Autosomal dominant polycystic kidney disease (ADPKD) is a common human genetic disease characterized by cyst formation in kidney tubules and other ductular epithelia. Cells lining the cysts have abnormalities in cell proliferation and cell polarity. The majority of ADPKD cases are caused by mutations in the PKD1 gene, which codes for polycystin-1, a large integral membrane protein of unknown function that is expressed on the plasma membrane of renal tubular epithelial cells in fetal kidneys. Because signaling from cell-cell and cell-matrix adhesion complexes regulates cell proliferation and polarity, we speculated that polycystin-1 might interact with these complexes. We show here that polycystin-1 colocalized with the cell adhesion molecules E-cadherin and α-, β-, and γ-catenin. Polycystin-1 coprecipitated with these proteins and comigrated with them on sucrose density gradients, but it did not colocalize, coprecipitate, or comigrate with focal adhesion kinase, a component of the focal adhesion. We conclude that polycystin-1 is in a complex containing E-cadherin and α-, β-, and γ-catenin. These observations raise the question of whether the defects in cell proliferation and cell polarity observed in ADPKD are mediated by E-cadherin or the catenins.

Background and objectives Masked hypertension and elevated nighttime BP are associated with increased risk of hypertensive target organ damage and adverse cardiovascular and renal outcomes in patients with normal kidney function. The significance of masked hypertension for these risks in patients with CKD is less well defined. The objective of this study was to evaluate the association between masked hypertension and kidney function and markers of cardiovascular target organ damage, and to determine whether this relationship was consistent among those with and without elevated nighttime BP.Design, setting, participants, & measurements This was a cross-sectional study. We performed 24-hour ambulatory BP in 1492 men and women with CKD enrolled in the Chronic Renal Insufficiency Cohort Study. We categorized participants into controlled BP, white-coat, masked, and sustained hypertension on the basis of clinic and 24-hour ambulatory BP. We obtained echocardiograms and measured pulse wave velocity in 1278 and 1394 participants, respectively. ResultsThe percentages of participants with controlled BP, white-coat, masked, and sustained hypertension were 49.3%, 4.1%, 27.8%, and 18.8%, respectively. Compared with controlled BP, masked hypertension independently associated with low eGFR (23.2 ml/min per 1.73 m 2 ; 95% confidence interval, 25.5 to 20.9), higher proteinuria (+0.9 unit higher in log 2 urine protein; 95% confidence interval, 0.7 to 1.1), and higher left ventricular mass index (+2.52 g/m 2.7 ; 95% confidence interval, 0.9 to 4.1), and pulse wave velocity (+0.92 m/s; 95% confidence interval, 0.5 to 1.3). Participants with masked hypertension had lower eGFR only in the presence of elevated nighttime BP (23.6 ml/min per 1.73 m 2 ; 95% confidence interval, 26.1 to 21.1; versus 21.4 ml/min per 1.73 m 2 ; 95% confidence interval, 26.9 to 4.0, among those with nighttime BP ,120/70 mmHg; P value for interaction with nighttime systolic BP 0.002).Conclusions Masked hypertension is common in patients with CKD and associated with lower eGFR, proteinuria, and cardiovascular target organ damage. In patients with CKD, ambulatory BP characterizes the relationship between BP and target organ damage better than BP measured in the clinic alone.

Background New-onset diabetes after transplantation (NODAT) is a major post-transplant complication associated with lower allograft and recipient survival. Our objective was to determine if metabolic syndrome pre-transplant is independently associated with NODAT development. Methods We recruited 640 consecutive incident non-diabetic renal transplant recipients from 3 academic centers between 1999 and 2004. NODAT was defined as use of hypoglycemic medication, a random plasma glucose >200 mg/dL, or 2 fasting glucose levels ≥126 mg/dL beyond 30 days post-transplant. Results Metabolic syndrome was common pre-transplant (57.2 %). NODAT developed in 31.4% of recipients one year post-transplant. Participants with metabolic syndrome were more likely to develop NODAT compared to recipients without metabolic syndrome (34.4% v. 27.4%, p=0.057). Recipients with increasing number of positive metabolic syndrome components were more likely to develop NODAT (metabolic syndrome score-prevalence at 1 year: 0-0.0%, 1-24.2, 2-29.3%, 3-31.0%, 4-34.8%, and 5-73.7%, p=0.001). After adjustment for demographics, age by decade (HR-1.34 (1.20-1.50), p<0.0001), African American race (HR-1.35 (1.01-1.82), p=0.043), cumulative prednisone dosage (HR-1.18 (1.07-1.30), p=0.001), and metabolic syndrome (HR-1.34 (1.00-1.79), p=0.047) were independent predictors of development of NODAT at 1 year post-transplant. In a multivariable analysis incorporating the individual metabolic syndrome components themselves as covariates, the only pre-transplant metabolic syndrome component to remain an independent predictor of NODAT was low HDL (HR-1.37 (1.01-1.85), p=0.042). Conclusions Metabolic syndrome is an independent predictor for NODAT and is a possible target for intervention to prevent NODAT. Future studies to evaluate if modification of metabolic syndrome factors pre-transplant reduces NODAT development are needed.

Background: Low physical activity (PA) has been associated with higher rates of cardiovascular disease (CVD) and mortality in the general population. Despite the benefits of kidney transplantation, kidney transplant recipients (KTRs) remain at elevated risk for CVD and mortality compared to individuals without kidney disease. Methods: A prospective cohort of 507 adult KTRs from three academic centers completed the Physical Activity Scale for the Elderly (PASE) at transplantation. PASE scores were divided into tertiles. Results: PA was lower with older age, history of CVD, smoking, and diabetes. During the median 8-year follow-up period, 128 individuals died, among whom 101 had a functioning allograft. In multivariable Cox regression for all-cause mortality, greater PA was strongly associated with better survival (HR: 0.52 for most active vs. inactive tertiles, 95% CI: 0.31–0.87, p = 0.01). Secondary analyses, in which (1) death with a functioning graft was the primary outcome, and (2) PASE scores were converted to the metabolic equivalent of task, revealed similar results. We did not find an association between change of PA after transplantation and mortality. Conclusions: PA at the time of kidney transplantation is a strong predictor of all-cause mortality and death with graft function. Evaluation of PA level among kidney transplant candidates may be a useful method to risk-stratify patients for survival after kidney transplantation. Kidney transplant candidates and recipients should also be encouraged to be physically active.

Inadequate secretion of vasopressin during fluid removal by hemodialysis may contribute to the cardiovascular instability that complicates this therapy and administration of exogenous hormone, by supporting arterial pressure, may facilitate volume removal. To test this, we measured plasma vasopressin in patients with end-stage renal disease (ESRD) during hemodialysis and found that despite significant fluid removal, plasma vasopressin concentration did not increase. We further found that ESRD did not alter the endogenous removal rate of plasma vasopressin and that plasma hormone is not dialyzed. Finally, in a randomized, double-blinded, placebo-controlled trial in 22 hypertensive patients, we examined the effect of a constant infusion of a non-pressor dose of vasopressin on the arterial pressure response during a hemodialysis in which the target fluid loss was increased by 0.5 kg over the baseline prescription. We found that arterial pressure was more stable in the patients receiving vasopressin and that while only one patient (9%) in the vasopressin group had a symptomatic hypotensive episode, 64% of the patients receiving placebo had such an episode (P=0.024). Moreover, increased fluid removal was achieved only in the vasopressin group (520+/-90 ml vs 64+/-130 ml, P=0.01). Thus, administration of non-pressor doses of vasopressin to hypertensive subjects improves cardiovascular stability during hemodialysis and allows increased removal of excess extracellular fluid. Inadequate vasopressin secretion during hemodialysis-induced fluid removal is a likely contributor to the intradialytic hypotension that limits fluid removal.