Medicine, School of Medicine, Soonchunhyang University, ... 218 µg/dl. Renal sonography revealed bilateral normal- .... Van deVyver FL, DeBore ME. Does lead ...
J Occup Health 2000; 42: 260–262
Case Study
Chronic Lead Nephropathy with Excessive Body Lead Burden Hyun-Cheol AHN1, Kyu-Yoon HWANG1, Sae-Yong HONG2, DongHo YANG2, Byung-Kook LEE1, and Andrew C. TODD3 1
Department of Preventive Medicine and Institute of Industrial Medicine, School of Medicine, Soonchunhyang University, 2 Department of Internal Medicine, Soonchunhyang Hospital, Republic of Korea, and 3 Department of Community and Preventive Medicine, Mount Sinai Medical Center, New York, USA Key words: Lead, Nephropathy, Bone, Chelation
Case 1. A 50-yr-old man, a secondary lead smelting worker, was examined because of persistent renal insufficiency and intermittent gouty arthritis. Four yr earlier, his serum creatinine had fluctuated between 2.1 and 2.5 mg/dl, and creatinine clearance and serum uric acid levels were 40 to 54 ml/min/1.73 m2 and 9.9 to 12.3 mg/dl, respectively. He had worked intermittently at several lead-smelting plants for approximately 17 yr between 1968 and 1994. Air lead monitoring in 1993–94 at his work site showed it in excess of the threshold limit value (TLV) for lead in Korea (0.05 mg/m3). The man was completely removed from further exposure after he was diagnosed as having lead poisoning by a regular special health examination in September 1994. We had examined his health condition by regular health check-up annually since 1988, but no specific symptoms and abnormal screening findings related to renal function were observed until 1994. He presented with fatigue, dizziness, numbness, facial edema, and polyarthralgia for several years before admission. However, he denied headache, wrist drops, and abdominal pain. The remainder of his medical and familial histories were non-contributory. On physical examination, his blood pressure was 120/80 mmHg, and other vital signs were normal. He had a slightly pale face, mild edema on both legs, and reddish nodules on the left ankle and great toe. Results of laboratory studies showed the following values: normocytic normochromic anemia (hemoglobin, 10.7 g/dl) with basophilic stippling of erythrocytes; albumin, 4.2 mg/dl; total cholesterol, 225 Received Nov 18, 1999; Accepted May 12, 2000 Correspondence to: B.-K. Lee, Department of Preventive Medicine and Institute of Industrial Medicine, School of Medicine, Soonchunhyang University, 23–20 Bongmyung-Dong, Chunan, Chungnam 330-100, Republic of Korea
mg/dl; sodium, 140 mEq/L; potassium, 5.0 mEq/L; C3, 140 mg/dl; C4, 50 mg/dl; IgG/IgA/IgM, 1,520/220/165 mg/dl; blood lead, 62.0 µg/dl; and zinc protoporphyrin, 218 µg/dl. Renal sonography revealed bilateral normalsized kidneys. Renal biopsy showed focal moderate atrophy or loss of proximal tubules with prominent interstitial fibrosis. Also, 22% of glomeruli showed global sclerosis and arterioles exhibited patchy hyaline deposits (Fig. 1-A). An ultra-structural study revealed an absence of immune complex depositions. The schedule of the lead mobilization test (LMT) is summarized in Table 2. Baseline urinary excretion of lead was 106 µ g/d, and after the first LMT with an intravenous infusion of 1 g calcium disodium ethylenediamine tetraacetic acid (CaEDTA), urine lead increased to 3,934 µg/d (Table 1). Cortical bone lead was assessed (in units of µg Pb/g bone mineral) after 30 min of measurement at the left mid-tibia shaft using 109Cd K-shell X-ray fluorescence (K-XRF)1, 2). Tibial bone lead level was 337 µg Pb/g bone mineral. At present, after treatment with 50 g CaEDTA over 11 months, serum creatinine has fallen to less than 2.0 mg/dl (about 1.5 to 1.9 mg/dl) and CaEDTA chelatable lead has decreased to 3,028 µg/d. However, blood lead has been sustained at a high level (59.3 µg/dl).
Case 2. A 45-yr-old worker was admitted to our hospital for evaluation of chronic lead nephropathy and intermittent hypertension. He had worked at secondary lead smelting factories for nearly 15 yr between 1974 and 1991. His working environment showed over TLV for lead (Table 1). Before his lead poisoning, he did not have any leadrelated symptoms and abnormal screening results according to our regular health check-up. Mild hypertension was noted and well controlled with captopril® 25 mg/d. The serum creatinine levels ranged from 1.7 to 2.1 mg/dl until 1998. He complained of dizziness, numbness, joint pains, insomnia, palpitation, and anxiety. There were no headache, chest pain, and dyspnea. No other history was specific. His blood pressure was 140/100 mmHg and pulse was regular at 80 beats per min without murmurs. He showed lead pallor on the face. Laboratory results were as follows: microcytic hypochromic anemia (hemoglobin, 10 g/dl) with basophilic stippling of erythrocytes; sodium, 134 mEq /L; potassium, 4.7 mEq/ L; C3, 80 mg/dl; C4, 62 mg/dl; IgG/IgA/IgM, 1,250/200/ 100 mg/dl ; blood lead, 44.5 µ g/dl ; and zinc protoporphyrin, 128 µg/dl. Urinalysis revealed protein (++), but no blood cells. His glomerular filtration rate (GFR) was 47 ml/min by renal scan (Tc-DPTA). Renal sonography was normal. Renal biopsy showed extensive severe atrophy or loss of proximal tubules with interstitial fibrosis, and 67% of glomeruli were found to have global
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sclerosis (Fig. 1-B). Ultra-structurally, no electron dense deposits were revealed. Epithelial foot processes showed slightly focal effacement. The urine lead before LMT was 272 µg/d. After LMT with CaEDTA, 24 h urine lead showed an increase to 2,190 µg/d, and the tibial lead level was measured as 303 µg Pb/g bone mineral. Following the 1-yr course of chelation therapy with 50 g CaEDTA, serum creatinine fell to about 1.5–1.8 mg/dl. The blood lead and CaEDTA chelatable lead were also slightly reduced to 35.2 µg/dl and 1,910 µg/d, respectively.
A
Discussion
B
Fig. 1. Light microscopy results of two cases with chronic lead nephropathy—A: showing moderate atrophy of proximal renal tubules and prominent interstitial fibrosis in case 1, 50-yr-old lead worker (HE stain, × 200). B: showing global sclerosis of glomerulus in case 2, 45-yr-old lead worker (PAS stain, × 400).
Lead is a well-known nephrotoxin, associated with renal dysfunction in occupational and environmental studies. In general, subjects with blood lead levels exceeding 60 µg/dl are at a definite risk of developing renal failure3, 4). Chronic high-dose lead exposure also causes development of gout and hypertension5). The two patients had occupational histories of chronic lead exposure. Meaningful increases of chelatable urine lead and elevated bone lead levels by XRF measurement revealed excessive lead body burdens, despite the passage of over 4–7 yr from complete cessation of exposure to lead. Bone lead measurement using K-XRF accounts for total body lead burden and shows a significant correlation with CaEDTA chelatable lead6, 7). Thus, these two measures represent cumulative lead exposure and body burden. The diagnosis of chronic lead nephropathy was based on the results of renal biopsy as well as the above described findings. Although progress toward
Table 1. Summary of laboratory results of two cases Case 1 Mean ± SD (Range; n)
Case 2 Mean ± SD (Range; n)
During active work (yr) Air lead (mg/m3), recent 2 yr Blood lead (µg/dl), recent 4 yr Serum Creatinine (mg/dl), recent 2 yr
1968–1994 0.95 ± 1.34 (0.06–6.66; 3) 78.9 ± 6.7 (73.8–88.7; 4) 2.3 ± 0.3 (2.1–2.5; 2)
1974–1991 3.33 ± 4.32 (0.15–10.87; 3) 74.0 ± 16.2 (58.6–97.6; 5) 1.9 ± 0.3 (1.7–2.1; 2)
During worker’s compensation (yr) Blood lead (µg/dl) Serum Creatinine (mg/dl) Tibial bone lead (µg Pb/g bone mineral)
1994–1998 68.0 ± 3.8 (62.9–71.7; 6) 2.0 ± 0.1 (1.9–2.1; 2) 337
1991–1998 41.0 ± 1.7 (38.5–43.3; 5) 1.9 ± 0.3 (1.7–2.1; 2) 303
During chleation (yr) Blood lead (µg/dl)* Serum Creatinine (mg/dl)* Chelatable lead (µg/d)** Baseline After first LMT After last LMT
1998–1999 52.3 ± 5.3 (43.1–62.8; 11) 1.7 ± 0.2 (1.5–1.9; 11)
1998–1999 35.1 ± 3.1 (31.0–41.0; 12) 1.7 ± 0.1 (1.5–1.8; 12)
106 3,934 3,028
272 2,190 1,910
LMT: lead mobilization test using intravenous injection of calcium disodium ethylendiamine tetra-acetic acid (CaEDTA). *Blood lead and serum creatinine were measured before each chelation. **Chelatable lead was measured after first injection of 1 g CaEDTA.
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Table 2. Summary of lead mobilization test in two cases
Dosage (g CaEDTA)/d Consecutive d/cycle Number of cycles Interval between cycles (wk) Total amount of CaEDTA (g)
Case 1
Case 2
1 3–5 11 4–8 50
1 2–5 12 4–8 50
nephropathy is not so clear due to a lack of data on these cases before lead exposure, their regular health examinations did not contain abnormal screening results until lead poisoning became apparent. After 50 g CaEDTA treatment (details in Table 2), the renal functions of both cases were slightly improved as serum creatinine levels were under 2 mg/dl. Our results were consistent with a report in which Wedeen et al.8) showed that 4 of 8 patients given CaEDTA 3 times a week for 6 or 50 months had increases of glomerular filtration rate greater than 20%. However, in our cases, blood lead levels were not reduced as much as expected. This finding may be due to the internal sources of lead such as bone lead. Although Batumen et al.9) reported a progressive fall of body lead stores after about 30 g CaEDTA treatment in normal renal function, guidelines for CaEDTA chelation therapy in chronic lead poisoning are not clear. Further studies are required to determine the effects of chelation therapy on the bone lead store and renal function, especially in chronic lead nephropathy.
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