cells. PT-specific Atr-knockout (ATRRPTC-/-) mice exhibited greater kidney function impairment, DNA damage, and fibrosis than did WT mice in response to kidney injury induced by either cisplatin, bilateral ischemia-reperfusion, or unilateral ureteral obstruction. ATRRPTC-/- mice had more cells in the G2/M phase after injury than did WT mice after similar treatments. In conclusion, PT ATR activation is a key component of the DDR, which confers a protective effect mitigating the maladaptive repair and consequent fibrosis that follow kidney injury.

Circulating Apolipoprotein L1 is associated with insulin resistance-induced abnormal lipid metabolism.

Circulating ApolipoproteinL1 (ApoL1) is a component of pre-ß-high-density lipoprotein (HDL), however little is known about the relationship of ApoL1 with cardiometabolic factors. Considering previous studies reporting the correlation of ApoL1 to triglyceride, we have hypothesized that ApoL1 associates with insulin-related metabolism. The current study examined their associations in 126 non-diabetic subjects and 36 patients with type 2 diabetes (T2DM). Non-diabetic subjects demonstrated triglyceride (standardized coefficients [s.c.] = 0.204, p < 0.05), body mass index (s.c. =0.232, p < 0.05) and HDL cholesterol (s.c. = -0.203, p < 0.05) as independent determinant of ApoL1 levels, and the significant elevation of ApoL1 in metabolic syndrome. Lipoprotein fractionation analysis revealed the predominant distribution of ApoL1 in large HDL fraction, and the significant increase of ApoL1 in large LDL fraction in high ApoL1 samples with insulin resistance. In T2DM, ApoL1 was higher in T2DM with metabolic syndrome, however ApoL1 was lower with ß cell dysfunction. Insulin significantly promotes ApoL1 synthesis and secretion in HepG2 cells. In conclusion, circulating ApoL1 may be associated with abnormal HDL metabolism in insulin resistant status. This may suggest a regulation of insulin signal on the ApoL1 level, leading to offer a novel insight to the ApoL1 biology.

Clinical evaluation of presepsin considering renal function.

Presepsin, a glycoprotein produced during bacterial phagocytosis, is used as a sepsis marker for bacterial infections. However, presepsin levels are affected by renal function, and the evaluation criteria according to kidney function or in chronic kidney diseases remain controversial. Furthermore, presepsin may be increased by sample stirring, but no studies have evaluated this effect.In this study, we excluded the effect of stirring by standardizing the blood collection conditions, analyzed the influence of kidney function on presepsin concentrations, and recalculated the reference range based on the findings. EDTA-whole blood from 47 healthy subjects and 85 patients with chronic kidney disease was collected to measure presepsin by PATHFAST. Presepsin was found to be significantly correlated with the levels of creatinine (r = 0.834), eGFRcreat (r = 0.837), cystatin-C (r = 0.845), and eGFRcys (r = 0.879). Furthermore, in patients with CKD, presepsin levels stratified by eGFRcys showed a significant increase in the CKD G2 patient group and with advancing glomerular filtration rate stage. The following values were obtained: Normal: 97.6 ± 27.4 pg/mL, CKD G1: 100.2 ± 27.6 pg/mL, CKD G2: 129.7 ± 40.7 pg/mL, CKD G3: 208.1 ± 70.2 pg/mL, CKD G4: 320.2 ± 170.1 pg/mL, CKD G5: 712.8 ± 336.3 pg/mL. The reference range, calculated by a nonparametric method using 67 cases of healthy volunteers and patients with chronic kidney disease G1, was found to be 59-153 pg/mL, which was notably lower than the standard reference range currently used. Presepsin concentrations were positively correlated with a few biomarkers of renal function, indicating the necessity to consider the effect of renal function in patients with renal impairment. Using the recalculated reference range considering kidney function may improve the accuracy of evaluating presepsin for diagnosis of sepsis compared to the standard reference currently in use.

Involvement of Elf3 on Smad3 activation-dependent injuries in podocytes and excretion of urinary exosome in diabetic nephropathy.

Diabetic nephropathy (DN) is among the most serious complications of diabetes mellitus, and often leads to end-stage renal disease ultimately requiring dialysis or renal transplantation. The loss of podocytes has been reported to have a role in the onset and progression of DN. Here, we addressed the activation mechanism of Smad3 signaling in podocytes. Expression of RII and activation of Smad3 were induced by AGE exposure (P<0.05). Reduction of the activation of RII-Smad3 signaling ameliorated podocyte injuries in Smad3-knockout diabetic mice. The bone morphogenetic protein 4 (BMP4) significantly regulated activation of RII-Smad3 signalings (P<0.05). Moreover, the epithelium-specific transcription factor, Elf3was induced by AGE stimulation and, subsequently, upregulated RII expression in cultured podocytes. Induction of Elf3 and activation of RII-Smad3 signaling, leading to a decrease in WT1 expression, were observed in podocytes in diabetic human kidneys. Moreover, AGE treatment induced the secretion of Elf3-containing exosomes from cultured podocytes, which was dependent on the activation of the TGF-ß-Smad3 signaling pathway. In addition, exosomal Elf3 protein in urine could be measured only in urinary exosomes from patients with DN. The appearance of urinary exosomal Elf3 protein in patients with DN suggested the existence of irreversible injuries in podocytes. The rate of decline in the estimated Glomerular Filtration Rate (eGFR) after measurement of urinary exosomal Elf3 protein levels in patients with DN (R2 = 0.7259) might be useful as an early non-invasive marker for podocyte injuries in DN.

The utility and limitation of inferior vena cava diameter as a dry weight marker.

BACKGROUND: IVC diameter on expiration (IVCdexp) is measured by echocardiography routinely. It is used to estimate volume status and designated as a definitive marker for determining dry weight (DW) in patients undergoing hemodialysis (HD). METHODS: A cross-sectional study. Outpatients (n = 107), and inpatients (n = 35) undergoing HD were enrolled. IVCdexp was measured on non-dialysis days in outpatients and dialysis days before and after the dialysis session in inpatients. In outpatients, the relationship of IVCdexp with echocardiography findings and clinical characteristics was analyzed. IVCdexp was compared with the other DW markers as a predictive factor for intradialytic hypotension. In inpatients, IVCdexp was analyzed by dividing inpatients with or without fluid in extravascular space. RESULTS: IVCdexp ranged from 5.4 to 16.9 mm in outpatients who had optimal DW. IVCdexp could reflect on volume status, but not predictive for intradialytic hypotension and not suggestive of fluid in extravascular space. CONCLUSIONS: IVCdexp was a rough marker to estimate volume status and only useful in suggesting apparent hypervolemia or hypovolemia. We should know that the IVCdexp value is affected by a lotof factors and not a definitive marker for estimating practical DW. J. Med. Invest. 66 : 172-177, February, 2019.