bims-fikidi 2018-05-20 papers

bims-fikidi

Biomed News

on Fibroblast growth factor 23 in chronic kidney disease

Issue of 2018–05–20
ten papers selected by
Regina Goetz, New York University Langone Medical Center

Updates on the Mechanisms and the Care of Cardiovascular Calcification in Chronic Kidney Disease.
Denosumab-Associated Severe Hypocalcemia in a Patient With Chronic Kidney Disease.
Cardiovascular Risk Prediction in CKD.
HIF Activation Against CVD in CKD: Novel Treatment Opportunities.
Cardiovascular Disease and Diabetic Kidney Disease.
Vitamin D and Calcimimetics in Cardiovascular Disease.
Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease.
Clinical Studies of Interventions to Mitigate Cardiovascular Risk in Peritoneal Dialysis Patients.
Cardiovascular Disease Risk in Children With Kidney Disease.
Introduction: Kidney Disease and Cardiovascular Disease.

Semin Nephrol. 2018 May;pii: S0270-9295(18)30025-1. [Epub ahead of print]38(3): 233-250

Updates on the Mechanisms and the Care of Cardiovascular Calcification in Chronic Kidney Disease.

Lucie Hénaut, Jean-Marc Chillon, Saïd Kamel, Ziad A Massy.

  In chronic kidney disease (CKD), the progressive decrease in renal function leads to disturbances of mineral metabolism that generally cause secondary hyperparathyroidism. The increase in serum parathyroid hormone is associated with reduced serum calcium and calcitriol levels and/or increased serum fibroblast growth factor-23 and phosphate levels. The resulting CKD-associated disorder of mineral and bone metabolism is associated with various other metabolic dysregulations such as acidosis, malnutrition, inflammation, and accumulation of uremic toxins. It favors the occurrence of vascular calcification, which results from an imbalance between numerous inhibitors and promoters of soft-tissue mineralization. This review provides an overview of the most recent state of knowledge concerning the mechanisms that lead to the development of vascular calcification in the CKD setting. It further proposes directions for potential new therapeutic targets.

Keywords:  Chronic kidney disease; inhibitors; promoters; treatments; vascular calcification

DOI:  https://doi.org/10.1016/j.semnephrol.2018.02.004
Am J Med Sci. 2018 May;pii: S0002-9629(17)30523-2. [Epub ahead of print]355(5): 506-509

Denosumab-Associated Severe Hypocalcemia in a Patient With Chronic Kidney Disease.

Sohail Abdul Salim, Lakshmi Ramachandran Nair, Litty Thomas, Vishnu Garla, Venkataraman Palabindala, Mohit Agarwal, Tibor Fülöp.

  Denosumab is a monoclonal antibody directed against the receptor activator of nuclear factor kappa B ligand (RANKL). Denosumab has been shown to reduce the risk of skeletal-related events, including spinal cord compression, pathologic fracture and hypercalcemia of malignancy in patients with bone metastases. Hypocalcemia is a known side effect of denosumab, occurring in an estimated 8-14% of the patients. Here, we present an asymptomatic patient with stage-5 chronic kidney disease and severe hypocalcemia who had received denosumab 1 month earlier.

Keywords:  Alkaline phosphatase; End-stage renal disease; Hypercalcemia of malignancy; Parathyroid hormone; RANKL inhibitor

DOI:  https://doi.org/10.1016/j.amjms.2017.09.008
Semin Nephrol. 2018 May;pii: S0270-9295(18)30023-8. [Epub ahead of print]38(3): 208-216

Cardiovascular Risk Prediction in CKD.

Shoshana H Ballew, Kunihiro Matsushita.

  Cardiovascular disease is an important complication for patients with chronic kidney disease (CKD), warranting accurate risk prediction, but clinical guidelines are inconsistent regarding whether or how to use information on measures of CKD for predicting risk. Recent large meta-analyses have shown that key CKD measures (estimated glomerular filtration rate and albuminuria) improve cardiovascular risk prediction beyond traditional risk factors, especially when albuminuria is added to prediction models. In addition, several recent studies have shown that the use of filtration markers other than serum creatinine, cystatin C, and β2-microglobulin can improve cardiovascular risk prediction. In case the goal is to best estimate cardiovascular risk, recent studies have shown that measures reflecting pathophysiological processes in the cardiovascular system, such as coronary artery calcium score or high-sensitivity cardiac troponin T, can be useful in CKD populations. This review compares the current major clinical guidelines and synthesizes the growing body of evidence on traditional and nontraditional predictors for improving cardiovascular risk prediction in persons with CKD.

Keywords:  Albuminuria; cardiovascular disease; estimated glomerular filtration rate; risk prediction

DOI:  https://doi.org/10.1016/j.semnephrol.2018.02.002
Semin Nephrol. 2018 May;pii: S0270-9295(18)30027-5. [Epub ahead of print]38(3): 267-276

HIF Activation Against CVD in CKD: Novel Treatment Opportunities.

Tetsuhiro Tanaka, Kai-Uwe Eckardt.

  Cardiovascular disease is a common and serious complication in patients with chronic kidney disease (CKD). One of the fundamental functions of the cardiovascular system is oxygen delivery, therefore cardiovascular disease inherently is linked to insufficient tissue oxygenation. Advances in our knowledge of cellular oxygen sensing by a family of prolyl hydroxylases (PHDs) and their role in regulating hypoxia-inducible factors (HIFs) have led to the discovery of PHD inhibitors as HIF stabilizers. Several small-molecule PHD inhibitors are currently in clinical trials for the treatment of anemia in CKD. An additional advantage of PHD inhibition may be found in the potential impact on cardiovascular consequences associated with CKD. Several preclinical studies have suggested a potential benefit of HIF activation in myocardial infarction, cardiac remodeling, atherosclerosis, and peripheral artery disease. Ameliorating glucose and lipid metabolism and lowering blood pressure may also contribute to cardiovascular protection. On the other hand, the broad spectrum of HIF-dependent functions also may include unwanted side effects. Clinical application of PHD inhibitors therefore necessitates careful evaluation of the net systemic effect of HIF activation.

Keywords:  CKD; CVD; HIF; PHD inhibitor

DOI:  https://doi.org/10.1016/j.semnephrol.2018.02.006
Semin Nephrol. 2018 May;pii: S0270-9295(18)30024-X. [Epub ahead of print]38(3): 217-232

Cardiovascular Disease and Diabetic Kidney Disease.

Muhammad Maqbool, Mark E Cooper, Karin A M Jandeleit-Dahm.

  Diabetic kidney disease commonly is associated with an increased risk of cardiovascular disease. There are traditional common risk factors for both conditions including hypertension and poor glycemic control. However, it is likely that there are other pathophysiological mechanisms that explain the clinical phenomenon of increased cardiovascular disease in diabetic patients with chronic kidney and vice versa. Current management of both conditions includes aggressive glucose and blood pressure control. The protective role of treating dyslipidemia has been shown for cardiovascular disease, but the results for renal disease are not as clear. The advent of new classes of glucose-lowering agents such as sodium glucose co-transporter2 inhibitors and glucagon-like peptide-1 agonists has resulted in impressive effects on both cardiovascular and renal disease in diabetes. However, how these drugs act independently of glucose lowering to confer both kidney and cardiovascular protection has not been fully elucidated. Nevertheless, these new treatments provide optimism for reducing both microvascular and macrovascular complications in diabetes, which represent the major causes of morbidity and premature mortality in this condition.

Keywords:  Cardiovascular disease; diabetes; diabetic nephropathy; hyperlipidemia; hypertension; treatments

DOI:  https://doi.org/10.1016/j.semnephrol.2018.02.003
Semin Nephrol. 2018 May;pii: S0270-9295(18)30026-3. [Epub ahead of print]38(3): 251-266

Vitamin D and Calcimimetics in Cardiovascular Disease.

Kenneth Lim, Takayuki Hamano, Ravi Thadhani.

  Cardiovascular disease has earned its place as one of the leading noncommunicable diseases that has become a modern-day global epidemic. The increasing incidence and prevalence of chronic kidney disease (CKD) has added to this enormous burden, given that CKD is now recognized as an established risk factor for accelerated cardiovascular disease. In fact, cardiovascular disease remains the leading cause of death in the CKD population, with significant prognostic implications. Alterations in vitamin D levels as renal function declines has been linked invariably to the development of cardiovascular disease beyond a mere epiphenomenon, and has become an important focus in recent years in our search for new therapies. Another compound, cinacalcet, which belongs to the calcimimetic class of agents, also has taken center stage over the past few years as a potential cardiovasculoprotective agent. However, given limited well-designed randomized trials to inform us, our clinical practice for the management of cardiovascular disease in CKD has not been adequately refined. This article considers the biological mechanisms, regulation, and current experimental, clinical, and trial data available to help guide the therapeutic use of vitamin D and calcimimetics in the setting of CKD and cardiovascular disease.

Keywords:  Vitamin D; arterial stiffening; calcimimetics; calcium sensing receptors (CaSRs); cardiovascular; heart failure; left ventricular function; vascular calcification

DOI:  https://doi.org/10.1016/j.semnephrol.2018.02.005
J Pediatr. 2018 May 09. pii: S0022-3476(18)30424-4. [Epub ahead of print]

Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease.

ESCAPE Study Group

   OBJECTIVE: To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis.
STUDY DESIGN: A dataset comprising 385 patients from the ARegPKD international registry study was analyzed for potential risk markers for dialysis during the first year of life.
RESULTS: Thirty-six out of 385 children (9.4%) commenced dialysis in the first year of life. According to multivariable Cox regression analysis, the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, a low Apgar score, and the need for postnatal breathing support were independently associated with an increased hazard ratio for requiring dialysis within the first year of life. The increased risk associated with Apgar score and perinatal assisted breathing was time-dependent and vanished after 5 and 8 months of life, respectively. The predicted probabilities for early dialysis varied from 1.5% (95% CI, 0.5%-4.1%) for patients with ARPKD with no prenatal sonographic abnormalities to 32.3% (95% CI, 22.2%-44.5%) in cases of documented oligohydramnios or anhydramnios, renal cysts, and enlarged kidneys.
CONCLUSIONS: This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life, may be helpful in prenatal parental counseling in cases of suspected ARPKD.

Keywords:  PKHD1; ciliopathy; oligohydramnios; renal replacement therapy

DOI:  https://doi.org/10.1016/j.jpeds.2018.03.052
Semin Nephrol. 2018 May;pii: S0270-9295(18)30028-7. [Epub ahead of print]38(3): 277-290

Clinical Studies of Interventions to Mitigate Cardiovascular Risk in Peritoneal Dialysis Patients.

Dev Jegatheesan, Yeoungjee Cho, David W Johnson.

  Cardiovascular disease (CVD) is highly prevalent in the peritoneal dialysis (PD) population, affecting up to 60% of cohorts. CVD is the primary cause of death in up to 40% of PD patients in Australia, New Zealand, and the United States. Cardiovascular mortality rates are reported to be approximately 14 per 100 patient-years, which are 10- to 20-fold greater than those of age- and sex-matched controls. The excess risk of CVD is related to a combination of traditional risk factors (such as hypertension, dyslipidemia, obesity, smoking, sedentary lifestyle, and insulin resistance), nontraditional (kidney disease-related) risk factors (such as anemia, chronic volume overload, inflammation, malnutrition, hyperuricemia, and mineral and bone disorder), and PD-specific risk factors (such as dialysis solutions, glycation end products, hypokalemia, residual kidney function, and ultrafiltration failure). Interventions targeting these factors may mitigate cardiovascular risk, although high-level clinical evidence is lacking. This review summarizes the evidence relating to cardiovascular interventions targeting modifiable CVD risk factors in PD patients, as well as highlighting the key recommendations of the International Society for Peritoneal Dialysis Cardiovascular and Metabolic Guidelines.

Keywords:  Cardiovascular disease; disease management; metabolic diseases; peritoneal dialysis; practice guidelines; risk assessment

DOI:  https://doi.org/10.1016/j.semnephrol.2018.02.007
Semin Nephrol. 2018 May;pii: S0270-9295(18)30030-5. [Epub ahead of print]38(3): 298-313

Cardiovascular Disease Risk in Children With Kidney Disease.

Christine B Sethna, Kumail Merchant, Abigail Reyes.

  Cardiovascular disease is a major cause of death in individuals diagnosed with kidney disease during childhood. Children with kidney disease often incur a significant cardiovascular burden that leads to increased risk for cardiovascular disease. Evidence has shown that children with kidney disease, including chronic kidney disease, dialysis, kidney transplantation, and nephrotic syndrome, develop abnormalities in cardiovascular markers such as hypertension, dyslipidemia, left ventricular hypertrophy, left ventricular dysfunction, atherosclerosis, and aortic stiffness. Early identification of modifiable risk factors and treatment may lead to a decrease of long-term cardiovascular morbidity and mortality, but evidence in this population is lacking.

Keywords:  Left ventricular hypertrophy; cIMT; chronic kidney disease; dialysis; hypertension; kidney transplant; nephrotic syndrome; pediatric

DOI:  https://doi.org/10.1016/j.semnephrol.2018.02.009
Semin Nephrol. 2018 May;pii: S0270-9295(18)30033-0. [Epub ahead of print]38(3): 207

Introduction: Kidney Disease and Cardiovascular Disease.

Masaomi Nangaku.

DOI: https://doi.org/10.1016/j.semnephrol.2018.03.001