Human glomerular filtration rate

Renal Effects. The characteristics of early or acute lead-induced nephropathy in humans include nuclear inclusion bodies, mitochondrial changes, and cytomegaly of the proximal tubular epithelial cells dysfunction of the proximal tubules (Fanconi s syndrome) manifested as aminoaciduria, glucosuria, and phosphaturia with hypophosphatemia and increased sodium and decreased uric acid excretion. These effects appear to be reversible. Characteristics of chronic lead nephropathy include progressive interstitial fibrosis, dilation of tubules and atrophy or hyperplasia of the tubular epithelial cells, and few or no nuclear inclusion bodies, reduction in glomerular filtration rate, and azotemia. These effects are irreversible. The acute form is reported in lead-intoxicated children, whose primary exposure is via the oral route, and sometimes in lead workers. The chronic form is reported mainly in lead workers, whose primary exposure is via inhalation. Animal studies provide evidence of nephropathy similar to that which occurs in humans, particularly the acute form (see Section 2.2.3.2). 

Information is available on the renal toxicity of ingested lead in several species, including rats, dogs, monkeys, and rabbits. The results indicate that histopathological changes in the kidneys of lead-treated animals are similar to those in humans (see Section 2.2.1.2). Reduced glomerular filtration rates and aminoaciduria were reported in some of the animal studies. Key animal studies on lead-induced renal toxicity will be discussed below. 

Renal elimination of foreign compounds may change dramatically with increasing age by factors such as reduced renal blood flow, reduced glomerular filtration rate, reduced tubular secretory activity, and a reduction in the number of functional nephrons. It has been estimated that in humans, beginning at age 20 years, renal function declines by about 10% for each decade of life. This decline in renal excretion is particularly important for drugs such as penicillin and digoxin, which are eliminated primarily by the kidney. 

The major route of fluoride excretion is via the kidney and urine 40-60% of the daily intake is excreted in the urine with an elimination half-life of about 5 h [17,85]. Fluoride excretion is influenced by a number of factors, including glomerular filtration rate, urinary flow and urinary pH. The excretion of fluoride in urine is reduced in individuals with impaired renal function. Urine fluoride excretion is 0.79 mg/day in humans with normal renal function, 0.53 mg/day in those with questionable and 0.27 mg/day in those with impaired renal function [86],... 

The extra-renal excretion of the extracellular gadolinium complexes is negligible and no significant absorption after enteral application has been observed. The elimination half-life depends on the glomerular filtration rate, and on the cardiovascular function. No significant differences between the gadolinium chelates have been observed, their terminal half-lives in blood are in the range of 15 to 75 minutes in animals and 1-2 h in humans [65-67]. 

Renal function is depressed by opioids. It is believed that in humans this is chiefly due to decreased renal plasma flow. Opioids can decrease systemic blood pressure and glomerular filtration rate. In addition, opioids have been found to have an antidiuretic effect in humans. Mechanisms may involve both the CNS and peripheral sites, but the relative contributions of each are unknown. Opioids also enhance renal tubular sodium reabsorption. The role of opioid-induced changes in antidiuretic hormone (ADH) release is controversial. Ureteral and bladder tone are increased by therapeutic doses of the opioid analgesics. Increased sphincter tone may precipitate urinary retention, especially in postoperative patients. Occasionally, ureteral colic caused by a renal calculus is made worse by opioid-induced increase in ureteral tone. 

However, there is still a wide gap in the understanding of the nephrotoxic effects caused by certain therapeutic agents such as cyclosporin, analgesics, and nonsteroidal anti-inflammatory agents. Several chemical substances disturb the glomerular filtration rate (GFR) and related renal functions in animals and humans. 

Foscarnet competitively inhibits Na -Pj cotransport in animal and human kidney proximal tubule brush border membrane vesicles, reversibly inhibiting sodium-dependent phosphate transport [48, 49]. Renal cortical Na-K-ATPase and alkaline phosphatase activity are not inhibited by foscarnet, nor is proline, glucose, succinate, or Na" transport [48,49]. Foscarnet induces isolated phosphaturia without hypophosphatemia in thyroparathyroidectomized rats maintained on a low phosphorus diet, without affecting glomerular filtration rate, urinary adenosine 3 5 -cyclic monophosphate (cAMP) activity, or urinary calcium, sodium or potassium excretion [48,50]. Sodium-Pj cotransport in brush border membrane vesicles from human renal cortex was reported to be even more sensitive to inhibition by foscarnet than in rat renal brush border membrane vesicles [49]. 

In human, the pathophysiology of inferleukin-2 induced renal dysfunction is still poorly understood. Interleukin-2 may act directly on the vascular tonus and endothelial integrity or may stimulate generation of other cytokines, which in turn would increase vascular permeability. Occurrence of an intrinsic renal lesion has been suggested by Shalmi et ah [194] who showed that glomerular filtration rate is altered in 90% of the patients [mean decrease of 43%] whereas renal plasma flow decreases is only slightly altered [mean decrease 5%] in 50% of the patients. 

Arant BS Jr. Developmental patterns of renal functional maturation compared in the human neonate. J Pediatr 1978 92 705-712. van den Anker, de Groot R, Broerse HM, et al. Assessment of glomerular filtration rate in preterm infants by serum creatinine Comparison with inulin clearance. Pediatrics 1995 96 1156-1158. 

Tomoda et al.157 reported on altered renal response to enhanced endogenous serotonin after tryptophan administration in essential hypertension in human subjects. The altered renal response (renal plasma flow, glomerular filtration rate) to tryptophan found in essential hypertension was considered to be partly related to the exaggerated efferent arteriolar constriction induced by endogenously formed serotonin. In essential hypertension, there was a baseline overproduction of renal serotonin, which may have contributed to a reduction in renal excretory capability. 

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