Tubulopathy

Tubulopathy
Specialty	Nephrology

Tubulopathy is a disease affecting the renal tubules of the nephron.^[1]

Tubulopathic processes may be inflammatory or noninflammatory, though inflammatory processes are often referred to specifically as tubulitis.^[2][3]

Characteristics of Some Inherited Tubulopathies^[4]

Disorder [OMIM Number]	Protein Defect	Chromosome Localization	Inheritance	Clinical Features/Notes	Biochemical Features
Proximal Tubule
Lowe's syndrome (oculocerebral dystrophy [309000]	OCRL1	Xq26.1	XR	Hydrophthalmia, cataract, mental retardation, hyporeflexia, hypotonia and progressive kidney failure, normotensive	Plasma: ↓K, ↓CO2; Urine: ↑LMWP, ↑AA, ↑PO4, ↑K
Wilson's disease [277900]	ATP7B	13q14.3-q21.1	AR	Liver disease or neurologic symptoms, or both, Kayser–Fleischer rings, normotensive	Plasma: ↑free copper, abnormal LFTs; Urine: ↑copper excretion, ↑LMWP, ↑AA, ↑PO4, ↑Glycosuria
Dent's disease (X-linked recessive hypophophatemic rickets)[300009]	CLCN5	Xp11.22	XR	Nephrocalcinosis, nephrolithiasis, rachitic and osteomalacic bone disease, progressive kidney failure, normotensive	Plasma: ↓PO4, N/↓K; Urine: ↑LMWP, ↑AA, ↑K, ↑Ca, ↑PO4, ↑Glycosuria
X-linked dominant hypophosphatemic rickets [307800	PHEX	Xp22.2-p22.1	XD	Growth retardation, rachitic and osteomalacic bone disease, hypophosphatemia, and renal defects in phosphate reabsorption and vitamin D metabolism	Plasma: ↓PO4, ↑ALP; Urine: ↑PO4
Loop of Henle
Bartter's syndrome	NKCC2 (type 1)	15q15-21.1	AR	Polyuria, polydipsia, muscle weakness, hypovolemia, normotensive or hypotensive (all types). Maternal polyhydramnios, premature birth, perinatal salt wasting, nephrocalcinosis and kidney stones (type 1 and 2), milder phenotype with normocalciuria(type 3), sensorineural deafness, motor retardation, renal failure (type 4)	Plasma: ↑renin, ↓K, ↑CO2, mild ↓Mg in some patients; Urine: ↑Ca
[601678]	ROMK (type 2)	11q24	AR
[241200]	C1C-Kb (type 3, classic)	1p36	AR
[607364]		1p31	AR
[602522]	Barttin (type 4)
Hypomagnesemic hypercalciuric nephrocalcinosis (magnesium-losing kidney)[248250]	PCLN1	3q27	AR	Nephrocalcinosis, renal failure, ocular/hearing defects, polyruria, polydipsia, recurrent urinary tract infections, recurrent renal colic, normotensive	Plasma: ↓Mg, ↑PTH; Urine: ↑Ca, ↑Mg
Distal Tubule/Collecting Duct
Liddle's syndrome [177200]	ENaC (activating)	16p13-p12	AD	Early, and frequently severe, hypertension, stroke	Plasma: ↓renin, ↓K, ↓Mg, ↑CO2; Urine: ↑K
Pseudohypoaldosteronism type 1a [264350]	ENaC (inactivating)	12p13, 16p13-p12	AR	Presents in infancy with salt-wasting and hypotension, Cough, respiratory infections	Plasma: ↑renin, ↓Na, ↑K, ↓CO2; Urine: ↑K
Pseudohypoaldosteronism type 1b [177735]	Mineralocorticoid receptor	4q31.1	AD	Presents in infancy with salt-wasting and hypotension. Milder than type 1a and remits with age	Plasma: ↑renin, ↓Na, ↑K, ↓CO2; Urine: ↑K
Pseudohypoaldosteronism type 2 (Gordon's syndrome) [145260]	Unknown (?WNK)	1q31-q42, 12p13, 17q21-q22	AD	Hypertension (± muscle weakness, short stature, intellectual impairment). Correction of physiologic abnormalities by thiazide diuretics	Plasma: ↓renin, ↑K, ↓CO2, ↑Cl; Urine: ↓K
Gitelman's syndrome [263800]	NCCT	16q13	AR	Hypotension, weakness, paresthesias, tetany, fatigue, and salt craving, Presentation generally much later in life than in Bartter's and hypocalciuria is typical	Plasma: ↑renin, ↓K, ↓Mg, ↑CO2; Urine: ↓calcium:creatinine excretion ratio (useful in distinguishing Gitelman's and Bartter's)(Note: biochemically can mimic thiazide use)
X-linked nephrogenic diabetes insipidus type 1 [304800]	V2 receptor	Xq28	XR	Hyperthermia, polyuria, polydipsia, dehydration, inability to form concentrated urine, intellectual disability if diagnosis delayed. Symptoms in infancy	Hyperosmolar plasma, dilute urine
Autosomal dominant nephrogenic diabetes insipidus type 2 [192340]	AQP2	12q13	AD and AR	Polyuria, polydipsia, dehydration, inability to form concentrated urine. Symptoms after first year of life	Hyperosmolar plasma, dilute urine

AA: Aminoaciduria; AD:autosomal dominant; AR: autosomal recessive; LFT's: Liver function tests; LMWP: low molecular weight proteinuria; XD: X-linked dominant; XR: X-linked recessive; PTH: Parathyroid hormone

References

1. "tubulopathy" at Dorland's Medical Dictionary
2. Ferrara P, D'Aleo CM, Rigante D, et al. (2003). "Amoxicillin-induced nephritis and tubulitis in a child". Urol. Int. 71 (1): 124–6. doi:10.1159/000071111. PMID 12845278.
3. Robertson H, Wong WK, Talbot D, Burt AD, Kirby JA (January 2001). "Tubulitis after renal transplantation: demonstration of an association between CD103+ T cells, transforming growth factor beta1 expression and rejection grade". Transplantation. 71 (2): 306–13. doi:10.1097/00007890-200101270-00024. PMID 11213078.
4. Burtis, C.A.; Ashwood, E.R. and Bruns, D.E. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 5th Edition. Elsevier Saunders. p.1574-1575

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