II. Definitions
- Chronic Kidney Disease
- Abnormal Kidney structure or function lasting more than 3 months, with associated health implications
- Estimated Glomerular Filtration Rate (eGFR) <60 ml/min OR
- Positive Kidney damage markers (e.g. albuminuria) OR
- Polycystic or dysplastic Kidneys
-
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. Precautions
- Chronic Kidney Disease diagnosis and prevention has a significant impact on morbidity and mortality
- Yet up to 90% of those with CKD are undiagnosed
- However, there is also an expected physiologic decrease in eGFR with age
- There is an associated overdiagnosis of CKD without microabluminuria in over age 65 to 75 years old
- In elderly patients, eGFR alone does not predict who will advance to ESRD
- Employ Shared Decision Making in CKD at advanced age and Exercise caution in aggressive management
- Ellam (2016) BMJ 352: h6559 [PubMed]
- Liu (2021) JAMA Intern Med 181(10): 1359-66 [PubMed]
- Roth (2023) Am Fam Physician 107(6): 657-8 [PubMed]
V. 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)
- Chronic Viral Hepatitis (Hepatitis B, Hepatitis C)
- Malignancy (Multiple Myeloma, Renal Cell Cancer)
-
Glomerulonephritis and other glomerular diseases (21%)
- Includes Vasculitis and Autoimmune Conditions (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
- Infection with scarring
VI. 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
- Older age (>60 years)
- 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)
- Black patients have 3 fold greater risk of CKD than white patients
- Gender-related risk
- Chronic Kidney Disease (CKD) is more common in women
- Men are more likely to progress to End-stage Renal Disease (ESRD)
VII. 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
VIII. 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
IX. Symptoms: Stage 4-5
X. Signs
XI. 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
XII. 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 ml/min 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
XIII. Labs: Screening for Chronic Kidney Disease
- Indications
- Diabetes Mellitus
- Hypertension
- Cardiovascular disease
- 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)
- Serum Cystatin C may be used for confirmation (but not in AKI, inflammation or Thyroid dysfunction)
- Urine Albumin to Creatinine Ratio
- Urinalysis with microscopy
- Serum Creatinine (with Estimated Glomerular Filtration Rate)
- 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)
- https://www.kidney.org/professionals/kdoqi/gfr_calculator
- Do not use the race variable in the calculation
- Cockcroft-Gault equation
- Used only to calculate medication Renal Dosing
- Modification of Diet in Renal Disease (MDRD)
- CKD-EPI is preferred
- Chronic Kidney Disease Epidemiology Collaboration Equation or CKD-EPI (preferred standard)
- Estimations generally as accurate as 24 hour urine
- Assess for Proteinuria
- Proteinuria (and albuminuria) is a stronger predictor for CKD progression than eGFR
- Urine Albumin to Creatinine Ratio
- First morning void is preferred
- Persistently elevated levels >3 months is sufficient diagnostic criteria alone for Chronic Kidney Disease
- Background
- 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
- Urine Albumin to Creatinine Ratio is standardized whereas Protein to Creatinine ratio is lab assay specific
- 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
XIV. 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
XV. 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
XVI. Labs: Initial
- 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 and Serum Calcium)
- Fasting lipid profile
- Hemoglobin A1C
- Complete Blood Count (CBC)
- Serum Phosphorus (in CKD stage 4 to 5)
- 25-hydroxyvitamin D (in CKD stage 4 to 5)
- Other diagnostics
- Renal Ultrasound (see below)
- Baseline Electrocardiogram
- Coronary disease is a common complication of CKD
- 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
XVII. Labs: Monitoring in Advanced Disease (Stage 4 to 5 CKD)
-
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
- Screen for Anemia every 6 months in CKD 4 to 5 (every 12 months in CKD 3)
- Other labs to obtain at baseline in Anemia, and then as indicated
- Complete Blood Count with differential
-
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 6 to 12 months in CKD 3
- Obtain every 3 to 6 months in CKD 4
- Obtain every 1 to 3 months in CKD 5
- Serum Intact Parathyroid Hormone (iPTH)
- Obtain baseline, then as indicated
- Obtain every 6 to 12 months in CKD 4
- Obtain every 3 to 6 months in CKD 5
- 25-hydroxyvitamin D
- Obtain at baseline, then as indicated
- Dual Energy XRAY Absorptiometry (DEXA Scan)
- Obtain baseline in CKD 3 to 5, and then as indicated
XVIII. 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
XIX. Imaging: Other advanced imaging
- Consider CT or MRI of Kidneys and Liver
- Consider Voiding Cystourethrogram
XX. 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
XXI. Management: Secondary Prevention
XXII. Management: Nephrology Referral
- 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
- Indications
- Chronic Kidney Disease Stage 4 (GFR <30 ml/minute)
- One or more GFR values in past 12 months <30 mL/min
- Unexplained decline in GFR >15 mL/min between two readings
- Consider initial evaluation when GFR <60 ml/minute
- Blood Pressure > 130/80 (consistently) despite Antihypertensive medications
- Hemoglobin < 10 g/dL
- Hyperparathyroidism (PTH > 72 pg/mL) despite correcting for any Vitamin D Deficiency
- Chronic Kidney Disease with rapid progression
- Acute failure complicating Chronic Kidney Disease
- Unclear etiology for Renal Failure
- Hereditary Kidney Disease
- Renal biopsy
- Nephrotic sediment (e.g. lipiduria)
- Unexplained Microscopic Hematuria
- 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/day
- 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)
XXIII. Management: End Stage Renal Disease
- See End Stage Renal Disease for renal replacement, Anemia, Anorexia, Advanced Directives and other symptomatic management
XXIV. 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
- 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 Pericarditis or Hemodialysis Associated Pericarditis
- 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
- Bullous Disease of Hemodialysis (pseudoporphyria)
- Nephrogenic Fibrosing Dermopathy
- Acquired Perforating Dermatosis
- 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
XXV. Course
- Kidney Failure Risk Calculator
- 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
XXVI. Prognosis
XXVII. 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]
- Goodbred (2023) Am Fam Physician 108(6): 554-61 [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]