Common Renal Diseases
Dr Mesfn Tassew, Pediatrician, AGHMC.
APRIL 2021
Outline
 Introduction
 DISEASES PRESENTING PRIMARILY WITH HEMATURIA
 Nephritic Syndrome Post-streptococcal Glomerulonephritis
 DISEASES PRESENTING WITH PROTEINURIA
 Nephrotic syndrome
 AKI and CKD
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INTRODUCTION …
Kidney
Function
 Excretion
of metabolic waste
products & foreign chemicals
 Regulation
of water & electrolyte
 Regulation
of arterial pressure
 Regulation
of acid base balance
4
 Secretion
,metabolism & excretion of
hormones( erythropoetin
 Gluconeogenesis
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Anatomy
• Anatomy
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Glomerular disease

Abnormalities of glomerular function
that
can be caused by damage to the major
components of the glomerulus:


Epithelium (podocytes), Basement membrane,

Capillary endothelium, & mesangium.
Two chief pathogenesis are recognized:

Deposition of antigen-antibody complexes in
glomeruli


In situ immune complex deposition
Circulating immune complex deposition

Endogenous or exogeneous antigen[ DNA,
Nuclear proteins, IgA, drugs]
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HEMATURIA and PROTEINURIA
• Hematuria and proteinuria are manifestation of disease of glomeruli
• Hematuria, defined as the persistent presence of more than 5 red blood cells
(RBCs)/high power field (HPF) in uncentrifuged urine.
• The presence of 10-50 RBCs/µL may suggest underlying pathology, but
significant hematuria is generally considered as > 50 RBCs/HPF
• Hematuria from within the glomerulus, the tubular system or Lower urinary tract
• Proteinuria
• Normal urine protein is <150mg/24hr, for albumin 5-10mg/day
• 30 to 300mg/day mod albuminuria, >300mg/day is severe
• Nephrotic range >3.5gm/24hr
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Disease Presented by Hematuria
Nephritic Syndrome
(E.g. APSGN)
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Acute Glomerulonephritis: Nephritic Syndrome
 Introduction (APSGN)
 Acute glomerulonephritis or nephritic syndrome is characterized by sudden-onset
hematuria (macroscopic or microscopic), proteinuria, hypertension, edema, and
acute kidney injury. E.g. APSGN Acute Post-streptococcal Glomerulonephritis
 The presence of cola-colored or tea-colored urine without clots and red blood cell
casts on urinalysis suggest hematuria of a glomerular origin.
 The typical patient develops an acute nephritic syndrome 1-2 wk. after an
antecedent streptococcal pharyngitis or 3-6 wk after a streptococcal pyoderma
 Epidemics of nephritis have been described in association with throat (serotypes M1, M4, M25,
and some strains of M12) and skin (serotype M49) infections.
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Etiology
 − Follows infection with nephrogenic strains of group A betahemolytic streptococci of the throat (mostly in cold weather) or skin
(in warm weather)
 − Diffuse mesangial cell proliferation with an increase in mesangial matrix;
lump bumpy deposits of immunoglobulin (Ig) and complement on glomerular
basement membrane and in mesangial
 − Mediated by immune mechanisms but complement activation is mostly
through the alternate pathway.
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Clinical presentation
 − Most common in 5–12 years old (corresponds with typical age for strep throat)
 − 1–2 weeks after strep pharyngitis or 3–6 weeks after skin infection
(impetigo)
 − Ranges from asymptomatic microscopic hematuria to acute renal failure
 – Edema, hypertension, hematuria (classic triad)
 − Constitutional symptoms—malaise, lethargy, fever, abdominal or flank
pain
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Diagnosis
 Diagnosis
 − Urinalysis—RBCs, RBC casts, protein 1–2 +, low C3 (lasts 6mo)
 − Mild normochromic anemia (hemodilution and low-grade hemolysis)
 For diagnosis of prior Strep infection
 Throat culture
 Use streptozyme (slide agglutination), which detects antibodies to streptolysin O,
DNase B, hyaluronidase, streptokinase, and nicotinamide-adenine dinucleotidase.
 Consider biopsy only in presence of acute renal failure, nephrotic
syndrome, absence of streptococcal or normal complement; or if present
>2 months after onset
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Treatment (in-patient, if severe) and Cx
 − Antibiotics for 10 days (penicillin)
 − Sodium restriction,
 -- Diuresis
 − Fluid and electrolyte
management
 − Control hypertension (calcium
channel blocker, vasodilator, or
angiotensin-converting enzyme
inhibitor)
 − Complete recovery in >95%
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•

. higher risk for HTN
At
encephalopathy 10%

The acute phase generally resolves
within 6-8 wk.

Urinary protein excretion and
hypertension up to 4-6 wk after onset,


Microscopic hematuria can persist for
1-2 yrs.
CHF, Uremia, Seizure, Acidosis,
electrolyte imbalance
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Treatment continued
• Early systemic antibiotic therapy
for streptococcal throat and skin
infections does not eliminate the
risk of GN.
• Family members of patients
with acute GN, especially young
children, should be considered
at risk and be cultured for group
A B-hemolytic streptococci and
treated if positive
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• A 10 day course of systemic
antibiotic therapy with penicillin
is recommended to limit the
spread of the nephritogenic
organisms, antibiotic therapy
does not affect the natural
history of APSGN, and
recurrences are extremely rare
• Family pets, particularly dogs,
have also been reported as
carriers..
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Others
• Alport
• IgA nephropathy (Berger disease)
• Most common cause of chronic
glomerular disease worldwide
• Hereditary nephritis (X-linked dominant);
renal biopsy shows foam cells
• Clinical presentation
• Asymptomatic hematuria and intermittent
gross hematuria 1–2 days after upper
respiratory infection
• – Most commonly presents with gross
hematuria in association URT and GI
infection
• – Then mild proteinuria, mild to moderate
hypertension
• – Normal C3
• The synpharyngitic (concomitant with an
upper respiratory illness) presentation of IgA
nephritis differentiates it from acute PSGN,
in which a prior history of sore throat is
present.
• Hearing deficits (bilateral sensorineural,
never congenital); females have subclinical
hearing loss
• Ocular abnormalities (pathognomonic is
extrusion of central part of lens into
anterior chamber
• Most important primary treatment is blood
pressure control
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Others
 HUS
 Henoch-Schönlein purpura
 Small vessel vasculitis with good
prognosis
 Present with purpuric rash, joint
pain, abdominal pain
 Most common cause of acute
renal failure in young children
 Microangiopathic hemolytic
anemia, thrombocytopenia, and
uremia == TRAID
 Most from E. coli O157:H7 (shiga
toxin–producing)
 Most from undercooked meat or
unpasteurized milk; spinach
 Also from Shigella, Salmonella,
Campylobacter, viruses, drugs,
idiopathic
 Most resolve spontaneously; antiinflammatory medications,
steroids: steroid
 Treatment is supportive and
management of complication
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Disease of Proteinuria
Nephrotic syndrome
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Nephrotic syndrome
 Defn: This is a group of signs and symptoms Characterized:
 − Proteinuria (>40 mg/m2/hour) >3,5 g/24 hrs (> 0,05 g/kg/24hrs), +++
 − Hypoalbuminemia (<2.5 g/dL)
 − Edema
 − Hyperlipidemia (reactive to loss of protein) and lipiduria
 Can be primary or secondary

Primary


Minimal change disease, Membranoproliferative glomerulonephritis, Focal
segmental glomerulosclerosis
Secondary to Systemic disease

Diabetes mellitus, HIV/AIDS, SLE and other connective tissue disorders
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Minimal change disease
• Clinical presentation
• − Most common between 2 and 6 years of
age
• − May follow minor infections
• Edema—localized initially around eyes
and lower extremities; anasarca with
serosal fluid collections less common
• − Common—diarrhea, abdominal pain,
anorexia
• − Uncommon—hypertension, gross
hematuria
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Diagnosis
And
Treatment
• Treatment
• Diagnosis
• − Mild—outpatient ; if severe—hospitalize
•
Urinalysis shows proteinuria (3–4 +)
• − Some with microscopic hematuria
•
−
• − 24-hour urine protein—40 mg/m2/hour
in children but now preferred initial test
is a spot urine for protein/creatinine ratio
>2
• − Serum creatinine usually normal but
may be increased slightly
• − Serum albumin <2.5 g/dL
• − Elevated serum cholesterol and
triglycerides
• − C3 and C4 normal
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− Start prednisone for 4–6 weeks, then taper 2–3 months
without initial biopsy
• − Consider biopsy with hematuria,
hypertension, heart failure, or if no response
after 8 weeks of prednisone (steroid resistant)
• − If severe—fluid restriction, plus intravenous
25% albumin infusion, followed by diuretic to
mobilize and eliminate interstitial fluid
• − Re-treat relapses (may become steroiddependent or resistant); may use alternate
agents (cyclophosphamide, cyclosporine,
high-dose pulsed methylprednisolone);
• renal biopsy with evidence of steroid
dependency
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Complication and prognosis
• Complications
• − Infection is the major complication; make sure immunized against
Pneumococcus and Varicella and check PPD
• − Most frequent is spontaneous bacterial peritonitis (S. pneumoniae most
common)
• − Increased risk of thromboembolism (increased prothrombotic factors and
decreased fibrinolytic factors) but really with aggressive diuresis
• Prognosis
• − Majority of children have repeated relapses; decrease in number with age
• − Those with steroid resistance and who have focal segmental
glomerulosclerosis have much poorer prognosis (progressive renal
insufficiency).
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AKI-Definition
Defined as the abrupt loss of kidney function that results in;

Retention of urea and other nitrogenous waste products

Dysregulation of extracellular volume and electrolytes.

Loss of acid base regulation.


These loss of kidney function is detected by Serum creatinine which is used to estimate GFR.
The term Acute Kidney Injury (AKI) has largely replaced acute renal failure (ARF) as it more clearly
defines renal dysfunction;


As a continuum rather than a discrete finding of failed kidney

This term also highlights that injury to kidney that does not results in “failure”
The Acute Dialysis Quality initiatives (ADQI) group proposed a consensus graded definition, called
the RIFLE criteria
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Epidemiology and risks
• Approximately 13 – 18% of all people admitted to hospital have AKI, the
mortality depends on the severity, setting (i.e. ITU or not) and other patient
factors but is estimated to be 25 – 30%.
• Patients should be investigated for AKI under the following conditions;
hypovolaemic, limited access to fluids, recent use of nephrotoxic drugs
(NSAIDs, aminoglycosides, ACE inhibitors, Ang- II antagonists and diuretics),
heart failure, liver disease, history of AKI, current CKD, sepsis, urological
obstruction, diabetes and also aged over 65 if adult. For children, the same
conditions apply but also; diarrhoea, symptoms of nephritis, hypotension or
haematological malignancy.
• Investigation is done via measurement of serum creatinine.
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Causes of AKI
Pre-renal, Intrinsic to the kidneys, or Post-renal.
• Pre-renal 55% causes include heart failure, dehydration, sepsis and liver damage which can all
affect the flow of blood to the kidneys, which in turn affects GFR and renal function. Anything
causing hypovolaemia, hypoxia, massive systemic inflammatory responses and dramatic changes
in RBF can potentially cause pre-renal AKI, which accounts for 65% of all cases.
• Intrinsic renal injury 45% originates from the kidneys themselves, i.e. glomerular nephritis
(haematuria and proteinuria) or nephrotic syndrome (proteinuria without haematuria). It can also be
caused by drugs with nephrotoxic potential, like NSAIDs, aminoglycosides, Ang-II antagonists, ACE
inhibitors and more.
• Post-renal causes of AKI 5% are those which block the flow of urine along the ureters, or urethra.
Origins include benign prostatic hyperplasia, tumours which impact on the aforementioned tubes
and kidney stones.
• One of the commonest causes of AKI is sepsis,.
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Investigations
• Renal function test
• Serum electrolyte; Na, K, Ca, Po4, Cl, HCO3
• Renal ultrasound, VCUG
• Vit D, PTH
• CBC, iron studies
• Echo, ECG
• Others to diagnose eatiology
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Monitoring AKI Risk
• The best way to monitor AKI causes is via urine output. A reduced output
(oliguria) can indicate AKI from any of the three aforementioned causes, i.e.
dehydration (pre-renal), kidney damage (intrinsic) or kidney stones (post-renal).
•
•
•
•
•
•
•
Temperature should be 36 – 38°C,
Systolic pressure should be 101 – 179mmHg,
Pulse should be 51 – 101 BPM,
Oxygen saturation should be above 96%,
respiration rate is anywhere from 9 – 20
BPM and urine output should be greater than 0.5mL/Kg/hour.
Weight monitored twice daily for fluid retention, as well as creatinine,.
• The first step in managing AKI is to identify and treat the underlying causes, and not the
presenting symptoms in isolation. Then potential nephrotoxic drugs should be addressed, IV fluids
administered if necessary, and the patient monitored with observations of urine output, serum
creatinine, U’s and E’s.
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Principle of management
• Maintenance of fluid and electrolyte
• Monitor input and output, diuretics,
fluids
Indication for dialysis in ARF
Anuria/oliguria
Severe fluid overload unresponsive to management
• Management of complications
• Hyperkalemia, hyponatremia, CHF, HTN,
Acidosis, Anemia
Persistent hyperkalemia K+ > 6.5 meq/l, K+ 5.5-6.5
meq/l with ECG changes
Hyponatremia: Na+ < 120 meq/l if symptomatic
• Supportive management
• Nutritional support, trearting infection
• Dialysis
• Peritoneal or Hemodialysis
• Intermittent or continuous
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Severe metabolic acidosis unresponsive to
management. Neurologic symptoms (altered
mental status, seizures) BUN >100-150 mg/dL
(or lower if rapidly rising)
Ca:PO4 imbalance, with hypocalcemic tetany.
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Chronic Renal Failure
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Chronic Kidney Disease
• Chronic kidney disease (CKD) is defined as renal injury (proteinuria)
and/or a glomerular filtration rate <60 mL/min/1.73 m2 for >3 mo.
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Pathogenesis
• Hyperfiltration injury may be an important pathway of glomerular
destruction, independent of the underlying cause of renal injury.
• As nephrons are lost, the remaining nephrons undergo structural and
functional hypertrophy (increase in GBF).
• The driving force for glomerular filtration is thereby increased in the surviving
nephrons.
• Although this compensatory hyperfiltration temporarily preserves total
renal function, it can cause progressive damage to the surviving glomeruli,
possibly by a direct effect of the elevated hydrostatic pressure on the
integrity of the capillary wall and/or the toxic effect of increased protein
traffic across the capillary wall.
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Pathogenesis
• In addition to progressive injury with ongoing structural or metabolic
genetic diseases, renal injury can progress despite removal of the
original insult.
• Progressively, as the population of sclerosed nephrons increases, the
surviving nephrons suffer an increased excretory burden, resulting in a
vicious cycle of increasing glomerular blood flow and hyperfiltration
injury
• Unclted hypertension can exacerbate disease progression by causing
arteriolar nephrosclerosis and by increasing the hyperfiltration injury.
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Proteinuria
• Proteins that traverse the glomerular capillary wall can exert a direct
toxic effect on tubular cells and recruit monocytes and macrophages,
enhancing the process of glomerular sclerosis and tubulointerstitial
fibrosis.
• Hyperphosphatemia can increase progression of disease by leading to
calcium phosphate deposition in the renal interstitium and blood vessels.
• Hyperlipidemia, a common condition in CKD patients, can adversely
affect glomerular function through oxidant-mediated injury.
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Clinical presentation
• Varied and depends on the underlying renal disease
• Children and adolescents with CKD from chronic glomerulonephritis can present with
edema, hypertension, hematuria, and proteinuria.
• Infants and children with congenital disorders (renal dysplasia and obstructive uropathy)
can present in the neonatal period with FTT, polyuria dehydration, UTI, or overt renal
insufficiency.
• Congenital kidney disease is diagnosed with prenatal USG in many infants, allowing early
diagnostic and therapeutic intervention.
• Children with familial juvenile nephronophthisis can have a very subtle presentation with
nonspecific complaints such as headache, fatigue, lethargy, anorexia, vomiting, polydipsia,
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polyuria, and growth failure over a number of years.
Investigation
AND
• Renal function test
• Serum electrolyte; Na, K, Ca,
Po4, Cl, HCO3
• Renal ultrasound
• VCUG
• Vit D, PTH
• CBC, iron studies
• Echo, ECG
• Others to diagnose eatiology
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Treatment
•
•
•
•
•
•
•
•
•
•
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Fluid and electrolyte management
Correction of acidosis
Nutrition
Growth
MBD
Anaemia
Hypertension
Immunization
Drug dose adjustment
RRT; HD, PD, kidney transplant
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GRACIAS
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