Glomerular hyperfiltration is a phenomenon that can occur in various clinical conditions including kidney disease. No single definition of glomerular hyperfiltration has been agreed upon, and the pathophysiological mechanisms, which are likely to vary with the underlying disease, are not well explored. Glomerular hyperfiltration can be caused by afferent arteriolar vasodilation as seen in patients with diabetes or after a high-protein meal, and/or by efferent arteriolar vasoconstriction owing to activation of the renin-angiotensin-aldosterone system, thus leading to glomerular hypertension. Glomerular hypertrophy and increased glomerular pressure might be both a cause and a consequence of renal injury; understanding the renal adaptations to injury is therefore important to prevent further damage. In this Review, we discuss the current concepts of glomerular hyperfiltration and the renal hemodynamic changes associated with this condition. A physiological state of glomerular hyperfiltration occurs during pregnancy and after consumption of high-protein meals. The various diseases that have been associated with glomerular hyperfiltration, either per nephron or per total kidney, include diabetes mellitus, polycystic kidney disease, secondary focal segmental glomerulosclerosis caused by a reduction in renal mass, sickle cell anemia, high altitude renal syndrome and obesity. A better understanding of the mechanisms involved in glomerular hyperfiltration could enable the development of new strategies to prevent progression of kidney disease.
The progression of ADPKD clearly occurs in childhood and manifests as an increase in cyst number and renal size. This study identifies children at risk for rapid renal enlargement who may benefit the most from future therapeutic interventions.
SummaryBackground and objectives The purpose of this study was to determine whether glomerular hyperfiltration (GH) occurring early in autosomal dominant polycystic kidney disease (ADPKD) is indicative of more rapid disease progression in children.Design, setting, participants, & measurements One hundred eighty children with ADPKD (ages 4 to 18 years) with normal renal function were examined by renal ultrasound. Renal volume was calculated using a standard formula for a modified ellipsoid. Creatinine clearance was calculated from serum creatinine and 24-hour urine creatinine. GH was defined as creatinine clearance Ն140 ml/min per 1.73 m 2 .Results Thirty-two children had GH (mean age 11.4 Ϯ 3.6 years) and 148 had normal renal function (mean age 10.8 Ϯ 3.9 years). Patients with GH at baseline demonstrated an increased rate of total renal volume growth (: rate of change ϭ ϩ19.3 Ϯ 10.8 cm 3 /year) over 5 years compared with those without GH at baseline ( ϭ Ϫ4.3 Ϯ 7.7 cm 3 /year), P ϭ 0.008. Those with GH at baseline experienced a faster decline in creatinine clearance in subsequent years ( ϭ Ϫ5.0 Ϯ 0.8 ml/min per 1.73 m 2 per year) compared with those without GH at baseline ( ϭ ϩ1.0 Ϯ 0.4 ml/min per 1.73 m 2 per year), P Ͻ 0.0001.
ConclusionsThis study revealed that occurrence of GH in ADPKD children is associated with a significantly faster decline in renal function and higher rate of kidney enlargement over time. GH combined with the increased renal volume may therefore be used as an early marker for a more severe progression of ADPKD in children.
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