Hemodialysis treatment in patients with Balkan endemic nephropathy: an epidemiological study

AIM: To analyze hemodialysis (HD) treatment of patients with Balkan endemic nephropathy (BEN) from five endemic villages in the South Morava Region of Serbia. Analyses of patterns of incidence may generate hypotheses about the underlying causes of BEN, and prevalence data provide information on the current and likely future burden on health services for managing BEN. METHODS: A total of 143 end-stage kidney disease patients (ESKD) with BEN were admitted to the renal replacement program from 1974 to 2004: 121 to HD, 15 peritoneal dialysis, and 7 kidney transplantation. As a control group, 117 patients with other kidney disease (chronic pyelonephritis, glomerulonephritis, and ischemic nephropathy) admitted to HD at the time of BEN patients and matched by age and gender were studied. RESULTS: Most of the BEN patients (93.4%) treated by HD were born from 1917 to 1941. The majority of patients (79.3%) started HD from 1977 to 1991 (period of 15 years). The mean age of BEN patients starting HD treatment was 49.1 years in the period from 1974 to 1978, and increased steadily in the following years, being 72.5 years in the last period of study (2004-2006) The mean survival time of BEN males was 4.70 (95% CI 3.66-5.75) and for females was 5.02 (95% CI 1.47-4.53). Difference between males and females was not statistically significant (log rank 0.14, p = 0.7, P > 0.5). Mean survival times of 4.84 (95% CI 3.97-5.70) in BEN patients and 3.1 (95% CI 2.78-3.84) in other kidney disease patients were found. Difference between BEN patients and controls was statistically significant (log rank 8.38, p = 0.0038, P < 0.01). CONCLUSION: The population of endemic villages around the South Morava River admitted to HD treatment after 1974 was exposed to environmental toxicant(s) from 1917 to 1941. The most intense effect of environmental exposure was in that period, with ESKD in patients in their forties. The exposure to environmental toxicants has diminished, so ESKD of BEN has become less frequent and manifested in the older age, mean 72.5 in the period from 2004 to 2006. Different type of exposure was registered in some other endemic regions in Serbia and abroad.     

Placental growth factor and placental protein 13 in patients with Balkan endemic nephropathy,a worldwide disease

Abstract

Background: Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial kidney disease occurring in people living in along the tributaries of the Danube River. The aim of the study was to determine serum level and urinary excretion of placental growth factor (PlGF) and placental protein 13 (PP13) in patients with BEN. Methods: Thirty patients with BEN from the South Morava River region of Serbia and 18 controls were studied. Age of patients was 74?yr (53–87) and 73?yr (66–83) in controls. Results: In patients with BEN, serum creatinine was significantly higher than in controls (129.7 vs. 83.2?µmol/L, respectively), but GFR was lower in patients than in controls (40.7 vs. 54.6?mL/min). Serum PlGF was significantly higher in BEN patients than in controls (9.90 vs. 6.80?pg/mL), urinary excretion being significantly lower in patients (0.20 vs. 0.90?pg/mmol creat.). Serum PP13 was significantly lower in BEN patients (208.2 vs. 291.0?pg/mL). Urinary excretion of PP13 was also significantly lower in BEN patients than in controls (32.5 vs. 182.5?pg/mmol creat). In multivariate regression analysis BEN, sex and age were significant determinants of the observed changes in PlGF and PP13. Conclusion: Important changes of PlGF and PP13 in patients with BEN were demonstrated, where kidney disease, female sex, and the age have been significant determinants.     

High prevalence of colon adenomas in end‐stage kidney disease patients on hemodialysis undergoing renal transplant evaluation

The aim of this study was to determine whether patients with end‐stage kidney disease (ESKD) on hemodialysis (HD) undergoing kidney transplant evaluation are at higher risk for colonic neoplasia than the general population. This is a retrospective cohort study of patients with ESKD who underwent a first screening colonoscopy while undergoing kidney transplant evaluation. Data were collected on the prevalence of adenomatous polyps and advanced adenomas in 70 patients with ESKD and 70 controls, undergoing their first screening colonoscopy, matched for age, gender, and endoscopist. At the time of the colonoscopy, an average time on HD was 3.2 ± 2.9 yr. The prevalence of adenomatous polyps was significantly higher in ESKD on HD (54.3% vs. 32.9%, p = 0.008) than in controls. In a multivariate analysis controlling for other factors, ESKD on HD remained a risk factor for the presence of adenomas (OR 3.06, 95% CI 1.21, 7.73). No colonoscopy‐related complications were reported in the patients with ESKD on HD. We demonstrate a significantly higher prevalence of adenomatous polyps in patients with ESKD undergoing a first screening colonoscopy as part of kidney transplant evaluation. In addition, colonoscopy can be safely performed in this population.     

Evaluation of Criteria for the Diagnosis of Balkan Endemic Nephropathy

Background. The diagnosis of Balkan endemic nephropathy (BEN) is often made using Danilovic's criteria. The aim of this study was to determine the prevalence, sensitivity, specificity, and predictive value of Danilovic's criteria and several additional indices. Methods. The study included 19 BEN patients, 23 BEN-suspected patients, 34 patients with other kidney diseases, and 23 healthy controls. The sensitivity and specificity of Danilovic's criteria was calculated, and these criteria, in addition to age, sex, blood pressure, creatinine clearance, glucosuria, urine osmolality, alkaline phosphatase, alpha 1-microglobulin, fractional sodium excretion, tubular phosphate reabsorption, kidney length, and volume, were combined in a logistic regression. Results. All examined persons were from a BEN-affected village (criterion 1), and all BEN, BEN-suspected patients, and 12/23 healthy controls were from BEN families (criterion 2). None of the remaining Danilovic's criteria was found in the healthy controls. The prevalence of proteinuria, low specific gravity, and anemia (criteria 3–5) differed insignificantly among the patient groups. Azotemia and shrunken kidney (criteria 6 and 7) were significantly more frequent in BEN than in other patients. Only proteinuria showed high sensitivity and specificity in differentiating BEN and BEN-suspected patients from healthy persons, but no criteria differentiated BEN or BEN-suspected from other kidney diseases. Proteinuria is a significant predictor of both BEN and BEN-suspected vs. healthy persons, and alpha 1-microglobulinuria is a significant predictor of BEN vs. other kidney diseases. Conclusion. Danilovic's criteria enabled a diagnosis of BEN only in chronic renal failure and differential diagnosis between BEN and healthy persons but not between BEN and other kidney diseases. Out of the examined indices of proximal tubular disorders, only alpha 1-microglobulinuria significantly discriminated BEN from other kidney diseases.     

Evaluation of a predictive model of end-stage kidney disease in a French-based cohort

Background

The risk of ESKD is highly heterogeneous among renal diseases, and risk scores were developed to account for multiple progression factors. Kidney failure risk equation (KFRE) is the most widely accepted, although external validation is scarce. The objective of this study was to evaluate the usefulness of this score in a French case–control cohort and test the pertinence of the proposed thresholds.

Methods

A retrospective case–control study comparing a group of patients starting renal replacement therapy (RRT) to a group of patients with CKD stages 3–5. Multivariate analysis to assess the predictors of ESKD risk. Discrimination of 4-, 6- and 8-variable scores using ROC curves and compared with eGFR alone and albumin/creatinine ratio (ACR) alone.

Results

314 patients with a ratio of 1 case for 1 control. In multivariate analysis, increasing age and higher eGFR were associated with a lower risk of ESKD (OR 0.62, 95% CI 0.48–0.79; and OR 0.72, 95% CI 0.59–0.86, respectively). The log-transformed ACR was associated with a higher risk of ESKD (OR 1.25 per log unit, 95% CI 1.02–1.55). The 4-variable score was significantly higher in the RRT group than in the CKD-ND group, and was more efficient than the eGFR (AUROC 0.66, 95% CI 0.60–0.72, p?=?0.018) and the log-transformed ACR (AUROC 0.63 95% CI 0.60–0.72, p?=?0.0087) to predict ESKD. The 6-variable score including BP metrics and diabetes was not more discriminant as the 4-variable score. The 8-variable score had similar performance compared with the 4-score (AUROC 8-variable score: 0.70, 95% CI 0.64–0.76, p?=?0.526). A 40% and 20% score thresholds were not superior to eGFR?<?15 and 20 mL/min/1.73 m², respectively. A 10% threshold was more specific than an eGFR?<?30 mL/min/1.73 m².

Conclusion

KFRE was highly discriminant between patients progressing to ESKD vs those non-progressing. The 4-variable score may help stratify renal risk and referral in the numerous patients with stage 3 CKD. Conversely, the proposed thresholds for creating vascular access or preemptive transplantation were not superior to eGFR alone.

     

Pulmonary Hypertension among Patients on Dialysis and Kidney Transplant Recipients

Pulmonary arterial hypertension (PAH) is a serious cardiac complication among patients with end-stage renal disease (ESRD). We investigated pulmonary hypertension and its associated factors among patients who were on chronic dialysis and kidney transplant recipients. One hundred-eighty patients in three groups of hemodialysis (HD), peritoneal dialysis (PD), and kidney transplant were studied. Demographic and clinical characteristics and echocardiographic findings were evaluated. A multivariable linear regression model was used to find factors associated with pulmonary artery pressure. The mean age of participants was 50.3 ± 15.5 years and 63.9% were male. We found pulmonary hypertension (mean pulmonary artery pressure >25 mmHg) in 31.6%, 8.3%, and 5% of the patients on HD, PD, and transplant recipients, respectively (p < 0.001). In multivariate analyses, being on HD (B = 5.276, confidence interval [CI] 95%: 1.211–9.341), age (B = –0.319, CI 95%: –0.501 to –0.138), smoking (B = 11.631, CI 95%: 1.847–21.416), systolic cardiac dysfunction (B = 6.313, CI 95%: 3.073–9.554), and diastolic cardiac dysfunction (B = 5.227, CI 95%: 1.176–9.277) were associated with systolic pulmonary artery pressure. These results showed that pulmonary hypertension is a frequent cardiac complication among patients with ESRD, and the type of renal replacement therapy (HD), systolic and diastolic cardiac dysfunction, and smoking are associated with increased pulmonary artery pressure. Further studies with larger sample sizes and also prospective studies are recommended in this regard.     

Increased risk of modality failure with higher serum uric acid level in continuous ambulatory peritoneal dialysis patients: a prospective cohort study

BackgroundPeritoneal dialysis (PD) is one of the most important kidney replacement therapies for patients with end‐stage kidney disease (ESKD). PD technique failure can lead to an escalated cost and increased infectious and cardiovascular risk, up and including to death. The accumulation of uric acid (UA) was associated with adverse outcomes in ESKD patients. However, the relationship between serum UA and technique failure is little explored.MethodsHere, a total of 266 continuous ambulatory peritoneal dialysis (CAPD) patients (age, 41.8 ± 12.6 years; 125 males) were enrolled and followed up for 31.7 months. Serum UA levels were examined at baseline and each visit. Subjects were divided into three groups according to their baseline serum UA concentrations. Multivariable Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of PD technique failure.ResultsThe level of serum UA increased gradually as time prolonged. During the follow-up period, 77 (28.9%) patients occurred PD technique failure, of which 56 (21.1%) transferred to hemodialysis (HD) and 21 (7.9%) died. Compared to the lowest UA tertile, after adjusting for potential confounders, HRs of technique failure in tertile 2 and tertile 3 were 1.82 (95% CI: 0.95–3.49) and 2.03 (95% CI: 1.05–3.92), respectively, and p for trend was 0.043. Adjusted HRs of all-cause technique failure, transferring to HD and mortality with each 1 mg/dL increase in serum UA were 1.20 (95% CI: 1.03–1.40, p = 0.019), 1.22 (95% CI: 1.01–1.48, p = 0.039), and 1.25 (95% CI: 0.94–1.67, p = 0.128), respectively.ConclusionHigher serum UA level predicted higher risk of technique failure in CAPD patients.     

In-hospital mortality of heparin-induced thrombocytopenia in end-stage kidney disease. A retrospective national population-based cohort study

Aim

Heparin induced thrombocytopenia (HIT) and end stage kidney disease (ESKD) are independent conditions associated with increased mortality and morbidity, however, whether ESKD is an independent risk factor for increased mortality in HIT admissions is not well studied. Therefore, we aimed to compare in-hospital mortality in HIT admissions based on their ESKD status.

Methods

This is a retrospective cohort study of HIT hospitalizations aged 18 and older using the 2016–2019 national inpatient sample (NIS) database.

Results

From 2016 to 2019 we had 12 161 admissions for HIT among 28 484 087 total hospitalizations. The annual incidence rate for HIT admissions per 100 000 admissions were: 47, 46, 41.1, and 36.6, respectively (p < .001) in 2016, 2017, 2018, and 2019 respectively. Among HIT admissions, the mean age was 64.3 years, 46.8% were females, 68% were Whites and 16% were Blacks. Black patients have a significantly higher likelihood of in-hospital mortality than White patients (aOR 1.25; 95% CI: 1.06, 1.48; p = .007). Patients who did not have any insurance or self-pay had higher mortality compared to Medicare (aOR 1.64; 95% CI: 1.13, 2.38; p = .009). ESKD status was not associated with higher or lower in-hospital mortality among HIT admissions (aOR 1.002; 95% CI: 0.84, 1.19; p = .981) after adjusting for age, sex, race, and insurance status.

Conclusion

There are no higher or lower odds of in-hospital mortality in the ESKD subgroup in HIT admissions in adults. Decreasing incidence of HIT hospitalizations was seen over the years from 2016 to 2019.     

Hepatitis C Infection and Related Factors in Hemodialysis Patients in China: Systematic Review and Meta-Analysis

Background and Aims. To provide a comprehensive and reliable tabulation of available data on the epidemiological characteristics and risk factors for hepatitis C virus (HCV) infection in maintenance hemodialysis (HD) patients in China, and to help inform prevention programs and guide future research. Methods. A systematic review was constructed based on the computerized literature database by two reviewers independently. Ninety-five percent confidence intervals (CI) of infection rates were calculated using the approximate normal distribution model. Odds ratios and 95% CI were calculated by fixed or random effects models. Results. Forty-three studies met our inclusion criteria. The pooled prevalence of HCV infection among HD patients in China was 41.1% (95% CI 39.5–42.6%). No significant difference was found in HCV infection rates between male and female HD patients (OR = 0.75, 95% CI 0.52–1.07, p = 0.11). HD patients with blood transfusion were 5.65 times more likely to be infected with HCV than HD patients without blood transfusion. A longer duration of HD was associated with increased HCV prevalence. Co-infection with hepatitis B virus did not increase the probability of HCV infection among HD patients (OR = 1.19, 95% CI 0.34–3.20, p = 0.73). Conclusions. Viral hepatitis is still one of the main complications in HD patients, with hepatitis C being the most common one. The key to reducing the incidence of viral hepatitis in HD patients is to control contagion and reduce the frequency of blood transfusion and cross-infection.     

Impact of hemoglobin levels on renal and non-renal clinical outcomes differs by chronic kidney disease stages: the Gonryo study

Background

Anemia greatly affects the development of renal and cardiovascular outcomes in chronic kidney disease (CKD) patients. However, the impact based on CKD stage remains unclear.

Methods

We prospectively followed 2,602 Japanese CKD patients under the care of nephrologists. CKD was defined according to cause, estimated glomerular filtration rate <60 mL/min, and/or proteinuria. Patient outcomes [primary end-points: cardiovascular events (CVEs), all-cause mortality, and end-stage kidney disease (ESKD) requiring renal replacement therapy] were assessed in association with basal hemoglobin (Hb) levels (<10, 10–12 and ≥12 g/dL), stratified by CKD stages.

Results

During follow-up, 123 patients developed CVEs, 41 died, and 220 progressed to ESKD. For stages G3, G4 and G5, ESKD frequencies were 2.8, 64.4, and 544.8 person-years, while CVEs and death were 25.6, 45.6, and 76.3 person-years, respectively. The combined endpoint rate was significantly higher in patients with Hb <10 versus Hb 10–12 g/dL, but a higher risk for CVEs and death with Hb <10 g/dL was found only in G3 [hazard ratio (HR) 4.49, (95 % confidence interval (95 % CI) 2.06–9.80)]. In contrast, risk for ESKD with Hb <10 g/dL was found only in G4 [HR 3.08 (95 % CI 1.40–6.79)] and G5 [HR 1.43 (95 % CI 1.01–2.05)]. No increased risks with higher Hb levels were found.

Conclusion

The impact of renal anemia of Hb <10 g/dL on clinical outcomes differed by CKD stage, with a significantly high risk for CVEs and all-cause mortality in G3 and progression to ESKD in G4 and G5.

     

Hemodialysis Patients' Willingness to Undergo Kidney Transplantation: An Observational Study

Background

The number of dialysis patients is increasing, with only 20% undergoing kidney transplantation. In Saudi Arabia, no studies had examined transplantation barriers from the patients' perspectives. We aimed in this study to estimate hemodialysis (HD) patients' willingness to undergo kidney transplantation and to explore its underlying determinants.

Effects of far infrared therapy on arteriovenous fistulas in hemodialysis patients: a meta-analysis

Background: Far infrared (FIR) therapy may have a beneficial effect on maturity and function of arteriovenous fistulas (AVFs) in hemodialysis (HD) patients. Therefore, we performed this pooled analysis to assess the protective effects of FIR therapy in HD patients.

Methods: The randomized controlled trials (RCTs) and quasi-RCTs of FIR therapy for HD patients were searched from multiple databases. Relevant studies were screened according to the predefined inclusion criteria. The meta-analyses were performed using RevMan 5.2 software (The Cochrane Collaboration, Oxford, UK).

Results: Meta-analysis showed that FIR therapy could significantly increase the vascular access blood flow level (MD, 81.69?ml/min; 95% CI, 46.17–117.21; p?p?p?p?p?Conclusions: FIR therapy can reduce AVFs occlusion rates and needling pain level, while significantly improve the level of vascular access blood flow, AVFs diameter and the primary AVFs patency.     

Microalbuminuria as a possible marker of risk of Balkan endemic nephropathy

Aim: To evaluate whether microalbuminuria could be a marker of early tubular damage in individuals at risk of developing Balkan endemic nephropathy (BEN). Methods: A cross-sectional study was used to determine urinary albumin-to-creatinine ratio (UACR) in a test group of 61 participants from a BEN endemic region and control group of 64 participants from a nearby non-endemic region, both recruited from the general population of Bosnia and Herzegovina. The correlation between UACR and urinary b2 microglobulin-to-creatinine ratio (UBCR) and the receiver operating characteristic curve for UACR were analyzed in the test groups of 58 participants. The correlation analysis was also performed in a subset of nine subjects with elevated UBCR. Results: Medians, interquartile ranges and confidence intervals (CI) for medians of UACR in the test and control groups were 2 mg/mmol, 0.975–8.247 mg/mmol, 1.3472–3.2691 mg/mmol and 1 mg/mmol, 0.695–1.41 mg/mmol, 0.8466–1.2053 mg/mmol, respectively (P = 0.0001). Microalbuminuria was found in 30 of the 61 examinees in the test group, in contrast to six of the 64 examinees in the controls (P < 0.0001). Participants from the endemic region had 9.3 times the odds of having microalbuminuria in contrast to participants from the non-endemic region. Pearson's correlation coefficients r of the log-transformed ratios and Kendall–tau coefficients of rank correlation in the group of 58 and in a subset of nine subjects with elevated UBCR were: 0.55 (P < 0.0001); 0.317 (P = 0.0005) and 0.59 (P = 0.045); 0.48 (P = 0.037), respectively. The area under the curve for UACR was 0.882 (P = 0.0001), sensitivity 100% and specificity 67.3%. Conclusion: Microalbuminuria may be a useful marker of early tubular injury in individuals at risk of developing BEN.     

Observational study of risk factors associated with clinical outcome among elderly kidney transplant recipients in Sweden – a decade of follow-up

Kidney transplantation (Ktx) in elderly has become increasingly accepted worldwide despite their higher burden of comorbidities. We investigated important risk factors affecting long-term patient and graft survival. We included all (n = 747) Ktx patients >60 years from 2000 to 2012 in Sweden. Patients were age-stratified, 60–64, 65–69 and >70 years. Follow-up time was up to 10 years (median 7.9 years, 75% percentile >10 years). Primary outcome was 10-year patient survival in age-stratified groups. Secondary outcomes were 5-year patient and graft survival in age-stratified groups and the impact of risk factors including Charlson comorbidity index (CCI) on patient and graft survival. Mortality was higher in patients >70 years, after 10 years (HR 1.94; 95% CI 1.24–3.04; P = 0.004). Males had a higher 10-year risk of death (HR 1.39; CI 95% 1.04–1.86; P = 0.024). Five-year patient survival did not differ between age groups. In multivariate Cox analysis (n = 500), hazard ratio for 10-year mortality was 4.6 in patients with CCI ≥7 vs. <4 (95% CI 2.42–8.62; P = 0.0001). Higher CCI identified ESKD patients with 4.6 times higher risk of death after Ktx. We suggest that this index should be used as a part of the preoperative evaluation in elderly.     

Detection of renal dysfunctions in family members of patients with Balkan endemic nephropathy

BACKGROUND/AIM: Recent studies have questioned whether new cases of Balkan endemic nephropathy (BEN) are occurring. The aim of the present study was to find out whether new members with renal dysfunctions can be identified among family members of BEN patients from the Kolubara region. METHODS: The study included 47 family members of 5 BEN patients on hemodialysis (HD) and 17 members of 3 non-BEN patients on HD. Their medical and epidemiological histories were taken, an objective survey made, and all persons were examined for global and tubular kidney function. RESULTS: Seven BEN family members (2 with previously known BEN) had creatinine clearance (Ccr) below the 75th percentile rank according to sex and age. All non-BEN family members had normal Ccr and no evidence of previous renal disorders. Hypertension was found in 20 (43%) BEN and 6 (35%) non-BEN family members. No significant differences in the frequency of renal function disorders (proteinuria, alpha1-microglobulinuria, urine specific gravity, osmolality, functional excretion of sodium, tubular phosphate resorption) or anemia were found between the groups. Renal disorders were detected in 18 BEN family members without previously detected disease, 3 of whom fulfilled criteria for a diagnosis of BEN and another 2 for BEN-suspected persons. CONCLUSION: New cases of BEN are still arising among the affected families in the Kolubara region.     

The impact of socioeconomic status and geographic remoteness on access to pre-emptive kidney transplantation and transplant outcomes among children

Background

Low socioeconomic status (SES) and geographic disparity have been associated with worse outcomes and poorer access to pre-emptive transplantation in the adult end-stage kidney disease (ESKD) population, but little is known about their impact in children with ESKD. The aim of our study was to determine whether access to pre-emptive transplantation and transplant outcomes differ according to SES and geographic remoteness in Australia.

Methods

Using data from the Australia and New Zealand Dialysis and Transplant Registry (1993–2012), we compared access to pre-emptive transplantation, the risk of acute rejection and graft failure, based on SES and geographic remoteness among Australian children with ESKD (≤18 years), using adjusted logistic and Cox proportional hazard modelling.

Results

Of the 768 children who commenced renal replacement therapy, 389 (50.5 %) received living donor kidney transplants and 28.5 % of these (111/389) were pre-emptive. There was no significant association between SES quintiles and access to pre-emptive transplantation, acute rejection or allograft failure. Children residing in regional or remote areas were 35 % less likely to receive a pre-emptive transplant compared to those living in major cities [adjusted odds ratio (OR) 0.65, 95 % confidence interval (CI) 0.45–1.0]. There was no significant association between geographic disparity and acute rejection (adjusted OR 1.03, 95 % CI 0.68–1.57) or graft loss (adjusted hazard ratio 1.05, 95 % CI 0.74–1.41).

Conclusions

In Australia, children from regional or remote regions are much less likely to receive pre-emptive kidney transplantation. Strategies such as improved access to nephrology services through expanding the scope of outreach clinics, and support for regional paediatricians to promote early referral may ameliorate this inequity.

     

Sevelamer Use,Vitamin K Levels,Vascular Calcifications,and Vertebral Fractures in Hemodialysis Patients: Results from the VIKI Study

Hyperphosphatemia is a risk factor for vascular calcifications (VCs), which are part of the chronic kidney disease-mineral and bone disorders (CKD-MBD). Vitamin K-dependent proteins such as matrix Gla protein (MGP) and bone Gla proteins (BGP, or osteocalcin) can inhibit VCs and regulate bone mineralization. In this analysis of the Vitamin K Italian (VIKI) study, the relationship between vitamin K status, vertebral fractures (VFs) and VCs in 387 hemodialysis (HD) patients with (N = 163; 42.1%) or without N = 224; 57.9%) sevelamer was evaluated. Levels of vitamin K vitamers K1 and K2 or menaquinones (MK; MK4–7), total and undercarboxylated (uc) forms for both BGP and MGP were determined. Although no differences in clinical characteristics were noted, lower levels of MK4 (0.45 versus 0.6 ng/mL, p = .01) and a greater MK4 deficiency was observed in sevelamer-treated patients (13.5% versus 5.4%, p = .005). Multivariate logistic regression revealed that MK4 deficiency was associated with sevelamer use (odds ratio [OR] = 2.64, 95% confidence interval [CI] 1.25–5.58, p = .011) and aortic calcification (OR = 8.04, 95% CI 1.07–60.26, p = .04). In the same logistic model, sevelamer amplified the effect of total BGP levels on the odds of VFs in patients with total BGP <150 μg/L compared with those with total BGP ≥150 μg/L (OR = 3.15, 95% CI 1.46–6.76, p = .003). In contrast, there was no such effect in those untreated (total BGP <150 μg/L versus total BGP ≥150 μg/L: OR = 1.21, 95% CI 0.66–2.23, p = .54]; p = .049 for effect modification by sevelamer). Sevelamer may interfere with MK4 levels in HD patients and interact with low BGP levels to increase bone fractures in CKD patients. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Association of short-term blood pressure variability with cardiovascular mortality among incident hemodialysis patients

Objective: To investigate the association of short-term blood pressure variability (BPV) with cardiovascular mortality in hemodialysis (HD) patients, using a reliable index called average real variability (ARV), and to assess the factors associated with ARV in incident HD population.

Methods: A total of 103?HD patients were recruited, with 44-h ambulatory blood pressure monitoring performed after the midweek HD session. Systolic BPV was assessed by SD, coefficient of variation (CV), and ARV, respectively. Laboratory data were obtained from blood samples before the midweek HD. All patients were followed up for 24 months.

Results: According to the median of BPV indices, the comparisons between patients with the low and high values were conducted. Kaplan–Meier analysis showed the survival curves corresponding to median of SD and CV exhibit similar performance for the low and high groups (p?=?.647, p?=?.098, respectively). In contrast, patients with higher ARV had a lower survival rate than those with lower ARV (77.8% vs. 98.0%, p?=?.002). After adjustment for demographics and clinical factors, ARV (HR: 1.143; 95% CI: 1.022–1.279, p?=?.019) and high-sensitivity C-reactive protein (HR: 1.394; 95% CI: 1.025–1.363, p?=?.021) were associated with increased risk of cardiovascular mortality in HD patients. Age and interdialytic weight gain (IDWG) were related factors for ARV (β?=?0.065, p?=?.005; β?=?0.825, p?=?.003, respectively).

Conclusions: Greater ARV was independently associated with increased risk of cardiovascular mortality in HD patients. Age and IDWG were independent related factors for ARV.     

Beta2-Microglobulin and Alpha1-Microglobulin as Markers of Balkan Endemic Nephropathy,a Worldwide Disease

Background:?Urine beta2-microglobulin (beta2-MG) was mainly used as a tubular marker of Balkan endemic nephropathy (BEN) but recently alpha1-microglobulin (alpha1-MG) was proposed for the diagnosis of BEN. In this study, the potential of urine beta2-MG, alpha1-MG, albumin, and total protein in the differentiation of BEN from healthy persons and patients with glomerulonephritis (GN) and nephrosclerosis (NS) was examined.?Methods:?This study involved 47 patients with BEN, 36 with GN, 11 with NS, 30 healthy subjects from BEN families, and 46 healthy subjects from non-BEN families.?Results:?In BEN patients area under the curve (AUC) for urine beta2-MG (0.828) and alpha1-MG (0.782) was higher than for urine albumin (0.740), but in GN patients AUC for urine protein (0.854) and albumin (0.872) was significantly higher than for the two low molecular weight proteins. AUC for all four urinary markers in NS patients was significantly lower than in BEN patients, ranging between 500 and 595. Median urine beta2-MG excretion in BEN patients was 17.5 times higher than in GN patients and 18.3 times higher than in controls; median alpha1-MG excretion was higher only 3.0 and 2.25 times, respectively. In the differentiation of BEN from healthy controls, beta2-MG had higher sensitivity and specificity at the cutoff levels (p < 0.001) than alpha1-MG (p < 0.05). In the differentiation of BEN from GN, beta2-MG was the best marker.?Conclusion:?All four urinary markers can be used for the differential diagnosis of BEN, beta2-MG being the best. Like in aristolochic acid nephropathy, beta2-MG seems to be an early marker of tubular damage in BEN.     

Incidence of Fever of Unknown Origin and Subsequent Antitubercular Medications in Hemodialysis Patients: A Two-Year Prospective Study

Background. Hemodialysis (HD) patients are susceptible to atypical tuberculosis (TB), especially among patients presenting with fever of unknown origin (FUO), because of their impaired cellular immunity. Diagnostic trials of anti-TB drugs are therefore recommended in some TB endemic countries, including Japan, though clinical evidence for this therapy is scarce. Methods. We prospectively collected data for incident cases of clinical FUO for two years in 78 of 169 dialysis facilities in Aichi prefecture, located in central Japan. Clinical FUO was defined as sustained fever without any localizing signs and no infiltration on chest x-rays after a one-week antibiotic trial. The baseline characteristics, subsequent body temperatures on the days of HD therapy, and names of antibiotics including anti-TB drugs with the durations of medication were reported until fever alleviation or fever sustainment for over eight weeks. Results. We identified 15 newly developed clinical FUO patients among 8,125 HD patients. The incidence rate was estimated to be 92 (95% CI, 26–158) per 100,000 person-years. This corresponds to 244 cases per year among 264,473 HD patients in Japan. Anti-TB drugs were secondarily prescribed in 8 of 15 clinical FUO patients (53%). No improved fever alleviation was observed when anti-TB drugs were secondarily prescribed compared with cases in which other antibiotics were preferred. Conclusion. We investigated the incidence of FUO in HD patients and found that the rate was not very high, whereas anti-TB drugs were frequently used for FUO cases. The efficacy of this diagnostic therapy should be elucidated in large-scale studies.