AITC-0902-Chronic_Kidney_Disease-RO

©Copyright Annals of Internal Medicine, 2009Ann Int Med. 150 (3): ITC2-1.

in the clinic

Chronic Kidney Disease


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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


What factors increase the risk for CKD?


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


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


Screening and Prevention


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


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


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


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


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


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


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


Diagnosis


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


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


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


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


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


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


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


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


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


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


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


Treatment


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


What measures do stakeholders use to evaluate the quality of care for patients with CKD?

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AITC-0902-Chronic_Kidney_Disease-RO