Renal function 17 to 23 years after chelation therapy for childhood plumbism

Abstract

An elegant retrospective description of an epidemic of chronic renal failure occurring in patients with histories of untreated childhood lead poisoning in Queensland, Australia established beyond reasonable doubt the existence of lead nephropathy. However, a retrospective uncontrolled report from Boston in 1963 refuted the claim that there are serious renal consequences of untreated childhood lead poisoning. We conducted a controlled prospective, longitudinal study to examine the effects of childhood lead poisoning on renal function 17 to 23 years after chelation therapy. The present study reports the results of renal functional tests in a unique cohort of study subjects (N = 62) with significant lead poisoning (initial PbB > 100 micrograms/dl) diagnosed and treated between 1966 and 1972 and their age-matched control siblings (N = 19; initial PbB < 40 micrograms/dl). During the past nine years serial determinations of renal function on all study subjects and control siblings were obtained. Mean values of systolic and diastolic blood pressures, serum creatinine, serum beta 2-microglobulin, fractional excretion beta 2-microglobulin, urinary protein:creatinine ratio, serum phosphate, tubular reabsorption of phosphate, serum uric acid, and urinary specific gravity were similar in study subjects compared with sibling controls. The frequency of abnormal values for these tests was similar in the two groups. Multiple linear regression analyses failed to demonstrate a significant influence of the presence of plumbism or initial PbB on serum creatinine or systolic or diastolic blood pressure. A modest increase in serum creatinine values was observed over a nine year period in four of 62 study subjects (1.4, 1.4, 1.5, 1.6 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Lead Level and Measured Glomerular Filtration Rate in Children with Chronic Kidney Disease

“…At lead levels representative of current environmental exposure (blood levels < 10 µg/dL), several cross-sectional and a few prospective studies have reported an association with kidney dysfunction or progression of chronic kidney disease (CKD) (Åkesson et al 2005; Ekong et al 2006; Fadrowski et al 2010; Kim et al 1996; Lin et al 2003, 2006; Muntner et al 2003, 2005; Navas-Acien et al 2009; Payton et al 1994; Staessen et al 1992; Tsaih et al 2004; Yu et al 2004). However, data in children are scarce and less consistent than in adults (de Burbure et al 2006; Fadrowski et al 2010; Moel and Sachs 1992; Staessen et al 2001). …”

Aminoaciduria and glycosuria following severe childhood lead poisoning

“…We speculate that, with the abatement of environmental lead sources, the body lead burden of the subjects will continue to decline, resulting in possible resolution of the proximal tubular dysfunction over time. Because urinary excretion of amino acids and glucose was not evaluated in the study of Moel et al [20], we do not know if the frequency of these tubular abnormalities has declined or remained unchanged.…”

“…Similarly, in a study involving 62 adolescents from Baltimore, 11±16 years after childhood lead poisoning, there was no evidence of excessive mobilizable lead and no evidence of nephropathy [19]. Moel et al [20] studied 62 subjects with severe childhood lead poisoning from Chicago, along with 19 age-matched control siblings, 17±23 years after the children had undergone chelation therapy. They found no difference between the study subjects and controls in any of the parameters studied, including serum Cr, urinary excretion of b2-microglobulin, and systolic or diastolic blood pressure.…”

“…Similar retrospective studies from Boston [18], Baltimore [19], and Chicago [20] have failed to show any evidence of renal dysfunction following childhood lead poisoning, leading the authors to conclude that lead nephropathy is not a common sequela of lead poisoning in the United States. To explain the discrepancy, it has been suggested that the lead toxicity in the Queensland population was of a different type and with a more protracted course than that observed in the United States [19].…”

Toxic environmental exposures and kidney health in children

“…The kidneys of these individuals were found to be contracted and small, with histologic changes of interstitial fibrosis, hypertensive vascular changes, and “alterative glomerulitis” [47, 48], which is a term coined by Kimmelstiel and Wilson in 1936 to describe histological findings of nuclear proliferation and irregular pyknotic nuclei in the glomerular tuft adjacent to the vascular pole seen in hypertension-induced glomerulosclerosis [49]. Although subsequent studies of adults who suffered childhood lead poisoning have reported hypertension [50, 51], persistent partial Fanconi’s syndrome [52], and individual cases consistent with lead nephropathy [50], they have not demonstrated overall increased mortality or statistically significant decreased kidney function [53]. A possible explanation for this discrepancy may be that the children in the Queensland epidemic were untreated, whereas children in subsequent studies were treated with chelation therapy.…”