The potassium regulator patiromer affects serum and stool electrolytes in patients receiving hemodialysis.

Hyperkalemia is a common and an important cause of death in maintenance hemodialysis patients. Here we investigated the effect of patiromer, a synthetic cation exchanger, to regulate potassium homeostasis. Serum and stool electrolytes were measured in 27 anuric patients with hyperkalemia receiving hemodialysis (mainly 2 mEq/L dialysate) during consecutive two weeks of no-treatment, 12 weeks of treatment with patiromer (16.8g once daily), and six weeks of no treatment. The serum potassium decreased from a mean of 5.7 mEq/L pre-treatment to 5.1 mEq/L during treatment and rebounded to 5.4 mEq/L post-treatment. During the treatment phase, serum calcium significantly increased (from 8.9 to 9.1 mg/dL) and serum magnesium significantly decreased (from 2.6 to 2.4 mg/dL) compared to pre-treatment levels. For each one mEg/L increase in serum magnesium, serum potassium increased by 1.07 mEq/L. Stool potassium significantly increased during treatment phase from pre-treatment levels (4132 to 5923 µg/g) and significantly decreased post-treatment to 4246 µg/g. For each one µg/g increase in stool potassium, serum potassium significantly declined by 0.05 mEq/L. Stool calcium was significantly higher during the treatment phase (13017 µg/g) compared to pre-treatment (7874 µg/g) and post-treatment (7635 µg/g) phases. We estimated that 16.8 g of patiromer will increase fecal potassium by 1880 µg/g and reduce serum potassium by 0.5 mEq/L. Thus, there is a complex interaction between stool and blood potassium, calcium and magnesium during patiromer treatment. Long term consequence of patiromer-induced changes in serum calcium and magnesium remains to be studied.

Gut microbiome in chronic kidney disease: challenges and opportunities.

More than 100 trillion microbial cells that reside in the human gut heavily influence nutrition, metabolism, and immune function of the host. Gut dysbiosis, seen commonly in patients with chronic kidney disease (CKD), results from qualitative and quantitative changes in host microbiome profile and disruption of gut barrier function. Alterations in gut microbiota and a myriad of host responses have been implicated in progression of CKD, increased cardiovascular risk, uremic toxicity, and inflammation. We present a discussion of dysbiosis, various uremic toxins produced from dysbiotic gut microbiome, and their roles in CKD progression and complications. We also review the gut microbiome in renal transplant, highlighting the role of commensal microbes in alteration of immune responses to transplantation, and conclude with therapeutic interventions that aim to restore intestinal dysbiosis.

Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD.

BACKGROUND AND OBJECTIVES: CD14 plays a key role in the innate immunity as pattern-recognition receptor of endotoxin. Higher levels of soluble CD14 (sCD14) are associated with overall mortality in hemodialysis patients. The influence of kidney function on plasma sCD14 levels and its relationship with adverse outcomes in patients with CKD not yet on dialysis is unknown. This study examines the associations between plasma levels of sCD14 and endotoxin with adverse outcomes in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured plasma levels of sCD14 and endotoxin in 495 Leuven Mild-to-Moderate CKD Study participants. Mild-to-moderate CKD was defined as presence of kidney damage or eGFR<60 ml/min per 1.73 m(2) for ≥3 months, with exclusion of patients on RRT. Study participants were enrolled between November 2005 and September 2006. RESULTS: Plasma sCD14 was negatively associated with eGFR (ρ=-0.34, P<0.001). During a median follow-up of 54 (interquartile range, 23-58) months, 53 patients died. Plasma sCD14 was predictive of mortality, even after adjustment for renal function, Framingham risk factors, markers of mineral bone metabolism, and nutritional and inflammatory parameters (hazard ratio [HR] per SD higher of 1.90; 95% confidence interval [95% CI],1.32 to 2.74; P<0.001). After adjustment for the same risk factors, plasma sCD14 was also a predictor of cardiovascular disease (HR, 1.30; 95% CI, 1.00 to 1.69; P=0.05). Although plasma sCD14 was associated with progression of CKD, defined as reaching ESRD or doubling of serum creatinine in models adjusted for CKD-specific risk factors (HR, 1.24; 95% CI, 1.01 to 1.52; P=0.04), significance was lost when adjusted for proteinuria (HR, 1.19; 95% CI, 0.96 to 1.48; P=0.11). There was neither correlation between plasma endotoxin and sCD14 (ρ=-0.06, P=0.20) nor was endotoxin independently associated with adverse outcome during follow-up. CONCLUSIONS: Plasma sCD14 is elevated in patients with decreased kidney function and associated with mortality and cardiovascular disease in patients with CKD not yet on dialysis.