Parathyroid Hormone Concentrations in Maintenance Hemodialysis: Longitudinal Evaluation of Intact and Biointact Assays.

RATIONALE & OBJECTIVE: Management of chronic kidney disease mineral and bone disorder requires parathyroid hormone (PTH) concentrations. "Biointact" PTH immunoassays detect "whole" PTH (wPTH), whereas "intact" immunoassays measure PTH plus PTH fragments (iPTH). We aimed to determine whether longitudinal changes in PTH concentrations can be evaluated using biointact and intact immunoassays alike. STUDY DESIGN: Open noninterventional longitudinal cohort study. SETTING & PARTICIPANTS: PTH concentrations were measured quarterly up to 5 times in 102 hemodialysis patients. PREDICTORS & TESTS COMPARED: Age, sex, phosphate levels, and others as clinical predictors for PTH trend. Tests compared were iPTH immunoassays from Siemens and Roche and wPTH immunoassays from Roche and DiaSorin. OUTCOMES: PTH concentration trend; regression equations; test bias. ANALYTICAL APPROACH: Predictive regression-to-the-mean model for PTH slope; Bland-Altman plots, Passing-Bablok regression, and reference change values for test comparisons. RESULTS: wPTH concentrations were similar with both immunoassays (wPTH-Roche = 11.7 + 0.97 × wPTH-DiaSorin, r = 0.99; mean ± 1.96 SD bias, 8.2 ± 43.3 pg/mL [17.5% ± 40.9%], by Bland-Altman plots). iPTH-Siemens concentrations were higher than iPTH-Roche concentrations (iPTH-Siemens = -5.4 + 1.33 × iPTH-Roche, r = 0.99; mean ± 1.96 SD bias, 84.0 ± 180.2 pg/mL [21.1% ± 29.8%], by Bland-Altman plots). iPTH-Roche and iPTH-Siemens concentrations were 2- and 2.5-fold higher than wPTH concentrations, respectively. Full agreement among all 4 immunoassays in detecting both significant and insignificant changes in PTH concentrations, upward or downward from one quarter to the next, was reached in 87% of consecutive measurements. In a predictive model, baseline PTH concentrations > 199 pg/mL (wPTH-Roche), 204 pg/mL (wPTH-DiaSorin), 386 pg/mL (iPTH-Roche), and 417 pg/mL (iPTH-Siemens) correctly predicted declining PTH concentration trend in 62% to 68% of patients, but age, sex, hemodialysis vintage, and calcium and phosphate levels were no significant predictors. LIMITATIONS: Limited number of immunoassays, only 59 patients attended all quarterly samplings. CONCLUSIONS: wPTH-Roche and wPTH-DiaSorin concentrations were similar, while iPTH was higher than wPTH concentrations. The iPTH-Siemens immunoassay is either higher calibrated or detects more fragments than iPTH-Roche. However, longitudinal PTH concentration changes largely coincided with all tested immunoassays.

Bioimpedance spectroscopy for fluid status assessment in patients with decompensated liver cirrhosis: Implications for peritoneal dialysis.

Bioimpedance spectroscopy (BIS) is routinely used in peritoneal dialysis patients and might aid fluid status assessment in patients with liver cirrhosis, but the effect of ascites volume removal on BIS-readings is unknown. Here we determined changes in BIS-derived parameters and clinical signs of fluid overload from before to after abdominal paracentesis. Per our pre-specified sample size calculation, we studied 31 cirrhotic patients, analyzing demographics, labs and clinical parameters along with BIS results. Mean volume of the abdominal paracentesis was 7.8 ± 2.6 L. From pre-to post-paracentesis, extracellular volume (ECV) decreased (20.2 ± 5.2 L to 19.0 ± 4.8 L), total body volume decreased (39.8 ± 9.8 L to 37.8 ± 8.5 L) and adipose tissue mass decreased (38.4 ± 16.0 kg to 29.9 ± 12.9 kg; all p < 0.002). Correlation of BIS-derived parameters from pre to post-paracentesis ranged from R² = 0.26 for body cell mass to R² = 0.99 for ECV. Edema did not correlate with BIS-derived fluid overload (FO ≥ 15% ECV), which occurred in 16 patients (51.6%). In conclusion, BIS-derived information on fluid status did not coincide with clinical judgement. The changes in adipose tissue mass support the BIS-model assumption that fluid in the peritoneal cavity is not detectable, suggesting that ascites (or peritoneal dialysis fluid) mass should be subtracted from adipose tissue if BIS is used in patients with a full peritoneal cavity.

Effect of Thyroid Hormones on Kidney Function in Patients after Kidney Transplantation.

Elevated levels of thyroid-stimulating-hormone (TSH) are associated with reduced glomerular filtration rate (GFR) and increased risk of developing chronic kidney disease even in euthyroid patients. Thyroid hormone replacement therapy has been shown to delay progression to end-stage renal disease in sub-clinically hypothyroid patients with renal insufficiency. However, such associations after kidney transplantation were never investigated. In this study the association of thyroid hormones and estimated GFR (eGFR) in euthyroid patients after kidney transplantation was analyzed. In total 398 kidney transplant recipients were assessed retrospectively and association between thyroid and kidney function parameters at and between defined time points, 12 and 24 months after transplantation, was studied. A significant inverse association was shown for TSH changes and eGFR over time between months 12 and 24 post transplantation. For each increase of TSH by 1 µIU/mL, eGFR decreased by 1.34 mL/min [95% CI, -2.51 to -0.16; p = 0.03], corresponding to 2.2% eGFR decline, within 12 months. At selected time points 12 and 24 months post transplantation, however, TSH was not associated with eGFR. In conclusion, an increase in TSH between 12 and 24 months after kidney transplantation leads to a significant decrease in eGFR, which strengthens the concept of a kidney-thyroid-axis.

Diagnostic and Prognostic Value of Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) in Focal Segmental Glomerulosclerosis and Impact of Detection Method.

The plasma soluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker for focal segmental glomerulosclerosis (FSGS), but its value is under discussion because of ambiguous results arising from different ELISA methods in previous studies. The aim of this study was to compare diagnostic performance of two leading suPAR ELISA kits and examine four objectives in 146 subjects: (1) plasma suPAR levels according to glomerular disease (primary, secondary and recurrent FSGS after kidney transplantation, other glomerulonephritis) and in healthy controls; (2) suPAR levels based on glomerular filtration rate; (3) sensitivity and specificity of suPAR for FSGS diagnosis and determination of optimal cut-offs; (4) suPAR as prognostic tool. Patients with FSGS showed significant higher suPAR values than patients with other glomerulonephritis and healthy individuals. This applied to subjects with and without chronic kidney disease. Although both suPARnostic™ assay and Quantikine Human uPAR ELISA Kit exerted high sensitivity and specificity for FSGS diagnosis, their cut-off values of 4.644 ng/mL and 2.789 ng/mL were significantly different. Higher suPAR was furthermore predictive for progression to end-stage renal disease. In summary, suPAR values must be interpreted in the context of population and test methods used. Knowing test specific cut-offs makes suPAR a valuable biomarker for FSGS.

Taurolidine-based catheter lock regimen significantly reduces overall costs, infection, and dysfunction rates of tunneled hemodialysis catheters.

Catheter-related infections and dysfunction are the main catheter complications causing morbidity and mortality in hemodialysis patients. However, there are no consistent data for the choice of catheter lock solutions for tunneled hemodialysis lines. In this prospective, multicenter, randomized, controlled trial, two lock regimens using three commercial catheter lock solutions were compared in 106 hemodialysis patients with a newly inserted tunneled central catheter. In the taurolidine group, TauroLock™-Hep500 was used twice per week and TauroLock™-U25,000 once a week. In the citrate group, a four percent citrate solution was used after each dialysis. Both groups were compared regarding catheter-related infections, catheter dysfunction, and costs. Over a period of 15,690 catheter days, six catheter-related infections occurred in six of 52 patients in the taurolidine group, but 18 occurred in 13 of 54 patients in the citrate group, corresponding to 0.67 and 2.7 episodes of catheter-related infections per 1000 catheter days, respectively (Incidence Rate Ratio 0.25, 95% confidence interval, 0.09 to 0.63). Catheter dysfunction rates were significantly lower in the taurolidine group (18.7 vs. 44.3/1000 catheter days) and alteplase rescue significantly more frequent in the citrate group (9.8 vs. 3.8/1000 catheter days). These differences provided significant catheter-related cost savings of 43% in the taurolidine group vs. citrate group when overall expenses per patient and year were compared. Thus, use of taurolidine-based catheter lock solutions containing heparin and urokinase significantly reduced complications related to tunneled hemodialysis catheters when compared to four percent citrate solution and was overall more cost-efficient.

Nephrocystin-4 regulates Pyk2-induced tyrosine phosphorylation of nephrocystin-1 to control targeting to monocilia.

Nephronophthisis is the most common genetic cause of end-stage renal failure during childhood and adolescence. Genetic studies have identified disease-causing mutations in at least 11 different genes (NPHP1-11), but the function of the corresponding nephrocystin proteins remains poorly understood. The two evolutionarily conserved proteins nephrocystin-1 (NPHP1) and nephrocystin-4 (NPHP4) interact and localize to cilia in kidney, retina, and brain characterizing nephronophthisis and associated pathologies as result of a ciliopathy. Here we show that NPHP4, but not truncating patient mutations, negatively regulates tyrosine phosphorylation of NPHP1. NPHP4 counteracts Pyk2-mediated phosphorylation of three defined tyrosine residues of NPHP1 thereby controlling binding of NPHP1 to the trans-Golgi sorting protein PACS-1. Knockdown of NPHP4 resulted in an accumulation of NPHP1 in trans-Golgi vesicles of ciliated retinal epithelial cells. These data strongly suggest that NPHP4 acts upstream of NPHP1 in a common pathway and support the concept of a role for nephrocystin proteins in intracellular vesicular transport.