Mineral bone disease (MBD) has proven to be a Pandora’s box for most clinicians treating chronic kidney disease (CKD), including end-stage kidney disease (ESKD). Although the body of literature highlighting the various bone metabolic abnormalities associated with ESKD as definite risk factors for mortality, cardiovascular disease, increased risk of fractures, and other musculoskeletal complications grows stronger, the therapeutic agents to deal with these abnormalities continue to keep us on edge (Table 1).
Reasons for skepticism among nephrologists regarding novel drugs for MBD
Appropriate and timely management of hyperkalemia is an important component of a nephrology practice. Hyperkalemia can result from increased K+ intake in the diet, impaired distribution between intracellular and extracellular spaces, and decreased kidney excretion. Risk factors associated with the development of hyperkalemia include older age, male sex, diabetes, underlying kidney disease, as well as intake of certain medications that affect the renin angiotensin aldosterone system (RAAS).
Prior to the advent of sodium zirconium cyclosilicate (SZC) and patiromer, only sodium polystyrene sulfonate (SPS) was available as a potassium exchange resin (1). Approved by the
Most nephrologists learn early in their training that the most common immunosuppressant regimen for patients with a kidney transplant consists of a calcineurin inhibitor (CNI), mycophenolic acid (usually mycophenolate mofetil [MMF]), with or without some corticosteroid. Let’s take a quick look at two emerging outside-the-box immunosuppression tools.
The new kid on the block
CNIs have long been a thorn in kidney transplantation’s side—with a laundry list of adverse effects ranging from tremors to electrolyte disturbances to paradoxical nephrotoxicity (1). One newer drug that has provided a CNI-free option in some patients is belatacept (approved
The last two years have brought several promising trials with novel therapies for the treatment of membranous nephropathy, the most common etiology of nephrotic syndrome in adults (1, 2).
Currently, the mainstay of treatment is steroids in combination with alkylating agents (modified Ponticelli regimen) or calcineurin inhibitors (3). With the identification of auto-antibodies against the phospholipase-2 receptor (PLA2R) comes the potential for new therapies (4, 5), including monoclonal antibodies against CD20 on B-lymphocytes: rituximab and obinutuzumab (4).
In 2019, the MENTOR randomized controlled trial showed that rituximab was
Ms. H is a 33-year-old Hispanic woman referred from a primary care clinic for proteinuria. Her only past medical history is hypertension on a single agent, amlodipine. She has had three children and had a tubal ligation for contraception. She reports that her pregnancies were uncomplicated with no history of preeclampsia or gestational diabetes. Her physical exam was unremarkable with blood pressure 130/70 mm Hg, and she has no edema.
Her laboratory data revealed a normal comprehensive metabolic panel with serum creatinine of 1.6 mg/dL and complete blood counts, although her serologies were noted for the following:
Drug discovery and development is a lengthy and expensive process. Testing new agents in humans at an early stage can reduce the time and costs involved in identifying drugs that are likely to succeed in clinical studies. Implementation of a new drug in practice also requires the development of useful biomarkers of disease and of the drug’s efficacy, as well as sensitive molecular imaging techniques.
Nephrology relied on only a handful of therapeutics during the 1970s to 2000s for managing anemia, bone-mineral disease, glomerular diseases, and transplantation-related events. In the past 2 decades, there has been a steady rise in
Mohammed Elsadany, Yifeng Yang, Sonali Gupta, and Joseph Mattana
It has been well known for many years that cardiovascular disease disproportionately affects patients with chronic kidney disease (CKD) and kidney failure, both through acceleration of atherogenesis as a consequence of reduced kidney function and through the various comorbidities with which our patients are frequently afflicted. Despite growing mechanistic insights into kidney–heart interactions, atherogenesis, cardiac hypertrophy, valvular heart disease, and other phenomena and into new therapies that are available, patients with kidney disease continue to experience an excessive burden of cardiovascular disease and events.
Cardiovascular disease, particularly coronary artery disease, is more often a condition of the older individual, but
Mohammed Elsadany, Yifeng Yang, Sonali Gupta, and Joseph Mattana
Patients with chronic kidney disease (CKD) are at higher risk for premature cardiovascular disease and events in comparison with the general population. This appears to result from a complex interplay of various metabolic and vascular factors. There are some underlying differences in the lipid profile of CKD patients versus individuals without CKD. Among them are an abundance of small, dense, atherogenic LDL particles; elevated concentrations of triglycerides; reduced HDL cholesterol concentrations; altered lipoproteins; and the presence of lipoprotein and chylomicron remnants—findings that are characteristic of the lipid profile in this population. Among other variables that affect the heightened propensity of
P eople with kidney disease are medically complex, and kidney disease may have an impact on the development of therapies to treat the many comorbidities affecting this population. Cardiovascular disease is a common and significant comorbidity among these patients, and individuals with kidney disease make up a sizeable proportion (30% to 60%) of patients with cardiovascular disease (1, 2). Yet, patients with kidney disease have often been excluded from cardiovascular clinical trials (1–4), thus limiting the evidence to guide treatment recommendations of cardiovascular disease for these patients.
Yifeng Yang, Mohammed Elsadany, Sonali Gupta, and Joseph Mattana
Dyslipidemia has long been established as a traditional risk factor for cardiovascular disease in the general population. Dyslipidemia, characterized especially by elevated LDL and VLDL, is well known to be associated with higher atherosclerotic cardiovascular disease risk and is a large public health threat.
In patients with chronic kidney disease (CKD) and end stage renal disease (ESRD), cardiovascular disease is accelerated with an even larger impact, compared with the general population. Multiple variables are thought to contribute to this heightened propensity to and accelerated course of cardiovascular disease, including significant alterations in lipoprotein metabolism such as decreased HDL and increased