Shaun G.S. Grewal, MD
Gerald L. Andriole, MD, FACS
BASICS
DESCRIPTION
• Defined as presence of kidney damage or impaired GFR (<60 mL/min/1.73 m2) for >3 mo (1)
– if less than 3 months considered acute kidney injury (AKI)
– Irrespective of cause kidney damage defined as:
Pathologic abnormalities
Urinary, blood, or imaging abnormalities
Kidney transplantation
• Classification based on Kidney Disease Outcomes Quality Initiative (NKF KDOQI):
– Stage 1: Kidney damage with normal renal function (GFR >90 mL/min/1.73 m2)
– Stage 2: Mild renal dysfunction (GFR 60–89 mL/min/1.73 m2)
– Stage 3: Moderate renal dysfunction (GFR 30–59 mL/min/1.73 m2)
– Stage 4: Severe renal dysfunction (GFR 15–30 mL/min/1.73 m2)
– Stage 5: Kidney failure (GFR <15 or dialysis mL/min/1.73 m2)
EPIDEMIOLOGY
Incidence
• Stage 1 or 2 CKD progress to more advanced stages at 0.5% per year
• Stage 3 or 4 progress to end-stage renal disease at 1.5% per year (3)
Prevalence
• 10% in noninstitutionalized adults
– Corresponds to >20 million people (4)
– 398,000 treated by dialysis in 2000, expected to increase to >2 million people by 2030 (2)
– Prevalence in US population
Stage 1: 1.8%
Stage 2: 3.2%
Stage 3: 7.7%
Stage 4/5: 0.35% (3)
RISK FACTORS
• Diabetes
• Hypertension
• Cardiovascular disease
• Family history
• Age >60
• Urinary tract obstruction
• Urinary calculi
• Nephrotoxic drugs
• Obesity
• Neoplasia
• Loss of kidney mass
• Race
– African American, American Indian, Hispanic, Asian, or Pacific Islander
Genetics
• Complex phenotype impacted by various genetic factors in addition to environmental factors and comorbid disease
– CYP4A11 gene involved in renal vasoconstriction and natriuresis and is associated with increased risk in African Americans (6)
– APOL1 associated with focal segmental glomerulosclerosis and hypertension associated ESRD (7)
PATHOPHYSIOLOGY
• Heterogenous condition with various causes
– Diabetic kidney disease
– Nondiabetic kidney disease
Glomerular disease
Vascular diseases
Tubulointerstitial disease
Cystic disease (polycystic kidney disease)
– Transplant nephropathy
Acute rejection
Chronic rejection
Calcineurin toxicity
Glomerulonephropathy
ASSOCIATED CONDITIONS
See risk factors
GENERAL PREVENTION
• Screening and treatment of associated risk factors
– Screening selected populations:
Age >50
History of DM (diabetes melitus), HTN (hypertension), or CV (cardiovascular) disease
Family history
Exposure to nephrotoxins
DIAGNOSIS
HISTORY
• Silent, asymptomatic until late stages
– Evaluate for symptoms of associated conditions/risk factors
• Symptoms of uremia in ESRD
– Anorexia
– Decreased urine output
– Increased thirst
– Mental status changes
– Muscle cramps
– Nausea
– Vomiting
PHYSICAL EXAM
• Physical exam findings uncommon until late stages of disease
– Findings associated with increased risk
BP >130/85
Obesity/increased waist circumference
– Manifestations of advanced kidney disease
Volume overload/edema
Pruritus
Visual disturbances
Weight Loss
Confusion
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Chemistry
– Elevated creatinine
– Elevated blood urea nitrogen
– Hyperkalemia
– Acidosis
– Hyperphosphatemia
• Urinalysis with microscopy
– Hematuria
– Casts: RBC (glomerulonephritis), WBC (interstitial nephritis)
– Fat bodies (nephrotic syndrome)
• Hyperparathyroidism
– Results from altered calcium and phosphorus metabolism
• Anemia
• Proteinuria/albuminuria
– Albuminuria indicates increased glomerular permeability to macromolecules
– Albumin to creatinine ratio >30 mg/g indicates increased risk of CKD progression, ESRD, cardiovascular and all cause mortality.
• GFR
– Estimated GFR (mL/min/1.73 m2) = 1.86 × (SCR)−1.154 × (age)−0.203 × (0.742 if female) × (1.1212 if African American)
Imaging
• Broad range of findings depending on etiology and imaging modality (US, CT scan, MRI, angiography, isotope scans)
– Hydronephrosis: Potentially reversible
– Polycystic kidneys
– Atrophic kidneys
– Increased echogenicity (on ultrasound)
– Renal artery stenosis
– Cortical scarring
Diagnostic Procedures/Surgery
• Renal biopsy is indicated in selected cases and choices can vary greatly with nephrologists
– Isolated glomerular hematuria with proteinuria
– Nephrotic syndrome
– Acute nephritic syndrome
– Acute/rapidly progressive kidney disease
• Urologic evaluation if gross or microscopic hematuria
– Cystoscopy
– Upper tract imaging
• Angiography (CT or MR angiogram) if suspected atherosclerotic renovascular disease (asymmetric renal size)
Pathologic Findings
• Renal biopsy findings
– Reveals tubulointerstitial, glomerular, or vascular disease
– May also be seen on nephrectomy/partial nephrectomy specimens
DIFFERENTIAL DIAGNOSIS
• Kidney damage with duration >3 mo is diagnostic regardless of cause
• Differentiate from acute kidney disease based on duration and underlying etiology
– Acute kidney injury
– Alport syndrome
– Autosomal dominant polycystic kidney disease.
– Chronic glomerulonephritis
– Diabetic nephropathy
– Goodpasture syndrome
– Multiple myeloma
– Nephrolithiasis
– Nephrosclerosis
– Rapidly progressive glomerulonephritis
– Renal artery stenosis
– Systemic lupus erythematosus
– Urinary obstruction
– Wegener granulomatosis
TREATMENT
GENERAL MEASURES
• Use CKD staging to guide management (ie, risk for progression and complications of CKD). See table in Section II “Chronic Kidney Disease (CKD).”
• Goal is reduction of morbidity and mortality from associated comorbidities
– Patient more likely to die of cardiovascular disease than progress to dialysis (3)
– Blood glucose control (HbA1c <7)
– Treatment of proteinuria and hypertension
– Treatment of dyslipidemia to prevent cardiovascular events
– Addressing alterations in bone metabolism (hyperphosphatemia, Vitamin D deficiency)
– Prevention of contrast-induced nephropathy (patient at risk if GFR <60)
– Avoidance of Gadolinium when GFR <30 to prevent nephrogenic systemic fibrosis
MEDICATION
First Line
• ACE inhibitors (ACE-I) (captopril, enalapril, ramipril, others) or angiotensin II receptor blockers (ARBs) (losartan, olmesartan, telmisartan others)
– Indicated with random protein to creatinine ratio >200 mg/G
– Do not use ACE-I and Angiotensin II receptor blockers (ARBs) concurrently: Risk of hypotension and worsening renal function
– Monitor for hypotension, hypokalemia, or worsening renal function
– Common ACE-I side effects include cough, angioedema, or allergy
• Statin therapy
– Goal LDL (low density lipids) <100 and triglyceride <150
– Side effects include myalgia, liver dysfunction, GI disturbance, and rash
Second Line
• Erythropoiesis-stimulating agents
– Optimal hemoglobin unknown
– Increased risk of cardiovascular events and death with hemoglobin >11 g/dL
– Indicated to prevent transfusion-related risks (patient with Hg <10 and rate of decline suggesting need for blood transfusion)
Examples include erythropoietin α and darbepoetin α
SURGERY/OTHER PROCEDURES
• Dialysis access as appropriate (vascular or peritoneal)
• Renal transplantation
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
• Dietary modifications
• Patient education
• Smoking cessation
• Weight loss
Complementary & Alternative Therapies
Avoidance of herbal remedies which may have nephrotoxic effects.
ONGOING CARE
PROGNOSIS
• Variable depending on stage, patient risk factors, and management of comorbidities
– 10–100 × increased risk of cardiovascular comorbidities in ESRD patients
– 13–29% 1-yr mortality in patients initiating hemodialysis (5)
COMPLICATIONS
• CKD patients at increased risk of progression, cardiovascular disease, hypertension, anemia, disorders of mineral metabolism, and death
• Degree of proteinuria correlates with risk of progression
FOLLOW-UP
Patient Monitoring
• Stage 1-2
– Monitor GFR, proteinuria, and blood pressure
Clinical abnormalities rare at this stage but patients must be monitored for progression
Monitor HbA1c and microalbumin in diabetics
Evaluation every 12 mo, at least every 6 mo if proteinuria present
• Stage 3
– Monitor GFR, proteinuria, blood pressure, HbA1c, serum electrolytes, and hemoglobin
Elevations of phosphorous, potassium, and anemia may be seen
Evaluation every 3 mo
Referral to nephrology when GFR approaches 30 mL/min
• Stage 4
– Monitor GFR, proteinuria, blood pressure, HbA1c, serum electrolytes, and hemoglobin
Significant electrolyte abnormalities common; monthly follow-up with nephrology
• Stage 5
– Severe electrolyte abnormalities and anemia present: Ongoing follow-up with renal replacement therapy
Patient Resources
• National Kidney Foundation
– www.kidney.org/patients
REFERENCES
1. National Kidney Foundation : K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis. 2002;39:S1–S266.
2. Coresh J, Byrd-Holt D, Astor BC, et al. Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000. J Am Soc Nephrol. 2005;16:180–188.
3. Stevens LA, Li S, Wang C, et al. Prevalence of CKD and comorbid illness in elderly patients in the United States: Results from the Kidney Early Evaluation Program (KEEP). Am J Kidney Dis. 2010;55(3 suppl 2):S23–S33.
4. Coresh J, Astor BC, Greene T, et al. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis. 2003;41:1–12.
5. Chan M, Dall AT, Fletcher KE, et al. Outcomes in patients with chronic kidney disease referred late to nephrologists: A meta-analysis. Am J Med. 2007;120:1063–1070.
6. Keene KL, Mychaleckyj JC, Leak TS, et al. Exploration of the utility of ancestry informative markers for genetic association studies of African Americans with type 2 diabetes and end stage renal disease. Hum Genet. 2008;124:147–154.
7. Hsu CC, Kao WH, Coresh J, et al. Apolipoprotein E and progression of chronic kidney disease. JAMA. 2005;293:2892–2899.
ADDITIONAL READING
KDIGO. Summary of recommendation statements. Kidney Int. 2013;3(suppl):5.
See Also (Topic, Algorithm, Media)
• Acute Kidney Injury, Adult (Renal Failure, Acute)
• Chronic Kidney Disease, Pediatric (Renal Failure, Chronic)
• See Table in Section II “Chronic Kidney Disease (CKD).”
CODES
ICD9
• 585.5 Chronic kidney disease, Stage V
• 585.6 End stage renal disease
• 585.9 Chronic kidney disease, unspecified
ICD10
• N18.5 Chronic kidney disease, stage 5
• N18.6 End stage renal disease
• N18.9 Chronic kidney disease, unspecified
CLINICAL/SURGICAL PEARLS
• Degree of proteinuria predicts progression.
• Differentiate from acute renal failure based on duration.
• Treat potentially reversible causes (ie, hydronephrosis).