RTA Flashcards
Blood pH in RTA
NAGMA (hyperchloremic) in the setting of near normal or normal GFR
Types of RTA
Proximal (Type II), Distal (Type I), Combined proximal and distal (Type III), Hyperkalemic (Type IV)
RTA that results from impaired bicarbonate reabsorption
Proximal
RTA that results from failure to secrete acid
Distal
Approximately 90% of filtered bicarbonate is reabsrobed in the
Proximal tubule
Proximal RTA usually occurs as a component of global proximal tubular dysfunction or Fanconi syndrome, which is characterized by
1) LMW proteinuria 2) Glycosuria 3) Phosphaturia 4) Amino aciduria 5) Proximal RTA
Drugs that can cause secondary pRTA
1) Gentamicin 2) Cisplatin 3) Ifosfamide 4) Sodium valproate
Nutritional condition that can cause pRTA
Kwashiorkor
Isolated autosomal recessive pRTA is caused by mutations in
Gene encoding the sodium bicarbonate transporter NBC1
Cystinosis is suggested by what clinical finding
Cystine crystals in the cornea
Cystinosis is confirmed by measurement of
Increased leukocyte cystine content
Specific therapy for Cystinosis is available with cysteamine which acts to
Bind to cystine and convert it to cysteine
T/F Oral cysteamine as treatment for Cystinosis does not achieve adequate levels in ocular tissues, so additional therapy with cysteamine eyedrops is required.
T
A rare X-linked disorder characterized by congenital cataracts, mental retardation, and Fanconi syndrome
Lowe syndrome
In Lowe syndrome, kidneys show
Nonspecific tubulointerstitial changes; Thickening of glomerular basement membrane; And changes in proximal tubule mitochondria
Present in the 1st 2 yr of life with severe tubular dysfunction and growth failure
Cystinosis
Typically present in infancy with cataracts, progressive growth failure, hypotonia, and Fanconi syndrome
Lowe syndrome
Patients with isolated, sporadic, or inherited pRTA present with ____ in the 1st yr of life.
Growth failure
How does patients with primary Fanconi syndrome compare to those with isolated pRTA
Patients with Fanconi syndrome have additional symptoms secondary to phosphate wasting
Urinalysis in patients with isolated pRTA shows
Generally unremarkable except for an acidic urine pH <5.5
Urinary indices in patients with Fanconi syndrome
1) Phosphaturia 2) Aminoaciduria 3) Glycosuria 4) Uricosuria 5) Elevated urinary sodium or potassium
In distal RTA, urine pH cannot be reduced to ___ despite the presence of severe metabolic acidosis
Less than 5.5
Why is there hyperchloremia in distal RTA
Loss of sodium bicarbonate distally, owing to lack of H+ to bind to in the tubular lumen, results in increased chloride absorption (HCO3-Cl exchanger on the basolateral membrane)
Why is there hypokalemia in distal RTA
Inability to secrete H+ is compensated by increased K+ secretion distally
Bone disease is common in distal RTA because
There is mobilization of organic components from bone to serve as buffers to chronic acidosis
Distal RTA is distinguished from pRTA by the presence of
1) Nephrocalcinosis 2) Hypercalciuria
pRTA is distinguished from dRTA by the presence of
Phosphate and massive bicarbonate wasting
Characterized by cystic dilation of the terminal portions of the collecting ducts as they enter the renal pyramids
Medullary sponge kidney
Inability to concentrate urine
Hyposthenuria
Type IV RTA occurs as the result of
Impaired aldosterone production (hypoaldosteronism) or impaired renal responsiveness to aldosterone (pseudohypoaldosteronism)
Mechanism for acidosis in Type IV RTA
Aldosterone has a direct effect on the H+/ATPase responsible for hydrogen secretion; Hyperkalemia –> inhibition of ammoniagenesis and hence H excretion
Mechanism for hyperkalemia in Type IV RTA
Aldosterone is a potent stimulant for K secretion in the collecting tubule
More common cause of Type IV RTA: Adrenal gland disorder (e.g. Addison disease, CAH) vs Aldosterone unresponsiveness
Aldosterone unresponsiveness
Absence of aldosterone leads to what basic pattern of electrolyte imbalance
Elevated urinary sodium with inappropriately low urinary K
First step in the evaluation of a patient with suspected RTA
1) Confirm presence of NAGMA 2) Identify electrolyte abnormalities 3) Assess renal function 4) Rule out other causes of bicarbonate loss such as diarrhea
Patients who have persistent metabolic acidosis despite correction of volume depletion likely has RTA
F, protracted diarrhea can deplete their total-body bicarbonate stores and can have persistent acidosis despite apparent restoration of volume status; where a patient has a recent history of severe diarrhea, full evaluation for RTA should be delayed for several days to permit adequate time for reconstitution of total-body bicarbonate stores
Conditions that can lead to falsely low bicarbonate levels, often in association with an elevated serum K
1) Traumatic blood draws such as heel-stick specimens 2) Small volumes of blood in “adult-size” specimen collection tubes 3) Prolonged specimen transport time at room temp
NAGMA with normal or low K suggests what types of RTA
I or II
Formula for anion gap
Na - (Cl+HCO3)
NAGMA is demonstrated by an anion gap of
Less than 12
HAGMA is demonstarted by an anion gap of
> 20
Steps in evaluation of possible RTA
1) First step as above 2) Urine pH to distinguish distal from proximal causses (less than 5.5 = pRTA, >6 = dRTA) 3) (Optional) Compute urine anion gap [(urine Na + urine K) - urine Cl 4) UA (glycosuria, proteinuria, hematuria) 5) Ca-Crea ratio 6) Renal UTZ
Urine anion gap in distal RTA
(+) gap suggests a deficiency of ammoniagenesis and, thus, the possibility of dRTA
Urine anion gap in pRTA
(-) gap is consistent with proximal tubule bicarbonate wasting
Mainstay of therapy in all forms of RTA
Bicarbonate replacement
Patients with this type of RTA often require large quantities of bicarbonate
pRTA
Large quantities of bicarbonate is defined as
20mEq/kg/24hr
Base requirement for distal RTAs is generally in the range of
2-4mEqs/kg/24hr
Syndrome manifesting with RTA that usually requires phosphate supplementation
Fanconi syndrome
Patients with this type of RTA should be monitored for development of hypercalciuria
Distal RTA
Patients with symptomatic hypercalciuria (recurrent gross hematuria, nephrocalcinosis, or nephrolithiasis) can require what medication
Thiazide diuretics to decrease urine Ca excretion
Patients with type IV RTA can require chronic treatment for hyperkalemia with
Na-K exchange resin (Kayexalate)
T/F Patients with treated isolated proximal or distal RTA can demonstrate improvement in growth
T, provided serum bicarbonate is maintained within normal levels
Rickets may be present in primary RTA, particularly in what type of RTA
pRTA
Bone demineralization without overt rickets usually is detected in what type of RTA
Type I or distal RTA
T/F The circulating levels of 1,25(OH)2D in patients with either type of RTA are generally decreased
F, generally normal; decreased in cases where there is a concomitant CKD
Bone demineralization in distal RTA probably relates to
Dissolution of bone because the calcium carbonate in bone serves as a buffer against the metabolic acidosis due to the hydrogen ions retained by patients with RTA
Management for rickets in patients with distal RTA
Bicarbonate supplement
Management for rickets in patients with pRTA
Both bicarbonate and oral phosphate supplements
This is required to offset the secondary hyperparathyroidism that complicates oral phosphate therapy in patients with RTA
Vitamin D
Patients with Type II RTA and primary Fanconi syndrome may present with “double osteomalacia” which is defined as
Bone demineralization + Vitamin D deficiency
