Factors associated with chronic musculoskeletal pain in patients with chronic kidney disease.

BACKGROUND: Chronic musculoskeletal (MS) pain is common in patients with chronic kidney disease (CKD) undergoing haemodialysis. However, epidemiological data for chronic MS pain and factors associated with chronic MS pain in patients with early- or late-stage CKD who are not undergoing dialysis are limited. METHOD: A cross-sectional study to evaluate the prevalence of chronic MS pain and factors associated with chronic MS pain in patients with early- and late-stage CKD who were not undergoing dialysis, was conducted. In addition, the distribution of pain severity among patients with different stages of CKD was evaluated. RESULTS: Of the 456 CKD patients studied, 53.3% (n = 243/456) had chronic MS pain. Chronic MS pain was independently and significantly associated with hyperuricemia as co-morbidity, as well as with the calcium × phosphate product levels. In CKD patients with hyperuricemia, chronic MS pain showed a negative, independent significant association with diabetes mellitus as a co-morbidity (odds ratio: 0.413, p = 0.020). However, in the CKD patients without hyperuricemia as a co-morbidity, chronic MS pain showed an independent significant association with the calcium × phosphate product levels (odds ratio: 1.093, p = 0.027). Furthermore, stage-5 CKD patients seemed to experience more severe chronic MS pain than patients with other stages of CKD. CONCLUSION: Chronic MS pain is common in CKD patients. Chronic MS pain was independently and significantly associated with hyperuricemia as co-morbidity, and with the calcium × phosphate product levels in early- and late-stage CKD patients who were not on dialysis.

Diflunisal versus tafamidis on neuropathy and cardiomyopathy in hereditary transthyretin amyloidosis.

OBJECTIVES: Hereditary transthyretin (TTR) amyloidosis (ATTRv) is frequently complicated by polyneuropathy (ATTRv-PN) and cardiomyopathy (ATTRv-CM). The long-term efficacy of diflunisal on both polyneuropathy and cardiomyopathy in ATTRv patients, especially those with non-V30M genotypes, has not been fully investigated and compared with that of tafamidis. METHODS: We compared the structural and biochemical characteristics of A97S-TTR complexed with tafamidis with those of diflunisal, and prospectively followed up and compared the progression of polyneuropathy and cardiomyopathy between ATTRv-PN patients taking diflunisal and those taking tafamidis. RESULTS: Both diflunisal and tafamidis effectively bind to the two thyroxine-binding sites at the A97S-TTR dimer-dimer interface and equally and almost sufficiently reduce amyloid fibril formation. Thirty-five ATTRv-PN patients receiving diflunisal and 22 patients receiving tafamidis were enrolled. Compared with no treatment, diflunisal treatment significantly delayed the transition of FAP Stage 1 to 2 and Stage 2 to 3 and decreased the deterioration in parameters of the ulnar nerve conduction study (NCS). The progression of FAP stage or NCS parameters did not differ between patients treated with diflunisal and those treated with tafamidis. Both diflunisal and tafamidis treatments significantly decreased radiotracer uptake on 99mTc-PYP SPECT and stabilized cardiac wall thickness and blood pro-B-type natriuretic peptide levels. No significant adverse events occurred during diflunisal or tafamidis treatment. INTERPRETATIONS: The binding patterns of both tafamidis and diflunisal to A97S-TTR closely resembled those observed in the wild type. Diflunisal can effectively delay the progression of polyneuropathy and cardiomyopathy with similar efficacy to tafamidis and may become a cost-effective alternative treatment for late-onset ATTRv-PN.

Association between cold dialysis and cardiovascular survival in hemodialysis patients.

BACKGROUND: Higher cardiovascular mortality has been noted in patients with chronic kidney disease (CKD). CKD patients are also known to have impaired energy expenditure but the role of energy expenditure in cardiovascular disease is not yet known. Furthermore, the association between cold dialysis (CD) and clinical outcomes in hemodialysis patients is unclear. METHODS: This was a single-center retrospective cohort study consisting of two groups: a CD group with dialyzate temperature <35.5 °C and a standard dialysis (SD) group with dialyzate temperature between 35.5 and 37 °C. The end points of the study were overall mortality, cardiac mortality and non-cardiac mortality. The study analyzed the associations between dialyzate temperature and long-term survival in CD and SD groups. Propensity score analysis was used to control for intergroup baseline differences. RESULTS: Baseline characteristics of both groups were similar. Kaplan-Meier analysis showed that CD was significantly associated with a lower risk for overall mortality (P = 0.006) and cardiac mortality (P = 0.023) but not for non-cardiac mortality or infectious mortality. After multivariate Cox regression analysis, adjusting for propensity scores and other possible confounding factors, CD remained a significant beneficial factor for overall mortality (P = 0.030) and cardiac mortality (P = 0.034). CONCLUSION: Our studies show that CD is significantly and independently associated with a lower risk for overall mortality and cardiac mortality.

Maternal pregnancy-induced hypertension increases the subsequent risk of neonatal candidiasis: A nationwide population-based cohort study.

OBJECTIVE: Neonatal candidiasis is a leading infectious cause of significant morbidity and mortality in premature birth mainly due to impaired physical barriers and immature immune system of fetus. Maternal pregnancy-induced hypertension (PIH) has been reported to be able to disturb the neonatal immune system, which could cause the increased possibility of neonatal infection. Therefore, we hypothesized that maternal PIH may increase the risk of neonatal candidiasis. The aim of this study was to evaluate whether PIH increased the risk of neonatal candidiasis and identify the predictive risk factors. MATERIALS AND METHODS: Patients with newly diagnosed PIH between January 1, 2000, and December 31, 2013 were selected from the Taiwan National Health Insurance Research Database (NHIRD). For each patient in the PIH cohort, 4 subjects without PIH, matched for age and year of delivery, were randomly selected as the comparison cohort. A Cox proportional regression model was used to estimate the risks of neonatal candidiasis in both cohorts. RESULTS: Among the 23.3 million individuals registered in the NHIRD, 29,013 patients with PIH and 116,052 matched controls were identified. Patients with PIH had a higher incidence of neonatal candidiasis than did those without PIH. According to the multivariate analysis, PIH (odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.11-3.19, p < 0.0228), single parity (OR = 1.91, 95% CI = 1.00-3.65, p < 0.0499), and preterm birth (OR = 3.57, 95% CI = 1.84-6.93, p = 0.0002) were independent risk factors for the development of neonatal candidiasis. CONCLUSION: Patients who had a history of PIH was associated with an increased risk of having infants who develop neonatal candidiasis compared with those without PIH. Additionally, preterm birth was an independent risk factor for the development of neonatal candidiasis.

Long-term compliance of vaginal pessaries: Does stress urinary incontinence matter?

Vaginal pessary treatment for pelvic organ prolapse (POP) is relatively safe and cost-effective. Since long-term use is an important key to keep the benefit of pessary treatment, we would like to investigate the factors which might affect the compliance of vaginal pessaries. In this retrospective study, 65 women were included, and we found poor compliance in women with severe stress urinary incontinence (SUI) after reduction (1-hour pad test >10 gm vs ≦10 gm, 57.1% vs. 84.3%, P = .027). Besides, women younger than 60 years-old also had poor compliance (age ≦60-year-old vs >60-year-old, 58.3% vs 83.0%, P = .04). Other factors such as POP stage, history of hysterectomy, and types of pessaries, did not show significant influence on the long-term compliance in this study. Therefore, to evaluate the severity of SUI after reduction before providing pessary treatment is important to predict long-term compliance. Meanwhile, long-term pessary treatment seems to be more acceptable to elderly patients.

Peliosis hepatis complicated by portal hypertension following renal transplantation.

Peliosis hepatis (PH) is a vascular lesion of the liver that mimics a hepatic tumor. PH is often associated with underlying conditions, such as chronic infection and tumor malignancies, or with the use of anabolic steroids, immunosuppressive drugs, and oral contraceptives. Most patients with PH are asymptomatic, but some present with abdominal distension and pain. In some cases, PH may induce intraperitoneal hemorrhage and portal hypertension. This study analyzed a 46-year-old male who received a transplanted kidney nine years prior and had undergone long-term immunosuppressive therapy following the renal transplantation. The patient experienced progressive abdominal distention and pain in the six months prior to this study. Initially, imaging studies revealed multiple liver tumor-like abnormalities, which were determined to be PH by pathological analysis. Because the hepatic lesions were progressively enlarged, the patient suffered from complications related to portal hypertension, such as intense ascites and esophageal varices bleeding. Although the patient was scheduled to undergo liver transplantation, he suffered hepatic failure and died prior to availability of a donor organ.

Association between uremic toxins and depression in patients with chronic kidney disease undergoing maintenance hemodialysis.

OBJECTIVE: Patients with chronic kidney disease (CKD) who are undergoing maintenance hemodialysis have a higher prevalence of depression than the general population. The underlying cause of this association is unknown, but may be related to accumulation of uremic toxins. Little is known about the association of accumulation of uremic toxins and depression in hemodialysis patients. METHOD: We conducted a cross-sectional study of 209 CKD patients from a single institution to evaluate the associations of a soluble small uremic toxin (urea), a soluble large uremic toxin (ß2 microglobulin) and two protein-bound uremic toxins [total p-cresol sulfate (PCS) and indoxyl sulfate (IS)] with the presence of depression. RESULTS: A total of 47 patients (22.4%) had depression. Depressive patients had lower body mass index, lower serum creatinine, lower serum albumin and lower total IS. Univariate and multivariate logistic regression analyses that adjusted for age, gender and other statistically significant variables indicated that depression was significantly and independently associated with lower serum albumin and lower total IS. The levels of urea, ß2 microglobulin and PCS were not significantly associated with depression. CONCLUSION: Our results indicate that depression in patients with CKD was significantly and independently associated with lower serum albumin and lower total IS. However, the pathological mechanisms underlying these associations are unknown.

Low plasma DHEA-S increases mortality risk among male hemodialysis patients.

OBJECTIVE: The incidence of chronic kidney disease (CKD) is on the rise. CKD patients are at high risk of cardiovascular (CVD) and all-cause mortality. CKD patients have several endocrine disorders, including low levels of dehydroepiandrosterone sulfate (DHEA-S). In the general population, low levels of DHEA-S are associated with high CVD and all-cause mortality. The aim of this study was to analyze the prognostic value of plasma DHEA-S on the survival of CKD patients on hemodialysis. METHOD: This was a single-center prospective cohort study on two hundred CKD patients on hemodialysis, which assessed the prognostic value of plasma DHEA-S on their survival. RESULT: We found that plasma DHEA-S levels were negatively associated with age, and positively associated with dialysis duration and plasma creatinine, albumin, and phosphate levels in hemodialysis men. Elderly patients with co-morbidities (i.e. diabetes mellitus, congestive heart failure, and chronic obstructive pulmonary disease), poorer fluid control which was evaluated by higher cardiothoracic ratio, and low plasma creatinine and albumin levels seemed to have poor prognosis in hemodialysis men. Furthermore, low plasma DHEA-S levels were significantly associated with CVD-related [hazard ratio (HR)=3.877; P=0.021], non-CVD-related (HR=3.522; P=0.016), and all-cause mortality (HR=3.667; P=0.001) in hemodialysis men. But low plasma DHEA-S levels were not significantly associated with CVD-related, non-CVD-related, and all-cause mortality in hemodialysis women. Multivariate Cox regression analysis suggested that low plasma DHEA-S levels are significantly and independently associated with all-cause mortality in hemodialysis men (HR=2.933; P=0.033). CONCLUSION: The study suggested that low plasma DHEA-S was independently and significantly associated with all-cause mortality in CKD hemodialysis men.

Higher serum potassium level associated with late stage chronic kidney disease.

BACKGROUND: The serum potassium (K+) level is kept in a narrow range to sustain normal physiology within the human body by the kidneys. The serum K+ level in different stages of chronic kidney disease (CKD) remains undefined. METHODS: We conducted a cross-sectional study to observe the serum K+ level in patients without clinical manifestations of hyperkalemia in the late stages of CKD (stages 3-5). A total of 531 patients with late stage CKD were included and followed up for at least 1 year, from March 2006 to May 2007. The patients were sub-grouped by stages of CKD, which were determined by a "Modification of Diet in Renal Disease" equation estimating the glomerular filtration rate (eGFR). The serum creatinine, eGFR and K+ levels were recorded at least twice during the study. We analyzed the average K+ level in these late-stage CKD patients. RESULTS: The average K+ level increased along with renal function deterioration in the late stages of CKD (stage 3: 4.36 ± 0.49; stage 4: 4.50 ± 0.55; stage 5: 4.69 ± 0.73 mEq/L, p < 0.05). Men and patients with diabetes mellitus, a low eGFR, and a low hemoglobin might have higher levels of serum K+. We also noticed that there was a linear increase in the standard deviation of the serum K+ level as renal function deteriorated. The use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers was not associated with hyperkalemia in our patients. CONCLUSION: Our results reflected that the serum K+ level increased in correlation with the decline in the eGFR in the late stages of CKD. Also, male gender, diabetes mellitus, and anemia might be risk factors for higher K+ levels in CKD patients. The variation in the serum K+ level became wider as renal failure progressed.

Ureteral endometriosis with obstructive uropathy.

Endometriosis is a common disease, but ureteral involvement is rare. The symptoms and signs of ureteral endometriosis mimic those of ureteral malignancy. This case report describes a woman who presented with chronic back pain for 5 years. Imaging studies showed a right small contracted kidney with hydronephrosis and a bladder tumor. Endometriosis of the right lower ureter was ultimately diagnosed. The patient was healthy without recurrence during follow-up. It is difficult to differentiate between ureteral endometriosis and malignancy; in fact, renal loss may occur before diagnosis. Ureteral endometriosis should be considered for women with ureteral obstruction manifesting as chronic backache.

Molecular detection and phylogenetic analysis of the alkane 1-monooxygenase gene from Gordonia spp.

The alkB gene encodes for alkane 1-monooxygenase, which is a key enzyme responsible for the initial oxidation of inactivated alkanes. This functional gene can be used as a marker to assess the catabolic potential of bacteria in bioremediation. In the present study, a pair of primers was designed based on the conserved regions of the AlkB amino acid sequences of Actinobacteria, for amplifying the alkB gene from the genus Gordonia (20 Gordonia strains representing 13 species). The amplified alkB genes were then sequenced and analyzed. In the phylogenetic tree based on the translated AlkB amino acid sequences, all the Gordonia segregated clearly from other closely related genera. The sequence identity of the alkB gene in Gordonia ranged from 58.8% to 99.1%, which showed higher sequence variation at the inter-species level compared with other molecular markers, such as the 16S rRNA gene (93.1-99.8%), gyrB gene (77.5-97.3%) or catA gene (72.4-99.5%). The genetic diversity of four selected loci also showed that the alkB gene might have evolved faster than rrn operons, as well as the gyrB or catA genes, in Gordonia. All the available actinobacterial alkB gene sequences derived from the whole genome shotgun sequencing projects are phylogenetically characterized here for the first time, and they exclude the possibility of horizontal gene transfer of the alkB gene in these bacterial groups.

Both CXCR3 and CXCL10/IFN-inducible protein 10 are required for resistance to primary infection by dengue virus.

We examined the extent to which CXCR3 mediates resistance to dengue infection. Following intracerebral infection with dengue virus, CXCR3-deficient (CXCR3(-/-)) mice showed significantly higher mortality rates than wild-type (WT) mice; moreover, surviving CXCR3(-/-) mice, but not WT mice, often developed severe hind-limb paralysis. The brains of CXCR3(-/-) mice showed higher viral loads than those of WT mice, and quantitative analysis using real-time PCR, flow cytometry, and immunohistochemistry revealed fewer T cells, CD8(+) T cells in particular, in the brains of CXCR3(-/-) mice. This suggests that recruitment of effector T cells to sites of dengue infection was diminished in CXCR3(-/-) mice, which impaired elimination of the virus from the brain and thus increased the likelihood of paralysis and/or death. These results indicate that CXCR3 plays a protective rather than an immunopathological role in dengue virus infection. In studies to identify critical CXCR3 ligands, CXCL10/IFN-inducible protein 10-deficient (CXCL10/IP-10(-/-)) mice infected with dengue virus showed a higher mortality rate than that of the CXCR3(-/-) mice. Although CXCL10/IP-10, CXCL9/monokine induced by IFN-gamma, and CXCL11/IFN-inducible T cell alpha chemoattractant share a single receptor and all three of these chemokines are induced by dengue virus infection, the latter two could not compensate for the absence of CXCL10/IP-10 in this in vivo model. Our results suggest that both CXCR3 and CXCL10/IP-10 contribute to resistance against primary dengue virus infection and that chemokines that are indistinguishable in in vitro assays differ in their activities in vivo.

Does human ochratoxin A aggravate proteinuria in patients with chronic renal disease?

BACKGROUND: Ochratoxin A (OTA) is a nephrotoxic metabolite occurring in foodstuffs. In the last decade, OTA-induced nephropathy in man and animals have been confirmed by previous literature. The correlation between OTA and the severity of CRI and nephrotic syndrome was also researched. Therefore, this study was designed to determine whether OTA also played an important role in renal insufficiency of patients with chronic renal diseases in Taiwan. METHODS: The patients in this study were divided into nonnephrotic syndrome and nephrotic syndrome groups, first, to look for the relation between urine protein and OTA. And then these patients were also divided into six groups: (I) patients with chronic glomerulonephritis; (II) patients with chronic interstitial nephritis; (III) patients with diabetes mellitus; (IV) patients with hypertension; (V) patients with other diseases; (VI) patients with unknown reasons. For all groups, laboratory evaluation of kidney such as serum creatinine, urinary creatinine, creatinine clear rate, urinary protein, and urinary analysis were carried out coupled with determination of ochratoxin A level in urine. RESULTS: Higher levels of OTA were found in patients with nephrotic syndrome. There was a significantly positive correlation (P<0.001) between 24-hr OTA and 24-hr urine protein. On the other hand, the mean excretion of OTA in DM group (group III) was found significantly higher compared to the other groups (P<0.05). Distinct differences (P<0.01) were found especially when DM group was compared with patients with chronic glomerulonephritis (group I; P=0.0019), patients with chronic interstitial nephritis (group II; P=0.0032) and patients with hypertension (group IV; P=0.0062). CONCLUSION: The results could lead to the conclusion that OTA could play an important role in proteinuria of patients with chronic renal diseases in Taiwan. And OTA may play a role in diabetes patients with nephropathy. Further longitudinal study is needed to clarify the role of OTA in diabetic nephropathy.