Cystatin C: current position and future prospects.

Abstract Cystatin C is a low-molecular-weight protein which has been proposed as a marker of renal function that could replace creatinine. Indeed, the concentration of cystatin C is mainly determined by glomerular filtration and is particularly of interest in clinical settings where the relationship between creatinine production and muscle mass impairs the clinical performance of creatinine. Since the last decade, numerous studies have evaluated its potential use in measuring renal function in various populations. More recently, other potential developments for its clinical use have emerged. This review summarises current knowledge about the physiology of cystatin C and about its use as a renal marker, either alone or in equations developed to estimate the glomerular filtration rate. This paper also reviews recent data about the other applications of cystatin C, particularly in cardiology, oncology and clinical pharmacology. Clin Chem Lab Med 2008;46:1664-86

Age-related associations of hypertension and diabetes mellitus with chronic kidney disease

<p>Abstract</p> <p>Background</p> <p>Studies suggest end-stage renal disease incidence and all-cause mortality rates among patients with chronic kidney disease (CKD) differ by age. The association of diabetes mellitus and hypertension with CKD across the adult lifespan is not well established.</p> <p>Methods</p> <p>Data from NHANES 1999–2004 were used to determine the association of risk factors for stage 3 or 4 CKD (n = 12,518) and albuminuria (n = 12,778) by age grouping (20 to 49, 50 to 69, and ≥70 years). Stage 3 or 4 CKD was defined as an estimated glomerular filtration rate of 15 to 59 ml/min/1.73 m²and albuminuria as an albumin to creatinine ratio ≥30 mg/g.</p> <p>Results</p> <p>For adults 20 to 49, 50 to 69 and ≥70 years of age, the prevalence ratios (95% confidence interval) of stage 3 or 4 CKD associated with hypertension were 1.94 (0.86 – 4.35), 1.51 (1.09 – 2.07), 1.31 (1.15 – 1.49), respectively (p-trend = 0.038). The analogous prevalence ratios (95% confidence interval) were 3.01 (1.35 – 6.74), 1.61 (1.15 – 2.25), 1.40 (1.15 – 1.69), respectively, for diagnosed diabetes mellitus (p-trend = 0.067); and 2.67 (0.53 – 13.4), 1.35 (0.69 – 2.63), 1.08 (0.78 – 1.51), respectively, for undiagnosed diabetes mellitus (p-trend = 0.369). The prevalence ratios of albuminuria associated with hypertension and diagnosed and undiagnosed diabetes mellitus were lower at older age (each p < 0.05).</p> <p>Conclusion</p> <p>Among US adults, diabetes mellitus and hypertension are associated with CKD and albuminuria regardless of age. However, the associations were stronger at younger ages.</p

Early chronic kidney disease: diagnosis, management and models of care

Chronic kidney disease (CKD) is prevalent in many countries, and the costs associated with the care of patients with end-stage renal disease (ESRD) are estimated to exceed US$1 trillion globally. The clinical and economic rationale for the design of timely and appropriate health system responses to limit the progression of CKD to ESRD is clear. Clinical care might improve if early-stage CKD with risk of progression to ESRD is differentiated from early-stage CKD that is unlikely to advance. The diagnostic tests that are currently used for CKD exhibit key limitations; therefore, additional research is required to increase awareness of the risk factors for CKD progression. Systems modelling can be used to evaluate the impact of different care models on CKD outcomes and costs. The US Indian Health Service has demonstrated that an integrated, system-wide approach can produce notable benefits on cardiovascular and renal health outcomes. Economic and clinical improvements might, therefore, be possible if CKD is reconceptualized as a part of primary care. This Review discusses which early CKD interventions are appropriate, the optimum time to provide clinical care, and the most suitable model of care to adopt

Improved estimation of glomerular filtration rate (GFR) by comparison of eGFRcystatin C and eGFRcreatinine

Objective. GFR-prediction equations based upon cystatin C and creatinine have better diagnostic performance in estimating GFR than equations based upon only one of the two markers. The present work concerns in what way a comparison between separate estimations of GFR based upon cystatin C (eGFR(cystatin C)) or creatinine (eGFR(creatinine)) can be used to evaluate the diagnostic performance of a combined cystatin C-and creatinine-based estimation of GFR. Methods. The difference between eGFR(cystatin C) and eGFR(creatinine) was compared with measured GFR (iohexol clearance) and a combined cystatin C- and creatinine-based estimation of GFR in a Swedish-Caucasian cohort of 857 adult patients. Results. A difference between eGFR(cystatin C) and eGFR(creatinine) of >= 40% indicated a markedly reduced diagnostic performance of the combined cystatin C- and creatinine-based estimation of GFR. Conclusion. Comparison of the agreement between eGFR(cystatin C) and eGFR(creatinine) can be used to evaluate the diagnostic performance of combined cystatin C-and creatinine-based estimations of GFR. If 'threshold values' for discordance are exceeded, it must be considered whether the clinical context requires the use of an invasive gold standard method to measure GFR. In some clinical contexts either creatinine or cystatin C are known to be invalidated as markers of GFR and in these situations the use of only the cystatin C-or the creatinine-based GFR estimate should be considered when the 'threshold values' are exceeded

Plasmapheresis reverses all side-effects of a cisplatin overdose – a case report and treatment recommendation

BACKGROUND: Cisplatin is widely used as an antineoplastic agent since it is effective against a broad spectrum of different tumours. Nevertheless, it has several potential side effects affecting different organ systems and an overdose may lead to life-threatening complications and even death. CASE PRESENTATION: We report on a 46-year old woman with non-small cell lung cancer who accidentally received 225 mg/m(2 )of cisplatin, which was threefold the dose as scheduled, within a 3-day period. Two days later, the patient presented with hearing loss, severe nausea and vomiting, acute renal failure as well as elevated liver enzymes. In addition, she developed a severe myelodepression. After plasmapheresis on two consecutive days and vigorous supportive treatment, the toxicity-related symptoms improved and the patient recovered without any sequelae. CONCLUSION: To date, no general accepted guidelines for the treatment of cisplatin overdoses are available. Along with the experience from other published cases, our report shows that plasmapheresis is capable of lowering cisplatin plasma and serum levels efficiently. Therefore, plasma exchange performed as soon as possible can ameliorate all side effects of a cisplatin overdose and be a potential tool for clinicians for treatment. However, additional intensive supportive treatment-modalities are necessary to control all occurring side effects

Dropout in a longitudinal, cohort study of urologic disease in community men

BACKGROUND: Reasons for attrition in studies vary, but may be a major concern in long-term studies if those who drop out differ systematically from those who continue to participate. Factors associated with dropout were evaluated in a twelve-year community-based, prospective cohort study of urologic disease in men. METHODS: During 1989–1991, 2,115 randomly selected Caucasian men, ages 40–79 years from Olmsted County, Minnesota were enrolled and followed with questionnaires biennially; 332 men were added in follow-up. A random subset (~25%) received a urologic examination. Baseline characteristics including age, benign prostatic hyperplasia (BPH) symptoms, comorbidities, and socioeconomic factors were compared between subjects who did and did not participate after the twelfth year of follow-up. RESULTS: Of the 2,447 men, 195 died and were excluded; 682 did not participate in 2002. Compared with men in the 40–49 year age group, men ≥ 70 years of age at baseline had a greater relative odds of dropout, 2.65 (95% CI: 1.93, 3.63). In age-adjusted analyses, relative to men without stroke, men who had suffered a stroke had a higher odds of dropout, age-adjusted OR 3.07 (95% CI: 1.49, 6.33). Presence of at least one BPH symptom was not associated with dropout, (age-adjusted OR 1.12 (95% CI: 0.93, 1.36)). CONCLUSION: These results provide assurance that dropout was not related to primary study outcomes. However, factors associated with dropout should be taken into account in analyses where they may be potential confounders