DESCRIPTION

• Kidney Disease: Improving Global Outcomes (KDIGO) categories by GFR estimation (in mL/min/1.73 m²):
  • G1: kidney damage with normal or increased GFR ≥90
  • G2: mild ↓ GFR 60 to 89; G3a: mild to moderate ↓ GFR 45 to 59
  • G3b: moderate to severe ↓ GFR 30 to 44
  • G4: severe ↓ GFR 15 to 29
  • G5: kidney failure: GFR <15 or dialysis
• CKD per albumin-to-creatinine ratio (ACR) category:
  • A1: normal to mildly increased: <30 mg/g or <3 mg/mmol
  • A2: moderately increased: 30 to 300 mg/g or 3 to 30 mg/mmol
  • A3: severely increased: >300 mg/g or >30 mg/mm

EPIDEMIOLOGY

• African Americans are 3.6 times more likely to develop CKD than Caucasians.
• Similar in both sexes; however, rate of end-stage renal disease (ESRD) is 1.6 times higher in males than females.

ETIOLOGY AND PATHOPHYSIOLOGY

• Progressive destruction of kidney nephrons; GFR will drop gradually, and plasma creatinine (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/1.73 m². Anemia develops from decreased renal synthesis of erythropoietin.
• Renal parenchymal/glomerular
  • Nephritic: hematuria, red blood cell (RBC) casts, hypertension (HTN), variable proteinuria
    • Focal proliferative: IgA nephropathy, systemic lupus erythematosus (SLE), Henoch-Schönlein purpura, Alport syndrome, proliferative glomerulonephritis, crescentic glomerulonephritis
    • Diffuse proliferative: membranoproliferative glomerulonephritis, SLE, cryoglobulinemia, rapidly progressive glomerulonephritis (RPGN), Goodpasture syndrome
  • Nephrotic: proteinuria (>3.5 g/day), hypoalbuminemia, hyperlipidemia, and edema
    • Minimal change disease, membranous nephropathy, focal segmental glomerulosclerosis
    • Amyloidosis, diabetic nephropathy
• Vascular: HTN, thrombotic microangiopathies, vasculitis (Wegener), scleroderma, crush injury
• Interstitial tubular: infections, obstruction, toxins, allergic interstitial nephritis, multiple myeloma, connective tissue disease, cystic disease, nephrolithiasis
• Postrenal: obstruction (benign prostatic hyperplasia [BPH]), neoplasm, neurogenic bladder

RISK FACTORS

Type 1 or 2 diabetes mellitus (DM) (most common); age > 60 years; low socioeconomic status; obesity; smoking; drug use; chronic infection (hepatitis B and C, HIV); cardiovascular disease (HTN, renal artery stenosis, atherosclerosis); prior kidney transplant; BPH; autoimmune disease, vasculitis; connective tissue disease; nephrotoxic drugs (nonsteroidal anti-inflammatory drugs [NSAIDs], lithium, sulfonamide, aminoglycosides, vancomycin, PPIs, allopurinol, loop diuretics, chemotherapeutic agents); congenital anomalies; obstructive uropathy; renal aplasia/hypoplasia/dysplasia/reflux nephropathy

HISTORY

Patients with CKD stages 1 to 3 are usually asymptomatic; can present with oliguria, nocturia, polyuria, change in urinary frequency, bone disease, edema, HTN, dyspnea, fatigue, depression, weakness, pruritus, ecchymosis, anorexia, nausea, vomiting, hyperlipidemia, claudication, erectile dysfunction, decreased libido, amenorrhea

PHYSICAL EXAM

Check for volume status (pallor, BP/orthostatic; edema; jugular venous distention; weight); skin for sallow complexion or uremic frost; ammonia-like odor; murmurs; bruits; pericarditis; pleural effusions; enlarged prostate; CNS changes such as asterixis; confusion; seizures; coma; and peripheral neuropathy.

DIAGNOSTIC TESTS & INTERPRETATION

MEDICATION

• HTN: Adults with elevated blood pressure and CKD G1 to 3 should be treated to a target systolic blood pressure of 120 mm Hg using standardized office measurements. Renal transplant patients should have a target blood pressure of <130/80 mm Hg (1)[C].
  • ACE-I or ARB recommended for diabetic and nondiabetic adults with albumin excretion >30 mg/24 hr based on evidence of benefits.
    • An ACE-I or ARB can still be considered in patients with no albuminuria. Those patients, however, are at less risk of CKD progression.
    • Avoid combining ACE-I, ARB, and DRI therapy in diabetic and nondiabetic patients with CKD.
    • Advise contraception in women who are receiving ACE-I or ARB therapy and discontinue in women who are considering pregnancy or have become pregnant (2)[C].
  • Calcium channel blockers (CCB) or ARB is first line in adult kidney transplant patients for prevention of allograft failure and minimization of possible drug-induced side effects.
  • In children with CKD, 24-hour mean arterial pressure by ABPM should be lowed to <50th percentile for age, sex, and height. In this population, an ACE-I or ARB is first line.
  • A combination between a low-Na diet plus the use of an ACE-I or ARB leads to significant reduction in proteinuria (3)[C].
• Secondary hyperparathyroidism
• For GFR <45 mL/min/1.73 m², monitor for hyperphosphatemia, hypocalcemia, and vitamin D deficiency if intact PTH is elevated.
• Calcimimetic agents (oral cinacalcet or IV etelcalcetide) are not FDA approved for use in patients with CKD not on dialysis. These should be reserved for ESRD patients (3)[C].
• Hyperphosphatemia: Maintain normal serum phosphate levels using the following:
  • Stages 3 to 5 CKD (not on dialysis): Restrict dietary phosphate to 800 to 1,000 mg/day.
  • Noncalcium phosphate binders (with meals): sevelamer, lanthanum
  • Calcium binders have not been associated with improvement in mortality or cardiovascular outcomes (3)[C].
  • Vitamin D: inactive vitamin D₂ (ergocalciferol) or vitamin D₃ (cholecalciferol), calcitriol (active vitamin D 1,25 [OH]): Vitamin D may increase absorption of phosphate by intestines and should not be started until serum phosphate concentration is controlled.
• Anemia: Treat with iron replacement therapy with or without erythropoietin-stimulating agents (ESAs). Consider ESA if Hb >9 g/dL and <10 g/dL. ESA initiation not recommended for Hb >10 g/dL. If using ESA, goal Hb range 10 to 11 g/dL, not to exceed 11.5 g/dL.
• Hyperlipidemia: statins with low-density lipoprotein (LDL) goal <70 mg/dL
• Glycemic control: Goal HbA1c range 6.5–8.0%. HbA1c may be falsely low in patients with decreased RBC; glucose logs may be more accurate reflection of glycemic control. Metformin use should be reviewed for GFR between 30 and 44 mL/min/1.73 m² and discontinued if GFR <30 mL/min/1.73 m². Use SGLT2 inhibitors along with metformin in patients with type II DM and GFR >30 mL/min/1.73 m² (2)[C]. SGLT2 inhibitors can be used for patients with and without DM to control disease progression.
• Metabolic acidosis: Start treatment with Na bicarb when bicarbonate <22 mEq/L with goal to maintain in normal range.

ISSUES FOR REFERRAL

• Nephrology consult:
  • GFR <15 mL/min/1.73 m²: immediate, GFR 15 to 29 mL/min/1.73 m²: urgent, GFR 30 to 59 mL/min/1.73 m²: nonurgent referral, GFR 60 to 89 mL/min/1.73 m²: not required unless with comorbidities
  • Rapid decline of eGFR (>5 mL/min/1.73 m² per year), nondiabetics with heavy proteinuria (24-hour urine protein >500 mg, urine PCR >0.5, urine PCR >300), diabetics with >3 g proteinuria or hematuria, management of complications (metabolic management, electrolyte abnormalities, acidosis, etc.)
• Urology consult for hematuria, renal masses, complex renal cysts, symptomatic nephrolithiasis, hydronephrosis
• Registered Dietitian/psychology/social work/physical therapy/occupational therapy consultation to assist with dietary options, behavioral modification, access to food resources, and mobility
• Renal replacement: Prepare for dialysis or transplant when GFR <30 mL/min/1.73 m².

ADDITIONAL THERAPIES

• Aspirin for secondary prevention for patients with established cardiovascular disease
• For mild pain associated with CKD, acetaminophen is considered first-line therapy. Oral, parental, and even topical NSAIDs are generally not recommended.
• For moderate to severe pain, opioids may be indicated, but the risk of overdose or toxicity is increased since many are renally excreted. Oxycodone, fentanyl, and methadone are preferred, but dose adjustment is still recommended. Meperidine is contraindicated in CKD. Codeine and morphine should be used with caution.
• Chronic pain syndromes may be treated with anticonvulsants and gabapentinoids, which should be renally dosed.

COMPLEMENTARY & ALTERNATIVE MEDICINE

Caution with herbal supplements as these are generally not regulated and may contain excessive amounts of potassium and phosphorus. They may also interact with metabolism of prescription drugs.

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

• For use of contrast in imaging, patients should have eGFR >30 mL/min/1.73 m². Volume expansion with IV isotonic saline prior to and following iodinated contrast is recommended.
• Metformin should be held prior to iodinated contrast imaging and resumed after 48 hours.

FOLLOW-UP RECOMMENDATIONS

DIET

<2 g Na per day; limit processed foods, refined carbohydrates, and sweetened beverages. Restrict potassium and phosphorus if indicated. In CKD stage 3 to 5, restrict protein to 0.6 g/kg/day if nondiabetic and 0.8 g/kg/day if diabetic. Mediterranean diet is generally recommended. Restrict fluids depending on volume status; can consider iron and vitamin D supplementation (4)[C].

PROGNOSIS

Progression is defined as 25% decrease in GFR from baseline. Rapid progression is decrease in GFR by >5 mL/min/1.73 m²/year. Patients with CKD gradually progress to ESRD.

COMPLICATIONS

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

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)

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)