RENAL SYSTEM

RENAL TUBULAR ACIDOSIS

 INTRODUCTION

Lungs and Kidneys are responsible for Normal acid

base balance
Alveolar ventilation removes CO2
Kidneys reabsorb filtered Bicarbonate and excrete
a daily quantity of Hydrogen ion equal to that
produced by the metabolism of dietary proteins.
Hydrogen ions are excreted primarily by
enhancing the excretion of ammonium ions in the
urine
DEFINITION
The term "renal tubular acidosis" (RTA)
refers to a group of disorders in
which, despite a relatively well-
preserved glomerular filtration
rate, metabolic acidosis develops
because of defects in the ability of the
renal tubules to perform the normal
functions required to maintain acid-
base balance.
INCIDENCE

Predominant age: All ages

Predominant sex: Male > Female (with

regard to type II RTA with isolated defect
in bicarbonate reabsorption)
TYPES

Distal / type 1 RTA

Proximal / type 2 RTA
Hypoaldosteronism / type 4 RTA
Type 3 / mixed RTA (not in use)
Type 1-Distal RTA

Distal RTA (dRTA) is the classical form

of RTA. Inability of the distal tubule to
acidify the urine. Due to impaired
hydrogen ion secretion, increased backleak
of secreted hydrogen ions, or impaired
sodium reabsorption (causing less negative
potential in the lumen and hence less
hydrogen/potassium secretion).
Urine pH >5.5.
PATHOPHYSIOLOGY
failure of acid secretion by the alpha
intercalated cells of the cortical collecting
duct of the distal nephron.
it leads to an inability to acidify the urine to
a pH <5.3
renal excretion is the primary means of
eliminating acid from the body, there is
consequently a tendency towards acidemia
There is an inability to excrete H+
while K+ cannot be reabsorbed, leading to
acidemia (as H+ builds up in the body) and
hypokalemia (as K+ cannot be reabsorbed).
the substance of the kidney develops stones
bilaterally
 RISK FACTORS

Genetics
Autosomal dominant or recessive. May
occur in association with other genetic
diseases (e.g., Ehlers-Danlos
syndrome, hereditary elliptocytosis, or
sickle cell nephropathy). The autosomal
recessive form is associated with
sensorineural deafness.
 ETIOLOGY
• Genetic
• Sporadic
• Autoimmune diseases:
rheumatoid arthritis (RA), SLE •
• Hematologic diseases:
Sickle cell disease, hereditary
elliptocytosis
• Medications:
Amphotericin B, lithium, K+- •
sparing diuretics
• Toxins:
Toluene, glue
• Hypercalciuria, diseases
causing nephrocalcinosis
• Vitamin D intoxication
• Medullary cystic disease
• Glycogenosis type III
• Fabry disease
Wilson disease
• Hypergammaglobulinemic
syndrome
• Obstructive uropathy
• Chronic pyelonephritis
Chronic renal transplant
rejection
• Leprosy
• Hepatic cirrhosis
• Malnutrition
CLINICAL MANIFESTATIONS

non-anion gap metabolic

acidosis
growth failure
nephrocalcinosis
hypercalciuria
 Defect of the proximal tubule in
bicarbonate (HCO3) reabsorption.
HCO3 fully reabsorbed only when
plasma HCO3 concentration <15–16
mEq/L (compared with normal
threshold of 24 mEq/L). Urine pH <5.5
unless plasma HCO3 above
reabsorptive threshold.
It is caused by a failure of the proximal
tubular cells to reabsorb filtered
bicarbonate from the urine, leading to
urinary bicarbonate wasting and
subsequent acidemia.
The distal intercalated cells function
normally, so the acidemia is less severe
than dRTA and the urine can acidify to a
pH <5.3.
it is usually associated with a generalized
dysfunction of the proximal tubular cells
called Fanconi's syndrome.
Clinical manifestations -
phosphaturia, glycosuria, amin
oaciduria, uricosuria, and
tubular proteinuria. The
principal feature of Fanconi's
syndrome is bone
demineralization due to
phosphate wasting.
-Autosomal dominant form is rare.
-Autosomal recessive form is
associated with ophthalmologic
abnormalities and mental
retardation. Occurs in Fanconi
syndrome, which is associated with
several genetic diseases
Diseases associated with Fanconi syndrome
Sporadic
Multiple myeloma & other dysproteinemic
states
Amyloidosis
Heavy-metal poisoning
Medications:
Acetazolamide, sulfanilamide, ifosfamide, o
utdated tetracycline, topiramate
Autoimmune disease
Interstitial renal disease
Nephrotic syndrome
Congenital heart disease
Defects in calcium metabolism
growth failure in the 1st year of life
polyuria
dehydration
anorexia
vomiting
constipation
hypotonia
Patients with primary Fanconi
syndrome will have additional
symptoms
Those with systemic diseases will
present with additional signs and
symptoms specific to their underlying
disease
 Type 3 RTA-Combined
proximal and distal RTA
Extremely rare autosomal recessive syndrome
with features of both type I and type II
(juvenile RTA).
Combined dRTA and pRTA is also observed as
the result of inherited carbonic anhydrase II
deficiency. Mutations in the gene encoding this
enzyme give rise to an autosomal recessive
syndrome of osteopetrosis, renal tubular
acidosis, cerebral calcification, and mental
retardation.
•
Type 4 RTA
Due to aldosterone resistance or deficiency
that results in hyperkalemia.
It was included in the classification of renal
tubular acidoses as it is associated with a
mild (normal anion gap) metabolic acidosis
due to a physiological reduction in
proximal tubular ammonium excretion
(impaired ammoniagenesis), which is
secondary to hypoaldosteronism, and
results in a decrease in urine buffering
capacity.
Urine pH <5.5.
RISK FACTORS

Some cases familial, such as

pseudohypoaldosteronism type
I (autosomal dominant)
 ETIOLOGY
Medications: Nonsteroidal anti-inflammatory
drugs, angiotensin-converting enzyme
inhibitors, angiotensin receptor
blockers, heparin/LMW heparin, calcineurin
inhibitors (tacrolimus, cyclosporine) (1)
Diabetic nephropathy
Obstructive nephropathy
Nephrosclerosis due to hypertension
Tubulointerstitial nephropathies
Primary adrenal insufficiency
Pseudohypoaldosteronism(end-organ
resistance to aldosterone)
Gordon syndrome
Sickle cell nephropathy
CLINICAL MANIFESTATIONS
with growth failure in the first few years of
life
Polyuria
Dehydration
Rarely, with life-threatening hyperkalemia
Patients with obstructive uropathies may
present acutely with signs and symptoms of
pyelonephritis
hyperkalemic non-anion gap metabolic
acidosis
Alkaline or acidic urine
Elevated urine sodium levels &
inappropriately low urine potassium levels
reflect the absence of aldosterone effect.
History collection
Often asymptomatic (particularly
type IV)
Failure to thrive in children
Anorexia, nausea/vomiting
Weakness or polyuria (due to
hypokalemia)
Rickets in children
Osteomalacia in adults
Constipation
Polydipsia
Electrolytes - hyperchloremic metabolic
acidosis.
Plasma anion gap normal (anion gap = Na - [Cl +
HCO3])
Hypokalemia or normokalemia
Hyperkalemia
Plasma HCO3 (in untreated RTA)
Blood urea nitrogen and creatinine usually
normal (rules out renal failure as cause of
acidosis)
Urine pH: Inappropriately alkaline (pH >5.5)
Urine culture: Rule out UTI with urea-splitting
organism and chronic infection
Urine anion gap: Reflects unmeasured urine
anions, so inversely related to urine NH4+ (or
acid) excretion. Positive urine anion gap in an
acidemic patient indicates impaired renal acid
excretion.
Urine calcium:
High in type I
Typically normal in type II
A renal ultrasound - to identify underlying
structural abnormalities such as obstructive
uropathies as well as to determine the presence
of nephrocalcinosis.
correction of the acidemia with oral sodium
bicarbonate, sodium citrate or potassium citrate.
This will reverse bone demineralization
Hypokalemia and urinary stone formation and
nephrocalcinosis can be treated with potassium
citrate tablets
Patients with proximal RTA often require large
quantities of bicarbonate, up to 20 mEq/kg/24 hr
in the form of sodium bicarbonate or sodium
citrate solution
The base requirement for distal RTAs is generally in
the range of 2-4 mEq/kg/24 hr.
Patients with Fanconi syndrome generally require
phosphate supplementation .
Patients with distal RTA should be monitored for the
development of hypercalciuria. Symptomatic
hypercalciuria, nephrocalcinosis, or nephrolithiasis
may require thiazide diuretics to decrease urine
calcium excretion.
Patients with type IV RTA may require chronic
treatment for hyperkalemia with sodium-potassium
exchange resin
Administration of sufficient bicarbonate to reverse
acidosis stops bone dissolution and the
hypercalciuria.
Proximal RTA is treated with both bicarbonate and
oral phosphate supplements to heal bone disease.
Vitamin D is needed to offset the secondary
hyperparathyroidism that complicates oral
phosphate therapy
The mainstay of therapy in all forms of RTA is
bicarbonate replacement .
 PROGNOSIS

• Depends on associated
disease, otherwise good with therapy

• Transient forms of all types of RTA

may occur.
 COMPLICATIONS
• Nephrocalcinosis, nephrolithiasis
(type I)
• Hypercalciuria (type I)
• Hypokalemia (type I, type II if given
bicarbonate)
• Hyperkalemia (type IV, some causes
of type I)
• Osteomalacia (type II due to
phosphate wasting)