Dotinurad restores exacerbated kidney dysfunction in hyperuricemic patients with chronic kidney disease.

BACKGROUND: In this study, we aimed to clarify the beneficial effects of urate-lowering treatment with the novel agent dotinurad on renal function in patients with chronic kidney disease (CKD) and hyperuricemia (HUA). METHODS: Thirty-five patients with CKD (mean age 65.4 ± 14.8 years, 23 men) diagnosed with HUA were recruited. Changes in eGFR before and after dotinurad administration were assessed. Patients first underwent a 3-month observation period and then 3 months treatment with dotinurad. RESULTS: During the observation period, mean eGFR (mL/min/1.73 m2) declined significantly. The baseline eGFR was 31.8 ± 16.4 and the serum urate level (sUA, mg/dL) was 8.1 ± 1.7. During the treatment period, eGFR recovered to 36.5 ± 17.5 and sUA decreased to 6.7 ± 1.0. The increase in eGFR after dotinurad administration was correlated with a decrease in sUA (R = 0.375, p = 0.0263). CONCLUSION: Dotinurad administration to patients with CKD and HUA appears to be beneficial in restoring kidney function. Dotinurad may represent a potential medication for the prevention of kidney function decline caused by HUA.

Kidney damage relates to agonal bacteremia: a single-center retrospective study.

BACKGROUND: Agonal bacteremia, diagnosed with postmortem positive blood culture results, is considered a possible contributing factor to death. We hypothesized that some premortem organ damage, such as kidney damage, can enhance agonal bacteremia. METHODS: We performed a postmortem blood and alveolar fluid culture study in 30 cadavers and evaluated the relationship between blood culture results and clinical parameters, including organ damage (brain, heart, lung, kidney, liver and gastrointestinal tract). RESULTS: A total of 23 cases (76.7%) were positive for blood culture; the number of cultured species was one in 12 cases, two in 7 cases, and three in 4 cases. The ratio of agonal bacteremia was significantly higher in patients with heart damage (100%, n = 13) and those with kidney damage (end-stage kidney damage, acute kidney injury, obstructive kidney failure, or metastatic kidney tumours) (100%, n = 13). The mean number of cultured species was 0.67 ± 0.98 in heart or kidney damage, 1.40 ± 0.55 in heart damage only, 1.40 ± 0.55 in kidney damage only, and 2.00 ± 0.93 in heart and kidney damage. As the number of damaged organs increased (0 organs, no heart/kidney damage; 1 organ, heart or kidney damage; and 2 organs, heart and kidney damage), the mean number of cultured species increased significantly (p for trend = 0.001964). CONCLUSION: Premortem kidney damage relates to agonal bacteremia.

Upward-directed exit-site of the swan-neck catheter and "Easy-to-disinfect the backside area of exit-site" may prevent PD complications.

BACKGROUND: Upward-directed exit-site has been believed to be the worst for frequent ESI by an old retrospective study using straight catheters. No comparison study of 3 exit-site directions using swan-neck catheter has been performed regarding which direction is the best for our endpoints, Easy-to-see the backside area of exit-site: ESBE, Easy-to-disinfect the backside area of exit-site: EDBE, reduction of both exit-site infection (ESI), symptomatic catheter dislocation and peritonitis. METHODS: We assessed the relationship of exit-site direction with our endpoints in a quantitative cross-sectional, multicentered questionnaire survey. Patients who received either non-surgical catheter implantation or exit-site surgery were excluded. RESULTS: The numbers (percentage) of exit-site directions in included 291 patients were upward 79 (26.0), lateralward 108 (37.5) and downward 105 (36.5). Cochran-Armitage analysis showed a significant step-ladder increase in the prevalence of ESI as the direction changed from upward to lateralward to downward (0.15 ± 0.41, 0.25 ± 0.54, 0.38 ± 0.69 episodes/patient-year, p = 0.03). Multivariable regression analysis revealed the upward exit-site independently associates with both higher frequency of ESBE (OR 5.55, 95% CI 2.23-16.45, p < 0.01) and reduction of prevalence of ESI (OR 0.55, 95%CI 0.27-0.98, p = 0.04). Positive association between the prevalence of symptomatic catheter dislocation and ESI (OR 2.84, 95% CI 1.27-7.82, p = 0.01), and inverse association between EDBE and either prevalence of symptomatic catheter dislocation (OR 0.27, 95% CI 0.11-0.72) or peritonitis (OR 0.48, 95% CI 0.23-0.99) observed. CONCLUSION: Upward-directed swan-neck catheter exit-site may be the best for both ESBE and prevention of ESI. EDBE may reduce catheter dislocation and peritonitis. Symptomatic catheter dislocation may predict ESI.

A Case of Successfully Treated Roseomonas mucosa-induced Peritonitis Diagnosed by Mass Spectrometry.

Roseomonas mucosa is difficult to identify using routine analytical techniques. We herein report a case of peritoneal dialysis (PD)-related peritonitis caused by R. mucosa identified using matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry (MS). A 70-year-old woman was admitted to our hospital with PD-related peritonitis. Blood agar medium of dialysate culture derived colony pale pink in color, and the organism was identified as R. mucosa using MALDI-TOF MS. She was successfully treated with ciprofloxacin and meropenem without catheter removal. To our knowledge, this is the first case of R. mucosa peritonitis in which technique failure has been avoided.

Anti-glomerular Basement Membrane Disease Concomitant with MPO-ANCA Positivity Concurrent with High Serum Levels of Interleukin-26 Following Coronavirus Disease 2019 Vaccination.

As coronavirus disease 2019 (COVID-19) vaccine booster campaigns progress worldwide, new reports of complications following COVID-19 vaccination have emerged. We herein report a case of new-onset anti-glomerular basement membrane (GBM) disease concomitant with myeloperoxidase-antineutrophil cytoplasmic antibody positivity concurrent with high levels of interleukin (IL)-26 following the second dose of the Pfizer-BioNTech COVID-19 vaccine. The temporal association with vaccination in this case suggests that an enhanced neutrophilic immune response through IL-26 may have triggered necrotizing glomerulonephritis and a T-cell-mediated immune response to GBMs, leading to the development of anti-GBM antibodies, with an enhanced B-cell response after the vaccination triggering anti-GBM IgG and the onset of anti-GBM disease.

Lower range of serum uric acid level increases risk of rapid decline of kidney function in young and middle-aged adults: the Yuport Medical Checkup Center Study.

BACKGROUND: The effect of low serum uric acid (sUA) levels on kidney function is unclear. This study aimed to clarify the relationship between low sUA levels and the rapid decline in kidney function. METHODS: We examined the relationship between sUA levels and kidney function decline in health check-up examinees. A total of 10,547 participants were enrolled using data from the Yuport Medical Checkup Center Study between 1998 and 2002 for baseline and data from 2002 to 2006 as the follow-up period in Japan. According to sUA level (mg/dL), we classified the participants into the following six groups: (1) 2.0-2.9 (n = 247), (2) 3.0-3.9 (n = 1457), (3) 4.0-4.9 (n = 2883), (4) 5.0-5.9 (n = 2899), (5) 6.0-6.9 (n = 2010), and (6) 7.0-7.9 (n = 1,051). The relationship between sUA level and rapid decline in estimated glomerular filtration rate (ΔeGFR ≥ 3 mL/min/1.73 m2/year) was examined using a logistic regression model. RESULTS: During study period (5.4 ± 1.6 years), the incidence of rapid eGFR decline for the respective sUA groups (2.0-2.9, 3.0-3.9, 4.0-4.9, 5.0-5.9, 6.0-6.9, 7.0-7.9) were as follows: 4.5%, 4.0%, 2.4%, 3.3%, 3.1%, 3.4%. The crude and adjusted odds ratios (OR) for rapid eGFR decline were significantly higher in the 2.0-2.9 (OR:1.93 and 1.86) and 3.0-3.9 (OR:1.72 and 1.73) groups than in the 4.0-4.9 groups (reference). Stratified analysis of age differences revealed that the detrimental effect of low sUA was not evident in older adults (age ≥ 65 years). CONCLUSION: A lower normal sUA level is related to an increased risk for a rapid decline in kidney function.

Minimal change disease soon after Pfizer-BioNTech COVID-19 vaccination.

We report on the onset of minimal change disease (MCD) presenting with anasarca after a second dose of the messenger RNA (mRNA)-based Pfizer-BioNTech vaccine against coronavirus disease 2019 (COVID-19). A 75-year-old previously healthy male was admitted with rapidly progressive anasarca and proteinuria of 7.7 g/day following the second dose. A kidney biopsy revealed MCD with nephrotic syndrome. He was treated with intravenous methylprednisolone followed by prednisolone, leading to complete remission after 35 days in the hospital. Since definite causality between the vaccine and MCD remains unclear, awareness of this potential adverse effect of mRNA vaccines is important to determine its true incidence and frequency.

A Slight Decrease in the Serum Albumin Level Is Associated with the Rapid Progression of Kidney Dysfunction, Even within the Normal Range.

Objective A low-normal albumin level is associated with a high risk of cardiovascular disease and mortality in the general population. However, the relationship between the serum albumin level and the future decline in the kidney function is unclear. We evaluated the effect of the serum albumin level on the decline in the kidney function in the general population. Methods The data used were from 11,000 participants in a voluntary health checkup program conducted between 1998 and 2006 in Japan. The primary outcome for the kidney function was a difference in the estimated glomerular filtration rate (ΔeGFR) of≥3 mL/min/1.73 m2/year. The association of the risk of a decreased kidney function with the albumin level was determined using a logistic regression analysis. We fit separate multivariable logistic regressions for the serum albumin levels (g/dL) as a continuous variable and as categorical data, classified as ≤4.3 (n=2,530), 4.4-4.6 (n=5,427), and≥4.7 (n=3,043). Results Of the 11,000 participants, 346 had a ΔeGFR/year of≥3. Compared with the participants with albumin levels of≥4.7 g/dL, the risk of a decline in the kidney function was higher not only in those with albumin levels of ≤4.3 g/dL [adjusted odds ratio (OR) =2.10, 95% confidence interval (CI): 1.20-2.93] but also in those with levels of 4.4-4.6 g/dL (adjusted OR=1.53, 95% CI: 1.14-2.05). Conclusion A decreased albumin level is an independent risk factor for a rapid decline in the kidney function, even within the normal range.

Reflex Anuria Following Retrograde Pyelography: A Case Report and Literature Review.

A case of acute kidney injury due to reflex anuria that was caused by retrograde pyelography and required temporary hemodialysis is reported. An 83-year-old Japanese woman presented with anuria 2 days after undergoing bilateral retrograde pyelography for the investigation of gross hematuria. Retrograde pyelography showed no apparent abnormality, such as malignancy or urolithiasis, but pyelorenal extravasation of contrast medium was remarkable. Her anuria improved promptly after hemodialysis, allowing her treatment to conclude with only one hemodialysis session, and a normal renal function was restored with no sequelae. The details of this case and a review of the relevant literature are presented.

Prediction of presepsin concentrations through commensurate decline in kidney function in the elderly.

BACKGROUND: Presepsin is a useful biomarker to diagnose sepsis. However, the correlation between plasma presepsin concentrations and kidney function in the elderly with chronic kidney disease (CKD) remains to be elucidated. We determined whether plasma presepsin concentrations were influenced by kidney function decline in the elderly. METHODS: One hundred seventy outpatients with CKD aged ≥65 y were enrolled. Plasma presepsin concentrations were measured using immunoassay analysis. The relationship between plasma presepsin concentration and kidney function was assessed. RESULTS: The median age of patients of this cohort was 778 (72-85) y and the mean estimated glomerular filtration rate was 51.8 ±â€¯28.1 ml/min/1.73 m2. Plasma presepsin concentrations in those with CKD G4-G5 (362 pg/ml [273-553]) were significantly higher than in those with CKD G1-G2 (111 pg/ml [91-113]) and CKD G3 (145 pg/ml [124-205]) (p < 0.001, p < 0.001, respectively). A high correlation between plasma presepsin concentrations and kidney function was observed (R2 = 0.733, p < 0.001). Even after adjusting for confounders, plasma presepsin concentrations were independently associated with kidney function. CONCLUSIONS: Increases in plasma presepsin concentrations were exponentially correlated to kidney function decline in the elderly with CKD.

Spot urine protein/creatinine ratio as a reliable estimate of 24-hour proteinuria in patients with immunoglobulin A nephropathy, but not membranous nephropathy.

BACKGROUND: Proteinuria is known to be associated with both kidney function deterioration and cardiovascular diseases. While proteinuria estimation from 24-h urine samples has traditionally been considered as the standard method for assessment of the degree of urinary protein excretion, sample collection is associated with several technical problems such as inaccurate collection and the potential spread of drug-resistant pathogens. Therefore, the spot urine protein/creatinine ratio (PCR) assessment is currently recommended as an alternative. While the utility of PCR has been validated, studies on the association between spot urine PCR and 24-h proteinuria (24HP) in patients with chronic glomerular nephritis (CGN) and nephrotic syndrome (NS) are limited. This study aimed to evaluate whether an estimated result from a spot urine PCR could sufficiently approximate the daily urine protein excretion amount from a 24-h urine sample in patients with immunoglobulin A nephropathy (IgAN), minimal change disease (MCD), and membranous nephropathy- nephrotic syndrome (MN-NS). METHODS: The study participants included 161 patients with IgAN, MCD, or MGN-NS at the Jikei University Kashiwa Hospital and Kanagawa Prefecture Shiomidai Hospital. The correlation between spot urine PCR and a 24-h urine protein was investigated using linear regression analysis with Spearman's correlation (r) coefficient and intraclass correlation coefficient (ICC). RESULTS: While high correlation coefficients (r = 0.86, P < 0.001) and substantial agreement (ICC: 0.806, P < 0.001) were observed in patients with IgAN, similar correlations were not observed in patients with MCD or MN-NS. In the patients with MCD, r was 0.53 (P < 0.001), which signified a slight correlation, and in the patients with MN-NS, r was 0.289 (P = 0.17), which was not statistically significant. CONCLUSIONS: This study revealed that spot urine PCR is a reliable estimate of 24HP value in patients with IgAN. In contrast, there is a considerable difference between the daily urine protein excretion amount based on a 24-h urine sample and that which is calculated from spot urine PCR in patients with NS.

Relationship between Xanthine Oxidoreductase Redox and Oxidative Stress among Chronic Kidney Disease Patients.

Xanthine oxidase (XO), an isoform of xanthine oxidoreductase (XOR), is thought to increase the cardiovascular burden among chronic kidney disease (CKD) patients via oxidative radical production. Plasma XOR redox, which is characterized by the ratio of XO to total XOR, changes under different oxidative conditions associated with kidney dysfunction. However, the relationship between plasma XOR redox and oxidative stress (OS) is unclear. Thus, we aimed to clarify whether OS is related to XOR redox. We used the redox state of human serum albumin (HSA) as a marker to investigate the status of OS in CKD patients. HSA is composed of human mercaptoalbumin (HMA), which possesses not oxidized cysteine residues, reversibly oxidized human nonmercaptoalbumin-1 (HNA-1), and strongly oxidized human nonmercaptoalbumin-2 (HNA-2). The subjects included 13 nondialysis patients (7 males and 6 females) with varying degrees of kidney function. We found that ƒ(HMA) was negatively (R = -0.692, P = 0.0071) and ƒ(HNA-1) was positively (R = 0.703, P = 0.0058) correlated with plasma XO/XOR. ƒ(HNA-2) showed no correlation with XO/XOR (R = 0.146, P = 0.6412), indicating that plasma XOR redox is not related to the irreversible oxidation of HSA. In conclusion, plasma XOR redox is closely related to HSA redox, particularly reversible oxidation of HSA.

Translational Research of Peritoneal Dialysis Solution with Dissolved Molecular Hydrogen.

BACKGROUND: Improved biocompatibility of peritoneal dialysis solution (PDS) is crucial for peritoneal membrane preservation, thereby ensuring long-term peritoneal dialysis (PD) and preventing encapsulating peritoneal sclerosis. We previously reported the protective effect of molecular hydrogen (H2) on mesothelial cells from PDS in nonuremic rats. SUMMARY: In the present study, we examined the effect of H2-containing PDS (commercially available neutral pH type) regarding the protection of peritoneal tissue in experimental chronic kidney disease rats. Furthermore, we conducted a 2-week clinical trial in which H2-containing PDS was used in place of standard PDS and its feasibility was examined. In the experimental study, test solutions were injected through the subcutaneous port into the abdomen for 3 weeks. Histological study revealed a significant increase in the number of mesothelial cells and a significant decrease in peritoneal thickness in the H2-PD group as compared to the control and PD groups. Also, results of immunostaining analysis revealed increased vimentin and apoptotic cells in the membrane of the PD group, indicating that H2 may play a role in ameliorating PDS-induced peritoneal injury and preserving peritoneal integrity. In the clinical trial with 6 prevalent PD patients, all subjects completed the study with no adverse effects. Moreover, there were substantial changes in surrogate markers, such as increased CA125 and mesothelin, in the effluent in selected cases, suggesting enhanced mesothelial regeneration by H2. Key Message: H2-enriched PDS is a candidate novel PDS with improved biocompatibility. Further, our results support the significance of H2-PD clinical trials in the future.

Measurement of daily sodium excretion in patients with chronic kidney disease; special reference to the difference between the amount measured from 24 h collected urine sample and the estimated amount from a spot urine.

It is important to grasp a patient's daily sodium intake in the management of chronic kidney disease, as sodium intake is widely recommended at 6 g/day or less. There are multiple equations widely known for estimating the daily sodium excretion from a spot urine sample, but these are aimed at healthy people. There are few reports that validate equations in patients with chronic kidney disease. The purpose of this study is to evaluate whether the amount of measured daily sodium excretion from a sample collected for 24-h urine (24HU) is equal to that of using an equation from a spot urine sample (SU) in patients with chronic kidney disease. One hundred sixty-two patients with chronic kidney disease from Kanagawa Prefecture Shiomidai Hospital, Japan and the Jikei University Kashiwa Hospital, Japan participated in the study. Daily sodium excretion was measured from 24HU and compared with it from SU by using the formula according to Tanaka et al. Sodium excretion by 24HU was 2744 mg/day and estimating daily sodium excretion from SU was 3315 mg/day. The coefficient of determination was 0.17 (p < .001) in multivariate regression analysis. The coefficient of determination was extremely low. Thus, there is a considerable difference between the amount of sodium excretion calculated from a 24HU and that from a SU in patients with chronic kidney disease.

Interventional nephrology: current status and clinical impact in Japan.

BACKGROUND: Current status and clinical significance of interventional nephrology has not been reported from Japan. METHODS: Questionnaires were mailed twice to the directors of all 534 Japanese certificated nephrology training institutions in 2014. The main questions were current performance, categorized annual procedure volume and managers of peritoneal dialysis (PD) access, vascular access (VA) surgery, endovascular intervention, and kidney biopsy. Frequencies of nephrologist involvement between high volume center and low volume center and association between the level of nephrologists' involvement to each procedure and annual procedure volume were examined. RESULTS: 332 (62.2%) institutions answered performance of all procedures and 328 (61.4%) institutions answered all procedure volume. Kidney biopsy, VA surgery, endovascular intervention and PD access surgery were performed by any doctors in 94.2, 96.3, 88.4, and 76.2% and each involvement of nephrologist was 93.9, 54.1, 53.1 and 47.6%, respectively. Cochran-Armitage analyses demonstrated significant increases in all 4 procedure volume with greater management by nephrologists (p < 0.01). Nephrologists involvement to VA surgery associated with procedure volume increase in not only VA surgery, but also PD catheter insertion (p < 0.01) and kidney biopsy (p < 0.05). And nephrologists involvement to PD catheter insertion also associated with surgical volume increase in both VA surgery (p < 0.01) and endovascular intervention (p < 0.05). CONCLUSIONS: Main manager of all 4 procedures was nephrologist in Japan. Each procedure volume increased as nephrologists become more involved. Acquisition of one specific procedure by nephrologist associated with increase not only in this specific procedure volume, but also the other procedure volume.

Possible clinical effects of molecular hydrogen (H2) delivery during hemodialysis in chronic dialysis patients: Interim analysis in a 12 month observation.

BACKGROUND AND AIM: It is supposed that enhanced oxidative stress and inflammation are involved with the poor clinical outcomes in patients on chronic dialysis treatment. Recent studies have shown that molecular hydrogen (H2) is biologically active as an anti-inflammatory agent. Thus, we developed a novel hemodialysis (E-HD) system which delivers H2 (30 to 80 ppb)-enriched dialysis solution, to conduct a prospective observational study (UMIN000004857) in order to compare the long-term outcomes between E-HD and conventional-HD (C-HD) in Japan. The present interim analysis aimed to look at potential clinical effects of E-HD during the first 12 months observation. SUBJECTS AND METHOD: 262 patients (140, E-HD; 122, C-HD) were subjected for analysis for comprehensive clinical profiles. They were all participating in the above mentioned study, and they had been under the respective HD treatment for 12 consecutive months without hospitalization. Collected data, such as, physical and laboratory examinations, medications, and self-assessment questionnaires on subjective symptoms (i.e., fatigue and pruritus) were compared between the two groups. RESULTS: In a 12-month period, no clinical relevant differences were found in dialysis-related parameters between the two groups. However, there were differences in the defined daily dose of anti-hypertensive agents, and subjective symptoms, such as severe fatigue, and pruritus, which were all less in the E-HD group. Multivariate analysis revealed E-HD was an independent significant factor for the reduced use of anti-hypertensive agents as well as the absence of severe fatigue and pruritus at 12 months after adjusting for confounding factors. CONCLUSION: The data indicates E-HD could have substantial clinical benefits beyond conventional HD therapy, and support the rationale to conduct clinical trials of H2 application to HD treatment.

Dialyzer-related Thrombocytopenia due to a Polysulfone Membrane.

A 72-year-old Japanese woman was admitted to our hospital with rapidly progressive glomerulonephritis associated with anti-glomerular basement membrane antibody. Hemodialysis (HD) therapy was initiated on the day of admission using a biocompatible polysulfone (PS) membrane. Her platelet count (PLT; ×10(4)/µL) decreased gradually from 58.7 (day 1) to 5.8 (day 25). Considering the possibility of dialyzer-related thrombocytopenia (DRT), we measured her PLT count before and after the HD session on day 72, which revealed a dramatic decrease of 7.5 to 4.3. This finding suggested that the PS dialyzer caused PLT depletion. After discontinuation of the PS dialyzer, DRT was resolved.