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: 1.25). 04/2012; 16(4):622-8. DOI: 10.1007/s10157-012-0611-9
Source: PubMed

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.

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    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.
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    ABSTRACT: Background Autosomal-dominant polycystic kidney disease (ADPKD) is the most common form of cystic kidney disease. The mammalian target of rapamycin (mTOR) pathway is associated with progressive kidney enlargement. The drug sirolimus suppresses mTOR signaling but plays an uncertain role in the treatment of ADPKD. The objective of our study was to conduct a meta-analysis of randomized controlled trials (RCTs) to present an objective appraisal of the efficacy and safety of sirolimus therapy in patients with ADPKD. Methods We conducted a meta-analysis of RCTs performed in adults with ADPKD, and compared the effect of sirolimus on total kidney volume (TKV), glomerular filtration rate (GFR), cyst volume, and daily urinary protein excretion. Safety was evaluated based on analysis of blood pressure, lipid profile, complete blood count, infection, and other reported adverse events. Results Four RCTs were included. The sirolimus therapy group had smaller TKV than the control group. The mean difference (MD) of TKV post-treatment compared with the control group was −234.74 (P = .01). However, GFR did not reach a statistically significant difference between groups. Standard mean difference (SMD) of GFR after therapy was 0.24 (95% confidence interval [CI], 0.05–0.52; P = .11), but sirolimus seemed to increase urine protein excretion (P = .002). There was no statically significant difference in leukocytes, hemoglobin, platelets, and blood pressure between groups. Aphthous stomatits and pharyngitis are reported more commonly in the sirolimus therapy group compared with the control group (P < .000001). Conclusions In ADPKD patients, treatment with sirolimus is safe and can effectively slow kidney growth, but it seems not to slow down the decrease of GFR.
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