Association of uric acid with kidney function and albuminuria: the Uric Acid Right for heArt Health (URRAH) Project

Background Hyperuricemia is commonly observed in patients with chronic kidney disease (CKD). However, a better understanding of the relationship among uric acid (UA) values, glomerular filtration rate (GFR) and albuminuria may shed light on the mechanisms underlying the excess of cardiovascular mortality associated with both chronic kidney disease and hyperuricemia and lead to better risk stratification. Our main goal was to study the relationships between serum uric acid and kidney disease measures (namely estimated GFR [eGFR] and albuminuria) in a large cohort of individuals at cardiovascular risk from the URic acid Right for heArt Health (URRAH) Project database. Methods Clinical data of 26,971 individuals were analyzed. Factors associated with the presence of hyperuricemia defined on the basis of previously determined URRAH cutoffs for cardiovascular and all-cause mortality were evaluated through multivariate analysis. Chronic kidney disease was defined as eGFR < 60 ml/min per 1.73 m2 and/or abnormal urinary albumin excretion diagnosed as: (i) microalbuminuria if urinary albumin concentration was > 30 and ≤ 300 mg/L, or if urinary albumin-to-creatinine ratio (ACR) was > 3.4 mg/mmol and ≤ 34 mg/mmol; (ii) macroalbuminuria if urinary albumin concentration was > 300 mg/L, or if ACR was > 34 mg/mmol. Results Mean age was 58 ± 15 years (51% males, 62% with hypertension and 12% with diabetes), mean eGFR was 81 ml/min per 1.73m22with a prevalence of eGFR < 60 and micro- or macroalbuminuria of 16, 15 and 4%, respectively. Serum uric acid showed a trend towards higher values along with decreasing renal function. Both the prevalence of gout and the frequency of allopurinol use increased significantly with the reduction of eGFR and the increase in albuminuria. Hyperuricemia was independently related to male gender, eGFR strata, and signs of insulin resistance such as body mass index (BMI) and triglycerides. Conclusions The lower the eGFR the higher the prevalence of hyperuricemia and gout. In subjects with eGFR < 60 ml/min the occurrence of hyperuricemia is about 10 times higher than in those with eGFR > 90 ml/min. The percentage of individuals treated with allopurinol was below 2% when GFR was above 60 ml/min, it increased to 20% in the presence of CKD 3b and rose further to 35% in individuals with macroalbuminuria. Graphic abstract

Assessment of the degree of adherence of medical laboratories to KDIGO 2012 guideline for evaluation and management of CKD in Czechia and Slovakia

Introduction: The aim of the study is to assess the degree of adherence of medical laboratories to Kidney Disease Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) in laboratory practice in Czechia and Slovakia. Materials and methods: An electronic questionnaire on adherence to KDIGO 2012 guideline was designed by an external quality assessment (EQA) provider SEKK spol. s.r.o. The questionnaire was placed and distributed through website to all medical biochemistry laboratories in Czechia and Slovakia (N = 396). Results: A total of 212 out of 396 laboratories responded to the questions, though some laboratories only answered some questions, those applicable to their practice. A total of 48 out of 212 laboratories adopted the KDIGO 2012 guideline in full extent. The metrological traceability of creatinine measurement to standard reference material of SRM 967 was declared by 180 out of 210 laboratories (two of the responding laboratories did not measure creatinine). Thirty laboratories are not well educated on traceability of creatinine measurement and seven laboratories do not calculate estimated glomerular filtration rate (eGFR). Both urinary albumin concentration and albumin to creatinine ratio are reported by 144 out of 175 laboratories (37 of the responding laboratories did not measure urinary albumin). Conclusion: Majority of laboratories in Czechia and Slovakia adopted some parts of the KDIGO 2012 guideline in their practice, but only 23% of the laboratories apply them completely. Thus, further education and action should be conducted to improve its implementation.

Clinical Utility of Urinaryβ2-Microglobulin in Detection of Early Nephropathy in African Diabetes Mellitus Patients

Background. Studies have indicated that diabetic tubulopathy may occur earlier than glomerulopathy, therefore providing a potential avenue for earlier diagnosis of diabetic nephropathy. Urinary beta-2-microglobulin (β2m) was investigated in this study as a potential biomarker in the detection of early nephropathy in type 2 diabetics.Methods. One hundred and two diabetic subjects and 103 controls that met the inclusion criteria had data (sociodemographic, medical history, physical examination, and laboratory) collected. Urinaryβ2m levels and urinary albumin concentration (UAC) were determined.Results. Elevated urinaryβ2m was more frequent among the diabetics (52%, 95% CI: 42.1–61.8%) than among the controls (32%, 95% CI: 22.9–41.2%). The frequency of microalbuminuria was higher in the diabetics (35.3%, 95% CI: 25.9–44.7%) than in the controls (15.5%, 95% CI: 8.4–22.6%). There was a positive correlation between urinaryβ2m and UAC (rho = 0.38,p<0.001). Multivariate analysis showed BMI (OR: 1.23, 95% CI: 1.05–1.45), eGFR (OR: 0.97, 95% CI: 0.94–0.99), and presence of microalbuminuria (OR: 3.94, 95% CI: 1.32–11.77) as independent predictors of elevated urinary beta-2-microglobulin among the diabetics.Conclusion. Urinaryβ2m may be useful, either as a single test or as a component of a panel of tests, in the early detection of diabetic nephropathy.

Characterization of Immunochemically Nonreactive Urinary Albumin

Background: Conventional immunoassays underestimate the urinary albumin concentration because intact albumin in urine exists in two forms, immunoreactive and immunochemically nonreactive. Methods: Urinary albumin concentration measured by HPLC (which measures total albumin, i.e., the sum of immunoreactive albumin + immunochemically nonreactive albumin) or RIA was compared with densitometric analysis of albumin bands in diabetic urine samples separated by either native polyacrylamide gel electrophoresis (PAGE) or reducing sodium dodecyl sulfate (SDS)-PAGE. Immunochemically nonreactive albumin was also isolated from diabetic urine (relative amount detected, 70–80% of the expected) and was tested for contamination by common urinary proteins by native PAGE, ELISA, and capillary electrophoresis. Results: Urinary albumin concentrations measured by native PAGE and HPLC were better correlated (r2 = 0.83) than concentrations measured by native PAGE and RIA (r2 = 0.62) because under native conditions both native PAGE and HPLC detect total albumin and not only the immunoreactive albumin alone that is measured by RIA. Urinary albumin concentrations measured by reducing SDS-PAGE and RIA were better correlated (r2 = 0.84) than concentrations measured by reducing SDS-PAGE and HPLC (r2 = 0.65) because under reducing conditions immunochemically nonreactive albumin is unstable and fragments into many smaller peptides. The partially purified preparation was found to contain &lt;1% contamination by common urinary proteins and is stable to freezing and frequent freeze/thaw cycles. Conclusions: The results are consistent with the interpretation that immunochemically nonreactive albumin has a limited number of polypeptide chain scissions and is held together by noncovalent intrachain bonding and disulfide bonds. Detection of this molecule is likely to be of clinical importance in diagnosing kidney disease as well as cardiovascular disease.