Glomerular Hyperfiltration and Renal Progression in Children with Autosomal Dominant Polycystic Kidney Disease
ABSTRACT 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.
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 ≥140 ml/min per 1.73 m(2).
Thirty-two children had GH (mean age 11.4 ± 3.6 years) and 148 had normal renal function (mean age 10.8 ± 3.9 years). Patients with GH at baseline demonstrated an increased rate of total renal volume growth (β: rate of change = +19.3 ± 10.8 cm(3)/year) over 5 years compared with those without GH at baseline (β = -4.3 ± 7.7 cm(3)/year), P = 0.008. Those with GH at baseline experienced a faster decline in creatinine clearance in subsequent years (β = -5.0 ± 0.8 ml/min per 1.73 m(2) per year) compared with those without GH at baseline (β = +1.0 ± 0.4 ml/min per 1.73 m(2) per year), P < 0.0001.
This 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.
- SourceAvailable from: Godela M Brosnahan[Show abstract] [Hide abstract]
ABSTRACT: 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.Nature Reviews Nephrology 02/2012; 8(5):293-300. DOI:10.1038/nrneph.2012.19 · 8.37 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Autosomal dominant polycystic kidney disease is a lifelong progressive disorder. However, how age, blood pressure, and stage of chronic kidney disease (CKD) affect the rate of kidney function deterioration is not clearly understood. In this long-term observational case study up to 13.9 years (median observation period for slope was 3.3 years), serum creatinine was serially measured in 255 mostly adult patients. The glomerular filtration rate was estimated (eGFR) using a modified Modification of Diet in Renal Disease Study method. The total kidney volume (TKV) has been measured in 86 patients at one center since 2006. As age increased, eGFR declined significantly (P < 0.0001), but the annual rate of decline of eGFR did not correlate with age or initially measured eGFR. In patients with CKD stage 1, eGFR declined at a rate which was not significantly different from other advanced CKD stages. Hypertensive patients had lower eGFR and larger TKV than normotensive patients at a young adult age. The slopes of regression lines of eGFR and TKV in relation to age were not different between high and normal blood pressure groups. The declining rate of eGFR was relatively constant and did not correlate with age or eGFR after adolescence. eGFR was already low in young adult patients with hypertension. As age increased after adolescence, eGFR declined and TKV increased similarly between normal and high blood pressure groups. eGFR starts to decline in patients with normal eGFR, suggesting that the decline starts earlier than previously thought.Clinical and Experimental Nephrology 04/2012; 16(4):622-8. DOI:10.1007/s10157-012-0611-9 · 1.71 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Die autosomal-dominante polyzystische Nierenerkrankung (ADPKD) ist die häufigste erbliche Nierenerkrankung und verantwortlich für 15% der Nierentransplantationen in Deutschland. Die Diagnose wird durch Sonographie und die Familienanamnese gestellt, eine genetische Diagnostik spielt in der Routine keine Rolle. Die Hälfte der Betroffenen benötigt zwischen dem 50. und 60. Lebensjahr eine Nierenersatztherapie. Die häufigsten Komplikationen sind Zysteninfektion und zystenbedingte Schmerzen, die schwerste die selten auftretende Ruptur von intrakraniellen Aneurysmen. Die Therapie der ADPKD besteht in der Blutdruckkontrolle, der Modifikation von Risikofaktoren sowie der Therapie von Komplikationen. Diese Übersicht bespricht die aktuelle Literatur zur ADPKD. Vorgestellt und vertieft werden neue Erkenntnisse über den frühen Verlauf der ADPKD bei Kindern, aktuelle Zahlen zu intrakraniellen Aneurysmen sowie klinische Studien zur Therapie der ADPKD. Abstract Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease and is the underlying cause for renal failure in 15% of patients receiving a kidney transplant in Germany. The diagnosis is made by ultrasound and family history and genetic testing does not play any role in routine clinical practice. Half of the affected individuals will require renal replacement therapy between 50 and 60 years of age. The most common complications are cyst infections and cyst-related pain and the most severe but rare complication is rupture of an intracranial aneurysm. The mainstay of ADPKD therapy is blood pressure control and modification of risk factors as well as management of complications. This review surveys the current literature on ADPKD and special attention is given to novel observations on the early course of ADPKD in children, new data on intracranial aneurysms and results from clinical intervention trials.Der Nephrologe 05/2012; 7(3):259-268. DOI:10.1007/s11560-011-0619-2