Chronic Kidney Disease

- Nephrotic: proteinuria (>3.5 g/day), hypoalbuminemia, hyperlipidemia, and edema - Minimal change disease, membranous nephropathy, focal segmental glomerulosclerosis - Amyloidosis, diabetic nephropathy

- GFR can be estimated by multiple equations (freely available in medical calculators), including MDRD equation: - GFR (mL/min/1.73 m2) = 175 пїЅ [(serum Cr Ојmol/1/88.4)-1.154] пїЅ [age (years)-0.203] пїЅ 0.742 for females or 1.21 for African American - Often used as estimate in electronic health records

- Cr clearance (CrCl) can be calculated using Cockroft-Gault formula - CrCl (male) = ([140 - age] пїЅ weight (kg)/(serum Cr пїЅ 72)] - CrCl (female) = CrCl (male) пїЅ 0.85 - Formula used for determining cut points for renally adjusted medications

- Urine analysis - Urine microscopy: WBC casts in pyelonephritis, RBC casts in glomerulonephritis/vasculitis, dysmorphic RBCs - Urine electrolytes: sodium, Cr, urea (if on loop diuretics) - Proteinuria/albuminuria - 24-hour urine collection: >30 to 300 mg/24 hr (20 to 200 Ојg/min) is microalbuminuria and >300 mg/24 hr (>200 Ојg/min) is macroalbuminuria. - Albumin/Cr ratio (ACR): See "Description."пїЅ

- Hematology: normochromic, normocytic anemia; increased bleeding time - Chemistry - Elevated BUN, Cr, hyperkalemia, metabolic acidosis - Increased parathyroid hormone, decreased 25-(OH) vitamin D, hypocalcemia, hyperphosphatemia - Hyperlipidemia, decreased albumin

11 Mancia пїЅG, Fagard пїЅR, Narkiewicz пїЅK, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31(7):1281-1357.22 Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Inter Suppl. 2013;3:1-150. www.kdigo.org/clinicalpracticeguidelines/pdf/CKD/KDIGO2012CKD_GL.pdf

para>GFR normally decreases with age, despite normal creatinine (Cr). Adjust renally cleared drugs for GFR in the elderly. пїЅ

Pediatric Considerations

CKD definition is not applicable for children <2 years because of lower GFR even when corrected for body surface area. Calculated GFR based on serum Cr is used in this age group.

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Pregnancy Considerations

Renal function in CKD may deteriorate during pregnancy. Cr >1.5 and hypertension (HTN) are major risk factors for worsening renal function.
Increased risk of premature labor, preeclampsia, and/or fetal loss
ACE inhibitors and angiotensin receptor blockers (ARBs) are contraindicated due to teratogenicity. Use diuretics with caution.

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EPIDEMIOLOGY

Majority of people with CKD in stages 1 to 3
African Americans are 3.6 times more likely to develop CKD than Caucasians.
Predominant sex: Similar in both sexes; however, incidence rate of end-stage renal disease (ESRD) is 1.6 times higher in males than females.

Incidence

Estimated annual incidence of 1,700/1 million population пїЅ

Prevalence

Overall prevalence of CKD is 14.2%. Unadjusted prevalence/incidence rates of ESRD (stage 5) are 1,752 and 362.4/1 million, respectively. Numbers do not reflect the burden of earlier stages of CKD (stages 1 to 4), which are estimated to affect 13.1% of the population nationwide or 26.3 million in the United States. пїЅ

ETIOLOGY AND PATHOPHYSIOLOGY

Progressive destruction of kidney nephrons; GFR will drop gradually, and plasma Cr values will approximately double, with 50% reduction in GFR and 75% loss of functioning nephrons mass. Hyperkalemia usually develops when GFR falls to <20 to 25 mL/min. Anemia develops from decreased renal synthesis of erythropoietin. пїЅ

Renal parenchymal/glomerularNephritic: hematuria, RBC casts, HTN, variable proteinuriaFocal proliferative: IgA nephropathy, systemic lupus erythematosus (SLE), Henoch-Sch пїЅnlein purpura, Alport syndrome, proliferative glomerulonephritis, crescentic glomerulonephritisDiffuse proliferative: membranoproliferative glomerulonephritis, SLE, cryoglobulinemia, rapidly progressive glomerulonephritis (RPGN), Goodpasture syndromeNephrotic: proteinuria (>3.5 g/day), hypoalbuminemia, hyperlipidemia, and edemaMinimal change disease, membranous nephropathy, focal segmental glomerulosclerosisAmyloidosis, diabetic nephropathy
Vascular: HTN, thrombotic microangiopathies, vasculitis (Wegener), scleroderma
Interstitial-tubular: infections, obstruction, toxins, allergic interstitial nephritis, multiple myeloma, connective tissue disease, cystic disease
Postrenal: obstruction (benign prostatic hyperplasia), neoplasm, neurogenic bladder

Genetics

Alport syndrome, Fabry disease, sickle cell anemia, SLE, and autosomal dominant polycystic kidney disease can lead to CKD.
Polymorphisms in gene that encodes for podocyte nonmuscle myosin IIA are more common in African Americans than Caucasians and appear to increase risk for nondiabetic ESRD.

RISK FACTORS

Type 1 or 2 diabetes mellitus (DM); most common
Age >60 years
Cardiovascular disease (e.g., HTN [common], renal artery stenosis, atheroemboli)
Previous kidney transplant
Urinary tract obstruction (e.g., benign prostatic hyperplasia)
Autoimmune disease, vasculitis/connective tissue disorder
Family history of CKD
Nephrotoxic drugs (lithium, salicylate, high-dose or chronic NSAIDs, sulfa)
Congenital anomalies, obstructive uropathy, renal aplasia/hypoplasia/dysplasia, reflux nephropathy
Hyperlipidemia
Low income/education/ethnic minority status
Obesity/smoking/heroin use
Chronic infection (hepatitis B, hepatitis C, HIV)

GENERAL PREVENTION

Treat reversible causes: hypovolemia, infections, diuretics, drugs (NSAIDs, aminoglycosides, IV contrast).
Treat risk factors: DM, HTN, hyperlipidemia, smoking, and obesity; adjust medication doses to prevent renal toxicity.

COMMONLY ASSOCIATED CONDITIONS

HTN, DM, cardiovascular disease пїЅ

DIAGNOSIS

HISTORY

Patients with CKD stages 1 to 3 are usually asymptomatic; can present with пїЅ

Oliguria, nocturia, polyuria, hematuria, change in urinary frequency
Bone disease
Edema, HTN, dyspnea
Fatigue, depression, weakness
Pruritus, ecchymosis
Metallic taste in mouth, anorexia, nausea, vomiting
Hyperlipidemia, claudication, restless legs
Erectile dysfunction, decrease libido, amenorrhea

PHYSICAL EXAM

Volume status (pallor, BP/orthostatic; edema; jugular venous distention; weight)
Skin: sallow complexion, uremic frost
Ammonia-like odor (uremic fetor)
Cardiovascular: Assess for murmurs, bruits, pericarditis.
Chest: pleural effusion
Rectal: enlarged prostate
CNS: asterixis, confusion, seizures, coma, peripheral neuropathy

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

GFR can be estimated by multiple equations (freely available in medical calculators), including MDRD equation:GFR (mL/min/1.73 m2) = 175 пїЅ [(serum Cr Ојmol/1/88.4)-1.154] пїЅ [age (years)-0.203] пїЅ 0.742 for females or 1.21 for African AmericanOften used as estimate in electronic health records
Cr clearance (CrCl) can be calculated using Cockroft-Gault formulaCrCl (male) = ([140 - age] пїЅ weight (kg)/(serum Cr пїЅ 72)]CrCl (female) = CrCl (male) пїЅ 0.85Formula used for determining cut points for renally adjusted medications
Urine analysisUrine microscopy: WBC casts in pyelonephritis, RBC casts in glomerulonephritis/vasculitis, dysmorphic RBCsUrine electrolytes: sodium, Cr, urea (if on loop diuretics)Proteinuria/albuminuria24-hour urine collection: >30 to 300 mg/24 hr (20 to 200 Ојg/min) is microalbuminuria and >300 mg/24 hr (>200 Ојg/min) is macroalbuminuria.Albumin/Cr ratio (ACR): See "Description."пїЅ
Hematology: normochromic, normocytic anemia; increased bleeding time
ChemistryElevated BUN, Cr, hyperkalemia, metabolic acidosisIncreased parathyroid hormone, decreased 25-(OH) vitamin D, hypocalcemia, hyperphosphatemiaHyperlipidemia, decreased albumin

ALERT

Drugs that may alter lab result:

Cimetidine: inhibits Cr tubular secretion
Trimethoprim: inhibits Cr and K+ secretion and may cause/worsen hyperkalemia
Cefoxitin and flucytosine: increases serum Cr
Diltiazem and verapamil (like ACE/ARBs) have significant antiproteinuric effects in patients with CKD.
Ultrasound (initial test of choice): Small, echogenic kidneys; may see obstruction (e.g., hydronephrosis); cysts; kidneys may be enlarged with HIV and diabetic nephropathy.
Doppler ultrasound to assess for renovascular disease, thrombosis
Noncontrast CT scan: obstruction, calculi, cysts, neoplasm, renal artery stenosis
MRI/MRA: Avoid gadolinium because of the risk of nephrogenic systemic fibrosis.
Renal arteriogram for renal artery stenosis can be therapeutic (angioplasty or stenting).
Renal scan to screen for differential function between kidneys
Retrograde pyelogram: if strong suspicion for obstruction despite negative finding on ultrasound

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Follow-Up Tests & Special Considerations

Serology: antinuclear antibody (ANA); double-stranded DNA, antineutrophil cytoplasmic antibody; complements (C3, C4, CH50); anti-glomerular basement membrane (GBM) antibodies; hepatitis B, C; and HIV screening
Serum and urine immunoelectrophoresis

Diagnostic Procedures/Other

Biopsy: hematuria, proteinuria, acute/progressive renal failure, nephritic or nephrotic syndrome пїЅ

TREATMENT

GENERAL MEASURES

Lowering salt intake to <2 g/day of sodium in adults, unless contraindicated (1)[C]
Minimize radiocontrast exposure; prehydrate; N-acetylcysteine use is controversial. Avoid nephrotoxins (NSAIDs, aminoglycosides, etc.).
Renal replacement: Prepare for dialysis or transplant when GFR <30 mL/min/1.73 m2.
Vaccines: pneumococcal, influenza
Encourage smoking cessation, encourage weight loss (if applicable), and limit alcohol consumption.

MEDICATION

ISSUES FOR REFERRAL

Nephrology consult: GFR <15: immediate
GFR 15 to 29: urgent
GFR 30 to 59: nonurgent referral
GFR 60 to 89: not required unless with comorbidities

SURGERY/OTHER PROCEDURES

Placement of dialysis access or transplantation пїЅ

INPATIENT CONSIDERATIONS

Admission Criteria/Initial Stabilization

Uremia: nausea/vomiting, fluid overload, pericarditis, uremic encephalopathy, resistant HTN, hyperkalemia, metabolic acidosis, hyperphosphatemia пїЅ

ONGOING CARE

DIET

Nutrition consult for CKD diet: Protein restriction in early CKD is controversial but may be beneficial in ESRD; restricted intake of phosphates; sodium and water restriction to avoid volume overload; potassium restriction if hyperkalemic пїЅ

PATIENT EDUCATION

National Kidney Federation patient Web site at: http://www.kidney.org/patients пїЅ

PROGNOSIS

Patients with CKD gradually progress to ESRD, with bad prognoses. 5-year survival rate for U.S. patients on dialysis is ~35%. пїЅ

COMPLICATIONS

HTN, anemia, secondary hyperparathyroidism, renal osteodystrophy, sleep disturbances, infections, malnutrition, electrolyte imbalances, platelet dysfunction/bleeding, pseudogout, gout, metabolic calcification, sexual dysfunction пїЅ

REFERENCES

CODES

ICD10

N18.9 Chronic kidney disease, unspecified
Q63.9 Congenital malformation of kidney, unspecified
N18.3 Chronic kidney disease, stage 3 (moderate)
Q61.4 Renal dysplasia
Q61.8 Other cystic kidney diseases
Q61.5 Medullary cystic kidney
N18.5 Chronic kidney disease, stage 5
N18.4 Chronic kidney disease, stage 4 (severe)
N18.1 Chronic kidney disease, stage 1
N18.6 End stage renal disease
N18.2 Chronic kidney disease, stage 2 (mild)

ICD9

585.9 Chronic kidney disease, unspecified
753.3 Other specified anomalies of kidney
585.3 Chronic kidney disease, Stage III (moderate)
753.15 Renal dysplasia
753.10 Cystic kidney disease, unspecified
585.6 End stage renal disease
585.4 Chronic kidney disease, Stage IV (severe)
585.2 Chronic kidney disease, Stage II (mild)
585.1 Chronic kidney disease, Stage I
753.16 Medullary cystic kidney
585.5 Chronic kidney disease, Stage V

SNOMED

709044004 Chronic kidney disease (disorder)
44513007 Congenital anomaly of the kidney (disorder)
433144002 Chronic kidney disease stage 3 (disorder)
204949001 Renal dysplasia (disorder)
82525005 Congenital cystic kidney disease (disorder)
46177005 End stage renal disease (disorder)
433146000 Chronic kidney disease stage 5 (disorder)
431857002 Chronic kidney disease stage 4 (disorder)
431856006 Chronic kidney disease stage 2 (disorder)
431855005 Chronic kidney disease stage 1 (disorder)
204958008 Nephronophthisis (disorder)

CLINICAL PEARLS

Maintaining BP <140/90 mm Hg is imperative (in patients not on dialysis).
Avoid nephrotoxins including ACE/ARB in acute kidney injury (AKI) with or without CKD.
CKD is a CHD risk equivalent.