Pediatric Medical Genetics - S. I. Smiian 2003

Hereditary nephropathies
Tubulopathies

Tubulopathies are tubular dysfunctions characterized by an early partial or generalized impairment of tubular Functions accompanied by normal or slightly reduced Glomerular Filtration.

The underlying mechanism of the disease involves disorders in the tubular transport of Organic compounds or electrolytes. These are most commonly associated with impaired reabsorption, and less frequently with defects in tubular secretion.

The transport of various compounds across Cell membranes is driven by three main processes:

1. Simple diffusion along a concentration gradient.

2. Facilitated Diffusion directly between nearly equal concentrations of a substance on both sides of the membrane.

3. Active Transport against a significantly higher electrochemical gradient.

Simple diffusion is a relatively slow and non-specific process that does not play a significant role in maintaining Homeostasis.

Facilitated diffusion is mediated by carrier Proteins that are specific to the transported substance. Initially, the carrier protein binds to the Active Site. The rate of simple diffusion depends on the speed at which these complexes are formed. In addition, competitive inhibition plays a certain role when A number of compounds with similar chemical structures act upon the active site and compete with one another. Furthermore, substances competing for the transport protein may exert an inhibitory effect on the membrane transport of other substances.

Unlike facilitated diffusion, active transport of compounds across cell membranes requires the expenditure of cellular energy involving all Enzymes of the energy-generating systems. The transport process is completed by the release of substances, which is mediated by enzymes. Consequently, hereditarily determined disorders of this transport mechanism should be classified as enzymopathies, although cases of a genetically determined structural abnormality in the carrier protein molecule are also possible.

In addition to the mechanisms mentioned above, another potential cause of primary tubulopathies should be noted: altered sensitivity of Membrane Receptors to Hormonal Influences. In this case, the tubular apparatus of the nephron loses its ability to regulate homeostasis, which leads to the clinical manifestations of the disease.

Thus, the Pathogenesis of hereditary primary tubulopathies can be associated with the following factors: altered Structure of carrier proteins, enzymopathies, reduced sensitivity of tubular epithelial cell receptors to Hormones, and Changes in the overall structure of cytomembranes (dysplasias).

Secondary tubulopathies occur when the transport systems of the renal tubules are damaged in either hereditary or acquired Metabolic Disorders due to metabolic disturbances outside the nephron. Toxic substances pass through the glomerular filter in excess, suppress diffusion or active transport processes, and inhibit tubular reabsorption by competing with compounds of similar chemical structure.

Based on The Mechanism of impaired tubular transport, the following types are distinguished:

— primary (hereditary renal enzymopathies associated with Genetic Defects in the enzymes involved in tubular secretion and reabsorption);

— secondary, resulting from systemic metabolic disorders in the body and secondary acquired renal damage.

There are numerous classifications of tubulopathies. In addition to the syndromic categorization presented in the general Classification above, There is a classification based on the localization of the defect (Table 10):

Class="center">Table 10 Classification of tubulopathies by defect localization

From a clinical perspective, identifying specific syndromes that help suspect tubulopathy in a child is of paramount importance.

Polyuria may be the sole manifestation of the disease, particularly in nephrogenic diabetes insipidus, renal glucosuria, or renal salt-wasting syndrome. Rickets-like bone changes (Renal osteodystrophy) may manifest as renal tubular acidosis, phosphate diabetes, or de Toni-Debré-Fanconi syndrome. Nephrolithiasis also points to the presence of tubulopathies.