Related Experiment Video
Updated: Feb 14, 2026
Isolation of Primary Human Proximal Tubule Epithelial Cells and Their Use in Creating a Microphysiological Model of the Renal Proximal Tubule
Published on: May 9, 2025
Fluoride-associated ultrastructural changes and apoptosis in human renal tubule: a pilot study
J A Quadri1, S Sarwar1, A Sinha2
11 Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
Insights
High fluoride levels in children with nephrotic syndrome correlate with kidney damage. This study found increased apoptosis and ultrastructural changes in kidney biopsies of children with elevated urinary fluoride concentrations, indicating fluoride-associated nephrotoxicity.
Area of Science:
- Nephrology
- Toxicology
- Biochemistry
Background:
- Kidney susceptibility to fluoride toxicity is linked to renal anatomy and function.
- Children with renal impairments often exhibit dental and skeletal fluorosis symptoms.
- Fluoride may interfere with renal physiology, potentially causing pathogenesis.
Purpose of the Study:
- To evaluate fluoride-associated nephrotoxicity in children.
- To investigate the correlation between urinary fluoride levels and kidney damage.
Main Methods:
- Screened 156 patients with childhood nephrotic syndrome.
- Measured urinary and serum fluoride levels.
- Performed ultrastructural and apoptotic analysis on kidney biopsies from selected groups using transmission electron microscopy and TUNEL assay.
Main Results:
- 32 patients showed significantly high urinary (4.01 ± 1.83 ppm) and serum fluoride levels.
- Kidney biopsies revealed ultrastructural changes like nuclear disintegration and endoplasmic reticulum blebbing.
- Increased apoptosis and tubular epithelial damage (swelling, lysis, vacuolation, necrosis) were observed in the high fluoride group.
Conclusions:
- Elevated fluoride levels are associated with significant kidney damage in children with nephrotic syndrome.
- Fluoride exposure can induce ultrastructural alterations and apoptosis in renal tubular epithelial cells.
- Findings highlight the nephrotoxic potential of fluoride, particularly in vulnerable pediatric populations.
Abstract:
The susceptibility of the kidneys to fluoride toxicity can largely be attributed to its anatomy and function. As the filtrate moves along the complex tubular structure of each nephron, it is concentrated in the proximal and distal tubules and collecting duct. It has been frequently observed that the children suffering from renal impairments also have some symptoms of dental and skeletal fluorosis. The findings suggest that fluoride somehow interferes with renal anatomy and physiology, which may lead to renal pathogenesis. The aim of this study was to evaluate the fluoride-associated nephrotoxicity. A total of 156 patients with childhood nephrotic syndrome were screened and it was observed that 32 of them had significantly high levels ( p ≤ 0.05) of fluoride in urine (4.01 ± 1.83 ppm) and serum (0.1 ± 0.013 ppm). On the basis of urinary fluoride concentration, patients were divided into two groups, namely group 1 (G-1) ( n = 32) containing normal urine fluoride (0.61 ± 0.17 ppm) and group 2 (G-2) ( n = 32) having high urine fluoride concentration (4.01 ± 1.83 ppm). Age-matched healthy subjects ( n = 33) having normal levels of urinary fluoride (0.56 ± 0.15 ppm) were included in the study as control (group 0 (G-0)). Kidney biopsies were taken from G-1 and G-2 only, who were subjected to ultrastructural (transmission electron microscopy) and apoptotic (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling) analysis. Various subcellular ultrastructural changes including nuclear disintegration, chromosome condensation, cytoplasmic ground substance lysis, and endoplasmic reticulum blebbing were observed. Increased levels of apoptosis were observed in high fluoride group (G-2) compared to normal fluoride group (G-1). Various degrees of fluoride-associated damages to the architecture of tubular epithelia, such as cell swelling and lysis, cytoplasmic vacuolation, nuclear condensation, apoptosis, and necrosis, were observed.
Related Concept Videos
01:24Renal Tubule and Collecting Duct
Proximal Convoluted Tubule (PCT):
The PCT is the initial segment of the renal tubule, extending from the Bowman's capsule that encloses the glomerulus. Its convoluted structure and microvilli-lined cells increase the surface area for reabsorption. The PCT reabsorbs glucose, amino acids, sodium, and water from the filtrate, ensuring essential...
01:30Apoptosis
01:21Pilot and Numeric Relaying
01:24Serum Studies: Renal Function Tests
01:17Factors Affecting Renal Clearance: Renal Impairment
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
01:20Renal Corpuscle
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous...