Introduction

By
Assist Prof.
Dr.Amin Turki
By
Assist Prof.
Dr.Amin Turki
L1. Nephrology and urology
Main renal functions:
Maintain fluid and electrolyte balance, and excrete metabolic waste products through glomerular filtration and tubular secretion.
Metabolic function: gluconeogenesis.
Endocrine function: Renin and erythropoietin productions, Vitamin D activation.

Common renal manifestations:

NEONATE:
Flank mass: due to multicystic dysplasia, urinary tract obstruction (hydronephrosis), polycystic disease, tumor
Hematuria: due to acute tubular/cortical necrosis, urinary tract malformation, trauma, renal vein thrombosis
Anuria and oliguria: due to renal agenesis, obstruction, acute tubular necrosis, vascular thrombosis

CHILD and ADOLESCENT:

Cola red-colored urine : Hemoglobinuria (hemolysis); myoglobinuria (rhabdomyolysis); pigmenturia (porphyria, urate, beets, drugs); hematuria (infection, glomerulonephritis, Henoch-Schönlein purpura, hypercalciuria, stones)
Gross hematuria: Infection, glomerulonephritis, trauma, benign hematuria, renal stones, tumor
Edema : Nephrotic syndrome, glomerulonephritis, acute/chronic renal failure, cardiac/liver disease
Hypertension: Acute glomerulonephritis, acute/chronic renal failure, obstruction, cysts, dysplasia, coarctation of the aorta, renal artery stenosis
Polyuria: Diabetes mellitus, central and nephrogenic diabetes insipidus, obstruction, dysplasia, hypokalemia, hypercalcemia, psychogenic polydipsia, sickle disease/trait, polyuric renal failure, diuretic abuse
Oliguria: Dehydration, acute tubular necrosis, acute glomerulonephritis, interstitial nephritis, hemolytic uremic syndrome
Urgency: Neurogenic bladder, urinary tract infection, vaginitis, hypercalciuria, foreign body.
DIAGNOSTIC STUDIES:
1. Glomerular Filtration Rate (GFR):
Is measured most accurately by infusion of a substance that is freely filtered by the glomerulus but is not metabolized, reabsorbed, or secreted in or by the tubules.
The GFR is calculated as follows:
GFR = U x V/ P
where :[U] is urine concentration of a substance (mg/dL) used to measure clearance
[P] is serum concentration of a substance (mg/dL) used to measure clearance
V is urine flow rate (mL/min).
GFR is corrected to a body surface area of 1.73 m2 to allow comparison between different sized individuals.
In a full-term newborn, an uncorrected GFR is 4 to 5 mL/min and corrects to approximately 40 mL/min/1.73 m2.
GFR increases rapidly after birth to achieves adult values (100 to 120 mL/min/1.73 m2). At age of 2 years. After that, GFR and body size increase proportionately, so GFR remains stable.


2. Plasma creatinine:
Creatinine is a product of muscle metabolism produced at a relatively constant rate and cleared by renal excretion. It is freely filterable by the glomerulus and not reabsorbed by the renal tubules.
With stable kidney function, creatinine production and excretion are equal; thus, plasma creatinine concentrations remain constant.
Plasma creatinine concentration alone is not adequate measure of renal function because it depends on the size and muscle mass of the child, the child’s hydration state, the GFR, individual meat intake, and commonly used drugs such as aspirin, cimetidine, and trimethoprim reduce tubular creatinine secretion and increasing plasma creatinine concentration so its falsely indicating renal dysfunction.
Creatinine clearance (Ucr x V \ Pcr) can be used as a rough estimation of GFR, but it is often overestimate the GFR when renal function is decreased.

3. Blood urea nitrogen (BUN):

Is increased in renal failure but it is not adequate measure of renal function as alone because it greatly altered by hydration, nutrition, catabolism, and tissue breakdown.

Conditions affecting B U N independently of GFR:

Increased BUN
Decreased BUN
Reduced effective blood volume (prerenal azotemia)
Catabolic states (G.I. bleeding, corticosteroid use).
High-protein diets.
Tetracycline
Liver disease
Malnutrition
Sickle cell anemia
SIADH


4. Urinalysis (GUE):
Is a useful screen for renal abnormalities. The urine is collected in midstream or by
bladder catheterization. It should be examined within 1 hour after collection to avoid destruction of formed elements. Urinalysis includes the followings:
Color and turbidity.
Macroscopical examination using urine dipstick for urinary pH, protein, hemoglobin, glucose, ketones, bilirubin, nitrites (for bacteriurea), leukocyte esterase and urinary specific gravity.
Microscopical examination for crystals, cells (WBC, RBC), casts, and infecting organisms.
5. Imaging studies:
Ultrasound: assesses kidney size, degree of dilation, stones and differentiates cortex and medulla in addition to bladder visualization.
Pulsed Doppler studies assess arterial and venous blood flow.
Voiding cystourethrogram involves repeated filling of the bladder to detect vesicoureteral reflux and to evaluate the urethra.
Intravenous pyelogram (IVP) evaluate kidney structure and function
Computed tomography (CT) and magnetic resonance Imaging (MRI) have mostly replaced the IVP to evaluate kidney structure and function.
Radionuclide studies can define renal size, scars, and renal function/excretion.

Proteinuria:

Normal physiology:
**Large plasma proteins such as albumin and globulin are prevented from entering the urinary space by the charge and the size of selective proteins of the glomerular capillary wall.
** Smaller proteins (low-molecular-weight proteins) can cross the capillary wall but are reabsorbed by the proximal tubule.
**A very small amount of protein that normally appears in the urine is the result of
normal tubular secretion. The normally excreted protein mostly is Tamm-Horsfall protein which is a protective glycoprotein secreted by the tubules that inactivates cytokines.
Types of proteinuria:
Glomerular proteinuria, caused by abnormality of the glomerular capillary wall.
Tubular proteinuria, caused by tubular injury or dysfunction that leads to ineffective reabsorption of mostly low-molecular-weight proteins
Increased production of plasma proteins (in multiple myeloma, rhabdomyolysis, or hemolysis) which may cause the production or release of very large amounts of protein that are filtered at the glomerulus and exceed the absorptive capacity of the proximal tubule.


Measurement of urinary protein:
1. Urine Dipstick:
It is a qualitative measurement of urinary protein. It primarily detect albuminuria and are less sensitive for other forms of proteins (low-molecular-weight proteins, or gamma globulins).
The dipstick is reported as following:

Urine Dipstick
Urinary protein concentration
negative or trace
< 30 mg/dL
1+
30-100 mg/dL
2+
100-300 mg/dL
3+
300-1000 mg/dL
4+
>1000 mg/dL
False-positive results can occur with a very high urine pH (>7.0), a highly concentrated urine specimen, or contamination of the urine with blood.
False-negative test results can occur in patients with dilute urine or a large volume of urine output or in disease states in which the predominant urinary protein is not albumin.

2. Timed (24 hr)urine collections:

Its more accurate regarding urine protein excretion than randomly performed dipstick test.
Urinary protein excretion in normal child is less than 100 mg/m2/day or a total of 150 mg/day.
In neonates, normal urinary protein excretion is higher, up to 300 mg/m2, because of reduced reabsorption of filtered proteins.
More specifically, normal protein excretion in children is ≤4 mg/m2/hr; abnormal proteinuria is defined as excretion of 4-40 mg/m2/hr; and nephrotic-range proteinuria is defined as >40 mg/m2/hr.


3. Urine protein-to-creatinine ratio (urinary P\ C ratio):
It measure in an untimed (spot) urine specimen which largely replaced timed urine collection. It should be performed on a first morning voided urine specimen to eliminate the possibility of orthostatic (postural) proteinuria
A ratio of <0.5 in children <2 yr of age and <0.2 in children >2 yr of age suggests normal urinary protein excretion. A ratio greater than 2 suggests nephrotic-range proteinuria.

Microalbuminuria is defined as the presence of albumin in the urine above the normal level but below the detectable range of urine dipstick methods (< 30 mg/dL).
Microalbuminuria in children is associated with obesity and it predict the development of diabetic nephropathy in type 1 diabetes mellitus.

Causes of proteinuria:

1. Transient proteinuria:
Fever
Exercise
Dehydration
Cold exposure
Congestive heart failure
Seizure
Stress

2. Orthostatic (postural proteinuria).

3. Glomerular diseases with isolated proteinuria:
Nephrotic syndrome (all types)
Amyloidosis
Diabetic nephropathy
Sickle cell nephropathy


4. Glomerular diseases with proteinuria as a prominent features:
Acute post streptococcal GN.
Ig A nephropathy
Henoch-Schönlein purpura nephritis
Lupus (SLE) nephritis
Reflux nephropathy

5. Tubular diseases:

Cystinosis
Wilson disease
Galactosemia
Acute tubular necrosis
Renal dysplasia
Polycystic kidney disease
Reflux nephropathy
Drugs (penicillamine, lithium, NSAID)
Heavy metals (lead, gold, mercury)