Autosomal Dominant Tubulointerstitial Kidney Disease

Abstract

In recent years, the definitions and classifications of congenital tubulo-interstitial kidney diseases have been significantly revised. This is primarily due to the achievements in the molecular biology and genetics, which made it possible to significantly clarify the role of a number of genes encoding certain proteins that are closely involved in kidney functions. In 2015, KDIGO proposed to unify the terminology, diagnostic criteria and approaches to monitoring conditions associated with mutations of the MUC1, UMOD, HNF1B and REN genes, which led to the development of ideas about the new nosology - autosomal dominant tubulointerstitial kidney disease (ADTKD). A brief description of the basic information about the ADTKD compiled the content of this message.

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“…1 It i's considered to be that the signaling role of RAR is the main factor in the development of pronephros, the germination of the ureteral germ in metanephros and the early development of the genitals. 1,12 According to the results of a foreign study, during RNA sequencing as a result of GREB1L knockdown in vitro, a sharp decrease in the activity of key PAX2 and PTH1R molecules involved in kidney development was detected, which confirms the important role of the GREB1L gene in the development of metanephros Figure 1. 8 However, the mechanism of regulation of renal function by the GREB1L gene and variants of its interactions with key regulators remain unknown.…”

“…3,[14][15][16][17][18] Autosomal dominant tubulointerstitial kidney disease type 1 (ADTKD) is a rare genetically determined disease, mainly caused by pathogenic variants in the UMOD gene (chromosomal locus 16p2, encodes uromodulin protein), which lead to the development of familial juvenile hyperuricemic nephropathy type 1 (OMIM:162000), medullary cystic kidney disease type 2 (OMIM:603860) and glomerular cystic kidney disease (OMIM:609886). 12 The listed conditions have been combined into the term ADTKD-UMOD since 2015 Figure 3. ADTKD-UMOD is more often detected among Chinese patients than European population, and among all patients with CRF occurs in 0.9% of cases.…”

“…ADTKD-UMOD is more often detected among Chinese patients than European population, and among all patients with CRF occurs in 0.9% of cases. 12 It is assumed that pathogenic variants inherited by autosomal dominant type in the UMOD gene disrupt the maturation and intraepithelial uromodulin transport, resulting in reduced protein excretion into the lumen of the tubule. At an early stage, ADTKD-UMOD is manifested by hypouricosuric hyperuricemia (with fractional uric acid excretion decrease <5%), however, in 20% of patients, persistent hyperuricemia and severe arterial hypertension (AH) are not observed.…”

“…In the presence of the ADTKD-UMOD, the concentration of uromodulin in the urine decreases, renal function decreasing progresses, joint syndrome of the type of gout with thumb and ankle lesions joins in adolescence, tubulointerstitial lesions are detected with nephrobiopsy. 12,19 Urinary syndrome is presented in the form of an "empty" urinary sediment (single Er., daily proteinuria <500 mg), as well as nocturia and enuresis. 12,19 Cases of gout have been described in patients with pathogenic variants in the UMOD gene, while among patients with ADTKD-UMOD with impaired concentration function, gout is more common and begins much earlier.…”

“…12,19 Urinary syndrome is presented in the form of an "empty" urinary sediment (single Er., daily proteinuria <500 mg), as well as nocturia and enuresis. 12,19 Cases of gout have been described in patients with pathogenic variants in the UMOD gene, while among patients with ADTKD-UMOD with impaired concentration function, gout is more common and begins much earlier. 20 A reduction in plasma volume and a higher reabsorption activity of the proximal tubules may explain the phenotype of hyperuricemia in ADTKD-UMOD.…”