Correlation and Prognostic Utility of B-Type Natriuretic Peptide and Its Amino-Terminal Fragment in Patients With Chronic Kidney Disease

Abstract BACKGROUND Chronic renal inflammation and fibrosis are common sequelae in diabetes mellitus (DM) and are major causes of premature mortality. Although upregulation of NPPC expression occurs in response to renal inflammation in experimental animals, nothing is known of the molecular forms of C-type natriuretic peptide (CNP) products in urine of people with DM or links with renal function. METHODS ProCNP products in urine were characterized with HPLC and a range of antisera directed to specific epitopes of amino-terminal proCNP (NTproCNP). The 5-kDa intact peptide was quantified in spot urine samples from healthy adults and 202 participants with DM selected to provide a broad range of renal function. RESULTS The predominant products of proCNP in urine were consistent with the 2-kDa fragment (proCNP 3–20) and a smaller peak of intact (5-kDa) fragment (proCNP 1–50, NTproCNP). No peaks consistent with bioactive forms (proCNP 82–103, 50–103) were identified. The urine NTproCNP to creatinine ratio (NCR) was more reproducible than the albumin to creatinine ratio (ACR) and strongly associated with the presence of chronic kidney disease. In models predicting independence, among 10 variables associated with renal function in DM, including plasma NTproCNP, only 3 (sex, ACR, and plasma creatinine) contributed to NCR. CONCLUSIONS Characterization of the products of proCNP in urine confirmed the presence of NTproCNP. In spot random urine from study participants with DM, NCR is inversely associated with estimated glomerular filtration rate. In contrast to ACR, NCR reflects nonvascular factors that likely include renal inflammation and fibrosis.

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Evolution of the hedgehog Gene Family

Genetics ◽

10.1093/genetics/142.3.965 ◽

1996 ◽

Vol 142 (3) ◽

pp. 965-972 ◽

Cited By ~ 2

Author(s):

Sudhir Kumar ◽

Kristi A Balczarek ◽

Zhi-Chun Lai

Keyword(s):

Intercellular Communication ◽

Short Range ◽

Gene Duplications ◽

Future Directions ◽

Amino Terminal ◽

Terminal Fragment ◽

Carboxyl Terminal ◽

Multicellular Organisms ◽

Amino Terminal Fragment

Abstract Effective intercellular communication is an important feature in the development of multicellular organisms. Secreted hedgehog (hh) protein is essential for both long- and short-range cellular signaling required for body pattern formation in animals. In a molecular evolutionary study, we find that the vertebrate homologs of the Drosophila hh gene arose by two gene duplications: the first gave rise to Desert hh, whereas the second produced the Indian and Sonic hh genes. Both duplications occurred before the emergence of vertebrates and probably before the evolution of chordates. The amino-terminal fragment of the hh precursor, crucial in long- and short-range intercellular communication, evolves two to four times slower than the carboxyl-terminal fragment in both Drosophila hh and its vertebrate homologues, suggesting conservation of mechanism of hh action in animals. A majority of amino acid substitutions in the amino- and carboxyl-terminal fragments are conservative, but the carboxyl-terminal domain has undergone extensive insertion-deletion events while maintaining its autocleavage protease activity. Our results point to similarity of evolutionary constraints among sites of Drosophila and vertebrate hh homologs and suggest some future directions for understanding the role of hh genes in the evolution of developmental complexity in animals.

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