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Chronic Kidney Disease
Urooj Najm, MBBS
Najm Hasan Siddiqui, MD
image BASICS
Chronic kidney disease (CKD) is defined as structural or functional abnormalities of the kidney for ≥3 months, as determined by either pathologic abnormalities or markers of damage—including abnormalities in blood or urine tests, histology, imaging studies, or history of kidney transplant—or a GFR <60 mL/min/1.73 m2 for ≥3 months.
DESCRIPTION
  • In 2012, Kidney Disease Improving Global Outcome (KDIGO) classified CKD in six categories by GFR estimation:
    • G1: kidney damage with normal or increased GFR ≥90 mL/min/1.73 m2
    • G2: mild ↓ GFR 60 to 89 mL/min/1.73 m2
    • G3a: mild to moderate ↓ GFR 45 to 59 mL/min/1.73 m2
    • G3b: moderate to severe ↓ GFR 30 to 44 mL/min/1.73 m2
    • G4: severe ↓ GFR 15 to 29 mL/min/1.73 m2
    • G5: kidney failure: GFR <15 mL/min/1.73 m2 or dialysis
  • CKD per albumin-to-creatinine ratio (ACR) category:
    • A1: normal to mildly increased: <30 mg/g or <3 mg/mmol
    • A2: moderately increased: 30 to 300 mg/g or 3 to 30 mg/mmol (formerly called microalbuminuria)
    • A3: severely increased: >300 mg/g or >30 mg/mmol (formerly called macroalbuminuria)
  • System(s) affected: renal/urinary, cardiovascular, skeletal, endocrine, metabolic, hematologic, lymphatic, immune, neurologic
  • Synonym(s): chronic renal failure; chronic renal insufficiency
Geriatric Considerations
GFR normally decreases with age, despite normal creatinine (Cr). Adjust renally cleared drugs for GFR in the elderly.
Pediatric Considerations
CKD definition is not applicable for children <2 years because of lower GFR even when corrected for body surface area. Calculated GFR based on serum Cr is used in this age group.
Pregnancy Considerations
  • Renal function in CKD may deteriorate during pregnancy. Cr >1.5 and hypertension (HTN) are major risk factors for worsening renal function.
  • Increased risk of premature labor, preeclampsia, and/or fetal loss
  • ACE inhibitors and angiotensin receptor blockers (ARBs) are contraindicated due to teratogenicity. Use diuretics with caution.
EPIDEMIOLOGY
  • Majority of people with CKD in stages 1 to 3
  • African Americans are 3.6 times more likely to develop CKD than Caucasians.
  • Predominant sex: Similar in both sexes; however, incidence rate of end-stage renal disease (ESRD) is 1.6 times higher in males than females.
Incidence
Estimated annual incidence of 1,700/1 million population
Prevalence
Overall prevalence of CKD is 14.2%. Unadjusted prevalence/incidence rates of ESRD (stage 5) are 1,752 and 362.4/1 million, respectively. Numbers do not reflect the burden of earlier stages of CKD (stages 1 to 4), which are estimated to affect 13.1% of the population nationwide or 26.3 million in the United States.
ETIOLOGY AND PATHOPHYSIOLOGY
Progressive destruction of kidney nephrons; GFR will drop gradually, and plasma Cr values will approximately double, with 50% reduction in GFR and 75% loss of functioning nephrons mass. Hyperkalemia usually develops when GFR falls to <20 to 25 mL/min. Anemia develops from decreased renal synthesis of erythropoietin.
  • Renal parenchymal/glomerular
    • Nephritic: hematuria, RBC casts, HTN, variable proteinuria
      • Focal proliferative: IgA nephropathy, systemic lupus erythematosus (SLE), Henoch-Schönlein purpura, Alport syndrome, proliferative glomerulonephritis, crescentic glomerulonephritis
      • Diffuse proliferative: membranoproliferative glomerulonephritis, SLE, cryoglobulinemia, rapidly progressive glomerulonephritis (RPGN), Goodpasture syndrome
    • Nephrotic: proteinuria (>3.5 g/day), hypoalbuminemia, hyperlipidemia, and edema
      • Minimal change disease, membranous nephropathy, focal segmental glomerulosclerosis
      • Amyloidosis, diabetic nephropathy
  • Vascular: HTN, thrombotic microangiopathies, vasculitis (Wegener), scleroderma
  • Interstitial-tubular: infections, obstruction, toxins, allergic interstitial nephritis, multiple myeloma, connective tissue disease, cystic disease
  • Postrenal: obstruction (benign prostatic hyperplasia), neoplasm, neurogenic bladder
Genetics
  • Alport syndrome, Fabry disease, sickle cell anemia, SLE, and autosomal dominant polycystic kidney disease can lead to CKD.
  • Polymorphisms in gene that encodes for podocyte nonmuscle myosin IIA are more common in African Americans than Caucasians and appear to increase risk for nondiabetic ESRD.
RISK FACTORS
  • Type 1 or 2 diabetes mellitus (DM); most common
  • Age >60 years
  • Cardiovascular disease (e.g., HTN [common], renal artery stenosis, atheroemboli)
  • Previous kidney transplant
  • Urinary tract obstruction (e.g., benign prostatic hyperplasia)
  • Autoimmune disease, vasculitis/connective tissue disorder
  • Family history of CKD
  • Nephrotoxic drugs (lithium, salicylate, high-dose or chronic NSAIDs, sulfa)
  • Congenital anomalies, obstructive uropathy, renal aplasia/hypoplasia/dysplasia, reflux nephropathy
  • Hyperlipidemia
  • Low income/education/ethnic minority status
  • Obesity/smoking/heroin use
  • Chronic infection (hepatitis B, hepatitis C, HIV)
GENERAL PREVENTION
  • Treat reversible causes: hypovolemia, infections, diuretics, drugs (NSAIDs, aminoglycosides, IV contrast).
  • Treat risk factors: DM, HTN, hyperlipidemia, smoking, and obesity; adjust medication doses to prevent renal toxicity.
COMMONLY ASSOCIATED CONDITIONS
HTN, DM, cardiovascular disease
image DIAGNOSIS
PHYSICAL EXAM
  • Volume status (pallor, BP/orthostatic; edema; jugular venous distention; weight)
  • Skin: sallow complexion, uremic frost
  • Ammonia-like odor (uremic fetor)
  • Cardiovascular: Assess for murmurs, bruits, pericarditis.
  • Chest: pleural effusion
  • Rectal: enlarged prostate
  • CNS: asterixis, confusion, seizures, coma, peripheral neuropathy
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • GFR can be estimated by multiple equations (freely available in medical calculators), including MDRD equation:
    • GFR (mL/min/1.73 m2) = 175 × [(serum Cr &mgr;mol/1/88.4)-1.154] × [age (years)-0.203] × 0.742 for females or 1.21 for African American
    • Often used as estimate in electronic health records
  • Cr clearance (CrCl) can be calculated using Cockroft-Gault formula
    • CrCl (male) = ([140 - age] × weight (kg)/(serum Cr × 72)]
    • CrCl (female) = CrCl (male) × 0.85
    • Formula used for determining cut points for renally adjusted medications
  • Urine analysis
    • Urine microscopy: WBC casts in pyelonephritis, RBC casts in glomerulonephritis/vasculitis, dysmorphic RBCs
    • Urine electrolytes: sodium, Cr, urea (if on loop diuretics)
    • Proteinuria/albuminuria
      • 24-hour urine collection: >30 to 300 mg/24 hr (20 to 200 &mgr;g/min) is microalbuminuria and >300 mg/24 hr (>200 &mgr;g/min) is macroalbuminuria.
      • Albumin/Cr ratio (ACR): See “Description.”
  • P.199

  • Hematology: normochromic, normocytic anemia; increased bleeding time
  • Chemistry
    • Elevated BUN, Cr, hyperkalemia, metabolic acidosis
    • Increased parathyroid hormone, decreased 25-(OH) vitamin D, hypocalcemia, hyperphosphatemia
    • Hyperlipidemia, decreased albumin
  • Cimetidine: inhibits Cr tubular secretion
  • Trimethoprim: inhibits Cr and K+ secretion and may cause/worsen hyperkalemia
  • Cefoxitin and flucytosine: increases serum Cr
  • Diltiazem and verapamil (like ACE/ARBs) have significant antiproteinuric effects in patients with CKD.
  • Ultrasound (initial test of choice): Small, echogenic kidneys; may see obstruction (e.g., hydronephrosis); cysts; kidneys may be enlarged with HIV and diabetic nephropathy.
  • Doppler ultrasound to assess for renovascular disease, thrombosis
  • Noncontrast CT scan: obstruction, calculi, cysts, neoplasm, renal artery stenosis
  • MRI/MRA: Avoid gadolinium because of the risk of nephrogenic systemic fibrosis.
  • Renal arteriogram for renal artery stenosis can be therapeutic (angioplasty or stenting).
  • Renal scan to screen for differential function between kidneys
  • Retrograde pyelogram: if strong suspicion for obstruction despite negative finding on ultrasound
Follow-Up Tests & Special Considerations
  • Serology: antinuclear antibody (ANA); double-stranded DNA, antineutrophil cytoplasmic antibody; complements (C3, C4, CH50); anti-glomerular basement membrane (GBM) antibodies; hepatitis B, C; and HIV screening
  • Serum and urine immunoelectrophoresis
Diagnostic Procedures/Other
Biopsy: hematuria, proteinuria, acute/progressive renal failure, nephritic or nephrotic syndrome
image TREATMENT
GENERAL MEASURES
  • Lowering salt intake to <2 g/day of sodium in adults, unless contraindicated (1)[C]
  • Minimize radiocontrast exposure; prehydrate; N-acetylcysteine use is controversial. Avoid nephrotoxins (NSAIDs, aminoglycosides, etc.).
  • Renal replacement: Prepare for dialysis or transplant when GFR <30 mL/min/1.73 m2.
  • Vaccines: pneumococcal, influenza
  • Encourage smoking cessation, encourage weight loss (if applicable), and limit alcohol consumption.
MEDICATION
  • HTN: Goal is BP <130/80 mm Hg (in nonhemodialysis patients) and <140/90 mm Hg (in patients on hemodialysis) in the nephrology literature, but more recent analysis based on outcomes suggests a universal BP target of <140/90 mm Hg (2).
  • Antihypertensive agents should be selected based on the type of CKD and presence of cardiovascular disease.
  • Long-acting (once daily) agents should be prescribed preferentially and given at bedtime.
  • ACE inhibitors (drugs of choice) or ARBs for BP control and antiproteinuric effect
    • Potential for hyperkalemia
    • Can tolerate up to 30% rise in serum Cr unless hyperkalemia develops
    • If goal is not reached, add diuretic; thiazides are recommended for GFR ≥30 mL/min/1.73 m2; loop diuretics are recommended for GFR <30 mL/min/1.73 m2), followed by diltiazem or verapamil or a &bgr;-blocker.
  • Secondary hyperparathyroidism
    • Cinacalcet, paricalcitol (decrease PTH levels)
  • Recommended serum phosphate maintenance levels for CKD patients:

    Stage

    mg/day

    mmol/L

    Normal range (may vary by institution)

    2.5-4.5

    0.81-1.45

    Stages 3 and 4 CKD (not on dialysis)

    2.7-4.6

    0.87-1.49

    Stage 5 and ALL stages on dialysis

    3.5-5.5

    1.13-1.78

    • Stages 3 to 5 CKD (not on dialysis): Restrict dietary phosphate to 800 to 1,000 mg/day.
      • Calcium-containing phosphate binders (with meals): calcium carbonate, calcium acetate (risk of hypercalcemia)
      • Noncalcium phosphate binders (with meals): sevelamer, lanthanum
      • Vitamin D: inactive vitamin D 25 (ergocalciferol or cholecalciferol), calcitriol (active vitamin D 1,25 [OH]): Vitamin D may increase absorption of phosphate by intestines and should not be started until serum phosphate concentration is controlled.
    • Anemia: ferrous sulfate, erythropoietin-stimulating agents (ESAs): Before starting ESAs, nonrenal causes of anemia/iron stores should be checked. Start when Hgb <10 g/dL; goal range 10 to 11 g/dL, not to exceed 11.5 g/dL
    • Hyperlipidemia: Statins with low-density lipoprotein (LDL) goal is similar to coronary heart disease patients (LDL <70 to 100).
    • Glycemic control: Target HbA1c 7.0%, but it should be individualized based on life expectancy of patient, risk for adverse events related to glucose control, and patient preference (1). Tighter control may slow progression of microalbuminuria but may not reduce progression to ESRD and death in patients with type 2 diabetes. Use of metformin is not advised with serum Cr ≥1.5 mg/dL in males and ≥ 1.4 mg/dL in females because of possible risk of lactic acidosis.
    • Metabolic acidosis: Start treatment when bicarb <20 mEq/L; goal 23 to 29 mEq/L
      • Sodium bicarbonate: daily dose of 0.5 to 1 mEq/kg/day or sodium citrate (should be avoided in patients taking aluminum-containing antacid)
ISSUES FOR REFERRAL
  • Nephrology consult: GFR <15: immediate
  • GFR 15 to 29: urgent
  • GFR 30 to 59: nonurgent referral
  • GFR 60 to 89: not required unless with comorbidities
SURGERY/OTHER PROCEDURES
Placement of dialysis access or transplantation
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Uremia: nausea/vomiting, fluid overload, pericarditis, uremic encephalopathy, resistant HTN, hyperkalemia, metabolic acidosis, hyperphosphatemia
image ONGOING CARE
DIET
Nutrition consult for CKD diet: Protein restriction in early CKD is controversial but may be beneficial in ESRD; restricted intake of phosphates; sodium and water restriction to avoid volume overload; potassium restriction if hyperkalemic
PATIENT EDUCATION
National Kidney Federation patient Web site at: http://www.kidney.org/patients
PROGNOSIS
Patients with CKD gradually progress to ESRD, with bad prognoses. 5-year survival rate for U.S. patients on dialysis is ˜35%.
REFERENCES
1. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31(7): 1281-1357.
2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Inter Suppl. 2013;3:1-150. www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf
See Also
&NA;
  • Hydronephrosis; Nephrotic Syndrome; Polycystic Kidney Disease; Proteinuria
  • Algorithm: Anuria or Oliguria
Codes
&NA;
ICD10
  • N18.9 Chronic kidney disease, unspecified
  • Q63.9 Congenital malformation of kidney, unspecified
  • N18.3 Chronic kidney disease, stage 3 (moderate)
Clinical Pearls
&NA;
  • Maintaining BP <140/90 mm Hg is imperative (in patients not on dialysis).
  • Avoid nephrotoxins including ACE/ARB in acute kidney injury (AKI) with or without CKD.
  • CKD is a CHD risk equivalent.