Estimated Glomerular Filtration Rate (eGFR): A Serum Creatinine-Based Test for the Detection of Chronic Kidney Disease and its Impact on Clinical Practice

Abstract Chronic kidney disease (CKD) is an important epidemic and public health problem that is associated with a significant risk for vascular disease and early cardiovascular mortality as well as progression of kidney disease. Currently it is classified into five stages based on the glomerular filtration rate (GFR) as recommended by many professional guidelines. Radiolabelled methods for measuring GFR are accurate but not practical and can be used only on a very limited scale while the traditional methods require timed urine collection with its drawback of inaccuracy, cumbersomeness and inconvenience for the patients. However, the development of formula-based calculation of estimated GFR (eGFR) has offered a very practical and easy approach for converting serum creatinine value into GFR result taking into consideration patient's age, sex, ethnicity and weight (depending on equation type). The commonly used equations include Cockraft and Gault (1976), Modification of Diet in Renal Disease (MDRD) (1999) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (2009). It is the implementation of these equations particularly the MDRD that has raised the medical awareness in the diagnosis and management of CKD and its adoption by many guidelines in North America and Europe. The impact and pitfalls of each of these equations in the screening, diagnosis and management of patients with CKD are presented and discussed in this review

Reference Ranges of Serum Anti-Müllerian Hormone in Healthy Reproductive-aged Omani Women

Objectives: Anti-Müllerian hormone (AMH), a glycoprotein that belongs to the transforming growth factor-beta superfamily, is important for women’s health. We aimed to determine the age-specific reference range of serum AMH in healthy Omani women from reproductive ages to menopause. Methods: This cross-sectional cohort study was conducted among a group of healthy 20–50 years old Omani women. The participants were required to have body mass index < 32 kg/m2 regular periods, no history of chronic illness, polycystic ovary syndrome, or gynecological operation. They were also required to not be using any hormonal contraceptive. Serum concentrations of AMH, follicle-stimulating hormone, luteinizing hormone, progesterone, and hemoglobin A1c were measured. AMH-age nomogram and AMH levels were compared between the six selected age groups. Results: The subjects were 319 Omani women aged 20–50 years. Serum AMH concentrations were found to decrease progressively with increasing age. An exponential model defined as √AMH = 479.02 × 0.91age was selected to explain the reduction in AMH with age (R2 = 0.298). The median AMH levels were 26.61 pmol/L for those aged 20–25 years, 20.89 pmol/L for 26–30 years, 19.92 pmol/L for 31–35 years, 13.71 pmol/L for 36–40 years, 9.24 pmol/L for 41–45 years, and 0.68 pmol/L for 46–50 years. The recommended 2.5thto 97.5thpercentiles of AMH level, as reference ranges for various age groups, were found to be: 10.63–55.64 pmol/L (20–25 years), 3.74–61.88 pmol/L (26–30 years), 5.49–47.56 pmol/L (31–35 years), 2.15–48.91 pmol/L (36–40 years), 0.92–41.26 pmol/L (41–45 years), and 0.14–5.10 pmol/L (46–50 years).Conclusions: This study (the first in Oman) determined the age-specific reference ranges of serum AMH in healthy Omani women in the age range of 20–50 years

Comparison between Three Different Equations for the Estimation of Glomerular Filtration Rate in Omani Patients with Type 2 Diabetes Mellitus

Objectives: Estimated glomerular filtration rate (eGFR) is an important component of a patient’s renal function profile. The Modification of Diet in Renal Disease (MDRD) equation and the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation are both commonly used. The aim of this study was to compare the performance of the original MDRD186, revised MDRD175 and CKD-EPI equations in calculating eGFR in type 2 diabetes mellitus (T2DM) patients in Oman. Methods: The study included 607 T2DM patients (275 males and 332 females, mean age ± standard deviation 56 ± 12 years) who visited primary health centres in Muscat, Oman, during 2011 and whose renal function was assessed based on serum creatinine measurements. The eGFR was calculated using the three equations and the patients were classified based on chronic kidney disease (CKD) stages according to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines. A performance comparison was undertaken using the weighted kappa test. Results: The median eGFR (mL/min/1.73 m2) was 92.9 for MDRD186, 87.4 for MDRD175 and 93.7 for CKD-EPI. The prevalence of CKD stage 1 was 55.4%, 44.7% and 57% while for stages 2 and 3 it was 43.2%, 54% and 41.8%, based on MDRD186, MDRD175 and CKD-EPI, respectively. The agreement between MDRD186 and CKD-EPI (к 0.868) was stronger than MDRD186 and MDRD175 (к 0.753) and MDRD175 and CKD-EPI (к 0.730). Conclusion: The performances of MDRD186 and CKD-EPI were comparable. Considering that CKD-EPI-based eGFR is known to be close to isotopically measured GFR, the use of MDRD186 rather than MDRD175 may be recommended

Estimated Glomerular Filtration Rate (eGFR): A Serum Creatinine-Based Test for the Detection of Chronic Kidney Disease and its Impact on Clinical Practice

Chronic kidney disease (CKD) is an important epidemic and public health problem that is associated with a significant risk for vascular disease and early cardiovascular mortality as well as progression of kidney disease. Currently it is classified into five stages based on the glomerular filtration rate (GFR) as recommended by many professional guidelines. Radiolabelled methods for measuring GFR are accurate but not practical and can be used only on a very limited scale while the traditional methods require timed urine collection with its drawback of inaccuracy, cumbersomeness and inconvenience for the patients. However, the development of formula- based calculation of estimated GFR (eGFR) has offered a very practical and easy approach for converting serum creatinine value into GFR result taking into consideration patient’s age, sex, ethnicity and weight (depending on equation type). The commonly used equations include Cockraft and Gault (1976), Modification of Diet in Renal Disease (MDRD) (1999) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (2009). It is the implementation of these equations particularly the MDRD that has raised the medical awareness in the diagnosis and management of CKD and its adoption by many guidelines in North America and Europe. The impact and pitfalls of each of these equations in the screening, diagnosis and management of patients with CKD are presented and discussed in this review

Serum Myoglobin in Patients with Thyroid Dysfunction

Objectives: To assess the pattern of change in serum myoglobin concentration in subjects with thyroid dysfunction. Methods: Serum samples were selected from 150 subjects with suspected thyroid disorder who were referred to the Royal Hospital, Muscat, Oman. The subjects were 35 males and 115 females, aged 14-56 years with mean ± SD of 34.3 ± 12.7 years. They were classified on the basis of thyroid stimulating hormone (TSH) and free thyroxine (FT4) into 3 groups, each consisting of 50 subjects: hypothyroid, hyperthyroid, and euthyroid subjects. Results: The mean serum myoglobin concentration was higher in hypothyroid patients compared to hyperthyroid and euthyroid subjects (mean ± SD was 38.5 ± 23.1 µg/L in hypothyroid; 18.1 ± 7.0µg/L in hyperthyroid; 17.4 ± 5.7µg/L in euthyroid). There was a significant difference in myoglobin concentration between hypothyroid and euthyroid groups (F = 36.1, p&lt; 0.001), however, there was no significant difference between the hyperthyroid and euthyroid groups. When the mean ± 2SD for myoglobin in euthyroid subjects was calculated, the reference range was 6-29 µg/L. Of the hypothyroid subjects, 29 (58%) had high myoglobin and 21 (42%) had normal myoglobin level. No significant correlation was noticed between TSH or FT4 and myoglobin in all studied subjects. Conclusion:Raised serum myoglobin may be observed in patients with hypothyroidism. Hence hypothyroidism should be considered in the differential diagnosis of patients with raised serum myoglobin concentration

Chromogranin A as a Biochemical Marker for Neuroendocrine Tumors: A Single Center Experience at Royal Hospital, Oman

Objectives: To evaluate the significance of serum chromogranin A (CgA) status in patients with and without different neuroendocrine tumors (NETs) by conducting a retrospective assessment of the diagnostic utility and limitations of CgA as a biomarker for NETs in a tertiary care hospital in Oman. Methods: We conducted a retrospective analysis of CgA requests referred to the Clinical Biochemistry Laboratory, Royal Hospital, Oman over a 24-month period (April 2012 to March 2014). During this time, 302 CgA tests for 270 patients (119 males and 151 females; age range 11–86 years and mean±standard deviation (SD) 44.0±18.0 years), were requested. Of these CgA tests, 245 tests were performed for 245 patients investigated for the diagnosis of NETs, and 57 CgA tests were performed for 25 patients with diagnosed NETs who were undergoing follow-up. Serum CgA levels were analyzed using the enzyme-linked immunosorbent assay based on a cut-off value of 22 IU/L. Results: Of the 302 CgA tests reviewed, 197 (65.2%) were within the quoted normal range; however, 105 (34.8%) had CgA > 22 IU/L. Of the 245 patients with first-line CgA, 38 patients (15.5%) had NET that included carcinoid, pheochromocytoma, pancreatic NET, adrenal adenoma, prostatic adenocarcinoma, gastrointestinal NET, medullary thyroid carcinoma, Schwannoma, lung small cell carcinoma, parathyroid adenoma, and pituitary macroadenoma. The mean±SD of CgA in these patients with NETs was 205.0±172.0 IU/L. Meanwhile, there were 45 (18.3%) patients with CgA > 22 IU/L (83.0±116.0 IU/L) who did not have NETs. The conditions/diseases included: essential hypertension, chronic kidney disease, heart failure, peptic ulcer, chronic diarrhea, use of proton pump inhibitors, and other chronic diseases (hypothyroidism, asthma, diabetes mellitus). Of the 25 patients with known NET who were followed-up, there were 57 CgA results (29 with CgA ≤ 22 IU/L and 28 with CgA > 22 IU/L). The overall clinical sensitivity of CgA in the diagnosis of NETs was 84.2%, overall specificity was 78.2%, positive predictive value was 41.5%, negative predictive value was 96.4%, and overall efficiency was 79.2%. In patients with individual NET, a good reflection in CgA was noticed in the follow-up period following surgery or therapy. Conclusions: Serum CgA is a sensitive and effective noninvasive laboratory test for the clinical detection and management of NETs. Awareness of the pitfalls of the tests in patients with non-NET conditions, particularly chronic diseases and use of certain drugs, is important to be considered during the interpretation of the CgA levels

Serum Myoglobin in Patients with Thyroid Dysfunction

Objectives: To assess the pattern of change in serum myoglobin concentration in subjects with thyroid dysfunction. Methods: Serum samples were selected from 150 subjects with suspected thyroid disorder who were referred to the Royal Hospital, Muscat, Oman. The subjects were 35 males and 115 females, aged 14-56 years with mean ± SD of 34.3 ± 12.7 years. They were classified on the basis of thyroid stimulating hormone (TSH) and free thyroxine (FT4) into 3 groups, each consisting of 50 subjects: hypothyroid, hyperthyroid, and euthyroid subjects. Results: The mean serum myoglobin concentration was higher in hypothyroid patients compared to hyperthyroid and euthyroid subjects (mean ± SD was 38.5 ± 23.1 µg/L in hypothyroid; 18.1 ± 7.0µg/L in hyperthyroid; 17.4 ± 5.7µg/L in euthyroid). There was a significant difference in myoglobin concentration between hypothyroid and euthyroid groups (F = 36.1, p&lt; 0.001), however, there was no significant difference between the hyperthyroid and euthyroid groups. When the mean ± 2SD for myoglobin in euthyroid subjects was calculated, the reference range was 6-29 µg/L. Of the hypothyroid subjects, 29 (58%) had high myoglobin and 21 (42%) had normal myoglobin level. No significant correlation was noticed between TSH or FT4 and myoglobin in all studied subjects. Conclusion:Raised serum myoglobin may be observed in patients with hypothyroidism. Hence hypothyroidism should be considered in the differential diagnosis of patients with raised serum myoglobin concentration

Indicators of Renal Glomerular and Tubular Functions in Patients with Beta-Thalassaemia Major: A cross sectional study at the Royal Hospital, Oman

Objectives: There are limited data concerning the assessment of renal function in beta-thalassaemia major, with no study of such involvement in Omani patients. The objective of this study was to establish the pattern of renal glomerular and tubular function using traditional and specific laboratory tests in patients with beta-thalassaemia major. Methods: This cross-sectional study, from January–July 2008, included 30 patients of the Thalassaemia Clinic at the Royal Hospital, Oman, with transfusion-dependent homozygous beta-thalassaemia major. They included 15 males and 15 females, aged 16-32 years with mean ± standard deviation of 21.23 ± 3.42 years. The medical records were reviewed and renal function states assessed as follows: serum creatinine, estimated glomerular filtration rate (eGFR); urea; phosphate, fractional excretion of filtered sodium (FENa); urine albumin: creatinine index; urine ß2-microglobulin:creatinine index; tubular reabsorption of phosphate (TRP), and tubular maximum phosphate reabsorption (TmP)/GFR. Results: All patients had eGFR &gt;90 ml/min/1.73m2; serum creatinine &lt;90 μmol/L; serum urea &lt;6.0 mmol/L, and urine albumin:creatinine &lt;2.5 mg/mmol. Only 2 (6.7%) patients had FENa &gt;1% and 3 (10.0%) patients had urine ß2-microglobulin: creatinine &gt;22 μg/mmol. All patients had TRP &gt;0.85, of whom seven (23.3%) patients had values within the range of 0.85-0.95 and 23 (76.7%) had values &gt;0.95. Also, all patients had TmP/GFR &gt;1.0 mmol/L, of whom only one (3.3%) patient had TmP/GFR of 1.0–1.5, and 29 (96.7%) patients had TmP/GFR &gt;1.5 mmol/L. Finally, 24 (80%) patients had serum phosphate &gt;1.4 mmol/L. Linear regression revealed a highly significant correlation between serum phosphate and TmP/GFR (r = 0.904, P &lt; 0.001). Conclusion: Renal function, glomerular and tubular, appears to be well preserved in beta-thalassaemia major. Almost all renal function indicators were within the recommended ranges. Raised TmP/GFR and TRP were noted in the majority of patients, reflecting an up-trend in serum phosphate and therefore increasing renal phosphate reabsorption

Validity of Serum Testosterone, Free Androgen Index, and Calculated Free Testosterone in Women with Suspected Hyperandrogenism

Objectives: There are technical limitations for the currently available methods of measuring serum total and free testosteronein females. The study objectives were to evaluate the usefulness of serum total testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), and calculated free testosterone (CFT) in the assessment of androgen status in women investigated for suspected hyperandrogenism.Methods: This is a case control study that was conducted during the period from 1st May 2011 to 31st October 2011 on 122 patients aged (18-45 years) whom were referred to the Clinical Biochemistry Laboratory from the Endocrinology and Gynecology Clinics, Royal Hospital, Oman. Women with no clinical feature or laboratory data indicative of hormonal dysfunction and with midluteal progesterone >30 nmol/L were selected as controls (group 1; n=18). The patients were divided into subgroups based on the clinical/laboratory diagnosis of polycystic ovary syndrome (PCOS [group 2; n=19), hirsutism (group 3; n=18), menstrual disturbances (irregularities) or infertility (group 4; n=49), as well as combination of PCOS or hirsutism and menstrual disturbances or infertility (group 5;n=18). Serum total testosterone and SHBG were measured, FAI was calculated as percentage ratio of total testosterone to SHBG values, and CFT was calculated according to Vermeulen equation.Results: There was a statistically significant difference in the mean levels of testosterone, FAI and CFT in each patient group compared with the control group. For diagnosing hyperandrogenism, each indicator was selected at the recommended cut-off: testosterone >3.0 nmol/L, SHBG 5%, and CFT >32 pmol/L. In group 2, 89.5% and 94.7% of the patients had increased FAI and CFT, respectively; compared with 36.4% for increased testosterone. In group 3, 88.9% and 88.9% of the patients had similarly increased FAI and CFT, respectively; compared with 66.7% for testosterone. In group 4, patients had 63.3% and 73.5% elevated FAI and CFT, respectively; compared with 53.1% for testosterone, while in group 5, patients had 83.3% and 88.9% elevated FAI and CFT, respectively, compared with 61.1% for testosterone.Conclusion: The diagnosis of hyperandrogenism was most obvious when using CFT or FAI than testosterone alone. It is thus recommended to include these calculated parameters (CFT and/or FAI) in the routine investigation and assessment of women with disorders related to clinical or biochemical hyperandrogenism