Nephrocalcinosis in glucose-galactose malabsorption: nephrocalcinosis and proximal tubular dysfunction in a young infant with a novel mutation of SGLT1

Tunçel, Tuba; Ecevıt, Çiğdem; Altınöz, Serdar; Öztürk, Aysel; Temizkan, Ali Kemal; Maeda, Morihiro; Kasahara, Michihiro

doi:10.1007/s00431-008-0681-6

Cited by 20 publications

(24 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Absorbed glucose then diffuses back into the blood from basolateral side of cells via GLUT transporters in a Na + -independent manner (Wright et al, 2011). Humans with mutations in SLC5A1 gene encoding SGLT1 suffer from an intestinal disease known as glucose-galactose malabsorption but have little or no sign of glucosuria (Soylu et al, 2008; Wright et al, 2011; Xin and Wang, 2011). However, people with mutations in SLC5A2 gene encoding SGLT2 develop severe glucosuria (Lee et al, 2012; Santer and Calado, 2010; Yu et al, 2011) with urinary excretions of glucose as high as 160 g per day (Bakris et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

A novel SGLT is expressed in the human kidney

Kothinti

Blodgett

North

et al. 2012

European Journal of Pharmacology

View full text Add to dashboard Cite

Selective inhibitors of sodium-glucose cotransporter 2 (SGLT2)-mediated reabsorption of glucose in the proximal tubule of the kidney are being developed for the treatment of diabetes. SGLT2 shares high degree of homology with SGLT3; however, very little is known about the expression and functional role of SGLT3 in the human kidney. Indeed, the SGLT2 inhibitors that are currently in clinical trials might affect the expression and/or the activity of SGLT3. Therefore, the present study examined the expression of SGLT3 mRNA and protein in human kidney and in a human proximal tubule HK-2 cell line. The results indicated that human SGLT3 (hSGLT3) message and protein are expressed both in vivo and in vitro. We also studied the activity of hSGLT3 protein following its over-expression in mammalian kidney-derived COS-7 cells and in HK-2 cells treated with the imino sugar deoxynojirimycin (DNJ), a potent agonist of hSGLT3. Over-expression of hSGLT3 in COS-7 cells increased intracellular sodium concentration by 3-fold without affecting glucose transport. Activation of hSGLT3 with DNJ (50 μM) increased sodium uptake in HK-2 cells by 5.5 fold and this effect could be completely blocked with SGLT inhibitor phlorizin (50 μM). These results suggest that SGLT3 is expressed in human proximal tubular cells where it serves as a novel sodium transporter. Up-regulation of the expression of SGLT3 in the proximal tubule in diabetic patients may contribute to the elevated sodium transport in this segment of the nephron that has been postulated to promote hyperfiltration and renal injury.

show abstract

Section: Discussionmentioning

confidence: 99%

A novel SGLT is expressed in the human kidney

Kothinti

Blodgett

North

et al. 2012

European Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

“…Using an animal model, Suzuki et al [33] demonstrated that a gain of function haplotype in TRPV6 plays a role in calcium stone formation in certain forms of absorptive hypercalciuria. This could be a plausible mechanism for the nephrocalcinosis seen in our patients and the cases already reported [4, 7]. Reasons for persistent nephrocalcinosis despite adequate diet are unclear.…”

Section: Discussionmentioning

confidence: 74%

“…Although there are over 40 mutations of SLC5A1 that have been linked to GGM [36], only 2 other patients with nephrocalcinosis and GGM have their mutations described in the literature [7, 8]. Therefore, there are insufficient data for genotype-phenotype associations at this point [18, 36].…”

Section: Discussionmentioning

confidence: 99%

“…In both infants, the osmotic diarrhea was so profuse that it was mistaken for polyuria, highlighting the importance of objective urine output collection with catheters in infants. Mistaking profuse osmotic diarrhea for polyuria is not unique to the 2 cases presented here [4, 7, 9]. A high index of suspicion of a malabsorption disorder such as GGM should arise if the losses are found to be gastrointestinal.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Two Cases of Mistaken Polyuria and Nephrocalcinosis in Infants with Glucose-Galactose Malabsorption: A Possible Role of 1,25(OH)<sub>2</sub>D<sub>3</sub>

et al. 2017

View full text Add to dashboard Cite

Background/Aims: Glucose-galactose malabsorption (GGM) is a rare and potentially fatal disorder. The autosomal recessive mutation of the SGLT1 gene interferes with the active glucose transport in the gut resulting in osmotic diarrhea and failure to thrive (FTT). Two nonrelated infants with GGM are presented as well as a novel mutation in SGLT1. Case Presentation: The first case consulted for FTT and presented with hypercalcemia and hypercalciuria. His mother had self-medicated with high doses of vitamin D. The second case consulted for macroscopic hematuria, and presented with dehydration and secondary acute kidney injury. In both cases, the profuse diarrhea, initially mistaken for polyuria, promptly resolved after the introduction of glucose-galactose-free milk. Investigations showed bilateral nephrocalcinosis and high levels of 1,25(OH)₂D₃ in both patients. We hypothesize that the upregulation of epithelial calcium channels (TRPV6) and 1,25(OH)₂D₃ are possible factors involved in the pathophysiology of nephrocalcinosis sometimes seen in GGM. Furthermore, a novel intronic SGLT1 mutation (c.207+2dup) is described. Conclusion: These 2 cases demonstrate that a malabsorption disorder such as GGM can present with nephrocalcinosis and/or hypercalcemia, with increased 1,25(OH)₂D₃ levels in infants. Prompt recognition of GGM is sometimes difficult but crucial.

show abstract

“…Finding renal abnormalities is also another clue to suspect GGM as the sodium/glucose co‐transporter‐1 is present in both intestinal cells and in renal tubules. Renal abnormalities were reported in association with GGM, namely hematuria, nephrocalcinosis and renal tubular acidosis, rickets, nephrogenic diabetes insipidus, and renal stones. Neonatal irreversible renal failure was not reported before.…”

Section: Discussionmentioning

confidence: 99%