International practice patterns of dyslipidemia management in patients with chronic kidney disease under nephrology care: is it time to review guideline recommendations?

BACKGROUND: In contrast to guidelines related to lipid therapy in other areas, 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend conducting a lipid profile upon diagnosis of chronic kidney disease (CKD) and treating all patients older than 50 years without defining a target for lipid levels. We evaluated multinational practice patterns for lipid management in patients with advanced CKD under nephrology care. METHODS: We analyzed lipid-lowering therapy (LLT), LDL- cholesterol (LDL-C) levels, and nephrologist-specified LDL-C goal upper limits in adult patients with eGFR < 60 ml/min from nephrology clinics in Brazil, France, Germany, and the United States (2014-2019). Models were adjusted for CKD stage, country, cardiovascular risk indicators, sex, and age. RESULTS: LLT treatment differed significantly by country, from 51% in Germany to 61% in the US and France (p = 0.002) for statin monotherapy. For ezetimibe with or without statins, the prevalence was 0.3% in Brazil to 9% in France (< 0.001). Compared with patients not taking lipid-lowering therapy, LDL-C was lower among treated patients (p < 0.0001) and differed significantly by country (p < 0.0001). At the patient level, the LDL-C levels and statin prescription did not vary significantly by CKD stage (p = 0.09 LDL-C and p = 0.24 statin use). Between 7-23% of untreated patients in each country had LDL-C ≥ 160 mg/dL. Only 7-17% of nephrologists believed that LDL-C should be < 70 mg/dL. CONCLUSION: There is substantial variation in practice patterns regarding LLT across countries but not across CKD stages. Treated patients appear to benefit from LDL-C lowering, yet a significant proportion of hyperlipidemia patients under nephrologist care are not receiving treatment.

Serum Biomarkers of Iron Stores Are Associated with Increased Risk of All-Cause Mortality and Cardiovascular Events in Nondialysis CKD Patients, with or without Anemia.

BACKGROUND: Approximately 30%-45% of patients with nondialysis CKD have iron deficiency. Iron therapy in CKD has focused primarily on supporting erythropoiesis. In patients with or without anemia, there has not been a comprehensive approach to estimating the association between serum biomarkers of iron stores, and mortality and cardiovascular event risks. METHODS: The study included 5145 patients from Brazil, France, the United States, and Germany enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study, with first available transferrin saturation (TSAT) and ferritin levels as exposure variables. We used Cox models to estimate hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACE), with progressive adjustment for potentially confounding variables. We also used linear spline models to further evaluate functional forms of the exposure-outcome associations. RESULTS: Compared with patients with a TSAT of 26%-35%, those with a TSAT ≤15% had the highest adjusted risks for all-cause mortality and MACE. Spline analysis found the lowest risk at TSAT 40% for all-cause mortality and MACE. Risk of all-cause mortality, but not MACE, was also elevated at TSAT ≥46%. Effect estimates were similar after adjustment for hemoglobin. For ferritin, no directional associations were apparent, except for elevated all-cause mortality at ferritin ≥300 ng/ml. CONCLUSIONS: Iron deficiency, as captured by TSAT, is associated with higher risk of all-cause mortality and MACE in patients with nondialysis CKD, with or without anemia. Interventional studies evaluating the effect on clinical outcomes of iron supplementation and therapies for alternative targets are needed to better inform strategies for administering exogenous iron.

A real-world longitudinal study of anemia management in non-dialysis-dependent chronic kidney disease patients: a multinational analysis of CKDopps.

Previously lacking in the literature, we describe longitudinal patterns of anemia prescriptions for non-dialysis-dependent chronic kidney disease (NDD-CKD) patients under nephrologist care. We analyzed data from 2818 Stage 3-5 NDD-CKD patients from Brazil, Germany, and the US, naïve to anemia medications (oral iron, intravenous [IV] iron, or erythropoiesis stimulating agent [ESA]) at enrollment in the CKDopps. We report the cumulative incidence function (CIF) of medication initiation stratified by baseline characteristics. Even in patients with hemoglobin (Hb) < 10 g/dL, the CIF at 12 months for any anemia medication was 40%, and 28% for ESAs. Patients with TSAT < 20% had a CIF of 26% and 6% for oral and IV iron, respectively. Heart failure was associated with earlier initiation of anemia medications. IV iron was prescribed to < 10% of patients with iron deficiency. Only 40% of patients with Hb < 10 g/dL received any anemia medication within a year. Discontinuation of anemia treatment was very common. Anemia treatment is initiated in a limited number of NDD-CKD patients, even in those with guideline-based indications to treat. Hemoglobin trajectory and a history of heart failure appear to guide treatment start. These results support the concept that anemia is sub-optimally managed among NDD-CKD patients in the real-world setting.

Anemia and iron deficiency among chronic kidney disease Stages 3-5ND patients in the Chronic Kidney Disease Outcomes and Practice Patterns Study: often unmeasured, variably treated.

BACKGROUND: International variation in anemia assessment and management practices in chronic kidney disease (CKD) is poorly understood. METHODS: We performed a cross-sectional analysis of anemia laboratory monitoring, prevalence and management in the prospective Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps). A total of 6766 participants with CKD Stages 3a-5ND from nephrology clinics in Brazil, France, Germany and the USA were included. RESULTS: Among patients with anemia (hemoglobin <12 g/dL), 36-58% in Brazil, the USA and Germany had repeat hemoglobin measured and 40-61% had iron indices measured within 3 months of the index hemoglobin measurement. Anemia was more common in the USA and Brazil than in France and Germany across CKD stages. Higher ferritin and lower iron saturation (TSAT) levels were observed with lower hemoglobin levels, and higher ferritin with more advanced CKD. The proportion of anemic patients with ferritin <100 ng/mL or TSAT <20% ranged from 42% in Brazil to 53% in France and Germany, and of these patients, over 40% in Brazil, Germany and the USA, compared with 27% in France, were treated with oral or intravenous iron within 3 months after hemoglobin measurement. The proportion of patients with hemoglobin <10 g/dL treated with erythropoiesis-stimulating agents ranged from 28% in the USA to 57% in Germany. CONCLUSIONS: Hemoglobin and iron stores are measured less frequently than per guidelines. Among all regions, there was a substantial proportion of anemic patients with iron deficiency who were not treated with iron, highlighting an area for practice improvement in CKD care.

International study of health care organization and financing: development of renal replacement therapy in Germany.

The German health system represents the case of a global budget with negotiated fees and competing medical insurance companies. Physicians in private practice and non-profit dialysis provider associations provide most dialysis therapy. End-stage renal disease (ESRD) modalities are well integrated into the overall health care system. Dialysis therapy, independent of the mode of treatment, is reimbursed at a weekly flat rate. Mandatory health insurance covers health expenses, including those related to ESRD, for more than 90% of the population. Both employees and employers contribute to the premium for this insurance. Private medical insurance covers the remainder of the population. Access to treatment, including dialysis therapy, is uniformly available.

Evaluation of serum beta-carboxy-terminal cross-linking telopeptide of type I collagen as marker of bone resorption in chronic hemodialysis patients.

BACKGROUND: The carboxy-terminal cross-linking telopeptide of type I collagen (beta-CrossLaps, beta-CTX) is released into the circulation during degradation of type I collagen and serves as a marker of bone resorption. beta-CTX is known to undergo a diurnal rhythm in normal individuals and to accumulate in chronic renal failure. beta-CTX has a potential role in noninvasive diagnosis of renal bone disease. METHODS: Serum beta-CTX was compared to parathyroid hormone (PTH) and other biochemical bone markers in 90 unselected hemodialysis patients. RESULTS: Mean beta-CTX was elevated above the normal range (1.72 +/- 0.93 microg/l); there were large individual variations. Serum beta-CTX was significantly correlated with various PTH assays (r >0.56) and with tartrate-resistant acid phosphatase 5b (TRACP 5b, r = 0.629), bone-specific alkaline phosphatase (r = 0.404) and osteocalcin (r = 0.534, all correlations p < 0.001). The correlation between beta-CTX and PTH was significantly higher than the correlation between TRACP 5b and PTH. Several factors which could confound interpretation of serum beta-CTX were assessed in further studies: (i) There was no recognizable influence of the time of blood sampling (morning dialysis shift versus afternoon dialysis shift) on serum beta-CTX. (ii) Serum beta-CTX was not significantly related to residual diuresis of patients. CONCLUSIONS: We found a high association between beta-CTX and other established markers of bone and calcium metabolism demonstrating the potential utility of beta-CTX as marker of bone resorption in renal bone disease. However, further studies employing bone histology are still warranted to exactly define the influence of glomerular retention on serum beta-CTX in end-stage renal disease.