Urinary excretion of thyroid hormone in CKD patients: a proof-of-concept of nephrogenic hypothyroidism.

PURPOSE: Patients with chronic kidney disease (CKD) complicated by hypothyroidism exhibit a higher prevalence of urine protein than that in the general population. This study was aimed at investigating thyroid hormones and thyroid hormone-binding proteins excreted in urine to elucidate the urine protein-associated underlying mechanisms of hypothyroidism. METHODS: Between November 2016 and August 2018, thyroid function (serum free T3 [sFT3], free T4 [sFT4], and thyroid-stimulating hormone [sTSH]), kidney function (estimated glomerular filtration rate [eGFR]), thyroid antibodies and albumin (Alb) were evaluated in 99 Japanese CKD patients with proteinuria at our outpatient clinic. A urine examination was also performed to assess the following parameters: total T3, total T4, TSH, Alb, preAlb, thyroid-binding globulin, and protein. RESULTS: The median patient age at study recruitment was 60 years; 50 patients (50.5%) were male. The median eGFR and Alb level were 20.3 ml/min/1.73 m2 and 3.8 g/dL, respectively. 21 patients (21.2%) were diagnosed with nephrotic syndrome (NS). The median sFT3, sFT4, and sTSH levels were within normal limits. Approximately 70% of the patients had thyroid dysfunction and 51.5% had overt or subclinical hypothyroidism without predominantly antibody positive. Regarding NS and non-NS patients, age and Alb were significantly different between these groups, while sex and eGFR were not significant, but the urinary T4 and TSH levels were higher in the NS group; thus, more severe hypothyroid. CONCLUSION: We found a significant association between hypothyroidism and NS regardless of sex and antibodies. Urinary loss of thyroid hormones must be a factor influencing hypothyroidism independent of autoimmunity.

Fibroblast growth factor 23-Klotho and mineral metabolism in the first year after pediatric kidney transplantation: A single-center prospective study.

BACKGROUND: The role of fibroblast growth factor 23 (FGF23) levels in mineral metabolism before and after kidney transplantation in pediatric patients is poorly understood. METHODS: We prospectively evaluated 24 patients under 18 years of age (4.5 [3.3-9.8] years) who underwent living kidney transplantation between July 2016 and March 2018, and measured intact FGF23 and serum αKlotho levels, and other parameters of mineral metabolism before and after transplantation (Day 7, 1 and 4 months, and 1 year). Relationships between parameters were examined by linear analysis. RESULTS: FGF23 level was 440.8 [63.4-5916.3] pg/ml pre-transplant and decreased significantly to 37.1 [16.0-71.5] pg/ml at Day 7 post-transplant (-91.6%, p < .001). Thereafter, it remained at normal levels until 1 year. αKlotho level was 785 [568-1292] pg/ml pre-transplant and remained low at Day 7 and 1 month post-transplant, with an increasing trend at 4 months. Post-transplant phosphorus levels were significantly decreased compared with pre-transplant, with a lowest level of 1.7 [1.3-2.9] mg/dl, -5.7 [-6.8, -3.8] SD at Day 4, followed by gradual recovery. Phosphorus levels and the ratio of tubular maximum phosphate reabsorption were significantly and negatively associated with pre-transplant FGF23 until 4 months of post-transplant. Pre-transplant αKlotho was negatively associated with pre-transplant FGF23 but not FGF23 or other parameters after transplantation. CONCLUSION: FGF23 in pediatric kidney transplant patients decreased rapidly after transplantation and associated with post-transplant hypophosphatemia and increased phosphorus excretion. Post-transplant αKlotho was low early post-transplant but tended to increase subsequently. Post-transplant αKlotho was unaffected by pre-transplant FGF23 or other factors, suggesting pre-transplant chronic kidney disease status has no effect.

Deep venous thrombosis in a kidney transplant recipient with COVID-19: a case report.

The outcomes of COVID-19 in kidney transplant recipients have shown high mortality. In addition to their immunocompromised states, kidney transplant recipients frequently have certain exacerbation risk comorbidities of COVID-19, such as diabetes mellitus, hypertension, and chronic kidney disease. Several concomitant diseases develop during the course of COVID-19, one of which is thromboembolism, which can potentially lead to a critical condition. However, thromboembolic complications in kidney transplant recipients with COVID-19 have not been fully addressed in previous studies. A 62-year-old man, who underwent kidney transplantation 17 years ago, was diagnosed with COVID-19 and was admitted to our hospital. Although the patient was in remission at the start of the hospitalization, his condition became severe on day 7 after admission, with fever, elevated white blood cell counts (10,000/µL) and a high C-reactive protein level (6.9 mg/dL). Although the patient was not under forced bed rest, an ultrasound study on day 10 detected deep venous thrombosis (DVT), with an elevated D-dimer level (6.2 µg/dL). We withdrew the mycophenolate mofetyl and the tacrolimus dosage but did not administer any specific treatment for COVID-19. The patient achieved successful clearance of SARS-CoV-2 on day 16. The DVT disappeared after systematic heparin treatment and oral rivaroxaban for 2 months. DVT occurred in a kidney transplant recipient with COVID-19 who was not bedridden and might manifest when the clinical status was exacerbated during hospitalization.

Prevalence of hypothyroidism in Japanese chronic kidney disease patients.

Background: Major symptoms of progressive chronic kidney disease (CKD) are similar to those of hypothyroidism. Hidden symptoms of hypothyroidism underlying CKD are often observed in clinical practice. This study aimed to ascertain the frequency of hypothyroidism complicated by CKD, and to analyze factors impacting thyroid function.Methods: During the period from April 2012 through October 2016, 510 CKD patients at our outpatient clinic were measured thyroid and kidney function for diagnosing hypothyroidism (overt hypothyroidism, OH; subclinical hypothyroidism, SH; non-thyroidal illness, NTI) and evaluating the stage of CKD. All patients were over 15 years of age.Results: There were significant differences in age, estimated glomerular filtration rate (eGFR), urinary protein (UP), and serum albumin (Alb) among patients with OH, SH, and NTI compared to the normal group in univariate and multivariate analyses. UP showed the highest odds ratio of OH, SH, and NTI but no differences were recognized in gender in each group. Frequency distribution showed that the prevalence of thyroid dysfunction was greater among more severe stage of CKD with higher amount of UP. OH and SH did not show high positive ratio of anti-thyroglobulin antibody (TgAb) and anti-thyroid peroxidase antibody (TPOAb). NTI and normal subjects showed higher positive ratio as 50.0% and 42.9% of TgAb and TPOAb than OH and SH.Conclusions: Hypothyroidism complicated by CKD exhibited a high prevalence. Age, eGFR, UP, and serum Alb were related to the prevalence of hypothyroidism, whereas gender was not and this was contradicted to the prevalence of hypothyroidism in general population. The prevalence of OH and SH was higher among patients with higher stage of CKD with increased UP. Hypothyroidism complicated by CKD may involve different onset mechanisms unrelated to antithyroid antibodies (ATAb). In CKD patients, assessments of OH and SH, as well as NTI, are needed for proper diagnosis.

Epidemiologic features of Kawasaki disease distinguished by seasonal variation: an age-specific analysis.

PURPOSE: The purpose of this study was to review the seasonal variation of Kawasaki disease (KD) by an age-specific analysis to clarify the distribution of infectious agents. METHODS: Data obtained from nationwide surveys of KD in Japan, which targeted patients for 12 years (2003-2014), were analyzed. The monthly numbers of patients were classified into the following age groups: 0-11 months, 1 year, 2-3 years 5 months, and 3 years 6 months-4 years. Factors associated with disease onset were analyzed using a 12-month moving average method. RESULTS: In winter, a sharp peak was observed in all age groups, but this was notably sharper in the 1-year age group. Plateaus in disease occurrence were observed in two periods: from March to May in the 2- to 4-year age group and from June to August in the 0- to 11-month age group. Seasonal index was analyzed into two factors that differed depending on the age group. CONCLUSIONS: The age-specific analysis of KD clearly identified age-related differences in the seasonal occurrence of this disease.

Brain Natriuretic Peptide and Body Fluid Composition in Patients with Chronic Kidney Disease: A Cross-Sectional Study to Evaluate the Relationship between Volume Overload and Malnutrition.

BACKGROUND/AIM: Fluid volume overload occurs in chronic kidney disease (CKD), leading to the compensatory release of natriuretic peptides. However, the elevated cardiac peptides may also be associated with malnutrition as well as volume overload. METHODS: Body fluid composition was measured in 147 patients with CKD between 2009 and 2015, and its relationship to brain natriuretic peptide (BNP) levels was examined. Body fluid composition was separated into three components: (a) a water-free mass consisting of muscle, fat, and minerals; (b) intracellular water (ICW) content, and (c) extracellular water (ECW) content. Excess fluid mass was calculated using Chamney's formula. RESULTS: The measured BNP levels in the tertile groups were 10.9 ± 5.4, 36.3 ± 12.5, and 393 ± 542 pg/ml, respectively. Patients in a higher log-transformed BNP level tertile were more likely to be older, to have a higher frequency of cardiac comorbidities, pulse pressure, C-reactive protein levels, and proteinuria, and to have lower serum sodium, kidney function, and serum albumin (p < 0.05). In body fluid composition, decreased body mass was significantly associated with the ECW-to-ICW ratio in relation to the downward ICW slope (r = -0.235, p = 0.004) and was strongly correlated with excess fluid mass (r = -0.701, p < 0.001). The ECW-to-ICW ratio and excess fluid mass was independently associated with the BNP levels. CONCLUSION: Fluid volume imbalance between intra- and extracellular water regulated by decreased cell mass was independently associated with BNP levels, which may explain the reserve capacity for fluid accumulation in patients with CKD.

Seasonal patterns of legionellosis in Saitama, 2005-2009.

Sporadic cases of legionellosis have increased in Saitama Prefecture. This study aimed to understand the characteristics and incidence of legionellosis in Saitama Prefecture by studying the corresponding data from Tokyo and all over Japan. We analyzed cases of legionellosis registered from 2005 through 2009 in the annual reports of the Infectious Disease Surveillance Center. There were two peaks in the incidence of legionellosis in Japan between June and November, and a trough between February and May every year. Similar seasonal characteristics were observed in both Tokyo and Saitama. Proper management of risk factors-such as cooling towers and other aerosol-generating devices, before and during the seasonal increase in these incidences-is essential as a prophylactic measure against legionellosis.

[A diffuse outbreak of enterohemorrhagic Escherichia coli O157:H7 related to the Japanese-style pickles in Saitama, Japan].

We have experienced an outbreak of enterohemorrhagic E. coli O157:H7 (Shiga-like toxin 1 & 2 producing) in child independence support facilities in the all dormitory system, in Saitama August 2001. There were 13 patient and EHEC O157s were detected in a total of 29 specimens. As a result of epidemic inspection and microbiological investigation. We recognized that the causative food was Japanese-style pickles named "Wafu-Kimuchi" which had been sold in Saitama and Tokyo area. As the same period, several infections caused by EHEC O157 were considered the same origin in Saitama (8 patients in 5 families). Furthermore some infections happened also in Tokyo. It was made clear this outbreak was a part of a diffuse outbreak caused by Wafu-Kimuchi. In diffuse outbreaks, it is important to grasp a common feature of the individual cases in a wide area. The exchange of epidemic information between two or more municipalities and the guess of the identity in the DNA levels of strains were the key role to the elucidation of this case.

Prevalence of pandemic thermostable direct hemolysin-producing Vibrio parahaemolyticus O3:K6 in seafood and the coastal environment in Japan.

Although thermostable direct hemolysin (TDH)-producing Vibrio parahaemolyticus has caused many infections in Asian countries, the United States, and other countries, it has been difficult to detect the same pathogen in seafoods and other environmental samples. In this study, we detected and enumerated tdh gene-positive V. parahaemolyticus in Japanese seafoods with a tdh-specific PCR method, a chromogenic agar medium, and a most-probable-number method. The tdh gene was detected in 33 of 329 seafood samples (10.0%). The number of tdh-positive V. parahaemolyticus ranged from <3 to 93/10 g. The incidence of tdh-positive V. parahaemolyticus tended to be high in samples contaminated with relatively high levels of total V. parahaemolyticus. TDH-producing strains of V. parahaemolyticus were isolated from 11 of 33 tdh-positive samples (short-necked clam, hen clam, and rock oyster). TDH-producing strains of V. parahaemolyticus were also isolated from the sediments of rivers near the coast in Japan. Representative strains of the seafood and sediment isolates were examined for the O:K serovar and by the PCR method specific to the pandemic clone and arbitrarily primed PCR and pulsed-field gel electrophoresis techniques. The results indicated that most O3:K6 tdh-positive strains belonged to the pandemic O3:K6 clone and suggested that serovariation took place in the Japanese environment.

[A rapid screening method for the detection of E. coli O157 by an automated enzyme-linked fluorescent immunoassay].

VIDAS ECO is useful as a rapid method for detecting E. coli O157 from food samples, because one can obtain the results within 1 hour by examining the enrichment broth after a 18 hour incubation. In addition, one can handle a large amount of sample, owing to its simplicity. No false negative were recognized in the present experiment and diffuse outbreak samples cases, which confirmed the usefulness of ECO as a screening method. Besides, regarding ECO positive samples, we could confirm by the following day, that they were false positive, by a combined test using an isolation medium after a bead-enzyme-linked immunosorbent assay.

Genome Variation among Listeria monocytogenes Isolates Derived from Epidemiologically Related Raw Milk and Other Strains.

Listeria monocytogenes strains were examined by restriction-enzyme analysis of chromosomal DNA using a total of 18 restriction enzymes. Ten of the 6-base restriction enzymes and one 8-base restriction enzyme produced distinguishable fragments among these strains. Six strains (serotype 1/2a) recovered from raw milk suspected of the same contaminant were compared with seven epidemiologically unrelated strains (serotype 1/2a) using 10 of the 6-base restriction enzymes. The restriction enzyme patterns of the six raw milk isolates were identical to each other, but differed from those of the other strains. Restriction-enzyme analysis of the chromosomal DNA of L. monocytogenes by using the 6-base restriction enzymes may be a useful method of epidemiological analysis for listeriosis outbreaks.