II. Definitions
- Chronic Kidney Disease
- Abnormal Kidney structure or function lasting more than 3 months, with associated health implications
- End Stage Renal Disease
- Kidney Function not adequate for longterm survival without Dialysis or Renal Transplant
- Stage 5 Chronic Kidney Disease (GFR <15 ml/min/1.73m2)
III. Epidemiology
- Chronic Kidney Disease (2016)
- Prevalence in U.S.: 47 million (14-15% of the adult U.S. population)
- Accounts for 20% of all medicare costs ($52 Billion/year in 2014)
- End Stage Renal Diseases
- Prevalence 2002: 435,000 in U.S.
- Prevalence 2016: 660,000 in U.S.
- Prevalence 2018: 750,000 in U.S.
- Accounts for 10% of all medicare fee-for-service costs
IV. Causes: Percentage is that of conditions responsible for ESRD
-
Diabetes Mellitus (37%)
- See Diabetic Nephropathy
- Glycemic control is critical to slow progression
- Type I Diabetes Mellitus (represents 5% of ESRD patients)
- Progresses to ESRD in 40% of patients
- Type II Diabetes Mellitus (represents 32% of ESRD patients)
- Progresses to ESRD in 20% of patients
- Type II Diabetes is 10 times as common as Type
- Hypertension or Hypertensive Kidney Disease (30% overall, 40% in black patients)
- Human Immunodeficiency Virus Infection (HIV Infection)
-
Glomerulonephritis and other glomerular diseases (21%)
- Includes Vasculitis (e.g. Systemic Lupus Erythematosus)
- Hereditary conditions
- Polycystic Kidney Disease (7%)
- Alport Syndrome
- Medullary Cystic disease
- Tubulointerstitial disease (4%)
- Infection with scarring
- Chronic Urinary Tract Infections (Pyelonephritis)
- Reflux nephropathy in children
- Urologic obstruction
- Nephrolithiasis (obstruction)
- Benign Prostatic Hyperplasia (BPH)
- Medication-induced Nephrotoxicity (Nephrotoxins)
- Infection with scarring
V. Risk Factors
- Diabetes Mellitus (leading cause)
- Autoimmune Conditions
- Chemical exposures (Lead, Cadmium, Arsenic, Mercury, Uranium)
- Nephrotoxin exposure (e.g. Intravenous Contrast Related Acute Renal Failure)
- Family History of Chronic Kidney Disease
- Hypertension
- Low birth weight
- Lower Urinary Tract Obstruction
- Cancer
- Nephrolithiasis
- Advanced age
- Acute Kidney Injury in past
- Decreased Renal Mass
- Serious systemic infection (e.g. Sepsis)
- Recurrent Urinary Tract Infections
- Minority status (blacks, native american, asian, pacific islander)
VI. History
- Recent infections
-
Sexually Transmitted Infection (STI, STD) risk factors including IV Drug Abuse
- HIV Infection
- Hepatitis B Infection
- Hepatitis C Infection
-
Arthritis or dermatitis
- Systemic Lupus Erythematosus
- Cryoglobulinemia
- Urinary symptoms
- PMH
- Diabetes Mellitus
- Present for 5-10 years: Microalbuminuria, Pre-Hypertension
- Present for 10-15 years: Albuminuria, Retinopathy, Hypertension
- Hypertension
- Severe Hypertension
- End-organ effects
- Diabetes Mellitus
-
Family History
-
Autosomal Dominant Polycystic Kidney Disease
- Affects men and women in every generation
- May also occur less frequently if Autosomal Recessive
- Alport Syndrome (X-linked recessive)
- Affects men in every generation
-
Autosomal Dominant Polycystic Kidney Disease
VII. Exam
-
Vital Signs
- Hypertension
- Increased Body Mass Index
-
Eye Exam
- Hypertensive Retinopathy (A-V Nicking)
- Diabetic Retinopathy
- Cardiovascular Exam
- Carotid Bruit (Cerebrovascular Disease)
- Decreased peripheral pulses (Peripheral Vascular Disease)
- Lower Extremity Edema (e.g. Congestive Heart Failure)
- Ventricular Hypertrophy
- Abdominal Exam
- Renal artery bruit (e.g. Renal Artery Stenosis)
- Flank Pain (e.g. Ureterolithiasis, Pyelonephritis)
- Bladder Distention (outflow obstruction)
-
Musculoskeletal Exam
- Arthritis or synovitis
- Skin Exam
VIII. Symptoms: Stage 4-5
IX. Signs
X. Criteria: Chronic Kidney Disease (at least one of the following criteria)
- GFR < 60 ml/min/1.73 m2 (based on two GFR calculations 3 months or more apart)
- Men: Serum Creatinine >1.5 mg/dl
- Women: Serum Creatinine >1.3 mg/dl
- Significant Proteinuria or albuminuria for >3 months (positive on 2 of 3 samples in 3-6 months)
- Urine Albumin to Creatinine Ratio >30 mg/g (Microalbuminuria, moderate) or >300 mg/g (severe)
- Urine Protein to Creatinine Ratio is less sensitive (but useful in albumin ratio >500 mg/g)
- Urine Albumin to Creatinine Ratio >30 mg/g (Microalbuminuria, moderate) or >300 mg/g (severe)
- Structural Kidney Disease or Kidney damage for >3 months
- Identify with renal Ultrasound
- Other criteria
- All Renal Transplant patients have Chronic Kidney Disease regardless of GFR or Proteinuria
XI. Stages: NKF Classification System
- Stage 1: GFR >90 ml/min despite Kidney damage
- Microalbuminuria present
- Stage 2: Mild reduction (GFR 60-89 min/min)
- GFR of 60 may represent 50% loss in function
- Parathyroid Hormone starts to increase
- Stage 3: Moderate reduction (GFR 30-59 ml/min, 3a: 45-59, 3b: 30-44)
- Calcium absorption decreases
- Malnutrition onset
- Anemia secondary to Erythropoietin deficiency
- Left Ventricular Hypertrophy
- Stage 4: Severe reduction (GFR 15-29 ml/min)
- Stage 5: Kidney Failure (GFR <15 ml/min)
- References
XII. Labs: Screening for Chronic Kidney Disease
- Indications
- Diabetes Mellitus
- Hypertension
- Age over 55-60 years old
- Consider in Family History of Chronic Kidney Disease (see causes listed above)
- Tests
- Serum Creatinine (with Estimated Glomerular Filtration Rate)
- Urine Albumin to Creatinine Ratio
- Urinalysis with microscopy
- Assess Glomerular Filtration Rate (GFR)
- Estimations generally as accurate as 24 hour urine
- See Creatinine Clearance for exceptions
- GFR may also be estimated from Serum Cystatin C instead of Serum Creatinine
- Consider if abnormal GFR based on Creatinine Clearance suspected to be False Positive
- Formulas
- Chronic Kidney Disease Epidemiology Collaboration Equation or CKD-EPI (preferred standard)
- Cockcroft-Gault equation
- Used only to calculate medication Renal Dosing
- Modification of Diet in Renal Disease (MDRD)
- CKD-EPI is preferred
- Estimations generally as accurate as 24 hour urine
- Assess for Proteinuria
- Previously Urinalysis dipstick was used to triage testing for spot Urine Protein or albumin
- As of 2012, Urinalysis is no longer recommended for Urine Protein screening
- Urine Albumin to Creatinine Ratio is recommended instead as a first-line study
- Assess other urinary sediment on Urinalysis
- Microscopic Hematuria
- Urine White Blood Cells (pyuria)
- Cellular Casts
- Lipiduria (seen in nephrotic sediment)
- Indicated by Fatty Casts, oval fat bodies, or free fat in urine sediment
- Increases significance of Proteinuria
- Eosinophiluria
- Tubulointerstitial disease
- Atheroembolic dsisease
XIII. Labs: Urine sediment found in causes of Chronic Kidney Disease
-
Polycystic Kidney Disease
- Protein to Creatinine ratio 200-1000 mg/g
- Red Blood Cells present
-
Diabetic Nephropathy
- Albumin to Creatinine ratio 30-300 early (and exceeds 300 in later disease)
- Hereditary Nephritis
- Protein to Creatinine ratio <1000 mg/g
- Red Blood Cells, tubular cells and Granular Casts present
- Hypertensive Nephropathy
- Protein to Creatinine ratio 200-1000 mg/g
- Noninflammatory Glomerular Disease
- Protein to Creatinine ratio >1000 mg/g
- Proliferative Glomerulonephritis
- Protein to Creatinine ratio >500 mg/g
- Red Blood Cells, Red Blood Cell Casts, White Blood Cells, White Blood Cell Casts present
- Tubulointerstitial Nephritis
- Protein to Creatinine ratio 200-1000 mg/g
- Red Blood Cells, White Blood Cells, White Blood Cell Casts present
- IgA Nephropathy or Rapidly Progressive Glomerulonephritis (RPGN)
- Dysmorphic urinary Red Blood Cells or
- Red Blood Cell Casts
XIV. Labs: Findings in Chronic Kidney Disease Stages 3-4
-
Anemia (Normochromic, Normocytic)
- Hematocrit decreases
- Serum Creatinine > 2-3
- Glomerular Filtration Rate <20-30
- Results from decreased Erythropoietin synthesis
- Hematocrit decreases
- Azotemia
- Decreased Serum Protein
- Serum chemistry abnormalities
XV. Labs: Initial presentation
- Screening labs (see above)
- Serum Creatinine (with Estimated Glomerular Filtration Rate)
- Urine Albumin to Creatinine Ratio
- Urinalysis with microscopy
- Evaluates for intrinsic renal disease causes
- Basic labs
- Basic metabolic panel (includes serum Electrolytes)
- Fasting lipid profile
- Hemoglobin A1C
- Serum Calcium
- Serum Phosphorus
- Complete Blood Count (CBC)
- Vitamin D
- Additional labs as indicated
- Antinuclear Antibody (ANA)
- Urine and Serum Protein Electrophoresis
- Hepatitis B Serology (HBsAg)
- Membranous Nephropathy
- Membranoproliferative nephritis)
- Hepatitis C Serology (xHBC Antibody)
- Membranous Nephropathy
- Membranoproliferative Glomerulonephritis
- Mixed Cryoglobulinemia
- HIV Test
- Focal and segmental glomerulosclerosis
- Antistreptolysin O Antibody (ASO Titer)
- Antineutrophil Cytoplasmic Antibody (ANCA)
- Granulomatosis with Polyangiitis (previously known as Wegener's Granulomatosis)
- Microscopic Polyangiitis
- Pauci-immune Rapidly Progressive Glomerulonephritis
- Anti-Glomerular Basement Membrane Antibody (Anti-GBM Antibody)
- Goodpasture Syndrome (xGBM Antibody associated with rapid progression)
- Consider serum complement studies (C3, C4, CH50)
- Post-Streptococcal Glomerulonephritis
- Membranoproliferative Glomerulonephritis
- Lupus Nephritis
- Cryoglobulinemia
- Cryoglubulin Test
- Cryoglobulinemia
- Eosinophiluria
- Tubulointerstitial Disease
- Other diagnostics
- Consider baseline Electrocardiogram (coronary disease is a common complication of CKD)
XVI. Labs: Monitoring
-
General labs
- Basic metabolic panel (Serum Creatinine and serum Electrolytes) every 3-12 months or more
- Urine Albumin to Creatinine Ratio every 12 months
-
Anemia monitoring (at least annually, or more often as indicated)
- Complete Blood Count with differential
- Reticulocyte Count
- Serum Iron
- Serum Ferritin
- Serum Transferrin
- Vitamin B12
- Serum Folate
-
Malnutrition monitoring (every 6-12 months, up to every 1 to 3 months in stage 4-5 CKD)
- Serum Albumin
- Body weight
- Dietary history
- Bone disorders
- See Chronic Kidney Disease related Bone Disease (Renal Osteodystrophy)
- Alkaline Phosphatase
- Obtain at baseline
- Obtain every 12 months in Stage 4 and 5 CKD
- Serum Calcium and Serum Phosphorus
- Obtain every 3 to 6 months (as often as every 1 to 3 months in Stage 5 CKD)
- 25-hydroxyvitamin D and Intact Parathyroid Hormone (iPTH)
- Obtain at baseline
- Obtain every 3 to 6 months in Stage 4 (or every 1 to 3 months in Stage 5)
XVII. Imaging: Renal Ultrasound (indicated in most patients on initial presentation)
-
Doppler Ultrasound
- Renal veins: Venous thrombosis
- Renal arteries: Lower efficacy in diagnosing Renal Artery Stenosis
-
General findings
- Nephrocalcinosis
- Hydronephrosis
- Renal Mass or complex cysts (concerning for malignancy risk)
- Renal stones
- Increased echogenicity
- Renal disease
- Enlarged Kidneys
- Renal tumors
- Infiltrating disease
- Nephrotic Syndrome related conditions
- Asymmetric Kidney size or scarred Kidneys
- Vascular disease
- Urologic disease
- Tubulointerstitial disease
- Small, hyperechoic Kidneys
- Chronic Kidney Disease
XVIII. Imaging: Other advanced imaging
- Consider CT or MRI of Kidneys and Liver
- Consider Voiding Cystourethrogram
XIX. Diagnosis: Renal Biopsy
- Indications
- Hematuria and low Creatinine Clearance or Proteinuria
- Nephrotic range Proteinuria
- Chronic Renal Failure with normal or large Kidneys
- Acute Renal Failure of unknown cause
- Contraindications
- Renal length <9 cm
- Severe Hypertension
- Multiple large Renal Cysts
- Uncorrected bleeding tendency
- Hydronephrosis
- Acute infection
XX. Management: Secondary Prevention
- Protocols
- Proteinuria (Microalbuminuria or Macroalbuminuria)
-
Coronary Artery Disease Prevention
- Aspirin 81 mg orally daily
- Statin for most patients
- Control Hypertension
-
Hypertension (common in ESRD)
- Hypertension correlates with volume status
- Modify hemodilaysis to maintain normovolemia
- Sodium Restriction 2 g/day
- Antihypertensives
- Ambulatory or home Blood Pressure measurements are more preferred for BP monitoring over Dialysis center BPs
- Hypertension correlates with volume status
-
Diabetes Mellitus
- Maintain careful Blood Glucose Monitoring in ESRD (higher risk for Hypoglycemia)
- Hemodialysis typically helps improve Hyperglycemia management
-
Hemoglobin A1C may be inaccurate in ESRD (esp. on Hemodialysis)
- Glucose monitoring logs are preferred
-
Insulin is preferred in ESRD or GFR <30 ml/min/1.73m2
- Many other diabetic medications (e.g. Metformin) are contraindicated in low GFR
- Alternatives include Glipizide (but risk of Hypoglycemia) and Repaglinide
- Medication limitations for GFR <30 ml/min
- Avoid Metformin and Flozins (SGLT2 Inhibitors) in Type II Diabetes
- Avoid Bisphosphonates
- Avoid Direct Oral Anticoagulants
- Avoid NSAIDs
- For Bowel Preparation, use Polyethylene glycol (PEG) instead of Magnesium or Phosphorus preparations
-
Vaccination
- Influenza Vaccine
- Tetanus Vaccine
- Hepatitis B Vaccine
- Pneumococcal Vaccine (Pneumovax-23 and Prevnar 13)
- Covid-19 Vaccine
- Recombinant Shingles Vaccine (Shingrix) if indicated
- Cancer Screening is not recommended in End Stage Renal Disease (ESRD)
- Life Expectancy in ESRD is not sufficient to warrant longterm cancer screening
XXI. Management: Nephrology Referral
- Indications
- Chronic Kidney Disease Stage 4 (GFR <30 ml/minute)
- Consider initial evaluation when GFR <60 ml/minute
- Chronic Kidney Disease with rapid progression
- Unexplained decrease in GFR >30% over 4 months
- Annual GFR decline >5 ml/min/1.73m2
- Kidney Failure Risk Calculator estimates one year ESRD risk >10-20%
- Acute failure complicating Chronic Kidney Disease
- Unclear etiology for Renal Failure
- Hereditary Kidney Disease
- Renal biopsy
- Nephrotic sediment (e.g. lipiduria)
- RBC Casts (indicates an urgent referral)
- Extensive or recurrent Nephrolithiasis
- Urine Eosinophils
- Refractory Hypertension despite at least 3 antihypertensives
- Significant Proteinuria
- 24 Hour Urine Protein > 1000 mg
- Protein to Creatinine ratio >500-1000 mg/g
- Albumin to Creatinine ratio >300 mg/g despite 6 months on ACE Inhibitor (or ARB)
- Acute Tubular Necrosis
- Significant comorbidity (e.g. cardiovascular disease)
- Complications of Chronic Kidney Disease
- Anemia of Chronic Kidney Disease
- Bone and mineral disorders of Chronic Kidney Disease
- Hyperkalemia (Potassium >5.5 meq despite modification of therapy)
- Chronic Kidney Disease Stage 4 (GFR <30 ml/minute)
- Goals of Nephrology Care
- Initiate disease specific management including complications and related comorbidity
- Intervene to slow Chronic Kidney Disease progression
- Planning for Hemodialysis, conservative management or Renal Transplantation
- Coordinate with multidisciplinary care
XXII. Management: End Stage Renal Disease
-
Hemodialysis or Peritoneal Dialysis
- See Hemodialysis
- See Peritoneal Dialysis
- Absolute Dialysis Indications
- Uremic Symptoms
- Uremic Pericarditis
- Relative Dialysis Indications
- Hypervolemia
- Hyperkalemia or other Electrolyte abnormalities
- Severe Metabolic Acidosis
- Creatinine Clearance <10 ml/min (<15 ml/min in Diabetes Mellitus)
-
Renal Transplantation
- Improves overall survival and quality of life in comparison to Dialysis and conservative management
- Refer to Renal Transplant when GFR <30 ml/min/1.73m2 to allow for adequate planning, preparation, wait list time
- As of 2020, the median time of Renal Transplant wait list is 4 years
- Less rejection if transplant before Dialysis started
- Conservative management options (palliative approach)
- Optimizes quality of life over prolongation of life
- Survival benefit of Hemodialysis is reduced in elderly and comorbidity
- Uremia symptoms may not significantly improve with Hemodialysis
- Hemodialysis is associated with increased medical interventions
- More than half of chronic Hemodialysis patients regret their decision to undergo Hemodialysis
- Non-Dialysis with Hospice care
- Delayed Dialysis until Creatinine Clearance <5 ml/min (similar morbidity and mortality)
- Optimizes quality of life over prolongation of life
XXIII. Management: Anemia
-
Erythropoietin (EPO)
- Efficacy
- Initial studies showed benefit for Erythropoietin
- Recent studies show no benefit and higher risk of Cerebrovascular Accident
- Outcomes are the same with and without normalized Hemoglobin via erythropoetin
- Morbidity and patient sense of well-being is not improved on erythropoetin
- Pfeffer (2009) N Engl J Med 361 [PubMed]
- Indications for Erythropoeitin
- Hemoglobin <9 mg/dl
- Adverse effects
- Increased risk of Cerebrovascular Accident
- Efficacy
-
Iron Supplementation
- Often indicated in Hemodialysis patients
-
Parenteral replacement is often needed (decreased oral absorption)
- Non-Dextran IV Iron
- Indicated in significant Iron Deficiency refractory to oral replacement
- Options: Ferumoxytol (Feraheme), iron sucrose (venafer) or Sodium Ferric Gluconate (Ferrlecit)
- Ferric pyrophosphate (Triferic)
- Available in 2015 (U.S.)
- Indicated for maintenance iron infusion
- May be delivered inline with Hemodialysis
- Non-Dextran IV Iron
- References
- (2015) Presc Lett 22(4)
XXIV. Management: Anorexia and Protein Energy Wasting in ESRD
- Minimize Uremia with adequate Dialysis frequency
- Consider Major Depression, Gastroparesis, and Xerostomia
-
Protein Energy Wasting Findings
- BMI < 23 kg/m2
- Unintentional Weight Loss (>5% over 3 months or >10% over 6 months)
- Serum Albumin <3.8 g/dl
-
General Measures
- Dietician Consultation
- High Protein diet 1.0 to 1.2 g Protein/kg/day in ESRD
- Contrast with the limited Protein diet in Chronic Kidney Disease to prevent progression
- Consider dietary Protein Supplementation
- Medications
- Dronabinol 2.5 mg orally before meals
- Megestro 400 mg orally daily
- Prednisone 10 mg orally daily
XXV. Management: Symptomatic Management in ESRD
-
Agitation
- Haloperidol 1 mg PO, IV or IM every 12 hours
-
Dyspnea
- Regular Physical Activity to prevent deconditioning
- Fentanyl (Duragesic) 12.5 mg IV or SQ every two hours as needed for end-of-life
-
Fatigue
- Treat Anemia if present
- Consider Depression Management with Fluoxetine 20 mg daily or Sertraline 50 mg daily
-
Nausea and Vomiting
- Minimize Uremia with adequate Dialysis frequency
- Ondansetron 4 mg orally every 8 hours
- Metoclopramide (Reglan) 5 mg twice daily
- Haloperidol (Haloperidol) 0.5 mg orally every 8 hours
-
Pruritus
- Minimize Uremia with adequate Dialysis frequency
- Phosphate Binders
- Standar Dry Skin therapy (e.g. barrier creams)
- Ondansetron 4 mg orally every 8 hours
- Hydroxyzine (Atarax or Vistaril), 25 mg orally every 6 hours
- Naltrexone (Revia) 50 mg orally daily
- Phototherapy (UV-B Light)
-
Insomnia
- See Sleep Hygiene
- Treat Restless Leg Syndrome
- Treat Obstructive Sleep Apnea
- Zolpidem 5 mg orally at bedtime
- Temazepam (Restoril) 15 mg orally at bedtime
XXVI. Management: Advanced Directives in ESRD
-
Cardiopulmonary Resuscitation (CPR)
- Survival in ESRD is only 8% at hospital discharge and 3% at six months
- Contrast with CPR in non-ESRD with survival of 12% at discharge and 9% at six months
- Discuss Do-Not-Reuscitate status at routine visits
- Hospice
XXVII. Complications
- Cardiovascular Disorders
- See Hypotension in the Dialysis Patient
- Coronary Artery Disease (21% of ESRD cases)
- Peripheral Vascular Disease
- Cardiac Arrhythmias
- Congestive Heart Failure
- Uremic Cardiomyopathy
- Erectile Dysfunction
- Uremic Pericarditis
- Severe Refractory Hypertension
- Pulmonary Edema
- High-output Heart Failure (secondary to Anemia or Arteriovenous Fistula)
- Calciphylaxis
- Life-threatening, small vessel Occlusion in skin and fatty tissue presenting with necrotic skin lesions
- Uremic Pericardial Effusion
- Consider in Chronic Renal Failure with Dyspnea
- Risk of Cardiac Tamponade (consider in any ill ESRD patient)
- Hematologic
- Pancytopenia
- Anemia (Normochromic, Normocytic)
- Thrombocytopenia
- Leukopenia
- Pancytopenia
- Neurologic disorders
- Subdural Hematoma
- Consider in any altered LOC patient with ESRD
- Uremic encephalopathy (Memory Loss, slurred speech, asterixis)
- Dialysis Dementia
- Associated with >2 years on Dialysis
- Diagnosis of exclusion
- Peripheral Neuropathy (e.g. extremity Paresthesias)
- Restless Leg Syndrome
- Sleep Disorders
- Thiamine deficiency (and Wernicke's Encephalopathy)
- Subdural Hematoma
- Fluids, Electrolytes and Nutrition
- Metabolic Acidosis
- Associated with increased mortality and other adverse outcomes
- Improves with Dialysis
- Consider Bicarbonate Supplementation in persistently low serum bicarbonate
- Muscle wasting and Malnutrition
- Pseudogout
- Uremia (Nausea, Vomiting, Anorexia)
- Hyperphosphatemia (see Renal Osteodystrophy)
- Metabolic Acidosis
- Gastrointestinal disorders
- Skin disorders
- Pruritus
- Calciphylaxis
- Uremic frost
- Occurs in end-stage renal disease with high BUN (untreated or missed Hemodialysis)
- Crystallized urea from sweat forms and deposits on the skin
- Uremic frost resembles Seborrhea
- Miscellaneous disorders
XXVIII. Course
- Progression of Chronic Kidney Disease (<55 mmHg) is predictable
- Glomerular Filtration Rate (GFR) decreases -4 ml/min per year if no intervention
- Intensive management may halt GFR decline
- Major causes of death in ESRD
XXIX. Prognosis
- Annual mortality of ESRD: 24%
- Five Year survivalof ESRD
- All ages: 38%
- Age over 65 years: 18%
XXX. References
- (2018) Presc Lett 25(8)
- Golder (2003) AAFP Board Review, Seattle
- (2002) Am J Kidney Dis 39:s1-266 [PubMed]
- Baumgarten (2011) Am Fam Physician 84(10): 1138-48 [PubMed]
- Gaitonde (2017) Am Fam Physician 96(12): 776-83 [PubMed]
- Hood (1996) Postgrad Med 100(5):163-75 [PubMed]
- Snyder (2005) Am Fam Physician 72(9):1723-32 [PubMed]
- (2007) Am J Kidney Dis 49(2 suppl 2):S12-S154 [PubMed]
- O'Connor (2012) Am Fam Physician 85(7):705-10 [PubMed]
- Rivera (2012) Am Fam Physician 86(8): 749-54 [PubMed]
- Wouk (2021) Am Fam Physician 104(5): 493-99 [PubMed]