Renal capacity

The major population at risk for aluminum loading and toxicity consists of individuals with renal failure. In a study by Alfrey (1980), 82% of nondialyzed uremic patients and 100% of dialyzed uremic patients had an increased body burden of aluminum. The decreased renal function and loss of the ability to excrete aluminum, ingestion of aluminum compounds to lessen gastrointestinal absorption of phosphate, the aluminum present in the water used for dialysate, and the possible increase in gastrointestinal absorption of aluminum in uremic patients can result in elevated aluminum body burdens. The increased body burdens in uremic patients has been associated with dialysis encephalopathy (also referred to as dialysis dementia), skeletal toxicity (osteomalacia, bone pain, pathological fractures, and proximal myopathy), and hematopoietic toxicity (microcytic, hypochromic anemia). Pre-term infants may also be particularly sensitive to the toxicity of aluminum due to reduced renal capacity (Tsou et al. 1991)... 

These investigations of lithium handling by the kidneys have provided information which is useful for prevention and treatment of lithium intoxication. In general, all conditions associated with salt depletion strongly impair renal capacity to eliminate lithium. 

When I joined the Department of Pediatrics at the Massachusetts General Hospital, Drs. Butler, Talbot and Gamble were at work devising their life-raft ration for castaways (Gamble and Butler, 1944). In the course of these studies it was of importance to define the minimal water requirement for urine formation. Their elucidation of this parameter prompted Dr. Edgar Schoen, and myself (Crawford t, 1952) greatly aided by Dr. Arnold Nicosia s introduction of the Thermistor for osmometry (Crawford and Nicosia, 1952) to look at the other side of the coin, to see if there existed a maximal renal capacity for water excretion. As shown in Figure 1, this too, proved to be a finite quantity. When normal subjects... 

Fig. 9. The water requirement and tolerance of the infant as compared with those of the adult. Note that the infant s minimal water requirement is increased by relatively larger insensible and stool losses and an appreciable diversion of water to new protoplasm for growth. The water tolerance of the neonate is reduced by a slight reduction in the renal capacity to dilute accompanied by a substantially prolonged time for adaptation to a water load. Tolerance is also variably reduced by diet breast milk, for example, limits water excretion capacity because of its very small osmoti-cally active residue. (Talbot, 1959).

Disorders of lipoprotein metabolism involve perturbations which cause elevation of triglycerides and/or cholesterol, reduction of HDL-C, or alteration of properties of lipoproteins, such as their size or composition. These perturbations can be genetic (primary) or occur as a result of other diseases, conditions, or drugs (secondary). Some of the most important secondary disorders include hypothyroidism, diabetes mellitus, renal disease, and alcohol use. Hypothyroidism causes elevated LDL-C levels due primarily to downregulation of the LDL receptor. Insulin-resistance and type 2 diabetes mellitus result in impaired capacity to catabolize chylomicrons and VLDL, as well as excess hepatic triglyceride and VLDL production. Chronic kidney disease, including but not limited to end-stage... 

Bile ducts Various intravenous cholegraphic agents, e.g., iodipamide Biligrafin Anion transport Lin SK et al (1977) Iodipamide kinetics Capacity-limited biliary excretion with simultaneous pseudo-first-order renal excretion. J Pharm Sci 66 1670-1674... 

West JR, Smith HW, Chasis H. 1948. Glomemlar filtration rate, effective renal blood flow, and maximal tubular excretory capacity in infancy. J Pediatr 32 10-18. 

In an ideal pure preparation of Na,K-ATPase from outer renal medulla, the al subunit forms 65 70% of the total protein and the molar ratio of a to is 1 1, corresponding to a mass ratio of about 3 1 [1,5]. Functionally the preparation should be fully active in the sense that each a/ unit binds ATP, Pj, cations and the inhibitors vanadate and ouabain. The molecular activity should be close to a maximum value of 7 000-8 000 Pj/min. The highest reported binding capacities for ATP and phosphate are in the range 5-6 nmol/mg protein and close to one ligand per otjS unit [29], when fractions with maximum specific activities of Na,K-ATPase [40 50 pmo Pj/min mg protein) are selected for assay. 

Nitrogen compounds commonly determined are creatinine, urea, and uric acid. Creatinine is an end product of the energy process occurring within the muscles, and is thus related to muscle mass. Creatinine in urine is commonly used as an indicator and correction factor of dilution in urine. Creatinine in serum is an indicator of the filtration capacity of the kidney. Urea is the end product of the nitrogen luea cycle, starting with carbon dioxide and ammonia, and is the bulk compoimd of urine. The production of uric acid is associated with the disease gout. In some cases, it appears that the excess of uric acid is a consequence of impaired renal excretion of this substance. 

As nephron mass decreases, both the distal tubular secretion and GI excretion are increased because of aldosterone stimulation. Functioning nephrons increase FEK up to 100% and GI excretion increases as much as 30% to 70% in CKD,30 as a result of aldosterone secretion in response to increased potassium levels.30 This maintains serum potassium concentrations within the normal range through stages 1 to 4 CKD. Hyperkalemia begins to develop when GFR falls below 20% of normal, when nephron mass and renal potassium secretion is so low that the capacity of the GI tract to excrete potassium has been exceeded.30... 

Protonated THAM (with CP or HCO, ) is excreted in the urine at a rate that is slightly higher than creatinine clearance. As such, THAM augments the buffering capacity of the blood without generating excess C02. THAM is less effective in patients with renal failure and toxicities may include hyperkalemia, hypoglycemia, and possible respiratory depression. 

The renal excretion of drugs depends on glomerular filtration, tubular secretion, and tubular absorption. A twofold increase in glomerular filtration occurs in the first 14 days of life [36], The glomerular filtration rate continues to increase rapidly in the neonatal period and reaches a rate of about 86 mL/min per 1.73 m2 by 3 months of age. Children 3-13 years of age have an average clearance of 134 mL/min per 1.73 m2 [37]. Tubular secretion approaches adult values between 2 and 6 months [11], There is more variability observed in maturation of tubular reabsorption capacity. This is likely linked to fluctuations in urinary pH in the neonatal period [38],... 

Roels H, Lauwerys R, Konings J, et al. 1994. Renal function and hyperfiltration capacity in lead smelter workers with high bone lead. Occup Environ Med 51 505-512. 

The a ns wer is a. (Hardman, pp 1525-1528.) Pa r a thyroid ho r m o ne is synthesized by and released from the parathyroid gland increased synthesis of PTI1 is a response to low serum Ca concentrations. Resorption and mobilization of Ca and phosphate from bone are increased in response to elevated PTI1 concentrations. Replacement of body stores of Ca is enhanced by the capacity of PTH to promote increased absorption of Ca by the small intestine in concert with vitamin D, which is the primary factor that enhances intestinal Ca absorption. Parathyroid hormone also causes an increased renal tubular reabsorption of Ca and excretion of phosphate. As a consequence of these effects, the extracellular Ca concentration becomes elevated. 

The lethal effects of cadmium are thought to be caused by free cadmium ions, that is, cadmium not bound to metallothioneins or other proteins. Free cadmium ions may inactivate various metal-dependent enzymes however, cadmium not bound to metallothionein may have the capacity to directly damage renal tubular membranes during uptake (USPHS 1993). 

A large proportion of the mercury in the kidney is bound to metallothionein, which has a capacity to bind mercury strongly [37-39]. The role for metallothionein in the kidney is probably protective [37]. Chronic dosing of rats with mercuric chloride over a period of 3 weeks induced an approximately 6-fold increase in the renal metallothionein levels, which provides an explanation for the almost linear increase of mercury in kidneys over several weeks of daily exposure. A protective role of metallothionein would explain findings that the... 

Cell Lines. Cell lines, derived from tissue of various species, are commercially available from tissue culture banks. These cell populations are immortalized in that they possess the capacity to permanently proliferate in culture. Such cellular models can be studied in short-term suspension (hours) or longer-term monolayer culture (days, weeks, months). Since cell lines have been extensively cultured or passaged for multiple generations, the degree or retention (or loss) of kidney-specific morphology and function is an important limitation that is not thoroughly addressed for a number of renal cell lines. One renal cell line that has been relatively well characterized is the pig kidney cell line, LLC-PK,. 

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