Impaired Saltiness Perception Contributes to Higher Sodium Intake Among Patients With Chronic Kidney Disease: A Cross-Sectional Two-Center Study.

OBJECTIVE: Dietary sodium restriction is important in the prognosis of patients with chronic kidney disease (CKD). The association between saltiness perception and sodium intake among CKD patients is unclear, and the factors that influence saltiness are also not fully understood. We evaluated saltiness perception in CKD patients employing a cost-effective saltiness perception test using sodium solutions and evaluated the association between saltiness perception, sodium intake, and the influencing factors. DESIGN AND METHODS: CKD outpatients not undergoing dialysis were enrolled from two medical centers and underwent saltiness perception tests together with 24-hour urine collections to measure daily sodium intake. Participants who perceived saltiness using the test solution containing 25 mM sodium were regarded to have "preserved" saltiness perception, while those unable to perceive saltiness were regarded as having "impaired" saltiness perception. RESULTS: Of the total 132 participants, the median daily sodium intake was 3.36 g (range; 0.51-9.95 g/day), and 43 (32.6%) were ex- or current smokers. When participants were divided into 3 groups (G) according to daily sodium intake level: low (G1; 0.51-2.61 g/day), middle (G2; 2.62-3.99 g/day), and high (G3; 4.06-9.95 g/day), there was an obvious difference in impaired saltiness perception between three groups: 6.8% in G1, 50.0% in G2 and 86.4% in G3 (P value = 8.035 × 10-14, Cochran-Armitage test). In a multiple regression analysis in which the saltiness perception was adopted as a subjective variable, smoking habit (ex- or current smoker) and nonadherence to dietary sodium restriction were identified as significant explanatory variables. CONCLUSION: We revealed the clear relationship between higher daily sodium intake and impaired saltiness perception that is related to nonadherence to dietary sodium restriction and smoking habit, both of which could be intervened by nutritional counseling and public health education.

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.

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.

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.

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.

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.

Comparison of albuminuria test and urine test strip in Japanese hypertensive patients: AVA-E study.

BACKGROUND: Albuminuria is thought to reflect generalized endothelial dysfunction. In hypertensive patients, albuminuria is related to the risk for cardiovascular disease (CVD) events. Thus, screening for albuminuria is critical for risk stratification in hypertensive patients. However, the actual state of albuminuria in Japanese patients without diabetes remains unclear due to insurance coverage. METHODS: The CLINITEK microalb creatinine test® is a urine test paper that can assess albumin excretion corrected for urine creatinine levels in only 60 seconds without any special equipment. The semi-quantitative albuminuria test and urine proteinuria test were performed on 8,181 Japanese hypertensive patients, and the clinical significance of the test was evaluated by comparison with the urine test strip method. RESULTS: Albumin creatinine ratio (ACR) < 30 mg/g creatinine, ACR 30 - 299 mg/g creatinine, and ACR ≥ 300 mg/g creatinine on the albuminuria test were present in 70.0%, 25.7%, and 4.3%, respectively, of patients with a negative urine protein test strip result. Furthermore, in patients with a negative urine protein test strip result, ACR ≥ 30 mg/g creatinine was independently associated with previous CVD (odds ratio: 1.25, 95% confidence interval: 1.00 - 1.57, p < 0.05) after adjustment for estimated glomerular filtration rate, age, sex, BMI, smoking, dyslipidemia, diabetes, and blood pressure categories on multivariate logistic regression analysis. CONCLUSIONS: We considered that urine test strip was inadequate test to evaluate albuminuria. Easy and quick albuminuria test on the CLINITEK MICROALB CREATININE TEST might be useful test to risk stratification of hypertensive patients compared to urine test strip.

Comparison of predictive value for first cardiovascular event between Japanese GFR equation and coefficient-modified CKD-EPI equation.

BACKGROUND: The most superior GFR-estimating equation from the viewpoint of cardiovascular disease (CVD) prediction remains unclear. Thus, we performed cross-sectional comparison between two GFR-estimating equations (Japanese GFR equation and coefficient-modified CKD-EPI equation) and CVD incidence using Japanese nationwide "specific health checkup" data. METHODS: We recruited Japanese residents (241,159 individuals; mean 63 years; male, 38.6 %) who had not experienced CVD event (cardiac disease or stroke, or both). We calculated estimated GFR using two equations, and compared their predictive value for first symptomatic CVD event within 1 year. RESULTS: Of all subjects, the mean GFR estimated by the Japanese GFR equation (JPN-eGFR) modified for Japanese was 75.83 ± 16.18 mL/min/1.73 m(2), and that by the coefficient-modified CKD-EPI equation (mCKDEPI-eGFR) was 76.39 ± 9.61 mL/min/1.73 m(2). Area under the receiver operating characteristics curves (95 % confidence intervals) for predicting CVD event by mCKDEPI-eGFR vs. JPN-eGFR were 0.596 (0.589-0.603) vs. 0.562 (0.554-0.569). Using mCKDEPI-eGFR, the crude odds ratio (OR) for CVD incident in the 4th quartile group was far more than double (OR 2.46, 95 % CI 2.29-2.66) that in the 1st quartile group. Using JPN-eGFR, the crude OR in the 4th quartile group was less than double (OR 1.61, 95 % CI 1.51-1.73) that in the 1st quartile group. However, such superior predictive value of mCKDEPI-eGFR disappeared after adjustment for confounding factors (age, gender, BMI, presence of proteinuria, hypertension, diabetes, dyslipidemia and current smoking). CONCLUSION: GFR estimated by the coefficient-modified CKD-EPI equation was more closely related to CVD incidence than that estimated by the Japanese GFR equation. However, it is possible that low mCKDEPI-eGFR also reflects some cardiovascular risk(s) other than kidney dysfunction.

Effect of a hydrogen (H2)-enriched solution on the albumin redox of hemodialysis patients.

Elevated oxidative stress (OS) is associated with severe cardiovascular disease and premature death among patients treated with hemodialysis (HD). Oxidative stress is enhanced by contact between blood and dialysis membranes during HD sessions. This study aimed to clarify whether hydrogen (H2), which is a known antioxidant, is capable of suppressing increased OS induced during HD sessions. Eight patients on regular HD treatment were studied. Two HD sessions were performed in a cross-over design trial using standard and hydrogen-enriched solutions (mean of 50 p.p.b. H2; H2-HD). Blood samples were obtained from the inlet and outlet of the dialyzer during HD to determine changes in plasma levels of glutathione, hydrogen peroxide, and albumin redox state as a marker of OS. Comparison of inlet and outlet blood revealed significant decreases in total glutathione and reduced glutathione, as well as significant increases in hydrogen peroxide in both HD treatments. However, the mean proportion of reversibly oxidized albumin in outlet serum was significantly lower than that in inlet serum following the H2-HD session, whereas no significant changes were found in the standard solution session, suggesting that "intra-dialyzer" OS is reduced by H2 -HD. In conclusion, the application of H2-enriched solutions could ameliorate OS during HD.

Effect of allopurinol on cardiovascular incidence among hypertensive nephropathy patients: the Gonryo study.

BACKGROUND: The present study aimed to clarify the beneficial effect of allopurinol on cardiovascular morbidity and mortality in a cohort of hypertensive nephropathy patients with impaired kidney function. METHODS: One hundred and seventy-eight patients diagnosed with hypertensive nephropathy and presenting with impaired kidney function (estimated glomerular filtration rate <45 mL/min/1.73 m(2)) were recruited from nephrology clinics. Oral allopurinol was prescribed in 67 of these patients. The effects of allopurinol use on the development of cardiovascular disease (i.e. ischemic heart disease, congestive heart failure, and stroke) and all-cause death was analyzed using the Cox proportional hazard model. RESULTS: During the follow-up of 18.4 months (mean), 28 primary events occurred. Basal use of allopurinol was a significant beneficial factor (hazard ratio = 0.342, p = 0.0434, standard error = 0.53058) after adjusting for confounding factors. CONCLUSION: The use of allopurinol in hypertensive subjects with impaired kidney function appears to be beneficial in preventing cardiovascular morbidity and all-cause mortality, indicating that this xanthine oxidase inhibitor protects the vascular system, at least in this specific group.

A lower level of reduced albumin induces serious cardiovascular incidence among peritoneal dialysis patients.

BACKGROUND: Human serum albumin is composed of human mercaptoalbumin (HMA) with cysteine residues having reducing powers and of oxidized human non-mercaptoalbumin. Previously, we reported that a lower HMA level is closely related to serious cardiovascular disease (CVD) incidence and mortality among hemodialysis patients. However, the relationship between HMA level and CVD incidence among peritoneal dialysis (PD) patients is unclear. METHODS: We measured the redox state of human serum albumin using high-performance liquid chromatography in 30 continuous ambulatory PD patients. The association between HMA and incidental CVD events was evaluated. RESULTS: Eight patients experienced symptomatic CVD events (5 patients died) at the 5-year follow-up. The concentration and fraction of HMA (cHMA and f(HMA), respectively) showed significantly lower values in patients with CVD than those without CVD (cHMA 1.58 ± 0.39 and 2.16 ± 0.43 g/dL, f(HMA) 48.9 ± 5.4 and 56.4 ± 8.6%, respectively). Multiple forward stepwise regression analysis using cHMA and f(HMA) as the criterion variables was performed, and C-reactive protein and hemoglobin were adopted as significant explanatory variables in the former equation, whereas urea nitrogen was adopted in the latter equation. Multiple logistic regression analysis revealed that cHMA is a statistically, and f(HMA) is a marginally significant explanatory variable of CVD incidence (p = 0.0369, R = -0.260 and p = 0.0580, R = -0.214, respectively). CONCLUSIONS: Lower HMA level, which might be caused by chronic inflammation, anemia and accumulation of dialyzable uremic toxin(s), is closely related to serious CVD incidence among PD patients.

Decrease in reduced-form albumin among chronic kidney disease patients: new insights in cardiovascular complications.

From the perspective of free cysteine residue (Cys-34), human serum albumin (HSA) comprises a mixture of human mercaptoalbumin (HMA), in which the Cys-34 is not oxidized, human non-mercaptoalbumin (HNA)-1, which has a disulfide bond that can be reversibly oxidized, mainly by cysteine, and HNA-2, which is strongly oxidized to form sulfinic (-SO(2) H) or sulfonic (-SO(3) H) species. We have developed a convenient high-performance liquid chromatographic (HPLC) system for the clear separation of HSA into HMA, HNA-1 and HNA-2, and we have studied the dynamic changes of HSA-redox under various states of chronic kidney disease, in both a clinical and an experimental setting. In this article, we discuss the relationship between HSA-redox (especially the decrease of the reduced form), dialyzable uremic toxins and incident cardiovascular disease based on our recent investigations.

The redox state of albumin and serious cardiovascular incidence in hemodialysis patients.

Human serum albumin is composed of human mercaptoalbumin (HMA) with cysteine residues having reducing powers and oxidized human non-mercaptoalbumin. The aim of this study is to clarify whether such redox state of albumin (HSA-redox) influences the incidence of cardiovascular disease (CVD) in chronic kidney disease patients on regular hemodialysis (HD). We measured HSA-redox using high-performance liquid chromatography in 86 anuric HD patients. The association between HSA-redox and incidental CVD events was evaluated. Twenty patients experienced symptomatic CVD events (16 patients died) at the 2-year follow-up. The fraction of HMA (f(HMA)) showed a significantly lower value in patients with CVD than that without CVD, in both pre-HD (36.5 ± 5.8% and 44.6 ± 9.8%, respectively) and post-HD (57.2 ± 6.2% and 67.2 ± 7.4%, respectively). The adjusted odds ratio (OR) for the incidental CVD event in patients with pre-HD f(HMA) < 40% was 5.0 (95% CI; 1.2 to 21.3), and that in patients with post-HD f(HMA) < 60% was 20.6 (3.2 to 134.7). Likewise, the adjusted OR for the CVD death in patients with pre-HD f(HMA) < 40% was 2.5 (0.6 to 12.5), and that in patients with post-HD f(HMA) < 60% was 25.6 (2.5 to 262.8). In conclusion, HSA-redox is closely related to serious CVD incidence and mortality among HD patients.