Lead nephropathy hypertension

Boscolo P, Galli G, Iannaccone A, et al. 1981. Plasma renin activity and urinary kallikrein excretion in lead-exposed workers as related to hypertension and nephropathy. Life Sci 28 175-184. 

WedeenRP. 1988. Bone lead, hypertension, and lead nephropathy. Environ Health Perspect 78 57-60. 

Chronic lead nephropathy in moonshiners, more often than not, is accompanied by gout and hypertension, in accord with 19 century descriptions of plumbism and reports from Austraha [1]. A statistically significant odds ratio of 2.4 has been reported for moonshine consumption and end-stage renal disease, suggesting a causal association with lead in fhe absence of symptomatic lead poisoning [31]. 

Hyperuricemia and gout are common among individuals with excessive exposure to lead, apparently the result of decreased excretion and increased production of uric acid. Although hyperuricemia invariably accompanies azotemia, gout is uncommon in patients with renal failure except in those with lead nephropathy. Half of uremic patients with lead nephropathy have clinical gout [18] but in the absence of renal failure, gout cannot usually be attributed to lead despite coexisting hypertension [23, 37]. 

Lead-induced hyperuricemia may contribute to chronic lead nephropathy. Uric acid per se induces endothelial cell injury, renal microvascular disease, and hypertension, at least in part mediated by oxidative stress [38]. Independent of uric acid, reactive oxygen species induced by lead have been imphcated in endothelial cell injury, increased vascular reactivity, and the production of hypertension in humans and experimental animals [39]. 

Lead nephropathy does not account for renal failure in all hypertensives with kidney disease any more than it accounts for renal failure in all gout patients with kidney disease. The heavy metal may, however, contribute to the association of gout with hypertension, as well as to the variable incidence of renal failure in each of these conditions. 

Lead nephropathy is important because it is one of the few renal diseases that is preventable. Moreover, lead-induced acute renal dysfunction can sometimes be reversed by chelation therapy [19, 28, 63]. The salutary effect of chelation therapy appears to be on the acute reduction in GFR and the acute elevation of blood pressure associated with elevated blood lead concentration rather than on the long-term effects of cumulative exposure associated with endothelial dysfunction, hypertension, and interstitial nephritis. There is no evidence that such therapy reverses established interstitial nephritis. The partial remission achieved among moonshiners and lead workers appears to represent reversal of the physiologic effects of acute poisoning superimposed on chronic lead nephropathy. No improvement in renal function has been observed once advanced interstitial nephritis is present and the steady-state serum creatinine concentration exceeds about 3 mg/ dL [64]. 

Solvents have been implicated as inducers of glomerulonephritis [72], while the association between chronic interstitial nephritis and analgesic abuse is acknowledged [73] and the association between hypertensive renal disease (nephrosclerosis) and lead nephropathy continues to be explored [74, 75]. According... 

There is also clear evidence that the sequel of lead inducing a chronic nephropathy with hypertension can occur. At times, this hypertension may be sufficiently severe to be malignant and may precipitate an early demise [22]. In more chronic cases, the hypertension may be of moderate degree and not be sufficient to cause progressive deterioration of renal function [43]. However, when confronted with a patient with hypertension and mild renal damage, it can be difficult to determine which came first and particularly difficult to determine whether lead was a contributor to the renal damage that caused the hypertension. In such cases, the hypertensive mechanism would be the same as those associated with other varieties of chronic renal disease. By contrast, many patients with chronic lead nephropathy have demonstrated suppressed plasma renin concentrations indicative of a hyporeninemic hypoaldosteronism [44]. 

Exhibiting a pattern of eicosanoid excretion noted in essential hypertension, lead-exposed workers showed an increase in TxB2 and a decrease in PGE2 and 6-keto-PGF] in fhe mine [63]. In contrast to the reabsorpfive defect of acute lead nephropathy, saturnine gout is characterized by renal retention of uric acid. The clearance and maximal secretion rate for para-aminohippurate have been found to be variable in patients with occupational lead nephropathy. A reduced maximal reabsorpfive rate for glucose has been reported, but simultaneous, matched controls were not obtained [69]. 

Scinchez-Fructuoso Al, Blanco J, Montserrat C, Ortega L, Arroyo M, Fernandez C, Prats D, Barrientos A. Experimental lead nephropathy treatment with calcium disodium ethylenediaminetetraacetate. Am J Kidney Dis 2002 40 59-67. Scinchez-Fructuoso Al, Toralbo A, Arroyo M, Lunque M, Ruilope LM, Santos JL, Cruceyra A, Barrientos A. Occult lead intoxication as a cause of hypertension and renal failure. Nephrol Dial Transplant 1996 11 1775-1780. 

Lead nephropathy has also been complicated by the toxicological interactions of chronic kidney disease with adverse cardiovascular effects such as hypertension. Hypertension, as noted in this chapter, is a risk factor for Pb-associated and non-Pb-associated kidney disease, while mechanisms for inducing hypertension include the participation of kidney biochemistry and physiology via, for example, the renin—angiotensin pathway. 

LEAD NEPHROPATHY IN INDIVIDUALS WITH GOUT AND HYPERTENSION... 

Lead is toxic to the kidney, cardiovascular system, developiag red blood cells, and the nervous system. The toxicity of lead to the kidney is manifested by chronic nephropathy and appears to result from long-term, relatively high dose exposure to lead. It appears that the toxicity of lead to the kidney results from effects on the cells lining the proximal tubules. Lead inhibits the metaboHc activation of vitamin D in these cells, and induces the formation of dense lead—protein complexes, causing a progressive destmction of the proximal tubules (13). Lead has been impHcated in causing hypertension as a result of a direct action on vascular smooth muscle as well as the toxic effects on the kidneys (12,13). 

Nephropathy has been associated with chronic lead poisoning. " A study of two large cohorts of heavily exposed lead workers followed through 1980 demonstrated a nearly threefold excess of deaths attributed to chronic nephritis or other hypertensive disease, primarily kidney disease. Most of the excess deaths occurred before 1970, among men who began work before 1946, suggesting that current lower levels of exposure may reduce the risk. Experimental animal studies suggest there may be a threshold for lead nephrotoxicity, and in workers, nephropathy occurred only in those with blood levels over 62p,g/dl for up to 12 years."... 

Patients with renal diseases leading to the nephrotic syndrome often present complex problems in volume management. These patients may exhibit fluid retention in the form of ascites or edema but have reduced plasma volume due to reduced plasma oncotic pressures. This is very often the case in patients with "minimal change" nephropathy. In these patients, diuretic use may cause further reductions in plasma volume that can impair GFR and may lead to orthostatic hypotension. Most other causes of nephrotic syndrome are associated with primary retention of salt and water by the kidney, leading to expanded plasma volume and hypertension despite the low plasma oncotic pressure. In these cases, diuretic therapy may be beneficial in controlling the volume-dependent component of hypertension. 

Lead Inorganic lead oxides and salts Gastrointestinal, respiratory Soft tissues redistributed to skeleton (> 90% of adult body burden) CNS deficits peripheral neuropathy anemia nephropathy hypertension reproductive toxicity Inhibits enzymes interferes with essential cations alters membrane structure Renal (major) feces and breast milk (minor)... 

The combination of diabetes mellitus and hypertension inexorably leads to diabetic nephropathy and is the major cause of end-stage renal failure. In numerous animal studies and in several small clinical trials, ACE inhibitors have been shown to significantly retard the loss of kidney function associated with diabetic nephropathy. A large, prospective, placebo-controlled study has clearly established that captopril slows the progression of diabetic nephropathy in patients with insulin-... 

In type 1 diabetes, diabetic nephropathy follows a predictable course from onset of diabetes to the onset of microalbuminuria to frank nephropathy to end-stage renal disease or death. Microalbuminuria (a tiny amount of protein in the urine) develops 10-14 years after onset of diabetes. Without treatment, clinical nephropathy follows within 5 years, and severe renal impairment leading to end-stage renal failure develops approximately 5 years later. Hypertension develops in association with microalbuminuria and progresses with diabetic nephropathy, further damaging the kidneys. Once end-stage renal disease (ESRD) is reached, the toxins in the body can no longer be cleared by the kidneys and, unless treated by dialysis, can build up to fatal levels. 

Exposure to lead in adults has been associated with hypertension, nephropathy, decreased hearing acuity, anemia, peripheral neuropathy, and encephalopathy. Onset of symptoms may be slow with chronic exposure. Anemia, common in chronically exposed adults and children, tends to be more severe in children. The life span of red blood cells decreases when lead concentrations in blood increase. In the past, the morphology of various blood cells was used to diagnose lead poisoning. Zero content is allowed in food (Food and Drug Administration). 

It is not known whether these changes are the result of a normal aging process (i.e., involutional) or the result of the interplay of pathology and age. Cumulative exposure to common causes of chronic kidney disease (CKD), such as (1) atherosclerosis, (2) hypertension, (3) heart failure, (4) diabetes,(5) obstructive nephropathy, (5) infection, (6) immune insult, (7) nephrotoxins such as lead, and (8) dietary protein increases with age and it is difficult to separate these effects from those of healthy aging. The decline in GFR with increasing age may be largely attributable to hypertension, atherosclerosis, or heart failure. In the absence of these or other identifiable causes of kidney disease, many older subjects have stable GFR over time. 

Vascular nephropathy in prolonged hypertension is associated with a degeneration of the arterial walls. The resulting nephrosclerosis is due to the loss of functional glomeruli, leading to diminished renal function. 

---