International Society of Nephrology.

Activation of mammalian target of rapamycin (mTOR) pathways may contribute to uncontrolled cell proliferation and secondary cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD). To assess the effects of mTOR inhibition on disease progression, we performed a randomized, crossover study (The SIRENA Study) comparing a 6-month treatment with sirolimus or conventional therapy alone on the growth of kidney volume and its compartments in 21 patients with ADPKD and GFR Ն40 ml/min per 1.73 m 2 . In 10 of the 15 patients who completed the study, aphthous stomatitis complicated sirolimus treatment but was effectively controlled by topical therapy. Compared with pretreatment, posttreatment mean total kidney volume increased less on sirolimus (46 Ϯ 81 ml; P ϭ 0.047) than on conventional therapy (70 Ϯ 72 ml; P ϭ 0.002), but we did not detect a difference between the two treatments (P ϭ 0.45). Cyst volume was stable on sirolimus and increased by 55 Ϯ 75 ml (P ϭ 0.013) on conventional therapy, whereas parenchymal volume increased by 26 Ϯ 30 ml (P ϭ 0.005) on sirolimus and was stable on conventional therapy. Percentage changes in cyst and parenchyma volumes were significantly different between the two treatment periods. Sirolimus had no appreciable effects on intermediate volume and GFR. Albuminuria and proteinuria marginally but significantly increased during sirolimus treatment. In summary, sirolimus halted cyst growth and increased parenchymal volume in patients with ADPKD. Whether these effects translate into improved long-term outcomes requires further investigation.

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ObjectiveTo assess the prevalence of microalbuminuria and kidney dysfunction in low-income countries and in the USA.DesignCross-sectional study of screening programmes in five countries.SettingScreening programmes in Nepal, Bolivia, the USA (National Health and Nutrition Examination Survey (NHANES) 2005–2008) Bangladesh and Georgia.ParticipantsGeneral population in Nepal (n=20 811), Bolivia (n=3436) and in the USA (n=4299) and high-risk subjects in Bangladesh (n=1518) and Georgia (n=1549).Primary and secondary outcome measuresEstimated glomerular filtration rate (eGFR)<60ml/min/1.73 m2 and microalbuminuria (defined as urinary albumin creatinine ratio values of 30–300 mg/g) were the main outcome measures. The cardiovascular (CV) risk was also evaluated on the basis of demographic, clinical and blood data.ResultsThe prevalence of eGFR<60ml/min/1.73 m2 was 19%, 3.2% and 7% in Nepal, Bolivia and the USA, respectively. In Nepal, 7% of subjects were microalbuminuric compared to 8.6% in the USA. The prevalence of participants with predicted 10-year CV disease (CVD) risk ≥10% was 16.9%, 9.4% and 17% in Nepal, Bolivia and in the USA, respectively. In Bangladesh and Georgia, subjects with eGFR<60 ml/min/1.73 m2 were 8.6% and 4.9%, whereas those with microalbuminuria were 45.4% and 56.5%, respectively. Predicted 10-year CVD risk ≥10% was 25.4% and 25% in Bangladesh and Georgia, respectively.ConclusionsRenal abnormalities are common among low-income countries and in the USA. Prevention programmes, particularly focused on those with renal abnormalities, should be established worldwide to prevent CVD and progression to end-stage renal disease.