# Beyond expensive innovations: affordable and effective strategies for managing tubulopathies in adults

**Authors:** Louise Nielsen, Lucile Figueres

PMC · DOI: 10.1093/ckj/sfag001 · Clinical Kidney Journal · 2026-01-09

## TL;DR

This paper reviews affordable and practical strategies for managing tubulopathies in adults, emphasizing non-targeted interventions and overlooked supportive care.

## Contribution

The paper proposes a resource-conscious approach to tubulopathies, highlighting phenotype-based care and the need for studies on patient-reported outcomes.

## Key findings

- Non-targeted measures like hydration and electrolyte supplementation remain core management strategies.
- Widely available drugs can be repurposed for specific tubular phenotypes.
- Supportive care components like patient education and adherence support are often overlooked.

## Abstract

Tubulopathies comprise a heterogeneous and still poorly defined group of inherited and acquired disorders in which tubular transport is disproportionately impaired, resulting in chronic electrolyte and acid–base disturbances with downstream complications such as nephrocalcinosis, nephrolithiasis, bone fragility and, in some entities, progressive chronic kidney disease. Over the past decade, high-cost targeted therapies have transformed outcomes for a subset of tubulopathy-related disorders with secondary tubular involvement (e.g. anti–fibroblast growth factor 23 therapy in X-linked hypophosphatemia), yet comparable innovations remain largely unavailable for primary tubular transport defects and access to these therapies is uneven across healthcare systems. In this narrative review, we synthesize current evidence and expert recommendations for pragmatic, phenotype-driven interventions that support daily care and may help prevent complications. Core management still relies on non-targeted measures, including individualized nutritional counselling, optimization of hydration and solute load, and tailored electrolyte and alkali supplementation. We also discuss the rational use of widely available drugs that can be repurposed in selected tubular phenotypes, such as thiazide and thiazide-like diuretics, potassium-sparing agents, azole antifungals in calcitriol-driven hypercalcaemic states and emerging data on sodium-glucose cotransporter 2 inhibitors. Finally, we emphasize supportive care components often overlooked in ‘drug-centred’ approaches, including structured patient education, adherence support and monitoring of extra-renal manifestations. Overall, this review argues for a more resource-conscious approach to tubulopathies: one that recognizes the lack of a consensual definition, prioritizes phenotype-based care bundles, and underscores the urgent need for larger prospective studies incorporating patient-reported outcomes and robust economic endpoints, particularly the out-of-pocket burden borne by patients and families.

## Linked entities

- **Chemicals:** calcitriol (PubChem CID 5280453)
- **Diseases:** X-linked hypophosphatemia (MONDO:0010619), nephrocalcinosis (MONDO:0001567), nephrolithiasis (MONDO:0008171), chronic kidney disease (MONDO:0005300)

## Full-text entities

- **Genes:** CYP4F3 (cytochrome P450 family 4 subfamily F member 3) [NCBI Gene 4051] {aka CPF3, CYP4F, CYPIVF3, LTB4H}, SLC34A3 (solute carrier family 34 member 3) [NCBI Gene 142680] {aka HHRH, NPT2C, NPTIIc}, PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}, CYP24A1 (cytochrome P450 family 24 subfamily A member 1) [NCBI Gene 1591] {aka CP24, CYP24, HCAI, HCINF1, P450-CC24}, FGF23 (fibroblast growth factor 23) [NCBI Gene 8074] {aka ADHR, FGFN, HFTC2, HPDR2, HYPF, PHPTC}, CLDN16 (claudin 16) [NCBI Gene 10686] {aka HOMG3, PCLN1}, AVPR2 (arginine vasopressin receptor 2) [NCBI Gene 554] {aka ADHR, DI1, DIR, DIR3, NDI, NDI1}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, SLC34A1 (solute carrier family 34 member 1) [NCBI Gene 6569] {aka FRTS2, HCINF2, NAPI-3, NPHLOP1, NPT2, NPTIIa}, SLC12A3 (solute carrier family 12 member 3) [NCBI Gene 6559] {aka NCC, NCCT, TSC}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}, CLDN19 (claudin 19) [NCBI Gene 149461] {aka HOMG5}, NR3C2 (nuclear receptor subfamily 3 group C member 2) [NCBI Gene 4306] {aka MCR, MLR, MR, NR3C2VIT}, CYP51A1 (cytochrome P450 family 51 subfamily A member 1) [NCBI Gene 1595] {aka CP51, CYP51, CYPL1, LDM, P450-14DM, P450L1}, RRAGD (Ras related GTP binding D) [NCBI Gene 58528] {aka HOMG7, RAGD, bA11D8.2.1}
- **Diseases:** metabolic syndrome (MESH:D024821), calcium overload (MESH:D019190), hepatic insufficiency (MESH:D048550), Salt (MESH:D013651), ion loss (MESH:D016388), nephrolithiasis (MESH:D053040), melanoma (MESH:D008545), hypercalcitriolemic conditions (MESH:D020763), gastrointestinal symptoms (MESH:D012817), abscesses (MESH:D000038), HHRH (MESH:C562793), disturbances (MESH:D014832), gastroenteritis (MESH:D005759), Fanconi syndrome (MESH:D005198), X-linked hypophosphatemia (MESH:D053098), dysfunction of the renal tubules (MESH:D007673), Liddle syndrome (MESH:D056929), enamel (MESH:D003744), hyperkalemia (MESH:D006947), pain (MESH:D010146), Gordon syndrome/pseudohypoaldosteronism type II (MESH:D011546), fracture (MESH:D050723), tubular (MESH:D000230), Water-balance disorders (MESH:D000069578), diabetes (MESH:D003920), muscle weakness (MESH:D018908), ocular) abnormalities (MESH:D005124), renal potassium wasting (MESH:D011191), growth failure (MESH:D051437), electrolyte (MESH:D014883), secondary hyperparathyroidism (MESH:D006962), calciuric spikes (MESH:D031261), CKD (MESH:D051436), X-linked disorder (MESH:D040181), pulmonary oedema (MESH:D011654), obesity (MESH:D009765), bleeding (MESH:D006470), lithiasis (MESH:D020347), Inherited and acquired tubulopathies (MESH:D000163), granulomatous diseases (MESH:D006105), osteopenia (MESH:D001851), periapical infections (MESH:D010483), Vitamin D insufficiency (MESH:D014808), calcium nephrolithiasis (MESH:C563477), diarrhoea (MESH:D003967), Dental abnormalities (MESH:D014071), DEFINE TUBULOPATHIES (MESH:C557674), stone-forming tubulopathies (MESH:C536350), fatigue (MESH:D005221), adenine phosphoribosyltransferase (APRT) deficiency (MESH:C538228), hypokalemic (MESH:D020514), renal phosphate wasting (MESH:D019282), alkalosis (MESH:D000471), genetic defect (MESH:D030342), glucosuria (MESH:D006030), hypotension (MESH:D007022), primary hyperparathyroidism (MESH:D049950), bone demineralization (MESH:D018488), vomiting (MESH:D014839), bone fragility (MESH:C536063)
- **Chemicals:** Vitamin D (MESH:D014807), ibuprofen (MESH:D007052), Sodium chloride (MESH:D012965), potassium bicarbonate (MESH:C026329), Calcium carbonate (MESH:D002119), phosphate (MESH:D010710), salt (MESH:D012492), chlorthalidone (MESH:D002752), sugar (MESH:D000073893), cortisol (MESH:D006854), prostaglandin (MESH:D011453), oxalate (MESH:D010070), aldosterone (MESH:D000450), Ketoconazole (MESH:D007654), Azole (MESH:D001393), potassium citrate (MESH:D019357), imidazoles (MESH:D007093), Water (MESH:D014867), Electrolyte (MESH:D004573), empagliflozin (MESH:C570240), fluoride (MESH:D005459), eplerenone (MESH:D000077545), calcium oxalate (MESH:D002129), Ascorbic acid (MESH:D001205), triamterene (MESH:D014223), Chloride (MESH:D002712), glyoxylic acid (MESH:C031150), Thiazide (MESH:D049971), BioRender (-), sodium bicarbonate (MESH:D017693), Calcifediol (MESH:D002112), Sodium (MESH:D012964), 25-hydroxyvitamin D (MESH:C104450), Potassium (MESH:D011188), magnesium sulfate (MESH:D008278), cholecalciferol (MESH:D002762), Indomethacin (MESH:D007213), ergosterol (MESH:D004875), urea (MESH:D014508), hydrochlorothiazide (MESH:D006852), celecoxib (MESH:D000068579), magnesium citrate (MESH:C110422), citrate (MESH:D019343), spironolactone (MESH:D013148), Fluconazole (MESH:D015725), triazole (MESH:D014230), melanin (MESH:D008543), burosumab (MESH:C000601956), magnesium oxide (MESH:D008277), alkali (MESH:D000468), Dipyridamole (MESH:D004176), indapamide (MESH:D007190), calcitriol (MESH:D002117), potassium chloride (MESH:D011189), Amiloride (MESH:D000584), Calcium (MESH:D002118), 1,25-dihydroxyvitamin D (MESH:C097949), Magnesium (MESH:D008274), glucose (MESH:D005947)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** I130N

## Full text

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## References

86 references — full list in the complete paper: https://tomesphere.com/paper/PMC12963964/full.md

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Source: https://tomesphere.com/paper/PMC12963964