Renal disease progression in autosomal dominant polycystic kidney disease
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.
Full-textDOI: · Available from: Kikuo Nutahara, Jan 06, 2015
Clinical Journal of the American Society of Nephrology 04/2014; 9(5). DOI:10.2215/CJN.02480314 · 5.25 Impact Factor
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ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is a progressive genetic disorder characterized by the development of numerous kidney cysts that result in kidney failure. Little is known regarding the key patient characteristics and utilization of healthcare resources for ADPKD patients along the continuum of disease progression. This observational study was designed to describe the characteristics of ADPKD patients and compare them with those of patients with other chronic kidney diseases. This retrospective cohort study involved patients with a claim for ADPKD or PKD unspecified from 1/1/2000-2/28/2013 and ≥6 months of previous continuous enrollment (baseline) within a large database of administrative claims in the USA. A random sample of chronic kidney disease (CKD) patients served as comparators. For a subset of ADPKD patients who had only a diagnosis code of unspecified PKD, abstraction of medical records was undertaken to estimate the proportion of patients who had medical chart-confirmed ADPKD. In patients with linked electronic laboratory data, the estimated glomerular filtration rate was calculated via serum creatinine values to determine CKD stage at baseline and during follow-up. Proportions of patients transitioning to another stage and the mean age at transition were calculated. ADPKD patients were, in general, younger and had fewer physician visits, but had more specific comorbidities at observation start compared with CKD patients. ADPKD patients had a longer time in the milder stages and longer duration before recorded transition to a more severe stage compared with CKD patients. Patients with ADPKD at risk of rapid progression had a shorter time-to-end-stage renal disease than patients with CKD and ADPKD patients not at risk, but stage duration was similar between ADPKD patients at risk and those not at risk. These results suggest that distribution of patients by age at transition to next stage may be useful for identification of ADPKD patients at risk of rapid progression. The results also suggest that medical claims with diagnosis codes for "unspecified PKD", in absence of a diagnosis code for autosomal recessive polycystic kidney disease, may be a good proxy for ADPKD.Drugs in Context 04/2015; 4:212275. DOI:10.7573/dic.212275
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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.Transplantation Proceedings 01/2014; 46(1):66–74. DOI:10.1016/j.transproceed.2013.10.040 · 0.95 Impact Factor