Diagnosis and clinical biochemistry of inherited tubulopathies

SUMMARY, Epithelial ion channels and transporter proteins have physiologically important roles throughout the length of the nephron. Discovering the molecular identities of tubular epithelial cell proteins and their functional roles has increased understanding of both renal physiology and tubular diseases. Defects in tubular handling of solutes may present with nephrocalcinosis or nephrolithiasis, rickets, acid-base, electrolyte or blood pressure disturbances. Biochemical analysis of both serum and urine. together with clinical history and examination. remain fundamental for their diagnosis, whilst understanding of underlying molecular mechanisms allows appropriate management. The renal tubule is responsible for the regulation and control of the solute content of the body by reabsorption and secretion of water and ions. It does this by means of epithelial ion channels and transporters, which have specific locations and functions (Fig. I) and are highly regulated. Recent advances in molecular medicine have ~lIowed new insights into the precise mechan-I~ms underlying tubular disorders and have shed hght on both renal tubular physiology and the pharmacology of diuretics (Table I). In this review we give a brief overview of renal tubular P?ysiology with respect to electrolyte handling, dIscuss general reasons to suspect an inherited t~bulopathy in a patient, discuss the differential dIagnosis of hypokalaemia and review indivi-dual conditions with respect to clinical features and diagnosis. We have omitted discussion of nephrogenic diabetes insipidus, renal tubular acidoses and disorders of calcium-sensing because these have been recently reviewed in this journal, or elsewhere. ' 3 OVERVIEW OF PHYSIOLOGY Formation of urine relies on glomerular filtra-tion, tubular reabsorption and tubular secretion. Glomerular filtration produces> 160L of filtrate This article was prepared at the invitation of the Clinical LahoTlltory lnvestigution Standing Committee of the Associa-lion of Clinical Biochemists