2015. ckd - apa review

In the Clinic

Chronic KidneyDisease Screening and

Prevention

Diagnosis

Treatment

Practice Improvement

Tool Kit

Patient Information

Chronic kidney disease (CKD) affects morethan 20 million Americans, and over500 000 have end-stage renal disease(ESRD) (12). The most common causes of CKDare diabetes and hypertension. CKD is an inde-pendent risk factor for cardiovascular disease,cognitive dysfunction, hospitalization, and all-cause mortality. In older CKD patients, the riskfor cardiovascular disease and all-cause mortal-ity is often higher than the risk for progressionto ESRD and depends on the level of kidneyfunction, proteinuria, and age (35).

The CME quiz is available at www.annals.org/intheclinic.aspx. Complete the quiz to earn up to 1.5 CME credits.

Physician WritersPaul Drawz, MD, MHS, MSMahboob Rahman, MD, MS

CMEObjective: To review current evidence for screening, and prevention, diagnosis,treatment, and practice improvement of chronic kidney disease.

Funding Source: American College of Physicians.

Disclosures:Drs. Drawz and Rahman, ACP Contributing Authors, have disclosed no conictsof interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConictOfInterestForms.do?msNum=M14-2715.

With the assistance of additional physician writers, Annals of Internal Medicine editorsdevelop In the Clinic using resources of the American College of Physicians, includingACP Smart Medicine andMKSAP (Medical Knowledge and Self-Assessment Program).

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Other complications of CKD in-clude metabolic abnormalities,such as anemia, secondary hy-perparathyroidism, and electro-lyte disturbances. Themain goalsof treatment include slowing thedecline in kidney function, pre-venting cardiovascular disease,

treating complications, and facili-tating transition to renal replace-ment therapy when indicated.Management of these challengingpatients is best accomplishedthrough collaboration betweenprimary care providers andnephrologists.

Screening and PreventionWhich patients are at increasedrisk for CKD?The two most common causesof CKD in the United States arediabetes and hypertension (2).Table 1 shows other risk factorsfor CKD (67).

Should clinicians screenpatients for CKD?Universal screening for CKD inadults is not recommended. Infact, the U.S. Preventive ServicesTask Force recommends againstscreening in asymptomatic indi-viduals (8). However, individualsat increased risk for CKD shouldbe screened, such as those olderthan 55 years and those with hy-pertension and diabetes (9).

How should patients bescreened for CKD?Screening should test for markersof kidney damage and estimatethe glomerular ltration rate(GFR) (10). Therefore, it shouldinclude a serum creatinine mea-surement to estimate GFR, urinal-ysis to evaluate for leukocytesand red blood cells, and mea-surement of urine protein usingeither standard or albumin-specic dipsticks (6). Individualswho test positive for albuminor protein should have proteinmeasured to calculate a protein-to-creatinine or albumin-to-creatinine ratio (Table 2) (6).Patients with type 2 diabetesshould be screened for albumin-uria in a spot urine sample at thetime of diagnosis and then annu-ally using >30 mg/g creatinine as

the indicator for a positive testresult (11).

Are preventive measures usefulfor patients at increased riskfor CKD?In patients with diabetes, goodglycemic control reduces the riskfor CKD, and hyperglycemia isassociated with developmentand progression of diabetic ne-phropathy. Diabetic patientsshould use dietary interventions,oral hypoglycemic medications,and insulin as needed to main-tain a hemoglobin (Hb) A1c levelof about 7% (1214).

A total of 1375 participants from the DCCT (Di-abetes Control and Complications Trial) wasfollowed as part of the EDIC (Epidemiology ofDiabetes Interventions and Complications) ob-servational study. Over 22 years of follow-up,

Table 1. Risk Factors for ChronicKidney Disease

DiabetesHypertensionAutoimmune diseasesSystemic infectionsUrinary tract infectionsNephrolithiasisLower urinary tract obstructionHyperuricemiaAcute kidney injuryFamily history of chronic kidneydisease

Sociodemographic factorsOlder ageBlack raceSmokingHeavy alcohol useObesity

Nonsteroidal anti-inammatory drugs

1. Levey AS, de Jong PE,Coresh J, et al. The deni-tion, classication, andprognosis of chronic kid-ney disease: a KDIGOControversies Conferencereport. Kidney Int. 2011;80:17-28. [PMID:21150873]

2. 2013 Atlas of End-StageRenal Disease. Accessed atUnited States Renal DataSystem at www.usrds.org/2013/pdf/v2_ch1_13.pdfon 24 November 2014.

3. Go AS, Chertow GM, FanD, McCulloch CE, Hsu CY.Chronic kidney diseaseand the risks of death,cardiovascular events, andhospitalization. N Engl JMed. 2004;351:1296-305. [PMID: 15385656]

4. Rahman M, Pressel S,Davis BR, et al; ALLHATCollaborative ResearchGroup. Cardiovascularoutcomes in high-riskhypertensive patientsstratied by baseline glo-merular ltration rate. AnnIntern Med. 2006;144:172-80. [PMID:16461961]

5. Hallan SI, Matsushita K,Sang Y, et al; ChronicKidney Disease PrognosisConsortium. Age andassociation of kidney mea-sures with mortality andend-stage renal disease.JAMA. 2012;308:2349-60. [PMID: 23111824]

6. National Kidney Founda-tion. K/DOQI clinical prac-tice guidelines for chronickidney disease: evalua-tion, classication, andstratication. Am J KidneyDis. 2002;39:S1-266.[PMID: 11904577]

7. Krop JS, Coresh J, Chamb-less LE, et al. Acommunity-based study ofexplanatory factors for theexcess risk for early renalfunction decline in blacksvs whites with diabetes:the Atherosclerosis Risk inCommunities study. ArchIntern Med. 1999;159:1777-83. [PMID:10448782]

8. Qaseem A, Hopkins RH Jr,Sweet DE, Starkey M,Shekelle P; Clinical Guide-lines Committee of theAmerican College of Physi-cians. Screening, monitor-ing, and treatment ofstage 1 to 3 chronic kid-ney disease: A clinicalpractice guideline fromthe American College ofPhysicians. Ann InternMed. 2013;159:835-47.[PMID: 24145991]

9. Whaley-Connell AT, Sow-ers JR, Stevens LA, et al;Kidney Early EvaluationProgram Investigators.CKD in the United States:Kidney Early EvaluationProgram (KEEP) and Na-tional Health and Nutri-tion Examination Survey(NHANES) 1999-2004. AmJ Kidney Dis. 2008;51:S13-20. [PMID:18359403]

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intensive diabetes therapy reduced the inci-dence of an estimated GFR

Modication of Diet in Renal Dis-ease equation (see the Box) (19).A newer formula is the ChronicKidney Disease EpidemiologyCollaboration (CKD-EPI) equa-tion (see the Box). This equationmore precisely estimates GFR andmore accurately categorizes riskfor mortality and ESRD (2021).

Estimating GFR allows a moreaccurate measure of renal func-tion than serum creatinine alone,particularly in older patients (22).Clinicians should then classify thestage of CKD according to thepatient's estimated GFR andurine albumin-to-creatinine ratioas shown in the Figure (12).

What clinical manifestationsshould clinicians look for whenevaluating patients who mayhave CKD?Mild-to-moderate CKD (esti-mated GFR >30 mL/min/1.73 m2)is usually an asymptomatic disor-der with no physical ndings spe-cic to decreased kidney func-tion. However, a careful historyand physical examination canreveal the cause of CKD, and theexamination should focus onndings associated with diabetesand hypertension because theyare by far the most commoncauses of CKD. Patients withlong-standing, poorly controlleddiabetes who have other diabeticcomplications, such as retinopa-thy and peripheral neuropathy,are likely to have diabetic ne-phropathy, especially if they haveproteinuria. Similarly, patientswith long-standing hypertensionwith hypertensive retinopathyand a family history of hyperten-sion and CKD are likely to havehypertensive nephrosclerosis,especially if urinalysis revealsminimal proteinuria and no he-maturia (23). It is worth notingthat the presence of hyperten-sion or diabetes does not ruleout another cause of CKD, partic-ularly since hypertension is a con-sequence of CKD. In addition,

distinguishing between hyper-tensive and diabetic nephropa-thy is frequently difcult. How-ever, a biopsy is usually notrecommended because distin-guishing between diabetes andhypertension as the underlyingcause of CKD does not changemanagement.

If hypertension and diabetes arenot present, a careful history andphysical examination may revealother causes of CKD; for exam-ple, a history of heart failure orcirrhosis suggests decreased re-nal perfusion from decreasedeffective intravascular volume aswell as renal injury from inam-mation and activation of the sym-pathetic and renin-angiotensin-aldosterone systems (2425).Infection with hepatitis B or Cvirus or HIV may cause CKD andproteinuria, so clinicians shouldask all patients about intravenousdrug use and high-risk sexualbehavior. A family history of kid-ney disease may be a clue to thediagnosis of polycystic kidneydisease, the Alport syndrome(glomerulonephritis, ESRD, andhearing loss), or medullary cystickidney disease. Urinary fre-quency, hesitancy, incontinence,nocturia, dysuria, or hematuriamay reect underlying urinarytract disease, such as obstructionor infection (2627). A rash, ar-thritis, mononeuropathy, or sys-temic symptoms suggests vascu-litis or lupus. Clinicians shouldask about recent diarrhea, bleed-ing, and dehydration becausevolume loss may decrease renalperfusion and cause acute kidneyinjury, which predisposes to CKD(28). Finally, a thoroughmedica-tion history of prescription andover-the-counter drugs may reveala medication that can cause CKDor require dose-adjustment be-cause of loss of kidney function.

Physical examination should in-clude measuring blood pressureand checking for orthostasis in

Modication of Diet in RenalDisease equationGFR in mL/min/1.73 m2 = 186.3

(serumcreatinine inmg/dL)1.154 age0.203 (1.210 if black) (0.742 iffemale)

Chronic Kidney DiseaseEpidemiologyCollaboration equationGFR = 141 min(Scr/,1)

max(Scr/,1)1.209 0.993Age (1.018 if female) (1.159 ifblack)

Scr is serum creatinine, is 0.7 forfemales and 0.9 for males, is 0.329 for females and0.411 for males, minindicates the minimum ofScr/ or 1, and max indicatesthe maximum of Scr/ or 1.

18. U.S. Renal Data System.USRDS 2009 AnnualData Report: Atlas ofChronic Kidney Diseaseand End-Stage RenalDisease in the UnitedStates. Bethesda, MD:National Institutes ofHealth, National Instituteof Diabetes and Diges-tive and Kidney Dis-eases; Oct 2009. NIHPublication No.: 09-3176.

19. Levey AS, Coresh J, BalkE, et al; National KidneyFoundation. NationalKidney Foundation prac-tice guidelines forchronic kidney disease:evaluation, classication,and stratication. AnnIntern Med. 2003;139:137-47. [PMID:12859163]

20. Levey AS, Stevens LA,Schmid CH, et al; CKD-EPI (Chronic KidneyDisease EpidemiologyCollaboration). A newequation to estimateglomerular ltration rate.Ann Intern Med. 2009;150:604-12. [PMID:19414839]

21. Matsushita K, MahmoodiBK, Woodward M, et al;Chronic Kidney DiseasePrognosis Consortium.Comparison of risk pre-diction using the CKD-EPI equation and theMDRD study equation forestimated glomerularltration rate. JAMA.2012;307:1941-51.[PMID: 22570462]


patients with recent uid loss.The patient should also be evalu-ated for rashes and petechiae,and the fundus should be exam-ined for diabetic retinopathy (mi-croaneurysms, dot hemorrhages,and cotton wool spots) or hyper-tensive retinopathy (atrioventric-ular nicking, silver wiring, tortuos-ity, hemorrhages, exudates, andpapilledema). The physicianshould evaluate the patient forheart failure by looking for pul-monary rales, jugular venous dis-tention, an S3, and peripheraledema. A renal bruit suggestsrenal artery stenosis (29), andinamed joints suggest vasculitisor autoimmune processes. As-terixis and encephalopathy canindicate uremia and the needfor prompt initiation of dialysis(30).

What laboratory tests andimaging should be done?GFR should be estimated in ev-ery CKD patient through mea-surement of serum creatininelevels by using one of the equa-tions mentioned in the Box. Most

laboratories routinely report esti-mated GFR. Serum electrolytes(sodium, potassium, chloride,and bicarbonate) should be mea-sured along with a completeblood count; lipid prole; andurinalysis for specic gravity, pH,red blood cells, and leukocytecounts (19, 31). In patients with aGFR

be done to test for multiple my-eloma.

Proteinuria is useful for diagnos-ing CKD and assessing prognosisbecause it is an independentpredictor of the risk for both pro-gression of renal disease andcardiovascular disease (3233).Hematuria and other urinarysediment abnormalities can alsohelp in the differential diagnosisof CKD; for example, dysmorphicred blood cells and especiallyred blood cell casts suggest ac-tive glomerular disease. Becausepatients with CKD are at high riskfor cardiovascular disease (34),risk factors should be thoroughlyassessed; such assessment in-cludes a lipid prole. Finally, test-ing is needed for hyperkalemia,acidosis, hypocalcemia, and hy-perphosphatemia, especially instages 4 and 5 CKD.

How should clinicians classifyCKD and construct adifferential diagnosis?In addition to classifying patientsby GFR and albuminuria, clini-cians should determine the causeof CKD based on the presence orabsence of systemic disease andpresumed location of kidneydamage (glomerular, tubulointer-stitial, vascular, or cystic) (Table3) (12). For practical purposes,given the high prevalence of dia-

betes and hypertension in theUnited States, clinicians can clas-sify patients with CKD into 1 of 3broad categories: diabetic kid-ney disease; hypertensive kidneydisease; and nonhypertensive,nondiabetic kidney disease (2).

When should cliniciansconsider consulting with anephrologist for diagnosingpatients with possible CKD?A nephrology consultationshould be obtained early in thecourse of the diagnostic evalua-tion in patients with persistentproteinuria (albumin-to-creatinine ratio 300 mg/g), thenephritic syndrome (hematuria,proteinuria, and hypertension),sustained hematuria (red bloodcell casts or red blood cells >20/high-power eld), no clear causeof CKD, or type 2 diabetes withproteinuria but no coexistent reti-nopathy or neuropathy (12). Pa-tients whose kidney function de-clines relatively rapidly (>5 mL/min/1.73 m2 per year) may alsobenet from nephrology con-sultation. These patients mayhave a less common cause ofCKD, such as membranous ne-phropathy or lupus nephritis. Akidney biopsy may be requiredfor a denitive diagnosis, andimmunosuppressive therapiesmay be helpful in thesepatients.

Table 3. Classication of CKD Based on the Presence or Absence of Systemic Disease and the Kidney Location ofPathologic Findings*

Diseases Examples of Systemic Diseases Affecting the Kidney Examples of Primary Kidney Diseases (Absence ofSystemic Disease)

Glomerular Diabetes, systemic autoimmune diseases, systemicinfections (bacterial endocarditis, hepatitis B andC, HIV), drugs, neoplasia (including amyloidosis)

Diffuse, focal, or crescentic proliferativeglomerulonephritis; focal and segmentalglomerulosclerosis; membranous nephropathy;minimal change disease

Tubulointerstitial Systemic infections, autoimmune, sarcoidosis,drugs, urate, environmental toxins (lead,aristolochic acid), neoplasia (myeloma)

Urinary tract infections, stones, obstruction

Vascular Atherosclerosis, hypertension, ischemia,cholesterol emboli, systemic vasculitis,thrombotic microangiopathy, systemic sclerosis

ANCA-associated renal limited vasculitis,bromuscular dysplasia

Cystic andcongenital

Polycystic kidney disease, the Alport syndrome,Fabry disease

Renal dysplasia, medullary cystic disease,podocytopathies

* Adapted from reference 12.

32. Hunsicker LG, Adler S,Caggiula A, et al. Predic-tors of the progression ofrenal disease in theModication of Diet inRenal Disease Study.Kidney Int. 1997;51:1908-19. [PMID:9186882]

33. Miettinen H, Haffner SM,Lehto S, et al. Proteinuriapredicts stroke and otheratherosclerotic vasculardisease events in nondia-betic and non-insulin-dependent diabeticsubjects. Stroke. 1996;27:2033-9. [PMID:8898811]


TreatmentWhat nondrug therapiesshould clinicians recommend?Lifestyle and dietary modica-tions are effective for specictypes of CKD. Clinicians shouldadvise all patients with CKD toquit smoking; exercise for 30minutes most days of the week;limit alcohol intake (1 drink/dayfor women, 2 drinks/day formen); maintain body mass indexwithin the normal range (18.524.9 kg/m2); and eat a diet highin fruit, vegetables, and wholegrains (3435). The DASH diet isrecommended for patients with aGFR >60 mL/min/1.73 m2 andhigh-normal blood pressure orstage 1 hypertension but notthose with lower GFR (CKDstages 3 or 4) because it containsa higher-than-recommendedamount of protein, potassium,and phosphorous (34). Althoughsalt restriction in the generalpopulation is controversial, CKDpatients with hypertensionshould restrict their dietary saltintake to 1.3 g/kg/day) (12). Finally, patients withstage 4 or 5 CKD should considera low-protein diet (0.6 g/kg/day)under the guidance of a dieticianspecializing in renal disease(3740).

Which drugs and other agentscause acute kidney injury inpatients with CKD?

Patients with CKD are much morelikely to have acute kidney injuryfrom nephrotoxic agents thanpersons with normal renal func-tion. Therefore, known nephro-toxic medications, such asaminoglycoside antibiotics, am-photericin B, nonsteroidal anti-inammatory drugs (41), and ra-diocontrast agents, should beavoided. If radiocontrast agentsare essential, intravenous sodiumbicarbonate or 0.9% normal sa-line should be given before andafter the procedure for patientsat increased risk for contrast ne-phropathy (4243). Given the lowrisk and potential for benet,N-acetylcysteine before and afterradiocontrast induction can begiven to high-risk patients (4445). Exposure to high doses ofgadolinium contrast in patientswith stage 4 or 5 CKD shouldalso be avoided because of therisk for nephrogenic systemicbrosis (46). Finally, although notnecessarily a risk for renal injury,the dosing of several medica-tions needs to be adjusted toavoid other adverse effects (47).

In a study of primary angioplasty, 119 patientswere assigned to a double dose of N-acetyl-cysteine, 116 patients to standard-dose N-acetylcysteine, and 119 patients to placebo. Allpatients received intravenous uids for 12hours after the procedure at a rate of 1 mL/kg/h. Contrast mediuminduced nephropathy,dened as an increase in the serum creatinineof 25% or more, was observed in 8% of pa-tients in the double-dose group, 15% of pa-

Diagnosis... CKD is dened as kidney damage or a GFR

tients in the standard-dose group, and 33% ofthe patients in the placebo group (P < 0.001)(45).

In ACT (Acetylcysteine for Contrast-Induced Ne-phropathy Trial), 2308 patients undergoingangiography were randomly assigned to ace-tylcysteine 1200 mg or placebo twice daily fortwo doses before and two doses after the pro-cedure. Contrast-induced acute kidney injury,dened as an increase in serum creatinine25%, was observed in 12.7% of patients inthe acetylcysteine group and 12.7% of patientsin the control group (P = 0.97) (48).

What is the role of bloodpressure management?Patients with CKD are at high-riskfor cardiovascular disease, andtreatment of hypertension re-duces this risk (34). Patients withCKD and hypertension should betreated to a goal blood pressureof

patients with CKD due to in-creased risk for adverse renalevents and hyperkalemia (5758).

Patients treated with ACE inhibi-tors or ARBs need to be moni-tored closely for side effects,specically hypotension, GFRdecline, and hyperkalemia. Mea-sure blood pressure, GFR, andpotassium within 4 weeks of start-ing treatment or adjusting thedose if any of the following arepresent: systolic blood pressureless than 120 mm Hg or greaterthan 140 mm Hg; GFR less than60 mL/min per 1.73 m2; a declinein GFR greater than 15% in thelast 2 months; or a potassiumgreater than 4.5 mEq/L. Other-wise, these variables should bechecked within 12 weeks of initi-ating or altering the dose of ACEinhibitors or ARBs. In patientswith CKD, GFR may transientlydecline after an ACE inhibitor orARB is started. It is usually safe tocontinue the medication if GFRdecline is

the incidence of impaired estimated GFR 70 pg/mL). The authors matchedcalcitriol users to control participants on age,GFR, and time of rst indication for calcitrioluse. Calcitriol was associated with a decreasein all-cause mortality (hazard ratio, 0.74 [CI,

0.58 0.95]) after adjustment for multiple fac-tors, including age; sex; race; diabetes; coro-nary heart disease; systolic blood pressure;GFR; and levels of parathyroid hormone, albu-min, calcium, and phosphate (69).

HyperkalemiaHyperkalemia is a late manifesta-tion of CKD. Mild elevations oc-cur in stage 3, but signicant,dangerous elevations usually oc-cur only in stages 4 and 5 (66).Normal levels should be main-tained through dietary restrictionof potassium. Sodium polysty-rene sulfonate resin, which bindspotassium in the gut, can beused if necessary. Severe hyper-kalemia (typically >6 mEq/L) orhyperkalemic electrocardio-graphic changes requires urgentaction (70). Emergency treatmentincludes intravenous calcium glu-conate initially, intravenous glu-cose and insulin, intravenous bi-carbonate if acidosis is present,and sodium polystyrene sulfo-nate. If these measure fail, hemo-dialysis may be needed.

Metabolic acidosisCKD is associated with metabolicacidosis but, like hyperkalemia,signicant acidosis is rare until GFRdecreases below 30mL/min/1.73m2 (66). Chronic metabolic acido-sis contributes to progression ofCKD, insulin resistance, decreasedcardiorespiratory tness, and al-tered bonemetabolism (71). De-spite a weak evidence base,guidelines recommend alkali ther-apy for CKD patients with serumbicarbonate

and a low reticulocyte count arelikely to have the anemia of CKD,CKD is not necessarily the solecause of the anemia. The evalua-tion of patients with anemia andCKD should include hemoglobinand hematocrit, red blood cellindices, reticulocyte count, serumiron, percentage of transferrinsaturation, vitamin B12 and folatelevels, and serum ferritin (72).Patients with iron deciencyshould be evaluated to identifypotential sources of bleeding.

On the basis of studies that showimprovement in functional statusbut not mortality, current guide-lines suggest that clinicians con-sider treating most patients withCKD anemia with erythropoietinwhen hemoglobin level is be-tween 9 and 10 g/dL. Adequateiron stores are necessary for suc-cessful treatment of anemia ofCKD because iron is essential forhemoglobin formation and eryth-ropoiesis. Prescribe oral or intra-venous iron as needed to main-tain adequate iron stores (TSAT>20% and serum ferritin >100ng/mL). Hemoglobin should notbe normalized, but should bemaintained at a level 13 g/dL) may be associatedwith increased cardiovascularevents (73). Patients with activecancer or a history of strokeshould be treated with extra care(72).

In TREAT (Trial to Reduce Cardiovascular Eventswith Aranesp Therapy), 4038 patients with di-abetes, CKD, and anemia were randomly as-signed to darbepoetin- and a target hemo-globin of 13 g/dL versus placebo with rescuedarbepoetin- when hemoglobin levelsdropped below 9 g/dL. There was no differencein the rate of death or cardiovascular eventsbetween groups. Although both groups re-ported improvement in the FACT-Fatigue scorefrom baseline to 25 weeks, the improvementwas greater in the darbepoetin- group. How-ever, when compared with the placebo group,the group that received darbepoetin- had ahazard ratio for fatal or nonfatal stroke of 1.92(CI, 1.38 2.68) (74).

How should clinicians treatcardiovascular risk factors?Physicians must be aware of theelevated cardiovascular risk inpatients with CKD and aggres-sively reduce risk factors for ath-erosclerosis (34). Standard life-style recommendationssmokingcessation, 30 minutes of exer-cise/day most days of the week,alcohol intake limited to 1 drink/day for women and 2 drinks/dayfor men, and body mass indexmaintained within the normalrangeshould be recommended.

In addition to promoting lifestylemeasures, cardiovascular risk fac-tors need to be assessed by mea-suring blood pressure, obtaininga fasting lipid prole, and screen-ing for diabetes. Hypertensionand diabetes should be treated.The American College of Cardi-ology/American Heart Associa-tion guidelines for treating highcholesterol should be followed,albeit with a few exceptions:Given the high risk for cardiovas-cular disease among adults aged50 years or older with CKD,guidelines recommend treat-ment with a statin or statinezetimibe combination regard-less of cholesterol level and donot recommend targeting spe-cic total cholesterol or low-density lipoprotein levels in mostpatients (7577).

In the randomized, double-blind SHARP(Study of Heart and Renal Protection) trial,4650 patients with CKD were assigned to sim-vastatin 20 mg plus ezetimibe 10 mg dailyand 4620 were assigned to placebo. Majoratherosclerotic events were reduced by 17%(CI, 6-26) in the simvastatin ezetimibe group.However, there were no differences noted inrates of nonfatal myocardial infarction or deathfrom coronary heart disease (78).

How should clinicians monitorpatients with CKD?Progression of CKD and its com-plications (anemia, hyperphos-phatemia, secondary hyperpara-thyroidism, and malnutrition)should be monitored with an an-

70. Einhorn LM, Zhan M,Hsu VD, et al. The fre-quency of hyperkalemiaand its signicance inchronic kidney disease.Arch Intern Med. 2009;169:1156-62. [PMID:19546417]

71. Dobre M, Rahman M,Hostetter TH. Currentstatus of bicarbonate inCKD. J Am Soc Nephrol.2015;26:515-23. [PMID:25150154]

72. Kidney Disease: Improv-ing Global Outcomes(KDIGO) Anemia WorkGroup. KDIGO clinicalpractice guideline foranemia in chronic kidneydisease. Kidney IntSuppl. 2012; 2: 279335.

73. Singh AK, Szczech L,Tang KL, et al; CHOIRInvestigators. Correctionof anemia with epoetinalfa in chronic kidneydisease. N Engl J Med.2006;355:2085-98.[PMID: 17108343]

74. Pfeffer MA, BurdmannEA, Chen CY, et al; TREATInvestigators. A trial ofdarbepoetin alfa in type2 diabetes and chronickidney disease. N Engl JMed. 2009;361:2019-32. [PMID: 19880844]

75. Stone NJ, Robinson JG,Lichtenstein AH, et al;2013 ACC/AHA Choles-terol Guideline Panel.Treatment of blood cho-lesterol to reduce athero-sclerotic cardiovasculardisease risk in adults:synopsis of the 2013American College ofCardiology/AmericanHeart Association choles-terol guideline. AnnIntern Med. 2014;160:339-43. [PMID:24474185]

76. Tonelli M, Wanner C;Kidney Disease: Improv-ing Global OutcomesLipid Guideline Develop-ment Work Group Mem-bers. Lipid managementin chronic kidney dis-ease: synopsis of theKidney Disease: Improv-ing Global Outcomes2013 clinical practiceguideline. Ann InternMed. 2014;160:182.[PMID: 24323134]

77. Kidney Disease: Improv-ing Global Outcomes(KDIGO) Lipid WorkGroup. KDIGO ClinicalPractice Guideline forLipid Management inChronic Kidney Disease.Kidney Int Suppl. 2013;3: 259305.

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nual assessment of blood pres-sure; estimation of GFR; andmeasurement of hemoglobin,serum potassium, calcium, phos-phorous, parathyroid hormone,and albumin levels (6, 7980).More frequent monitoring shouldbe done in patients with moder-ate to severe CKD (Figure); a his-tory of rapid decline in kidneyfunction (>5 mL/min/1.73 m2 peryear); risk factors for faster pro-gression (smoking, poorly con-trolled hypertension or diabetes,and proteinuria); exposure to aknown cause of acute kidney in-jury, such as radiocontrast dye; oractive or changing therapeuticinterventions to treat CKD, hyper-tension, or proteinuria (6, 12).

What are the indications forrenal replacement therapy?Common indications to initiatedialysis are volume overload un-responsive to diuretics, pericardi-tis, uremic encephalopathy, ma-jor bleeding secondary to uremicplatelets, and hypertension thatdoes not respond to treatment(30). Hyperkalemia and meta-bolic acidosis that cannot bemanaged medically and progres-sive uremic symptoms, such asfatigue, nausea and vomiting,loss of appetite, evidence of mal-nutrition, and insomnia, are alsoindications for initiation of renalreplacement therapy (30, 81).

When should cliniciansconsider consulting anephrologist for treatingpatients with CKD?Managing progressive CKD canbe an enjoyable challenge forgeneral internists, especiallywhen done in partnership with anephrologist. Clinicians shouldconsider consulting a nephrolo-gist for managing complicationsof advanced CKD, such as ane-mia, bone disease, and hyperten-sion. Clinicians should consult anephrologist for advanced orcomplex renal disease for assis-tance in formulating or implement-

ing a care plan (12). In addition,nephrologists should be involvedin therapeutic decision-makingabout complex acute or chronicglomerular and tubulointerstitialdiseases, which often require im-munosuppressive therapy.

Clinicians should consult a neph-rologist when dialysis is antici-pated because a substantialbody of observational studiesshows a strong association be-tween care by a nephrologist inthe months before dialysis andsurvival on dialysis. As CKD pro-gresses, a nephrologist shouldbe consulted no later than whenGFR rst declines to

Practice ImprovementWhat do professionalorganizations recommendwith regard to prevention,screening, diagnosis andtreatment of CKD?Many of the recommendationsincluded in this review comefrom the Kidney Disease: Improv-ing Global Outcomes (KDIGO)guidelines. All of the KDIGOguidelines are available onlineat http://kdigo.org/home/guidelines/. Other CKD guide-lines are available through theUnited Kingdom's Renal Associ-ates (www.renal.org), AustraliaNew Zealand's national kidneyguideline group, Caring for Aus-tralasians with Renal Impairment(www.cari.org.au), and the Cana-dian Society of Nephrology(www.csnscn.ca).

What measures dostakeholders use to evaluatethe quality of care for patientswith CKD?The National Quality Forum(NQF) has established a numberof quality measures (www.qualityforum.org). The followingquality measures apply to CKDin adult patients:

1. Percentage of patientsyounger than 75 years of agewith diabetes screened for ne-phropathy (NQF no. 0062).

2. Percentage of patients withnondiabetic nephropathy treatedwith ACE inhibitors or ARBs (NQFno. 0621).

3. Percentage of patients withdiabetes and hypertensiontreated with ACE inhibitors orARBs (NQF no. 0546).

4. Percentage of patients withhypertension with blood pres-sure controlled to

In the Clinic

Tool KitChronic KidneyDisease

NIH MedLine Pluswww.nlm.nih.gov/medlineplus/ency/article/000471.htm

Information on chronic kidney disease from the NIH.

Guidelineshttps://www.kidney.org/professionals/guidelineshttps://www.kidney.org/sites/default/les/docs/ckd_evaluation_classication_stratication.pdf

www.nice.org.uk/guidance/cg182/resources/guidance-chronic-kidney-disease-pdf

http://kdigo.org/home/guidelines/ckd-evaluation-management/

Medical guidelines for clinical practice for the diagnosisand treatment of chronic kidney disease.

Patient Resourceshttp://nkdep.nih.gov/https://www.kidney.org/kidneydisease/aboutckdwww.mayoclinic.org/diseases-conditions/kidney-disease/basics/denition/con-20026778

http://kdigo.org/home/www.kidneyfund.org/kidney-disease/chronic-kidney-disease/

National Kidney Disease Education Programwith infor-mation for patients and caregivers (English).

http://nkdep.nih.gov/inicio.shtmlNational Kidney Disease Education Programwith infor-mation for patients and caregivers (Spanish). In

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WHAT YOU SHOULDKNOW ABOUT CHRONICKIDNEY DISEASE

What Is Chronic Kidney Disease?The kidneys play an important role in keeping thebody healthy. They remove waste from thebody, balance blood pressure, make importanthormones, and help keep bones strong. Withchronic kidney disease (CKD), the kidneys grad-ually stop working. CKD can cause other healthproblems, like:

Heart disease

Weak bones

Nerve damage

Fluid buildup

Weakened immune system

Other health problems

CKD is most often caused by diabetes or highblood pressure, but other factors can cause thekidneys to stop working.

What Are the Warning Signs ofCKD?

Many people with CKD will not notice symptomsuntil late in the disease. These symptoms caninclude:

Trouble sleeping and tiredness

Trouble concentrating

Feeling sick to your stomach or throwing up

Muscle cramping

Having no appetite

Itching

Swelling in your feet, ankles, or around youreyes

How Is CKD Diagnosed?Your doctor will ask you about your medical his-tory and any other health problems you haveand measure your blood pressure. Your doctoralso will check your blood and urine.

How Is CKD Treated?Treating CKD early can prevent or slow downmore damage to the kidneys so that your kid-neys keep working. Treatment can include:

Taking medicine to treat diabetes, high bloodpressure, or other health problems that aredamaging your kidneys

Avoiding cigarettes and drugs that may harmyour kidneys

Following a healthy diet and exercisingregularly

If your kidneys stop working, dialysis treatmentmay be needed. Dialysis involves using a tube toconnect your body to a dialysis machine for sev-eral hours a day on several days each week. Thedialysis machine will do some of the work thathealthy kidneys do, like removing waste and ex-tra uids from the body. If your kidneys stopworking, kidney transplantation also may be anoption.

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Questions for My Doctor How can I stop kidney disease from gettingworse?

What is the best treatment for my chronickidney disease?

How does my diabetes or high blood pressurehurt my kidneys?

Will I ever need dialysis or a kidney transplant?

Do I need to changemy diet or alcohol intake?

Can I still take the medicines I normally take?

Are there activities I should avoid?

Bottom Line The kidneys are important for keeping thebody healthy. With CKD, the kidneys graduallystop working.

Symptoms of CKD are often not noticed untillate in the disease.

Tests of the blood and urine can helpdiagnose CKD.

Treatment includes taking medicine andmanaging the health problems that damagethe kidneys. Dialysis and a kidney transplantare options for people whose kidneys stopworking.

For More InformationNational Kidney Foundationwww.kidney.org/kidneydisease/aboutckdNational Kidney Disease Education Programwww.nkdep.nih.govAmerican Association of Kidney Patientswww.aakp.org

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