Urinary markers for early detection of Diabetic Nephropathy in type 1 Diabetes Mellitus

Background: diabetic nephropathy [DN] is a serious complication of diabetic mellitus associated with increased risk of morbidity and mortality. Diagnostic markers to detect DN at early stage are important as early intervention can slow loss of kidney functions and improve patient outcomes. N-acetyl Beta d-glucosaminidase [NAG] is a lysosomal enzyme, present in high concentrations in renal proximal tubular cells, Gamma-glutamyltransferase [GGT] is an enzyme which located along the proximal tubular brush border, Malondialdehyde [MDA] is a highly toxic product, formed in part by lipid oxidation derived free radicals, Reactive carbonyl derivatives [RCD[S]] is an oxidative stress marker in urine, as a measure of the oxidative modification of proteins and beta-2-microglobulin is filtered by the glomerulus, absorbed and catabolized by the proximal tubules. The aim of this study is to investigate the urinary outcome of these markers as early detectors of diabetic nephropathy in type 1 diabetic children

Subjects and methods: This case-control study included 67 children with type 1 diabetes mellitus [33 male; 34 female], age [11.03 +/- 1.05 years] and thirty one age [10.58 +/- 1.11 years] and sex [13 male; 18 female] matched healthy children [13 male; 18 female]. Type 1 diabetic children were further subdivided into microalbuminuric and normoalbuminuric subgroups according to microalbuminuria concentration [30 mg/ g creatinine]. Age, sex, diabetic duration and the current daily insulin dose, and family history of diabetes, weight, height, body mass index, systolic and diastolic blood pressure were recorded. Fasting plasma glucose, glycated hemoglobin, blood urea nitrogen, plasma creatinine, urinary creatinine, micoalbumin, N-acetyl-B-D glucosaminidase [NAG], Gama glutamyl transferase [GGT], Beta-2-microglobulin, Malondialdehyde [MDA] and Reactive carbonyl groups [RCDS[S]] were measured in all subjects

Results: a significant increase in tubular injury markers of diabetes [NAG, GGT, beta-2-microglobulin] and oxidative stress parameters [MDA, RCDS[S]] as compared to control subjects was found. Microalbuminuric subjects showed a significant elevatation in the urinary markers including NAG, GGT, beta-2-microglobulin, MDA, RCDS[S] as compared to normoalbuminuric subjects. The studied urinary tubular enzymes [NAG, GGT], oxidative stress markers [MDA, RCDS[S]] and Beta-2- microglobulin showed positive correlations with one another

Conclusion: The results of this study introduced the possibility of depending on tubular enzymes [NAG, GGT], oxidative stress markers [MDA, RCDS[S]] and Beta2 microglobulin as early, reliable, and sensitive predictors for diabetic nephropathy. The NAG activity index proved to be the most sensitive biomarker, then beta-2- microglobulin for early discovering the tubule cells damage

Urinary excretion of beta2-microglobulin as a prognostic marker in immunoglobulin A nephropathy

BACKGROUND/AIMS: beta2-microglobulin (beta2-MG) is freely filtered at the glomerulus and subsequently reabsorbed and catabolized by proximal renal tubular cells. Urinary beta2-MG is an early and sensitive biomarker of acute kidney injury; however, its utility as a biomarker of immunoglobulin A nephropathy (IgAN) is unclear. METHODS: We included urinary beta2-MG levels in the routine laboratory examination of all inpatients with biopsy-proven IgAN at our hospital from 2006 to 2010. We retrospectively analyzed the correlation between beta2-MG levels and clinical parameters as a prognostic biomarker of IgAN. RESULTS: A total of 51 patients (30 males, 21 females; mean age, 33.01 +/- 12.73 years) with IgAN were included in this study. Initial demographic, clinical, and laboratory data for all patients are listed. The mean initial estimated glomerular filtration rate and 24-hour urine protein levels were 94.69 +/- 34.78 mL/min/1.73 m2 and 1.28 +/- 1.75 g/day, respectively. The mean level of urinary beta2-MG was 1.92 +/- 7.38 microg/mg creatinine. There was a significant correlation between initial serum creatinine (iSCr), urine protein creatinine ratio (UPCR), and the level of beta2-MG (r = 0.744, r = 0.667, p < 0.01). There was also a significant correlation between renal function tests and the level of urinary beta2-MG (p < 0.01). Cox regression analysis showed that albumin, beta2-MG, iSCr, and UPCR were significant predictors of disease progression in IgAN. CONCLUSIONS: Urinary beta2-MG levels showed a significant correlation with renal function and proteinuria in IgAN. Thus, we propose that urinary beta2-MG may be an additional prognostic factor in patients with IgAN.

Assessment of renal affection in opioid abusers admitted to Ain Shams university hospitals

Opioid abuse represents an often neglected risk factor for the development of wide spectrum of renal diseases. The aim of this study was to assess renal affection in opioid abusers. The current work was carried out on 25 adult opioid abusers admitted to Ain Shams University Hospitals in the period from April 2008 to October 2008, in addition to ten healthy adult individuals serving as controls. All subjects were subjected to sociodemographic study, full clinical evaluation and laboratory investigations that included assessment of serum creatinine, BUN, beta 2microglobulin [beta 2M] and CPK levels, screening for viral infections [HIV, HCV and HBV], detection of proteins in urine and urine screening for opioids. Results of this study revealed significant increase of both beta 2M and CPK serum levels in the studied opioid abusers compared to the control group with no significant difference between the two groups as regard serum creatinine and BUN. Proteinuria was detected in 40% of opioid abusers. Significant increase of infection was observed in opioid abusers including skin infection and viral infections. In conclusion, renal affection is a significant finding in opioid abusers. So, during treatment of opioid abusers it is recommended to assess beta 2M level and to test urine for proteinuria as they both are early and sensitive indicators of renal affection. Additionally, a campaign for awareness of the people about the complications of drug abuse should be carried out

Nephrotoxicity of long-term occupational exposure to gasoline in El-Minia governorate

The current study was carried out to evaluate the nephrotoxic effect of long-term occupational exposure to gasoline in El-Minia governorate. 76 male subjects aging 18-42 years were involved in this study. They were divided into 4 groups: control group 1: consists of 20 normal subjects with no history of long-term gasoline exposure or previous history of blood, hepatic or renal disorders, group II: consist of 15 gas stations workers for a period of 1 year +/- 2 months with daily exposure to gasoline, group III: consists of 21 gas stations workers for a period of 5 years +/- 2 months with daily exposure to gasoline, and group IV: consists of 20 gas stations workers for a period of 10 years +/- 2 months with daily exposure to gasoline. All subjects sere investigated for blood urea nitrogen [BUN], serum creatinine [S.Cr.], beta[2] microglobulin [beta[2]MG] and cystatin C. The levels BUN, S.Cr., beta[2]MG, and cystatin C of the subjects of group II were within normal with no significant differences when compared to those of group I. The values BUN, S.Cr., beta[2]MG, and cystatin C of the subjects of group III were significantly elevated when compared to those of groups I and II. The levels BUN, S.Cr., beta[2]MG, and cystatin C of the subjects of group IV were significantly elevated when compared to those of group I, II and III. In group III, there was a positive correlation between S.Cr. to the level of beta[2] MG. Also, there was a positive correlation of the level of S.Cr. to the levels of beta[2] MG, and cystatin C among the subjects of group IV. Long-term exposure of the gas station workers to gasoline may carry the risk of nephrotoxicity. This raises the importance of increasing the safety protective measures at these stations, and to develop a more safe fuel in the near future

Study of kidney function in asphyxiated full term newborn

Renal impairment in the neonates usually occurs following complicated labor and delivery with perinatal asphyxia, and it is usually in form of tubular insult. [Al Fred, 1996]. The clinical presentations of renal impairment in neonates is often subtle, lack of recognition of its occurrence has made this especially true when renal impairment follows perinatal asphyxia. To study kidney function in full term asphyxiated neonates. 24 asphyxiated FT newborn and 12 control were subjected to comprehensive history and renal function evaluation study. Routine urinalysis of cases, with perinatal hypoxia revealed proteinuria in 41.7% in patients. Many epithelial cells were found in 53.5% of the cases with perinatal asphyxia. Mean urine analysis for R.B.Cs of patients [6.33 RBCs/HPF +/- 4.02 RBCs/HPF]' which was significantly higher than that of controls [4.16 RBCs/HPF +/- 2.69 RBCs/HPF]. Mean urine analysis for pus cells of patients [2.84 pus cells/HPF +/- 1.59 pus cells/HPF] which was not significantly different than that of controls [3.08 pus cells/HPF + 3.87 pus cells/HPF]. Mean urinary beta 2 micro globulin concentration in patients [218.30 ng/ml +/- 100.93 ng/ml] was significantly higher than that of controls [144.316 ng/ml +/- 126.3 ng/ml] which is specific for tubular renal insult in renal impairment. Mean urinary urea in patients was [7.727 + 3.16 meq/l] which was not significant in relation to controls 96.80 +2.907 meq/l]. Mean urinary creatinine in patients was [1.30 +1.4 meq/l] which was not significantly different than controls [1.22 +1.09 meq/l]. Renal function must be evaluated in all asphyxiated newborn serum cratinine and heamaturia are sensitive indicators while urinary beta2 microlobin is more specific

Early detection of renal disease in occupational hydrocarbon exposure by using non Invasive biomarkers

Early detection of renal dysfunction resulting from exposure to a nephrotoxin is important since this is the first step in the progressive loss of renal functions and ultimately progression to renal failure which are characteristic of the nephrotoxic cascade. Using modem technology, minute quantities of LMWP and urinary enzymes can be measured. Excretory patterns that are characteristic for site and mechanism of renal injury often can be found. This study was carried out to investigate the link between the occupational hydrocarbon exposure and nephrotoxicity by using the non invasive urinary markers for early detection of subclinical reversible conditions. Twenty adult men works as paint sprayer [chronic exposure] composing the first group and compared them to twenty adult males with a minimal exposure matched age, weight, height, blood pressure and residential ares, composing the second group as a control group. The results showed a significant increase in B2-microglobulin [B2 mic] p<0.003, Retinol binding protein [RBP] p<0.001, N-acetyl-B-D-glucosaminidas [NAG] p<0.0001 in the first group as compared to the normal control group. Serum creatinine shows no difference between the two groups, As a conclusion, by using non invasive methods our results are in keeping with the hypothesis that hydrocarbon exposure through paint spraying may result in active proximal tubular damage which may be reduced by improvement of protection at their work site as heavy duty overalls, thick gloves and more important air-fed mask for the airway and face protection. Follow up studies are necessary to assess the prognostic value of early changes detected in workers chronically exposed to organic solvents

Urinary brta-2microglobulin level in urinary tract infections in infancy and childhood

Upper urinary tract infection is a serious bacterial illness among febrile infants and young children. Significant renal scarring may occur after a single episode especially with delayed diagnosis and treatment. In this study, we evaluated the value of measurement of urinary beta 2 microglobulin [B2-MG] in the differentiation between upper and lower urinary tract infections. Fifty children with urinary tract infections [UTis] aged between 1-12 years were studied: 15 children with acute pyelonephritis documented by positive DMSA scan, 15 children with acute cystitis documented by negative DMSA scan and 20 normal children as control. In all children, total leukocytic count [TLC], erythrocyte sedimentation rate [ESR], serum C reactive protein [CRP], blood urea and serum creatinine were measured. Also, B2-MG in 24 hours collected urine was measured using ELISA technique. It was found that TLc, ESR and RP were significantly higher in cases of acute pyelonephritis compared with those of cystitis. However, there was no statistically difference between the three studied groups as regards blood urea and serum creatinine. Urinary B2-MG was significantly higher in children with acute pyelonephritis compared with the other two groups [P= 0.01]. The sensitivity, specificity, and positive predictive value of urinary B2-MG in the diagnosis of acute pyelonephritis were 94.3%, 100% and 91.6% respectively. This study showed the importance of measuring of urinary B2-MG in children with urinary tract infection and the possibility of using this non invasive test in the differentiation between upper and lower UTIs

Determinación de microproteínas urinarias en orinas sin concentrar / Urinary low molecular weight proteins on unconcentrated urine

Se realizó la determinación cuali y cuantitativa de las microproteínas urinarias (MU): Alfa-1 microglobulina (A1m), proteína transportadora del retinol (RBP) y Beta-2 microglobulina (B2m), en 138 orinas de 24 h de recolección con pH superiores o iguales a 5.5, en pacientes adultos con distintos cuadros uroproteicos: 38 fisiólogicos, 59 glomerulares, 19 tubulares y 22 mixtos. Se describe la metodología analítica para optimizar la detección de las MU mediante la técnica de electroinmunofijación (EIF) con coloración argéntica, en orinas sin concentrar. El rango de sensibilidad para las distintas MU fue de 3-100mg/l. La cantidad de antisuero monoespecífico empleado por cm2 de gel fue: anti-A1m (4µl/cm2), anti-RBP (4µl/cm2) y antiB2m (2µl/cm2). La determinación cuantitativa se relizó por inmunodifusión radial (IDR) para RBP y B2m, y por electroinmunodifusión (EID) para A1m. La detección de MU en orinas sin concentrar mediante esta metodología de alta sensibilidad y la cuantificación de las mismas permitieron efectuar un correcto diagnóstico de proteinuria tubular y mixta superando las eventuales pérdidas o desnaturalización protéica que acarrean los clásicos métodos de concentración. La detección elevada de A1m (15-65 mg/l) en 12 de 59 orinas con proteinuria glomerular, plantea un interrogante sobre la cuantificación aislada de la MU para definir un patrón tubular

Some markers to elucidate the pathophysiology in early diabetic nephropathy

Diabetic nephropathy is one of the microvascular complications of diabetes mellitus, microalbuminuria is considered as an important predictor for the onset of diabetic nephropathy. The goal of this study is to search for other markers in the hope of enhancing the sensitivity and specificity of screening for this life threatening complication. In the present study, 82 diabetic patients [26 insulin dependent and 56 non insulin dependent] aged from 21-69 years, [57 males and 25 females], together with 18 apparently healthy control of matchable age and sex were subjected to estimation of serum levels of Interlukin-1B [IL-1B], N-acetyl-13-glucosaminidase [NAG], fructosamine, random blood glucose, urinary levels of NAG, B[2]-microglobulin [B[2]-MG] and creatinine. The study showed that all the parameters studied were significantly higher in diabetics compared to the control group and their levels were significantly higher in diabetics with longer duration of diabetes and serum IL-1B, NAG, urinary B[2]-MG/mg creatinine, and NAG/mg creatinine were significantly higher in non-insulin dependent compared to insulin dependent. No significant correlation could be observed between any of the parameters studied and random blood glucose or fructosamine. Serum IL-1B, urinary B[2]-MG and urinary and serum NAG may be considered a good markers in detecting early diabetic nephropathy

Beta - 2 microglobulin concentration as a marker of renal affection in asphyxiated newborns

This study was undertaken to evaluate the clinical usefulness of serum and urinary Beta 2 microglobulin [Beta 2 m] determination as a marker of renal damage following perinatal asphyxia. 24 newborns with severe birth asphyxia were included in the study along with 12 normal newborns who comprised the control group. The results revealed that the mean serum urea [mg/dl] was 72.9 +/- 43.2 in cases and 58.3 +/- 52.9 in controls with no significant difference while the mean serum creatinine [mg/dl] in cases was 1.7 +/- 0.88. This value was significantly higher than the mean value [0.7 +/- 33] in controls. The urinary Beta 2 microglobulin [ng/ml] in the cases was 218.3 +/- 100.9 which was significantly higher than controls [40.8 +/- 35.49]; while the serum Beta 2 microglobulin [ng/ml] in cases [46.16 +/- 22.2] was significantly lower than controls [68.83 +/- 34.3]. There was a negative significant correlation between B2 microglobulin in urine and values of Apgar score. We concluded that inspite of low sensitivity of urinary Beta 2 microglobulin, it can be considered as highly specific simple rapid noninvasive test for early detection of renal damage [mainly tubular affection] in neonates with birth asphyxia

Expression of apoptosis in diabetic nephropathy in patients with insulin dependent diabetes mellitus [IDDM]

The present study was designed to determine the level of bcl-2 as apoptotic modifiers in diabetic nephropathy of IDDM patients. Simultaneous determination of urinary N-acetyl glucoaminidase [NAG], beta 2-microglobulin [beta 2-MG] and microalbuminuria as indicators of early nephropathy in IDDM. Twenty-six children with IDDM and nephropathy in addition to 18 healthy control were involved in this study. They were chosen among those attending the pediatric department of EI-Minia university hospital. All patients were subjected to careful clinical, radiological and ultrasonographic examinations. Blood samples were taken at the clinic for random glucose determination by the glucose oxidase method and serum fructosamine assay. Plasma bcl-2 was determined by bcl-2 endogene human ELISA kits supplied by endogene corroborating, MA USA. NAG activity was determined photometrically. Twenty ml random urine sample was also collected from all subjects between 11 a.m. to 2 p.m. Urine sample from patients were stored at-20 ° until used for beta2-MG determination by ELISA technique. Urinary creatinine was determined by the method of Bonsens and Taussky. The healthy controls consisted of 18 volunteers matched in age and sex, with negative albuminuria by Albustix test, were subjected to the same investigations as the patients group. Our results proved that in IDDM patients, serum NAG, urinary NAG, NAG / creatinine, beta2-MG/creatinine and bcl -2 all were significantly increased compared to controls [P< 0.001]. Blood fructose level and urinary beta2-MG were also significantly increased [P < 0.05]. It was concluded that the assessment of bcl2, serum. NAG, urinary NAG and urinary beta2-MG are easily and accurate test for showing the glomerular and tubular renal damage in IDDM

Renal dysfunction detected by beta-2 microglobulinuria in sick neonates.

OBJECTIVE: To assess renal involvement in sick neonates referred to Neonatal Intensive Care Unit (NICU) using standard renal parameters and urinary beta 2 microglobulin (B2M) excretion. DESIGN: Descriptive study. SETTING: Level II NICU and Nephrology Division of Pediatric Tertiary hospital. SUBJECTS: Forty six term sick neonates transferred for neonatal care and forty healthy term neonates who served as normal controls for urinary B2M excretion. METHODS: Standard tests including estimation of BUN, serum creatinine, blood pH, serum bicarbonate, serum and urinary electrolytes, urine output, and urinalysis. Urinary B2M levels were estimated from urine collected on day 1 (D1) and day 3 (D3) in all and 18 neonates were tested on day 7 (D7) by radio-immunoassay method. RESULTS: Statistically significant elevation of mean values of urinary B2M were noted when sick neonates were compared with normal controls irrespective of primary disease, indicating tubular dysfunction (41/46 = 90%), whilst only 7 of these (17%) had abnormalities indicating renal involvement when judged by standard tests. Very high levels of urinary B2M were noted with birth asphyxia (n = 9), sepsis (n = 8) and renal disease (n = 7). Transient elevation of urinary B2M was noted in meconium aspiration syndrome (n = 4). Ten surgical cases with non renal congenital malformations showed high urinary B2M and 12/18 tested on D7 had persistently high urinary B2M due to multiple factors. CONCLUSIONS: Elevated urinary B2M in 90% sick neonates with apparently normal renal parameters in majority (34/41) indicates subclinical proximal tubular dysfunction especially in neonates with asphyxia, sepsis and congenital malformations. Persistent elevation of urinary B2M appear to be a sensitive diagnostic indicator for defining a group of neonates with subtle renal tubular dysfunction, the clinical relevance of which on long term basis is a subject for future study.

Sensitive indicators of renal dysfunction among workers exposed to cadmium

Cadmium-induced renal tubular dysfunction was examined in 28 male workers in 2 electroplating factories. Forty comparable apparently healthy administrators constituted the control group. Both groups were submitted to a battery of serum and urinary nephrotoxicity markers to assess the renal effects. The study revealed that chronic exposure to cadmium was associated with renal function impairment evidenced by increased frequencies of abnormal values of most of the nephrotoxicity markers used. Urinary NAG correlated well with all exposure indices, on the other hand urinary B[2] micrglobulin [B[2]M] showed a significant positive correlation only with blood cadmium level which was weaker than that of urinary NAG. Urinary NAG detected a larger proportion of abnormalities among the exposed workers than B[2]M. NAG was suggested to be a sensitive and useful marker for biological monitoring of workers exposed to cadmium

effect of extracorporeal shock wave lithotripsy [ESWL] on angiotensin I, N-acetyl-B-glucosaminidase, urinary marker proteins, parathyroid hormone, pancreatic amylase and muscle injury enzyme markers

To detect the source of relevant acute intrarenal side effects after extracorporeal shock wave lithotripsy [ESWL], urinary excretion of highly specific marker proteins [alpha 1 and beta 2 microglobulin], as well as tubular enzyme N-acetyl-beta-D glucosaminidase [NAG] were analyzed before and after ESWL. A highly significant increase in urinary marker proteins [alpha 1 M and beta 2 M] and urinary enzyme NAG were recognized immediately following ESWL. Alpha 1 M and NAG returned to their pre-ESWL levels but beta 2 M remained high till day 30. Plasma renin activity-PRA [angiotensin I] was highly significantly elevated immediately after ESWL and remained high after 1 month. The parathyroid hormone [PTH], CK-MB were highly significant elevated. Gamma glutamyl transferase [GGT], alanine aminotransferase [ALT], aspartate aminotransferase[AST], alkaline phosphatase[ALP] and pancreatic amylase were significantly higher than normal immediately after ESWL but all to their pre-ESWL values after 1 month

Electroinmunofijación de orinas sin concentrar por coloración con metales pesados / Immunofixation electrophoresis of unconcentrated urines with heavy metal staining

Se describe una técnica sencilla y altamente sensible para la identificación inmunológica de proteínas en orina sin concentración previa, basada en la alta sensibilidad de las tinciones con metales pesados, como plata y oro, al estado coloidal (100 veces más sensible que el azul brillante de Coomassie (CBB) R y G 250). Posteriormente a la corrida electroforética convencional se efectuó una inmunofijación utilizando una cantidad de antisuero monoespecífico en el orden de 3,5 µl/cm² de gel. El contacto antígeno-antisuero se mantuvo durante 30 minutos y posteriormente se efectuaron lavados con sucesivos recambios de solución fisiológica y se aplicaron las coloraciones argénticas, áurica y con CBB R 250. Bajo las condiciones de trabajo utilizadas se lograron identificar satisfactoriamente las cadenas livianas k y ? monoclonales en proteinurias de Bence Jones (BJ) positivo, y la ß2 microglobulina en proteinurias de tipo tubular, con un límite de sensibilidad del orden de los 5 x 10-4ug de proteína/mm2 de gel. Esta técnica resultó de gran utilidad en el estudio del cuadro uroproteico y se presenta como un método simple, rápido, de alta sensibilidad y baja relación costo/beneficio, para el estudio de los distintos cuadros de proteinuria en muestras sin concentrar

Urinary B-2 microglobulin and retinol binding protein and microalbuminuria in perinatal asphyxia

This study was carried out on twenty-eight full term neonates with perinatal asphyxia with average one, five and ten minutes Apgar scores of 1.6, 4.3 and 3.7, respectively. Ten full term healthy neonates were included as a control group with one, five and ten minutes Apgar scores of 7.3, 9.4 and 9.6, respectively. Both groups were tested on the second and fifth days of postnatal life as regards complete blood picture, complete urine analysis, culture and sensitivity for urine and blood, investigations for renal glomerular function included urinary concentration of albumin, blood urea and serum creatinine, investigations for renal tubular function included urinary beta-2-microglobulin [B2-m] and retinol binding protein [RBP], fractional excretion of sodium [FENa] and urine output per unit body weight per hour [ml/kg/hr]. Abdominal sonography was done for all cases to exclude any surgical problems. Renal failure index [RFI] was calculated at second and fifth days of postnatal life. It was concluded that measurement of urinary B2-m and RBP are convenient, sensitive, specific and early diagnostic tools for the detection of tubular damage in asphyxiated neonates. Blood urea and serum creatinine are good indicators of glomerular impairment only after the first two days of life. The tubular function is more sensitive than glomerular function in neonates. A low Apgar score, arterial PO2 and pH are good indicators of hypoxia. Oliguria is already considered as an ambiguous indicator of ARF and could indicate poor neurologic outcome in asphyxiated neonates

Elevated serum cadmium among workers of Assiut Cement Factory: source, assessment and toxicological studty

The present study was conducted on 72 male workers of Assiut Cement Factory complaining of some renal troubles together with 30 healthy controls. Significant increase in the level of serum and urinary cadmium was observed among those workers. Other renal variables including B2-microglabulin [B2-MG] and N-acetyl Beta-glucosaminidase [NAG] were also significantly increased denoting renal impairment. An interesting finding in this study was the elevation of serum calcium and serum alkaline phosphatase among the workers compared with controls. The levels of these bioindices were correlated with the level of serum and urinary cadmium. Dose response relations were observed between B2-MG and NAG and urinary cadmium. The source of cadmium was searched for including the waste products of the factory and its surroundings and the drinking water. Water of the well supplying the factory proved to be the main source of pollution among the workers