Chronic Renal Failure

Definitions
Kidney damage or glomerular filtration rate (GFR) <60 mL/min/1.73 m2 for >3 months.

Classification

Stage 1	Kidney damage with GFR >90 mL/min/1.73 m2
Stage 2	Kidney damage with mild ↓ GFR 60–89 mL/min/1.73 m2
Stage 3	Moderate ↓ GFR 30–59 mL/min/1.73 m2
Stage 4	Severe ↓ GFR 15–29 mL/min/1.73 m2
Stage 5	Kidney failure GFR < 15 mL/min/1.73 m2 or dialysis

Classification by The Kidney Disease Outcomes Quality Initiative (K/DOQI) of The National Kidney Foundation:


Aetiology

Renal parenchymal/ glomerula	Nephrotic: Characterized by proteinuria (>3.5 g/day), hypoalbuminemia, hyperlipidemia and edema: Nephritic: Characterized by hematuria, red blood cell (RBC) casts, hypertension, variable proteinuria
Vascular	HTN, thrombotic microangiopathies (HUS/TTP), vasculitides (such as Wegener granulomatosis), scleroderma
Interstitial-tubular	obstruction, toxins, allergic interstitial nephritis, multiple myeloma, connective tissue disease, cystic disease, congenital, infection, drugs (allopurinol)
Postrenal:	Obstruction from benign prostatic hyperplasia, metastatic neoplasm, neurogenic bladder

Pathophysiology
A kidney with injured nephrons can maintain GFR by hyperfiltration and compensatory hypertrophy of the remaining healthy nephrons.
Urea and Creatinine significantly increase only after total GFR has decreased to 50%
The adaptability increases glomerular capillary pressure, which damages the capillaries


Epidemiology
More common in adults; increasing incidence and prevalence with age
M:F =2:1
In 2003, 102,567 new patients initiated ESRD, an adjusted rate of 337.6/1,000,000
Blacks had an adjusted rate for ESRD 2.95 times greater: 995.7 million;
Native Americans and Latinos had high rates.
Majority of people with CKD in stages 1–3


Risk Factors
Diabetes mellitus (common)
Hypertension (HTN) (common)
Acute kidney injury
Urinary tract obstruction (e.g., benign prostatic hyperplasia)
Autoimmune disease/vasculitides
Family history
Chronic, high-dose nonsteroidal anti-inflammatory drug (NSAID) or salicylate use
Long-term lithium use
Hyperlipidemia
Smoking


Presentation

Symptoms

*Stage 1-3: Generally asymptomatic Oliguria, nocturia, polyuria, change in urinary frequency Hematuria Bone disease Fatigue, depression, weakness,increased somnolence, failure to thrive Pruritus, tremor Metallic taste in mouth, uremia GI symptoms - Anorexia, nausea, vomiting, diarrhea Obesity Dyspnea Hypertension, Hyperlipidemia, Claudication Poorly controlled diabetes with retinopathy, neuropathy Pericarditis - Can be complicated by cardiac tamponade, Encephalopathy - Can progress to coma and death Peripheral neuropathy Restless leg syndrome Erectile dysfunction, decreased libido, amenorrhea Platelet dysfunction with tendency to bleeding

Signs

Complete physical plus ophthalmic exam; assess volume status (e.g., blood pressure with orthostatics; edema; jugular venous distention; weight) Skin: Sallow complexion, uremic “frost” Ammonia like odor (uremic fetor) Cardiovascular: Assess for mumurs, bruits, pericarditis Abdomen: Enlarged bladder Rectal: Enlarged prostate Central nervous system abnormalities (asterixis, confusion, seizures, coma), neuropathy

Investigation

Urinalysis	Urine microscopy: WBC/RBC casts, dysmorphic RBCs Urine electrolytes: Sodium, creatinine, urea (if on loop diuretics) Proteinuria/albuminuria: 24-hour urine collection is gold standard. Spot urine protein-to-creatinine ratio equally as good : 30–300 mg/day of albuminuria is classified as microalbuminuria (risk factor for cardiovascular disease)
FBC	Normochromic, normocytic anemia Increased bleeding time
Chemistry	Elevated BUN, creatinine, potassium,phosphate, parathyroid hormone, Decreased active vitamin D, calcium Hyperlipidemia Metabolic acidosis
Lipid profile	risk of cardiovascular disease.
Imaging	Ultrasound: 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 CT scan (noncontrast): Obstruction; calculi; cysts; neoplasm; renal artery stenosis MRI/MRA for greater resolution than CT, but avoid gadolinium due to risk of nephrogenic fibrosis Renal arteriogram for renal artery stenosis can be therapeutic as well diagnostic if angioplasty or stent done Renal scan to screen for differential function between kidneys Voiding cystourethrogram (VCUG) - Criterion standard for diagnosis of vesicoureteral reflux
Renal Biopsy	indications: Hematuria, proteinuria, unexplained renal failure

Formula
The Cockcroft-Gault formula for estimating CrCl

• CrCl (male) = ([140-age] X weight in kg)/(serum creatinine X 72)

• CrCl (female) = CrCl (male) X 0.85

Alternatively, the Modification of Diet in Renal Disease (MDRD) Study equation could be used to calculate the GFR.  However, MDRD underestimates measured GFR at levels >60 mL/min/1.73 m2


Management

Hypertension	ACEi or ARBs for HTN control and antiproteinuric effect If proteinuria >1 g/d, goal <125/75; if <1 g/d, <130/80 If goal not reached, add diuretic (thiazides, then loop diuretic), followed by diltiazem or verapamil or a β-blocker
Secondary hyperparathyroidism	Phosphorus binders taken with meals (calcium carbonate, calcium acetate, sevelamer, lanthanum), inactive vitamin D 25 (ergocalceferol or cholecalceferol), calcitriol
Anaemia	Erythropoietin, Start when Hgb <10 g/dL, goal 11–12
hyperlipidemia	Statin
Glycemic control	Goal HbA1C<7. Avoid metformin due to risk of metabolic acidosis.
Metabolic acidosis	Start bicarbonate supplement when bicarb <20
Surgery	Placement of dialysis access or transplantation for ESRD
Admission criteria	Uremia- Severe nausea and vomiting, fluid overload unresponsive to diuretics, pericarditis, uremic encephalopathy, resistant hypertension, hyperkalemia, metabolic acidosis, hyperphosphatemia:
Follow Up	Monitor blood presure, clinical status, volume status, blood chemistries, BUN, creatinine, urine protein, and GFR periodically, more often for advanced CKD.
Diet	Nutrition consult for CKD diet For GFR <60 mL/min/1.73 m2, assess protein andenergy intake; important to maintain adequate nutrition Restricted intake of phosphates Sodium restriction Potassium restriction if hyperkalemic

Prognosis
Greatest morbidity from cardiovascular disease

• Risk of death, especially from CVD, greater than risk of progressing to dialysis