Background: Urinary excretion of albumin indicates kidney damage and is recognized as a risk factor for progression of kidney disease and cardiovascular disease. The role of urinary albumin measurements has focused attention on the clinical need for accurate and clearly reported results. The National Kidney Disease Education Program and the IFCC convened a conference to assess the current state of preanalytical, analytical, and postanalytical issues affecting urine albumin measurements and to identify areas needing improvement.

Content: The chemistry of albumin in urine is incompletely understood. Current guidelines recommend the use of the albumin/creatinine ratio (ACR) as a surrogate for the error-prone collection of timed urine samples. Although ACR results are affected by patient preparation and time of day of sample collection, neither is standardized. Considerable intermethod differences have been reported for both albumin and creatinine measurement, but trueness is unknown because there are no reference measurement procedures for albumin and no reference materials for either analyte in urine. The recommended reference intervals for the ACR do not take into account the large intergroup differences in creatinine excretion (e.g., related to differences in age, sex, and ethnicity) nor the continuous increase in risk related to albumin excretion.

Discussion: Clinical needs have been identified for standardization of ( a ) urine collection methods, ( b ) urine albumin and creatinine measurements based on a complete reference system, ( c ) reporting of test results, and ( d ) reference intervals for the ACR.

Current Issues in Measurement and Reporting of Urinary Albumin Excretion

In several previous experiments to determine the composition of interstitial fluid, the results varied depending on the collecting technique, and the electrolyte concentrations differed from those of a hypothetical ultrafiltrate of plasma. In our approach, since a change of position from standing to supine is accompanied by hemodilution with interstitial fluid, we used the changes in hematocrit and composition of plasma in 20 subjects before and after lying down to calculate the composition of added interstitial fluid. The estimated protein concentration was 20.6 g/L, and the concentrations of total calcium and magnesium were low, in accord with a lower concentration of protein-bound calcium and magnesium. The activity of free cations was also lower, in agreement with a Donnan equilibrium potential of 1 mV across the endothelium. The concentration of leukocytes and platelets decreased according to the hemodilution, implying no escape or mobilization of these elements.

Composition of interstitial fluid.

https://purehost.bath.ac.uk/ws/files/142754094/Published_version.pdf

Aptamer-MIP hybrid receptor for highly sensitive electrochemical detection of prostate specific antigen

In the circulation, testosterone and other sex hormones are bound to binding proteins, which play an important role in regulating their transport, distribution, metabolism, and biological activity. According to the free hormone hypothesis, which has been debated extensively, only the unbound or free fraction is biologically active in target tissues. Consequently, accurate determination of the partitioning of testosterone between bound and free fractions is central to our understanding of how its delivery to the target tissues and biological activity are regulated and consequently to the diagnosis and treatment of androgen disorders in men and women. Here, we present a historical perspective on the evolution of our understanding of the binding of testosterone to circulating binding proteins. On the basis of an appraisal of the literature as well as experimental data, we show that the assumptions of stoichiometry, binding dynamics, and the affinity of the prevailing models of testosterone binding to sex hormone-binding globulin and human serum albumin are not supported by published experimental data and are most likely inaccurate. This review offers some guiding principles for the application of free testosterone measurements in the diagnosis and treatment of patients with androgen disorders. The growing number of testosterone prescriptions and widely recognized problems with the direct measurement as well as the computation of free testosterone concentrations render this critical review timely and clinically relevant.

A Reappraisal of Testosterone's Binding in Circulation: Physiological and Clinical Implications.

The renal collecting system serves the fine-tuning of renal acid–base secretion. Acid-secretory type-A intercalated cells secrete protons via a luminally expressed V-type H+-ATPase and generate new bicarbonate released by basolateral chloride/bicarbonate exchangers including the AE1 anion exchanger. Efficient proton secretion depends both on the presence of titratable acids (mainly phosphate) and the concomitant secretion of ammonia being titrated to ammonium. Collecting duct ammonium excretion requires the Rhesus protein RhCG as indicated by recent KO studies. Urinary acid secretion by type-A intercalated cells is strongly regulated by various factors among them acid–base status, angiotensin II and aldosterone, and the Calcium-sensing receptor. Moreover, urinary acidification by H+-ATPases is modulated indirectly by the activity of the epithelial sodium channel ENaC. Bicarbonate secretion is achieved by non-type-A intercalated cells characterized by the luminal expression of the chloride/bicarbonate exchanger pendrin. Pendrin activity is driven by H+-ATPases and may serve both bicarbonate excretion and chloride reabsorption. The activity and expression of pendrin is regulated by different factors including acid–base status, chloride delivery, and angiotensin II and may play a role in NaCl retention and blood pressure regulation. Finally, the relative abundance of type-A and non-type-A intercalated cells may be tightly regulated. Dysregulation of intercalated cell function or abundance causes various syndromes of distal renal tubular acidosis underlining the importance of these processes for acid–base homeostasis.

Aldosterone regulated acid-base transport in the collecting duct

The ionic activities and total molalities of sodium, potassium, calcium, lithium, and chloride in a solution of human serum albumin were measured at different values of pH between 4 and 9. The same quantities were measured simultaneously in a protein-free electrolyte solution in membrane equilibrium with the albumin solution. Taking the residual liquid-junction potential and bias from unselectivity of the electrodes into account, we determined the own, bound, and net charges of albumin. Chloride was amply bound at low pH, and calcium at high pH. The varying charge of ions bound to albumin opposed the effect of acid or base on the net charge. All ions were distributed across the membrane according to the same electric potential difference, which equalled the Donnan potential. The high concordance between observation and theory favors the Donnan theory and furthermore implies that the electrodes are as accurate in a solution with albumin as in a protein-free solution.

Poul Jannik Bjerrum

Papers

Ionic binding, net charge, and Donnan effect of human serum albumin as a function of pH.

IonicBinding,Net Charge,and DonnanEffectof HumanSerumAlbuminas a Functionof pH