Routine eGFR Research Articles

The Factors Associated With Mutant Epidermal Growth Factor Receptor Positivity in Patients With Lung Cancer: A Study From a Tertiary Care Center in Pakistan.

Objective In this study, we sought to elucidate the relationship between demographic and clinical factors and epidermal growth factor receptor tyrosine kinase (EGFR-TK) positivity in patients with advanced-stage lung cancer at a tertiary care center in Pakistan. Methods This analytical cross-sectional study was conducted from February 2020 to July 2023 at Shaikh Zayed Hospital, Lahore, Pakistan, in collaboration with the Centre of Excellence in Molecular Biology (CEMB), University of the Punjab. The study included 70 consecutive patients with advanced-stage lung cancer, and aimed to identify common EGFR mutations (Exon 19 deletion and Exon 21 L858R mutation), determine their frequency, and correlate EGFR-TK mutation positivity with clinical and non-clinical factors. Tissue acquisition and processing involved bronchoscopy, pleuroscopy, or percutaneous ultrasound-guided lung mass biopsy, followed by molecular analysis using polymerase chain reaction (PCR) extraction, amplification, and sequencing. The study employed convenient sampling and included adults aged over 18 years with histologically confirmed lung cancer. Results We enrolled 70 lung cancer patients, with a mean age of 60.87 years, and a male-to-female ratio of 1.4:1. The majority (61.4%) had adenocarcinoma, and 34.3% harbored a mutant EGFR-TK. EGFR mutations were more common in adenocarcinoma (91.7%) and associated with female non-smokers. Binary logistic regression analysis revealed that age <50 years and adenocarcinoma type were significant predictors of EGFR mutations. We found no significant associations with gender, smoking status, or other variables. These findings have implications for personalized treatment approaches in lung cancerpatients. Conclusions Our study reveals a high frequency of occult EGFR mutations (Exon 19 deletion and Exon 21 L858R mutation) in non-small cell lung cancer (NSCLC) patients, particularly among male smokers and female non-smokers. These findings emphasize the importance of routine EGFR mutation testing to identify patients who may benefit from targeted therapies, ultimately improving treatment outcomes.

Changes in renal function over time in outpatients with eGFR ≥ 30 mL/min/1.73 m2: implication for timing of renal function testing before contrast-enhanced CT imaging

PurposeTo evaluate the associations between comorbidities and kidney function decline at 6-month and 1-year follow-up in outpatients with initial estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2.Materials and methodsOutpatients aged 18 and older with confirmed diagnosis, who had eGFR ≥ 30 mL/min/1.73 m2 measured between April 2017 and March 2019, were included in this retrospective observational study. Of them, 30,595 included outpatients had 6-month eGFR test and 27,698 included outpatients had 1-year eGFR test. The outpatients were further divided into two groups based on initial eGFR: between 30 and 59 and ≥ 60 mL/min/1.73 m2. Impaired renal function was defined as eGFR declined to below 30 mL/min/1.73 m2. The comorbidities with P values less than 0.1 identified in univariable logistic regression models were entered into the multivariable analysis with backward selection, thereby identifying comorbidities that increased the risk of eGFR decline at 6-month and 1-year follow-up.ResultsOutpatients with initial eGFR between 30 and 59 mL/min/1.73 m2 were 175.94 times more likely to have eGFR decline at 6 months, and were 94.10 times more likely to have eGFR decline at 1 year, compared with their corresponding initial eGFR ≥ 60 counterparts. Multivariable logistic regression analyses disclosed that chronic kidney disease, hypertension, and heart failure were independent risk factors for eGFR decline in outpatients with initial eGFR between 30 and 59 mL/min/1.73 m2.ConclusionsOutpatients with initial eGFR ≥ 60 mL/min/1.73 m2 might not need routine eGFR test prior to contrast-enhanced CT scan for 1 year. In addition, chronic kidney disease, hypertension, and heart failure increased the risk of declined renal function, particularly, in outpatients with initial eGFR between 30 and 59 mL/min/1.73 m2.

Molecular follow-up of first-line treatment by osimertinib in lung cancer: Importance of using appropriate tools for detecting EGFR resistance mutation C797S

The C797S mutation encoded by EGFR exon 20 is classically observed as a tertiary event in EGFR-mutant non-small-cell lung carcinoma (NSCLC) primarily treated by first generation tyrosine kinase inhibitors (TKI) and secondarily treated by third-generation TKI, such as osimertinib, if the EGFR-T790M resistance mutation is detected. Recently, significant prolonged progression free survival has been observed following first-line osimertinib, in EGFR-mutant NSLC. While mechanisms of molecular resistance to first-generation TKI have been well studied, little is known about resistance induced by primary third-generation TKI treatments. We report the case of a 65 year-old female treated by first-line osimertinib for a multimetastatic exon 19-EGFR-mutant NSCLC. EGFR-C797S resistance mutation and PIK3CA mutation were detected together with the remaining EGFR-exon 19 deletion. This observation provides insights of acquired resistance to first line-osimertinib. It also highlights the importance of making molecular platforms which perform routine EGFR testing in lung cancer aware of the kind of therapeutic protocols given to the patient. Indeed, for rapid results or low-costs procedures, some targeted methods specifically targeting T790M may be used at relapse and may overlook alterations such as C797S or PIK3CA mutations. Targeted next generation sequencing is therefore a recommended option.

Microsecond-timescale MD simulation of EGFR minor mutation predicts the structural flexibility of EGFR kinase core that reflects EGFR inhibitor sensitivity

Approximately 15–30% of patients with lung cancer harbor mutations in the EGFR gene. Major EGFR mutations (>90% of EGFR-mutated lung cancer) are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs). Many uncommon EGFR mutations have been identified, but little is known regarding their characteristics, activation, and sensitivity to various EGFR-TKIs, including allosteric inhibitors. We encountered a case harboring an EGFR-L747P mutation, originally misdiagnosed with EGFR-del19 mutation using a routine diagnostic EGFR mutation test, which was resistant to EGFR-TKI gefitinib. Using this minor mutation and common EGFR-activating mutations, we performed the binding free energy calculations and microsecond-timescale molecular dynamic (MD) simulations, revealing that the L747P mutation considerably stabilizes the active conformation through a salt-bridge formation between K745 and E762. We further revealed why several EGFR inhibitors, including the allosteric inhibitor, were ineffective. Our computational structural analysis strategy would be beneficial for future drug development targeting the EGFR minor mutations.

Comparison and development of machine learning tools in the prediction of chronic kidney disease progression

BackgroundUrinary protein quantification is critical for assessing the severity of chronic kidney disease (CKD). However, the current procedure for determining the severity of CKD is completed through evaluating 24-h urinary protein, which is inconvenient during follow-up.ObjectiveTo quickly predict the severity of CKD using more easily available demographic and blood biochemical features during follow-up, we developed and compared several predictive models using statistical, machine learning and neural network approaches.MethodsThe clinical and blood biochemical results from 551 patients with proteinuria were collected. Thirteen blood-derived tests and 5 demographic features were used as non-urinary clinical variables to predict the 24-h urinary protein outcome response. Nine predictive models were established and compared, including logistic regression, Elastic Net, lasso regression, ridge regression, support vector machine, random forest, XGBoost, neural network and k-nearest neighbor. The AU-ROC, sensitivity (recall), specificity, accuracy, log-loss and precision of each of the models were evaluated. The effect sizes of each variable were analysed and ranked.ResultsThe linear models including Elastic Net, lasso regression, ridge regression and logistic regression showed the highest overall predictive power, with an average AUC and a precision above 0.87 and 0.8, respectively. Logistic regression ranked first, reaching an AUC of 0.873, with a sensitivity and specificity of 0.83 and 0.82, respectively. The model with the highest sensitivity was Elastic Net (0.85), while XGBoost showed the highest specificity (0.83). In the effect size analyses, we identified that ALB, Scr, TG, LDL and EGFR had important impacts on the predictability of the models, while other predictors such as CRP, HDL and SNA were less important.ConclusionsBlood-derived tests could be applied as non-urinary predictors during outpatient follow-up. Features in routine blood tests, including ALB, Scr, TG, LDL and EGFR levels, showed predictive ability for CKD severity. The developed online tool can facilitate the prediction of proteinuria progress during follow-up in clinical practice.

The Importance of Novel Inflammatory Biomarkers in Renal Disease.

Kidney disease, whether acute or chronic, represents a major health hazard. Acute kidney injury (AKI) detection is based mainly on serum creatinine, which is considered to delay prompt diagnosis and management, thus increasing substantially patient morbidity and mortality and prolonged hospitalization. Several biomarkers have been evaluated as early prognostic markers of AKI. However, the vast majority of them are still far from being implicated into clinical practice. On the other hand, routine eGFR estimation and proteinuria monitoring have contributed to previous identification of chronic kidney disease (CKD). Hence, more sensitive and specific biomarkers are needed to enable us recognize individuals at increased risk for progression of CKD to end-stage renal disease (ESRD) and occurrence of cardiovascular complications. This review focuses on the most important novel inflammatory biomarkers that have emerged for early prediction, monitoring and management of kidney disease.

Improving the measurement of longitudinal change in renal function: automated detection of changes in laboratory creatinine assay

IntroductionRenal function is reported using the estimates of glomerular filtration rate (eGFR). However, eGFR values are recorded without reference to the particular serum creatinine (SCr) assays used to derive them,...

Whole-genome sequencing of asian lung cancers: second-hand smoke unlikely to be responsible for higher incidence of lung cancer among Asian never-smokers.

Asian nonsmoking populations have a higher incidence of lung cancer compared with their European counterparts. There is a long-standing hypothesis that the increase of lung cancer in Asian never-smokers is due to environmental factors such as second-hand smoke. We analyzed whole-genome sequencing of 30 Asian lung cancers. Unsupervised clustering of mutational signatures separated the patients into two categories of either all the never-smokers or all the smokers or ex-smokers. In addition, nearly one third of the ex-smokers and smokers classified with the never-smoker-like cluster. The somatic variant profiles of Asian lung cancers were similar to that of European origin with G.C>T.A being predominant in smokers. We found EGFR and TP53 to be the most frequently mutated genes with mutations in 50% and 27% of individuals, respectively. Among the 16 never-smokers, 69% had an EGFR mutation compared with 29% of 14 smokers/ex-smokers. Asian never-smokers had lung cancer signatures distinct from the smoker signature and their mutation profiles were similar to European never-smokers. The profiles of Asian and European smokers are also similar. Taken together, these results suggested that the same mutational mechanisms underlie the etiology for both ethnic groups. Thus, the high incidence of lung cancer in Asian never-smokers seems unlikely to be due to second-hand smoke or other carcinogens that cause oxidative DNA damage, implying that routine EGFR testing is warranted in the Asian population regardless of smoking status.

Impact of routine reporting of estimated glomerular filtration rate using the CKD-EPI formula in a community population: A cross-sectional cohort study.

Most laboratories are moving to report estimated glomerular filtration rates (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. However, data on the prevalence of chronic kidney disease (CKD) in the population and its economic impact have to date been modelled using data derived from the modification of diet in renal disease (MDRD) equation. Evaluating the impact of CKD-EPI on prevalence has important implications for referral patterns and health expenditure. eGFR were calculated from 2 295313 creatinine results from 833334 patients using the MDRD and CKD-EPI formulae. The proportion of patients in each CKD stage was determined and annual rates of change of eGFR in patients assigned to a new CKD stage compared with their previous CKD stage calculated. The effects of age on eGFR were assessed. Reporting of eGFR using the CKD-EPI equation reduced the prevalence of CKD stages III-V from 9.2% to 7.6%. A total of 181126 patients were reclassified using CKD-EPI with 171298 changing to a better CKD stage. Reclassification rates were highest in CKD stages II and III. Patients reclassified from stage III to II tended to be younger or female. eGFR declines rapidly after the age of 60. Introduction of routine eGFR reporting using the CKD-EPI formula will reduce the population prevalence of CKD. CKD-EPI reporting better identifies patients at risk of further decline in renal function. Improvement in the classification should reduce unnecessary costs related to surveillance and referral. The impact of ageing on renal function should be appreciated.

Biomarkers (BM) France: Results of routine EGFR, HER2, KRAS, BRAF, PI3KCA mutations detection and EML4-ALK gene fusion assessment on the first 10,000 non-small cell lung cancer (NSCLC) patients (pts).

8000 Background: Personalized medicine is now a reality for advanced NSCLC pts on the basis of routine screening for EGFR mutation and ALK gene fusion assessment. The French NCI (INCa) also decided to additionally fund the routine assessment of 4 additional BM (HER2, KRAS, BRAF, PI3KCA). Methods: Starting on April 2012, these BM analyses were prospectively collected into a database head by the IFCT (www.ifct.fr) with 15-20,000 analyses awaited after one year. The physicians prescribing each of these BM analyses were then connected to this database and were asked to regularly complete epidemiological, clinical and therapeutic data for each corresponding patient. Results: 10,000 BM analyses were collected and entered into the BM France database at the time of this first analysis (January 2013). On the basis of available data, the patients were mainly male (63.8%), (ex)smokers (83.3%) and stage IV pts (64%). The tumors were mainly adenocarcinomas (76.1%). The samples for BM analysis were collected under bronchoscopy, surgery or transthoracic biopsy in 27.4, 28.1 and 24.2%, respectively. The 10,000 molecular profiles were characterized by 9.4% EGFR (including 0.8% EGFR resistant), 0.9% HER2, 26.9% KRAS, 1.6% BRAF, and 2.6% PI3KCA mutated and 4.0% EML4-ALK fusion genes. Double mutations were seen in 0.9% of the tumors. On January 2013, data on treatment were available for 18.6% of patients among whom 56.9% of patients received a treatment according to their molecular profile (labeled drugs or bio-guided trials). Updated data will be presented during the meeting. Conclusions: Biomarkers France is the largest ever conducted biomolecular study on advanced NSCLC patients and provides solid data on the value of a nationwide BM screening policy for NSCLC patients.

Economic analysis of TORCH: Erlotinib versus cisplatin and gemcitabine as first-line therapy for advanced non-small cell lung cancer (NSCLC).

e19031 Background: The TORCH (“Tarceva or Chemotherapy”) randomized phase III trial demonstrated that first-line erlotinib compared to cisplatin/gemcitabine in unselected advanced NSCLC patients yielded inferior survival, but no major differences in global quality of life. We determined the incremental costs and utility between arms, including in the EGFR mutation positive subgroup. Methods: Direct medical resource utilization data and EQ5D scores were collected prospectively during the trial. Costs for medications, outpatient visits, investigations and toxicity management including hospitalization were determined, and presented in 2012 Canadian dollars (CAD). The outcome of the analysis was the incremental cost per life year and quality-adjusted life-years (QALYs) gained. Results: The incremental mean cost per patient in the chemotherapy arm was $4,163CAD, largely related to drug and outpatient visit costs, while higher costs from hospitalization and adverse events were seen in the erlotinib arm. Mean overall and quality-adjusted survival times were longer in the chemotherapy arm. In the subset of patients with EGFR mutations (n=39), mean survival was not significantly different between arms (1.35 years for chemotherapy versus 1.29 years for erlotinib, p-value=0.86), but quality-adjusted survival favoured erlotinib treatment (i.e. mean QALYs were 1.04 for chemotherapy, and 1.40 for erlotinib). The incremental cost-effectiveness ratio for initial erlotinib in the EGFR mutation positive subgroup was $30,301 CAD per QALY. Conclusions: Initial chemotherapy in unselected advanced NSCLC yields better survival at minimal increased cost compared to erlotinib. In the EGFR mutation positive subgroup, first-line erlotinib is cost effective compared to first-line platinum doublet therapy, supporting routine EGFR genotyping to select first-line therapy in advanced NSCLC.

Primary lung adenocarcinoma occurring in a PTEN related syndrome (Cowden's disease): Routine EGFR sequencing also highlights two rare somatic mutations S768I and V769L

Cowden's syndrome is a rare autosomal dominant disorder that has been linked to germline mutations in the phosphatase and TENsin homolog (PTEN) gene. PTEN is a tumour suppressor gene that negatively regulates the PI3K–AKT–mTOR pathway. Cowden's syndrome is a multi-system disease with increased risks for a number of malignancies but very rarely for lung cancer.A systematic follow-up chest CT scan was performed to a 42 year's old female, light smoker. It showed a 20mm opacity of the left upper pulmonary lobe. Differential diagnose with benign tumours (such as hamartoma) was carefully searched. Procedures led to the diagnosis of a primitive lung adenocarcinoma. EGFR sequencing shows two rare somatic mutations (S768I and V769L).Lack of expression of PTEN is a non-sufficient condition leads to lung cancer formation alone. Nevertheless, it increases cell oncogenic potential. PTEN lacking in non small cell lung cancer is a frequent issue. It could be an alternative mechanism of non-efficacy of EGFR-TKI in cells with a sensitizing EGFR mutation.This case report, a very rare entity: a patient with a PTEN germline mutation and a lung adenocarcinoma harbouring two concomitant rare somatic mutations of EGFR. This observation comforts PTENs role in lung oncogenesis.

Direct serum and tissue assay for EGFR mutation in non-small cell lung cancer by high-resolution melting analysis

Biological therapy with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have noted promising outcomes for patients with non-small cell lung carcinoma (NSCLC), especially those with mutated EGFR. Tissue EGFR gene mutation testing can predict the benefit of taking a first-line EGFR-TKI, thus, allowing the physician to prescribe the most suitable therapy. Unfortunately, most lung cancer patients, especially NSCLC patients present with advanced disease that is surgically unresectable. The goal of this study was to develop high-resolution melting (HRM) assays to detect EGFR mutations in exons 18 to 21, compare their sensitivity and concordance to direct sequencing, and evaluate the feasibility and reliability of serum as a tissue alternate for routine EGFR mutation screening. EGFR mutations of 126 Formalin-Fixed Paraffin-Embedded (FFPE), 47 fresh frozen tissues and from 47 matched pre-operation serum specimens of NSCLC patients were screened by the HRM assays. EGFR mutations by HRM were confirmed through sequencing. We found 78 EGFR mutations in 70 FFPE tissues, 25 EGFR mutations in 24 fresh frozen tissues, with a mutation rate of 55.56% (70/126) and 51.06% (24/47), respectively. Most mutations were correctly identified by sequencing. EGFR mutations were detected in 22 serum samples from 24 tissue EGFR mutation-positive patients. The concordance rate between serum and tissue in EGFR mutation screening was 91.67%. We conclude that the HRM assay can provide convincing and valuable results both for serum and tissues samples, thus, it is suitable for routine serum EGFR mutation screening for NSCLC patients, especially those surgically unresectable.

Research and Standard Care: Lung Cancer in China

China has an enormous burden from rising tobacco consumption and lung cancer incidence. Governmental intervention on lung cancer prevention is insufficient, and both incidence and mortality related to lung cancer are still on the rise. Treatment guidelines are available, but heterogeneity in the quality of care between centers, especially the disparity between urban and rural areas, have resulted in inconsistent care to patients with lung cancer. Despite knowledge on molecular-targeted therapy, only a small fraction of patients have access to routine EGFR mutation analysis. Platinum-based doublet chemotherapy remains the most commonly used regimen irrespective of mutation status. On a positive note, both clinical and translational research on lung cancer are in rapid progress. The Chinese Thoracic Oncology Group (CTONG) has already contributed substantially to the care of patients with lung cancer and is expected to continue in the trend.

Reporting of the estimated glomerular filtration rate was associated with increased use of angiotensin-converting enzyme inhibitors and angiotensin-II receptor blockers in CKD

Many guidelines suggest that angiotensin-converting enzyme inhibitors and angiotensin-II receptor antagonists (collectively referred to as renin, angiotensin, aldosterone system blockers (RAAS blockers)) are the preferred treatment for hypertension in most patients with chronic kidney disease (CKD). Improving the recognition of CKD with the introduction of eGFR reporting was intended to have more patients recognized with and treated for this disease. To quantify this, we examined trends in RAAS-blocker use over an 88-month period before and after routine eGFR reporting in southwestern Ontario, Canada. An intervention analysis with seasonal time-series modeling on linked health administrative data for 45,361 ambulatory residents with CKD (eGFR stages 3-5) older than 65 years was performed with a primary outcome of RAAS-blocker usage. The reporting of eGFR was associated with a significant increase in the use of RAAS blockers, as the prescription rate was 571 per 1000 patients with CKD prior to reporting but improved to 607 per 1000 after reporting. There was a significant increase in RAAS-blocker use attributable to eGFR reporting of 19 per 1000 CKD patients. Since about 8% of the adult population has CKD, this equates to about 15,200 new patients receiving RAAS-blocker treatment by 1 year after the introduction of eGFR reporting in community laboratories. Thus, eGFR reporting contributes to improved, guideline-appropriate care of older patients with CKD.

The prevalence of renal anaemia in new dialysis patients before and after routine eGFR reporting: A single centre experience

Background: In March 2006, evidence-based guidelines for the management of chronic kidney disease (CKD) in adults in the UK were published including the recommendation that kidney function should be assessed by formula-based estimation of glomerular filtration rate (eGFR), using the 4-variable modification of diet in renal disease (MDRD) equation. The purpose of this study was to evaluate whether or not improved assessment of renal function by eGFR reporting followed by an intensive local education programme and local protocols affected the prevalence of renal anaemia at the time of starting dialysis for the first time. Methods: To do this, we collected data on haemoglobin levels in people starting renal replacement therapy (RRT) for the first time, during the 12 months immediately preceding eGFR reporting. We collected data for a further 12 months after eGFR was introduced; starting 6 months after the official date of introduction. Results: The proportion of people with Haemoglobin (Hb) levels ≥ 11 g/dl increased from 25.4% in the pre-eGFR era to 41.1% in the post eGFR era. In addition, average Hb levels were better in the post eGFR era (9.89 vs. 10.2 g/dl) although this did not reach statistically significance. In general, in the post eGFR era, people known to the renal services for less than 1 month prior to starting RRT had the worst Hb levels (8.7 g/dl). Hb levels were higher according to time of referral prior to RRT with peak Hb levels in people referred 6 - 9 months (11.5 g/dl) beforehand. Conclusions: It has been suggested that estimated GFR reporting may be associated with earlier recognition of kidney disease. This may have contributed to the increase in the proportion of people with optimal haemoglobin (≥11 g/dl) levels prior to starting renal replacement therapy. However a large number still start renal replacement therapy with severe anaemia. The increase in Hb levels in the post eGFR era could also result from better anaemia care which could be an effect of other guideline implementation.

Characterizing pre-dialysis care in the era of eGFR reporting: a cohort study

BackgroundChronic kidney disease (CKD) is a common disorder associated with increased morbidity and mortality. Primary care physicians (PCPs) care for the majority of pre-dialysis CKD patients; however, PCPs often do not recognize the presence of CKD based on serum creatinine levels. Prior studies suggest that PCPs and nephrologists deliver suboptimal CKD care. One strategy to improve disease awareness and treatment is estimated glomerular filtration rate (eGFR) reporting. We examined PCP and nephrologist CKD practices before and after routine eGFR reporting.MethodsWe conducted a retrospective cohort study of patients with CKD 3b-4 (eGFR < 45) seen at a university-based, outpatient primary care clinic. Using a chi-square or Fisher's exact test, we compared co-management rates, renal protective strategies, CKD documentation, and laboratory processes of care in 274 patients and 266 patients seen in a 6-month period prior to and following eGFR implementation, respectively.ResultsCKD co-management increased from 22.6% pre-eGFR to 48.5% post-eGFR (P < 0.0001). eGFR reporting did not improve angiotensin converting enzyme inhibitor or angiotensin receptor blocker use or quantitative urinary testing. However, non-steroidal anti-inflammatory drug avoidance (pre-eGFR 81.8% vs. post- eGFR 90.6%, P = 0.003) and phosphorus and parathyroid hormone testing improved (pre-eGFR vs. post-eGFR: 32.5% vs. 51.5%, P < 0.0001; 12.4% vs. 36.1%, P < 0.0001 respectively).ConclusionsA marked increase in CKD co-management was observed following eGFR implementation. Although some improvements in processes of care were noted, this did not include angiotensin converting enzyme inhibitor or angiotensin receptor blocker use. Overall care remained suboptimal despite eGFR reporting; further strategies are needed to improve PCP and nephrologist CKD care.

Albumin:Creatinine Ratio – A Flawed Measure? The Merits of Estimated Albuminuria Reporting

Current guidelines illogically recommend that a different approach is taken to the correction for creatinine generation rate when estimating glomerular filtration rate (GFR) and when interpreting urine albumin:creatinine ratio (ACR). Age, gender and race are routinely used to adjust for predicted muscle mass in GFR estimation, even though estimated GFR is expressed per unit body surface area. Conversely, ACR is at most adjusted with the use of gender-specific classification thresholds. This difference is surprising since the proportional effect of muscle mass on serum and urine creatinine is identical. Failure to adjust for creatinine generation rate compromises ACR, potentially adversely affecting management decisions and mislabelling individuals as having/not having CKD. A greater ACR is also a marker of low muscle mass, which has confounding prognostic effects. Determination of the optimal method to adjust ACR for estimated muscle mass should improve its performance. Routine reporting of the resulting ‘estimated albumin excretion rate’, as for routine eGFR reporting, would remove the need for gender-specific thresholds.

PUK22 HEALTH ECONOMIC ASPECTS OF USING SERUM CYSTATIN C FOR EARLY DETECTION OF CHRONIC KIDNEY DISEASE IN TYPE 2 DIABETICS IN GERMANY

CONTACT: Dr. Evelyn Walter IPF Institute for Pharmaeconomic Research Wolfgengasse 4/7 1010 Vienna, Austria Tel +43-1-5132007-13 Fax +43-1-5132007-15 Email: e.walter@ipf-ac.at Web: www.ipf-ac.at Objectives Diabetic nephropathy is a serious and common complication in diabetic patients. However the onset and the course of the diabetic nephropathy can be favourably influenced by appropriate therapy when detected early. In 2004 the independent international Kidney Disease Improving Global Outcome Organisation (KDIGO) recommended 2 laboratory tests for an early detection of chronic kidney disease (CKD): determination of serum creatinine to estimate glomerular filtration rate (eGFR) using the simplified equation derived from the Modification of Diet in Renal Disease Study (MDRD) and determination of proteinuria preferably microalbuminuria corrected for urine creatinine. Creatinine as a marker for eGFR has metabolic and technical limitations, especially in patients with only mild impairment of kidney function. As an alternative marker serum Cystatin C (CysC) has been proposed for early detection of CKD. Methods We developed a cost-utility-model to simulate the long-term consequences of diabetic nephropathy using CysC instead of creatinine to monitor renal function. Markov-modelling-techniques were used to describe complications and disease progression; one arm assessed the costs and effects of CysC reporting, disease progression and complications, and the other assessed the cost and effect of routine eGFR reporting. Probabilities of complications were derived from clinical and epidemiological studies. The model includes eleven a priori defined health states to describe the disease progression and occurrence of adverse events. Disease progression leads to a passover to the next health state; the others remain. The Markov-cycle length is one year.

Chronic kidney disease management in an academic internal medicine clinic

We sought to evaluate the current state of chronic kidney disease (CKD) management in our academic internal medicine clinic. A retrospective review was carried out involving all patients with laboratory evidence of CKD enrolled in our clinic. We evaluated the rate of CKD recognition as well as compliance with standard guidelines. We further subdivided our results based on physician training level, presence of diabetes, recognition of CKD, age, and race. Factors that significantly improved recognition and treatment of CKD in our study included presence of diabetes (p < 0.001), black race (p = 0.013), younger age (p = 0.004), and treatment by a resident physician (p = 0.009). Recognition of stage 3 CKD was associated with significant increases in urine protein analysis (p < 0.001) and nephrology consultation (p < 0.001). Chronic kidney disease remains under-recognized and undertreated despite well-publicized guidelines and widespread use of routine eGFR reporting.