The spectrum of polycystic kidney disease (PKD) comprises a family of inherited syndromes defined by renal cyst formation and growth, progressive renal function loss and variable extrarenal manifestations. The most common form, autosomal-dominant PKD is caused by mutations in one of two genes, PKD1 or PKD2. Recent developments in genomic and proteomic medicine have resulted in the discovery of novel genes implicated in the wide variety of less frequent, recessive PKD syndromes. Cysts are the disease, and overall cystic burden, measured by MRI as total kidney volume, is being established as the best available biomarker of disease progression. Current state-of-the-art therapy is aimed at quality treatment for chronic renal insufficiency and cyst-related complications. Recent therapeutic studies have focused on mechanisms reducing intracellular cyclic AMP levels, blocking the renin-angiotensin-aldosterone system and inhibiting the mTOR-signaling pathway. PKD therapies with vasopressin antagonists and somatostatin analogues result in the reduction of intracellular cAMP levels and have shown limited clinical success, but side effects are prominent. Similarly, mTOR pathway inhibition has not shown significant therapeutic benefits. While the HALT-PKD study will answer questions by the end of 2014 about the utility of renin-angiotensin-aldosterone system blockade and aggressive blood pressure control, the next generation of PKD therapy studies targeting proliferative mechanisms of cyst expansion are already under way. Advances in research on the molecular mechanisms of cystogenesis will help design novel targeted PKD therapies in the future.

Sleep disorder and poor sleep quality are common in chronic hemodialysis (HD) patients. They have been claimed as a cause of morbidity and mortality. The relationship between the degree of sleepiness and survival has not been studied. We studied the degree of sleepiness in 1,252 adult HD patients (age ≥20 years) recruited into the Dialysis Outcomes Practice Pattern Study in Japan (J-DOPPS III), using the Japanese version of the Epworth Sleepiness Scale (JESS) questionnaire. Demographic data were presented for three subgroups: low, intermediate, and high JESS score. Cox proportional hazard regression analysis was performed to estimate the independent effect of several variables on survival. The hazard ratio for mortality was 2.312 (95% CI 1.267-4.220; p = 0.006) for those with a high JESS score (vs. those with a low JESS score) after adjusting for age, vintage (length of time on HD), sex, diabetes, body mass index, cardiovascular disease, HD treatment regimen (time, frequency, and single-pool Kt/V), laboratory data (serum albumin, creatinine, and total cholesterol), and medication (antihypertensive drugs, erythropoietin, vitamin D, and phosphate binders). Patients ≥70 years of age with comorbid conditions (congestive heart failure, stroke, and diabetes) showed a significantly higher JESS score (≥16). The JESS score did not show interaction by age. Results showed that the degree of sleepiness is related to survival in Japanese HD patients, particularly in elderly patients.

Nearly all body organs and systems are affected by the toxicity of uremic compounds retained in the course of renal dysfunction. Knowledge about the origin, chemical structure and composition of the retained endogenous substances responsible for these symptoms is far from complete. Organic retention solutes present a great variety of properties which makes their accurate classification extremely difficult. Their potential toxicity remains to be elucidated with meticulous observation of clearly formulated rules guiding the process. Toxicity assessment is a complex process because not just one but several retained compounds may be simultaneously involved in the same biological and metabolic processes. The search for new uremic compounds and combining them into panels of substances involved in the same pathophysiological processes seems to offer a novel approach to identifying and explaining any so far unexplored specific effects of endogenous compounds on the body organs and systems.