Renal disease progression in autosomal dominant polycystic kidney disease

Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
Clinical and Experimental Nephrology (Impact Factor: 2.02). 04/2012; 16(4):622-8. DOI: 10.1007/s10157-012-0611-9
Source: PubMed


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.

Download full-text


Available from: Kikuo Nutahara, Jan 06, 2015
  • Source
    • "In up to about 50% by age 70, end-stage renal failure is diagnosed (Higashihara et al., 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: As ageing is a complex phenomenon characterized by intraindividual and interindividual diversities in the maintenance of the homeostatic condition of cells and tissues, changes in renal function are not uniform and depend on associated diseases and environmental factors. Multiple studies have investigated the possible underlying mechanisms of age-related decline in kidney function. Evolutionary, molecular, cellular and systemic theories have been postulated to explain the primarily disease independent age-related changes and adaptive responses. As peroxisome proliferator-activated receptors (PPARs) are involved in a broad spectrum of biological processes, PPAR activation might have an effect on the prevention of cell senescence. In this review, we will focus on the experimental and clinical evidence of PPAR agonists in a battle against the ageing kidney.
    Ageing Research Reviews 03/2014; 14(1). DOI:10.1016/j.arr.2014.01.006 · 4.94 Impact Factor
  • Source
    • "Various studies have shown that controlling hypertension slows down CKD development in patients with ADPKD [9]. A recent trial, however, has indicated that reduced glomerular filtration is a function of older age, and that there are no differences between hypertensive and normotensive patients [10]; hypertensionis present in nearly 90% of ADPKD patients once they have renal failure. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Some 7-10% of patients on replacement renal therapy (RRT) are receiving it because of autosomal dominant polycystic kidney disease (ADPKD). The age at initiation of RRT is expected to increase over time. Clinical data of 1,586 patients (7.9%) with ADPKD and 18,447 (92.1%) patients with other nephropathies were analysed from 1984 through 2009 (1984--1991, 1992--1999 and 2000--2009). The age at initiation of RRT remained stable over the three periods in the ADPKD group [56.7 +/- 10.9 (mean +/- SD) vs 57.5 +/- 12.1 vs 57.8 +/- 13.3 years), whereas it increased significantly in the non-ADPKD group (from 54.8 +/- 16.8 to 63.9 +/- 16.3 years, p < 0.001). The ratio of males to females was higher for non-ADPKD than for ADPKD patients (1.6--1.8 vs 1.1--1.2). The prevalence of diabetes was significantly lower in the ADPKD group (6.76% vs 11.89%, p < 0.001), as were most of the co-morbidities studied, with the exception of hypertension. The survival rate of the ADPKD patients on RRT was higher than that of the non-ADPKD patients (p < 0.001). Over time neither changes in age nor alterations in male to female ratio have occurred among ADPKD patients who have started RRT, probably because of the impact of unmodifiable genetic factors in the absence of a specific treatment.
    BMC Nephrology 09/2013; 14(1):186. DOI:10.1186/1471-2369-14-186 · 1.69 Impact Factor
  • Source
    • "The eGFR slope is relatively constant in relation to age (Fig. 4b). In our previous study, changes of reciprocal creatinine in 106 patients plotted against age showed that the progression patterns of renal function deterioration were different among patients [10]. Individual variation in renal functional progression might be a parallel characteristic to the wide distribution of kidney size growth, as shown in Fig. 3. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The significance of total kidney volume (TKV) as a biomarker of kidney function in autosomal dominant polycystic kidney disease (ADPKD) is controversial and has been reappraised. Between 2007 and 2012, 64 patients were followed with a mean 39.7-month observation period. TKV measurements by magnetic resonance imaging and estimation of renal function with estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation and 24-h urine creatinine clearance were repeated annually. TKV and its adjusted parameters (height-adjusted, body surface area-adjusted and log-converted TKV [log-TKV]) correlated with eGFR significantly. Among them, the correlation coefficient of log-TKV was most significant (r = -0.6688, p < 0.001). The eGFR slope correlated negatively with TKV slope (p < 0.05). TKV increased faster and became larger as chronic kidney disease (CKD) stage advanced. As age advanced, eGFR declined significantly (p < 0.001), but the eGFR slope remained constant. There was no significant correlation between TKV and age, but the log-TKV slope became smaller as age advanced. If baseline TKV was large, the eGFR slope was steeper (p < 0.05), which suggests that eGFR declines faster in patients with larger kidney volume. TKV is confirmed as a clinically meaningful surrogate marker in ADPKD. Log-TKV correlates with eGFR most significantly. Higher rates of kidney enlargement and larger kidney volume are associated with a more rapid decrease in kidney function. Kidney function decreased faster as CKD stage advanced, but its declining slope did not change significantly by age, at least after ~30 years of age.
    Clinical and Experimental Nephrology 07/2013; 18(1). DOI:10.1007/s10157-013-0834-4 · 2.02 Impact Factor
Show more