- Email: [email protected]
CKD for Primary Care Practitioners: Can We Cut to the Chase Without Too Many Shortcuts?
Editorial CKD for Primary Care Practitioners: Can We Cut to the Chase Without Too Many Shortcuts? Michael J. Choi, MD, was the Garabed Eknoyan Award recipient at the 2015 National Kidney Foundation Spring Clinical Meetings. This award was created to recognize an individual who has made exceptional contributions to promote the mission of the National Kidney Foundation in making lives better for people with kidney disease.
P
rimary care practitioners (PCPs) must treat the majority of the estimated 26 million adults with chronic kidney disease (CKD) in the United States because in this country, there are fewer than 10,000 practicing nephrologists and nephrology advanced practitioners combined1 (J.S. Davis, personal communication, January 2016). However, despite established clinical practice guidelines for CKD, PCPs may lack sufficient knowledge and understanding of the disease,2 and most feel unfamiliar with current recommendations.3 To increase CKD knowledge, an ideal guide for PCPs would identify screening approaches for high-risk individuals, present strategies to slow disease progression, provide medication safety advice, review initial treatment of CKD complications, and suggest criteria for referral to nephrology providers. Although prior CKD guidelines have included such information, they have not been successful as educational resources for PCPs. In 2002, the National Kidney Foundation published the KDOQI (Kidney Disease Outcomes Quality Initiative) clinical practice guideline for evaluation, classification, and stratification of CKD.4 Management recommendations with target ranges were derived from available evidence or expert opinion. However, a lack of evidence base had been cited as the most common barrier to guideline implementation among nephrology care practitioners.5 Subsequent clinical trial and cohort data led to the KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for the evaluation and management of CKD, which was published in 2013.6 The KDIGO document provided a detailed rationale for recommendations and suggestions to address areas of controversy among nephrologists, such as diagnostic criteria for CKD in the elderly.7 Originally published online April 15, 2016. Address correspondence to Michael J. Choi, MD, Johns Hopkins University of Medicine, Division of Nephrology, 1830 E Monument St, Rm 416, Baltimore, MD 21287. E-mail: mchoi3@ jhmi.edu Ó 2016 by the National Kidney Foundation, Inc. 0272-6386 http://dx.doi.org/10.1053/j.ajkd.2016.02.043 826
Major changes from the KDOQI guidelines included staging CKD by both estimated glomerular filtration rate (eGFR) and albuminuria categories because each showed independent associations with CKD progression, cardiovascular (CV) disease, and mortality. Cause of CKD, which also influences disease progression, was included as well. The CKD-EPI (CKD Epidemiology Collaboration) equation supplanted the MDRD (Modification of Diet in Renal Disease) Study equation for eGFR due to greater accuracy at eGFRs . 60 mL/min/1.73 m2. Stage 3 CKD was divided into categories G3a and G3b due to the better prognosis of kidney and nonkidney outcomes in the former category. Use of cystatin C–based eGFR equations was advocated in those with CKD-EPI eGFRs of 45 to 59 mL/min/1.73 m2 without albuminuria to confirm the diagnosis of stage G3a A1 CKD. KDIGO provided a guide for identifying factors associated with CKD progression, such as CKD cause, eGFR, albuminuria level, age, sex, race/ ethnicity, elevated blood pressure (BP), hyperglycemia, dyslipidemia, smoking, obesity, history of CV disease, and ongoing exposure to nephrotoxic agents. Some of these risk factors, including CV conditions, quality of life, and progression of CKD, are modifiable and therefore should be identified and treated because they may affect long-term outcomes. There are now kidney failure risk equations that use demographic and laboratory data to predict progression of CKD to kidney failure and that have been validated for accuracy in a multinational assessment.8 Estimating the risk for kidney failure may inform referral, care plans, and other therapeutic strategies, including frequency of monitoring and follow-up. The KDIGO CKD guideline used more caution in recommending specific treatment target goals for slowing progression or treating the complications of CKD compared to the prior KDOQI guideline. Emphasis shifted from achieving specific surrogate goal values to individualization of treatment. BP targets were slightly liberalized to ,140/90 mm Hg in those with an albumin-creatinine ratio (ACR) , 30 mg/g, with a suggestion of BP , 130/80 mm Hg in those with an ACR . 30 mg/g. Renin-angiotensinaldosterone system (RAAS) blockade treatment for hypertension in patients with CKD was endorsed if there was an increased ACR (.30 and .300 mg/g in those with and without diabetes, respectively). A goal hemoglobin A1c level of w7% was recommended for patients with both CKD and diabetes who are at low risk for hypoglycemia. Base supplementation for serum bicarbonate level , 22 mmol/L was suggested Am J Kidney Dis. 2016;67(6):826-829
Editorial
to slow CKD progression, although an upper bound was not explicitly given. The guideline emphasized the importance of GFR-based dose adjustments of renally cleared medications and temporary discontinuation of potential nephrotoxic medications in conditions that predispose to acute kidney injury. Notably, the guideline proposed moderating US Food and Drug Administration–mandated serum creatinine restrictions on metformin use in CKD. Specific criteria for referral to nephrology included acute kidney injury, eGFR, 30 mL/min/1.73 m2, albuminuria with albumin excretion . 300 mg/g, rapid CKD progression, unexplained hematuria or red blood cell casts, refractory hypertension, persistent abnormalities in serum potassium levels, or recurrent or extensive nephrolithiasis. Published a year later in 2014, the KDOQI commentary on the KDIGO CKD guideline generally agreed with the applicability of these worldwide guidelines to the United States.9 One divergence was that the KDOQI commentary explicitly advocated screening individuals at high risk for CKD with more assertion than the American College of Physicians clinical guideline.10 Another modification was limiting referral for patients with an ACR . 300 mg/g to those with an unclear cause of albuminuria or if there was no reduction in albuminuria despite RAAS blockade. In addition, the KDOQI commentary did not endorse the inclusion of etiology of CKD as part of the staging process. In 2012, before the appearance of the KDIGO CKD guideline, Levey and Coresh11 had published a seminar on CKD in the Lancet that targeted a primary care audience and presented CKD as a public health issue. In that article, a useful table summarizes key clinical trials in CKD progression, complications, and dialysis delivery, which often demonstrated benefit in surrogate outcomes but no improvement in hard clinical outcomes. The authors discussed barriers to successful clinical trials in CKD, including slow progression, competing risk for death, multiple comorbid conditions that may not respond to a specific intervention, and lack of symptoms until late-stage CKD. In late 2015, a KDOQI PCP Commentary group published a review12 in the American Journal of Medicine that attempts to present a pragmatic CKD guide for the PCP, with the majority of its authors consisting of the intended audience. The detailed rationale for recommendations normally provided to nephrologists is sacrificed for succinct advice targeting PCPs.13,14 The essential points of the KDOQI guide for PCPs are summarized in a figure (reproduced here as Fig 1). Screening of high-risk individuals is highlighted. Staging CKD by ACR and eGFR is repeatedly emphasized because ACR testing Am J Kidney Dis. 2016;67(6):826-829
often is not performed by PCPs, even in patients with type 2 diabetes.15 In the KDOQI guide for PCPs, the information for patient safety focuses on dosing common outpatient medications by eGFR. A table is provided that includes dosing of direct oral anticoagulants, but unfortunately it omits recommendations for newer diabetic medications. Consistent with recommendations in the KDIGO CKD guideline, the PCP guide advises reviewing metformin use in category 3b and suggests that it be avoided in category 4, though with consideration of the risk-benefit balance in those with stable GFRs. The PCP guide advises that eGFR be used for drug dosing, although other articles suggest that eGFR should be de-indexed (eGFR mL/min/ 1.73 m2 3 actual body surface area/1.73 m2) at extremes of body surface area.11,16 To slow CKD progression, the PCP guide suggests a BP goal , 140/90 mm Hg for those with an ACR , 30 mg/g, with consideration for ,130/ 80 mm Hg if ACR is . 300 mg/g (a higher threshold than the 30-mg/g cutoff recommended by KDIGO). More recently, SPRINT (Systolic Blood Pressure Intervention Trial)17 showed improved mortality with a systolic goal BP , 120 mm Hg, calling into question the optimum BP target in patients with CKD without diabetes and with no history of stroke.18 Specific findings regarding the effect of the lower goal on CKD progression are forthcoming. In SPRINT, mean eGFR and ACR in the CKD subgroup were w50 mL/min/1.73 m2 and w40 mg/g, respectively, reflecting the population cared for by PCPs. Importantly, the BP reading in SPRINT was a mean of 3 measurements obtained by an automated cuff after a 5-minute rest period (during which no conversation was permitted); therefore, these readings are likely to be lower than most PCP office measurements. The PCP guide recommends RAAS blockade for all patients with CKD with an ACR . 30 mg/g; however, for patients without diabetes, KDIGO had suggested an ACR threshold of .300 mg/g. Similar to KDIGO, the KDOQI guide for PCPs recommends a hemoglobin A1c target of 7% in patients with diabetes and oral alkali for those with bicarbonate levels , 22 mEq/L. The guide goes on to advise that treatment of CKD-related anemia involves nephrology referral for erythropoiesis-stimulating agent initiation if hemoglobin level decreases to ,10 g/dL when iron stores are replete. Suggestions for managing CKD– mineral and bone disorder in patients with CKD stage 3b and beyond includes baseline measurements of phosphate, 25-hydroxyvitamin D, and intact parathyroid hormone, as well as referral to nephrology for hyperphosphatemia or elevated intact parathyroid hormone level. Referral criteria are similar to those recommended by KDIGO, although referral for 827
Thavarajah, Knicely, and Choi
CKD A Category*
CKD G Category*
Figure 1. Schematic presented in the American Journal of Medicine review summarizes a practical approach to the detection and management of chronic kidney disease (CKD) for primary care practitioners. Lower blood pressure goals may be more favorable.18 Abbreviations: 25(OH)D, 25-hydroxyvitamin D; ACEi, angiotensin-converting enzyme inhibitor; ACR, albumin-creatinine ratio; AKI, acute kidney injury; ARB, angiotensin receptor blocker; ASA, acetylsalicylic acid/aspirin; A stage, albuminuria category; CAD, coronary artery disease; CKD-MBD, chronic kidney disease–mineral and bone disorder; CVA, cerebrovascular accident; CVD, cardiovascular disease; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; ESA, erythropoiesis-stimulating agent; G stage, glomerular filtration rate category; Hb, hemoglobin; HTN, hypertension; iPTH, intact parathyroid hormone; NSAIDs, nonsteroidal anti-inflammatory drugs; PICC, peripherally inserted central catheter line; PT INR, prothrombin time-international normalized ratio; RAAS, reninangiotensin-aldosterone system. Adapted with permission from Vassalotti et al.12 ˇ
patients with diabetes with an ACR . 300 mg/g is considered optional. With the increased CV risk in CKD, the KDOQI guide for PCPs adopts the “fire and forget” strategy to initiate statin-based therapy regardless of low-density lipoprotein (LDL) cholesterol levels in patients older than 50 years. This strategy is also recommended for higher risk patients younger than 50 years (eg, those with diabetes or 10-year risk for myocardial infarction [MI] . 10%). The “fire” rationale is largely based on an analysis of a large Canadian cohort of patients 828
with CKD that reported weaker associations between elevated LDL cholesterol level and MI in those with lower baseline eGFRs.19 In the study, hazard ratios for MI for patients with LDL cholesterol levels . 190 mg/dL compared with those with LDL cholesterol levels of 100 to 131 mg/dL were approximately 3 and 2 for patients with CKD stages 1 to 2 and 3 to 4, respectively. The “forget” rationale of not checking LDL cholesterol levels after starting therapy is controversial and acknowledged in the KDOQI guide for PCPs. When faced with patients Am J Kidney Dis. 2016;67(6):826-829
Editorial
with extremely high LDL cholesterol levels, many PCPs wish to confirm that levels have declined after statin therapy initiation and to assess medication adherence if the response is inadequate. Perhaps better advice would be “fire, but remember.” Barriers to physician adherence to clinical practice guidelines include lack of physician awareness and familiarity with specific guidelines and guidelines that may be cumbersome and confusing.20 Prior CKD guidelines provided comprehensive rationale for nephrologists. The KDOQI guide for PCPs did not reach the 3- to 5-page length considered optimal for printed educational materials for this audience,20 but hopefully it will provide some clarity for CKD screening, diagnosis, and comanagement for the PCP 15-minute visit. Sumeska Thavarajah, MD Daphne H. Knicely, MD Michael J. Choi, MD Johns Hopkins University School of Medicine Baltimore, Maryland
ACKNOWLEDGEMENTS The authors thank Jerry Yee, MD, for his careful review of the manuscript. Dr Choi is KDOQI Chair of Education and President-Elect. Support: None. Financial Disclosure: The authors declare that they have no relevant financial interests. Peer Review: Evaluated by the Deputy Editor and Editor-inChief.
REFERENCES 1. Berns JS, Ellison DH, Linas SL, Rosner MH. Training the next generation’s nephrology workforce. Clin J Am Soc Nephrol. 2014;9(9):1639-1644. 2. Vest BM, York TR, Sand J, Fox CH, Kahn LS. Chronic kidney disease guideline implementation in primary care: a qualitative report from the TRANSLATE CKD Study. J Am Board Fam Med. 2015;28(5):624-631. 3. Abdel-Kader K, Greer RC, Boulware LE, Unruh ML. Primary care physicians’ familiarity, beliefs, and perceived barriers to practice guidelines in non-diabetic CKD: a survey study. BMC Nephrol. 2014;15:64. 4. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2)(suppl 1):S1-S266. 5. Estrella MM, Jaar BG, Cavanaugh KL, et al. Perceptions and use of the National Kidney Foundation KDOQI guidelines: a survey of U.S. renal healthcare providers. BMC Nephrol. 2013;14: 230.
Am J Kidney Dis. 2016;67(6):826-829
6. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;1:136-150. 7. Glassock RJ, Rule AD. The implications of anatomical and functional changes of the aging kidney: with an emphasis on the glomeruli. Kidney Int. 2012;82(3):270-277. 8. Tangri N, Grams ME, Levey AS, et al; CKD Prognosis Consortium. Multinational assessment of accuracy of equations for predicting risk of kidney failure: a meta-analysis. JAMA. 2016;315(2):164-174. 9. Inker LA, Astor BC, Fox CH, et al. KDOQI US Commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014;63(5): 713-735. 10. Qaseem A, Hopkins RH, Sweet DE, et al. Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease: a clinical practice guideline from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2013;159(12):835-847. 11. Levey AS, Coresh J. Chronic kidney disease. Lancet. 2012;379(9811):165-180. 12. Vassalotti JA, Centor R, Turner BJ, et al. Practical approach to detection and management of chronic kidney disease for the primary care clinician. Am J Med. 2016;129(2): 153-162. 13. Kastner M, Estey EA, Hayden L, et al. The development of a guideline implementability tool (GUIDE-IT): a qualitative study of family physician perspectives. BMC Fam Pract. 2014;15:19. 14. Grudniewicz A, Bhattacharyya O, McKibbon KA, Straus SE. Redesigning printed educational materials for primary care physicians: design improvements increase usability. Implement Sci. 2015;10:156. 15. Szczech LA, Stewart RC, Su HL, et al. Primary care detection of chronic kidney disease in adults with type-2 diabetes: the ADD-CKD Study (awareness, detection and drug therapy in type 2 diabetes and chronic kidney disease). PLoS One. 2014;9(11):e110535. 16. Bouquegneau A, Vidal-Petiot E, Moranne O, et al. Creatinine-based equations for the adjustment of drug dosage in an obese population. Br J Clin Pharmacol. 2015;82(2):349-361. 17. Cushman WC, Whelton PK, Fine LJ, et al. SPRINT trial results: latest news in hypertension management. Hypertension. 2016;67(2):263-265. 18. SPRINT Research Group; Wright JT Jr, Williamson JD, Whelton PK, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22): 2103-2116. 19. Tonelli M, Muntner P, Lloyd A, et al. Association between LDL-C and risk of myocardial infarction in CKD. J Am Soc Nephrol. 2013;24(6):979-986. 20. Cabana MD, Rand CS, Powe NR, et al. Why don’t physicians follow clinical practice guidelines? A framework for improvement. JAMA. 1999;282(15):1458-1465.
829
P
rimary care practitioners (PCPs) must treat the majority of the estimated 26 million adults with chronic kidney disease (CKD) in the United States because in this country, there are fewer than 10,000 practicing nephrologists and nephrology advanced practitioners combined1 (J.S. Davis, personal communication, January 2016). However, despite established clinical practice guidelines for CKD, PCPs may lack sufficient knowledge and understanding of the disease,2 and most feel unfamiliar with current recommendations.3 To increase CKD knowledge, an ideal guide for PCPs would identify screening approaches for high-risk individuals, present strategies to slow disease progression, provide medication safety advice, review initial treatment of CKD complications, and suggest criteria for referral to nephrology providers. Although prior CKD guidelines have included such information, they have not been successful as educational resources for PCPs. In 2002, the National Kidney Foundation published the KDOQI (Kidney Disease Outcomes Quality Initiative) clinical practice guideline for evaluation, classification, and stratification of CKD.4 Management recommendations with target ranges were derived from available evidence or expert opinion. However, a lack of evidence base had been cited as the most common barrier to guideline implementation among nephrology care practitioners.5 Subsequent clinical trial and cohort data led to the KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for the evaluation and management of CKD, which was published in 2013.6 The KDIGO document provided a detailed rationale for recommendations and suggestions to address areas of controversy among nephrologists, such as diagnostic criteria for CKD in the elderly.7 Originally published online April 15, 2016. Address correspondence to Michael J. Choi, MD, Johns Hopkins University of Medicine, Division of Nephrology, 1830 E Monument St, Rm 416, Baltimore, MD 21287. E-mail: mchoi3@ jhmi.edu Ó 2016 by the National Kidney Foundation, Inc. 0272-6386 http://dx.doi.org/10.1053/j.ajkd.2016.02.043 826
Major changes from the KDOQI guidelines included staging CKD by both estimated glomerular filtration rate (eGFR) and albuminuria categories because each showed independent associations with CKD progression, cardiovascular (CV) disease, and mortality. Cause of CKD, which also influences disease progression, was included as well. The CKD-EPI (CKD Epidemiology Collaboration) equation supplanted the MDRD (Modification of Diet in Renal Disease) Study equation for eGFR due to greater accuracy at eGFRs . 60 mL/min/1.73 m2. Stage 3 CKD was divided into categories G3a and G3b due to the better prognosis of kidney and nonkidney outcomes in the former category. Use of cystatin C–based eGFR equations was advocated in those with CKD-EPI eGFRs of 45 to 59 mL/min/1.73 m2 without albuminuria to confirm the diagnosis of stage G3a A1 CKD. KDIGO provided a guide for identifying factors associated with CKD progression, such as CKD cause, eGFR, albuminuria level, age, sex, race/ ethnicity, elevated blood pressure (BP), hyperglycemia, dyslipidemia, smoking, obesity, history of CV disease, and ongoing exposure to nephrotoxic agents. Some of these risk factors, including CV conditions, quality of life, and progression of CKD, are modifiable and therefore should be identified and treated because they may affect long-term outcomes. There are now kidney failure risk equations that use demographic and laboratory data to predict progression of CKD to kidney failure and that have been validated for accuracy in a multinational assessment.8 Estimating the risk for kidney failure may inform referral, care plans, and other therapeutic strategies, including frequency of monitoring and follow-up. The KDIGO CKD guideline used more caution in recommending specific treatment target goals for slowing progression or treating the complications of CKD compared to the prior KDOQI guideline. Emphasis shifted from achieving specific surrogate goal values to individualization of treatment. BP targets were slightly liberalized to ,140/90 mm Hg in those with an albumin-creatinine ratio (ACR) , 30 mg/g, with a suggestion of BP , 130/80 mm Hg in those with an ACR . 30 mg/g. Renin-angiotensinaldosterone system (RAAS) blockade treatment for hypertension in patients with CKD was endorsed if there was an increased ACR (.30 and .300 mg/g in those with and without diabetes, respectively). A goal hemoglobin A1c level of w7% was recommended for patients with both CKD and diabetes who are at low risk for hypoglycemia. Base supplementation for serum bicarbonate level , 22 mmol/L was suggested Am J Kidney Dis. 2016;67(6):826-829
Editorial
to slow CKD progression, although an upper bound was not explicitly given. The guideline emphasized the importance of GFR-based dose adjustments of renally cleared medications and temporary discontinuation of potential nephrotoxic medications in conditions that predispose to acute kidney injury. Notably, the guideline proposed moderating US Food and Drug Administration–mandated serum creatinine restrictions on metformin use in CKD. Specific criteria for referral to nephrology included acute kidney injury, eGFR, 30 mL/min/1.73 m2, albuminuria with albumin excretion . 300 mg/g, rapid CKD progression, unexplained hematuria or red blood cell casts, refractory hypertension, persistent abnormalities in serum potassium levels, or recurrent or extensive nephrolithiasis. Published a year later in 2014, the KDOQI commentary on the KDIGO CKD guideline generally agreed with the applicability of these worldwide guidelines to the United States.9 One divergence was that the KDOQI commentary explicitly advocated screening individuals at high risk for CKD with more assertion than the American College of Physicians clinical guideline.10 Another modification was limiting referral for patients with an ACR . 300 mg/g to those with an unclear cause of albuminuria or if there was no reduction in albuminuria despite RAAS blockade. In addition, the KDOQI commentary did not endorse the inclusion of etiology of CKD as part of the staging process. In 2012, before the appearance of the KDIGO CKD guideline, Levey and Coresh11 had published a seminar on CKD in the Lancet that targeted a primary care audience and presented CKD as a public health issue. In that article, a useful table summarizes key clinical trials in CKD progression, complications, and dialysis delivery, which often demonstrated benefit in surrogate outcomes but no improvement in hard clinical outcomes. The authors discussed barriers to successful clinical trials in CKD, including slow progression, competing risk for death, multiple comorbid conditions that may not respond to a specific intervention, and lack of symptoms until late-stage CKD. In late 2015, a KDOQI PCP Commentary group published a review12 in the American Journal of Medicine that attempts to present a pragmatic CKD guide for the PCP, with the majority of its authors consisting of the intended audience. The detailed rationale for recommendations normally provided to nephrologists is sacrificed for succinct advice targeting PCPs.13,14 The essential points of the KDOQI guide for PCPs are summarized in a figure (reproduced here as Fig 1). Screening of high-risk individuals is highlighted. Staging CKD by ACR and eGFR is repeatedly emphasized because ACR testing Am J Kidney Dis. 2016;67(6):826-829
often is not performed by PCPs, even in patients with type 2 diabetes.15 In the KDOQI guide for PCPs, the information for patient safety focuses on dosing common outpatient medications by eGFR. A table is provided that includes dosing of direct oral anticoagulants, but unfortunately it omits recommendations for newer diabetic medications. Consistent with recommendations in the KDIGO CKD guideline, the PCP guide advises reviewing metformin use in category 3b and suggests that it be avoided in category 4, though with consideration of the risk-benefit balance in those with stable GFRs. The PCP guide advises that eGFR be used for drug dosing, although other articles suggest that eGFR should be de-indexed (eGFR mL/min/ 1.73 m2 3 actual body surface area/1.73 m2) at extremes of body surface area.11,16 To slow CKD progression, the PCP guide suggests a BP goal , 140/90 mm Hg for those with an ACR , 30 mg/g, with consideration for ,130/ 80 mm Hg if ACR is . 300 mg/g (a higher threshold than the 30-mg/g cutoff recommended by KDIGO). More recently, SPRINT (Systolic Blood Pressure Intervention Trial)17 showed improved mortality with a systolic goal BP , 120 mm Hg, calling into question the optimum BP target in patients with CKD without diabetes and with no history of stroke.18 Specific findings regarding the effect of the lower goal on CKD progression are forthcoming. In SPRINT, mean eGFR and ACR in the CKD subgroup were w50 mL/min/1.73 m2 and w40 mg/g, respectively, reflecting the population cared for by PCPs. Importantly, the BP reading in SPRINT was a mean of 3 measurements obtained by an automated cuff after a 5-minute rest period (during which no conversation was permitted); therefore, these readings are likely to be lower than most PCP office measurements. The PCP guide recommends RAAS blockade for all patients with CKD with an ACR . 30 mg/g; however, for patients without diabetes, KDIGO had suggested an ACR threshold of .300 mg/g. Similar to KDIGO, the KDOQI guide for PCPs recommends a hemoglobin A1c target of 7% in patients with diabetes and oral alkali for those with bicarbonate levels , 22 mEq/L. The guide goes on to advise that treatment of CKD-related anemia involves nephrology referral for erythropoiesis-stimulating agent initiation if hemoglobin level decreases to ,10 g/dL when iron stores are replete. Suggestions for managing CKD– mineral and bone disorder in patients with CKD stage 3b and beyond includes baseline measurements of phosphate, 25-hydroxyvitamin D, and intact parathyroid hormone, as well as referral to nephrology for hyperphosphatemia or elevated intact parathyroid hormone level. Referral criteria are similar to those recommended by KDIGO, although referral for 827
Thavarajah, Knicely, and Choi
CKD A Category*
CKD G Category*
Figure 1. Schematic presented in the American Journal of Medicine review summarizes a practical approach to the detection and management of chronic kidney disease (CKD) for primary care practitioners. Lower blood pressure goals may be more favorable.18 Abbreviations: 25(OH)D, 25-hydroxyvitamin D; ACEi, angiotensin-converting enzyme inhibitor; ACR, albumin-creatinine ratio; AKI, acute kidney injury; ARB, angiotensin receptor blocker; ASA, acetylsalicylic acid/aspirin; A stage, albuminuria category; CAD, coronary artery disease; CKD-MBD, chronic kidney disease–mineral and bone disorder; CVA, cerebrovascular accident; CVD, cardiovascular disease; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; ESA, erythropoiesis-stimulating agent; G stage, glomerular filtration rate category; Hb, hemoglobin; HTN, hypertension; iPTH, intact parathyroid hormone; NSAIDs, nonsteroidal anti-inflammatory drugs; PICC, peripherally inserted central catheter line; PT INR, prothrombin time-international normalized ratio; RAAS, reninangiotensin-aldosterone system. Adapted with permission from Vassalotti et al.12 ˇ
patients with diabetes with an ACR . 300 mg/g is considered optional. With the increased CV risk in CKD, the KDOQI guide for PCPs adopts the “fire and forget” strategy to initiate statin-based therapy regardless of low-density lipoprotein (LDL) cholesterol levels in patients older than 50 years. This strategy is also recommended for higher risk patients younger than 50 years (eg, those with diabetes or 10-year risk for myocardial infarction [MI] . 10%). The “fire” rationale is largely based on an analysis of a large Canadian cohort of patients 828
with CKD that reported weaker associations between elevated LDL cholesterol level and MI in those with lower baseline eGFRs.19 In the study, hazard ratios for MI for patients with LDL cholesterol levels . 190 mg/dL compared with those with LDL cholesterol levels of 100 to 131 mg/dL were approximately 3 and 2 for patients with CKD stages 1 to 2 and 3 to 4, respectively. The “forget” rationale of not checking LDL cholesterol levels after starting therapy is controversial and acknowledged in the KDOQI guide for PCPs. When faced with patients Am J Kidney Dis. 2016;67(6):826-829
Editorial
with extremely high LDL cholesterol levels, many PCPs wish to confirm that levels have declined after statin therapy initiation and to assess medication adherence if the response is inadequate. Perhaps better advice would be “fire, but remember.” Barriers to physician adherence to clinical practice guidelines include lack of physician awareness and familiarity with specific guidelines and guidelines that may be cumbersome and confusing.20 Prior CKD guidelines provided comprehensive rationale for nephrologists. The KDOQI guide for PCPs did not reach the 3- to 5-page length considered optimal for printed educational materials for this audience,20 but hopefully it will provide some clarity for CKD screening, diagnosis, and comanagement for the PCP 15-minute visit. Sumeska Thavarajah, MD Daphne H. Knicely, MD Michael J. Choi, MD Johns Hopkins University School of Medicine Baltimore, Maryland
ACKNOWLEDGEMENTS The authors thank Jerry Yee, MD, for his careful review of the manuscript. Dr Choi is KDOQI Chair of Education and President-Elect. Support: None. Financial Disclosure: The authors declare that they have no relevant financial interests. Peer Review: Evaluated by the Deputy Editor and Editor-inChief.
REFERENCES 1. Berns JS, Ellison DH, Linas SL, Rosner MH. Training the next generation’s nephrology workforce. Clin J Am Soc Nephrol. 2014;9(9):1639-1644. 2. Vest BM, York TR, Sand J, Fox CH, Kahn LS. Chronic kidney disease guideline implementation in primary care: a qualitative report from the TRANSLATE CKD Study. J Am Board Fam Med. 2015;28(5):624-631. 3. Abdel-Kader K, Greer RC, Boulware LE, Unruh ML. Primary care physicians’ familiarity, beliefs, and perceived barriers to practice guidelines in non-diabetic CKD: a survey study. BMC Nephrol. 2014;15:64. 4. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2)(suppl 1):S1-S266. 5. Estrella MM, Jaar BG, Cavanaugh KL, et al. Perceptions and use of the National Kidney Foundation KDOQI guidelines: a survey of U.S. renal healthcare providers. BMC Nephrol. 2013;14: 230.
Am J Kidney Dis. 2016;67(6):826-829
6. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;1:136-150. 7. Glassock RJ, Rule AD. The implications of anatomical and functional changes of the aging kidney: with an emphasis on the glomeruli. Kidney Int. 2012;82(3):270-277. 8. Tangri N, Grams ME, Levey AS, et al; CKD Prognosis Consortium. Multinational assessment of accuracy of equations for predicting risk of kidney failure: a meta-analysis. JAMA. 2016;315(2):164-174. 9. Inker LA, Astor BC, Fox CH, et al. KDOQI US Commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014;63(5): 713-735. 10. Qaseem A, Hopkins RH, Sweet DE, et al. Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease: a clinical practice guideline from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2013;159(12):835-847. 11. Levey AS, Coresh J. Chronic kidney disease. Lancet. 2012;379(9811):165-180. 12. Vassalotti JA, Centor R, Turner BJ, et al. Practical approach to detection and management of chronic kidney disease for the primary care clinician. Am J Med. 2016;129(2): 153-162. 13. Kastner M, Estey EA, Hayden L, et al. The development of a guideline implementability tool (GUIDE-IT): a qualitative study of family physician perspectives. BMC Fam Pract. 2014;15:19. 14. Grudniewicz A, Bhattacharyya O, McKibbon KA, Straus SE. Redesigning printed educational materials for primary care physicians: design improvements increase usability. Implement Sci. 2015;10:156. 15. Szczech LA, Stewart RC, Su HL, et al. Primary care detection of chronic kidney disease in adults with type-2 diabetes: the ADD-CKD Study (awareness, detection and drug therapy in type 2 diabetes and chronic kidney disease). PLoS One. 2014;9(11):e110535. 16. Bouquegneau A, Vidal-Petiot E, Moranne O, et al. Creatinine-based equations for the adjustment of drug dosage in an obese population. Br J Clin Pharmacol. 2015;82(2):349-361. 17. Cushman WC, Whelton PK, Fine LJ, et al. SPRINT trial results: latest news in hypertension management. Hypertension. 2016;67(2):263-265. 18. SPRINT Research Group; Wright JT Jr, Williamson JD, Whelton PK, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22): 2103-2116. 19. Tonelli M, Muntner P, Lloyd A, et al. Association between LDL-C and risk of myocardial infarction in CKD. J Am Soc Nephrol. 2013;24(6):979-986. 20. Cabana MD, Rand CS, Powe NR, et al. Why don’t physicians follow clinical practice guidelines? A framework for improvement. JAMA. 1999;282(15):1458-1465.
829