Clinical Prediction of High-Turnover Bone Disease After Kidney Transplantation.

Bone histomorphometric analysis is the most accurate method for the evaluation of bone turnover, but non-invasive tools are also required. We studied whether bone biomarkers can predict high bone turnover determined by bone histomorphometry after kidney transplantation. We retrospectively evaluated the results of bone biopsy specimens obtained from kidney transplant recipients due to the clinical suspicion of high bone turnover between 2000 and 2015. Bone biomarkers were acquired concurrently. Of 813 kidney transplant recipients, 154 (19%) biopsies were taken at a median of 28 (interquartile range, 18-70) months after engraftment. Of 114 patients included in the statistical analysis, 80 (70%) presented with high bone turnover. Normal or low bone turnover was detected in 34 patients (30%). For discriminating high bone turnover from non-high, alkaline phosphatase, parathyroid hormone, and ionized calcium had the areas under the receiver operating characteristic curve (AUCs) of 0.704, 0.661, and 0.619, respectively. The combination of these markers performed better with an AUC of 0.775. The positive predictive value for high turnover at a predicted probability cutoff of 90% was 95% while the negative predictive value was 35%. This study concurs with previous observations that hyperparathyroidism with or without hypercalcemia does not necessarily imply high bone turnover in kidney transplant recipients. The prediction of high bone turnover can be improved by considering alkaline phosphatase levels, as presented in the logistic regression model. If bone biopsy is not readily available, this model may serve as clinically available tool in recognizing high turnover after engraftment.

Health-related quality of life after kidney transplantation: who benefits the most?

The influence of dialysis modalities on HRQoL before and after kidney transplantation (KT) and the role of adherence to medication on HRQoL have not been fully studied. Sixty four dialysis patients who answered the 15D HRQoL survey during dialysis were surveyed again after KT. Adherence and employment were also investigated. The mean 15D score was highest among home hemodialysis patients (HHD) and lowest among in-center hemodialysis patients (icHD). After KT, the mean 15D score improved significantly in 78.6% of peritoneal dialysis patients (PD), 47.6% of HHD, and 53.8% of icHD. Then, mean 15D score remained unchanged in 28.6% of HHD and in 23.1% of icHD patients. A deterioration in the 15D score occurred in 14.3% of PD, 23.1% of icHD, and 23.8% of HHD patients, and this was influenced by the number of pills (P = 0.04). Adherence to medication was the lowest in PD, timing being the most challenging task showing a connection to higher creatinine concentration (never forgot 1.41 mg/dl vs. forgot 2.08 mg/dl P = 0.05). Employed patients had a higher mean 15D score. The icHD and PD patients benefited the most from KT and HHD the least. Low pill burden and employment were linked to a better HRQoL.

TGF-ß1 expression in kidney allograft protocol biopsies during cyclosporine A therapy.

BACKGROUND: TGF-ß1 expression has been described to increase along with time from transplantation and has also been linked to allograft dysfunction and toxic effects of cyclosporine. Our aim was to correlate intragraft TGF-ß1 expression with cyclosporine exposure after kidney transplantation.
 METHODS: Altogether 53 kidney allograft protocol biopsies from 42 patients on a low-dose cyclosporine-based regimen obtained at 3, 6, and 12 months were classified according to Banff and the chronic allograft damage index (CADI). TGF-ß1 expression in tubules, glomeruli, vessels, and inflammatory cells was semi-quantitatively scored and correlated with cyclosporine concentrations (C0 and C2), CADI, and graft function. 
 RESULTS: TGF-ß1 expression was mildly increased along time from transplantation, but the results were not statistically significant. TGF-ß1 expression was neither related to CADI nor to the use of ACE inhibitors/ARB. TGF-ß1 expression in the kidney was not correlated with C0 or C2 levels or kidney graft function during follow-up. 
 CONCLUSION: In protocol biopsies from patients on low-dose cyclosporine regimen, expression of TGB-ß1 was not significantly increased along time since transplantation, and did not correlate with cyclosporine exposure. Our findings suggest that the toxic effects of low-dose cyclosporine on TGF-ß expression may be milder than previously thought.

What happened in Finland to increase home hemodialysis?

Finland is geographically a rather large country with a relatively sparse population (5.3 million). Home hemodialysis (HHD) was started in Helsinki 40 years ago and in the early years it was only used in selected patients. However, by the late 1980s HHD almost disappeared owing to the advent of CAPD and new HD centers. Towards the end of the 1990s, it became evident that PD had limitations and new ways had to be found to individualize HD, improve the outcome, increase capacity, and limit the growth of costs of HD. After careful planning, HHD was reinstituted at the Helsinki University Hospital in 1998 and since then the program has grown steadily. By December 31, 2007, altogether 163 patients had started at home. This has required changes in the predialysis program where the "home first" policy was adopted. Other important features include close cooperation with other nephrological centers as well as centralized HHD training that also supports more remote hospitals. Since then this therapy has been started in several other academic and in some smaller hospitals, and at the end of last year about 4% of all Finnish dialysis patients (n=1.600) were on HHD (prevalence 11.8/million). In the Helsinki metropolitan area this treatment is the most economical modality (estimated annual global costs euro37.000), comparable to self-care satellite HD and CAPD. A successful HHD program requires a well-organized predialysis program, a highly motivated multidisciplinary team, and well-developed training networks.

Dialysate leukocytes, sICAM-1, hyaluronan and IL-6: predictors of outcome of peritonitis?

BACKGROUND/AIMS: Despite effective antibiotic therapy, peritonitis still remains a major problem in peritoneal dialysis (PD). The aim of the present study was to investigate changes of CRP, dialysate leukocytes and IL-6, hyaluronan (HA) and sICAM-1 in dialysate during and after peritonitis and their association to the outcome of peritonitis. METHODS: Dialysate IL-6, HA and sICAM-1 were measured at the onset and on day 4, at the end of the treatment and 2 months after onset of peritonitis. Furthermore, CRP and dialysate leukocytes were measured on days 1-4. RESULTS: All measured soluble factors were higher on the first and fourth day than at the end of the treatment. sICAM-1 and HA were lower at the end of the treatment in patients who later had a relapse/re-infection. IL-6 remained higher 2 months after clinically cured peritonitis. CRP and dialysate leukocytes were higher on day 4 in patients with poor outcome. CONCLUSIONS: Peritonitis causes increased excretion of soluble factors. Low concentrations of sICAM-1 and HA at the end of the treatment were negative prognostic indicators. Higher IL-6 levels after peritonitis could be a sign of ongoing inflammation in the peritoneal membrane. Delayed decrease in CRP and dialysate leukocytes may indicate poor outcome.