Abstract and Introduction
Abstract
Objective: Chronic kidney disease-mineral and bone disorders (CKD-MBDs) are a spectrum of abnormalities involving skeletal hormones, minerals, and bone turnover and mineralization. This paper focuses on what the endocrinologist should know about the assessment and management of skeletal and metabolic disorders in CKD-MBDs.
Methods: Relevant literature was reviewed to (1) define disturbances of minerals and hormones in the course of CKD; (2) identify the variable radiographic and histomorphometric changes of CKD-MBDs; (3) review the association among CKD-MBDs, vascular calcification, cardiovascular disease (CVD), and mortality; and (4) clarify issues in CKD-MBDs therapy.
Results: Assessment and treatment of CKD-MBDs is complicated by progressive changes in bone minerals and skeletal regulatory hormones as kidney function declines. CKD-MBDs are associated with fracture risk, and studies demonstrate that bone mineral density can be used to assess bone loss and fracture risk in these patients. Treatment of CKD-MBDs continues to evolve. Use of calcium, phosphate binders, vitamin D, vitamin D–receptor analogs, and drugs for osteoporosis and CKD-MBDs treatment are discussed in the context of safety and efficacy for patients with CKD.
Conclusion: The association of CKD with bone disease, vascular calcification, CVD, and mortality mandates earlier recognition and treatment of CKD-MBDs. Osteoporosis as a distinct entity can be diagnosed and managed in CKD, although assessment of osteoporosis becomes challenging in late (stage 4 to 5) CKD. Diabetes is common in early (stage 1 to 3) CKD. In addition, 96% of all individuals identified as having CKD have early CKD. The endocrinologist is uniquely positioned to address and treat both diabetes and many of the metabolic and skeletal disorders associated with early CKD-MBDs, including osteoporosis.
Introduction
Chronic kidney disease (CKD) is a serious condition associated with increased healthcare expenditures, decreased quality of life, and premature mortality. As reported by the National Health and Nutrition Examination Survey (NHANES) III, CKD affects 11% (19.2 million) of adult (aged 20 years and older) men and women in the United States,[1] and its incidence is likely to further increase with increasing longevity and the rising incidence of obesity and type 2 diabetes mellitus (T2DM). NHANES is a continuous data survey of health and nutritional status of U.S. adults, and results are analyzed and released periodically by the Centers for Disease Control. The NHANES noted a 15.9% increase in the prevalence of CKD between 1988 and 1994 and between 1999 and 2004. CKD is most common in persons ≥60 years of age (39.4% of this population) but also presents in persons aged 40 to 59 and 20 to 39 years (12.6 and 8.5% of these age groups, respectively).[2] T2DM is the leading cause of CKD in developed countries[3] and accounts for 45% of all cases of kidney failure.[4]
Kidney disease is defined as an abnormality of kidney structure or function with implications for the health of an individual.[5] The National Kidney Foundation (NKF) has traditionally categorized CKD into 5 stages based upon the glomerular filtration rate (GFR, expressed as mL/min/1.73 m2 and commonly reported as mL/min) (Table 1). In 2003, CKD prevalence by stage among the U.S. population was estimated at 3.3% (5.9 million) stage 1, 3.0% (5.3 million) stage 2, 4.3% (7.6 million) stage 3, and 0.2% each for stages 4 and 5.[1] The Kidney Disease Improving Global Outcomes (KDIGO) 2012 clinical practice guidelines recommend that CKD staging be classified not solely on GFR but also on cause of injury and albuminuria (Table 2).[5] The inclusion of cause of kidney disease in staging is fundamentally important to outcome and cause-specific treatment. Albuminuria is a marker of injury severity and is strongly associated with progression of kidney disease, independent of GFR, and can be defined as mild, moderate, or severe increase in urine albumin. The 2012 KDIGO classification also divided stage 3 CKD into G3a (45 to 59 mL/min) and G3b (30 to 44 mL/min) to acknowledge the significant differences in health outcomes and mortality between these categories (Fig. 1).[6]
Figure 1.
CKD stage and outcomes
Undiagnosed CKD may lead to the underrecognition of associated diseases and loss of time in treating comorbid diseases at earlier stages of CKD. The CKD prevalence is greater among persons with T2DM (40.2% versus 15.4% without T2DM), cardiovascular disease (CVD) (28.2% versus 15.4% without CVD), and hypertension (HTN) (24.6% versus 12.5% without HTN). As reported by Coresh et al,[1] of the 11% of adult Americans with CKD, 96% have stage 1 to 3 disease (GFR ≥30 mL/min). Thus, a sizeable number of patients with T2DM, CVD, and HTN are at risk for CKD and should be identified and screened for comorbid diseases related to CKD, to include mineral and bone disease. In a recent abstract reporting the screening of 12 million U.S. patient records between 2008 and 2011, 44,000 patients were found to have T2DM (mean age, 64 years). Of the patients with T2DM, 51% had CKD and 22% had stage 3 to 5 disease, although 76% of stage 3 to 5 CKD patients did not have any recorded diagnosis of CKD.[7] The automatic calculation of estimated GFR (eGFR) in patient laboratory reports will hopefully help increase awareness that CKD may be present.
KDIGO sponsored a conference addressing controversies in renal osteodystrophy in 2004 to (1) develop a clear, clinically relevant, and internationally acceptable definition and classification system; (2) develop a consensus for bone biopsy evaluation and classification; and (3) evaluate laboratory and imaging markers for the clinical assessment of patients with CKD. An ideal classification system for CKD-mineral and bone disorders (CKDMBDs) would allow categorization of patients based on readily available clinical diagnostic tools and would help guide treatment. The lack of adequate data and the nonlinearity of CKD does not allow for a classification based on severity or treatment at this time. The proposed KDIGO framework for classifying CKD-MBDs (Table 3) is based on the presence or absence of laboratory abnormalities, bone disease, and calcification of extraskeletal tissue and is meant to be a descriptive clinical model.[8] KDIGO recommends that the term "renal osteodystrophy" be used exclusively to define altered bone morphology identified by bone biopsy/histomorphometry and be subsequently reported as a unified TMV classification system, which is based upon the skeletal parameters of turnover (T), mineralization (M), and volume (V). Thus, the term CKD-MBDs is used to describe a broad clinical syndrome that develops as a systemic disorder characterized by a constellation of abnormalities in regulatory hormones and bone mineral, bone turnover and mineralization, and vascular or soft tissue calcification. CKD-MBDs acknowledges the entire spectrum of disease from early hormonal and mineral disturbances to the late stages of CKD and premature mortality.
Because 96% of all CKD cases fall into stages 1 to 3 and T2DM is common in early CKD, the endocrinologist is uniquely positioned to address and treat both T2DM and many of the comorbid diseases associated with CKD, as outlined by the NKF KDOQI guidelines for management of HTN, dyslipidemia, anemia, CVD, and nutrition (2) and as outlined in the newer KDIGO guidelines for metabolic bone disease.[9] This review will focus on what the endocrinologist should know about the development, assessment, and management of CKD-MBDs. For purposes of discussion, where not stated in the text, 'early CKD' refers to stage 1 to 3 disease and 'late CKD' refers to stage 4 to 5 disease. Stage 5 CKD is often referred to as end-stage renal disease (ESRD). We will not address issues associated with bone disease and kidney transplantation in ESRD.
Endocr Pract. 2014;20(5):500-516. © 2014 American Association of Clinical Endocrinologists
