Tags

Type your tag names separated by a space and hit enter

Tamm-Horsfall protein in recurrent calcium kidney stone formers with positive family history: abnormalities in urinary excretion, molecular structure and function.
Urol Res. 2007 Apr; 35(2):55-62.UR

Abstract

Tamm-Horsfall protein (THP) powerfully inhibits calcium oxalate crystal aggregation, but structurally abnormal THPs from recurrent calcium stone formers may promote crystal aggregation. Therefore, increased urinary excretion of abnormal THP might be of relevance in nephrolithiasis. We studied 44 recurrent idiopathic calcium stone formers with a positive family history of stone disease (RCSF(fam)) and 34 age- and sex-matched healthy controls (C). Twenty-four-hour urinary THP excretion was measured by enzyme linked immunosorbent assay. Structural properties of individually purified THPs were obtained from analysis of elution patterns from a Sepharose 4B column. Sialic acid (SA) contents of native whole 24-h urines, crude salt precipitates of native urines and individually purified THPs were measured. THP function was studied by measuring inhibition of CaOx crystal aggregation in vitro (pH 5.7, 200 mM sodium chloride). Twenty-four-hour urine excretion of THP was higher in RCSF(fam) (44.0 +/- 4.0 mg/day) than in C (30.9 +/- 2.2 mg/day, P = 0.015). Upon salt precipitation and lyophilization, elution from a Sepharose 4B column revealed one major peak (peak A, cross-reacting with polyclonal anti-THP antibody) and a second minor peak (peak B, not cross-reacting). THPs from RCSF(fam) eluted later than those from C (P = 0.021), and maximum width of THP peaks was higher in RCSF(fam)than in C (P = 0.024). SA content was higher in specimens from RCSF(fam) than from C, in native 24-h urines (207.5 +/- 20.4 mg vs. 135.2 +/- 16.1 mg, P = 0.013) as well as in crude salt precipitates of 24-h urines (10.4 +/- 0.5 mg vs. 7.4 +/- 0.9 mg, P = 0.002) and in purified THPs (75.3 +/- 9.3 microg/mg vs. 48.8 +/- 9.8 microg/mg THP, P = 0.043). Finally, inhibition of calcium oxalate monohydrate crystal aggregation by 40 mg/L of THP was lower in RCSF(fam) (6.1 +/- 5.5%, range -62.0 to +84.2%) than in C (24.9 +/- 6.0%, range -39.8 to +82.7%), P = 0.022, and only 25 out of 44 (57%) THPs from RCSF(fam)were inhibitory (positive inhibition value) vs. 25 out of 34 (74%) THPs from C, P < 0.05. In conclusion, severely recurrent calcium stone formers with a positive family history excrete more THP than healthy controls, and their THP molecules elute later from an analytical column and contain more SA. Such increasingly aggregated THP molecules predispose to exaggerated calcium oxalate crystal aggregation, an important prerequisite for urinary stone formation.

Authors+Show Affiliations

Renal Stone Clinic and Stone Research Laboratory, Policlinic of Internal Medicine, University Hospital, Berne, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17345077

Citation

Jaggi, Markus, et al. "Tamm-Horsfall Protein in Recurrent Calcium Kidney Stone Formers With Positive Family History: Abnormalities in Urinary Excretion, Molecular Structure and Function." Urological Research, vol. 35, no. 2, 2007, pp. 55-62.
Jaggi M, Nakagawa Y, Zipperle L, et al. Tamm-Horsfall protein in recurrent calcium kidney stone formers with positive family history: abnormalities in urinary excretion, molecular structure and function. Urol Res. 2007;35(2):55-62.
Jaggi, M., Nakagawa, Y., Zipperle, L., & Hess, B. (2007). Tamm-Horsfall protein in recurrent calcium kidney stone formers with positive family history: abnormalities in urinary excretion, molecular structure and function. Urological Research, 35(2), 55-62.
Jaggi M, et al. Tamm-Horsfall Protein in Recurrent Calcium Kidney Stone Formers With Positive Family History: Abnormalities in Urinary Excretion, Molecular Structure and Function. Urol Res. 2007;35(2):55-62. PubMed PMID: 17345077.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tamm-Horsfall protein in recurrent calcium kidney stone formers with positive family history: abnormalities in urinary excretion, molecular structure and function. AU - Jaggi,Markus, AU - Nakagawa,Yasushi, AU - Zipperle,Ljerka, AU - Hess,Bernhard, Y1 - 2007/03/08/ PY - 2006/11/14/received PY - 2007/02/10/accepted PY - 2007/3/9/pubmed PY - 2007/7/26/medline PY - 2007/3/9/entrez SP - 55 EP - 62 JF - Urological research JO - Urol Res VL - 35 IS - 2 N2 - Tamm-Horsfall protein (THP) powerfully inhibits calcium oxalate crystal aggregation, but structurally abnormal THPs from recurrent calcium stone formers may promote crystal aggregation. Therefore, increased urinary excretion of abnormal THP might be of relevance in nephrolithiasis. We studied 44 recurrent idiopathic calcium stone formers with a positive family history of stone disease (RCSF(fam)) and 34 age- and sex-matched healthy controls (C). Twenty-four-hour urinary THP excretion was measured by enzyme linked immunosorbent assay. Structural properties of individually purified THPs were obtained from analysis of elution patterns from a Sepharose 4B column. Sialic acid (SA) contents of native whole 24-h urines, crude salt precipitates of native urines and individually purified THPs were measured. THP function was studied by measuring inhibition of CaOx crystal aggregation in vitro (pH 5.7, 200 mM sodium chloride). Twenty-four-hour urine excretion of THP was higher in RCSF(fam) (44.0 +/- 4.0 mg/day) than in C (30.9 +/- 2.2 mg/day, P = 0.015). Upon salt precipitation and lyophilization, elution from a Sepharose 4B column revealed one major peak (peak A, cross-reacting with polyclonal anti-THP antibody) and a second minor peak (peak B, not cross-reacting). THPs from RCSF(fam) eluted later than those from C (P = 0.021), and maximum width of THP peaks was higher in RCSF(fam)than in C (P = 0.024). SA content was higher in specimens from RCSF(fam) than from C, in native 24-h urines (207.5 +/- 20.4 mg vs. 135.2 +/- 16.1 mg, P = 0.013) as well as in crude salt precipitates of 24-h urines (10.4 +/- 0.5 mg vs. 7.4 +/- 0.9 mg, P = 0.002) and in purified THPs (75.3 +/- 9.3 microg/mg vs. 48.8 +/- 9.8 microg/mg THP, P = 0.043). Finally, inhibition of calcium oxalate monohydrate crystal aggregation by 40 mg/L of THP was lower in RCSF(fam) (6.1 +/- 5.5%, range -62.0 to +84.2%) than in C (24.9 +/- 6.0%, range -39.8 to +82.7%), P = 0.022, and only 25 out of 44 (57%) THPs from RCSF(fam)were inhibitory (positive inhibition value) vs. 25 out of 34 (74%) THPs from C, P < 0.05. In conclusion, severely recurrent calcium stone formers with a positive family history excrete more THP than healthy controls, and their THP molecules elute later from an analytical column and contain more SA. Such increasingly aggregated THP molecules predispose to exaggerated calcium oxalate crystal aggregation, an important prerequisite for urinary stone formation. SN - 0300-5623 UR - https://www.unboundmedicine.com/medline/citation/17345077/Tamm_Horsfall_protein_in_recurrent_calcium_kidney_stone_formers_with_positive_family_history:_abnormalities_in_urinary_excretion_molecular_structure_and_function_ L2 - https://dx.doi.org/10.1007/s00240-007-0083-7 DB - PRIME DP - Unbound Medicine ER -