A case of renal sarcoidosis complicated by parotid gland and uterine lesions.

BACKGROUND: Sarcoidosis is a systemic disease that can affect multiple organs. While pulmonary sarcoidosis is most commonly observed, renal sarcoidosis occurs less frequently. We herein report a case of sarcoidosis with an exceptionally rare distribution including renal lesions. CASE PRESENTATION: A 51-year-old Japanese female was referred because of bilateral parotid swelling and renal dysfunction. Computed tomography scan showed the swelling of bilateral kidneys, parotid glands, and uterus. Ga scintigraphy also showed remarkable accumulation in these organs. Renal biopsy and cytological evaluations of parotid gland and uterus were performed and she was diagnosed as sarcoidosis of these organs. Treatment was initiated with prednisolone 40 mg/day and then renal dysfunction subsequently improved. In addition, the swelling of parotid glands and uterus improved and Ga accumulation in each organ had disappeared. CONCLUSION: This is a first case of renal sarcoidosis complicated by parotid glands and uterus lesions. Pathological findings and the reactivity observed in Ga scintigraphy indicated the presence of lesions in these organs.

Inactivation of SARS-CoV-2 variants by nitrogen-doped titanium dioxide loaded with metals as visible-light photocatalysts.

PURPOSE: We examined the inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by a nitrogen-doped titanium dioxide (N-TiO2) visible-light photocatalyst that was activated via light irradiation in the natural environment and was safe for human use as a coating material. METHODS: The photocatalytic activity of glass slides coated with three types of N-TiO2 without metal or loaded with copper or silver and copper was investigated by measuring acetaldehyde degradation. The titer levels of infectious SARS-CoV-2 were measured using cell culture after exposing photocatalytically active coated glass slides to visible light for up to 60 min. RESULTS: N-TiO2 photoirradiation inactivated the SARS-CoV-2 Wuhan strain and this effect was enhanced by copper loading and further by the addition of silver. Hence, visible-light irradiation using silver and copper-loaded N-TiO2 inactivated the Delta, Omicron, and Wuhan strains. CONCLUSION: N-TiO2 could be used to inactivate SARS-CoV-2 variants, including emerging variants, in the environment.

Visualization of estimated prevalence of CES-D positivity accounting for background factors and AIS scores.

Development of methods for population screening is necessary to improve the efficiency of secondary prevention of diseases. Until now, a common cutoff has been used for all people in the data set. However, if big data for health information can be used to modify individual cutoffs according to background factors, it may avoid wasting medical resources. Here we show that the estimated prevalence of the Center for Epidemiologic Studies Depression Scale positivity can be visualized by a heatmap using background factors from epidemiological big data and scores from the Athens Insomnia Scale. We also show that cutoffs based on the estimated prevalence can be used to decrease the number of people screened without decreasing the number of prevalent cases detected. Since this method can be applied to the screening of different outcomes, we believe our work can contribute to the development of efficient screening methods for various diseases.

First case of successful eradication of the sweet potato weevil, Cylas formicarius (Fabricius), using the sterile insect technique.

This paper presents the first case of the successful eradication of a Coleoptera pest species over a wide area using a combination of male annihilation technique (MAT) and sterile insect technique (SIT) application. The sweet potato weevil, Cylas formicarius, is one of the most destructive and widely distributed pests of sweet potato, Ipomoea batatas. A project to eradicate it was launched in 1994 on Kume Island, Okinawa Prefecture, Japan. The MAT application was first used from November 1994 to January 1999 to reduce the density of wild populations. The distribution and densities of weevils were assessed by trapping them and surveying infestation rates in wild hosts and sweet potatoes in the field. The C. formicarius populations were suppressed by approximately 90% and plant infestations were reduced from 9.5% to less than 0.1% by using the MAT. Then, hundreds of thousands to millions of sterile weevils were released each week (ca. 460 million in total from 1999 to 2012). As a result, based on an analysis of 12748 stems and 48749 tubers, no weevil infections were detected in the stems or tubers of sweet potato since 1997. Since 2009, almost no wild weevils were captured in traps, and in wild host and sweet potato surveys no weevils have been found in any of the 580 locations and 8833 samples since October 2011. As of 28 December, 2012, C. formicarius is considered to have been eradicated from Kume Island. This paper describes the process of eradicating C. formicarius using SIT application integrated with MAT application for the first time and discusses some of the main challenges associated with the weevil eradication campaignl.

Transformed Mycosis Fungoides with a Cytotoxic T-Cell Phenotype.

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma and occasionally undergo large cell transformation (transformed MF, TMF), resulting in a poorer clinical outcome. We describe a case of TMF with an immunophenotypic shift. MF showed the CD4 + CD8- T-cell phenotype, while TMF exhibited the CD4-CD8 + T-cell phenotype. Moreover, TMF expressed cytotoxic markers of TIA1 and Granzyme B. A PCR analysis of T-cell receptor genes revealed peak sizes that were the same in both biopsies, indicating that these two lymphomas were derived from the same clone.

A Case of M-Type Phospholipase A2 Receptor-Associated Membranous Nephropathy With IgG4-Positive Cells Infiltration in the Interstitium.

A 70-year-old man was referred to our department for evaluation of nephrotic syndrome. Renal biopsy revealed membranous nephropathy (MN). Immunohistochemical analysis demonstrated IgG4-positive staining in the glomeruli and interstitial cells. The presence of serum anti-phospholipase A2 receptor (PLA2R) antibody and enhanced staining of PLA2R in the glomeruli was noted. Computed tomography unidentified the extrarenal lesions of IgG4-related disease. He was diagnosed with PLA2R-associated MN possibly complicated with IgG4 related kidney disease (IgG4-RKD). Storiform fibrosis, a typical manifestation of IgG4-RKD, was not apparent. We herein describe a case of serologically and histologically confirmed PLA2R-associated MN with IgG4+ cell infiltration into the interstitium without any signs of IgG4-RD.

Synthesis and activity of 3-oxo-α-ionone analogs as male attractants for the solanaceous fruit fly, Bactrocera latifrons (Diptera: Tephritidae).

A series of 3-oxygenated α-ionone analogs have been developed as highly specific male lures for the solanaceous fruit fly Bactrocera latifrons, a pest of solanaceous fruits. We compared the attractant and phagostimulant activities of analogs with or without (i) unsaturations at the 4,5- and/or 7,8-positions and (ii) oxygen moieties at the 3- and/or 9-positions of the ionone molecule. Since naturally occurring vomifoliol (V2) was found to induce a highly potent phagostimulant activity in B. latifrons males, related analogs including dehydrovomifoliol (V1), 6-hydroxy-α-ionone (U1), and 6-hydroxy-α-ionol (U2) were synthesized to evaluate their attractant and phagostimulant activities. Synthetic V1, V2, U1, and U2 exhibited low attractant activity, but their phagostimulant activity was relatively high. Optical isomers of 3-oxo-7,8-dihydro-α-ionone (P3) and V1 were prepared to examine the stereochemical specificity of attractants. (+)-(6R)-P3 and (+)-(6S)-V1 exhibited the corresponding activities, while their respective antipodal enantiomers were found entirely inactive.

Salt intake causes B-type natriuretic peptide elevation independently of blood pressure elevation in the general population without hypertension and heart disease.

ABSTRACT: Excessive salt intake causes hypertension and cardiovascular diseases (CVDs). B-type natriuretic peptide (BNP) is synthesized and released from the ventricle, and is a surrogate marker reflecting various CVDs. Moreover, when a slight BNP elevation is shown, it leads to a poor prognosis in the general population. However, the relationship between salt intake and BNP levels in the general population remains unclear, especially in those without hypertension and heart diseases.In this study, we recruited 1404 participants without hypertension and electrocardiogram abnormalities, who received regular annual health check-ups in Japan. Plasma BNP levels were measured, and daily salt intake levels were evaluated using urinary samples. In addition, some clinical parameters were obtained, and the data were cross-sectionally analyzed.The median of plasma BNP levels was 10.50 pg/mL, and daily salt intake was 8.50 ±â€Š1.85 g. When dividing participants into quartiles according to daily salt intake, those with the highest daily salt intake revealed the highest plasma BNP levels. Plasma BNP levels were significantly and positively associated with daily salt intake. Moreover, multiple linear regression analyses revealed that plasma BNP levels showed a significant positive association with daily salt intake levels after adjustments.Plasma BNP levels were significantly and positively associated with daily salt intake after adjustment in the general population. Plasma BNP levels may be a surrogate marker reflecting salt-induced heart diseases.

Baseline Urinary Angiotensinogen Excretion Predicts Deterioration of the Kidney Function in Patients with Chronic Kidney Disease.

Objective The intrarenal renin-angiotensin system (RAS) is activated in patients with chronic kidney disease (CKD), and urinary angiotensinogen (AGT) levels, a surrogate marker of the intrarenal RAS activation, are associated with blood pressure (BP) and urinary albumin excretion. In addition, it has been shown that changes in urinary AGT levels correlate with annual changes in the estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes and that elevated levels of urinary AGT in type 2 diabetic patients with albuminuria are a high-risk factor for worsening renal and cardiovascular complications. However, whether or not baseline urinary AGT levels predict deterioration of the kidney function in all patients with CKD is unclear. Methods We recruited 62 patients with CKD whose eGFR was >15 mL/min/1.73 m2. We performed 24-hour ambulatory BP monitoring at 30-min intervals and daily urinary collection to examine the urinary AGT levels and albumin excretion and measured the levels of plasma angiotensin II (Ang II), a surrogate marker of circulating RAS. In addition, annual changes in the eGFR were followed up for 3.4±1.5 years. Results Annual changes in the eGFR were significantly and negatively associated with urinary AGT levels (r=-0.31, p=0.015) as well as the age, systolic BP, and urinary albumin levels. In contrast, annual changes in the eGFR were not correlated with plasma Ang II levels. Furthermore, when dividing patients into quartiles according to urinary AGT levels, patients with the highest urinary AGT levels showed a progressive decline in the eGFR. Conclusion These results suggest that elevated baseline urinary AGT levels can predict renal dysfunction in patients with CKD.

Circadian rhythm of the intrarenal renin-angiotensin system is caused by glomerular filtration of liver-derived angiotensinogen depending on glomerular capillary pressure in adriamycin nephropathy rats.

Circadian fluctuation disorder of the intrarenal renin-angiotensin system (RAS) causes that of blood pressure (BP) and renal damage. In renal damage with an impaired glomerular filtration barrier, liver-derived angiotensinogen (AGT) filtered through damaged glomeruli regulates intrarenal RAS activity. Furthermore, glomerular permeability is more strongly affected by glomerular hypertension than by systemic hypertension. Thus, we aimed to clarify whether the circadian rhythm of intrarenal RAS activity is influenced by AGT filtered through damaged glomeruli due to glomerular capillary pressure. Rats with adriamycin nephropathy and an impaired glomerular filtration barrier were compared with control rats. In adriamycin nephropathy rats, olmesartan medoxomil (an angiotensin II type 1 receptor blocker) or hydralazine (a vasodilator) was administered, and the levels of intrarenal RAS components in the active and rest phases were evaluated. Moreover, the diameter ratio of afferent to efferent arterioles (A/E ratio), an indicator of glomerular capillary pressure, and the glomerular sieving coefficient (GSC) based on multiphoton microscopy in vivo imaging, which reflects glomerular permeability, were determined. Mild renal dysfunction was induced, and the systemic BP increased, resulting in increased A/E ratios in the adriamycin nephropathy rats compared with the control rats. Fluctuations in intrarenal RAS activity occurred in parallel with circadian fluctuations in glomerular capillary pressure, which disappeared with olmesartan treatment and were maintained with hydralazine treatment. Furthermore, the GSCs for AGT also showed similar changes. In conclusion, intrarenal RAS activity is influenced by the filtration of liver-derived AGT from damaged glomeruli due to circadian fluctuation disorder of the glomerular capillary pressure.

Long-term analysis of adalimumab in Japanese patients with moderate to severe hidradenitis suppurativa: Open-label phase 3 results.

This phase 3, multicenter, open-label single-arm study evaluated adalimumab (ADA) in Japanese patients with moderate to severe hidradenitis suppurativa (HS). Fifteen patients received ADA 160 mg s.c. at week 0, 80 mg at week 2 and 40 mg at week 4 and every week thereafter. At any time after week 52, patients were given the option to receive 80 mg ADA every other week or remain on 40 mg every week. The primary end-point (achievement of HS Clinical Response [HiSCR] at week 24) and results up to week 24 were published previously. Secondary end-points included total abscess and inflammatory nodule (AN) count, 30% or more and 1 unit or more reduction in Patient's Global Assessment of Skin Pain Numeric Rating Scale (NRS30), modified Sartorius score and quality of life (QoL). After 12 weeks of ADA treatment, the achievement rate in HiSCR was 86.7%; HiSCR achievement rate was sustained through week 52 at 66.7%. Improvements at week 12 were also seen in the proportion of patients achieving an AN count of 0-2; NRS30 response rate among the nine patients with a baseline NRS of 3 or more; mean decrease in modified Sartorius score (61.4); and QoL as assessed by Dermatology Life Quality Index and Treatment Satisfaction Questionnaire; these improvements were maintained through 52 weeks. Similar efficacy was observed when patients switched dosing from ADA 40 mg every week to ADA 80 mg every other week. There were no new safety findings with ADA 40 mg weekly dosing during the study, and no differences in safety were found between patients who switched to 80 mg ADA every other week and patients who remained on 40 mg every week. The results of this study indicate that long-term ADA treatment is effective and well tolerated in Japanese patients with moderate to severe HS.

Sodium-Glucose Cotransporter-2 Inhibitor Immediately Decreases Serum Uric Acid Levels in Type 2 Diabetic Patients.

BACKGROUND Sodium-glucose cotransporter-2 (SGLT2) inhibitors are new antihyperglycemic drugs for type 2 diabetes. SGLT2 inhibitors ameliorate cardiovascular morbidity and mortality as well as kidney disease progression by reducing body weight (BW), blood pressure (BP), visceral adiposity, albuminuria, and serum uric acid and blood glucose levels. However, it is not clear which effects are pronounced, and what mechanisms are associated with these effects. MATERIAL AND METHODS This study recruited patients with type 2 diabetes who were prescribed an SGLT2 inhibitor for the first time in our outpatient department. Clinical parameters were measured before and 6 months after the administration of the SGLT2 inhibitor, without the addition of new drugs and dose changes for all prescribed drugs. RESULTS This study recruited 24 patients with type 2 diabetes. No significant differences in BP, glycated hemoglobin (HbA1c) levels, and low-density lipoprotein cholesterol levels were observed after SGLT2 inhibitor administration. In contrast, BW and serum uric acid levels decreased significantly, and the fractional excretion of uric acid (FEUA) increased significantly after administration. While no significant relationships were observed between serum uric acid and FEUA with respect to the percentage changes from baseline values, the percentage changes in serum uric acid levels from baseline were significantly and positively associated with those in serum creatinine levels. CONCLUSIONS Serum uric acid levels were immediately decreased owing to the administration of SGLT2 inhibitor, but BP, blood glucose, and serum lipid levels were unchanged. These changes in serum uric acid levels may be associated with changes in renal function.

Chronotherapy with a Renin-angiotensin System Inhibitor Ameliorates Renal Damage by Suppressing Intrarenal Renin-angiotensin System Activation.

Objective The intrarenal renin-angiotensin system (RAS) is activated in chronic kidney disease (CKD) patients and is not suppressed at night in CKD patients showing nocturnal hypertension, contributing to renal damage. Furthermore, changes in RAS inhibitor administration from morning to evening, namely chronotherapy, ameliorates renal damage at night. We attempted to clarify whether or not chronotherapy ameliorates renal damage by suppressing the intrarenal RAS activity. Methods We recruited 34 CKD patients with RAS inhibitors in the morning. We conducted ambulatory blood pressure (BP) monitoring and urine collection and evaluated urinary albumin (Alb) and angiotensinogen (AGT), which are surrogate markers for intrarenal RAS activity during the day and at night, respectively. The same experiments were conducted after changing the administration time. The ratio of values associated with morning versus evening dosing was defined as the morning to evening (M/E) ratio. Results The M/E ratio of urinary Alb had a significant and positive relationship with that of urinary AGT during the day and at night in all CKD patients. However, no significant relationships were found between the M/E ratios of urinary Alb and AGT using multiple linear regression analyses. Conversely, there was a significant and positive relationship between the M/E ratios of urinary Alb and AGT at night but not during the day in CKD patients whose estimated glomerular filtration rate was <45 mL/min/1.73 m2 and whose night-to-day ratio of systolic BP was >0.90, even after adjustment. Conclusion This study indicated that chronotherapy with RAS inhibitors improved the renal damage via intrarenal RAS suppression, especially in CKD patients with an impaired renal function and nocturnal hypertension.

The Urinary Angiotensinogen to Urinary Albumin Ratio Reflects Whether the Renin-angiotensin System in the Kidney Is Activated due to Filtration of Plasma Angiotensinogen through the Damaged Glomeruli or the Production of Angiotensinogen in the Proximal Tubules.

Objective Urinary angiotensinogen (AGT) is a surrogate marker for intrarenal renin-angiotensin system (RAS) activity that plays an important role in the development of renal damage. Urinary AGT levels are determined by the filtration of plasma AGT through the damaged glomeruli and production of AGT in the proximal tubules. However, the relative merits of the filtration and production of urinary AGT levels in chronic kidney diseases (CKD) have not been clarified. Therefore, we investigated them in CKD patients. Methods We recruited 41 biopsy-proven patients diagnosed with IgA nephropathy (IgAN) in 31, membranous nephropathy (MN) in 5, and tubulointerstitial nephritis (TIN) in 5. The patients taking RAS blockers were excluded. Results The urinary albumin levels in MN patients were significantly higher and those in TIN patients significantly lower than in IgAN patients, and the urinary AGT levels in the MN and TIN patients were significantly higher than those in IgAN patients. Conversely, the urinary AGT-to-urinary albumin (urinary AGT/Alb) ratios were the same for IgAN and MN patients, and those of TIN patients were significantly higher than those of IgAN and MN patients. A multiple linear regression analysis revealed that the urinary AGT/Alb ratios had a significant positive association with IgAN and TIN after adjustments (ß=0.75, and p<0.01). Conclusion These data suggest that the origins of urinary AGT may differ according to the etiology of renal damage [i.e. glomerular damage (such as IgAN and MN) or tubulointerstitial damage (such as TIN)], and a higher urinary AGT/Alb ratio, as in TIN, may reflect AGT production in the kidney.

Monoclonal immunoglobulin G1 κ-type atypical antiglomerular basement membrane disease accompanied by necrotizing glomerulonephritis
.

INTRODUCTION: Patients without detectable serum antiglomerular basement membrane (GBM) antibodies but with GBM staining for immunoglobulins (Ig), absence of a crescentic phenotype, mild renal insufficiency, and absence of pulmonary hemorrhage have atypical anti-GBM diseases. We report the case of a 64-year-old man with slowly progressive glomerulonephritis. CASE HISTORY: A 64-year-old Peruvian man presented with persistent microscopic hematuria, proteinuria of 2.1 g/g creatinine (Cr), serum Cr 1.00 mg/dL, and C-reactive protein 0.80 mg/dL. Renal biopsy revealed necrotizing glomerulonephritis with 39% cellular crescent formation and diffuse segmental endocapillary proliferation. He had linear staining of monoclonal IgG1-κ in the capillary walls but no detectable serum anti-GBM antibodies. Because renal dysfunction was slowly progressing, steroid monotherapy was initiated, and serum Cr level decreased from 1.48 to 1.13 mg/dL. However, serum Cr increased again to 1.35 mg/dL owing to active glomerular damage with crescent formation and endocapillary proliferation, confirmed by the second renal biopsy at 9 months after therapy. Renal function improved after cyclophosphamide therapy. CONCLUSION: We described an atypical variant of anti-GBM disease due to monoclonal IgG1-κ. Unlike usual atypical anti-GBM disease cases, we observed crescent formation in our patient. Further investigations are needed to identify the cause of nondetectable serum anti-GBM antibodies and to describe the causal relationships between clinicopathological features and the pattern of IgG subclass and light chain in atypical anti-GBM disease.

A New System for Detecting Initial Colonization by Invasive Pests and Their Locations.

Quarantine pests in plants can be a serious agricultural problem; many eradication programs using area-wide control measures have been implemented worldwide to combat this threat. Surveillance measures using sex pheromone (in general, male-attractant) traps are also widely implemented for rapid control and eradication of invasive pests. If initial pest colonization can be determined based on temporal count data of trapped insects (i.e., males), and countermeasures are applied only during colonization, costs incurred by these countermeasures would be dramatically reduced, especially in areas with frequent invasions. In this study, we developed a system to detect initial pest colonization, and to narrow down colonized regions using estimated temporal count data of the sweet potato weevil, Cylas formicarius Fabricius (Coleoptera: Curculionidae), in Tsuken Island, Okinawa, Japan. We verified the system by comparing our estimates to actual colonization data obtained via regular host plant surveys. Results indicated that our system was able to successfully detect pest colonization and estimate colonized regions. In this study, we discuss the conditions (i.e., pest biology, environment, etc.) that are optimal for application of our system.

Twenty-four-week interim analysis from a phase 3 open-label trial of adalimumab in Japanese patients with moderate to severe hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic skin disease characterized by recurrent painful inflamed nodules/abscesses and draining fistulas that negatively impact quality of life. Adalimumab, a monoclonal antibody against tumor necrosis factor-α, has been approved in the EU, USA and Japan for the treatment of moderate to severe HS. This is an interim analysis of an ongoing phase 3, multicenter, open-label, single-arm study of the safety and efficacy of adalimumab weekly dosing in Japanese patients with moderate to severe HS. Fifteen patients received adalimumab 160 mg at week 0, 80 mg at week 2 and 40 mg every week thereafter starting at week 4. The fulfillment of Hidradenitis Suppurativa Clinical Response was assessed under adalimumab treatment; clinical response was assessed by skin pain, total abscess and inflammatory nodule count and modified Sartorius score; and quality of life and safety were assessed. At week 12, 86.7% of patients achieved clinical response, with improvements at week 12 across the primary and secondary end points generally sustained through week 24. Adalimumab weekly dosing was generally safe and well tolerated with no new safety findings through week 24. These results suggest that adalimumab is effective and well tolerated in Japanese patients with moderate to severe HS.

Recent developments in terminator technology in Saccharomyces cerevisiae.

Metabolically engineered microorganisms that produce useful organic compounds will be helpful for realizing a sustainable society. The budding yeast Saccharomyces cerevisiae has high utility as a metabolic engineering platform because of its high fermentation ability, non-pathogenicity, and ease of handling. When producing yeast strains that produce exogenous compounds, it is a prerequisite to control the expression of exogenous enzyme-encoding genes. Terminator region in a gene expression cassette, as well as promoter region, could be used to improve metabolically engineered yeasts by increasing or decreasing the expression of the target enzyme-encoding genes. The findings on terminators have grown rapidly in the last decade, so an overview of these findings should provide a foothold for new developments.

Increased heart rate is associated with intrarenal renin-angiotensin system activation in chronic kidney disease patients.

BACKGROUND: A higher heart rate is one of the risk factors for heart failure and cardiovascular disease. Activation of the intrarenal renin-angiotensin system (RAS) plays an important role in the development of hypertension and renal damage. However, the association between heart rate and intrarenal RAS activation is unclear. METHODS: We investigated the relationship between heart rate and urinary angiotensinogen (U-AGT) excretion, a surrogate marker for intrarenal RAS activity, in ten subjects without chronic kidney disease (CKD) and 72 CKD patients who were not taking medications that influence heart rate and RAS blockers (age 50.0 ± 17.4 years, 27 men and 45 women, serum creatinine (sCr) 1.85 ± 2.71 mg/dL, blood pressure 120.5 ± 15.8/72.9 ± 10.1 mmHg, heart rate 67.3 ± 8.9 /min, urinary protein excretion 1.27 ± 2.63 g/day, and U-AGT excretion 747.4 ± 2714.6 µg/day). RESULTS: As heart rate is influenced by behavior and emotion, we divided it into daytime and nighttime. Heart rate had a significant positive association with sCr levels during daytime and nighttime in CKD patients but not in non-CKD subjects. Moreover, although heart rate was not associated with U-AGT excretion levels in non-CKD subjects, it was associated with U-AGT excretion levels during daytime (r = 0.23 and p = 0.047) and nighttime (r = 0.45 and p < 0.01) in CKD patients. Multiple linear regression analysis revealed that heart rate had a significant positive association with the U-AGT excretion levels during nighttime, but not daytime, after adjustments for age, sex, body mass index, and sCr (ß = 0.31 and p = 0.034). CONCLUSION: Heart rate is associated with U-AGT excretion levels, especially during the nighttime, in CKD patients.

Salt Loading Aggravates the Relationship between Melatonin and Proteinuria in Patients with Chronic Kidney Disease.

Objective Salt loading induces renal damage independently of blood pressure (BP) elevation via reactive oxygen species and sympathetic activity. Melatonin, a hormone that regulates the circadian rhythm, has multiple functions, including anti-oxidant effects and the inhibition of sympathetic activity. We have shown that impaired melatonin secretion is associated with renal damage in chronic kidney disease (CKD) patients. However, the associations between salt loading, melatonin secretion, and urinary albumin and protein have not been clarified. Methods We recruited 32 CKD patients, conducted 24-hour ambulatory BP monitoring and collected daytime and nighttime urine while the patients were consuming a standard salt (10 g/day) or low salt (6 g/day) diet. The excretion levels of albumin, protein and 6-sulfatoxymelatonin (aMT6s), a metabolite of melatonin, in daytime and nighttime urine were investigated in patients consuming standard salt and low salt diets. Results The urinary aMT6s levels in daytime and nighttime of the patients consuming standard salt and low salt diets did not differ to a statistically significant extent. However, the urinary aMT6s levels in patients consuming a standard salt diet-but not patients consuming a low salt diet-were significantly and negatively correlated with the daytime and nighttime urinary albumin and protein levels. Contrarily, no significant correlations were found between the urinary aMT6s levels and the BP levels, renal function, and plasma angiotensin II levels in patients consuming either a standard salt or low salt diet. A multiple regression analysis adjusted for age, sex, and body mass index revealed that the urinary albumin and protein levels were significantly and negatively associated with the urinary aMT6s levels in patients consuming a standard salt diet, but not in patients consuming a low salt diet. Conclusion Salt loading aggravates the relationship between melatonin secretion and albuminuria or proteinuria.