Gene/Protein Disease Symptom Drug Enzyme Compound
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We examined whether the age at onset, gender, arthritic manifestations, and tophus formation in familial gout are different from those in nonfamilial gout, and we also examined the contributory effect of genetic association to the concurrence of hypertriglyceridemia, hypercholesterolemia, type 2 diabetes mellitus (DM), hypertension, obesity, and renal insufficiency with gout in Taiwan. A total of 21,373 gout patients' data from Ho-Ping Gout database were analyzed in this study retrospectively. The clinical and laboratory data were compared between familial and nonfamilial gout. Mean age at onset of gout in familial subjects was significantly 7.5 years lower than that of nonfamilial subjects (40.9 +/- 13.4 v 48.4 +/- 14.2 years, P =.0001), while gender, arthritic severity, and tophus formation were not significantly different between these 2 groups. Familial gout had lower serum triglyceride (TG), total cholesterol (TC), and percentage of hypertension than nonfamilial gout (182.4 +/- 125.3 v 195.9 +/- 135.8 mg/dL, P =.0001; 207.5 +/- 42.5 v 210.4 +/- 48.8 mg/dL, P =.0003; and 19.57% v 22.56%, P <.0001, respectively). Their serum creatinine, body mass index (BMI), and percentage of type 2 DM were not significantly different. Our results demonstrate that familial gout is associated with precocious onset. Furthermore, the contributory effect of genetic association to the concurrence of hyperlipidemia and hypertension with gout is less than that of environmental factors, while the effect of genetic association to the concurrence of obesity, type 2 DM, and renal insufficiency with gout is equivalent to that of environmental factors.
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PMID:Clinical features of familial gout and effects of probable genetic association between gout and its related disorders. 1158 94

The steady improvement in short-term success rates in renal transplant patients has translated into better long-term success rates and a large number of patients with long-functioning renal transplants. The necessity for the lifelong administration of immunosuppressive medications to prevent rejection, coupled with the presence in many patients of a variety of other medical problems dating from the period of renal insufficiency prior to the time of renal transplantation, has created a large group of patients with a unique and complex set of long-term medical care needs. Due to the constraints of managed care, considerations of geography, or patient preference, the long-term care of an increasing number of renal transplant recipients has shifted away from the transplant center to the community-based nephrologist or internist. For optimal care to be delivered, it is important that the physicians managing these patients be cognizant of the complex and interacting medical issues involved in their care. Appropriate management can significantly prolong the life of the allograft as well as that of the patient. Guidelines for understanding and managing some of the more important and common general medical problems facing the long-term renal transplant recipient (eg, infectious complications, cardiovascular disease, hypertension, diabetes, hyperlipidemia, malignancy, pregnancy, bone disease, dental care, preventive care) are addressed in this section.
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PMID:General health management and long-term care of the renal transplant recipient. 1172 2

In recent years several multicentric prospective studies have demonstrated the efficacy of some therapeutic measures to slow the progression of renal diseases. Inhibition of renin-angiotensin system (RAS) both by ACE inhibitors (ACEI) and angiotensin II receptor antagonists (ARA) is probably the strongest therapeutic alternative: The antiproteinuric effect of these drugs is an excellent surrogate marker and a predictor of the beneficial influences on the progression of renal failure. The type of renal disease, an inadequate control of blood pressure, and the presence of obesity may counteract the beneficial influences of RAS inhibition, whereas early treatment of all patients with significant proteinuria before the appearance of renal insufficiency and combined therapy with an ACEI and an ARA may augment it. Dietary protein restriction is a classic treatment of chronic renal insufficiency whose effectiveness has been validated by multicentric studies. However, a poor compliance of the patient and the risk of malnutrition with very strict protein restriction could limit the benefits of this treatment. Treatment of hyperlipidemia, prevention of obesity, avoidance of smoking, and regular physical exercise are interventions whose therapeutic potential is progressively recognized, particularly in type 2 diabetic nephropathy. Early correction of anemia may contribute to the slowing of renal disease progression. Although further studies are required, the accumulated evidence and the likelihood of additive beneficial effect of these therapeutic measures advise their combined implementation in patients with chronic renal diseases.
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PMID:Slowing the progression of renal failure. 1198 7

Earlier and more frequent sexual activity and the significant risk of pregnancy have increased the need for contraception among young adolescent girls. The problem for the physician is to choose a contraceptive method which will not affect future fertility or the psychological and biological maturity of adolescents. Condoms, diaphragms, and spermicides are quite effective if used correctly; they have no deleterious side effects, and they provide protection against sexually transmitted diseases. They appear to be well-adapted to the sporadic sexual activity of adolescents. The efficacy of combined oral contraceptives (OCs) is also high. Side effects depend on the synthetic estrogen component and are dose dependent. Absolute contraindications to OC use in women of any age include thromboembolic disease, cerebral vascular accidents, severe cardiac or hepatic disorders, breast or genital cancer, pregnancy, undiagnosed genital bleeding, and pituitary adenoma. Relative contraindications include hypertension, diabetes, hyperlipidemia, obesity, history of hepatitis, migraines, epilepsy, asthma, renal insufficiency, cystic breast disease, and mammary fibroadenomas. Combined OCs do not seem to interfere with subsequent maturation of the hypothalamopituitary axis. The frequency of ovulatory cycles in adolescents who have discontinued pill use is the same as that in adolescents who have never used pills. However, estrogens accelerate the process of maturation in the bones, so combined OCs should never be prescribed for girls who have not terminated their growth. Minidose OCs containing 30-45 mcg of ethinyl estradiol aggravate the relative hyperestrogenism of adolescents and are associated with menstrual problems, functional ovarian cysts, and breast problems. They should only be prescribed for adolescents with regular sexual activity, no less than 3 years following menarche, with regular ovulatory menstrual cycles and no history of breast disorders. Otherwise, a standard-dose combined pill with 50 mcg EE should be selected. Continuous dose progestin minipills depend on peripheral effects such as modifications in the cervical mucus for their contraceptive effects. They are associated with frequent menstrual problems, functional ovarian cysts, and extrauterine pregnancies. They may be indicated for adolescents with regular sexual activity but with contraindications to combined OCs. Trimonthly injections of medroxyprogesterone acetate have major effects on endocrine metabolism and should be used only for adolescents with severe mental problems. IUD efficacy is high but they may be less well tolerated by adolescents than by older women and the risk of infection may be heightened. They should only be used for adolescents with absolute contraindications to use of hormonal contraceptives who have no history of genital infections.
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PMID:[Choosing contraception for adolescents]. 1228 May 85

Understanding and modifying the causes of the high cardiovascular morbidity and mortality associated with renal disease is the greatest challenge faced by renal physicians. About one person in 20 has a serum creatinine level above normal (> or =1.5 mg/dl in males and > or =1.4 mg/dl in females), signifying mild kidney disease. People with hypertension, hyperlipidaemia, and/or diabetes (approximately 350000 people per million in the general population) have the highest risk of renal failure. Anaemia, extracellular volume expansion, increased angiotensin II and aldosterone levels, high calcium-phosphate product, inflammation, hyperhomocysteinaemia, and impaired nitric oxide synthesis all amplify the risk of cardiovascular disease in patients with renal failure. These factors may adversely affect the cardiovascular system by influencing the generation of reactive oxygen species, thus contributing to high oxidative stress. Further research into optimal follow-up of patients with mild renal insufficiency is needed. Identification of 'problematic' and/or treatment-resistant patients should be a primary goal. Greater understanding of the genetic and environmental precursors of diseases associated with renal insufficiency would also be beneficial, particularly for younger patients. Observational studies aimed at linking these risk factors to well-defined and measured renal and cardiovascular outcomes should increase knowledge of renal disease progression and cardiovascular risk in these populations.
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PMID:Cardiorenal risk as a new frontier of nephrology: research needs and areas for intervention. 1238 60

We report a patient with renal insufficiency who developed rhabdomyolysis 1 month after initiating cerivastatin and gemfibrozil for hyperlipidemia. Myopathy caused by HMG-CoA reductase inhibitors (statins) alone is rare, but occurs more frequently when a statin is used with gemfibrozil, a medication that likely has a direct toxic effect on muscles. Predisposing factors to the development of myopathy from the combination include use of medications affecting statin metabolism, higher doses of statins, renal insufficiency, diuretics, and hypothyroidism. It has been proposed that alternate-day therapy with a statin and fibrate, spacing of doses in a single day, or use of lower doses of statins may prevent the development of myopathy. Currently, no predictable method to determine who is at risk for myopathy exists, nor is there a reliable screening test. Therefore, patients should be advised to watch for generalized muscle pain or weakness, and if it occurs, stop medications and report symptoms immediately.
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PMID:Rhabdomyolysis from the combination of a statin and gemfibrozil: an uncommon but serious adverse reaction. 1242 21

Since its introduction in renal transplantation in 1999, sirolimus is being used by an increasing number of liver transplant centers. Compared to the calcineurin inhibitors, sirolimus acts through a separate signal transduction pathway and has a myriad of important biologic effects including: inhibition of lymphocyte proliferation, inhibition of fibrosis and fibroblast proliferation, and antineoplastic effects. The clinical side-effect profile of this drug is also different than calcineurin inhibitors. Most important, sirolimus does not cause glucose intolerance, hypertension, or renal insufficiency. As a result, this drug offers significant potential advantages over conventional immunosuppressive agents. However, sirolimus may cause hyperlipidemia and has also been associated with hepatic artery thrombosis in liver transplant recipients. This review will summarize the published data on sirolimus in liver transplantation, focusing on the potential advantages and disadvantage of the use of this drug in liver transplant recipients. Finally, the potential benefits of antifibrosis and antineoplastic effects of sirolimus in liver transplant recipients will be discussed.
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PMID:Sirolimus in liver transplantation. 1274 96

Metabolic and nutritional care implies procedures which involve normalization or improvement of metabolic deviations in chronic renal insufficiency and failure by dietary and medicamentous means. The therapeutic procedure not only improves some metabolic disorders associated with a decline of the excretory and metabolic endocrinological renal function but can have a positive impact also on progression of renal insufficiency. Conservative treatment thus involves low protein diets, modification of electrolyte and water intake, adjustment of the acid-base balance, Ca, P metabolism, haemogram, hypertension, proteinuria and hyperlipidaemia. In non-diabetic subjects it is sufficient to achieve a glomerular filtration of 0.2 ml/sec. and serum creatinine of 500-600 mumol/l.
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PMID:[Metabolic and nutrition care in patients with chronic renal insufficiency and chronic kidney failure]. 1290 71

The clinical features of 567 patients with crystal proven gout (489 males, 78 females) seen in a University Hospital in northern Thailand was reviewed. The mean age at onset and mean duration of disease was 60.0 +/- 11.7 years and 5.2 + 4.8 years, respectively. Recurrent attacks accounted for 94 per cent. The knee and ankle were the 2 most common joints affected during the first attack and each one was seen in 55.6 per cent of cases. During a recurrent attack, the ankle, knee and first metatarsophalangeal joint were the 3 most common joints affected and were seen in 94.5 per cent, 81.2 per cent and 80.2 per cent of cases, respectively. Thirty-six per cent of the patients had tophi. Hypertension, hyperlipidemia, diabetes mellitus and ischemic heart disease were commonly associated diseases. Thirty-five per cent had renal calculi, and fifty-four per cent had renal insufficiency. Of 59 patients who tested with normal renal function, twelve per cent were hyperexcretor. The clinical features of gout seen in the university hospital in northern Thailand were similar to those reported in Bangkok, but with a higher incidence of tophaceous gout, renal failure and renal calculi.
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PMID:A clinical study of crystal-proven gouty arthritis in a university hospital. 1464 72

While increased risk of cardiovascular disease (CVD) in patients with hyperlipidemia, chronic kidney disease (CKD), or end-stage renal disease (ESRD) is well documented, transient hyperlipidemia or intermittent renal disease as a consequence of relapsing nephrotic syndrome (NS) has not been studied. To investigate this enigma, 62 patients, between 25 and 53 years of age, who had steroid-responsive/dependent NS during childhood, were identified from the records of the Division of Pediatric Nephrology at Yale School of Medicine. Forty patients were located and contacted to ascertain symptoms or occurrences of CVD via a telephone interview. At the time of follow-up, 23-46 years after cessation of NS, none of these patients had ESRD or CKD. Three patients had experienced a myocardial infarction (MI): a 32-year-old male with a family history of CVD; a 41-year-old male with a history of heavy smoking, hypertension, diabetes mellitus, and elevated cholesterol; a 31-year-old male after a cocaine overdose. The occurrence of events (8%) and mortality from CVD (none) in this cohort of patients is comparable to patients of a similar age in the general population and is lower than that of patients of the same age who are on dialysis. The data suggest that relapsing NS during childhood does not place patients at increased risk for CVD mortality or morbidity compared with the general population. Consequently, it would appear that factors related to persistent proteinuria or renal insufficiency, rather than transient proteinuria and renal disease, contribute to the CVD documented in patients with CKD or ESRD.
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PMID:The risk of cardiovascular disease in adults who have had childhood nephrotic syndrome. 1508 19


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