November 2005
Volume 6; No. 3
Bulletin of the
INDIAN PEDIA
TRIC NEPHROL
OG
Y GROUP
PEDIATRIC
NEPHROLOG
OGY
IAP Specialty Chapter on Nephrology
Evaluation of Hematuria
Children with hematuria present either with (i) gross hematuria, (ii) glomerular or other urinary symptoms with
microscopic hematuria, or (iii) incidental detection of microscopic hematuria during urinalysis.
Definition
When the hematuria is gross or macroscopic, there is no difficulty in diagnosis. Microscopic hematuria has been
defined as a positive dipstick for blood on a single urine specimen, with microscopic confirmation for the presence of
more than 6 RBCs /mm3. In practice, 5 or more RBCs per high power field in all the three of three fresh urine
specimens collected over a week is accepted as hematuria.
Categorization of hematuria
Children can be categorized into: (i) gross hematuria, (ii) microscopic hematuria with clinical symptoms, (iii) asymptomatic
hematuria with proteinuria, and (iv) aysmptomatic microscopic (isolated) hematuria. The first two categories usually
indicate a serious underlying disease and need a complete evaluation. The third category suggest a chronic glomerular
disease and often require a renal biopsy. The fourth category is usually a benign disease and due to non-glomerular
conditions such as hypercalciuria, exercise or drugs.
Detection
Hematuria should be confirmed by dipstick examination and microscopy. Red colored urine can be due to conditions
other than hematuria. A careful history and examination of the urine differentiates between red colored urine and true
hematuria. A dipstick is used to screen for hematuria and a positive dipstick must be confirmed with
microscopic examination of the urine. The dipstick test is positive when hemoglobin is present in the urine either
in its free form (hemoglobinuria) or within RBCs. This test may also be positive in myoglobinuria, but negative in other
causes of red discoloration such as drugs, food pigments, anthrocyanin, porphyrin and urates.
Causes
The etiology of hematuria can be differentiated into glomerular or non-glomerular causes (Table 1). Common causes
are shown in Table 2.
Chairperson
Sushmita Banerjee
Secretary & Treasurer
Pankaj Hari
Editor
Arvind Bagga
Executive Members: VK Sairam, Jyoti Sharma, Sanjeev Bagai, Indira Agarwal, V Tamilarasi
Secretariat: Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110029
Fax: 91-11-26588663; 26588641 E-mail: pankajhari@hotmail.com
Discussion Group: kidped@yahoogroups.com
1
Table 1. Differentiating features between glomerular and non-glomerular hematuria
Feature
Glomerular
Non-glomerular
Color
Blood clots
Staining of urine
RBC morphology
Cola colored
Absent
Uniform
>15% dysmorphic RBCs
and/or > 5% acanthocytes
Present
2+ and more
Oliguria, edema, hypertension,
purpura, arthralgia
Bright red/ pink
Present
May vary with phase of urination
Eumorphic RBCs
RBC casts
Proteinuria
Associated features
Absent
<2+
Dysuria, pyuria, strangury,
frequency, enuresis
Table 2. Common causes of hematuria
Condition
Associated features
Glomerular
Post-infective GN
Henoch-Scholein purpura
Membranoproliferative GN
IgA nephropathy
Alport syndrome
Systemic lupus erythematosus
Edema, hypertension, oliguria, mild proteinuria
Purpura, arthralgia, abdominal symptoms
Edema, proteinuria, hypertension
Recurrent, synpharyngitic hematuria
Ear, eye abnormalities
Skin rashes, arthritis, multi-organ involvement
Non-glomerular
Lower urinary tract infection
Hypercalciuria, urolithiasis
Hemorrhagic cystitis
Hydronephrosis, Wilms’ tumor
Acute interstitial nephritis
Polycystic kidney disease
Fever, flank pain, dysuria
Colicky pain, graveluria, family history of renal stones
Drug intake or viral infection, suprapubic pain, passage of clots
Flank pain, abdominal mass
Fever, rash, eosinophilia, history of drug intake
Abdominal mass, hypertension
Hematuria may be a part of systemic diseases such as septicemia, DIC and coagulation disorders. In neonates,
microscopic hematuria is the presenting symptom with oliguria in acute tubular necrosis, and macroscopic hematuria
in acute cortical necrosis and renal vein thrombosis.
Evaluation of hematuria
Patients may be evaluated for hematuria as shown in Figs. 1-3.
Urinalysis
RBC -ve
Dipstick -ve
RBC+ve
Dipstick +ve
Other causes of
red urine
Dipstick +ve
RBC -ve
RBC morphology
RBC casts
Hemoglobin
Myoglobin
Glomerular
Non-glomerular
(See Fig. 2)
(See Fig. 3)
Fig. 1. Initial evaluation of hematuria
2
Once hematuria is considered of glomerular origin, a family history of hematuria should be asked for. In the absence
of family history, serum C3 estimation helps to differentiate between immune mediated and the non-immune causes.
If serum C3 is low along with a positive ASO/ anti DNAse B titre, a diagnosis of post streptococcal acute GN can be
made. A low C3 with a positive ANA/ anti dsDNA serology indicates SLE. A persistently low C3 with no other
positive serological markers suggests the possibility of membranoproliferative GN. Hematuria with normal C3 and
heavy (2+ or more) or persistent proteinuria suggests GN and the need for a renal biopsy
Glomerular hematuria
Family history of hematuria in first
degree relatives
Yes
No
C3
Hearing, visual defects
Renal failure
No
Thin GBM
disease
Yes
Alport
syndrome
Renal biopsy
Audiogram
Improved
Normal
Low
Proteinuria
ASO/Anti DNAse B
Mild
Heavy
-ve
PSGN
Follow-up for
6 months
Persistence
+ve
Chronic GN
Reassurance
ANA
+ve
-ve
SLE
MPGN
Renal biopsy
Fig. 2. Evaluation of glomerular hematuria. PSGN poststreptococcal GN, ANA
antinuclear antibody, MPGN membranoproliferative GN
References
1.
Cohen RA, Brown RS. Microscopic hematuria. N Engl J Med 2003; 348: 2330-2338.
2.
Diven SC, Travis LB. A practical primary care approach to hematuria in children. Pediatr Nephrol 2000; 14: 65-72.
3.
Vijayakumar M, Nammalwar BR. Approach to hematuria. In: Principles and Practice of Pediatric Nephrology. Eds Vijayakumar
M, Nammalwar BR. Jaypee Brothers, New Delhi, 2004; pp 138-143.
4.
Makker SP. Hematuria syndromes. In: Clinical Pediatric Nephrology. Eds Kher KK, Makker SP. McGraw-Hill, New York,
1992; pp 101-116.
Pragnya Ranganath, M. Vijayakumar, B.R. Nammalwar
Kanchi Kamakoti CHILDS Trust Hospital, Chennai
3
Non-glomerular hematuria
Urine culture
Negative
Positive
Renal imaging studies
USG, Doppler
UTI, pyelonephritis
Abnormal
Normal
Nephrolithiasis
Renal artery/vein thrombosis
Renal cystic diseases
Tumors, trauma
High > 0.21
Hypercalciuria/hyperoxaluria
(Confirm with 24 hr urine Ca, oxalate
Urine Ca/Cr
Normal
Bleeding disorders
Idiopathic
Fig. 3. Evaluation of non-glomerular hematuria. UTI urinary tract infection, Ca/Cr calcium to creatinine ratio
CME Pediatric Nephrourology
A program on Pediatric Nephrourology was jointly organized by the Guwahati branch of the IAP,
North East Chapter of ISN and Guwahati Medical College on 9 October 2005. Dr. RN Srivastava
stressed the importance of development of subspecialities for quality care of children. Prof. MM
Deka, Principal, Guwahati Medical College released the souvenir and Nandita Choudhary presided
over the inaugural meeting. Inspite of Durga Puja, there was participation of 100 delegates from
different parts of Assam including pediatricians, nephrologists, urologists, pediatric surgeons.
Faculty for the CME included: Drs. Srivastava, Sujit Chaudhary and Sushmita Banerjee. The
interactions during “Meet the Expert” made it the most successful session. Dr. Dipti Devi was the
Organizing Secretary for the CME.
4
Renal Glucosuria – A Case Report
Renal glucosuria is the excretion of glucose in urine in detectable amounts at normal blood glucose concentrations.
Benign renal glucosuria is a self-limiting process and requires no special medical care. Glucosuria associated with
other tubular disorders such as Fanconi syndrome, cystinosis, Wilson disease, hereditary tyrosinemia or oculocerebrorenal
syndrome requires other interventions. The condition is usually benign, but rarely glucosuria may cause polyuria (1).
Some authors state that renal glucosuria is a complex HLA-linked disease with increased susceptibility to multiple
autoantibody production and suggest caution with respect to its benign nature (2).
Case Report
A 7 year old Muslim boy, third product of non-consanguineous marriage came with the complaints of anorexia and
failure to thrive for 3 years and occasional burning micturition. Examination including anthropometry, ophthalmic and
systemic examination was normal. On investigations the blood counts, fasting and post prandial glucose, electrolytes,
pH, bicarbonate, phosphate and uric acid levels were normal. Urinalysis was normal except for reducing substances
on several occasions. Oral glucose tolerance test performed with 30 g of glucose, showed persistent glucosuria
inspite of normal blood sugar. Glycosylated hemoglobin, ultrasound abdomen and 24-hr urine aminoacids were normal.
Urine chromatography showed presence of glucose and traces of galactose. The family members were found to
have no reducing substance in urine.
A diagnosis of renal glucosuria was made. The parents were counseled about the benign nature of the disease and no
risk of progression to diabetes mellitus.
Discussion
The criteria used for diagnosis of renal glucosuria include: (i) glucosuria in absence of hypoglycemia, (ii) constant
glucosuria with minimal fluctuation with diet, (iii) normal oral glucose tolerance test, (iv) identifiable reducing substance
in the urine, and (v) normal storage and utilization of the carbohydrates.
In normal individuals, glucose is present in the glomerular filtrate at a concentration equal to that in plasma and is
reabsorbed in the proximal tubule by a sodium-dependent process (1). Normal urine contains small amounts of
glucose and other carbohydrates, called basal glucosuria. Increased amount of glucose beyond the basal excretion
rate i.e., frank glucosuria reflects reduced activity of tubular glucose reabsorption. Clinically, there are two conditions
due to primary disturbance of epithelial glucose transport: intestinal glucose-galactose malabsorption and benign
familial renal glucosuria. In the latter, both the renal threshold for glucose and maximal tubular glucose reabsorption
are diminished. The renal abnormality in primary glucosuria is specific to glucose and not other monosaccharides. The
inheritance pattern is autosomal recessive, although autosomal dominant transmission has been reported. The degree
of glucosuria is variable; the most severe defect shows minimal glucose threshold and extremely low levels of
maximal glucose reabsorption (type 0). The moderate and mild types show variable reductions of both functional
parameters (3). Familial renal glucosuria is divided in three types as follows:
•
Type A glucosuria (reduction in both glucose threshold and maximal glucose reabsorption rate).
•
In type B glucosuria (reduction in glucose threshold, but normal maximal reabsorptive rate).
•
Type O glucosuria (complete absence of glucose reabsorption) (3).
Glucose reabsorption is age dependent. In premature infants less than 30 weeks’ gestation, glucosuria is quite common
because the filtered load of glucose delivered to the kidney is too high for immature nephrons to handle. Glucosuria
normally occurs when the plasma glucose content is above 300 mg/dl, but some glucose may be seen in the urine at
plasma glucose level as low as 150 mg/dl because there is a great deal of variability in the glucose-handling capacity
of individual nephrons. This variability arises from variation in the length of the proximal tubule and differences in
glomerular size and location.
Tubular maximum for glucose (Tm glucose, mg/min/1.73m2) corrected for the glomerular filtration rate does not vary
5
as a function of age and can be interpreted using standard nomograms.
Plasma glucose concentration, glucose tolerance testing and glycosylated hemoglobin concentrations are normal.
Other renal abnormalities are absent. However there are families with glucosuria associated with uricosuria, in
absence of other features of renal tubular dysfunction.
Therapy is not necesary in patients with isolated renal glucosuria. The patient and family needs to be counseled
regarding the benign nature of the disease. If findings suggest other tubular disorders, specific interventions may then
be required. Rarely, in cases with significant glucosuria, glucose or other carbohydrates may be required during
episodes of physical activity to prevent hypoglycemia.
References
1.
Longo N. Inherited defects of membrane transport. In: Harrison’s Principles of Internal Medicine, 15th edn. Eds. Braunwald
E, Fauci AS, Kasper DL, et al. Mc Graw Hill, New York, 2004; pp 2309-15
2.
De Marchi S, Cecchin E, Basile A. Is renal glycosuria a benign condition? Proc Eur Dial Transpalnt Assoc 1983; 20:
681-5
3.
Brodehl J, Oemar BS, Hoyer PF. Renal glucosuria. Pediatr Nephrol 1987; 1: 502-8
DP Karmarkar, ST Ghatage, Girish Kakade, Priya Palkar
Shri Tatyasaheb Ghatage Charitable Trust’s Ghatage Pediatric Hospital & PG Institute,
Sangli, Maharashtra
Editorial Comment
The authors report a case of renal glucosuria, a benign and familial isolated disorder of proximal tubular glucose transport.
The causative gene SLC5A2, has recently been characterized, which encodes the kidney specific, low affinity/high capacity Na+/
glucose cotransporter, SGLT2. Better understanding of the underlying pathogenic mechanisms may be obtained by glucose
titration studies, which allow characterization of renal glucosuria into types A, B and O.
Ninth Asian Congress of Pediatric Nephrology
The Asian Congress, held from 28-30 October 2005 in Beijing (China), was attended by 380
delegates from 32 countries across the world. The theme of the Congress was ‘Caring for Children
with Renal Diseases in Today’s Asia’. State of the art guest lectures on clinical topics and cuttingedge research were the highlights of the Meeting. Ten delegates represented India. Drs. Kanitkar
and Hari deserve our congratulations on being awarded prizes for their high quality research
presentations.
A Workshop on Pediatric Nephrology, under the aegis of the Asian Society of Pediatric Nephrology,
is scheduled in Bangalore for 2006. The next Asian Congress will be held in Bangkok in 2008.
6
Urine Examination
Urine examination is a simple and readily available test to evaluate disorders of the renal tract. This article reviews
the utility of some tests available in routine practice.
Urinalysis should always be performed on a freshly voided urine sample (preferably within 30 minutes to avoid false
positive and negative results). A sample obtained after local cleaning with water is used for analysis. Freshly voided
urine is clear and pale to dark yellow. Some medications and foods can alter the urine color (Table 1). In alkaptonuria,
urine of the affected child becomes black on exposure to air, due to oxidation and polymerization of homogentisic acid.
The presence of cellular elements, casts, proteins and crystals (phosphates) gives urine a cloudy appearance. Urine
may appear turbid following prolonged storage, primarily due to precipitation of salts, which clears after addition of a
small amount of acid. The urine pH varies between 4.5-8.0. Under most conditions, the early morning pH is usually
between 5.0-5.5. Inability to achieve a low urine pH in the presence of systemic acidosis is characteristic of renal
tubular acidosis.
Specific gravity, measured with a refractometer, gives an estimate of the hydration status and the concentrating ability
of the kidneys. The normal specific gravity varies between 1015-1030. Low fixed (1010) specific gravity, on multiple
occasions, implies impaired concentration as in diabetes insipidus or end stage renal disease. Specific gravity of more
than 1.035 is due to contamination during storage, significant glucosuria, or if the patient has recently received highdensity radiopaque contrast media or low molecular weight dextran solutions. Assessment of urine osmolality provides
an accurate estimate of the ability to concentrate urine, but is not frequently available.
Protein
Normal 24-hr protein excretion is less than 150 mg. Nephrotic range proteinuria is defined as urinary
protein excretion more than 1 g/m2/24 hr. Precise determination of 24-hr urine protein is however, seldom necessary.
Protein excretion can be semiquantified on a spot specimen (preferably the first morning void) by using a urine protein
to creatinine ratio (Up/Uc); ratio of more than 0.2 indicates proteinuria and values >2 are nephrotic range! Dipsticks
detect protein by production of color with an indicator dye, tetrabromophenol blue. Presence of gross hematuria,
pyuria and bacteriuria may give false positive results with dipsticks. Precipitation by heat is a better semiquantitative
method, but is not very sensitive. The sulfosalicylic acid (3%) test can detect albumin, globulins and Bence-Jones
protein at low concentrations. False positive results may occur with intake of penicillins, cephalosporins, sulfonamides
and radiographic contrast.
Nitrite and Leukocyte esterase
A positive nitrite test is suggestive of significant bacteriuria. It is due to the
conversion of nitrate to nitrite by Gram-negative rods, such as E. coli. A positive leukocyte esterase test results from
the presence of white blood cells. Pyuria can be detected even if the urine sample contains damaged or lysed white
cells. A combination of leukocyte esterase and nitrite tests by dipsticks is reliable, but its sensitivity is low in infants,
who void frequently (Table 2).
Microscopy
It is important to examine multiple samples of urine for bacteria, red blood cells, leukocytes and
casts. A sample of fresh urine (usually 10-15 ml) is centrifuged in a test tube at a speed of (3-5000 rpm) for 5-10
minutes. The supernatant is decanted and 0.2 to 0.5 ml urine is left inside the tube. The sediment is resuspended in the
remaining supernatant. A drop of resuspended sediment is poured onto a glass slide, cover slip applied and examined
microscopically.
The presence of more than 5 red cells per high power field is suggestive of hematuria. Phase contrast microscopy
helps in differentiating between glomerular and non-glomerular hematuria. Presence of dysmorphic red blood cells
suggests glomerular hematuria (see related article in Bulletin). The detection of more than 5 leukocytes/HPF in a
centrifuged sample or more than 10/mm3 in an uncentrifuged sample may suggest urinary tract infection. However,
leukocytes may also be found with fever, glomerulonephritis (GN) or interstitial nephritis.
Epithelial cells can be normally seen in the urine specimen. Squamous epithelial cells from the skin surface or from the
7
outer urethra can appear in the urine. Urinary casts are formed only in the distal convoluted tubule or the collecting
duct. Hyaline casts are composed primarily of a mucoprotein (Tamm-Horsfall protein) secreted by tubule calls.
Presence of red cell casts suggests GN. White cell casts are found in pyelonephritis but may also be seen in GN.
The detection of crystals especially oxalates, phosphates and urates may be normal and not always indicative of
nephrolithiasis. If radiological evidence of stone disease is present, estimation of 24-hr urinary excretion of calcium,
oxalates, urates and phosphates is recommended. Estimates of the urinary excretion of these compounds are also
possible on spot (fasting) urine specimens. Urinary calcium excretion >4 mg/kg/d suggests hypercalciuria, as in
idiopathic hypercalciuria, renal tubular acidosis, vitamin D excess and prolonged immobilization.
Pathogens
Presence of bacteria on a fresh urine specimen correlates well with significant bacteriuria. Yeast
cells indicate contamination, but presence of budding yeast cells or hyphae within casts indicate fungal urinary infection.
Urine culture
Urine culture is the gold standard to diagnose urinary tract infections. Urine must be collected
carefully, to prevent contamination by periurethral flora, in a sterile bottle. A clean-catch urine specimen is often used;
obtaining a midstream sample is not always possible in young children. Washing the genitalia with soap and water can
minimize contamination by periuretheral and prepucial organisms. Antiseptic washes and forced prepucial retractions
are not required. Prompt plating of urine specimen, within one hour of collection, is important and the sample should
be refrigerated at 4o C, if delay is anticipated.
Culture of urine collected from a urobag, applied to the perineum, has an unacceptably high false positive rate.
However, a negative culture from the bag specimen has a high predictive value for absence of infection. In young
infants suprapubic aspiration or urethral catheterization is the best way to collect the sample, as a clean catch
specimen is difficult to procure. The colony counts should be interpreted based on the method of collection (Table 3).
Table 1. Causes of coloured urine.
Foods dyes, drugs and pigments
Beetroot, carotene
Riboflavin
Rifampicin
Phenolphthalein
•
•
•
•
•
•
Hematuria
Hemoglobinuria
Myoglobinuria
Bile pigments
Porphyria
Alkaptonuria
Table 2. Sensitivity and specificity of components of urinalysis
Test
Sensitivity %
Specificity %
83
53
73
81
78
98
81
83
99.8
70
Leukocyte esterase
Nitrite
Microscopy: leukocyturia
Microscopy: bacteriuria
Leukocyte esterase or nitrite or
microscopy positive
Table 3. Diagnosis of urinary tract infection*
Method of collection
Suprapubic aspiration
Urethral catheterization
Midstream clean catch
Colony counts (CFU/ml)
Probability of infection (%)
Any number
>50 X 103
>105
99
95
90-95
*Lower colony counts often found in infants, infection with S. saprophyticus, Mycoplasma, Candida spp.
8
References
1.
Liao JC, Churchill BM. Pediatric urine testing. Pediatr Clin North Am 2001; 48: 1425-40.
2.
Practice parameter. The diagnosis, treatment and evaluation of the initial urinary tract infection in febrile infants and young
children. American Academy of Pediatrics. Committee on Quality Improvement. Subcommittee on Urinary Tract Infection.
Pediatrics. 1999; 103: 843-52.
3.
Dalton RN, Haycock GB. Laboratory investigation. In: Baratt TM, Avner ED, Harmon WE (eds). Pediatric Nephrology, 4th edn.
Baltimore: Williams & Wilkins, 1999; 343-64
Shina Menon
Department of Pediatrics
All India Institute of Medical Sciences, New Delhi
Selected Abstracts
Abstracts from India at the Ninth Asian Congress of Pediatric Nephrology, Beijing (China)
The first two papers were awarded the Best Paper prize during the Congress.
Does serum cystatin C provide a reliable estimate of renal function in malnourished & normally nourished
boys?
Pankaj Hari, Arvind Bagga, R Lakshmy
All India Institute of Medical Sciences, New Delhi, India
Objective To determine whether serum creatinine and cystatin C levels are affected by the nutritional status in children.
Methods Serum levels of creatinine and cystatin C were estimated in 76 malnourished and 78 normally nourished boys
between 2-6 years of age without evidence of renal disease. Serum cystatin C level was measured by particle enhanced
immunoturbidimetry using the Cystatin PET kit (DAKO) on a Hitachi 717 Autoanalyzer.
Results The mean (SD) age of the subjects was 48.4 (15.6) months. The mean weight SD score was -1.0 (0.8) in
normally nourished group while it was -2.9 (0.7) in malnourished group. The mean height of normally nourished children
and malnourished children was 100.1 (9) and 91.6 (11) cm, respectively. The mean (95% confidence interval) serum
creatinine level in malnourished boys was significantly lower than normally nourished boys [0.41 (0.37-0.44) vs. 0.50
(0.46-0.54) mg/dl, P<0.003]. The mean serum cystatin C level was 1.0 (0.93 -1.2) mg/dl and 1.0 (0.89 -1.1) respectively
in normal and malnourished boys (P=0.7). Serum creatinine levels significantly correlated with weight SD score (r=0.22,
P=0.005) and height (r=0.33, P=0.000l). There was no correlation of serum cystatin with weight or height.
Conclusion In contrast to serum creatinine, cystatin C level was not affected by the nutritional status. Serum cystatin C
would thus provide a more reliable estimate of glomerular filtration rate in malnourished children than serum creatinine.
Histopathological diagnosis and treatment of steroid resistant nephrotic syndrome in children
Madhuri Kanitkar, VS Nijhawan, Manas K Behera
Armed Forces Medical College, Pune, India
Objective Therapy for children with steroid resistant nephrotic syndrome (SRNS) is often empirical. This study analyzes
the clinicopathological features and outcome in children presenting with SRNS treated with a combination of
methylprednisolone pulses, alternate day oral prednisolone and cyclophosphamide.
Methods 36 children with SRNS, excluding four with resistance due to infections, seen over a 3 year period underwent
a kidney biopsy. Idiopathic primary NS was noted in 26. These children were treated with six alternate day pulses of
methylprednisolone (MP) followed by oral cyclophosphamide for 12 weeks and alternate day tapering prednisolone.
Children with FSGS were continued on 4 fortnightly and 8 monthly MP pulses. Follow up was minimum 6 months. Data
9
analyzed retrospectively using the t-test & Wilcoxon Rank sum test for numerical values and the Chi square test for
categorical values followed by a multivariate analysis to determine the predictors for response.
Results There were 19 boys, 7 girls (M:F::2.7:1). Mean age 4.65+3.2 years. Commonest pathology was mesangioproliferative
glomerulonephritis (36%) with IgM deposits in 44%. Treatment was discontinued within six months in seven due to
either severe infections, or progression to renal failure. Remission noted in 18. Outcome significantly better if the histology
was minimal change (p<0.00l) and children were treated with pulse MP (p=0.016) and cyclophosphamide (p=0.07) but
poor with higher blood urea levels at presentation and 1gM (p=0.008) deposits.
Conclusions Pulse MP along with cyclophosphamide therapy are associated with severe infections, however they can
induce remission in a significant number of children on a univariate analysis. On a multivariate analysis model, children
with lower blood urea and higher albumin levels at presentation had a better outcome, but 1gM deposits on renal biopsy
predicted a poor outcome. Age, gender and other biochemical parameters at presentation did not have a bearing on the
response to therapy.
Does albumin infusion augment frusemide-induced diuresis in edematous children with nephrotic syndrome?
Pankaj Hari, Rajmohan D, Arvind Bagga
All India Institute of Medical Sciences, New Delhi, India
Objectives In a crossover trial, we compared the diuretic and natriuretic effects of combined albumin infusion along with
frusemide infusion alone in children with nephrotic syndrome and refractory edema.
Methods 10 children with nephrotic syndrome and edema refractory (weight loss less than 10% per day) to intravenous
frusemide given as bolus (4 mg/kg/d) were studied. Patients were randomized in a cross over manner to receive 20%
human albumin infused over 4 hr with frusemide infusion (HA+FU) (0.3 mg/kg/hr) or frusemide (FU) infusion alone.
Results Median (95% confidence interval) weight loss, cumulative urinary volume (UV), sodium excretion (UNa), osmolal
clearance (Cosm) and free water clearance (CH2O) during 24 h infusion of HA + FU or FU alone are shown below:
HA+ FU
FU
P
1.1 (1.8-3.5)
650 (348-1971)
25.8 (9.3-128
2979
(1679-5778)
-1802
0.3
0.0005
0.09
0.04
CH20
2.7 (0.2-7.4)
1630 (755-4343)
53.7 (25.2-359)
6336
(3117-8802)
-3765
(ml/d)
(-1888 - -6030)
(-1181 - -3846)
Weight loss (%)
UV (ml/d)
UNa (mEq/d)
Cosm (ml/d)
0.09
The rise in urinary volume, sodium excretion and osmolal clearance from the baseline were far greater after HA+FU than
FU infusion alone (P=0.005).
Conclusion The data suggests that albumin infusion potentates the diuretic and natriuretic effects of frusemide infusion
in children with nephrotic syndrome and refractory edema. We speculate that these effects might be mediated by expansion
of intravascular volume and release of atrial natriuretic peptide.
Antiproteinuric effect of enalapril versus combination of enalapril and irbesartan in steroid resistant
nephrotic syndrome (SRNS)
Vijesh S, Hari P, Vasudev V, Bagga A
All India Institute of Medical Sciences, New Delhi, India
Objective To compare the antiproteinuric efficacy of enalapril versus a combination of enalapril and irbesartan.
Methods In a non-blinded, randomized controlled trial, 17 patients with SRNS were enrolled. Patients in group A (n=8)
received enalapril (0.4 mg/kg/day) for 12 weeks. Those in group B (n=9) received enalapril (same dose) & irbesartan (4
10
mg/kg/day). None received daily or intravenous steroids, aIkylating agents, cyclosporine, NSAIDs or other
antihypertensives. Total and percentage reduction of 24-hr urine albumin excretion were determined.
Results The median age at treatment in groups A & B were 11 and 8 years respectively. Of 17 patients, 5 had minimal
change disease, 5 mesangioproliferative GN, 6 membranoproliferative GN and one FSGS. The groups were comparable
in their clinical and biochemical features at baseline. At 12 weeks, patients in group A showed 44.5% (median) reduction
in 24-hr urinary albumin (P 0.03), while those in group B showed a reduction of 39.7% (P 0.3). Patients in group B
showed a significant reduction in systolic blood pressure and hemoglobin levels. No significant change was found in
levels of serum potassium and creatinine (Table).
Conclusion Combination therapy with enalapril and irbesartan did not result in an additional reduction in proteinuria
compared to enalapril alone. Patients on combination therapy should be monitored for anemia, fall in blood pressure and
rise in serum creatinine and potassium.
Group A
24-hr urine albumin (g)
Systolic blood pressure (mm Hg)
Hemoglobin (g/dl)
Serum potassium (mEq/l)
Serum creatinine (mg/dl)
Group B
Baseline
Final
Baseline
Final
2.5
114
10.2
4.5
0.6
1.8*
112
11.4
4.3
0.65
1.8
110
11.9
4.3
0.5
1.1
100*
10.8*
4.9
0.6
* P<0.05
Clinical features and outcome of microscopic polyangiitis (MPA)
Goel R, Mantan M, Dinda A, Hari P, Bagga A
All India Institute of Medical Sciences, New Delhi, India
Aim To study the clinicopathological profile and outcome of MPA in children.
Methods Records of children presenting with MPA (13 patients, 7 boys) over the last 15 yr were retrieved. Case sheets
were reviewed for history of hematuria, oliguria, anasarca, rash, fever, hypertension and any systemic complaints.
Investigations included hemogram, renal and liver function tests, urinalysis, serum C3, ANCA serology; renal biopsy was
examined by light microscopy and immunofluorescence. MPA was defined as non-granulomatous, pauci-immune,
necrotizing vasculitis affecting small vessels. All patients received intravenous corticosteroids and cyclophosphamide for
six months followed by oral steroids and azathioprine.
Results The mean (SD) age at presentation was 8.4 (2.8) yrs. The chief clinical features were hematuria (69%), pallor
(92%), fever and anasarca (62% each), hypertension and maculopapular rash (54% each) and oliguria (39%). Seven
patients presented with rapidly progressive renal failure; others had normal renal functions. Mean serum creatinine at
presentation was 1.7 mg/dl. Four (31%) patients had a positive ANCA serology (3 had pANCA, 1 cANCA). Kidney
biopsy showed crescentic GN in 55% patients. At mean follow up of 5.9 (1.8) yr, 9 (70%) had normal renal functions
(mean serum creatinine 0.8 mg/dl) and four had chronic renal failure (CRF). All patients with CRF had high chronicity
index and crescentic GN on initial renal histology. End stage renal disease occurred in 3 subjects after 4.9 (1.7) yr who
then underwent dialysis and transplant.
Conclusions Patients with MPA may present with severe glomerulonephritis and are at risk for CRF. Serology for ANCA
was positive in a small proportion of patients. Early diagnosis and treatment of microscopic polyangiitis is likely to be
associated with a favorable outcome.
Post-streptococcal acute glomerulonephritis: is it still benign?
Mehul A. Shah, G. Swaranlatha
Rainbow Children’s Hospital and Apollo Hospitals Hyderabad, India
Objective Severe crescentic glomerulonephritis due to PSAGN with subsequent development of chronic kidney disease
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prompted this retrospective study of admitted children with PIAGN
Methods We reviewed the records of children admitted with PSAGN over 5 years period. Clinical features including
severity of hypertension at presentation, presence of nephritic-nephrotic features, renal failure, kidney biopsy, treatment
with corticosteroids, and outcome was analyzed. Diagnosis of PSAGN was made on clinical features, preceding history
of throat / skin infection, low serum complements, and renal histopathological findings in selected children.
Results 60 children (38 boys) were admitted with PSAGN. The presenting features were body swelling & decreased
urine output (100%), gross hematuria (40%), headaches (20%), seizures (7%), hypertension (100%), microscopic
hematuria (59/60), and azotemia (65%). The children were divided into following groups: 1) Typical AGN in 57%, 2)
Nephritic-Nephrotic features (12%), 3) RPGN (23%), 4) Recurrent PIAGN (3%), and 5) underlying chronic kidney
disease (5%). Kidney biopsy was performed in 19/60 (32%) children (all belonging to last 4 groups). Crescents were
noted in 5 biopsies. Most children were treated conservatively and 5/60 (8%) required dialysis. Corticosteroids were
administered in 14/60 (23%) children with RPGN with the mean duration being 6.3 months (range 5-11 months). 7/14 are
off steroids for >9 months and in remission. One patient with severe crescentic glomerulonephritis had delayed treatment
with steroids & required cyclophosphamide and mycophenolate mofetil for persistent renal failure.
Conclusions PSAGN can present with nephritic-nephrotic picture and is an important cause of RPGN. Kidney biopsy in
these two settings helps to confirm the pathology and rule out other etiologies. Most children treated with corticosteroids
had a favorable response and the only child with severe crescentic glomerulonephritis who was initiated late on steroids,
has chronic kidney disease.
The clinical significance of asymptomatic gross and microscopic hematuria in children
Bergstein J, Leiser J. Arch Pediatr Adolesc Med, 2005; 159.
Background Pediatricians are often referred patients with sudden onset of asymptomatic gross or microscopic hematuria.
However, the clinical significance of asymptomatic hematuria is unclear and the merit of a detailed evaluation has not been
confirmed.
Methods This report examines the underlying etiology in 582 children evaluated for asymptomatic gross or microscopic
hematuria. Twelve patients were excluded from further consideration because of a family history of hematuria leaving a
study group of 570 children. Evaluation included a personal and family history, physical examination and comprehensive
laboratory and radiological investigations.
Results Of 342 children with microscopic hematuria, no cause was found in 274 (80%) patients. The chief causes
detected were hypercalciuria (16%) followed by post-streptococcal glomerulonephritis (1%). Two patients underwent
kidney biopsy; one each had IgA nephropathy and membranoproliferative GN. Of 228 children with gross hematuria, no
cause was found in 86 (38%) patients. The most common cause was hypercalciuria (22%). Ten patients had clinically
important structural abnormalities. Fifty three patients underwent a renal biopsy; 36 had IgA nephropathy.
Conclusions These data suggest that a detailed diagnostic evaluation for causes of microscopic hematuria in children
may not be necessary. Asymptomatic microscopic hematuria in children was rarely associated with clinically important
disease of the urinary tract. No cause was found in a large majority of patients. Interestingly, not one patient with
microscopic hematuria had evidence of UTI or any radiological abnormality. Routine renal biopsy is not required in
children with microscopic hematuria. Rarely asymptomatic microscopic hematuria can be the first sign of occult renal
disease. However, in patients with microscopic hematuria due to occult glomerular disorders, progression to clinically
significant disease will be very often accompanied by the development of hypertension and/or proteinuria. Thus, longterm follow up of children with microscopic hematuria is necessary.
A clinically important cause for gross hematuria is much more common and a thorough diagnostic evaluation is justified
but for asymptomatic microscopic hematuria, the new message is ‘don’t look, don’t evaluate’.
Rupesh Jain
IPNA Fellow
All India Institute of Medical Sciences, New Delhi
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