Incidence of Multiple Paternity and Inbreeding in High-Density Brown Bear Populations on the Shiretoko Peninsula, Hokkaido, Japan.

Understanding the breeding ecology of a species is essential for the appropriate conservation and management of wildlife. In brown bears, females occasionally copulate with multiple males in one breeding season, which may lead to multiple paternity in a single litter. In contrast, inbreeding, a potential factor in the reduction of genetic diversity, may occur, particularly in threatened populations. However, few studies have reported the frequency of these phenomena in brown bear populations. Here, we investigated the incidence of multiple paternity and inbreeding in a high-density brown bear population on the Shiretoko Peninsula in Hokkaido, Japan. A total of 837 individuals collected from 1998 to 2017 were genotyped at 21 microsatellite loci, and parentage analysis was performed. Out of 70-82 litters with ≥2 offspring, 14.6-17.1% of litters were sired by multiple males. This was comparable to the rate reported in a Scandinavian population, although population density and litter size, factors that potentially affect the incidence of multiple paternity, differed between the 2 populations. Out of 222 mother-father mating pairs, 6 litters (2.7%) resulted from matings between fathers and daughters. Additionally, 1 (0.5%) and 4 (1.8%) cases of mating between maternal half-siblings and between paternal half-siblings, respectively, were observed; however, no cases of mating between mothers and sons or between full siblings were observed. Our results suggest that male-biased natal dispersal effectively limits mating between closely related individuals (aside from fathers and daughters) in brown bears.

Molecular phylogeography of the brown bear (Ursus arctos) in Northeastern Asia based on analyses of complete mitochondrial DNA sequences.

To further elucidate the migration history of the brown bears (Ursus arctos) on Hokkaido Island, Japan, we analyzed the complete mitochondrial DNA (mtDNA) sequences of 35 brown bears from Hokkaido, the southern Kuril Islands (Etorofu and Kunashiri), Sakhalin Island, and the Eurasian Continent (continental Russia, Bulgaria, and Tibet), and those of four polar bears. Based on these sequences, we reconstructed the maternal phylogeny of the brown bear and estimated divergence times to investigate the timing of brown bear migrations, especially in northeastern Eurasia. Our gene tree showed the mtDNA haplotypes of all 73 brown and polar bears to be divided into eight divergent lineages. The brown bear on Hokkaido was divided into three lineages (central, eastern, and southern). The Sakhalin brown bear grouped with eastern European and western Alaskan brown bears. Etorofu and Kunashiri brown bears were closely related to eastern Hokkaido brown bears and could have diverged from the eastern Hokkaido lineage after formation of the channel between Hokkaido and the southern Kuril Islands. Tibetan brown bears diverged early in the eastern lineage. Southern Hokkaido brown bears were closely related to North American brown bears.

Trichinella T9 in wild bears in Japan: Prevalence, species/genotype identification, and public health implications.

In Japan, the recent series of sporadic outbreaks of human trichinellosis caused by Trichinella (Nematoda: Trichocephalida) has occurred owing to the consumption of raw or insufficiently cooked meat from wild bears. However, the infection status and molecular characteristics of Trichinella larvae in Japanese wild bears remain poorly understood. This study investigated the prevalence of Trichinella spp. in brown bears (Ursus arctos) from Hokkaido, and Japanese black bears (Ursus thibetanus japonicus) from three prefectures (Aomori, Akita, and Iwate) in northern Japan, between April 2019 and August 2022. Trichinella larvae were detected in 2.5% (6/236) of the brown bears and 0.9% (1/117) of the Japanese black bears. Sequence analysis using two genetic loci, the internal transcribed spacer region of nuclear ribosomal DNA and the mitochondrial cytochrome c oxidase subunit I gene, revealed that the larvae collected from the seven infected bears were identical to one of the two haplotypes of Trichinella T9. The prevalence of Trichinella T9 is low but is maintained in bears in the Hokkaido and Iwate prefectures suggesting that undercooked meat from these animals could cause human infection. Thus, continued health education campaigns are needed to raise awareness of the potential risk of trichinellosis among hunters, meat suppliers, consumers, and local governmental health agencies.

Estimation of breeding population size using DNA-based pedigree reconstruction in brown bears.

Robust estimates of demographic parameters are critical for effective wildlife conservation and management but are difficult to obtain for elusive species. We estimated the breeding and adult population sizes, as well as the minimum population size, in a high-density brown bear population on the Shiretoko Peninsula, in Hokkaido, Japan, using DNA-based pedigree reconstruction. A total of 1288 individuals, collected in and around the Shiretoko Peninsula between 1998 and 2020, were genotyped at 21 microsatellite loci. Among them, 499 individuals were identified by intensive genetic sampling conducted in two consecutive years (2019 and 2020) mainly by noninvasive methods (e.g., hair and fecal DNA). Among them, both parents were assigned for 330 bears, and either maternity or paternity was assigned to 47 and 76 individuals, respectively. The subsequent pedigree reconstruction indicated a range of breeding and adult (≥4 years old) population sizes: 128-173 for female breeders and 66-91 male breeders, and 155-200 for female adults and 84-109 male adults. The minimum population size was estimated to be 449 (252 females and 197 males) in 2019. Long-term continuous genetic sampling prior to a short-term intensive survey would enable parentage to be identified in a population with a high probability, thus enabling reliable estimates of breeding population size for elusive species.

Demographic History of the Brown Bear (Ursus arctos) on Hokkaido Island, Japan, Based on Whole-Genomic Sequence Analysis.

Previous studies of the brown bear (Ursus arctos) on Hokkaido Island, Japan, have detected three geographically distinct subpopulations representing different mitochondrial lineages and shown that gene flow between subpopulations has occurred due to male-biased dispersal. In this study, we determined whole-genomic sequences for six Hokkaido brown bears and analyzed these data along with previously published genomic sequences of 17 brown bears from other parts of the world. We found that the Hokkaido population is genetically distinct from the other populations, keeping genetic diversity higher than the endangered populations in western Europe but lower than most populations on the continents. A reconstruction of historical demography showed no increase in population size for the Hokkaido population during the Eemian interglacial period (130,000-114,000 years ago). In a phylogenetic analysis of the autosomal data, the Hokkaido population formed a clade distinct from North American and European populations, showing that it has maintained genetic diversity independently from continental populations following geographical isolation on the island. This autosomal genetic similarity contrasts with the geographically separate mitochondrial lineages on Hokkaido and indicates the occurrence of male-driven gene flow between subpopulations.

Development of a noninvasive photograph-based method for the evaluation of body condition in free-ranging brown bears.

Body condition is an important determinant of health, and its evaluation has practical applications for the conservation and management of mammals. We developed a noninvasive method that uses photographs to assess the body condition of free-ranging brown bears (Ursus arctos) in the Shiretoko Peninsula, Hokkaido, Japan. First, we weighed and measured 476 bears captured during 1998-2017 and calculated their body condition index (BCI) based on residuals from the regression of body mass against body length. BCI showed seasonal changes and was lower in spring and summer than in autumn. The torso height:body length ratio was strongly correlated with BCI, which suggests that it can be used as an indicator of body condition. Second, we examined the precision of photograph-based measurements using an identifiable bear in the Rusha area, a special wildlife protection area on the peninsula. A total of 220 lateral photographs of this bear were taken September 24-26, 2017, and classified according to bear posture. The torso height:body/torso length ratio was calculated with four measurement methods and compared among bear postures in the photographs. The results showed torso height:horizontal torso length (TH:HTL) to be the indicator that could be applied to photographs of the most diverse postures, and its coefficient of variation for measurements was <5%. In addition, when analyzing photographs of this bear taken from June to October during 2016-2018, TH:HTL was significantly higher in autumn than in spring/summer, which indicates that this ratio reflects seasonal changes in body condition in wild bears. Third, we calculated BCI from actual measurements of seven females captured in the Rusha area and TH:HTL from photographs of the same individuals. We found a significant positive relationship between TH:HTL and BCI, which suggests that the body condition of brown bears can be estimated with high accuracy based on photographs. Our simple and accurate method is useful for monitoring bear body condition repeatedly over the years and contributes to further investigation of the relationships among body condition, food habits, and reproductive success.

Maternal human habituation enhances sons' risk of human-caused mortality in a large carnivore, brown bears.

Human habituation of large carnivores is becoming a serious problem that generates human-wildlife conflict, which often results in the removal of animals as nuisances. Although never tested, human habituation potentially reduces the fitness of adult females by reducing their offspring's survival as well as their own, due to an increased likelihood of human-caused mortality. Here, we tested this hypothesis in brown bears inhabiting Shiretoko National Park, Japan. We estimated the frequency of human-caused mortality of independent young (aged 1-4 years) born to mothers living in areas with different maternal levels of human habituation and different proximities to areas of human activity. The overall mortality rate was higher in males than in females, and in females living near a town than those in a remote area of park. Surprisingly, more than 70% of males born to highly habituated mothers living around a remote wildlife protection area were killed by humans; this proportion is greater than that for males born to less-habituated mothers living in almost the same area. The current study clarified that interactions among maternal human habituation, birthplace (proximity to town), age, and sex determine the likelihood of human-caused mortality of brown bears at an early stage of life.

Genetic diversity of the MHC class-II DQA gene in brown bears (Ursus arctos) on Hokkaido, Northern Japan.

To investigate genetic diversity of a major histocompatibility complex (MHC) gene in the brown bear (Ursus arctos) population on Hokkaido Island, northern Japan, we cloned and sequenced parts of exon 2 and intron 2 of the MHC class-II DQA gene from 32 brown bears. According to strict criteria for allele identification established by mammalian MHC nomenclature committees, four DQA types (Urar-DQA*01 to Urar-DQA*04) were identified. Of the four, however, Urar-DQA*04 had a 12-bp deletion not detected in a cDNA analysis, indicating that this is a pseudogene at a distinct locus generated by gene duplication. The nucleotide sequences of the other three DQA alleles, which were expressed (because detected from cDNA), were very similar, indicating lower DQA variation In the Hokkaido brown bear population than in other mammals. We attribute this low genetic diversity to (1) some limited effect of possible balancing selection; (2) bottlenecks and inbreeding after migration and isolation of the Hokkaido brown bear population from the Eurasian Continent; (3) a much slower evolutionary rate in DQA than in other MHC genes in the Hokkaido brown bear population.

Pathological regression by angiotensin II type 1 receptor blockade in patients with mesangial proliferative glomerulonephritis.

Although angiotensin II type 1 receptor blocker (ARB) therapy reduces proteinuria and retards the progression of renal injury in patients with glomerulonephritis, whether these drugs actually ameliorate pathological damages in human glomerulonephritis has not been determined. Fifteen patients with biopsy-proven mild-to-moderate mesangial proliferative glomerulonephritis (10 with immunoglobulin A [IgA] nephropathy and 5 with non-IgA mesangial proliferative glomerulonephritis) received ARB monotherapy. In these patients, repeated renal biopsy was performed after a mean of 28.1 months, and pathological changes (including the mesangial matrix expansion ratio and interstitial fibrosis expansion ratio) were quantitatively examined using an image analyzer. Clinical markers were also evaluated, including the serum creatinine, serum IgA, creatinine clearance (Ccr), 24-h urinary protein excretion, urinary N-acetyl-beta-D-glucosaminidase (NAG), and blood pressure. ARB therapy significantly reduced urinary protein excretion (0.68+/-0.63 to 0.20+/-0.32 g/day, p=0.016) and the blood pressure (systolic: 133.3+/-18.2 to 123.4+/-10.5 mmHg, p=0.041; diastolic: 79.4+/-11.9 to 72.0+/-8.2 mmHg, p=0.038). Although the global glomerular sclerosis ratio was unchanged (6.3+/-8.5% to 10.7+/-16.1%, p=0.33), the mesangial matrix expansion ratio (33.1+/-10.8% to 22.7+/-7.8%, p=0.001) and the interstitial fibrosis ratio (19.9+/-5.8% to 13.8+/-4.4%, p=0.034) were significantly reduced by ARB treatment. The levels of pathological improvement were similar between patients with IgA nephropathy and those with non-IgA mesangial proliferative glomerulonephritis. The results of the present study strongly suggest that ARB monotherapy can significantly reverse pathological changes, including mesangial matrix expansion and interstitial fibrosis, in human glomerulonephritis.

Glucose metabolism, insulin resistance, and renal pathology in non-diabetic chronic kidney disease.

BACKGROUND: The relation between insulin resistance and atherosclerosis is widely recognized, but it remains unknown whether glucose metabolism/insulin resistance is related to renal pathology in humans. METHODS: We quantitatively evaluated pathological changes in the glomeruli, tubulointerstitium, and vessels in renal biopsy specimens from 23 patients with non-diabetic chronic kidney disease (CKD), all of whom took a 75-gram oral glucose tolerance test. We correlated the renal pathological changes with fasting plasma glucose (FPG), fasting plasma insulin, 2-hour plasma glucose (2-h PG), 2-hour plasma insulin (2-h PI), homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index. RESULTS: HOMA-IR exceeded 1.73 in 11 patients (47.8%), and 2-h PI exceeded 64.0 microU/ml in 14 (60.9%). FPG significantly correlated with interstitial fibrosis (r = 0.532, p = 0.009). The significance was marginal in the correlation between FPG and tubular atrophy and arterio-arteriolosclerosis. Statistically significant correlation was also found between 2-h PG and arterio-arteriolosclerosis (r = 0.422, p = 0.04) and between HOMA-IR and interstitial fibrosis (r = 0.416, p = 0.04). CONCLUSION: Although precise mechanisms remain unknown, glucose metabolism/insulin resistance seem to play pathogenic roles in formation and progression of renal pathological changes, especially tubulointerstitial and vascular lesions, in non-diabetic CKD.

High-density lipoprotein cholesterol and left ventricular mass index in peritoneal dialysis.

OBJECTIVE: The prevalence of left ventricular hypertrophy (LVH) reaches 75% in patients with end-stage renal disease. In patients on peritoneal dialysis (PD), some factors, such as hypertension, volume overload, serum albumin, and residual renal function, have been reported to be related to LVH. Dyslipidemia often occurs in PD but it remains unclear whether dyslipidemia is related to LVH. We investigated the relationship between clinical parameters, including lipid profile, and left ventricular mass index (LVMI). METHODS: In this cross-sectional study, 34 patients undergoing PD for more than 1 year without combined therapy with hemodialysis were included. We recorded the patients' clinical data and related those parameters with LVMI as evaluated by echocardiography. RESULTS: The patients included 23 males and 11 females (age 62.2 +/- 12.1 years, duration on PD 31.6 +/- 15.6 months). Mean LVMI was 142 +/- 37 g/m2. In univariate analysis, urine volume (r = -0.493, p = 0.003), total cholesterol (r = -0.418, p = 0.01), high-density lipoprotein cholesterol (HDL-C; r = -0.374, p = 0.02), and human atrial natriuretic peptide (hANP; r = 0.600, p < 0.001) significantly correlated with LVMI. Stepwise multiple regression analysis showed that hANP (beta = 0.524, p = 0.001) and HDL-C (beta = -0.422, p = 0.007) were independently associated with LVMI (r2 = 0.32). CONCLUSION: Strict volume control and salt restriction is essential for prevention of LVH. The role of HDL-C in the development of LVH in PD patients remains to be determined.

Epizootiological survey of Trichinella spp. infection in carnivores, rodents and insectivores in Hokkaido, Japan.

In order to evaluate the present epidemiological situation of Trichinella infection in wild animals in Hokkaido, Japan, red foxes (Vulpes vulpes), raccoon dogs (Nyctereutes procyonoides) , brown bears (Ursus arctos) , martens (Martes melampus), rodents and insectivores captured in Hokkaido were examined for muscle larvae by the artificial digestion method from 2000 to 2006. Foxes (44/319, 13.8%), raccoon dogs (6/77, 7.8%) and brown bears (4/126, 3.2%) were found to be infected with Trichinella larvae and all other animal species evaluated were negative. Multiplex PCR and DNA sequencing revealed that larvae from a fox captured in Otofuke, in south-eastern Hokkaido, were T. nativa, and larvae from 27 animals including 21 foxes, 2 raccoon dogs and 4 brown bears captured in western Hokkaido were Trichinella T9.

Paternal phylogeographic structure of the brown bear (Ursus arctos) in northeastern Asia and the effect of male-mediated gene flow to insular populations.

BACKGROUND: Sex-biased dispersal is widespread among mammals, including the brown bear (Ursus arctos). Previous phylogeographic studies of the brown bear based on maternally inherited mitochondrial DNA have shown intraspecific genetic structuring around the northern hemisphere. The brown bears on Hokkaido Island, northern Japan, comprise three distinct maternal lineages that presumably immigrated to the island from the continent in three different periods. Here, we investigate the paternal genetic structure across northeastern Asia and assess the connectivity among and within intraspecific populations in terms of male-mediated gene flow. RESULTS: We analyzed paternally inherited Y-chromosomal DNA sequence data and Y-linked microsatellite data of 124 brown bears from Hokkaido, the southern Kuril Islands (Kunashiri and Etorofu), Sakhalin, and continental Eurasia (Kamchatka Peninsula, Ural Mountains, European Russia, and Tibet). The Hokkaido brown bear population is paternally differentiated from, and lacked recent genetic connectivity with, the continental Eurasian and North American populations. We detected weak spatial genetic structuring of the paternal lineages on Hokkaido, which may have arisen through male-mediated gene flow among natal populations. In addition, our results suggest that the different dispersal patterns between male and female brown bears, combined with the founder effect and subsequent genetic drift, contributed to the makeup of the Etorofu Island population, in which the maternal and paternal lineages show different origins. CONCLUSIONS: Brown bears on Hokkaido and the adjacent southern Kuril Islands experienced different maternal and paternal evolutionary histories. Our results indicate that sex-biased dispersal has played a significant role in the evolutionary history of the brown bear in continental populations and in peripheral insular populations, such as on Hokkaido, the southern Kuril Islands, and Sakhalin.

Peripheral arterial occlusive disease is more prevalent in patients with hemodialysis: comparison with the findings of multidetector-row computed tomography.

BACKGROUND: Peripheral arterial occlusive disease (PAOD) influences the mortality of patients on hemodialysis therapy. Although the ankle-brachial pressure index (ABI) is used widely to detect PAOD, it yields false-negative results because of calcifications of vascular walls. To more accurately assess the prevalence of PAOD, we investigated which noninvasive method, among ABI, toe-brachial pressure index, transcutaneous Po(2), and skin perfusion pressure (SPP), had superior sensitivity and specificity to the others. METHODS: Multidetector-row computed tomography was performed in 36 hemodialysis patients. We then compared the 4 noninvasive methods with findings of multidetector-row computed tomography and calculated the sensitivity and specificity of each method by means of receiver operating characteristic analysis. Irrespective of symptoms, PAOD is defined as the presence of complete obstruction in the case of lesions below the knee or more than 75% stenosis for lesions above the knee. RESULTS: Seven of 36 patients (19.4%) had an ABI less than 0.9. Sensitivity of the ABI was only 29.9%, whereas an SPP set at 50 mm Hg was more accurate, with sensitivity of 84.9% and specificity of 76.9%. A total of 41.4% of patients had an SPP less than 50 mm Hg. For lesions located above the knee, toe-brachial pressure index provided sensitivity of 91.7% and specificity of 86.7%. CONCLUSION: SPP is the most useful tool for detecting PAOD in hemodialysis patients, with accuracy of 84.9%. There is a strong possibility that more patients than previously expected have early PAOD.

A rare case of combined syndrome of inappropriate antidiuretic hormone secretion and Fanconi syndrome in an elderly woman.

An 83-year-old Japanese woman was admitted to our hospital with severe hyponatremia (sodium, 108 mEq/L [108 mmol/L]), hypokalemia, hypochloridemia, hypocalcemia, hypophosphatemia, and hypouricemia. Despite low plasma osmolarity (232 mOsm/kg [232 mmol/kg]), urine osmolarity (320 mOsm/kg) was greater than that of plasma, and she had increased urinary sodium excretion (88 mEq/L [88 mmol/L]) and an unsuppressed high plasma level of antidiuretic hormone (ADH; 5.5 pg/mL [5.1 pmol/L]). These findings indicated that she had syndrome of inappropriate ADH secretion (SIADH). In addition, she had a generalized reabsorption defect of the proximal tubules, including decreased tubular reabsorption of phosphate, increased fractional excretion of uric acid, glycosuria despite a normal blood glucose level, and panaminoaciduria. Thus, combined SIADH and Fanconi syndrome was diagnosed. The cause was thought to be the antidepressant paroxetine, which is a selective serotonin reuptake inhibitor (SSRI). Several of the abnormal values resolved within 1 week after discontinuation of this drug. Although the precise mechanism responsible was not elucidated, we report an extremely rare case of combined SIADH and Fanconi syndrome, probably caused by short-term SSRI therapy.

[Clinical analysis of time-course changes in minerals and parathyroid hormone levels during treatment with phosphate binders in hemodialysis patients with secondary hyperparathyroidism].

146 hemodialysis (HD) patients with secondary hyperparathyroidism (2 degrees HPT) were studied about the therapeutic effects of phosphate binders. We divided these patients into four groups; Group I: 59 patients treated with CaCO(3) (1.5-6.0 g/day), Group II: 42 cases with sevelamer hydrochloride (0.75-9.0 g/day), Group III: 30 with both CaCO(3) and sevelamer, Group IV: 15 with both CaCO(3) and cholestimide (1.5-6.0 g/day). These patients were prescribed several phosphate binders for at least 18 months. The serum levels of P, albumin-corrected Ca (Ca), Ca x P product and intact parathyroid hormone (iPTH) were serially determined. In Group I and IV, these four parameters showed no significant difference between at before administration and at after 1, 3, 6 and 12 months. In Group II, the values of iPTH, Ca and Ca x P product between at before sevelamer administration and at after 9 months were 199.43+/-94.40 vs 159.86+/-96.03 pg/mL (p<0.05), 9.48+/-1.12 vs 9.01+/-1.00 mg/dL (p<0.05) and 62.72+/-19.62 vs 50.44+/-25.97 mg(2)/dL(2) (p<0.05), respectively. In Group III, P showed significant decrease from 7.16+/-1.33 to 6.72+/-1.69 mg/dL (p<0.05) between at the time of adding sevelamer to CaCO(3) and at after nine months. These results indicate that sevelamer plays an excellent role in the treatment of 2 degrees HPT mainly by controlling Ca level and the combination therapy with CaCO(3) is useful for improvement of P level in patients undergoing HD.

Major decline in marine and terrestrial animal consumption by brown bears (Ursus arctos).

Human activities have had the strongest impacts on natural ecosystems since the last glacial period, including the alteration of interspecific relationships such as food webs. In this paper, we present a historical record of major alterations of trophic structure by revealing millennium-scale dietary shifts of brown bears (Ursus arctos) on the Hokkaido islands, Japan, using carbon, nitrogen, and sulfur stable isotope analysis. Dietary analysis of brown bears revealed that salmon consumption by bears in the eastern region of Hokkaido significantly decreased from 19% to 8%. In addition, consumption of terrestrial animals decreased from 56% to 5% in western region, and 64% to 8% in eastern region. These dietary shifts are likely to have occurred in the last approximately 100-200 years, which coincides with the beginning of modernisation in this region. Our results suggest that human activities have caused an alteration in the trophic structure of brown bears in the Hokkaido islands. This alteration includes a major decline in the marine-terrestrial linkage in eastern region, and a loss of indirect-interactions between bears and wolves, because the interactions potentially enhanced deer predation by brown bears.

Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for mtDNA typing in hokkaido brown bear (Ursus arctos yesoensis).

To develop an easy method of typing of mitochondrial DNA (mtDNA) in Hokkaido brown bears (Ursus arctos yesoensis), the PCR-RFLP technique was improved using four restriction enzymes: Mbo 1, Cfr 13 I, TspE 1, and Fok 1. This approach identified seven groups of mtDNA haplotypes, HB1/2/5-7, HB 3, HB4, HB8/9, HB10/11, HB12 and HB13 from 102 brown bears of northern, central and eastern Hokkaido.

Impact of coronary artery calcification in hemodialysis patients: Risk factors and associations with prognosis.

The risk factors of coronary artery calcification (CAC) and the impact of CAC on cardiovascular events, cardiovascular deaths, and all-cause deaths in hemodialysis (HD) patients have not been fully elucidated. We examined the CAC score (CACS) in 74 HD patients using electron-beam computed tomography. Fifty-six patients underwent a second electron-beam computed tomography after a 15-month interval to evaluate CAC progression. We evaluated (1) the risk factors for CAC and its progression and (2) the impact of CAC on the prognosis. In the cross-sectional study, HD vintage and high-sensitive C-reactive protein (hsCRP) were the independent risk factors for CAC. In the prospective cohort study, delta CACS (progression of CAC) was significantly correlated with hsCRP, fibrinogen, and serum calcium level in the univariate analysis. Stepwise multiple regression analysis revealed that only hsCRP was the independent risk factor for CAC progression in HD patients. Kaplan-Meier survival analysis revealed that cardiovascular events (P<0.0001), cardiovascular deaths (P=0.039), and all-cause deaths (P=0.026) were significantly associated with CACS. In conclusion, CAC had significantly progressed in HD patients during the 15-month observation period. Microinflammation was the only independent risk factor for CAC progression in HD patients. The advanced CAC was a significant prognostic factor in HD patients, i.e., which was strongly associated with future cardiovascular events, cardiovascular deaths, and all-cause deaths.