Hepatitis C virus (HCV) infection is widely prevalent among patients on hemodialysis (HD), but very rarely treated. The aim of our study is to evaluate the burdens of HCV suffered by patients on HD.
...The Dialysis Outcomes and Practice Patterns Study is an international, prospective, cohort study of patients on HD. We reviewed the HCV status of 76,689 adults enrolled between 1996 and 2015. We compared HCV-positive (HCV+) with HCV-negative (HCV-) patients for risk of mortality, hospitalization, decline in hemoglobin concentration <8.5 g/dl, and red blood cell transfusion. We also compared health-related quality of life scores using the Kidney Disease Quality of Life instrument and the Center for Epidemiologic Studies Short Depression Scale. We adjusted for age, sex, race, years on dialysis, 14 comorbid conditions (including hepatitis B infection), and serum albumin, phosphorus, and creatinine concentrations.
A total of 7.5% of patients were HCV+ at enrollment. Serum concentrations of alanine aminotransferase and aspartate aminotransferase were not markedly elevated in HCV+ patients on HD; the mean concentrations were only 22.6 and 21.8 U/L, respectively. Median follow-up was 1.4 years. Case-mix adjusted hazard ratios (95% confidence intervals) for HCV+ versus HCV- patients were 1.12 (1.05 to 1.20) for all-cause mortality, 5.90 (3.67 to 9.50) for hepatic-related mortality, 1.09 (1.04 to 1.13) for all-cause hospitalization, and 4.40 (3.14 to 6.15) for hepatic-related hospitalization. Quality of life measures indicated significantly worse scores for physical function, pain, vitality, mental health, depression, pruritus, and anorexia among HCV+ patients. The adjusted hazard ratio for transfusion was 1.36 (95% CI, 1.20 to 1.55) and incidence of hemoglobin concentration <8.5 g/dl was 1.12 (95% CI, 1.03 to 1.21). Only 1.5% of HCV+ patients received antiviral medication.
HCV infection among patients on HD is associated with higher risk of death, hospitalization, and anemic complications, and worse quality of life scores. Internationally, HCV infection is almost never treated in patients on HD. Our data provide a rationale for more frequent treatment of HCV in this population.
Hepatitis C virus (HCV) infection is common in dialysis patients and is associated with increased morbidity and mortality. We used the Dialysis Outcomes and Practice Patterns Study (DOPPS, 1996–2015) ...to assess trends in the prevalence, incidence, and risk factors for HCV infection as defined by a documented diagnosis or antibody positivity. Among prevalent hemodialysis patients, HCV prevalence was nearly 10% in 2012–2015. Prevalence ranged from 4% in Belgium to as high as 20% in the Middle East, with intermediate prevalence in China, Japan, Italy, Spain, and Russia. HCV prevalence decreased over time in most countries participating in more than one phase of DOPPS, and prevalence was around 5% among patients who had recently (<4 months) initiated dialysis. The incidence of HCV infection decreased from 2.9 to 1.2 per 100 patient-years in countries participating in the initial phase of DOPPS. Although most units reported no seroconversions, 10% of units experienced 3 or more cases over a median of 1.1 years. High HCV prevalence in the hemodialysis unit was a powerful facility-level risk factor for seroconversion, but the use of isolation stations for HCV-positive patients was not associated with significantly lower seroconversion rates. Overall, despite a trend toward lower HCV prevalence among hemodialysis patients, the prevalence of HCV infection remains higher than in the general population. Combined with a high prevalence of HCV infection among patients with Stage 5 CKD, high rates of HCV seroconversion in a subset of hemodialysis units may contribute to this disparity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Adrenocortical carcinoma is a rare, but potentially lethal, malignancy that is usually detected as an incidental finding on abdominal imaging studies or owing to hormonal complications. ...This report recounts an unusual presentation with leg edema due to compression of the inferior vena cava. The dearth of proven effective treatment is also addressed. Case presentation A 65-year-old White male physician presented with severe, bilateral pitting edema that extended from the toes to the thighs. It progressed over several months. He also experienced paroxysmal dyspnea. Evaluation of cardiac, hepatic, and renal function failed to determine a cause. Computed tomography revealed a tumor above the right kidney, with compression of the intrahepatic inferior vena cava and upstream distension. Serum cortisol and dehydroepiandrosterone sulfate concentrations were elevated, 24-hour urinary cortisol level was elevated, and serum adrenocorticotropic hormone and testosterone concentrations were suppressed. A 27-cm tumor, the right lobe of the liver, the right kidney, and 26 lymph nodes were resected. Histological study confirmed the diagnosis of adrenocortical carcinoma. Ki67 proliferation index was 26.7% (worse prognosis associated with index > 10%). Lymph nodes were negative for malignancy, but a separate 2.7-cm tumor was found near the renal hilum. Adjuvant mitotane chemotherapy was prescribed. Serum testosterone concentration returned to normal. High-dose hydrocortisone administration was needed because of adrenal suppression and CYP 3A4 induction by mitotane. Conclusion Imaging of the abdomen and pelvis should be conducted in cases of unexplained leg edema. In this case, a large adrenal cancer compressed the vena cava. Iron deficiency followed resection of the large tumor. Advanced stages of adrenocortical carcinoma are associated with poor prognosis. Mitotane chemotherapy is a standard but unproven adjuvant treatment that is associated with many complications, and its induction of hepatic CYP 3A4 enzymes necessitates adjustment of other medications. Keywords: Adrenocortical carcinoma, Mitotane, Ki67 index, Peripheral edema
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Intravenous (IV) iron is required for optimal management of anemia in the majority of hemodialysis (HD) patients. While IV iron prescription has increased over time, the best dosing strategy is ...unknown and any effect of IV iron on survival is unclear. Here we used adjusted Cox regression to analyze associations between IV iron dose and clinical outcomes in 32,435 HD patients in 12 countries from 2002 to 2011 in the Dialysis Outcomes and Practice Patterns Study. The primary exposure was total prescribed IV iron dose over the first 4 months in the study, expressed as an average dose/month. Compared with 100–199mg/month (the most common dose range), case-mix-adjusted mortality was similar for the 0, 1–99, and 200–299mg/month categories but significantly higher for the 300–399mg/month (HR of 1.13, 95% CI of 1.00–1.27) and 400mg/month or more (HR of 1.18, 95% CI of 1.07–1.30) groups. Convergent validity was proved by an instrumental variable analysis, using HD facility as the instrument, and by an analysis expressing IV iron dose/kg body weight. Associations with cause-specific mortality (cardiovascular, infectious, and other) were generally similar to those for all-cause mortality. The hospitalization risk was elevated among patients receiving 300mg/month or more compared with 100–199mg/month (HR of 1.12, 95% CI of 1.07–1.18). In light of these associations, a well-powered clinical trial to evaluate the safety of different IV iron-dosing strategies in HD patients is urgently needed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction: This study examines factors associated with erythropoiesis-stimulating agent (ESA) hyporesponsiveness, the duration of ESA hyporesponsiveness, the frequency of new episodes, and ...variation across countries. Methods: We used international Dialysis Outcomes and Practice Patterns Study data from 2015 to 2018 (N = 26,656) to investigate changes in ESA Resistance Index (ERI), calculated as epoetin dose divided by hemoglobin × body weight in patients on hemodialysis. We illustrated the proportion of patients who moved to other ERI quintiles over 12 months, and we studied the incidence and duration of ESA resistance. We examined case-mix factors associated with quintiles of ERI. Results: Most patients migrated out of their original ERI quintile within 4 months. Only 22% of patients in the top quintile of ERI at baseline (4.4% of all patients) remained in the top quintile during all 12 months of follow-up. A total of 42% of patients manifested an upper-quintile ERI during at least 1 month. Median duration of a new episode of ESA resistance was 2 months. Catheter hemoaccess, elevated C-reactive protein, lower transferrin saturation, lower serum albumin concentration, and recent hospitalization occurred more frequently among patients in the highest ERI quintile at baseline. ERI values were highest in the USA, Italy, and Mideastern nations and lowest in Russia and Japan. Discussion/Conclusion: It is a misconception to envision a sizable, fixed segment of the population with permanent resistance to ESA – resistance fluctuates frequently. The implications of these findings for prescription of ESAs and of hypoxia-inducible factor-prolyl hydroxylase inhibitors are discussed.
Hepatitis C virus (HCV) infection is associated with increased mortality among hemodialysis (HD) patients. Guidelines from Kidney Disease: Improving Global Outcomes recommend that infected HD ...patients awaiting renal transplantation be treated for HCV and that clinicians decide whether to treat other infected patients on a case-by-case basis. We evaluated the extent and outcome of HCV therapy among HD patients.
The Dialysis Outcomes and Practice Patterns Study is an observational study; 49,762 HD patients in 12 nations enrolled between 1996 and 2011. We reviewed HCV status, use of interferon or ribavirin, and survival over a median 1.4 years per study phase.
4,735 patients (9.5%) were HCV+. Only 48 (1.0%) of the 4,589 HCV+ patients with prescription data were receiving antiviral medication. Among the subset of 617 HCV+ patients also known to be on a waiting list for renal transplantation, only 3.7% were receiving treatment. After restricting to HCV+ patients with overlapping propensity for antiviral treatment, 4 (9.5%) of 42 treated patients and 638 (21.0%) of 3,037 untreated patients died. The hazard ratio for adjusted mortality comparing treated patients with untreated patients was 0.47 (95% CI, 0.17-1.26).
HD patients with hepatitis C infection very rarely receive antiviral therapy. Increased intervention might prolong survival for some patients and in particular might improve the prospects for those awaiting renal transplantation.
Predictors and consequences of altered mineral metabolism: The Dialysis Outcomes and Practice Patterns Study.
Altered mineral metabolism contributes to bone disease, cardiovascular disease, and other ...clinical problems in patients with end-stage renal disease.
This study describes the recent status, significant predictors, and potential consequences of abnormal mineral metabolism in representative groups of hemodialysis facilities (N = 307) and patients (N = 17,236) participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS) in the United States, Europe, and Japan from 1996 to 2001.
Many patients fell out of the recommended guideline range for serum concentrations of phosphorus (8% of patients below lower target range, 52% of patients above upper target range), albumin-corrected calcium (9% below, 50% above), calcium-phosphorus product (44% above), and intact PTH (51% below, 27% above). All-cause mortality was significantly and independently associated with serum concentrations of phosphorus (RR 1.04 per 1 mg/dL, P = 0.0003), calcium (RR 1.10 per 1 mg/dL, P < 0.0001), calcium-phosphorus product (RR 1.02 per 5 mg2/dL2, P = 0.0001), PTH (1.01 per 100 pg/dL, P = 0.04), and dialysate calcium (RR 1.13 per 1 mEq/L, P = 0.01). Cardiovascular mortality was significantly associated with the serum concentrations of phosphorus (RR 1.09, P < 0.0001), calcium (RR 1.14, P < 0.0001), calcium-phosphorus product (RR 1.05, P < 0.0001), and PTH (RR 1.02, P = 0.03). The adjusted rate of parathyroidectomy varied 4-fold across the DOPPS countries, and was significantly associated with baseline concentrations of phosphorus (RR 1.17, P < 0.0001), calcium (RR 1.58, P < 0.0001), calcium-phosphorus product (RR 1.11, P < 0.0001), PTH (RR 1.07, P < 0.0001), and dialysate calcium concentration (RR 0.57, P = 0.03). Overall, 52% of patients received some form of vitamin D therapy, with parenteral forms almost exclusively restricted to the United States. Vitamin D was potentially underused in up to 34% of patients with high PTH, and overused in up to 46% of patients with low PTH. Phosphorus binders (mostly calcium salts during the study period) were used by 81% of patients, with potential overuse in up to 77% patients with low serum phosphorus concentration, and potential underuse in up to 18% of patients with a high serum phosphorus concentration.
This study expands our understanding of the relationship between altered mineral metabolism and outcomes and identifies several potential opportunities for improved practice in this area.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To examine patterns of intravenous (IV) iron use across 12 countries from 1999 to 2011.
Trends in iron use are described among 32 192 hemodialysis (HD) patients in the Dialysis Outcomes and Practice ...Patterns Study. Adjusted associations of IV iron dose with serum ferritin and transferrin saturation (TSAT) values were also studied.
IV iron was administered to 50% of patients over 4 months in 1999, increasing to 71% during 2009-11, with increasing use in most countries. Among patients receiving IV iron, the mean monthly dose increased from 232 ± 167 to 281 ± 211 mg. Most countries used 3 to 4 doses/month, but Canada used about 2 doses/month, Italy increased from 3 to almost 6 doses/month and Germany used 5 to 6 doses/month. The USA and most European countries predominantly used iron sucrose and sodium ferric gluconate. A significant use of iron dextran was limited to Canada and France; iron polymaltose was used in Australia and New Zealand; and Japan used ferric oxide saccharate, chondroitin polysulfate iron complex and cideferron. Ferritin values rose in most countries: 22% of patients had ≥ 800 ng/mL in the recent years of study. TSAT levels increased to a lesser degree over time. Japan had much lower IV iron dosing and ferritin levels, but similar TSAT levels. In adjusted analyses, serum ferritin and TSAT levels increased signifcantly by 14 ng/mL and 0.16%, respectively, for every 100 mg/month higher mean monthly iron dose.
IV iron prescription patterns varied between countries and changed over time from 1999 to 2011. IV iron use and dose increased in most countries, with notable increases in ferritin but not TSAT levels. With rising cumulative IV iron doses, studies of the effects of changing IV iron dosing and other anemia management practices on clinical outcomes should be a high priority.
KDOQI practice guidelines recommend predialysis blood pressure <140/90mmHg; however, most prior studies had found elevated mortality with low, not high, systolic blood pressure. This is possibly due ...to unmeasured confounders affecting systolic blood pressure and mortality. To lessen this bias, we analyzed 24,525 patients by Cox regression models adjusted for patient and facility characteristics. Compared with predialysis systolic blood pressure of 130–159mmHg, mortality was 13% higher in facilities with 20% more patients at systolic blood pressure of 110–129mmHg and 16% higher in facilities with 20% more patients at systolic blood pressure of ≥160mmHg. For patient-level systolic blood pressure, mortality was elevated at low (<130mmHg), not high (≥180mmHg), systolic blood pressure. For predialysis diastolic blood pressure, mortality was lowest at 60–99mmHg, a wide range implying less chance to improve outcomes. Higher mortality at systolic blood pressure of <130mmHg is consistent with prior studies and may be due to excessive blood pressure lowering during dialysis. The lowest risk facility systolic blood pressure of 130–159mmHg indicates this range may be optimal, but may have been influenced by unmeasured facility practices. While additional study is needed, our findings contrast with KDOQI blood pressure targets, and provide guidance on optimal blood pressure range in the absence of definitive clinical trial data.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP