Nephrology: Vignettes 1

1. By what age of life, a child will achieve adult level of GFR (120 ml/min of 1.73 M2)?

Ans: By 2 yrs of age.

By about 3 months after birth, the GFR approaches about 50% of the adult value, and by about 1 year, it is about 80% of the adult level.

2. Hematuria:

All children who have hematuria require a thorough history and physical examination. It is important to determine if there are red blood cells (RBCs) in the urine, which localizes the bleeding to the urinary tract.

In general, the causes of hematuria in children include:

- glomerular disease (eg, postinfectious acute glomerulonephritis),

- hypercalciuria or renal stones,

- acute pyelonephritis or cystitis,

- drug toxicity (eg, vancomycin or gentamicin),

- renal malformation (ureteropelvic junction obstruction or tumor), or cystic disease (autosomal dominant polycystic kidney disease). Another cause is bladder malformation (eg, ureterocele).

3. Proteinuria:

a] Fixed (or nonorthostatic) proteinuria that occurs during both daytime and nighttime requires immediate evaluation.

- Significant fixed proteinuria (random urine protein to creatinine [P/C] ratio >0.5) indicates potentially progressive renal injury or inflammation.

- Although there are occasional causes of false-positive urine protein tests (eg, highly concentrated or alkaline urine), these conditions do not result in fixed proteinuria.

NB: In addition to the urine P/C ratio, measurement of the serum albumin is recommended to assess the severity and duration of proteinuria.

b] Transient proteinuria can be caused by fever and vigorous exercise; other inciting factors include stress, dehydration, and cold exposure.

4. A 4-month-old girl develops UTI. Ultrasonography : hydroureteral nephrosis of the left upper pole, and voiding cystourethrography shows a filling defect within the bladder .
Most likely cause is: Ureterocele.

a] Defn: A ureterocele is a cystic dilation of the ureter where it inserts into the bladder.
An intravesical ureterocele is contained entirely within the bladder. When a portion of the defect extends beyond the bladder (to the urethra or bladder neck), an extravesical ureterocele is present. Typically, the pelvocaliceal system draining into the ureterocele is obstructed.

ii) Incidence : 4 x more common in females. Almost exclusively in Caucasians.

Ureteroceles are associated with a duplex collecting system in 80% of children; the remainder are associated with a single collecting system.

b] Complications (Cx) it leads to: UTI is the commonest Cx.

- A ureterocele often results in a mass lesion within the bladder that may be seen on bladder ultrasonography or indirectly as a filling defect of the bladder on voiding cystourethrography. The lower pole of the kidney of a duplex collecting system may drain into an orthotopic site and is associated with vesicoureteral reflux (VUR) in approximately 50% of cases. In addition, VUR is seen in approximately 25% of the kidneys contralateral to the duplex kidney that has a ureterocele.
Thus, a Urterocelc:
Most commonly are associated with urinary tract infection in infants.

NB: Ureteroceles can be in 25% cases detected antenatally.

Older children present with voiding symptoms or hematuria associated with minimal trauma.

5. Postinfectious acute glomerulonephritis (PIAGN):

Commonest cause: group A beta-hemolytic streptococcal infection

Others: Staph aureus, S epidermidis, HIV, adenovirus, influenza A virus, and Epstein-Barr virus.

6. A previously healthy 10-year-old boy presents with facial and leg edema. He has had increasing swelling for about 2 weeks. He claims that he has been unable to tie his shoes completely and feels tired. He reports no history of abdominal pain, gross hematuria, or decreased urine output. Measurement of serum electrolytes reveals:

• Sodium, 132 mEq/L (132 mmol/L)
• Potassium, 4.6 mEq/L (4.6 mmol/L)
• Chloride, 92 mEq/L (92 mmol/L)
• Bicarbonate, 21 mEq/L (21 mmol/L)
• Blood urea nitrogen, 21 mg/dL (7.5 mmol/L)
• Creatinine, 1.8 mg/dL (159 mcmol/L)

His serum albumin concentration is 1.6 g/dL (16 g/L). His urinalysis reveals moderate blood and 4+ protein. Measurement of serum complements (C) reveal: C3, 41 mg/dL (low) and C4, 3 mg/dL (low).

Of the following, the MOST likely cause of this boy's symptoms is:

1) Ac post -infectious GN ii) Membranous proliferative GN (MPGN)
iii) MPGN iv) Minimal change GN

Answer is: MPGN

Note:

Low C3, Normal C4: APIGN
Low C3 , low C4: MPGN, LN

a] Serum C3 complements always is low at the onset of PIAGN (post-infectious ac GN), MPGN (membrano-proliferative), and in most cases of LN (lupus nephritis).

Serum C4 is normal in PIAGN, but generally is low in patients who have MPGN and lupus nephritis (LN). Here lies the answer of above question.

NOTE: In PIAGN, the C3 level returns to normal by 3 months; in NPGN and LN, this generally does not occur. Thus, a persistently low C3 value raises the suspicion of LN or MPGN.

Some more criteria:

- Certain diseases are more common in younger children (eg, minimal-change nephrotic syndrome [MCNS]) versus older children (eg, MGN).

- Second, associated features may be helpful. For example, although many patients who have NS may exhibit elevated blood pressure, this is unusual in patients who have MCNS and almost always is present in patients who have PIAGN.

7. Beckwith Wiedemann Sybdrome (BWS) and Wilms tumor:

BWS involves a chromosome 11p15.5 gene deletion, is characterized by somatic overgrowth and macroglossia.

Affected children: 3% - 5% risk of developing Wilms tumor.

Surveillance for the development of Wilms tumor should include :

i) measurement of serum alpha-fetoprotein,

ii) urinalysis for microscopic hematuria,

iii) and abdominal US every (q) 3 months for at least the first 5 years after birth.

NB: The most classic association with Wilms tumor is the WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation), which is related to chromosome 11p13 deletion.

8. proteinuria:

Benign causes:

conditions causing a positive dipstick result for urinary protein are one of the following: a very concentrated urine (specific gravity =1.020), alkaline urine (pH =7.5), or the presence of mucoproteins. In addition, acute illness may result in a small degree of proteinuria. The most important feature of these conditions is that the urinary dipstick result almost never exceeds a reading of 1+.

In the absence of these conditions,

Transient (orthostatic) : Orthostatic proteinuria (OP) occurs during the daytime but disappears when the person is supine (eg, asleep) for at least 2 hours. Benign condition.

Fixed: proteinuria is present at all times of the day, regardless of body position.

9. Levels of complements and type of Ac GN:

MPGN: C3 and C4 both are reduced

PIAGN: only C3 is low

10. Some more on AGN:

A 16-year-old boy reports that he had an episode of cola-colored urine associated with an upper respiratory tract infection 6 weeks ago. The only significant finding on his medical history is mild hearing loss. Today his blood pressure is 112/66 mm Hg. Urinalysis shows 3+ blood, 2+ protein, and 20 to 50 red blood cells per high-power field (RBC/HPF). Other laboratory findings include: BUN, S Creat, serum albumin are WNL. So are serum C3, C4 and ANA.

You discuss these results with his mother, who then tells you that she recalls being told she had blood in her urine. Urinalysis for the child's mother demonstrates 2+ blood with 10 to 20 RBC/HPF.

Of the following, a TRUE statement about this patient's disorder is that:

Ans: boys who have this condition are more likely to develop chronic renal failure than are girls

Note that the description is consistent with Alport syndrome.

Now read:

i) The normal complement components C3 and C4: Three likely diagnostic possibilities:

- immunoglobulin A glomerulonephritis,

- pauci-immune vasculitis,

- or familial nephritis.

The discovery of hematuria in the mother suggests familial nephritis.

ii) Familial nephritis: can be caused by

Alport syndrome (AS) or

thin glomerular basement membrane (GBM) disease.

Both disorders involve underlying defects of the GBM that result in a disruption of the glomerular capillary barrier. This barrier is comprised of the glomerular endothelial cell, the GBM, and the podocyte (visceral glomerular epithelial cell). Any disruption to this barrier permits access of restricted substances, such as red blood cells or protein, to the urinary space.

ALPORT SYNDROME:

AS is caused by a defect of type IV collagen, a component of the GBM.

The cause in 80% of cases is an X-linked disease involving a gene defect of COL4A5 (which codes for the alpha 5 chain of type IV collagen).

A common presentation: a male child who has asymptomatic microscopic hematuria that may become overt hematuria in the presence of a respiratory infection.

The renal lesion may progress to azotemia with nephrotic-range proteinuria in adolescence.

End-stage renal disease has been reported in 50% to 90% of affected males by age 30 years, depending on the severity of the genetic defect.

High-frequency sensorineural hearing loss (SNHL) occurs in approximately 50% of affected patients.

A number of patients also have ophthalmologic findings, with anterior lenticonus, a defect of the lens bowing into the anterior chamber, being the most common.

Due to the X-linked inheritance of this disorder in most patients, males often present earlier than females and have more severe disease. As such, males are more likely than females to develop chronic renal failure. As in this case, the evaluation of a male child who has persistent asymptomatic hematuria should include a dipstick urinalysis of the mother to screen for hematuria.

Based on the genetics of this disorder, 50% of male children of female carriers are affected. At present, there is no specific treatment for AS. Nephrologists focus on blood pressure control and reduction of proteinuria, often with the use of angiotensin-converting enzyme inhibitors.

Genetic defects of the alpha 3 or alpha 4 chain of type IV collagen result in an autosomal form of AS (autosomal recessive or dominant), which comprises the remaining 20% of cases of AS.

Thin GBM disease:

has overlapping characteristics with AS in that it runs in families,

is caused by a defect of the GBM,

and results in persistent microscopic hematuria.