The molecular basis of kidney stones

Current Opinion in Pediatrics

Volumn 16, Issue 2, 2004, Pages 188-193

  Langman, Craig B ^a,b  

^a NORTHWESTERN UNIVERSITY   (United States)

^b CHILDREN'S MEMORIAL HOSPITAL   (United States)

Author keywords

Cystinuria; Genetic diseases; Idiopathic hypercalciuria; Primary hyperoxaluria; Uric acid

Indexed keywords

VOLTAGE GATED POTASSIUM CHANNEL; VOLTAGE GATED SODIUM CHANNEL;

CYSTINURIA; DIAGNOSTIC APPROACH ROUTE; DISEASE ASSOCIATION; GENE MUTATION; GENETIC ASSOCIATION; GENETIC CORRELATION; GENETIC DISORDER; GENETIC SUSCEPTIBILITY; HUMAN; HYPERCALCIURIA; HYPEROXALURIA; HYPERURICOSURIA; HYPOPHOSPHATEMIA; NEPHROLITHIASIS; PRIORITY JOURNAL; PSEUDOHYPOALDOSTERONISM; REVIEW; URINARY EXCRETION;

CHLORIDE CHANNELS; CYSTINURIA; HUMANS; HYPEROXALURIA; HYPOPHOSPHATEMIA; KIDNEY CALCULI; SODIUM-POTASSIUM-CHLORIDE SYMPORTERS;

EID: 1642386993     PISSN: 10408703     EISSN: None     Source Type: Journal    
DOI: 10.1097/00008480-200404000-00013     Document Type: Review

References (27)

1. Raja KA, Schurman S, M'Dello DG, et al.: Responsiveness of hypercalciuria to thiazide in Dent's disease. J Am Soc Nephrol 2002, 13:2938-2944. An important clinical investigation about hypercalciuria suggests that the distal convoluted tubule works normally in patients with CLC-5 mutations.
2. +-ATPase specifically was reduced, the investigators have extended our knowledge of how CLC-5 mutations may affect endosomic acidification processes. This is a state-of-the-art example of molecular research at the bedside and should be read for knowledge about the specific disease as well as how to think about human-based molecular studies with human tissue studied in vitro.
3. Carballo-Trujillo I, Garcia-Nieto V, Moya-Angeler FJ, et al.: Novel truncating mutations in the CLC-5 chloride channel gene in patients with Dent's disease. Nephrol Dial Transplant 2003, 18:717-723. This is a nice study of a modern approach to the molecular defects in patients with Dent's disease. The paper adds an international flavor by studying Spanish patients.
4. Mo L, Xiong W, Qian T, et al.: Coexpression of complementary cDNA fragments and restoration of chloride-channel function in a Dent's disease mutation of CLC-5. Am J Physiol Cell Physiol 2003. Epub 2003, Sep:17. This study provides proof of principle for correction of truncated proteins involved in Dent's disease expression. This is how to do it.
5. Carr G, Simmons N, Sayer J: A role for CBS domain 2 in trafficking of chloride channel CLC-5. Biochem Biophys Res Commun 2003, 31:600-605. This represents an excellent extension of our knowledge of the meaning of the molecular structure of the CLC-5 protein.
6. Zelikovic I, Szargel R, Hawash A, et al.: A novel mutation in the chloride channel gene, CLCNKB, as a cause of Gitelman and Bartter syndromes. Kidney Int 2003, 63:24-32. This paper notes the difficulties in the phenotype-genotype correlations in these disorders and makes a great case for molecular diagnostic analysis. Again, this is an excellent example of bedside-to-bench clinical research.
7. Mayan H, Vered I, Mouallem M, et al.: Pseudohypoaldosteronism type II: marked sensitivity to thiazides, hypercalciuria, normomagnesemia, and low bone mineral density. J Clin Endocrinol Metab 2002, 87:3248-3254. This paper reminds us that even in well-characterized diseases, there is always something more to learn by a careful reanalysis of the patients-in this case, after stopping thiazides that were used to treat the hypertension and hyperkalemia.
8. Ruf R, Rensing C, Topaloglu R, et al.: Confirmation of the ATP6B1 gene as responsible for distal renal tubular acidosis. Pediatr Nephrol 2003, 18:105-109. This is continuation of excellent molecular sleuthing for tubular diseases by a group that finds new genes weekly.
9. Prie D, Huart V, Bakouh N, et al.: Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med 2002, 347:983-991. This represents an exhaustive search for a reason for the stone disease in well-characterized patients with altered phosphate handling by the kidney. See also the letter about the article and the authors' response (N Engl J Med 2003, 264-265).
10. Sermet-Gaudelus I, Garabedian M, Dechaux M, et al.: Hereditary hypophosphatemic rickets with hypercalciuria: report of a new kindred. Nephron 2001, 88:83-86. This and the next reference are provided just for background because they are outside the time line of the review proper.
11. Jones A, Tzenova J, Frappier D, et al.: Hereditary hypophosphatemic rickets with hypercalciuria is not caused by mutations in the Na/Pi cotransporter NPT2 gene. J Am Soc Nephrol 2001, 12:507-514.
12. Johnson SA, Rumsby G, Creegen D, et al.: Primary hyperoxaluria type 2 in children. Pediatr Nephrol 2002, 17:597-601. This article ties together some clinical and new molecular data in the rarely described patients with primary hyperoxaluria type II.
13. Coulter-Mackie MB, Tung A, Henderson HE, et al.: The AGT gene in Africa: a distinctive minor allele haplotype, a polymorphism (V326I), and a novel PH1 mutation (A112D) in black Africans. Mol Genet Metab 2003, 78:44-50. This exciting study demonstrates a new polymorphism on the minor allele and its association in PH1 with a new mutation in African blacks. The polymorphism does occur in whites, so be on the lookout for a disease in that ethnicity related to it.
14. Danpure CJ, Lumb MJ, Birdsey GM, et al.: Alanine: glyoxylate amino transferase peroxisome-to-mitochondrion mistargeting in human hereditary kidney stone disease. Biochim Biophys Acta 2003, 1647:70-75. This is an excellent review for beginners and experienced clinicians alike who are involved in oxalosis of the AGT enzyme actions in the cell in normal and diseased states. It provides a clear understanding of the complex nature of mistargeting of AGT to the mitochondria in the most common form of primary hyperoxaluria type I.
15. Santana A, Salido E, Torres A, et al.: Primary hyperoxaluria type I in the Canary Islands: a conformational disease due to I244T mutation in the P11L-containing alanine:glyoxylate aminotransferase. Proc Natl Acad Sci USA 2003, 100:7277-7282. Wow! What excitement this article produced when it demonstrated that the intracellular protein aggregation of AGT can be prevented by simple substances such as betaine. Stay tuned for more of small molecule therapeutics in the care of primary hyperoxaluria.
16. Zhang X, Roe SM, Hou Y, et al.: Crystal structure of alanine:glyoxylate aminotransferase and the relationship between genotype and enzymatic phenotype in primary hyperoxaluria type I. J Mol Biol 2003, 331:643-652. This is another excellent study in which the crystal structure of AGT is solved to 2.5A and an understanding of the majority of mutations in AGT that produce primary hyperoxaluria type I is discussed.
17. Lumb MJ, Birdsey GM, Danpure CJ: Correction of an enzyme trafficking defect in hereditary kidney stone disease in vitro. Biochem J 2003, 374:79-87. This is an excellent review of the subject with new data on small molecule therapeutics and a must read for those interested in the hyperoxaluric diseases.
18. Creegen DP, Williams EL, Hulton S, et al.: Molecular analysis of the glyoxylate reductase (GRHPR) gene and description of underlying primary hyperoxaluria type 2. Hum Mutat 2003, 22:497-506. This article is because it demonstrates that the protein for GRHPR is mostly hepatic, whereas the mRNA is widely distributed in the body.
19. Strologo LD, Pras E, Pontesilli C, et al.: Comparison between SLC3A1 and SLC7A9 cystinuria patients and carriers: a need for a new classification. J Am Soc Nephrol 2002, 13:2547-2553. This study started much of the controversy that led to significant new ideas about the molecular defects.
20. Botzenhart E, Vester U, Schmidt C, et al.: Cystinuria in children: distribution and frequencies of mutations in the SLC3A1 and SLC7A9 genes. Kidney Int 2002, 62:1136-1142. This study demonstrates the value of a comprehensive, multicenter study (Germany, in this case) for the study of a rare genetic disease. It is excellent work with more to come from this group.
21. LeClerc D, Boutros M, Suh D, et al.: SLC7A9 mutations in all three cystinuria subtypes. Kidney Int 2002, 62:1550-1559. This is an excellent analysis of the old classification system with modern molecular biology of cystinuria, laying to rest the belief about phenotype-genotype correlations.
22. Harnevik L, Fjellstedt E, Molbaek A, et al.: Mutation analysis of SLC7A9 in cystinuria patients in Sweden. Genet Test 2003, 7:13-20. Other countries are now weighing in with unique mutations with this article. This article adds to the body of evidence of other genes involved in cystinuria.
23. Schmidt C, Tomiuk J, Botzenhart E, et al.: Genetic variations of the SLC7A9 gene: allelic distribution of 13 polymorphic sites in German cystinuria patients and controls. Clin Nephrol 2003, 59:353-359. This article brings forth the concept of polymorphisms in cystinuria and is worth the read.
24. Schmidt C, Vester U, Wagner CA, et al.: Significant contribution of genomic rearrangements in SCL3A1 and SLC7A9 to the etiology of cystinuria. Kidney Int 2003, 64:1564-1572. This is the latest information about how mutations in these genes may bring about the disease and where there are still holes in our knowledge. Lots more to come!
25. Gianfrancesco F, Esposito T, Ombra MN, et al.: Identification of a novel gene and a common variant associated with uric acid nephrolithiasis in a Sardinian genetic isolate. Am J Hum Genet 2003, 72:1479-1491. This is a great read because there has been little new in the molecular biology of uric acid stone disease for quite some time, and we read about a new gene that is associated with the disease. This is a great venue for studying stone disease; state-of-the-art clinical investigation is represented by this study as well.
26. Gok F, Ichida K, Topaloglu R: Mutational analysis of the xanthine dehydrogenase gene in a Turkish family with autosomal recessive classical xanthinuria. Nephrol Dial Transplant 2003, 18:2278-2283. And who knew there was nonclassical xanthinuria? Seriously, this is another elegant study of a rare but important cause of pediatric stone diseases.
27. Turner JJ, Stacey JM, Harding B, et al. Uromodulin mutations cause familial juvenile hyperuricemic nephropathy. J Clin Endocrinol Metab 2003; 1398-1401. We end our review with an excellent laboratory involved in finding genes for diverse kidney disease, including almost all the ones discussed herein. The article raises new possibilities about the role of uromodulin in stone disease.