©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
in the clinic
Chronic Kidney Disease
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
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©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
What is the definition of chronic kidney disease (CKD)? The National Kidney Foundation Kidney Disease
Outcomes and Quality Initiative (KDOQI) guidelines define CKD as:
Kidney damage or a GFR <60 mL/min per 1.73 m2 for more than 3 mo
Functional abnormalities of the kidneys (proteinuria, albuminuria)
Abnormalities of the urinary sediment (dysmorphic erythrocytes)
Structural abnormalities as noted on imaging studies
This definition is controversial, because it labels older persons as having CKD if their GFR is <60 mL/min per 1.73 m2 (may be within normal range for older persons) but they have no evidence of kidney damage
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
What factors increase the risk for CKD?
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
How should clinicians screen patients for CKD? Many guidelines do not recommend population-based
screening for CKD in all adults
KDOQI guidelines of the National Kidney Foundation (NKF) do recommend screening individuals at increased risk for CKD
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
What can clinicians and patients do to prevent CKD? Primary prevention of CKD must address 2 principal risk
factors: diabetes and hypertension
For patients with diabetes, KDOQI guidelines recommend a hemoglobin A1c level <7.0%
Some data indicate that risk for cardiovascular disease (CVD) increases when hemoglobin A1c level is <6.5%
Patients with CKD due to diabetes might aim for a hemoglobin A1c level about 7.5% but not <7.0% while awaiting further evidence
Hypertension is the second most common risk factor for CKD in the U.S.
Blood pressure goal <140/90 mm Hg (<130/80 mm Hg if diabetes or CVD) through lifestyle modification and antihypertensive drugs, according to JNC 7 guidelines
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
Screening and Prevention
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
How should clinicians classify CKD and construct a differential diagnosis?
3 broad categories of CKD based on KDOQI guidelines
Diabetic kidney disease
Nondiabetic kidney disease (with subcategories of glomerular, tubulointerstitial, vascular [including hypertension], and cystic)
Kidney disease in the transplant recipient (including long-term rejection, drug toxicity, recurrent diseases, or transplant glomerulopathy)
Hypertension is more often a consequence of advancing CKD than a cause
However, African Americans with hypertension are particularly likely to develop CKD
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
What elements of the history and physical examination may be useful in determining the cause of CKD?
History of long-standing, poorly controlled diabetes or other diabetic complications
History of hypertension with hypertensive retinopathy or a family history of hypertension with CKD
Heart failure/cirrhosis leading to decreased renal perfusion
Risk factors for proteinuria + CKD (e.g., IV drug use, high-risk sex, history of hepatitis B or C or HIV infection)
Family history of kidney disease (e.g., polycystic kidneys, Alport disease)
Medications that may cause CKD or need dose adjustment
History of conditions causing dehydration, diarrhea, bleeding -- both short- and long-term effects on GFR
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
What elements of the history and physical examination may be useful in determining the cause of CKD?
Symptoms of autoimmune disease (rash, arthritis, constitutional symptoms)
Fundiscopic examination for diabetic or hypertensive retinopathy
Evidence of fluid overload (edema, crackles)
Orthostatic hypotension
Renal bruit
Asterixis, mental status changes signifying Encephalopathy
Pericaridal rub from uremia
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
What other studies should clinicians obtain in evaluating patients with CKD?
Estimate GFR (eGFR), serum electrolytes
Complete blood cell count; lipid profile; uric acid; serum albumin; spot urine albumin-creatinine or protein-creatinine ratio
Urinalysis for specific gravity, pH, erythrocytes, leukocyte counts
Proteinuria
Hematuria and other urinary sediment abnormalities. Dysmorphic erythrocytes/erythrocyte casts suggest active glomerular disease
Renal ultrasonography
If GFR <60 mL/min per 1.73 m2, serum calcium, phosphorus, parathyroid hormone, vitamin D levels to assess secondary hyperparathyroidism
ANA for lupus, serum antineutrophil cytoplasmic antibodies for vasculitis, hepatitis B/C, HIV serology
Patients >40 y, serum and urine protein immunoelectrophoresis for multiple myeloma
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
How should clinicians estimate GFR and the stage of CKD?
Estimate GFR with Modification of Diet in Renal Disease (MDRD) equation
Classify the stage of CKD according to the patient's GFR
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
When should clinicians ask a nephrologist to evaluate a patient in the early stages of CKD?
Obtain a nephrology consultation for:
Proteinuria >3.5 g per 24 h
Evidence of nephritis (hematuria, proteinuria, and hypertension)
An eGFR decline of 50% within a 1-year period
Type 2 diabetes with proteinuria but without retinopathy or neuropathy
KDOQI guidelines recommend referral for all patients with a GFR <30 mL/min per 1.73 m2
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
What are structural abnormalities of the kidney and their significance?
UltrasonographyGeneral appearance Nephrocalcinosis, stones, cysts, masses,
hydronephrosisIncreased echogenicity Cystic diseaseSmall, hyperechoic kidneys Usually indicates chronic kidney diseaseLarge kidneys Tumors, infiltrating disease, causes of the
nephritic syndrome, cystic diseaseSize difference / scarring Suggests vascular, urologic, or interstitial
diseaseDoppler interrogation May help detect venous thrombosisIntravenous pyelography Asymmetry of structure or function, stones, medullary sponge kidneyComputed tomography Obstruction, tumors, cysts, ureteral calculi MRI Masses, cysts, renal vein thrombosis renal artery stenosisNuclear scanning Asymmetry, renal artery stenosis, acute
pyelonephritis, scars
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
Diagnosis
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
What dietary modifications delay the progression of CKD?
DASH (Dietary Approaches to Stop Hypertension) diet
For prehypertension or stage 1 hypertension
High in fruits, vegetables, and dairy foods with little total saturated fat and cholesterol
Only for patients with a GFR >60 mL/min per 1.73 m2
because DASH has more protein, potassium, and phosphorous than recommended for stage 3 or 4 CKD
Restrict dietary sodium to <2.4 g/d
Patients with CKD and hypertension
Low-protein diet (0.6 g/kg per d)
Patients with stage 4 or 5 CKD
Should be well-nourished and under the care of a dietician specializing in renal disease
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
What drugs and other agents cause acute kidney injury in patients with CKD? Avoid known nephrotoxic agents (aminoglycoside
antibiotics, amphotericin B, nonsteroidal anti-inflammatory drugs ) and radiocontrast agents
If radiocontrast unavoidable, consider giving sodium bicarbonate, 0.45% normal saline, or N-acetylcysteine intravenously before and after the procedure
Whether these agents reduce contrast-induced nephropathy in patients with CKD is controversial
Avoid high doses of gadolinium contrast in patients with CKD stages 4 and 5
Increases risk for nephrogenic systemic fibrosis
Avoid metformin in patients with diabetes and CKD
Increases the risk for lactic acidosis
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
What is the role of blood pressure management in patients with CKD?
Treatment of hypertension reduces risk for CVD in patients with CKD; goal BP <130/80 mm Hg
CKD + hypertension often requires combination therapy to controlBP
For diabetic CKD or nondiabetic CKD with proteinuria, use an ACE inhibitor or an ARB
For CVD risk reduction, diuretics may be preferred, especially in the absence of diabetes and without proteinuria
Diuretics are often the base of combination therapy; they reduceextracellular fluid volume, lower BP, reduce risk for CVD in CKD
Level of GFR informs diuretic choice
Thiazide-type diuretic for eGFR >30 mL/min per 1.73 m2
Loop diuretic (furosemide) for eGFR <30 mL/min per 1.73 m2
Thiazides may potentiate effects of ACE inhibitors/ARBs/other antihypertensive agents
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
What is the role of glycemic control in patients with diabetes and CKD?
Poor glycemic control associated with development and progression of diabetic nephropathy
Causes alterations in tubuloglomerular feedback, abnormalities in polyol metabolism, and formation of advanced glycation endproducts
Recent evidence suggests that managing to a target hemoglobin A1c level of about 7.5% may be optimal
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
When should clinicians prescribe ACE inhibitors or ARBs to patients with CKD? Diabetes/proteinuria: main indications for ACE inhibitors/
ARBs
For diabetic kidney disease or spot urine total protein-creatinine ratio >200 mg/g, ACE inhibitor/ARBs initial antihypertensive agents
ACE inhibitor + ARB combined not recommended
Reduces proteinuria short-term
But increased risk for negative renal effects
No reduction major CV events
Check salt-depleted patients treated with ACE inhibitors/ARBs for hypotension, decline in GFR, hyperkalemia
Check within 12 wk of starting therapy or altering the dose
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
What metabolic complications occur with CKD and how to manage them?
Hyperphosphatemia and vitamin D deficiency
Causes hypocalcemia leading to secondary hyperparathyroidism, linked to renal osteodystrophy / increased mortality in dialysis patients
Significant derangements occur at GFR <30-40 mL/min per 1.73 m2
KDOQI guidelines: Dietary phosphorous restriction, phosphate binders, vitamin D supplementation
Hyperkalemia Mild elevations stage 3, severe elevations stages 4/5
Dietary restriction + prescription of sodium polystyrene sulfonate resin
Emergency treatment: IV calcium gluconate, IV glucose and insulin, IV bicarbonate for acidosis, sodium polystyrene sulfonate
Severe metabolic acidosis Rarely occurs until GFR is <30 mL/min per 1.73 m2
KDOQI guidelines: Treat with alkali to maintain serum bicarbonate levels >22 mmol/L
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
Should clinicians treat anemia in patients with CKD?
Anemia associated with decreased quality of life, left-ventricular hypertrophy, cardiovascular complications
Patients with normocytic, normochromic anemia, and a low reticulocyte count probably have anemia of CKD
Measure hemoglobin and hematocrit, erythrocyte indices, reticulocyte count, serum iron levels, total iron-binding capacity, percent transferrin saturation, serum ferritin levels in patients with anemia and CKD
In iron-deficient patients, look for a source of GI bleeding
Do not try to "normalize" hemoglobin levels
Adequate iron stores are necessary for successful treatment of anemia of CKD
Prescribe oral or intravenous iron as needed
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
How to treat cardiovascular risk factors in patients with CKD?
Measure BP, screen for diabetes, and treat hypertension and diabetes
Assess cardiovascular risk factors
Aggressively promote standard lifestyle recommendations
KDOQI expert panels recommend Adult Treatment Panel III guidelines to treat dyslipidemia in patients with stage 1-4 CKD
Obtain lipid profile annually or if kidney function worsens
Reduce LDL cholesterol <100 mg/dL after 3 mo of therapeutic lifestyle changes and treat with statins
Use fibrates to treat severe hypertriglyceridemia (>500 mg/dL) after trying lifestyle changes
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
How should clinicians monitor the progression of CKD? Annual assessment of BP; measurement of eGFR;
hemoglobin level; and serum potassium, calcium, phosphorous, parathyroid hormone, and albumin levels
Monitor more frequently if:
eGFR <60 mL/min per 1.73 m2
Rapid decline in kidney function (>4 mL/min per 1.73 m2
per year)
Risk factors for faster progression (smoking, poorly controlled hypertension or diabetes, older age, and proteinuria)
Exposure to a known cause of acute kidney injury (such as radiocontrast agents)
Active treatment of CKD, hypertension, or proteinuria
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
What are the indications for renal replacement therapy in patients with CKD?
Absolute indications
Volume overload unresponsive to diuretics
Pericarditis
Uremic encephalopathy
Major bleeding secondary to uremic platelet dysfunction
Hypertension that does not respond to treatment
Relative indications
Hyperkalemia
Moderate metabolic acidosis
Hyperphosphatemia
Hypercalcemia or hypocalcemia
Anemia
Subjective relative indications: fatigue, nausea and vomiting, loss of appetite, evidence of malnutrition, insomnia
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
When to refer patients with CKD to a nephrologist?
Advanced/complex renal disease or chronic glomerular diseases (often require immunosuppressive therapy)
Assistance in formulating or implementing a care plan for CKD
Consult no later than when the eGFR first falls <30 mL/min per 1.73 m2
To discuss treatment modalities for end-stage renal disease (peritoneal dialysis, hemodialysis, renal transplantation)
To prepare patients by providing counseling, psychoeducational interventions
To refer for dialysis access (peritoneal or hemodialysis)
Initiate dialysis promptly when appropriate
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
Treatment
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
What do professional organizations recommend with regard to prevention, screening, diagnosis, and treatment of CKD?
Many of the recommendations come from guidelines developed by the National Kidney Foundation (NKF) as part of their Kidney Disease Outcomes and Quality Initiative (KDOQI)
Prevention: Maintaining hemoglobin A1c level at <7.0%
Screening: Individuals at increased risk for CKD
Diagnosis: 3 broad categories, including diabetic kidney disease, nondiabetic kidney disease, and kidney disease in the transplant recipient
Treatment: Slow progression of disease and prevent cardiovascular complications
©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.
What measures do stakeholders use to evaluate the quality of care for patients with CKD?