Organic anion transporters (OATs) are located on either the basolateral or the apical membrane of the proximal tubule cell and mediate the absorption and secretion of various drugs and endogenous metabolites. It has been shown that cellular damage in acute kidney injury (AKI) involves three forms of injury: sublethal damage resulting in loss of cell polarity, cell death through apoptosis and necrosis. We hypothesize that cellular mistargeting of OAT proteins in AKI will change the profile of OAT proteins in urine. Thirty AKI patients were included in the study. AKI was defined by clinical course, daily urine output, response to fluid repletion, urinary sediment, fractional excretion of sodium (FeNa) and urine osmolality. Urinary OAT1, OAT3 and OAT4 protein abundance was measured from semiquantitative immunoblots of urine membrane fraction samples (exosome) collected from patients with AKI and from control subjects. Although all patients studied reached a similar severity of renal failure measured by serum creatinine, some of them recovered from AKI with supportive care only, while others required renal replacement therapy (RRT). OAT1 and OAT3, which are normally localized in the basolateral membrane of the proximal tubule cell, were detected at low levels in urine from control subjects and were increased significantly in all patients with AKI. OAT4 protein, which is normally localized in the luminal membrane of proximal tubule cells, was present in abundance in urine of control subjects. Interestingly, in patients with AKI who eventually recovered, urinary OAT4 was found to be significantly lower than in controls, while in patients who needed RRT, it was higher than in controls. We have shown that OATs are mistargeted in AKI. The urinary OAT protein profile can help us to learn about the pathophysiology of the disease and might be a marker of AKI severity. AKI patients with early reversible proximal tubular damage will have high urine OAT1 and OAT3 and low OAT4, while patients with severe AKI will have high urine OAT1, OAT3 and OAT4.

Background: Peritoneal dialysis (PD) is increasingly used for long-term management of refractory congestive heart failure (CHF). In this study, we investigated the outcome of patients with refractory CHF treated with PD, aiming to identify potential prognostic factors for long term-survival. Methods: This was a prospective observational study over a period of 42 months which included 37 refractory CHF patients. Results: Median survival on PD was 14 months (1-41 months). Long survivors had serum sodium >132 mEq/l (p < 0.001), serum albumin >3.2 g/dl (p < 0.001) and hospitalization rate <2 days per month a year before starting the treatment (p = 0.008). Patients in the lowest survival quartile had lower serum albumin (2.8 vs. 3.5 g/dl in longer survivors, p = 0.003) and serum sodium (126 vs. 137 mEq/l, p < 0.0001), higher serum leukocyte count (7,500 vs. 6,800/μl in long survivors, p = 0.033), higher glomerular filtration rate (39.4 vs. 29.9 ml/min/1.73 m2, p = 0.035), had more hospitalization before starting the treatment (3.4 vs. 1.9 days per month, p = 0.003) and lower estimated left ventricular mass index (113 vs. 137 g/m2, p = 0.035). Long-term survivors demonstrated significant improvement in the New York Heart Association functional class by a median of one class, reduced hospitalization rate by 55% and decrease in dependence on intravenous diuretics and vasoactive medications (73% drop in CHF day care visits during the first year of treatment). Conclusions: Survival of patients with refractory CHF treated with PD is highly variable. Serum sodium, serum albumin and hospitalization rate are important prognostic factors for long-term survival. Long survivors demonstrated improved functional status, reduced hospitalization and mortality rates.

Peritoneal dialysis is a feasible, cost-effective, home-based treatment of renal replacement therapy, based on the dialytic properties of the peritoneal membrane. As compared with hemodialysis, peritoneal dialysis is cheaper, survival rate is similar, residual kidney function is better preserved, fluid and solutes are removed more gradually and continuously leading to minimal impact on hemodynamics, and risks related to a vascular access are avoided. Those features of peritoneal dialysis are useful to treat refractory congestive heart failure patients with fluid overload. It was shown that in such patients, peritoneal dialysis improves functional status and quality of life, reduces hospitalization rate, and may decrease mortality rate. High levels of serum proinflammatory cytokines and fibrosis markers, among other factors, play an important part in congestive heart failure pathogenesis and progression. We demonstrated that those levels decreased following peritoneal dialysis treatment in refractory congestive heart failure patients. The exact mechanism of beneficial effect of peritoneal dialysis in refractory congestive heart failure is currently unknown. Maintenance of fluid balance, leading to resetting of neurohumoral activation towards a more physiological condition, reduced remodeling due to the decrease in mechanical pressure on the heart, decreased inflammatory cytokine levels and oxidative stress, and a potential impact on uremic toxins could play a role in this regard. In this paper, we describe the unique characteristics of the peritoneal membrane, principals of peritoneal dialysis and its role in heart failure patients.

Proinflammatory cytokines play a pathogenic role in congestive heart failure. In this study, the effect of peritoneal dialysis treatment on inflammatory cytokines levels in refractory congestive heart failure patients was investigated. During the treatment, the patients reached a well-tolerated edema-free state and demonstrated significant improvement in NYHA functional class. Brain natriuretic peptide decreased significantly after 3 months of treatment and remained stable at 6 months. C-reactive protein, a plasma marker of inflammation, decreased significantly following the treatment. Circulating inflammatory cytokines TNF-αand IL-6 decreased significantly after 3 months of peritoneal dialysis treatment and remained low at 6 months. The reduction in circulating inflammatory cytokines levels may be partly responsible for the efficacy of peritoneal dialysis for refractory congestive heart failure.

Background Peritoneal dialysis (PD) is increasingly used for the long‐term management of hypervolemic refractory congestive heart failure (CHF) patients, in particular when complicated by renal insufficiency. While PD has many advantages over hemodialysis (HD) in those patients, there is a controversy concerning survival superiority of PD compared to HD in this population. The aim of the study was to define typical patient profile and to compare outcomes of patients with CHF and renal failure treated with HD or PD. Methods This retrospective cohort study enrolled CHF patients treated with chronic PD or HD between the years 2009‐2018. Information at dialysis initiation included age, gender, body weight, blood pressure, cause of renal disease, comorbidities, hospitalizations, echocardiographic and laboratory parameters. Survival was compared between PD and HD patients using a Kaplan–Meier model and Cox regression analysis. Results CHF patients treated with PD had significantly higher eGFR and lower systolic blood pressure compared to HD treated patients. Median survival time was 13.32 (7.08, 23.28) months in the PD group and 19.68 (9.48, 39.24) months in the HD group, p=0.013. After adjustment for confounders the mortality risk among PD and HD patients was not significantly different: adjusted HR for death in PD versus HD patients was 1.44, P = 0.35 for 1‐ year and 1.69, p = 0.10 for 2‐year mortality. Number of hospitalizations was similar in both groups. Conclusions CHF patient profile was different in PD and HD. Two modalities were equally effective in the treatment of patients with CHF and renal failure considering different patient characteristics.