Kidneys renal toxins

Many of the same chemicals that are hepatotoxic are also nephrotoxic. A partial list of renal toxins is contained in Table 31.1. This list is drawn from the Scorecard kidney toxicant lists, which contains references to original sources... 

Given the almost constant exposure of humans to toxic chemicals (via air pollution, water pollution, or food contamination) and the filtration function of the kidneys, one could easily argue that the kidneys are almost constantly exposed to mixtures of toxic chemicals and that the uptake of additional xenobiotic chemicals creates new mixtures. As we have already seen earlier, many single chemicals have been shown to be renal toxins. Whether the observed nephrotoxic effects of any of these chemicals are because of its interactions with endogenous or other exogenous chemicals is unknown. What is known is that exposures to some chemical mixtures are toxic to the kidneys of test animals and humans. Examples of studies demonstrating mixture effects follow ... 

The sterile peritoneal dialysis solutions are infused continuously into the abdominal cavity, bathing the peritoneum, and are then continuously withdrawn. The purpose of peritoneal dialysis is to remove toxic substances from the body or to aid and accelerate the excretion function normal to the kidneys. The process is employed to counteract some forms of drug or chemical toxicity as well as to treat acute renal insufficiency. Peritoneal dialysis solutions contain glucose and have an ionic content similar to normal extracellular fluid. Toxins and metabolites diffuse into the circulating dialysis... 

No single toxin is responsible for all of the signs and symptoms of uremia observed in stage 4 or 5 CKD. Toxins accumulate as a result of increased secretion, decreased clearance secondary to reduced metabolism within the kidney, and/or decreased renal clearance of by-products of protein metabolism. 

Kidney failure not only decreases renal clearance of nicotine and cotinine, but also metabolic clearance of nicotine (Molander et al. 2000). Metabolic clearance of nicotine is reduced by 50% in subjects with severe renal impairment compared to healthy subjects. It is speculated that accumulation of uremic toxins may inhibit CYP2A6 activity or downregulate CYP2A6 expression in liver. Hepatic metabolism of several drugs is reduced in kidney failure, mainly via downregulation of CYP enzymes and/or inhibition of transporters (Nolin et al. 2003). 

The action of downward-draining herbs can move the bowels, thus eliminating toxins from the body when Liver and Kidney functions are impaired and they fail to remove toxic substances, such as in cirrhosis of the Liver and renal failure. If a toxic substance has been ingested, the action of downward-draining herbs can assist the body in eliminating it. 

Besides glucose, other analytes of clinical value can be possibly quantified by noninvasive spectral analysis. In vivo concentrations of lactate and urea are examples. The concentration of lactate in blood is used clinically to follow intensive care treatments, to identify cardiac or liver failure, to determine hypoxia of tissues from atherosclerosis, and to detect bacterial infection. In vivo urea levels are valuable for optimizing hemodialysis treatments and tracking the accumulation of toxins for people with end-stage renal failure or recent kidney transplant recipients. 

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. 

Chronic renal failure is associated with long-term exposure to toxins and is mostly related to the secondary pathological changes triggered by the initial injury. These secondary changes are compensatory mechanisms to maintain the function of the whole kidney, but they eventually result in... 

The primary function of the kidneys is to rid the body of waste materials that are either ingested or produced by metabolism, and to control the volume and composition of the body fluids. The toxins absorbed by the different routes are biotransformed and enter the blood. They are then eliminated through the urine, feces, and air. Since the kidneys receive approximately a quarter of the cardiac output, it is an important organ for the exposure of toxicants and their metabolites. Recent incidents of pet food toxicity and diethylene glycol toxicity indicate that contamination of animal and human food and drugs, respectively, can lead to severe mortahty and morbidity as a result of renal toxicity. 

Those involved in individual health assessment are concerned with the early detection of specific organ kidney injury. With regard to acute kidney injury (AKI), biomarkers may serve several additional purposes. That is, they may determine AKI subtypes (prerenal, intrinisic renal, or postrenal), identify the etiology of AKI (ischemia, toxins, sepsis, or a combination), differentiate AKI from other forms of acute kidney disease (urinary tract infections, glomerulonephrihs, intershtial nephritis), predict the AKI severity (risk stratification for prognostication as well as guide to therapy), monitor the course of AKI, and monitor the response to AKI interventions. For chronic kidney disease (CKD), they provide both evidence and severity of exposure and may be used to assess response to removal of offend-... 

This chapter will attempt to outline the extent of the problem in South Africa. We have confined our comments to toxins that have a major impact on renal function - although some (if not most ) toxins have secondary effects with consequent kidney failure. 

Uremic toxins are chemicals and waste products normally excreted by the kidneys and are responsible for many of the signs of kidney disease. Since 1840, more than 2000 toxic substances were reported in uremic blood. Obviously, the determination of such compounds is crucial for diagnosis and monitoring of renal disease and metabolic disorders. The concentrations of several uremic toxins in blood serum and urine are among the most important parameters in biochemistry and clinical chemistry. 

Lesaffer G, De Smet R, D Heuvaert T, et al. (2003) Comparative kinetics of the uremic toxin p-cresol versus creatinine in rats with and without renal failure. Kidney International 64 1365-1373. 

Renal replacement therapy—Any form of dialysis or hemofiltration used to support patients without adequate kidney function. Goals of renal replacement therapy are to remove excess fluid remove waste products and toxins and control electrolyte concentrations. 

OAT family plays a critical role in the renal excretion and detoxification of a wide variety of compounds including drugs, toxins, hormones, and neurotransmitter metabolites. OATs are primarily expressed in the kidney. In addition, OAT expression has been detected in liver, placenta, brain, and choroid plexus. At least five different OATs (OAT1, OAT2, OAT3, OAT4, and Uratl) have been detected in human tissues [109],... 

---