Screening for renal disease using serum creatinine: who are we missing?

BACKGROUND: Appropriate management and timely referral of patients with early renal disease often depend on the identification of renal insufficiency by primary care physicians. Serum creatinine (SCr) levels are frequently used as a screening test for renal dysfunction; however, patients can have significantly decreased glomerular filtration rates (GFR) with normal range SCr values, making the recognition of renal dysfunction more difficult. This study was designed to estimate the prevalence of patients who have significantly reduced GFR as calculated by the Cockcroft-Gault (C-G) formula, but normal-range SCR: METHODS: The study included 2781 outpatients referred by community physicians to an urban laboratory network for SCr measurement. GFR was estimated using the C-G formula. Patients were grouped according to the concordance of SCr level abnormalities (abnormal >130 micromol/l) with significantly abnormal C-G values (abnormal or =70 years old, 12.6% 60-69 years old, and 1.2% 40-59 years old. Analysis of historical available laboratory data for patients with abnormal SCr and abnormal C-G values showed that 2 years prior to the study period, 72% of this group had abnormal SCr, while 18% had normal SCr with abnormal C-G values, and 10% had normal SCr with normal C-G values. CONCLUSIONS: This study documents the substantial prevalence of significantly abnormal renal function among patients identified by laboratories as having normal-range SCR: Including calculated estimates of GFR in routine laboratory reporting may help to facilitate the early identification of patients with renal impairment.     

晚期妊娠妇女尿脱氧吡啶啉与尿肌酐比值的测定及临床意义

目的了解正常晚期妊娠(晚妊)妇女尿脱氧吡啶啉(deoxypyridinoline,DPD)和尿肌酐(creatinine,Cr)比值(DPD/Cr)及其与骨钙代谢关系.方法测定80例正常晚妊妇女(1ate normal pregnant women,LPW)及22例正常非孕妇女(normal nonpregnant women,NPW)尿DPD、尿Cr和血钙离子浓度(serum calcium,SCa),并计算DPD/Cr.尿DPD浓度用化学发光法测定.结果晚妊妇女尿DPD/Cr比值明显增高,与正常非孕妇女比较,差异有显著性(P＜0.001),晚妊妇女SCa与正常非孕妇女比较略有下降,但差异无显著性(P＞0.05).结论尿DPD/Cr较SCa能更准确、灵敏、特异地反映体内缺钙状况,是孕期保健中值得推荐的骨钙代谢监测指标.     

Risk factors of contrast-induced nephropathy after percutaneous coronary intervention: a retrospective analysis

ObjectiveContrast-induced nephropathy (CIN) is a serious complication in patients with acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). This study aimed to analyze the potential risk factors for CIN in patients undergoing PCI.MethodsPatients with ACS who underwent PCI treatment from January 2017 to January 2020 were selected. The patients’ characteristics and medical information were collected and compared.ResultsA total of 1331 patients undergoing PCI were included. The incidence of CIN was 15.33%. Logistic regression analyses showed that a left ventricular ejection fraction ≤45% (odds ratio [OR] 4.18, 95% confidence interval [CI] 1.10–7.36), serum creatinine levels ≤60 μmol/L (OR 3.03, 95% CI 1.21–5.57), age ≥65 years (OR 2.75, 95% CI 1.32–4.60), log N-terminal pro-B-type natriuretic peptide levels ≥2.5 pg/mL (OR 2.31, 95% CI 1.18–5.13), uric acid levels ≥350 μmol/L (OR 2.29, 95% CI 1.04–5.30), emergency percutaneous intervention (OR 1.35, 95% CI 0.34–3.12), and triglyceride levels ≤1.30 mmol/L (OR 1.10, 95% CI 0.01–2.27) were independent risk factors for CIN in patients who underwent PCI.ConclusionsEarly prevention is required to reduce the occurrence of CIN in patients who undergo PCI and have risk factors for CIN.     

Clopidogrel,prasugrel, ticagrelor or vorapaxar in patients with renal impairment: do we have a winner?

The optimal utilization of antiplatelet therapy in patients with renal impairment (RI) following acute coronary syndromes (ACS) represents an urgent, unmet and yet unsolved need with regards to the choice of agents, duration of treatment and potential dose/regimen adjustment. The lack of any large randomized trials designed and powered specifically in such high-risk patients, absence of the uniformed efficacy and safety data reporting policy to the FDA and endless overoptimistic publications based on post hoc analyses of primary trials sometimes exaggerating benefits and hiding risks, clouds reality. In addition, triaging RI patients is problematic due to ongoing kidney deterioration and the fact that such patients are prone to both vascular occlusions and bleeding. The authors summarize available FDA-confirmed evidence from the latest trials with approved antiplatelet agents, namely clopidogrel (CAPRIE, CURE, CREDO, CLARITY, CHARISMA); prasugrel (TRITON, TRILOGY); ticagrelor (PLATO, and PEGASUS); and vorapaxar (TRACER and TRA2P) in RI patient cohorts on top of aspirin as part of dual antiplatelet therapy (DAPT). We deliberately avoided any results unless they were verified by the FDA, with the exception of the recent PEGASUS, since Agency reviews are not yet available. Despite differences among the trials and DAPT choices, RI patients universally experience much higher (HR = 1.3–3.1) rates of primary endpoint events, and bleeding risks (HR = 1.7–3.6). However, only ticagrelor increases creatinine and uric acid levels above that of clopidogrel; has the worst incidence of serious adverse events, more adverse events, and inferior outcomes in patients with severe (eGFR <30 ml/min), especially in the lowest (eGFR <15 ml/min) RI subsets. Clopidogrel, prasugrel and vorapaxar appear safer. Moreover, less aggressive half dose (5 mg/daily) prasugrel and strict DAPT, are well justified in RI, but not predominantly triple strategies with vorapaxar as tested in TRA2P and especially in TRACER. In conclusion, data from clinical trials, their sub-studies and affiliated FDA reviews indicate that RI cause more vascular occlusions and bleeding in ACS patients treated with DAPT. Among the novel antiplatelet agents, prasugrel and vorapaxar, but probably not ticagrelor, offer advantage in RI patients.     

Selection of Routine Method for Determination of Glomerular Filtration Rate in Adult Patients

The precision and reproducibility of three different clearance methods as used in clinical routine assessment of glomerular filtration rate (GFR) were investigated in 51 patients: total [51Cr]EDTA plasma clearance (E); 24-hr endogenous creatinine clearance (C); and creatinine clearance estimated from the plasma creatinine concentration, weight, and sex-and age-dependent mean creatinine excretion rate (c). The precision and reproducibility (coefficient of variation) for single determinations were, in patients with E ≥ 30 ml/min, 5.5 and 4.1% (E); 26.9% (C); and 23.2 and 11.0% (c). The corresponding figures for E < 30 ml/min were 11.6 and 11.5% (E); 21.9% (C); and 21.4 and 6.5% (c). The precision of C could not be ameliorated by excluding single deviating determinations, but only by excluding patients for whom the precision of 15.5% for mean of three determinations of C (total material) could be reduced to 10% by excluding 25% of the patients. The present data indicate that E in most cases is the method of choice for assessment of GFR in clinical routine work. For changes in renal function, especially at low functional levels, c may be of value.     

Ischemia/Reperfusion-Induced Renal Failure in Rats as a Model for Evaluating Cell Therapies

Chronic renal failure is a devastating disease that leads to a multitude of complications. Cell therapy has emerged as a potential treatment modality for renal failure. However, efficacy testing on systemic renal function has been challenging due to the limited availability of reliable models that are fully characterized. In this study, we investigated the possibility of using renal ischemia/reperfusion (I/R) injury as a viable model for testing cell therapies. We examined functional and pathological changes in rat kidneys that were exposed to different ischemia times. Male Lewis rats were divided into five groups. Renal failure was induced by clamping both renal pedicles for combinations of 60, 75, and 90 min, followed by reperfusion. Age-matched healthy rats served as controls. Blood was collected at regular intervals for serum chemistry, and kidneys were harvested at the same intervals for histomorphological assessment. Serum creatinine levels of the animals with I/R injury increased significantly after 3 days and returned to normal levels at 4 weeks. Histologically, kidney tissue showed progressive glomerular and tubular deterioration with varying degrees of fibrosis. Animals exposed to 75- and 90-min ischemia combination times consistently generated more severe injury than the 60-min ischemia period. However, these groups resulted in a high mortality rate. A model in which one kidney is exposed to a shorter ischemia time (60 or 90 min) resulted in sustained renal damage with a lower mortality rate. This study shows that kidneys exposed to I/R result in renal tissue damage as well as decreased renal function. This model can be used to study both the short-term and longer-term effects of kidney disease by varying the length of the ischemic time. In particular, the use of longer ischemic times (75 and 90 min) could be used to study new therapies for acute renal disease, whereas shorter ischemic times (60 min) could be used to study therapies for chronic renal insufficiency.