RENAL SYSTEM

Acute Poststreptococcal Glomerulonephritis

1. Etiology
a. Acute poststreptococcal glomerulonephritis follows infection of the
throat or skin by certain "nephritogenic" strains of group A -hemolytic
streptococci. throat (serotype 12) and skin (serotype 49)
2. Pathology
a. Immunofluorescence microscopy reveals lumpy-bumpy deposits of
immunoglobulin and complement on the glomerular basement
membrane (GBM) and in the mesangium.
b. On electron microscopy, electron-dense deposits, or "humps," are
observed on the epithelial side of the GBM.
3. Pathogenesis:
a. The circulating immune complexes in poststreptococcal
glomerulonephritis are deposited on glomerular basement membrane
and complement activation through the alternative pathway.
4. Clinical Manifestations:
a. Age: 5-12 yr
b. The severity is variable
c. Tea or cola-colored urine,
d. Cardinal features: triad is called nephritic syndrome
i. Edema
ii. Hypertension
iii. Oliguria
e. Encephalopathy and/or heart failure owing to hypertension or
hypervolemia.
f. Malaise, lethargy, abdominal or flank pain, and fever are common.
g. The acute phase generally resolves within 6-8 wk. Although urinary
protein excretion and hypertension usually normalize by 4-6 wk after
onset, persistent microscopic hematuria may persist for 1-2 yr after the
initial presentation
5. Diagnosis:
a. Urinalysis demonstrates:
i. Red blood cells
ii. RBC casts,
iii. Proteinuria, and
iv. Polymorphonuclear leukocytes.
b. A mild normochromic anemia may be present from hemodilution and
low-grade hemolysis.
c. The serum C3 level is usually reduced in the acute phase
d. Confirmation of the diagnosis:
i. Positive throat culture
ii. A rising antibody titer to streptococcal antigen(s)
iii. The antistreptolysin O titer is elevated after a pharyngeal
infection
iv. Deoxyribonuclease (DNase) B antigen antibody titer in skin
infection
v. The Streptozyme test detects antibodies to streptolysin O, Dnase
B etc
vi. A low C3 level
e. Renal biopsy should be considered in:

i. Absence of evidence for streptococcal infection

ii. Normal complements levels.
iii. When hematuria and proteinuria, diminished renal function,
persist more than 2 mo after onset
6. Differential Diagnosis:
a. Diseases commonly presenting as acute nephritic syndrome include:
i. Postinfectious glomerulonephritis,
ii. Iga nephropathy,
iii. Membranoproliferative glomerulonephritis,
iv. Henoch-Schnlein purpura nephritis (HSP),
v. Systemic lupus erythematosus (SLE) nephritis,
vi. Wegener granulomatosis,
vii. Microscopic polyarteritis nodosa,
viii. Goodpasture syndrome, and
ix. Hemolytic-uremic syndrome.
7. Causes of Hematuria:
Glomerular diseases
Acute post infectious
glomerulonephritis
IgA nephropathy
Benign familial hematuria
Systemic infections(malaria,
leptospirosis, infective
endocarditis)
Membranoproliferative
glomerulonephritis
Focal segmental
glomerulosclerosis
Systemic lupus erythematosus
Hemolytic uremic syndrome
Henoch-Schonlein purpura
Alport's syndrome
Goodpasture's disease

Non-glomerular causes
Nephrolithiasis
Hypercalciuria
Viral hemorrhagic cystitis
Urinary tract infection

Vascular abnormalities: Renal vein or

artery thrombosis, A-V malformations
Trauma, Tumors, Exercise
Hematologic
Hydronephrosis
Renal cystic disease
Medications: NSAIDs, anticoagulants,
cyclophosphamide, ritonavir, indinavir
Tuberculosis
Munchaussen syndrome/ Munchaussen
by proxy

8. Agents that may Color Urine Red or pink:

Red cells, free hemoglobin, myoglobin,
Urates
Drugs: chloroquine, phenazopyridine
Beets, red dyes in food
Porphyrins
Rifampicin, pyridium
Bile pigments
Methemoglobinemia

9. Acute glomerulonephritis may also follow infection with:

i. Coagulase-positive & Coagulase-negative staphylococci
ii. Streptococcus pneumoniae, and gram-negative bacteria
iii. Bacterial endocarditis
iv. Fungal, rickettsial, and viral diseases, particularly, influenza

10.Complications:
a. Hypertension is seen in 60% of patients and may be associated with
hypertensive encephalopathy in 10% of cases.
b. Other potential complications include:
i. Heart failure,
ii. Hyperkalemia,
iii. Hyperphosphatemia,
iv. Hypocalcemia,
v. Acidosis,
vi. Seizures
vii. Uremia
11.Prevention:
a. Early systemic antibiotic therapy for streptococcal throat and skin
infections does not eliminate the risk of glomerulonephritis.
12.Treatment:
a. A 10-day course of systemic antibiotic therapy with penicillin to limit
the spread of the nephritogenic organisms,
b. But antibiotic therapy does not affect the natural history of
glomerulonephritis.
c. Treatment of hypertension:
i. Sodium restriction,
ii. Diuresis,
iii. Pharmacotherapy with calcium channel antagonists,
vasodilators, or angiotensin-converting enzyme inhibitors
d. Diet: In diet, sodium, potassium, and phosphorus should be restricted.
Protein intake should be restricted moderately while maximizing caloric
intake to minimize the accumulation of nitrogenous wastes.
i. Fluid: restrict fluid to 15 ml/kg for insensible water loss plus
previous day urine ouput
ii. Calories: no restriction; give 1000 cal + 100 per year of age +
10 % of of the two for infection; encourrage rice, jiggery and
some oil.
iii. Protein: < 1.75 gm/kg/day and if there is oliguria (<1
ml/kg/hour) restrict to 1 gm/kg/day; avoid pulses, egg, meat etc
iv. Sodium:
1. complte restriction during oliguria;
2. <2gm/day during diuretic phase;
3. 10 gm/day as normal urine ouput is restored.
v. Potassium: potassium shoud be avoided. Fruits, fruit juices,
coconut juice etc should be avoided.

e. Prognosis:
i. Complete recovery occurs in more than 95% of children
ii. Infrequently, the acute phase may be severe and lead to
glomerular hyalinization and chronic renal insufficiency.
iii. Recurrences are extremely rare.
NEPHROTIC SYNDROME
1. Epidemiology:
a. Nephrotic syndrome is 15 times more common in children than adults.
b. The incidence is 2-3/100,000 children; majority will have steroidsensitive minimal change disease.
2. Definitions: 4 important features
a. proteinuria (>3.5 g/24 hr in adults or 40 mg/m 2/hr in children),
Nephrotic-range proteinuria
b. Hypoalbuminemia (<2.5 g/dl),
c. Edema
d. Hyperlipidemia.
3. Etiology:
a. 90% have idiopathic nephrotic syndrome.
b. Causes of idiopathic nephrotic syndrome include:
i. Minimal change disease (85%),
ii. Mesangial proliferation (5%),
iii. Focal segmental glomerulosclerosis (10%).
iv. The remaining 10% of children: membranous nephropathy or
membranoproliferative glomerulonephritis
c. Pathophysiology:
i. Increase in permeability of the glomerular capillary wall, which
leads to massive proteinuria and hypoalbuminemia.
ii. Increase in serum lipid levels (cholesterol, triglycerides) due to
1. Increased synthesis of lipoproteins.
2. Increased urinary losses lipoprotein lipase
4. Idiopathic Nephrotic Syndrome:
a. Idiopathic nephrotic syndrome includes three histologic types:
i. minimal change disease,
ii. mesangial proliferation, and
iii. focal segmental glomerulosclerosis
b. Pathology:
i. Minimal change disease:85% of cases
1. The glomeruli appear normal under light miicroscope
2. Electron microscopy reveals effacement of the epithelial
cell foot processes.
ii. Mesangial proliferation (5% of total cases):
1. Diffuse increase in mesangial cells and matrix on light
microscopy.
2. Immunofluorescence microscopy may reveal mesangial
IgM and/or IgA staining.
3. Electron microscopy reveals increased numbers of
mesangial cells and matrix as well as effacement of the
epithelial cell foot processes.
iii. Focal segmental glomerulosclerosis (10% of total cases):
1. Glomeruli show mesangial proliferation and segmental
scarring on light microscopy

2. Immunofluorescence microscopy shows IGM and C3

staining in the areas of segmental sclerosis.
5. Clinical Manifestations:
a. Sex: common in males than in females (2:1)
b. Age: 2 to 6 yr.
Clincal featyres:
a. Initially presents with mild periorbital edema misdiagnosed as an
allergic disorder
b. With time, the edema becomes generalized, with the development of
ascites, pleural effusions, and genital edema.
c. Anorexia, irritability, abdominal pain, and diarrhea are common;
d. Hypertension and gross hematuria are uncommon.
6. The differential diagnosis of the child with marked edema:
a. Protein-losing enteropathy,
b. Hepatic failure,
c. Congestive heart failure,
d. Acute glomerulonephritis
e. Protein malnutrition( ascites and scrotal edema uncommon)
7. Diagnosis:
a. The urinalysis reveals 3+ or 4+ proteinuria;
b. Microscopic hematuria may be present in 20% of children.
c. Urinary protein excretion exceeds 3.5 g/24 hr in adults and 40
mg/m2/hr in children.
d. Spot urine protein to creatinine ratio exceeds 2.0.
e. The serum creatinine value is usually normal,
f. The serum albumin level is less than 2.5 g/dL,
g. Serum cholesterol and triglyceride levels are elevated.
h. C3 and C4 levels are normal.
i. Renal biopsy is not required for diagnosis in most children
8. Treatment:
a. Mild:
i. Children with mild to moderate edema may be managed as
outpatients.
ii. Initially a low sodium diet and may be normalized when the child
enters remission.
b. Severe form:
i. Children with severe symptomatic edema, including large pleural
effusions, ascites, or severe genital edema, should be hospitalized.
ii. Fluid restriction may be necessary if the child is hyponatremic.
iii. A swollen scrotum may be elevated with pillows
iv. Diuresis: in severe cases
i. by intravenous administration of chlorothiazide (10 mg/kg/dose)
followed by furosemide 30 min later (1-2 mg/kg/dose)
ii. Intravenous administration of 25% human albumin (0.5 g/ kg)
9. Steroid therapy:
1. In most cases steroid therapy may be initiated without renal biopsy.
2. Children with hematuria, hypertension, renal insufficiency,
hypocomplementemia and age < 1 yr or > 8 yr should be considered
for renal biopsy before treatment.
3. Before initiation of steroid, tuberculosis must be ruled out by Mx test.
4. Steroid initiation:

a. Prednisone 60 mg/m2/day (maximum daily dose, 80 mg), divided

into two to three doses for at least 4 consecutive weeks. 6 weeks
in some centers
b. 90% of children will respond to steroid therapy
c. Steroid response or remission is indicated by:
i. Urine trace or negative for protein for 3 consecutive days,
ii. The median time to remission of 10 days.
5. Steroid toxicity: cushingoid appearance, hypertension, cataracts,
and/or growth failure.
6. Steroid tapering:
a. After the initial 4-6 wk course, the prednisone dose should be
tapered to 40 mg/m2/day given every other day as a single morning
dose.
b. The alternate-day dose is then slowly tapered and discontinued over
the next 2-3 mo.
7. Definition of steroid resistance:
c. Children who continue to have proteinuria (2+ or greater) after 8 wk
of steroid therapy are considered steroid resistant,
d. A diagnostic renal biopsy should be performed.
8. Definition of Relapse:
a. Many children with nephrotic syndrome will experience at least one
relapse (3-4+ proteinuria plus edema
b. Relapses should be treated with daily divided-dose prednisone at
the doses noted earlier until the child enters remission (urine trace
or negative for protein for 3 consecutive days).
c. The prednisone dose is then changed to alternate-day dosing and
tapered over 1-2 mo.
9. Definition of Steroid depndance:
d. A subset of patients will relapse while on alternate-day steroid
therapy or within 28 days of stopping prednisone therapy. Such
patients are termed steroid dependent.
10.
Frequent relapsers:
a. Patients who respond well to prednisone therapy but relapse four or
more times in a 12-mo period are termed frequent relapsers.
11.
Definition of Steroid resistance:
a. Children who fail to respond to prednisone therapy within 8 wk are
termed steroid resistant
ii. Cyclophosphamide therapy:
1. Indications:
a. Steroid-dependent patients,
b. frequent relapsers, and
c. steroid- resistant patients
2. Corticosteroid toxicity
3. Dose:
a. The dose of cyclophosphamide is 2-3 mg/kg/24 hr given as a
single dose, for a total duration of 8-12 wk.
b. Alternate-day prednisone therapy is often continued during the
course of cyclophosphamide administration
4. Toxicity:
a. neutropenia, disseminated varicella, hemorrhagic cystitis,
alopecia,

b. sterility, and increased risk of future malignancy

iii. Methylprednisolone IV:
1. 30-mg/kg bolus (maximum 1,000 mg), with the first 6 doses given
every other day, followed by a tapering regimen for periods up to 18
mo.
2. Cyclophosphamide may be added to this regimen in selected patients.
iv. Cyclosporine:
1. Prolonged administration of cyclosporine (3-6 mg/kg/24 hr) has also
been effective in maintaining a prolonged remission in children with
nephrotic syndrome and is useful as a steroid- sparing agent.
2. Children must be monitored for side effects, including hypertension,
nephrotoxicity, hirsutism, and gingival hyperplasia.
10.Diet:
1. Excess of protein should be avoided. But moderate
protein intake (about 1.5-2 g/kg body weight) is
mandatory to compensate for the protein loss in the urine.
2. High amount of fats should be avoided as the
cholesterol and triglyceride levels tend to be high in
patients with Nephrotic syndrome.
3. The diet must be high in calories so as to conserve
proteins, yet low in fats.
4. Sodium in the diet should be kept minimum so as to
prevent fluid accumulation and oedema. Reduction of salt
intake (1-2 g per day) is advised for those with persistent
edema. The foods that are high in sodium content and
thereby should be avoided are salted food like:popcorns,
salted biscuits, snacks, chips, Papads, pickles etc
11.
Complications of Nephrotic syndrome:
a. Infection is the major complication of nephrotic syndrome due to:
i. Urinary losses of immunoglobulins and properdin factor B,
ii. Defective cell-mediated immunity,
iii. Immunosuppressive therapy,
iv. Malnutrition
v. Edema/ascites acting as a potential "culture medium."
b. Spontaneous bacterial peritonitis is the most frequent type of infection,
although sepsis, pneumonia, cellulitis, and urinary tract infections may
also be seen.
c. Streptococcus pneumoniae is the most common organism causing
peritonitis,
12.
Immunization: All children with nephrotic syndrome should receive:
i. Polyvalent pneumococcal
ii. Varicella vaccine
iii. Influenza vaccine
13.
Thromboembolism:
a. Children with nephrotic syndrome are also at increased risk for
thromboembolic events. Overaggressive diuresis should be avoided
and use of indwelling catheters limited because these factors may
increase the likelihood of clotting complications
14.
Prognosis:

a. The majority of children with steroid-responsive nephrotic syndrome

have repeated relapses, which generally decrease in frequency as the
child grows older
b. Children with steroid-resistant nephrotic syndrome generally have a
much poorer prognosis. These children develop progressive renal
insufficiency, ultimately leading to end-stage renal failure requiring
dialysis or renal transplantation.

ACUTE RENAL FAILURE

Definition
It is a clinical syndrome of sudden deterioration of renal function in which
kidney is unable to maintain fluid and electrolyte homeostasis and
characterized by an increase in:
Blood urea nitrogen (BUN)
Serum creatinine values,
Hyperkalemia,
Metabolic acidosis,
Hypertension.
Incidence: 2-3 % pediatric intensive care
Etiologic classification
1. Prerenal:
2. Dehydration
3. Hemorrhage
4. Septic Shock
5. Hypoalbuminemia : Redistribution of extracellular fluid
6. CCF
2. Renal:
1. Glomerulonephritis :
1. Post streptococcal
2. SLE
3. Henoch - Schonlein Purpura
4. Membranoproliferative
2. Hemolytic uremic syndrome
3. Acute tubular necrosis
4. Cortical necrosis
5. Renal vein thrombosis
6. Acute interstitial nephritis
7. Tumor infiltration
8. Tumor lysis syndrome
3. Post renal:
1. Posterior urethral valve
2. Urolithiasis
3. Hemorrhagic cystitis
4. Neurogenic bladder

Prerenal ARF:
1. Inadequate renal perfusion
2. Decreased GFR
3. No kidney disease
4. Correction of hypovolemia in time cures the condition
5. If not corrected in time renal parenchymal damage occurs
Clinical features
History
1. Vomiting and diarrhea - prerenal
2. Recent pharyngitis post streptococcal
3. Exposure to nephrotoxic drugs
4. Hydronephrosis diagnosed antenataly
5. Dribbling of urine with supra pubic swelling - PUV
Physical examination
1. Tachycardia and poor peripheral perfusion - prerenal
2. Edema and cardiac gallop post sreptococcal
3. Rash and arthritis: SLE; HSP
4. Bilatreal renal mass: obstructive uropathy
Some definitions
1. Proteinuria: >150 mg/24 hour
2. Haematuria: > 5 RBCs/HPF on 3 urine tests
3. Oliguria: < 0.5 ml/kg/hour; <1ml/kg/hr in infants
4. Uremia:
Illness accompanying kidney failure proceeding to decreased mental
acuity and coma
5. Azotemia:
Refers to high levels of urea, the abnormality can be
measured chemically but is not yet so severe as to produce
symptoms.
6. BUN:
Measurement of urea content of blood; urea is split into Co2
and ammonia and ammonia is measured which is the
nitrogen part of urea: 5-15 mg/dL
Lab findings
1. Anemia: dilutional; hemolytic in HUS
2. Leukopenia: SLE
3. Thrombocytopenia: HUS
4. Hyponatremia: dilutional
5. Metabolic acidosis
6. Elevated BUN, creatinine, uric acid, potassium, phosphates
7. Low C3: PSGN, SLE
8. Hematuria: Renal-Glomerular
9. WBCs in urine: interstitial disease
10.eosinophils: drug induced interstitial nephritis
11.Prerenal:
1. Sp.gravity : > 1020
2. U Osm
:
> 500 mOsm/kg

3. U Na

: < 20 mEq/L

1. Sp.gravity
2. U Osm
3. U Na

: < 1010
:
< 350 mOsm/kg
: > 40 mEq/L

12.Renal:

Imaging
1. CXR: cardiomegaly; pulmonary congestion
2. Ultrasound:
1. Hydronephrosis
2. Hydroureter
3. Renal biopsy
Treatment
Medical
1. Bladder catheter to estimate urine output
2. Correction of hypovolemia: 20 ml/kg NaCl over 30 mts
3. Diuretic challenge after correction of hypovolemia to rule out prerenal
condition:
1. Mannitol
0.5 gm/kg - single dose
2. Furosemide
2-4 mg/kg
3. Or Bumetanide
0.1 mg/kg
4. Dopamine:
2-3 g/kg/mt
4. Persisting ARF after diuretic challenge:
1. Fluid restriction: 400 ml/m2 / 24 hr+ equivalent of urine output
5. Management of Hyperkalemia
1. Serum K: >6 mEq / L
2. Produces cardiac arrhythmia; cardiac arrest, death
3. ECG:
1. Peaked T wave; 2.widening QRS; 3. ST depression; 4.
Ventricular arrhytmia;
5. Cardiac arrest
1. Treatment:
1. Oral kayexalate (resin) 1 g/kg/ 2 hourly
2. 10% Calcium gluconate1 ml/kg IV over 3- 5mts: counteracts
myocardial irritability due to hyperkalemia
3. Sodium bicarbonate 1-2 mEq/kg IV over 5-10 mts:
1. Insulin 0.1 u/kg with glucose 50% 1 ml/kg over 1 hour: Both shift
potassium from intravascular to intracellular compartment
6. Metbolic acidosis
1. Causes: Retention of H ions, phoasphate, and sulphate
2. Severe acidosis contributes to hyperkalemia
3. It is corrected by IV sodabicarb to raise pH to 7.2
4. Full correction may precipitate hypocalcemic tetany- alkalotic
tetany:
As the pH of blood increases, the protein in the blood becomes
more ionised into anions. This causes the free calcium present in
blood to bind strongly with protein
7. Hypocalcemia

1. Treated by reducing serum phosphorus level and not by IV Ca to

avoid Ca deposition in tissues
2. Low phosphate diet
3. Phosphate binders:
1. Calcium carbonate
2. Calcium acetate
8. Hyponatremia
1. Dilutional and hence fluid restriction
2. 3% Na Cl for convulsions
9. Uremic platelet dysfunction: GI bleeding is treated by H2 blocker
10.Hypertension:
1. Salt retsriction
2. Isradipine 0.05-0.15 mg/kg/dose
3. Amlodipine, propranolal etc
4. IV nitroprusside 1 10 g/kg infusion for encephalopathy
4. Diazepam for seizures
11.Other measures:
1. Washed red cell transfusion for anemia
2. Dietary restriction:
1. Sodium
2. Potassium
3. Phosphate
4. Protein
12.Dialysis
1. Indication:
1. Pulmonary edema due to volume overload
2. Persistent hyperkalemia
3. Severe metabolic acidosis
4. Uremic coma and Seizures
5. BUN > 100 mg/dL
6. Dialysis
2. Intermittent hemodialysis large venous catheter attached to
extracorporeal circuit
3. Peritoneal dialysis:
Hyperosmolar dialysate is infused into peritoneal cavity
via
trancutaneous catheter and drained by gravity after 45 mts;
done in cycles
4. Continuous renal replacement therapy (CRRT)
Double lumen catheter in subclavian or femoral vein;
connected to CRRT circuit;
Continuos passage of blood across highly permeable filter
13.Prognosis
1. Depends on underlying disease
2. Renal limited ARF: 1% mortality
3. Multiorgan failure: 90% mortality
4. Better recovery from prerenal causes

Poor recovery from bilateral renal vein thrombosis and rapidly progressing
glomerulonephritis