Kidneys susceptibility factors

Susceptibility factors can be readily used to develop screening programs for CKD. For example, older patients, those with low kidney mass or birth weight, and those with a family history of kidney disease should be routinely screened for CKD. 

Susceptibility factors increase the risk for kidney disease but do not directly cause kidney damage. Susceptibility factors include advanced age, reduced kidney mass and low birth weight, racial or ethnic minority, family history, low income or education, systemic inflammation, and dyslipidemia. 

Adverse effect Lactic acidosis due to biguanides Dose-relation toxic effect Time-course time-independent Susceptibility factors genetic (slow phenformin metabolizers) age disease (impaired liver, kidney, or cardiac function, alcoholism)... 

Mechanism and susceptibility factors Biguanides in high doses inhibit the oxidation of carbohydrate substrates by affecting mitochondrial function. Anoxidative carbohydrate metabolism stimulates the production of lactate. High lactate production leads to lactic acidosis (type B) with a low pH (<6.95). Hyperlactatemia was common in patients taking buformin, even without alcoholism or impaired liver, kidney, or cardiac function (70). 

Susceptibility factors disease (impaired liver or kidney function, alcoholism) drug interactions reduced food intake exercise... 

Individuals with susceptibility factors have an increased risk for the development of kidney disease, althongh these risk factors have not been proven to directly cause kidney damage. These factors inclnde... 

Although the data are not conclusive, hyperlipidemia has been associated as a susceptibility factor for CKD in both animal and human studies. The use of lipid-lowering agents in some animal models has been found to decrease the extent of glomerular injury when both underlying renal disease and hyperlipidemia are present. Therefore the correction of lipid abnormalities in patients with CKD was proposed to have a beneficial effect on the rate of progression of the disease. CKD with or without nephrotic syndrome is frequently accompanied by abnormalities in fipoprotem metabolism. The prevalence of hyperlipidemia appears to increase as kidney function declines and with the presence of the nephrotic syndrome. ... 

Urinary tract Nephrotoxicity is the major limiting factor for the use of colistimethate sodium, but the reported incidence of acute kidney damage has varied. The incidence of acute kidney damage and factors that may predict it have been evaluated retrospectively in 71 patients [104. The median daily dose of colistimethate was 4.6mg/kg and the mean treatment duration was 13 days. There was acute kidney damage in 38 patients at a median time of onset of 8 days. Six patients required renal replacement therapy. The incidence increased with duration of treatment and cumulative dose. Male sex, the concomitant use of cald-neurin inhibitors, hypoalbuminemia, and hyperbilirubinemia were independent susceptibility factors. Of 38 patients who developed acute kidney damage, 16 recovered by the time of discharge. 

Infection risk The risk of infections and serious infections with rituximab may be similar to that with the TNT antagonists. To date, there have been no reports from trials of an increased risk of tuberculosis or opportunistic infections with rituximab [162 ]. Some investigators have reported an increase in Pneumocystis jirovecii pneumonia, and increased number of infections has been documented in patients treated with maintenance rituximab for low-grade lymphoma and in patients with concomitant severe immunodeficiency, whether caused by HIV or immunosuppressive agents [152 ]. In rheumatoid arthritis, the susceptibility factors for severe infections include chronic lung and/or cardiac disease, extra-articular involvement, and low IgG before rituximab treatment [163 ]. After kidney transplantation, the off-label use of rituximab is associated with a high risk of infectious disease and death related to infectious disease [164 ]. 

Susceptibility factors Genetic There is a high incidence of new-onset diabetes melli-tus in transplant patients taking tacrolimus. One predisposing factor may be a polymorphism in the calpain-10 gene, which has previously been associated with an increased risk of type 2 diabetes in the general population. In 214 kidney transplant... 

The most important susceptibility factors are pre-existing chronic kidney disease (CKD eGFR below 60 mVmin) and chronic kidney disease associated with diabetes [15]. Other factors include age over 70 years, the presence of congestive heart failure, nephrotoxic drugs (loop diuretics, metformin, nonsteroidal anti-inflammatory agents), volume depletion, and repeated exposure within short periods of time (under 72 hours). 

Susceptibility factors Renal disease In a randomized study of raloxifene in 7707 postmenopausal women with chronic kidney disease, the incidence of adverse reactions was similar to that in a control group without kidney disease [53 ]. 

Susceptibility factors Ranolazine is metabolised mainly in the liver by the enzyme CYP 3 A4. Caution should be taken in patients that take other drugs known to interact with this enzyme. In patients with hepatic dysfunction, accumulation of ranolazine may occm. It is cleared mainly by the kidneys. Therefore, a dose reduction is recommended in patients with mild or moderate renal impairment. However, it is contraindicated in patients with severe renal impairment [34]. 

Intraspecies 3—An uncertainty factor of 3-fold was used, because the hemolytic response is likely to occur to a similar extent and with similar susceptibility in most individuals. This was based on the consideration that physiologic parameters (e.g., absorption, distribution, metabolism, structure of the erythrocyte and its response to arsine, and renal responses) are not likely to vary among individuals of the same species to such an extent that the response severity to arsine would be altered by an order of magnitude. Individual variability (i.e., variability in erythrocyte structure/ function or response of the kidney to hemolysis) ... 

Table 15.1 Factors Affecting the Susceptibility of the Kidney to Toxicants...

Preventing CIN is of particular importance in patients with diabetes and chronic kidney disease, as these are two of the most powerful independent risk factors for CIN (77), Diabetics are more susceptible to (CIN) than are the nondiabetics, and diabetics with pre-existing chronic kidney disease (CKD) are at even greater risk (78). In a recently proposed CIN risk-scoring system, patient characteristics such as diabetes, age >75, chronic congestive heart failure, admission with acute pulmonary edema, hypotension, anemia and chronic kidney disease and various procedure-related characteristics including increasing volumes of contrast media, and intra-aortic balloon pump use were all found to reliably contribute to increased risk (79). 

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