Renal Diseases

Anne Marie Beck

RENAL FUNCTION AND URINE STUDIES

Three essential attributes of renal function:
- Glomerular ultrafiltration
- Tubular absorption of filtered solutes and water
- Tubular secretion of organic and nonorganic ions

History

General: malaise and growth failure
Gastrointestinal (GI): feeding difficulties, vomiting, anorexia, and GI bleeding at times
Asymptomatic in many cases
Neonatal history
- Prenatal diagnosis of hydronephrosis or urinary tract abnormality
- Edematous/hypertrophied placenta (>25% of birth weight) suggests congenital nephrotic syndrome.
- Maternal infection. Congenital TORCH infections can present as neonatal nephrotic syndrome and seeding of renal parenchyma with infections (e.g., cytomegalovirus); maternal sepsis can cause hypoperfusion and injury to the infant’s kidneys.
- Perinatal asphyxia with macroscopic hematuria in neonatal period might suggest renal venous thrombosis in the same child with hematuria when older.
Family history: inherited renal conditions such as cystic kidney diseases (ARPKD, ADPKD, nephronophthisis), thin basement membrane disease, Alport syndrome, and some nephrotic syndromes because of inherited mutations. Specific inquiry regarding any family member on dialysis or with a kidney transplant is often insightful.
Past medical history: recurrent gross hematuria (IgA nephropathy), intermittent swelling, high blood pressure, medication exposures, and daytime or nocturnal enuresis
Dietary history

Physical Examination

Look for the following aspects of the physical examination to assist with diagnosing renal disease:

Growth and nutrition
Hydration status (edema or dehydration)
Circulation, including four extremity pulses, precordium, lungs (pulmonary edema), and abdominal palpation
Physical examination
- Maintain a broad focus in newborns, as many renal diseases are associated with other congenital defects (imperforate anus, VACTERL association, single umbilical artery, gonadal dysgenesis, and Wilms tumor).
- Palpate the abdomen for renal masses (enlarged kidney in renal vein thrombosis, renal tumors, and multicystic dysplastic kidneys).

Urinalysis

The following is a list of urinalysis findings that suggest or confirm renal disease:

Abnormalities of appearance
- Hematuria (confirm with urinalysis and microscopic examination)
- Cloudy: suggestive of infection/crystalluria
Abnormalities of urine volume
- Anuria: complete cessation of urine output
- Oliguria: insufficient urine for homeostasis (usually <500 mL/24 hr for adults or 1 mL/kg/hr in infants). See Table 24-1 for laboratory values that indicate a prerenal or renal cause.
- Polyuria: increased fluid intake, failure of antidiuretic hormone (ADH) release, resistance to ADH, and osmotic diuresis
Blood: tests for heme moiety (hemoglobin and myoglobin). If positive, it is necessary to confirm red blood cell (RBC) morphology by microscopic examination.
Protein: standard Clinistix detects albumin; less sensitive for free light-chain proteins (Bence Jones) or low-molecular-weight “tubular” proteins
Glucose: standard Clinistix detects glucose alone; to test for other sugars, a Clinitest is necessary.
Nitrite: 90% of common urinary pathogens are nitrite-forming bacteria.
Urinary concentration: tested by specific gravity, but osmolality is more accurate with large molecules such as glucose
Urine bilirubin: elevated in any disease that causes increased conjugated bilirubin in the bloodstream (negative in hemolytic disease)
Urine urobilinogen: increased in conditions that increase the production of bilirubin or decrease the liver’s ability to remove reabsorbed urobilinogen from the portal circulation (positive in both liver disease and hemolytic disease)
Microscopic examination
- In healthy children, 1-2 RBCs/high-power field (HPF) or 1-2 white blood cells (WBCs)/HPF is normal.
- Casts: precipitation of debris in renal tubules
  - Hyaline casts: low renal blood flow
  - Red cell casts: hematuria of glomerular origin suggestive of glomerulonephritis
  - Fatty casts (Maltese-cross structures): commonly seen in nephrotic syndrome
Crystals
- Calcium oxalate: hypercalciuria (envelope or dumbbell shape of crystals)
- Uric acid crystals: hyperuricosuria (appear as rhombic plates or rosettes)
- Hexagonal (benzene ring structure) cystine crystals: cystinuria
- Ammonium magnesium phosphate crystals: only form in alkaline pH; seen with urease-splitting organisms (coffin-lid appearance of crystals)
- Fine, needle-like crystals: tyrosinemia

TABLE 24-1 Laboratory Differentiation of Oliguria

Test	Prerenal oliguria^*	Intrinsic renal oliguria^*
Specific gravity	>1.020 (>1.015)	<1.010 (<1.010)
Urine osmolality (mOsmol/kg)	>500 (>400)	<350 (<400)
Urine/plasma osmolality	>1.3 (>2.0)	<1.3 (<1.0)
Urine sodium (mEq/L)	<20 (<30)	>40 (>70)
FE_Na	<1 (<2.5)	>3 (>10)
Urine/plasma urea	>8 (>30)	<3 (<6)
FE_Urea	<30	>70
Urine/plasma creatinine	>40 (>30)	<20 (<10)
FEβ_{2 microglobulin}	<0.4	>0.5
^*Indices for neonates who are >32 weeks are given in parentheses. FE, fractional excretion.

Calculating Creatinine Clearance

Schwartz formula: used to calculate the glomerular filtration rate (GFR) mL/min/1.73 m²
L = length in cm
k = constant of proportionality
- Full-term newborn through first year: 0.45
- Children up to 13 years: 0.55
- Adolescent males (13-21 years): 0.7
- Adolescent females (13-21 years): 0.57
- Child with chronic kidney disease: 0.413
- P_Cr = plasma creatinine
Blood urea nitrogen (BUN): not an accurate predictor of renal function
- Factors that increase serum BUN: GI hemorrhage, dehydration, increased protein intake, and increased protein catabolism (systemic infection, burns, glucocorticoid therapy, early phase of starvation)
- Factors that decrease serum BUN: high fluid intake, decreased protein intake, advanced starvation, and liver disease
Calculation of GFR using U × V/P
- To standardize: creatinine clearance
  - U_Cr = urinary concentration of creatinine
  - V = urine volume in 24 hours
  - P_Cr = plasma concentration of creatinine
  - SA = body surface area
- If a child >3 years of age has <15 mg/kg/day of creatinine in a 24-hour urine collection, it probably means that the collection did not actually occur over 24 hours or that not all the urine has been collected.
For normal values of GFR, see Table 24-2.
Renal function can be categorized as glomerular, tubular, or hormonal (Table 24-3).

TABLE 24-2 Normal Glomerular Filtration Rate (GFR) by Age

Age	GFR e(mL/min/1.73 m²)
Birth	20.8
1 week	46.6
3-5 week	60.1
6-9 week	67.5
3-6 months	73.8
6 months-1 year	93.7
1-2 years	99.1
2-5 years	126.5
5-15 years	116.7

ACUTE RENAL FAILURE

Defined as an increase in creatinine of 0.5 mg/dL over the baseline

TABLE 24-3 Summary of Diagnostic Renal Evaluation by Function

Glomerular function	Tubular function	Hormonal function
Blood urea nitrogen	Water metabolism Urine specific gravity Urine osmolality Maximal urine concentrating ability	Erythropoietin Hematocrit Reticulocyte
Serum creatinine and inulin clearance	Acid-base metabolism Urine pH	Vitamin D Serum 1,25-(OH)₂D₃ concentration
Iothalamate GFR study	Urine titratable acid excretion Urine ammonium excretion Urine-blood Pco₂ FE of bicarbonate at normal serum bicarbonate level	Serum calcium concentration 25-OH Vit D3

Etiology

Acute tubular necrosis (ATN): 45% (ischemia or nephrotoxins)
Prerenal: 21% (heart failure, sepsis, or volume depletion)
Acute on chronic: 13% (mostly ATN and prerenal disease)
Urinary tract obstruction: 10%
Glomerulonephritis or vasculitis: 4%
Acute interstitial nephritis: 2%

Laboratory Studies

Serum BUN/creatinine ratio (use with caution in children)
- Prerenal >20:1
- Other causes of high BUN: GI bleed, steroids, and tetracycline
- Other causes of low creatinine: reduced muscle mass in chronically ill children
Urinalysis
- Prerenal: hyaline casts
- Intrinsic renal disease: RBCs and WBCs, granular/RBC/WBC casts, or renal epithelial cells
Urine sodium concentration
- Prerenal: <20 mEq/L
- Intrinsic disease: >40 mEq/L
Fractional excretion of Na (FE_Na) = (U_Na·Cr)/(P_Na·U_Cr) × 100
- Prerenal: <1%
- ATN: >2%
- Unequivocal if 1%-2%
- Not useful if patients are taking diuretics
Fractional excretion (FE) of urea = (U_urea·P_Cr)/(P_urea·U_Cr) × 100
- Prerenal: <35%
- Intrinsic: >60%-65%
Urine osmolality
- Prerenal: >500 mOsmol
- Intrinsic: <450 mOsmol
Urine-to-plasma creatinine concentration
- Prerenal: >40
- Intrinsic: <20

METABOLIC ACIDOSIS

Increased anion gap
- An increase in unmeasured anions: diabetic ketoacidosis; lactic acidosis; uremia; and ingestion of salicylates, ethylene glycol, and methanol
- Severe diarrhea can also cause an increased anion gap acidosis in children and infants.
Normal anion gap
- GI bicarbonate loss (diarrhea, intestinal/pancreatic fistulas, resins)
- Renal tubular acidosis (RTA)
  - Type I: defective proton (H+) secretion
  - Type II: defective HCO3 reabsorption
  - Type IV: hypoaldosteronism
Tests for diagnosis of RTA (Table 24-4)
- Urine pH
  - pH: <5.5 proximal type I and type IV
  - pH: >5.5 distal type I
- Urine ammonia levels: low in distal type I
- Urine anion gap (urine sodium + potassium + chloride)
  - Negative in proximal type I
  - Positive in distal type I and type IV