Urinary enzymes, nephrotoxicity and renal disease

doi:10.1016/0300-483X(82)90092-0

Toxicology

Volume 23, Issues 2–3, 1982, Pages 99-134

https://doi.org/10.1016/0300-483X(82)90092-0 Get rights and content

Abstract

The value of urinary enzymes as non-invasive tests of renal integrity in toxicology and medicine is reviewed. Urinary enzymes provide very sensitive indicators of renal damage and although a wide variety of enzymes have been assayed, only a few have proved useful because of practical considerations. The assay of NAG and AAP have proved to be most valuable, while other enzymes, including LDH, lysozyme, kallikrein, carbonic anhydrase C, arylsulphatase A, alkaline phosphatase and γGT have proved to be useful in particular situations. The diagnostic potential of urinary enzymes is often enhanced by the simultaneous assay of more than one enzyme, particularly if the activities of the enzymes used are high in different regions of the nephron. Isoenzyme studies provide additional diagnostic information. Urinary enzyme assays are most useful when carried out in conjunction with simple non-invasive test of renal function, e.g. osmolality, and protein selectivity.

The marked susceptibility of the kidney to toxic damage and the effect of drugs on subcellular organelles are discussed. Further, the problems of assaying enzymes in urine are considered and the various ways in which they can be overcome is described. Recent improvements in techniques, including automation, miniphotometers and “dipstick” tests, are described. The importance of age is emphasised, and different ways of expressing enzyme activities, which allow for varying urine flow, is discussed.

Urinary enzymes can play a role in the detection of nephrotoxicity, monitoring the level of safe doses in patients, the evaluation of new drugs and in the control of industrial workers using hazardous chemicals. The most important nephrotoxins are certain antibiotics, heavy metals, herbicides and anti-inflammatory drugs. Urinary enzymes have considerable potential value for the early warning of rejection in transplant patients, screening for renal disease and for the detection of renal damage secondary to hypertension, diabetes and rheumatoid arthritis. The review concludes by considering how urinary enzymes will be used in the future as an aid to the toxicologist and clinician.

References (252)

U. Schmidt et al.
Kidney Int.
(1976)
B.G. Ellis et al.
Chem.-Biol. Interact.
(1975)
M. Sharratt
Renal function tests in laboratory animals
A. Cornell et al.
Clin. Chim. Acta
(1979)
P.R. Beck et al.
Clin. Chim. Acta
(1975)
J.M. Wellwood et al.
Clin. Chim. Acta
(1976)
S.M. Tucker et al.
Clin. Chim. Acta
(1975)
D. Maruhn
Clin. Chim. Acta
(1976)
D. Maruhn et al.
Clin. Chim. Acta
(1977)
N. Dance et al.
Clin. Chim. Acta
(1970)

J. Diezi et al.

Pharmacol. Ther.

(1979)

B.G. Ellis et al.

Chem.-Biol. Interact.

(1973)

M. Robinson et al.

J. Comp. Pathol.

(1976)

D.A. Feinfeld et al.

Kidney Int.

(1977)

T. Balazs

Toxicology

(1974)

R.G. Cottrell et al.

Food Cosmet. Toxicol.

(1976)

S.K. Tandon et al.

Toxicol. Appl. Pharmacol.

(1980)

W.E. Stroo et al.

Toxicol. Appl. Pharmacol.

(1977)

S.A. Kempson et al.

Chem.-Biol. Interact.

(1977)

P.J. Wright et al.

Biochem. Pharmacol.

(1974)

P.H. Whiting et al.

Clin. Chim. Acta

(1980)

D. Maruhn et al.

Clin. Biochem.

(1979)

M.A. Mansell et al.

Lancet

(1978)

P.H. Whiting et al.

Clin. Chim. Acta

(1979)

H.F. Carvajal et al.

Kidney Int.

(1975)

K. Nomiyama et al.

Toxicol. Appl. Pharmacol.

(1974)

E.O. Ngaha et al.

Biochem. Med.

(1977)

W.P. Raab

Clin. Chem.

(1972)

H. Mattenheimer

Ann. Clin. Lab. Sci.

(1977)

M.R. Schoenfeld

J. Am. Med. Assoc.

(1965)

D.A. Feinfeld et al.

Ligandinuria: an indication of tubular cell necrosis in Diagnostic Significance of Enzymes and Protein in Urine

D.G. Taylor et al.

Biochem. J.

(1971)

M. le Hir et al.

Histochemistry

(1979)

P.J.R. Boyd et al.

Kidney Int.

(1977)

D.T. Plummer et al.

Urinary enzymes as an index of kidney damage by toxic compounds in Nephrotoxicity: Interaction of Drugs and Membrane Systems

G. Horpacsy et al.

Clin. Chem.

(1976)

K. Andrassy et al.

Isolation and renal localisation of urokinase

W.J. Biewenga et al.

Tijdschr. Diergeneeskd.

(1978)

F.W. Tischendorf et al.

Klin. Wschr.

(1972)

P.D. Leathwood et al.

Enzymologia

(1969)

D. Coonrod et al.

J. Lab. Clin. Med.

(1969)

J.M. Wellwood

M.S. Thesis

G. Calcamuggi et al.

Minerva Med.

(1978)

D. Maruhn

Preparation of urine for enzyme determinations by gel filtration

D.N.S. Kerr

Acute Renal Failure in Renal Disease

S. Harding et al.

Br. Med. J.

(1978)

F.C. Reubi

Contr. Nephrol.

(1978)

Cited by (397)

Advances in Optical Sensors of N-Acetyl-β- d -hexosaminidase (N-Acetyl-β- d -glucosaminidase)
2022, Bioconjugate Chemistry
N-Acetyl-β-d-hexosaminidases (EC 3.2.1.52) are exo-acting glycosyl hydrolases that remove N-acetyl-β-d-glucosamine (Glc-NAc) or N-acetyl-β-d-galactosamine (Gal-NAc) from the nonreducing ends of various biomolecules including oligosaccharides, glycoproteins, and glycolipids. The same enzymes are sometimes called N-acetyl-β-d-glucosaminidases, and this review article employs the shorthand descriptor HEX(NAG) to indicate that the terms HEX or NAG are used interchangeably in the literature. The wide distribution of HEX(NAG) throughout the biosphere and its intracellular location in lysosomes combine to make it an important enzyme in food science, agriculture, cell biology, medical diagnostics, and chemotherapy. For more than 50 years, researchers have employed chromogenic derivatives of N-acetyl-β-d-glucosaminide in basic assays for biomedical research and clinical chemistry. Recent conceptual and synthetic innovations in molecular fluorescence sensors, along with concurrent technical improvements in instrumentation, have produced a growing number of new fluorescent imaging and diagnostics methods. A systematic summary of the recent advances in optical sensors for HEX(NAG) is provided under the following headings: assessing kidney health, detection and treatment of infectious disease, fluorescence imaging of cancer, treatment of lysosomal disorders, and reactive probes for chemical biology. The article concludes with some comments on likely future directions.
Current insights toward kidney injury: Decrypting the dual role and mechanism involved of herbal drugs in inducing kidney injury and its treatment
2020, Current Research in Biotechnology
Citation Excerpt :
Further from 18 human UGT enzymes identified kidney is known to express UGT1A6, UGT1A9 and UGT2B7. A brief discussion of their mechanisms leading to renal drug metabolism is discussed in subsequent sections (Price, 1982; Ichikawa et al., 1994). A brief compilation of synthetic and natural drugs/formulation affecting these enzymes is compiled in Table 4.
The kidney is essential for the physiological functions of the body. When exposed to high concentrations of toxins, these may induce the toxicity of the kidney (kidney injury), leading to renal failure and precipitating a condition called nephrotoxicity. The toxicity may result from hemodynamic changes and directly harm the cells and tissue, and causes obstruction of renal excretion. Nephrotoxicity can also be induced by renal impairment leads to kidney-specific detoxification and diminished kidney function by ischemia and toxicants/drugs. Considering the possible damage to kidneys by drugs, patients are using the naturally derived substance, including herbal drugs or nutraceuticals. However, the safety concerns of herbal drugs and formulation in inducing kidney injury are an area of research. The present review is a concerted effort to assemble information mainly focusing on the kidney injury, its comprehensive categorization, i.e., mechanism of interaction of various enzyme systems of kidneys with drugs of herbal and synthetic origin and their outcomes. Moreover, the review also put forth the details of herbal drug that precipitate kidney injury and ameliorate it. The review is being put forward with an incentive to provide researchers with a comprehensive and updated literature on kidney injury by drugs of natural and synthetic origin and their molecular targets in the kidney.
Diseases of the urinary system
2020, Sheep, Goat, and Cervid Medicine
Biomarkers of Drug Toxicity and Safety Evaluation
2019, Biomarkers in Toxicology
Some compounds can fail in the latter stages of development because of lack of efficacy and toxicity. To improve drug safety in the development, new biomarkers are needed, which can reduce the time-consuming process and cost of drug development. Traditional indicators of target organ toxicity used in drug preclinical safety studies are described. Severe adverse drug reactions are a major issue for drug therapy because they can cause serious disorders and be life-threatening. There is need for new efficient biomarkers of drug toxicity, which some of them can translate effectively from preclinical studies, and an important number of the biomarkers are described in this chapter. The safety biomarker should be validated and preclinical and clinical qualified. Several urinary kidney biomarkers in the context of preclinical development and clinical trials are presented in this chapter. Application of safety biomarkers in different phases of drug development is described.
Mechanisms Involved in the Renal Handling and Toxicity of Mercury
2018, Comprehensive Toxicology: Third Edition
One of the most important factors that determines the dispositional and toxicological fate of environmentally relevant forms of mercury in the body is the strong bonding affinity that exists between mercuric ions and reduced sulfur atoms of certain biomolecules. The formation of unique chemical species by the bonding of inorganic and organic mercuric ions in both extracellular and intracellular compartments of the body turns out to be a crucial part of the mechanisms involved in the handling and toxicity of inorganic and organic mercury in specific target tissues and organs, especially in the liver and kidneys. For example, certain membrane transporters present in renal proximal tubular epithelial cells have been shown to import certain species of mercury formed in extracellularly, while other transporters have been shown to export mercuric species formed in intracellular compartments of these target cells. Interestingly, the specific thiol S-conjugates that gain entry into the intracellular milieu of a target (renal) epithelial cell may not be the same type of thiol S-conjugate that is exported out of the cell. Over the last couple of decades, significant progress has been made in identifying membrane transporters in renal proximal tubular cells that take up and export certain thiol S-conjugates mercury. This chapter not only reviews the advances in understanding the roles of the transporters taking up and exporting endogenously formed species of mercury by renal tubular epithelial cells, but it also reviews some of the more relevant findings pertaining to key intracellular biochemical effects of mercuric ions that likely play a role in intoxicating proximal tubular cells. Moreover, discussion of factors that modify the proximal tubular uptake and subsequent toxicity of mercuric species has also been included.
Disorders of the Urinary System
2018, Equine Internal Medicine: Fourth Edition

View all citing articles on Scopus

^☆: The author wishes to acknowledge financial support from the National Kidney Research Fund, the Medical Research Council and the National Research and Development Corporation.

View full text

Review paperUrinary enzymes, nephrotoxicity and renal disease☆

Abstract

Kidney Int.

Chem.-Biol. Interact.

Clin. Chim. Acta

Clin. Chim. Acta

Clin. Chim. Acta

Clin. Chim. Acta

Clin. Chim. Acta

Clin. Chim. Acta

Clin. Chim. Acta

Pharmacol. Ther.

Chem.-Biol. Interact.

J. Comp. Pathol.

Kidney Int.

Toxicology

Food Cosmet. Toxicol.

Toxicol. Appl. Pharmacol.

Toxicol. Appl. Pharmacol.

Chem.-Biol. Interact.

Biochem. Pharmacol.

Clin. Chim. Acta

Clin. Biochem.

Lancet

Clin. Chim. Acta

Kidney Int.

Toxicol. Appl. Pharmacol.

Biochem. Med.

Clin. Chem.

Ann. Clin. Lab. Sci.

J. Am. Med. Assoc.

Ligandinuria: an indication of tubular cell necrosis in Diagnostic Significance of Enzymes and Protein in Urine

Biochem. J.

Histochemistry

Kidney Int.

Urinary enzymes as an index of kidney damage by toxic compounds in Nephrotoxicity: Interaction of Drugs and Membrane Systems

Clin. Chem.

Isolation and renal localisation of urokinase

Tijdschr. Diergeneeskd.

Klin. Wschr.

Enzymologia

J. Lab. Clin. Med.

M.S. Thesis

Minerva Med.

Preparation of urine for enzyme determinations by gel filtration

Acute Renal Failure in Renal Disease

Br. Med. J.

Contr. Nephrol.

Review paper
Urinary enzymes, nephrotoxicity and renal disease☆