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Renal Tubular Defects.
Renal Tubular Defects.
1. Neonatal (type 1 and 2) in utero presents as maternal polyhydramnios, secondary to fetal polyuria, is evident by
24-30 weeks' gestation. Delivery often occurs before term. The newborn has massive polyuria (rate as high as 12-
50 mL/kg/h). As neonates it presents as fever, dehydration and early onset of nephrocalcinosis
2. Classical (type 3) in infantile as polyuria and growth retardation. Nephrocalcinosis is not a feature.
3. Type 4 linked with sensorineural hearing loss due to mutation of Barttin gene at chromosome 1p
PHYSICAL FINDINGS
Due to the defective NKCC2 cotransporter, sodium ions are lost in the urine. Failure to reabsorb sodium causes both
salt loss (natriuresis) and water loss. This leads to volume depletion and hypotension which is sensed by the
juxtaglomerular cells. And high sodium chloride concentration in the filtrate of the DCT is sensed by the macula
densa cells. Both of these activate the RAAS and increases aldosterone levels. Aldosterone exacerbates hypokalemia
by promoting potassium and hydrogen ion excretion in exchange for sodium reabsorption.
Due to defective NKCC2 cotransporter, calcium is also lost in the urine, resulting in hypercalciuria. This
differentiates it from Gitelman, which is associated with hypocalciuria. Increased hypercalciuria over time results in
nephrocalcinosis and nephrolithiasis.
TREATMENT
Natriuresis causes polyuria while activation of RAAS causes polydipsia from stimulation of thirst center in the
hypothalamus.
Treatment is lifelong potassium-sparing diuretics, particularly those that inhibit RAAS, such as spironolactone
which is a mineralocorticoid receptor antagonist which helps counteract the increased aldosterone levels in
patients.
GITELMAN SYNDROME
ALSO CALLED FAMILIAL HYPOKALEMIA-HYPOMAGNESEMIA
Gitelman syndrome is similar to Bartter in that it is an autosomal recessive disease with secondary
hyperaldosteronism, hypokalemia, and alkalosis.
The autosomal recessive GS, or familial hypokalemic metabolic alkalosis with hypomagnesemia and low urinary
calcium excretion has a prevalence of approximately 1 in 40000
It results from transport defects located in the DCT caused by mutations in the gene (SLC12A3) that encodes the
thiazide-sensitive NaCl cotransporter (NCC).
In the majority of cases, symptoms do not appear before the age of six years and the disease is usually diagnosed
during adolescence or adulthood.
DISTINCTIVE CHARACTERISTICS
GS IS VERY OFTEN ASYMPTOMATIC
If symptoms occur, this is usually after the age of six years but the condition is often diagnosed in adolescents or
adults.
The initial presentation is usually the incidental discovery of an asymptomatic and isolated hypokalemia.
Some patients present with fatigue, dizziness, muscle weakness, cramps, vomiting, abdominal pain, fever, nocturia
and polyuria.
Facial Paresthesias may also occur and, occasionally, hypotension.
Some adult GS patients suffer from chondrocalcinosis, which is assumed to result from chronic
hypomagnesemia. It causes swelling, local heat, and tenderness over the affected joints.
Hypomagnesemia and hypocalciuria have always been considered obligate features for GS.
DIAGNOSIS
Asymptomatic patients often require no treatment but need outpatient monitoring once or twice yearly. A high-
sodium and potassium diet is recommended.
Lifelong magnesium supplementation is required. As high doses of magnesium cause diarrhea, normalization of
serum magnesium level is difficult to achieve.
Hypokalemia may require large amounts of potassium chloride supplements. If symptomatic, hypokalemia is
treated by a combination therapy of amiloride and spironolactone in addition to KCl supplementation.
Symptomatic chondrocalcinosis (pseudo-gout attacks) requires NSAID.
RENAL TUBULAR DEFECTS
FANCONI SYNDROME
Syndrome Site of defects Outcomes Causes Resembles
Fanconi syndrome PCT (AAs, Glu, • Hypokalemic acidosis • Hereditary: Wilson • Growth retardation
HCO3, & PO4) (proximal RTA). • disease, tyrosinemia, and rickets/osteopenia
Hypophosphatemia glycogen storage (hypophosphatemia)
disease.
• Drugs: Ifosfamide, • Volume depletion
cisplatin, tenofovir, (polyurea).
expired tetracyclines.
• Ischemia, MM, lead
poisoning.
LIDDLE SYNDROME
Syndrome Site of defects Outcomes Causes Resembles
Liddle syndrome Collecting Tub. • Hypokalemic AR • Hyperaldosteronism.
(enhanced Na metabolic alkalosis. (GoF mutation that • TTT: Amiloride.
reabsorption) inhibits Na channel
• HTN+ LOW degradation)
aldosterone
SAME/ SYNDROME OF APPARENT MINERALOCORTICOID EXCESS